Jeremy J. Heit, MD, PhD

All Publications

• Optimized Combination of b?values for IVIM Perfusion Imaging in Acute Ischemic Stroke Patients. Clinical neuroradiology Zhu, G., Heit, J. J., Martin, B. W., Marcellus, D. G., Federau, C., Wintermark, M. 2019

  Abstract

  PURPOSE: To determine the optimal combination of low b?values to generate perfusion information from intravoxel incoherent motion (IVIM) in patients with acute ischemic stroke (AIS) considering the time constraints for these patients.METHODS: A retrospective cohort study of AIS patients with IVIM MRI was performed. A two-step voxel-by-voxel postprocessing was used to derive IVIM perfusion fraction maps with different combinations of bvalues. Signal values within regions of ischemic core, non-infarcted ischemic hemisphere, and contralateral hemisphere were measured on IVIM (f, D*, fD*, D) parameter maps. Bland-Altman analysis and the Dice similarity coefficient were used to determine quantitative and spatial agreements between the reference standard IVIM (IVIM with 6 bvalues of 0, 50, 100, 150, 200, 1000?s/mm2) and other combinations of bvalues. Significance level was set at p?<0.05.RESULTS: There were 58 patients (36males, 61.3%; mean age 70.2?±13.4 years) included. Considering all IVIM parameters, the combination of bvalues of 0, 50, 200, 1000 was the most consistent with our reference standard on Bland-Altman analysis. The best voxel-based overlaps of ischemic regions were on IVIMD, while there were good voxel-based overlaps on IVIMf.CONCLUSION: The IVIM with these four bvalues collects diffusion and perfusion information from asingle short MRI sequence, which may have important implications for the imaging of AIS patients.

  View details for DOI 10.1007/s00062-019-00817-w

  View details for PubMedID 31375894

• Thrombectomy Results in Reduced Hospital Stay, More Home-Time, and More Favorable Living Situations in DEFUSE 3. Stroke Tate, W. J., Polding, L. C., Kemp, S., Mlynash, M., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. 2019: STROKEAHA119025165

  Abstract

  Background and Purpose- The DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) demonstrated that endovascular thrombectomy in the 6- to 16-hour time window improves functional outcomes of patients with evidence of salvageable tissue on baseline computed tomography or magnetic resonance imaging. The purpose of this study is to assess the effect of endovascular therapy on length of hospital stay, home-time during the first 3 months poststroke, and living situation poststroke in DEFUSE 3. Methods- Duration of hospital stay and home-time (number of days during the 90-day poststroke period that the patient resides in their own home or in that of a relative) were compared between treatment groups using the Wilcoxon rank-sum test. Patient living situation was assessed at discharge, 30 days, and 90 days on an ordinal 4-point scale (home, acute rehabilitation unit, institutionalized care, or hospice/death) and differences between groups were analyzed using the Cochran-Armitage trend test. Results- Median length of hospital stay was 9.1 (interquartile range, 6.2-15.0) days in the medical group versus 6.5 (interquartile range, 3.7-9.3) days in the endovascular group ( P<0.001). Median home-time during the first 90 days after stroke was 0 (interquartile range, 0-53) days in the medical group versus 55 (interquartile range, 0-83) days in the endovascular group ( P<0.001). The endovascular group had more favorable living situations at time of discharge ( P<0.001), 30 days ( P<0.001), and 90 days ( P<0.001) poststroke. Conclusions- Endovascular thrombectomy resulted in reduced hospital stay, more home-time, and more desirable living situations in the 90 days after stroke. These results provide evidence that endovascular therapy in the delayed time window can improve quality of life for stroke patients and reduce healthcare costs. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.119.025165

  View details for PubMedID 31288666

• Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial JAMA NEUROLOGY Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019; 76 (6): 682?89

  View details for DOI 10.1001/jamaneurol.2019.0118

  View details for Web of Science ID 000474834200011

• Response by de Havenon et al to Letter Regarding Article, "Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome" STROKE de Havenon, A., Albers, G. W., Heit, J. J. 2019; 50 (6): E166

  View details for DOI 10.1161/STROKEAHA.119.025713

  View details for Web of Science ID 000470074200014

• Response by Guenego and Heit to Letter Regarding Article, "Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy". Stroke Guenego, A., Heit, J. J. 2019: STROKEAHA119025863

  View details for DOI 10.1161/STROKEAHA.119.025863

  View details for PubMedID 31084321

• Response by de Havenon et al to Letter Regarding Article, "Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome". Stroke de Havenon, A., Albers, G. W., Heit, J. J. 2019: STROKEAHA119025713

  View details for PubMedID 31084323

• Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study STROKE Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019; 50 (5): 1172?77

  View details for DOI 10.1161/STROKEAHA.119.024928

  View details for Web of Science ID 000469350000042

• Superselective methohexital challenge prior to intracranial endovascular embolization JOURNAL OF CLINICAL NEUROSCIENCE Bican, O., Cho, C., Suarez-Roman, A., Viet Nguyen, Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019; 63: 68?71

  View details for DOI 10.1016/j.jocn.2019.01.051

  View details for Web of Science ID 000466249000013

• Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke. Neurology Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019

  Abstract

  OBJECTIVE: To determine if intravoxel incoherent motion (IVIM) magnetic resonance perfusion can measure the quality of the collateral blood flow in the penumbra in hyperacute stroke.METHODS: A 6 b values IVIM MRI sequence was acquired in stroke patients with large vessel occlusion imaged <16 hours of last seen well. IVIM perfusion measures were evaluated in regions of interest drawn in the infarct core (D < 600 mm2/s), in the corresponding region in the contralateral hemisphere, and in the dynamic susceptibility contrast penumbra. In patients with a penumbra >15 mL, images were reviewed for the presence of a penumbra perfusion lesion on the IVIM f map, which was correlated with infarct size metrics. Statistical significance was tested using Student t test, Mann-Whitney U test, and Fisher exact test.RESULTS: A total of 34 patients were included. In the stroke core, IVIM f was significantly lower (4.6 ± 3.3%) compared to the healthy contralateral region (6.3 ± 2.2%, p < 0.001). In the 25 patients with a penumbra >15 mL, 9 patients had an IVIM penumbra perfusion lesion (56 ± 76 mL), and 16 did not. Patients with an IVIM penumbra perfusion lesion had a larger infarct core (82 ± 84 mL) at baseline, a larger infarct growth (68 ± 40 mL), and a larger final infarct size (126 ± 81 mL) on follow-up images compared to the patients without (resp. 20 ± 17 mL, p < 0.05; 13 ± 19 mL, p < 0.01; 29 ± 24 mL, p < 0.05). All IVIM penumbra perfusion lesions progressed to infarction despite thrombectomy treatment.CONCLUSIONS: IVIM is a promising tool to assess the quality of the collateral blood flow in hyperacute stroke. IVIM penumbra perfusion lesion may be a marker of nonsalvageable tissue despite treatment with thrombectomy, suggesting that the IVIM penumbra perfusion lesion might be counted to the stroke core, together with the DWI lesion.

  View details for PubMedID 31019105

• Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3 MacLellan, A., Mlynash, M., Heit, J., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965907014

• Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy STROKE Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019; 50 (4): 917?22

  View details for DOI 10.1161/STROKEAHA.118.024134

  View details for Web of Science ID 000469347900033

• Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial JAMA NEUROLOGY Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Ortega-Gutierrez, S., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., Ortega-Gutierrez, S., Leira, E., McTaggart, R., Yaghi, S., Torbey, M., Powers, C. J., Kim-Tenser, M., Tenser, M., Lansberg, M., Marks, M., Leslie-Mazwi, T., Hurst, R., Kasner, S., Sarraj, A., Spiegel, G., Ansari, S. A., Prabhakaran, S., Altschul, D., de Havenon, A., Park, M., Fifi, J., Tuhrim, S., Hoesch, R., Blatter, D., Kayan, Y., Young, M., Stephens, R., Finch, I., Afshinnik, A., Ryan, R., Chaudhary, N., Brown, D., Feske, S., Aziz-Sultan, A., Smith, W., Cooke, D., Warach, S., Miley, J., Ahmed, A., Bradbury, E., Bozorgchami, H., Priest, R., Gropen, T., Harrigan, M., Kalafut, M., Ammirati, G., Meyer, B., Khalessi, A., Schlaug, G., Sen, S., Moftakhar, R., Streib, C., Jagadeesan, B. D., Toth, G., Uchino, K., Hsia, A., Liu, A., Jagadeesan, B. D., Streib, C., Vagal, A., Ringer, A. J., Willey, J. Z., Meyers, P. M., Zaidat, O. O., Froehler, M., Leifer, D., Patsalides, A., Lowenkopf, T., Deshmukh, V., Tirschwell, D., Hallam, D., DEFUSE 3 Investigators 2019; 76 (4): 447?53

  View details for DOI 10.1001/jamaneurol.2018.4587

  View details for Web of Science ID 000463873600013

• Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Stroke Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019: STROKEAHA119024928

  Abstract

  Background and Purpose- Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ?8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0-2). Results- Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI-). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI- patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI- ( P=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI- patients ( P=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7-8.6; P=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1-6.7; P=0.03). Mortality was 3% in RNI+ versus 18% in RNI- ( P=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1-7] versus 13 [IQR, 7.5-21]; P<0.001), smaller 24-hour infarction volume (21 [IQR, 5-32] versus 65 [IQR, 27-145] mL; P<0.001), and less 24-hour infarct growth (8 [IQR, 1-18] versus 37 [IQR, 16-105] mL; P<0.001) compared with RNI- patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9-7.1] versus 7.4 [IQR, 5.2-12.1] days in RNI-; P<0.001). Conclusions- RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30932783

• Cerebral foreign body reaction due to hydrophilic polymer embolization following aneurysm treatment by pipeline flow diversion device. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Geisbush, T. R., Marks, M. P., Heit, J. J. 2019: 1591019919830767

  Abstract

  The use of flow diverting stents for wide based, intracranial aneurysms has become an invaluable treatment option. While intracranial hemorrhage and ischemic stroke from dislodged atherosclerotic emboli are common adverse events, the potential for delayed granulomatous inflammation from possible hydrophilic polymer emboli is rarely recognized. We present a unique case in which visible chipping of the pusher wire for stent placement was observed, followed by clinical and radiographic evidence suggestive of a delayed foreign body reaction to intracranial hydrophilic polymer emboli. A 55-year-old woman underwent placement of a Pipeline embolization device for a left-sided, broad-based aneurysm at the base of the internal carotid artery and posterior communicating artery. Two months later she developed right-sided focal neurological deficits. Imaging showed ipsilateral focal edema and enhancing lesions with contrast. Although not confirmed with biopsy and histopathology, clinical and radiographic evidence suggests that this patient probably experienced a delayed foreign body reaction to hydrophilic polymer emboli from compromised procedural equipment during flow diverting stent placement. Although previously described, this is the first instance to our knowledge in whichvisible chipping of the pusher wire was observed on a Pipeline embolization device.

  View details for DOI 10.1177/1591019919830767

  View details for PubMedID 30922199

• Proposed achievable levels of dose and impact of dose-reduction systems for thrombectomy in acute ischemic stroke: an international, multicentric, retrospective study in 1096 patients. European radiology Guenego, A., Mosimann, P. J., Pereira, V. M., Nicholson, P., Zuber, K., Lotterie, J. A., Dobrocky, T., Marcellus, D. G., Olivot, J. M., Piotin, M., Gralla, J., Fahed, R., Wintermark, M., Heit, J. J., Cognard, C., RADON Investigators 2019

  Abstract

  BACKGROUND: International dose reference levels are lacking for mechanical thrombectomy in acute ischemic stroke patients with large vessel occlusions. We studied whether radiation dose-reduction systems (RDS) could effectively reduce exposure and propose achievable levels.MATERIALS AND METHODS: We retrospectively included consecutive patients treated with thrombectomy on a biplane angiography system (BP) in five international, high-volume centers between January 2014 and May 2017. Institutional Review Board approvals were obtained. Technical, procedural, and clinical characteristics were assessed. Efficacy, safety, radiation dose, and contrast load were compared between angiography systems with and without RDS. Multivariate analyses were adjusted according to Bonferroni's correction. Proposed international achievable cutoff levels were set at the 75th percentile.RESULTS: Out of the 1096 thrombectomized patients, 520 (47%) were treated on a BP equipped with RDS. After multivariate analysis, RDS significantly reduced dose-area product (DAP) (91 vs 140Gycm2, relative effect 0.74 (CI 0.66; 0.83), 35% decrease, p<0.001) and air kerma (0.46 vs 0.97Gy, relative effect 0.63 (CI 0.56; 0.71), 53% decrease, p<0.001) with 75th percentile levels of 148Gycm2 and 0.73Gy, respectively. There was no difference in contrast load, rates of successful recanalization, complications, or clinical outcome.CONCLUSION: Radiation dose-reduction systems can reduce DAP and air kerma by a third and a half, respectively, without affecting thrombectomy efficacy or safety. The respective thresholds of 148Gycm2 and 0.73Gy represent achievable levels that may serve to optimize current and future radiation exposure in the setting of acute ischemic stroke treatment. As technology evolves, we expect these values to decrease.KEY POINTS: Internationally validated achievable levels may help caregivers and health authorities better assess and reduce radiation exposure of both ischemic stroke patients and treating staff during thrombectomy procedures. Radiation dose-reduction systems can reduce DAP and air kerma by a third and a half, respectively, without affecting thrombectomy efficacy or safety in the setting of acute ischemic stroke due to large vessel occlusion.

  View details for DOI 10.1007/s00330-019-06062-6

  View details for PubMedID 30903333

• Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy. Stroke Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019: STROKEAHA118024134

  Abstract

  Background and Purpose- Hypoperfusion intensity ratio (HIR) is associated with collateral status in acute ischemic stroke patients with anterior circulation large vessel occlusion. We assessed whether HIR was correlated to patient eligibility for mechanical thrombectomy (MT). Methods- We performed a retrospective cohort study of consecutive acute ischemic stroke patients with a proximal middle cerebral artery or internal carotid artery occlusion who underwent MT triage with computed tomography or magnetic resonance perfusion imaging. Clinical data, ischemic core (mL), HIR (defined as time-to-maximum [TMax] >10 seconds/TMax >6 seconds), mismatch volume between core and penumbra, and MT details were assessed. Primary outcome was favorable HIR collateral score (HIR <0.4) between patients who underwent MT (MT+) and those who did not (MT-) according to American Heart Association guidelines both in the <6 hours and 6 to 24 hours windows. Secondary outcomes were favorable HIR score in MT- subgroups (National Institutes of Health Stroke Scale <6 versus core >70 mL) and core-penumbra mismatch volumes. Patients who did not meet guidelines were not included. Results- We included 197 patients (145 MT+ and 52 MT-). MT+ patients had a significantly lower median HIR compared with MT- patients (0.4 [interquartile range, 0.2-0.5] versus 0.6 [interquartile range, 0.5-0.8]; P<0.001) and a higher mismatch volume (96 versus 27 mL, P<0.001). Among MT- patients, 43 had a core >70 mL, and 9 had a National Institutes of Health Stroke Scale <6. MT- patients with National Institutes of Health Stroke Scale <6 had a lower HIR than MT- patients with core >70 mL (0.2 [interquartile range, 0.2-0.3] versus 0.7 [interquartile range, 0.6-0.8], P<0.001) but their HIR was not significantly different that MT+ patients. Conclusions- Patients who meet American Heart Association guidelines for thrombectomy are more likely to have favorable collaterals (low HIR). HIR may be used as a marker of eligibility for MT triage.

  View details for PubMedID 30841821

• Results From DEFUSE 3 Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome STROKE de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M. G., Leslie-Mazwi, T., Christensen, S., McTaggart, R. A., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J. J., DEFUSE 3 Investigators 2019; 50 (3): 632?38

  View details for DOI 10.1161/STROKEAHA.118.023407

  View details for Web of Science ID 000459699700024

• Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3 STROKE Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019; 50 (3): 626?31

  View details for DOI 10.1161/STROKEAHA.118.023177

  View details for Web of Science ID 000459699700023

• Persistent Target Mismatch Profile > 24 Hours After Stroke Onset in DEFUSE 3 STROKE Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019; 50 (3): 754?57

  View details for DOI 10.1161/STROKEAHA.118.023392

  View details for Web of Science ID 000459699700041

• Superselective methohexital challenge prior to intracranial endovascular embolization. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bican, O., Cho, C., Suarez-Roman, A., Nguyen, V., Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019

  Abstract

  Pharmacologic provocative testing (PT) and intraoperative neurophysiologic monitoring (IONM) both mitigate and predict risks associated with endovascular embolization procedures. We present a series of patients undergoing endovascular intracranial embolization predominantly for AVMs both under general anesthesia and awake with the use of IONM. We reviewed our database to identify all patients undergoing endovascular procedures between January 1, 2014 and January 1, 2016. Awake patients were tested with SSEP, EEG and real time neurologic examination while TcMEPs were performed in all anesthetized patients. BAEPs were performed in anesthetized patients if indicated. Methohexital was administered as an injection at a dose of 5?mg or 10?mg and repeat testing was performed if needed.Sixty-three endovascular procedures that met criteria were performed in 32 patients. 54 procedures in 28 patients were performed under general anesthesia, 9 procedures in 4 patients were performed in wakefulness. PT was negative in 61 procedures and subsequently completed embolizations without neurological sequelae. In two cases, the testing was positive and the procedure was terminated without embolization in one patient. The other patient underwent embolization at an alternative site without repeat PT. There were no new postoperative neurologic deficits after any of these procedures. Specificity of PT was 100% as none of the patients with a negative provocative test developed a new postoperative neurologic deficit after embolization. To our knowledge, this is the first review of PT with the use of neurophysiologic IONM techniques under general anesthesia. These data suggest a high specificity comparable to awake testing.

  View details for PubMedID 30772199

• Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3. Stroke Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023392

  Abstract

  Background and Purpose- Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods- We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results- Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P=0.17, Tmax >6 seconds 98 versus 100 mL; P=0.48) yet experienced less infarct growth (15 versus 59 mL; P<0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P<0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P<0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions- About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30735466

• Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial. JAMA neurology Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019

  Abstract

  Importance: Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups.Objective: To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.Design, Setting, and Participants: Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.Interventions or Exposures: Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.Main Outcomes and Measures: The primary outcome was the distribution of 90-day modified Rankin Scale scores.Results: Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P=.05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P=.01; transfer OR, 2.6; 95% CI, 1.3-4.8; P=.009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.Conclusions and Relevance: In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

  View details for PubMedID 30734042

• Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3. Stroke Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023177

  Abstract

  Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30727840

• Results From DEFUSE 3. Stroke de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M. G., Leslie-Mazwi, T., Christensen, S., McTaggart, R. A., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J. J., DEFUSE 3 Investigators 2019: STROKEAHA118023407

  Abstract

  Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin scale score of ?2). Additional outcomes include the full range of the modified Rankin scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30726184

• Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups: Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial. JAMA neurology Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Gutierrez, S. O., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., DEFUSE 3 Investigators 2019

  Abstract

  Importance: The DEFUSE 3 randomized clinical trial previously demonstrated benefit of endovascular thrombectomy for acute ischemic stroke in the 6- to 16-hour time window. For treatment recommendations, it is important to know if the treatment benefit was universal.Objective: To determine the outcomes among patients who may have a reduced effect of thrombectomy, including those who are older, have milder symptoms, or present late.Design, Setting, and Participants: DEFUSE 3 was a randomized, open-label, blinded end point trial conducted from May 2016 to May 2017. This multicenter study included 38 sites in the United States. Of 296 patients who were enrolled in DEFUSE 3, 182 patients met all inclusion criteria and were randomized and included in the intention-to-treat analysis, which was conducted in August 2017. These patients had acute ischemic strokes due to an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion computed tomography or magnetic resonance imaging. The study was stopped early for efficacy.Interventions: Endovascular thrombectomy plus medical management vs medical management alone.Main Outcomes and Measures: Functional outcome at day 90, assessed on the modified Rankin Scale. Multivariate ordinal logistic regression was used to calculate the adjusted proportional association between endovascular treatment and clinical outcome (shift in the distribution of modified Rankin Scale scores expressed as a common odds ratio) among patients of different ages, baseline stroke severities, onset-to-treatment times, locations of the arterial occlusion, and imaging modalities used to document the presence of salvageable tissue (computed tomography vs magnetic resonance imaging).Results: This study included 182 patients (median [interquartile range] age, 70 [59-80] years; median [interquartile range] National Institutes of Health Stroke Scale score, 16 [11-21], and 92 women [51%]). In the overall cohort, independent predictors of better functional outcome were younger age, lower baseline National Institutes of Health Stroke Scale score, and lower serum glucose level. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1 (95% CI, 1.8-5.4). There was no significant interaction between this treatment effect and age (P=.93), National Institutes of Health Stroke Scale score (P=.87), time to randomization (P=.56), imaging modality (P=.49), or location of the arterial occlusion (P=.54).Conclusions and Relevance: Endovascular thrombectomy, initiated up to 16 hours after last known well time in patients with salvageable tissue on perfusion imaging, benefits patients with a broad range of clinical features. Owing to the small sample size of this study, a pooled analysis of late time window endovascular stroke trials is needed to confirm these results.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

  View details for PubMedID 30688974

• Thrombectomy for acute ischemic stroke in nonagenarians compared with octogenarians. Journal of neurointerventional surgery Sussman, E. S., Martin, B., Mlynash, M., Marks, M. P., Marcellus, D., Albers, G., Lansberg, M., Dodd, R., Do, H. M., Heit, J. J. 2019

  Abstract

  Multiple randomized trials have shown that endovascular thrombectomy (EVT) leads to improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Elderly patients were poorly represented in these trials, and the efficacy of EVT in nonagenarian patients remains uncertain.We performed a retrospective cohort study at a single center. Inclusion criteria were: age 80-99, LVO, core infarct <70?mL, and salvageable penumbra. Patients were stratified into octogenarian (80-89) and nonagenarian (90-99) cohorts. The primary outcome was the ordinal score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included dichotomized functional outcome (mRS ?2?vs mRS ?3), successful revascularization, symptomatic intracranial hemorrhage (ICH), and mortality.108 patients met the inclusion criteria, including 79 octogenarians (73%) and 29 nonagenarians (27%). Nonagenarians were more likely to be female (86% vs 58%; p<0.01); there were no other differences between groups in terms of demographics, medical comorbidities, or treatment characteristics. Successful revascularization (TICI 2b-3) was achieved in 79% in both cohorts. Median mRS at 90 days was 5 in octogenarians and 6 in nonagenarians (p=0.09). Functional independence (mRS ?2) at 90 days was achieved in 12.5% and 19.7% of nonagenarians and octogenarians, respectively (p=0.54). Symptomatic ICH occurred in 21.4% and 6.4% (p=0.03), and 90-day mortality rate was 63% and 40.9% (p=0.07) in nonagenarians and octogenarians, respectively.Nonagenarians may be at higher risk of symptomatic ICH than octogenarians, despite similar stroke- and treatment-related factors. While there was a trend towards higher mortality and worse functional outcomes in nonagenarians, the difference was not statistically significant in this relatively small retrospective study.

  View details for DOI 10.1136/neurintsurg-2019-015147

  View details for PubMedID 31350369

• Arterial-Spin Labeling MRI Identifies Residual Cerebral Arteriovenous Malformation Following Stereotactic Radiosurgery Treatment. Journal of neuroradiology. Journal de neuroradiologie Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2019

  Abstract

  Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow?-?up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k?=?0.92; 95% CI: 0.8-1.0; p?

  View details for PubMedID 30658138

• Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience. Journal of neurointerventional surgery Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019

  Abstract

  The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.We performed a retrospective cohort study of patients aged <18 years presenting within 24?hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test.Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4?s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

  View details for PubMedID 31097548

• Arterial Spin-Labeling MRI Identifies Hypervascular Meningiomas. AJR. American journal of roentgenology Mayercik, V., Ma, M., Holdsworth, S., Heit, J., Iv, M. 2019: 1?5

  Abstract

  OBJECTIVE. Preoperative identification of hypervascular meningiomas can potentially detect those that may benefit from presurgical embolization, which may help to minimize intraoperative blood loss. In this study, we investigate if increased blood flow within meningiomas seen on arterial spin-labeling (ASL) MRI correlates with increased tumor vascularity seen on digital subtraction angiography (DSA). MATERIALS AND METHODS. A retrospective study was performed of 39 meningiomas in 34 patients who underwent ASL MRI and DSA between January 2008 and January 2017. Two raters independently calculated normalized tumor blood flow (TBF) on postprocessed ASL images using ROI analysis. They also recorded the presence or absence of tumor blush on DSA in each case. Interrater agreement was assessed with intraclass correlation coefficient (ICC). Performance of ASL MRI to identify tumor blush was determined with area under the ROC curve (AUC). RESULTS. In 27 female and seven male patients (mean age, 62.8 years), mean normalized TBF for meningiomas with tumor blush on DSA was significantly higher than those without tumor blush (p < 0.001). Mean normalized TBF for the group with tumor blush and the group without tumor blush group was 4.7 ± 1.1 and 1.5 ± 1.1, respectively, for rater 1 and 4.9 ± 5.3 and 1.5 ± 1.1, respectively, for rater 2. ICC was excellent (0.91). AUC for using normalized TBF to identify tumor vascularity on DSA was 0.82 (95% CI, 0.72-0.91), and a normalized TBF cut point of 2.7 yielded 88% sensitivity and 67% specificity. CONCLUSION. ASL MRI shows potential as a noninvasive screening tool for identifying hypervascular meningiomas.

  View details for DOI 10.2214/AJR.18.21026

  View details for PubMedID 31361532

• Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? JOURNAL OF NEUROINTERVENTIONAL SURGERY Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018; 10 (12): 1132-+

  View details for DOI 10.1136/neurintsurg-2018-013784

  View details for Web of Science ID 000452800300012

• Advanced Neuroimaging of Acute Ischemic Stroke: Penumbra and Collateral Assessment. Neuroimaging clinics of North America Heit, J. J., Zaharchuk, G., Wintermark, M. 2018; 28 (4): 585?97

  Abstract

  Acute ischemic stroke (AIS) occurs when there is a sudden loss in cerebral blood flow due to embolic or thromboembolic occlusion of a cerebral or cervical artery. Patients with AIS require emergent neuroimaging to guide treatment, which includes intravenous thrombolysis and endovascular mechanical thrombectomy (EMT). Recent advances in AIS treatment by EMT has been driven in part by advances in computed tomography (CT) and MR imaging neuroimaging evaluation of ischemic penumbra and pial collateral vessels. The authors review advanced noninvasive brain imaging by CT and MR imaging for the evaluation of AIS focusing on penumbral and collateral imaging.

  View details for DOI 10.1016/j.nic.2018.06.004

  View details for PubMedID 30322595

• Hypoperfusion ratio predicts infarct growth during transfer for thrombectomy ANNALS OF NEUROLOGY Guenego, A., Mlynash, M., Christensen, S., Kemp, S., Heit, J. J., Lansberg, M. G., Albers, G. W. 2018; 84 (4): 616?20

  View details for DOI 10.1002/ana.25320

  View details for Web of Science ID 000447367000015

• New developments in clinical ischemic stroke prevention and treatment and their imaging implications JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Heit, J. J., Wintermark, M. 2018; 38 (9): 1533?50

  View details for DOI 10.1177/0271678X17694046

  View details for Web of Science ID 000443291300010

• Consensus statement on current and emerging methods for the diagnosis and evaluation of cerebrovascular disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Donahue, M. J., Achten, E., Cogswell, P. M., De Leeuw, F., Derdeyn, C. P., Dijkhuizen, R. M., Fan, A. P., Ghaznawi, R., Heit, J. J., Ikram, M., Jezzard, P., Jordan, L. C., Jouvent, E., Knutsson, L., Leigh, R., Liebeskind, D. S., Lin, W., Okell, T. W., Qureshi, A. I., Stagg, C. J., van Osch, M. P., van Zijl, P. M., Watchmaker, J. M., Wintermark, M., Wu, O., Zaharchuk, G., Zhou, J., Hendrikse, J. 2018; 38 (9): 1391?1417

  Abstract

  Cerebrovascular disease (CVD) remains a leading cause of death and the leading cause of adult disability in most developed countries. This work summarizes state-of-the-art, and possible future, diagnostic and evaluation approaches in multiple stages of CVD, including (i) visualization of sub-clinical disease processes, (ii) acute stroke theranostics, and (iii) characterization of post-stroke recovery mechanisms. Underlying pathophysiology as it relates to large vessel steno-occlusive disease and the impact of this macrovascular disease on tissue-level viability, hemodynamics (cerebral blood flow, cerebral blood volume, and mean transit time), and metabolism (cerebral metabolic rate of oxygen consumption and pH) are also discussed in the context of emerging neuroimaging protocols with sensitivity to these factors. The overall purpose is to highlight advancements in stroke care and diagnostics and to provide a general overview of emerging research topics that have potential for reducing morbidity in multiple areas of CVD.

  View details for PubMedID 28816594

• Positive pharmacologic provocative testing with methohexital during cerebral arteriovenous malformation embolization CLINICAL IMAGING Bican, O., Cho, C., Lee, L., Viet Nguyen, Le, S., Heit, J., Lopez, J. 2018; 51: 155?59

  View details for DOI 10.1016/j.clinimag.2018.02.014

  View details for Web of Science ID 000445321000022

• Hypoperfusion Ratio predicts infarct growth during transfer for thrombectomy. Annals of neurology Guenego, A., Mlynash, M., Christensen, S., Kemp, S., Heit, J. J., Lansberg, M. G., Albers, G. W. 2018

  Abstract

  We hypothesized that automated assessment of collaterals on computed-tomography (CT) perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N=28) and assessed their collaterals based on the hypoperfusion intensity ratio (HIR) prior to transfer. Infarct growth rate was strongly correlated with HIR (r= 0.78, p<0.001). ROC analysis identified an HIR of ?0.5 as optimal for predicting infarct growth. Patients with HIR ? 0.5 had a median infarct growth rate of 10.1 mL/h (IQR: 6.4-18.4) compared with 0.9 mL/h (IQR: 0-2.8), p< 0.001) in patients with a HIR < 0.5. Patients with an HIR above ? 0.5 had an 83% probability of significant core growth, whereas patients with HIR <0.5 had an 88% probability of core stability. These preliminary data have the potential to guide decision making regarding whether repeat brain imaging should be performed after transfer to a comprehensive stroke center. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30168180

• Endovascular Treatment in the DEFUSE 3 Study. Stroke Marks, M. P., Heit, J. J., Lansberg, M. G., Kemp, S., Christensen, S., Derdeyn, C. P., Rasmussen, P. A., Zaidat, O. O., Broderick, J. P., Yeatts, S. D., Hamilton, S., Mlynash, M., Albers, G. W. 2018

  Abstract

  BACKGROUND AND PURPOSE: Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).METHODS: Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0-2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging.RESULTS: TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17-6.56; P=0.019. Good functional outcome (90-day modified Rankin Scale score of 0-2) increased with better TICI scores (P=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients (P=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A (P=0.0015) and TICI 2B (P=0.0002) patients.CONCLUSIONS: Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.118.022147

  View details for PubMedID 29986935

• Early Cerebral Vein After Endovascular Ischemic Stroke Treatment Predicts Symptomatic Reperfusion Hemorrhage STROKE Cartmell, S. D., Ball, R. L., Kaimal, R., Telischak, N. A., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018; 49 (7): 1741?46

  View details for DOI 10.1161/STROKEAHA.118.021402

  View details for Web of Science ID 000436125600035

• Positive pharmacologic provocative testing with methohexital during cerebral arteriovenous malformation embolization. Clinical imaging Bican, O., Cho, C., Lee, L., Nguyen, V., Le, S., Heit, J., Lopez, J. 2018; 51: 155?59

  Abstract

  A middle-aged patient underwent staged endovascular embolization of a Spetzler-Martin grade V right parietal arteriovenous malformation(AVM).In the fifth endovascular embolization, after methohexital 10?mg injection into a right posterior choroidal artery feeding the AVM nidus, there was an immediate change in the electroencephalogram (EEG) with simultaneous loss of motor evoked potentials (MEPs) in the bilateral upper and lower extremities and a delayed change in somatosensory evoked potential responses (SSEPs). No embolization was made and procedure was terminated. This case demonstrates the utility of intraoperative neurophysiologic monitoring (IONM) with pharmacologic provocative testing in predicting and mitigating the risks prior to the proposed embolization.

  View details for PubMedID 29501883

• Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine Albers, G. W., Marks, M. P., Kemp, S., Christensen, S., Tsai, J. P., Ortega-Gutierrez, S., McTaggart, R. A., Torbey, M. T., Kim-Tenser, M., Leslie-Mazwi, T., Sarraj, A., Kasner, S. E., Ansari, S. A., Yeatts, S. D., Hamilton, S., Mlynash, M., Heit, J. J., Zaharchuk, G., Kim, S., Carrozzella, J., Palesch, Y. Y., Demchuk, A. M., Bammer, R., Lavori, P. W., Broderick, J. P., Lansberg, M. G. 2018; 378 (8): 708?18

  Abstract

  Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms.We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

  View details for PubMedID 29364767

• Neuro-Interventional Management of Acute Ischemic Stroke. Neuroimaging clinics of North America Hacein-Bey, L., Heit, J. J., Konstas, A. A. 2018; 28 (4): 625?38

  Abstract

  Restoration of cerebral blood flow is the most important step in preventing irreversible damage to hypoperfused brain cells after ischemic stroke from large-vessel occlusion. For those patients who do not respond to (or are not eligible for) intravenous thrombolysis, endovascular therapy has become standard of care. A shift is currently taking place from rigid time windows for intervention (time is brain) to physiology-driven paradigms that rely heavily on neuroimaging. At this time, one can reasonably anticipate that more patients will be treated, and that outcomes will keep improving. This article discusses in detail recent advances in endovascular stroke therapy.

  View details for DOI 10.1016/j.nic.2018.06.011

  View details for PubMedID 30322598

• Early Cerebral Vein After Endovascular Ischemic Stroke Treatment Predicts Symptomatic Reperfusion Hemorrhage. Stroke Cartmell, S. C., Ball, R. L., Kaimal, R., Telischak, N. A., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

  Abstract

  Parenchymal hemorrhage (PH) after endovascular mechanical thrombectomy in acute ischemic stroke leads to worse outcomes. Better clinical and imaging biomarkers of symptomatic reperfusion PH are needed to identify patients at risk. We identified clinical and imaging predictors of reperfusion PH after endovascular mechanical thrombectomy with attention to early cerebral veins (ECVs) on postreperfusion digital subtraction angiography.We performed a retrospective cohort study of consecutive acute ischemic stroke patients undergoing endovascular mechanical thrombectomy at our neurovascular referral center. Clinical and imaging characteristics were collected from patient health records, and random forest variable importance measures were used to identify predictors of symptomatic PH. Predictors of secondary outcomes, including 90-day mortality, functional dependence (modified Rankin Scale score, >2), and National Institutes of Health Stroke Scale shift, were also determined. Diagnostic test characteristics of ECV for symptomatic PH were determined using a receiver operating characteristic analysis. Differences between patients with and without symptomatic PH were assessed with Fisher exact test and the Wilcoxon rank sum (Mann-Whitney U test) test at the 0.05 significance level.Of 64 patients with anterior circulation large-vessel occlusion identified, 6 (9.4%) developed symptomatic PH. ECV was the strongest predictor of symptomatic PH with more than twice the importance of the next best predictor, male sex. Although ECV was also predictive of 90-day mortality and functional dependence, other characteristics were more important than ECV for these outcomes. The sensitivity and specificity of ECV alone for subsequent hemorrhage were both 0.83, with an area under the curve of 0.83 and 95% confidence interval of 0.66 to 1.00.ECV on postendovascular mechanical thrombectomy digital subtraction angiography is highly diagnostic of subsequent symptomatic reperfusion hemorrhage in this data set. This finding has important implications for post-treatment management of blood pressure and anticoagulation.

  View details for PubMedID 29739912

• Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

  Abstract

  Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (?=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; ?=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; ?=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

  View details for PubMedID 29555872

• Dual-Energy Computed Tomography Applications in Neurointervention. Journal of computer assisted tomography Wolman, D. N., Patel, B. P., Wintermark, M., Heit, J. J. 2018

  Abstract

  Dual-energy computed tomography (CT) combines the high spatial resolution of standard CT with the ability to improve contrast resolution, reduce artifact, and separate materials of different atomic weights and energy-based attenuation through postprocessing. We review the underlying physical principles and applications of dual-energy CT within the context of patients undergoing preprocedural and postprocedural evaluation for neurointerventional therapies. The broad imaging categories of cerebral ischemia and hemorrhage, head and neck angiography, and the spine are reviewed.

  View details for PubMedID 30052616

• Sofia intermediate catheter and the SNAKE technique: safety and efficacy of the Sofia catheter without guidewire or microcatheter construct. Journal of neurointerventional surgery Heit, J. J., Wong, J. H., Mofaff, A. M., Telischak, N. A., Dodd, R. L., Marks, M. P., Do, H. M. 2018; 10 (4): 401?6

  Abstract

  Neurointerventional surgeries (NIS) benefit from supportive endovascular constructs. Sofia is a soft-tipped, flexible, braided single lumen intermediate catheter designed for NIS. Sofia advancement from the cervical to the intracranial circulation without a luminal guidewire or microcatheter construct has not been described.To evaluate the efficacy and safety of the new Sofia Non-wire Advancement techniKE (SNAKE) for advancement of the Sofia into the cerebral circulation.Consecutive patients who underwent NIS using Sofia were identified. Patient information, SNAKE use, and patient outcome were determined from electronic medical records. Sofia advancement to the cavernous internal carotid artery or the V2/V3 segment junction of the vertebral artery was the primary outcome measure. Secondary outcomes included arterial vasospasm and arterial dissection.263 Patients (181 females, 69%) who underwent a total of 305 NIS using Sofia were identified. SNAKE (SNAKE+) was used in 187 procedures (61%). Two hundred and ninety-three procedures (96%) were technically successful, which included 184 SNAKE+ NIS and 109 SNAKE- NIS. Primary outcome was achieved in all SNAKE+ procedures, but not in five SNAKE- procedures (2%). No arterial dissections were identified among 305 interventions. In the intracranial circulation, a single SNAKE+ patient (0.5%) had non-flow limiting arterial vasospasm involving the petrous internal carotid. Three SNAKE+ patients (1.6%) and one SNAKE- patient (0.8%) demonstrated external carotid artery branch artery vasospasm during dural arteriovenous fistula or facial arteriovenous malformation treatment.SNAKE is a safe and effective technique for Sofia advancement. Sofia is a highly effective and safe intermediate catheter for a variety of NIS.

  View details for PubMedID 28768818

• Current Clinical State of Advanced Magnetic Resonance Imaging for Brain Tumor Diagnosis and Follow Up. Seminars in roentgenology Iv, M., Yoon, B. C., Heit, J. J., Fischbein, N., Wintermark, M. 2018; 53 (1): 45?61

  View details for PubMedID 29405955

• Wingspan stent delivery catheter fracture and the TRAP technique for endovascular salvage. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Jagani, M., Do, H. M., Heit, J. J. 2018; 24 (1): 106?10

  Abstract

  Background Intracranial atherosclerotic disease may result in ischemic infarction and has a high rate of recurrent ischemic strokes despite medical therapy. Patients who fail medical therapy may undergo endovascular treatment with cerebral artery angioplasty and possible Wingspan stent placement. We present a unique case of Wingspan delivery microcatheter fracture that resulted in a retained foreign body and an endovascular salvage maneuver. Case description An elderly patient presented with an acute ischemic stroke due to a severe stenosis in the proximal left middle cerebral artery (MCA). The patient failed non-invasive medical treatment and underwent endovascular treatment with angioplasty and Wingspan stent placement. Following Wingspan stent deployment, the stent delivery catheter fractured, and the retained catheter fragment resulted in MCA occlusion. The foreign body was retrieved by balloon catheter inflation within an intermediate catheter adjacent to the proximal end of the fractured catheter and removal of the entire construct (TRAP technique). Conclusions Wingspan delivery microcatheter fracture is a rare event. The TRAP technique may be used for successful retrieval of a retained foreign body.

  View details for PubMedID 29125024

• Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M., Martin, B. W., Zhu, G., Marks, M. P., Zaharchuk, G., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. 2018

  Abstract

  Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09±0.03 versus 0.13±0.01;P=0.03), reduced diffusion coefficientD(0.82±0.05 versus 0.92±0.07×10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18±0.40 versus 1.83±0.40×10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011±0.002) and DCI+ (0.013±0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

  View details for DOI 10.1161/STROKEAHA.117.020395

  View details for PubMedID 29439196

• Reply . AJNR. American journal of neuroradiology Heit, J. J. 2018

  View details for DOI 10.3174/ajnr.A5584

  View details for PubMedID 29449284

• Ischemic Stroke Treatment Trials: Neuroimaging Advancements and Implications. Topics in magnetic resonance imaging Patel, V. P., Heit, J. J. 2017; 26 (3): 133-139

  Abstract

  There have been significant advancements in the treatment of acute ischemic stroke in the last 2 decades. Recent trials have placed a significant emphasis on minimizing the time from symptom onset to stroke treatment by reperfusion therapies, which decreases the cerebral infarct volume and improves clinical outcomes. These clinical advances have paralleled and been aided by advances in neuroimaging. However, controversy remains regarding how much time should be spent on neuroimaging evaluation versus expediting patient treatment. In this review article, we examine the key endovascular stroke trials published in the past 25 years, and we briefly highlight the failures and successes of endovascular stroke trials performed in the past 4 years. We also discuss the advantages and disadvantages of using time from symptom onset versus neuroimaging in determining endovascular stroke therapy candidacy.

  View details for DOI 10.1097/RMR.0000000000000118

  View details for PubMedID 28277455

• Fluoroscopic C-Arm and CT-Guided Selective Radiofrequency Ablation for Trigeminal and Glossopharyngeal Facial Pain Syndromes. Pain medicine (Malden, Mass.) Telischak, N. A., Heit, J. J., Campos, L. W., Choudhri, O. A., Do, H. M., Qian, X. 2017

  Abstract

  ?Percutaneous radiofrequency ablation (RFA) of the gasserian ganglion through the foramen ovale and the glossopharyngeal nerve at the jugular foramen is a classical approach to treating trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN), respectively. However, it can be technically challenging with serious complications. We have thus developed a novel technique utilizing C-arm and computerized tomography (CT) guidance to block TN and GPN. Our goals were to describe a three-dimensional image-based technique to improve patient comfort and to decrease procedural time associated with needle guidance.Consecutive procedures were reviewed.?Academic hospital.Three patients with classical TN and GPN and 15 patients with atypical facial pain (AFP) were treated. Numeric rating scale (NRS) scores for pain at pretreatment and at one, three, and 12?months post-treatment were recorded. The primary clinical outcome (50% or more reduction in NRS) and secondary adverse clinical outcome (hematoma, facial numbness, etc.) were monitored.?We had a 100% technical success with respect to appropriate needle positioning. All three classical TN/GPN patients had both immediate and sustained pain relief. Complications were minimal. The 15 AFP patients, however, showed more variable results, with only five (33%) having sustained pain relief, while in the other 10 (67%) patients, we observed suboptimal response.?We present a novel method and single-center experience with C-arm and CT-guided RFA of facial pain. Quick and accurate needle placement will help future advancements in the RFA algorithm so that more durable and consistent effects can be attained, reducing uncertainty with respect to needle placement as a confounder. The RFA procedure in our study had a satisfying effect for classical TN/GPN patients but was less successful for AFP patients, though it did mirror the results from previous studies.This study is limited by its small sample size and nonrandomized design.

  View details for DOI 10.1093/pm/pnx088

  View details for PubMedID 28472393

• Resting-State BOLD MRI for Perfusion and Ischemia. Topics in magnetic resonance imaging Kroll, H., Zaharchuk, G., Christen, T., Heit, J. J., Iv, M. 2017; 26 (2): 91-96

  Abstract

  Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

  View details for DOI 10.1097/RMR.0000000000000119

  View details for PubMedID 28277456

• Advanced MRI Measures of Cerebral Perfusion and Their Clinical Applications. Topics in magnetic resonance imaging Lanzman, B., Heit, J. J. 2017; 26 (2): 83-90

  Abstract

  Cerebral blood flow measurement by magnetic resonance imaging perfusion (MRP) techniques is broadly applied to patients with acute ischemic stroke, vasospasm following aneurysmal subarachnoid hemorrhage, chronic arterial steno-occlusive disease, cervical atherosclerotic disease, and primary brain neoplasms. MRP may be performed using an exogenous tracer, most commonly gadolinium-based intravenous contrast, or an endogenous tracer, such as arterial spin labeling (ASL) or intravoxel incoherent motion (IVIM). Here, we review the technical basis of commonly performed MRP techniques, the interpretation of MRP imaging maps, and how MRP provides valuable clinical information in the triage of patients with cerebral disease.

  View details for DOI 10.1097/RMR.0000000000000120

  View details for PubMedID 28277457

• Guest Editorial. Topics in magnetic resonance imaging Heit, J. J. 2017; 26 (2): 55-?

  View details for DOI 10.1097/RMR.0000000000000121

  View details for PubMedID 28375950

• Real-Time Fluoroscopic and C-Arm Computed Tomography Evaluation of Ommaya Reservoir Integrity. Cureus Moraff, A. M., Hayden Gephart, M., Shuer, L. M., Heit, J. J. 2017; 9 (3)

  Abstract

  We describe a case of a 24-year-old patient with relapsed acute myelogenous leukemia involving the central nervous system. After placement of an Ommaya reservoir for intrathecal chemotherapy administration, the patient developed progressive headache, nausea, and drowsiness and was found to have an enlarging subdural collection underlying the Ommaya. To exclude leakage of the Ommaya system into the subdural space, real-time fluoroscopic and C-arm computed tomographic evaluation of the Ommaya reservoir was performed after iodinated contrast injection into the reservoir. This novel technique demonstrated complete integrity of the Ommaya reservoir without evidence of blockage or leakage of the system. The patient underwent uncomplicated evacuation of the subdural collection without replacement of the Ommaya reservoir and made an excellent recovery. This technique for real-time interrogation of the Ommaya reservoir may have additional utility in the evaluation for Ommaya reservoir dysfunction.

  View details for DOI 10.7759/cureus.1097

  View details for PubMedID 28413743

• Contemporary Imaging of Cerebral Arteriovenous Malformations. AJR. American journal of roentgenology Tranvinh, E., Heit, J. J., Hacein-Bey, L., Provenzale, J., Wintermark, M. 2017: 1-11

  Abstract

  Brain arteriovenous malformation (AVM) rupture results in substantial morbidity and mortality. The goal of AVM treatment is eradication of the AVM, but the risk of treatment must be weighed against the risk of future hemorrhage.Imaging plays a vital role by providing the information necessary for AVM management. Here, we discuss the background, natural history, clinical presentation, and imaging of AVMs. In addition, we explain advances in techniques for imaging AVMs.

  View details for DOI 10.2214/AJR.16.17306

  View details for PubMedID 28267351

• Real-Time Fluoroscopic and C-Arm Computed Tomography Evaluation of Ommaya Reservoir Integrity CUREUS Moraff, A. M., Gephart, M., Shuer, L. M., Heit, J. J. 2017; 9 (3)

  View details for DOI 10.7759/cureus.1097

  View details for Web of Science ID 000453620000035

• Imaging of Intracranial Hemorrhage. Journal of stroke Heit, J. J., Iv, M., Wintermark, M. 2017; 19 (1): 11-27

  Abstract

  Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage.

  View details for DOI 10.5853/jos.2016.00563

  View details for PubMedID 28030895

• Pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Heit, J. J., Telischak, N. A., Do, H. M., Dodd, R. L., Steinberg, G. K., Marks, M. P. 2017; 23 (6): 614?19

  Abstract

  Background Subarachnoid hemorrhage (SAH) secondary to rupture of a blister aneurysm (BA) results in high morbidity and mortality. Endovascular treatment with the pipeline embolization device (PED) has been described as a new treatment strategy for these lesions. We present the first reported case of PED retraction and foreshortening after treatment of a ruptured internal carotid artery (ICA) BA. Case description A middle-aged patient presented with SAH secondary to ICA BA rupture. The patient was treated with telescoping PED placement across the BA. After 5 days from treatment, the patient developed a new SAH due to re-rupture of the BA. Digital subtraction angiography revealed an increase in caliber of the supraclinoid ICA with associated retraction and foreshortening of the PED that resulted in aneurysm uncovering and growth. Conclusions PED should be oversized during ruptured BA treatment to prevent device retraction and aneurysm regrowth. Frequent imaging follow up after BA treatment with PED is warranted to ensure aneurysm occlusion.

  View details for PubMedID 28758549

• Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies. Journal of neuroimaging : official journal of the American Society of Neuroimaging Zhang, M., Telischak, N. A., Fischbein, N. J., Steinberg, G. K., Marks, M., Zaharchuk, G., Heit, J. J., Iv, M. 2017

  Abstract

  Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (? = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.

  View details for PubMedID 29205641

• Introduction. Topics in magnetic resonance imaging : TMRI Heit, J. J. 2017

  View details for DOI 10.1097/RMR.0000000000000121

  View details for PubMedID 28277458

• New developments in clinical ischemic stroke prevention and treatment and their imaging implications. Journal of cerebral blood flow and metabolism Heit, J. J., Wintermark, M. 2017: 271678X17694046-?

  Abstract

  Acute ischemic stroke results from blockage of a cerebral artery or impaired cerebral blood flow due to cervical or intracranial arterial stenosis. Ischemic stroke prevention seeks to minimize the risk of developing impaired cerebral perfusion by controlling vascular and cardiac disease risk factors. Similarly, ischemic stroke treatment aims to restore cerebral blood flow through recanalization of an occluded artery or dilation of a severely narrowed artery that supplies cerebral tissue. Stroke prevention and treatment are increasingly informed by imaging studies, and neurovascular and cerebral perfusion imaging has become essential in in guiding ischemic stroke prevention and treatment. Here we review the latest advances in ischemic stroke prevention and treatment with an emphasis on the neuroimaging principles emphasized in recent randomized trials. Future research directions that should be explored in ischemic stroke prevention and treatment are also discussed.

  View details for DOI 10.1177/0271678X17694046

  View details for PubMedID 28195500

• Percutaneous use of a dual lumen Scepter XC balloon for embolization of a complex facial arteriovenous malformation: a technical report CLINICAL NEURORADIOLOGY Heit, J., Connolly, I., Choudhri, O. 2016; 26 (4): 485-491

  View details for DOI 10.1007/s00062-016-0515-2

  View details for PubMedID 27142059

• Detection and characterization of intracranial aneurysms: a 10-year multidetector CT angiography experience in a large center. Journal of neurointerventional surgery Heit, J. J., Gonzalez, R. G., Sabbag, D., Brouwers, H. B., Ordonez Rubiano, E. G., Schaefer, P. W., Hirsch, J. A., Romero, J. M. 2016; 8 (11): 1168-1172

  Abstract

  CT angiography (CTA) is increasingly used for the detection, characterization, and follow-up of intracranial aneurysms. A lower threshold to request a CT angiogram may render a patient population that differs from previous studies primarily evaluated with conventional angiography. Our objective was to broaden our knowledge of the factors associated with aneurysm rupture and patient mortality in this population.All CTA studies performed over a 10-year period at a large neurovascular referral center were reviewed for the presence of an intracranial aneurysm. Patient demographics, mortality, CTA indication, aneurysm location, size, and rupture status were recorded.2927 patients with aneurysms were identified among 29?003 CTAs. 17% of the aneurysms were ruptured at the time of imaging, 24% of aneurysms were incidentally identified, and multiple aneurysms were identified in 34% of patients. Aneurysms most commonly arose from the supraclinoid internal carotid artery (22%), the middle cerebral artery (18%), and the anterior communicating artery (13%). Male sex, age <50?years, aneurysms >6?mm, and aneurysms arising from the anterior communicating artery, posterior communicating artery, or the posterior circulation were independent predictors of aneurysm rupture. Independent mortality predictors included male sex, posterior circulation aneurysms, intraventricular hemorrhage, and intraparenchymal hemorrhage.These results indicate that aneurysms detected on CTA that arise from the anterior communicating artery, posterior communicating artery, or the posterior circulation, measure >6?mm in size, occur in men, and in patients aged <50?years are associated with rupture.

  View details for DOI 10.1136/neurintsurg-2015-012082

  View details for PubMedID 26553878

• Detection and characterization of intracranial aneurysms: a 10-year multidetector CT angiography experience in a large center JOURNAL OF NEUROINTERVENTIONAL SURGERY Heit, J. J., Gonzalez, R. G., Sabbag, D., Brouwers, H. B., Rubiano, E. G., Schaefer, P. W., Hirsch, J. A., Romero, J. M. 2016; 8 (11): 1168-1172

  Abstract

  CT angiography (CTA) is increasingly used for the detection, characterization, and follow-up of intracranial aneurysms. A lower threshold to request a CT angiogram may render a patient population that differs from previous studies primarily evaluated with conventional angiography. Our objective was to broaden our knowledge of the factors associated with aneurysm rupture and patient mortality in this population.All CTA studies performed over a 10-year period at a large neurovascular referral center were reviewed for the presence of an intracranial aneurysm. Patient demographics, mortality, CTA indication, aneurysm location, size, and rupture status were recorded.2927 patients with aneurysms were identified among 29?003 CTAs. 17% of the aneurysms were ruptured at the time of imaging, 24% of aneurysms were incidentally identified, and multiple aneurysms were identified in 34% of patients. Aneurysms most commonly arose from the supraclinoid internal carotid artery (22%), the middle cerebral artery (18%), and the anterior communicating artery (13%). Male sex, age <50?years, aneurysms >6?mm, and aneurysms arising from the anterior communicating artery, posterior communicating artery, or the posterior circulation were independent predictors of aneurysm rupture. Independent mortality predictors included male sex, posterior circulation aneurysms, intraventricular hemorrhage, and intraparenchymal hemorrhage.These results indicate that aneurysms detected on CTA that arise from the anterior communicating artery, posterior communicating artery, or the posterior circulation, measure >6?mm in size, occur in men, and in patients aged <50?years are associated with rupture.

  View details for DOI 10.1136/neurintsurg-2015-012082

  View details for Web of Science ID 000386746200016

• Headway Duo microcatheter for cerebral arteriovenous malformation embolization with n-BCA. Journal of neurointerventional surgery Heit, J. J., Faisal, A. G., Telischak, N. A., Choudhri, O., Do, H. M. 2016; 8 (11): 1181-1185

  Abstract

  Cerebral arteriovenous malformations (AVMs) are uncommon vascular lesions, and hemorrhage secondary to AVM rupture results in significant morbidity and mortality. AVMs may be treated by endovascular embolization, and technical advances in microcatheter design are likely to improve the success and safety of endovascular embolization of cerebral AVMs.To describe our early experience with the Headway Duo microcatheter for embolization of cerebral AVMs with n-butyl-cyanoacrylate (n-BCA).Consecutive patients treated by endovascular embolization of a cerebral AVM with n-BCA delivered intra-arterially through the Headway Duo microcatheter (167?cm length) were identified. Patient demographic information, procedural details, and patient outcome were determined from electronic medical records.Ten consecutive patients undergoing cerebral AVM embolization using n-BCA injected through the Headway Duo microcatheter were identified. Presenting symptoms included headache, hemorrhage, seizures, and weakness. Spetzler Martin grades ranged from 1 to 5, and AVMs were located in the basal ganglia (2 patients), parietal lobe (4 patients), frontal lobe (1 patient), temporal lobe (1 patient), an entire hemisphere (1 patient), and posterior fossa (1 patient). 50 arterial pedicles were embolized, and all procedures were technically successful. There was one post-procedural hemorrhage that was well tolerated by the patient, and no other complications occurred. Additional AVM treatment was performed by surgery and radiation therapy.The Headway Duo microcatheter is safe and effective for embolization of cerebral AVMs using n-BCA. The trackability and high burst pressure of the Headway Duo make it an important and useful tool for the neurointerventionalist during cerebral AVM embolization.

  View details for DOI 10.1136/neurintsurg-2015-012094

  View details for PubMedID 26603031

• Initial experience with SOFIA as an intermediate catheter in mechanical thrombectomy for acute ischemic stroke. Journal of neurointerventional surgery Wong, J. H., Do, H. M., Telischak, N. A., Moraff, A. M., Dodd, R. L., Marks, M. P., Ingle, S. M., Heit, J. J. 2016

  Abstract

  The benefits of mechanical thrombectomy for emergent large vessel occlusion (ELVO) have been established. Combined mechanical/aspiration (Solumbra) and a direct aspiration as a first pass technique (ADAPT) are valid procedures requiring an intermediate catheter for clot suction. Recently, SOFIA (Soft torqueable catheter Optimized For Intracranial Access) was developed as a single lumen flexible catheter with coil and braid reinforcement, but its suitability for mechanical thrombectomy had not been evaluated.To describe our initial experience with SOFIA in acute stroke intervention and evaluate its efficacy and safety.All patients with ELVO undergoing endovascular stroke intervention with SOFIA were identified. Demographic, presentation, treatment, and complication data were recorded. Primary outcome was Thrombolysis in Cerebral Infarction (TICI) 2b/3 revascularization rate and the number of passes required. Secondary outcomes included complication rates and discharge National Institute of Health Stroke Scale (NIHSS) score.33 patients with a mean age of 72?years were treated for ELVO with SOFIA and IV tissue plasminogen activator was administered in 67%. Vessel occlusion involved the internal carotid artery (15.2%), M1 (48.5%), and M2 (24.2%) segments, and posterior circulation (12.1%). Median presentation NIHSS score was 14 (IQR 11-19) and discharge NIHSS 4 (IQR 2-14). The Solumbra technique represented 94% of treatments and ADAPT 3%. The TICI 2b/3 revascularization rate was 94%, including 48.5% TICI 3 with an average of 1.6 passes. The symptomatic reperfusion hemorrhage rate was 6%. Procedural complications occurred in four patients, but were unrelated to SOFIA. Mortality was 21%, secondary to failed revascularization, hemorrhagic transformation, and baseline medical condition.Mechanical and aspiration thrombectomy with SOFIA is safe and effective with high revascularization rates. Its trackability, stability, and luminal size make SOFIA suitable for stroke intervention.

  View details for DOI 10.1136/neurintsurg-2016-012750

  View details for PubMedID 27789787

• Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm. Journal of neurointerventional surgery Khatibi, K., Heit, J. J., Telischak, N. A., Elbers, J. M., Do, H. M. 2016; 8 (8)

  Abstract

  A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  View details for DOI 10.1136/neurintsurg-2015-011753.rep

  View details for PubMedID 26122324

• Detection of Cortical Venous Drainage and Determination of the Borden Type of Dural Arteriovenous Fistula by Means of 3D Pseudocontinuous Arterial Spin-Labeling MRI AMERICAN JOURNAL OF ROENTGENOLOGY Amukotuwa, S. A., Heit, J. J., Marks, M. P., Fischbein, N., Bammer, R. 2016; 207 (1): 163-169

  Abstract

  The risk of intracranial dural arteriovenous fistula is linked to its pattern of venous drainage (Borden type), in particular the presence of cortical venous drainage. The purpose of this study was to assetss the accuracy of 3D pseudocontinuous arterial spin-labeling (ASL) MRI for noninvasive delineation of venous drainage.This retrospective study included 34 patients with a dural arteriovenous fistula who had undergone both digital subtraction angiography (DSA) and 3D pseudocontinuous ASL MRI. Two neuroradiologists blinded to the DSA results independently assessed ASL images for the presence of cortical vein hyperintensity (cortical venous drainage) and the distribution of venous hyperintensity (Borden type). DSA was used as the reference standard. The sensitivity and specificity of 3D pseudocontinuous ASL MRI for the detection of cortical venous drainage were determined. Intermodality and interobserver agreement for Borden type was determined by use of the weighted kappa statistic.Three-dimensional pseudocontinuous ASL MRI had high sensitivity (91%) and specificity (96%) for the detection of cortical venous drainage. Borden type was correctly identified with very good intermodality (weighted ? = 0.82) and interobserver (weighted ? = 0.85) agreement in 88% of patients.Three-dimensional pseudocontinuous ASL MRI is highly accurate for the detection of cortical venous drainage and determination of Borden type. With this technique, high-risk fistulas requiring treatment can be reliably differentiated from low-risk lesions. Although it cannot replace DSA, incorporating 3D pseudocontinuous ASL into an MRI protocol for assessment of dural arteriovenous fistula can facilitate treatment planning.

  View details for DOI 10.2214/AJR.15.15171

  View details for PubMedID 27082987

• Reply. AJNR. American journal of neuroradiology Heit, J. J., Rabinov, J. D. 2016; 37 (6): E54-?

  View details for DOI 10.3174/ajnr.A4802

  View details for PubMedID 27056429

• Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398

  Abstract

  The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

  View details for DOI 10.1161/STROKEAHA.115.012364

  View details for PubMedID 27073243

• Perfusion Computed Tomography for the Evaluation of Acute Ischemic Stroke Strengths and Pitfalls STROKE Heit, J. J., Wintermark, M. 2016; 47 (4): 1153-1158

  View details for DOI 10.1161/STROKEAHA.116.011873

  View details for Web of Science ID 000372853200040

• Cerebral Angiography for Evaluation of Patients with CT Angiogram-Negative Subarachnoid Hemorrhage: An 11-Year Experience AMERICAN JOURNAL OF NEURORADIOLOGY Heit, J. J., Pastena, G. T., Nogueira, R. G., Yoo, A. J., Leslie-Mazwi, T. M., Hirsch, J. A., Rabinov, J. D. 2016; 37 (2): 297-304

  View details for DOI 10.3174/ajnr.A4503

  View details for Web of Science ID 000369111200025

• Guidelines and parameters: percutaneous sclerotherapy for the treatment of head and neck venous and lymphatic malformations. Journal of neurointerventional surgery Heit, J. J., Do, H. M., Prestigiacomo, C. J., Delgado-Almandoz, J. A., English, J., Gandhi, C. D., Albequerque, F. C., Narayanan, S., Blackham, K. A., Abruzzo, T., Albani, B., Fraser, J. F., Heck, D. V., Hussain, M. S., Lee, S., Ansari, S. A., Hetts, S. W., Bulsara, K. R., Kelly, M., Arthur, A. S., Patsalides, A., Pride, G. L., Powers, C. J., Alexander, M. J., Meyers, P. M., Jayaraman, M. V. 2016

  View details for DOI 10.1136/neurintsurg-2015-012255

  View details for PubMedID 26801946

• Perfusion Computed Tomography for the Evaluation of Acute Ischemic Stroke: Strengths and Pitfalls. Stroke; a journal of cerebral circulation Heit, J. J., Wintermark, M. 2016

  View details for PubMedID 26965849

• Cerebral Angiography for Evaluation of Patients with CT Angiogram-Negative Subarachnoid Hemorrhage: An 11-Year Experience. AJNR. American journal of neuroradiology Heit, J. J., Pastena, G. T., Nogueira, R. G., Yoo, A. J., Leslie-Mazwi, T. M., Hirsch, J. A., Rabinov, J. D. 2016; 37 (2): 297?304

  Abstract

  CT angiography is increasingly used to evaluate patients with nontraumatic subarachnoid hemorrhage given its high sensitivity for aneurysms. We investigated the yield of digital subtraction angiography among patients with SAH or intraventricular hemorrhage and a negative CTA.An 11-year, single-center retrospective review of all consecutive patients with CTA-negative SAH was performed. Noncontrast head CT, CTA, DSA, and MR imaging studies were reviewed by 2 experienced interventional neuroradiologists and 1 neuroradiologist.Two hundred thirty patients (mean age, 54 years; 51% male) with CTA-negative SAH were identified. The pattern of SAH was diffuse (40%), perimesencephalic (31%), sulcal (31%), isolated IVH (6%), or identified by xanthochromia (7%). Initial DSA yield was 13%, including vasculitis/vasculopathy (7%), aneurysm (5%), arteriovenous malformation (0.5%), and dural arteriovenous fistula (0.5%). An additional 6 aneurysms/pseudoaneurysms (4%) were identified by follow-up DSA, and a single cavernous malformation (0.4%) was identified by MRI. No cause of hemorrhage was identified in any patient presenting with isolated intraventricular hemorrhage or xanthochromia. Diffuse SAH was due to aneurysm rupture (17%); perimesencephalic SAH was due to aneurysm rupture (3%) or vasculitis/vasculopathy (1.5%); and sulcal SAH was due to vasculitis/vasculopathy (32%), arteriovenous malformation (3%), or dural arteriovenous fistula (3%).DSA identifies vascular pathology in 13% of patients with CTA-negative SAH. Aneurysms or pseudoaneurysms are identified in an additional 4% of patients by repeat DSA following an initially negative DSA. All patients with CT-negative SAH should be considered for DSA. The pattern of SAH may suggest the cause of hemorrhage, and aneurysms should specifically be sought with diffuse or perimesencephalic SAH.

  View details for PubMedID 26338924

• Development of Arteriovenous Fistula After Revascularization Bypass for Moyamoya Disease: Case Report OPERATIVE NEUROSURGERY Feroze, A. H., Kushkuley, J., Choudhri, O., Heit, J. J., Steinberg, G. K., Do, H. M. 2015; 11 (1): E202-E206

  View details for DOI 10.1227/NEU.0000000000000558

  View details for Web of Science ID 000364210300001

  View details for PubMedID 25251198

• Development of arteriovenous fistula after revascularization bypass for Moyamoya disease: case report. Neurosurgery Feroze, A. H., Kushkuley, J., Choudhri, O., Heit, J. J., Steinberg, G. K., Do, H. M. 2015; 11: E202-6

  Abstract

  Moyamoya disease is a rare cerebrovascular disorder often treated by direct and indirect revascularization bypass techniques given a typically devastating disease course and poor response to medical therapy. In this report, we describe the formation and subsequent management of a de novo arteriovenous fistula identified in the setting of a patient treated with direct bypass surgery, a previously unreported phenomenon.A 51-year-old female presenting with Suzuki stage IV bilateral moyamoya disease underwent bilateral extracranial to intracranial (EC-IC) STA-MCA bypass without complication at our institution. At six-month follow-up, she demonstrated no evidence of residual neurologic deficits or continued symptoms despite documentation of an arteriovenous fistula arising at the site of the right EC-IC bypass upon routine follow-up cerebral angiography.We present the first reported case of de novo arteriovenous fistula formation following superficial temporal artery (STA) to middle cerebral artery (MCA) bypass for the treatment of moyamoya disease. Treatment of such iatrogenic arteriovenous fistulae fed by a patent bypass vessel may prove challenging without associated compromise of the bypass, meriting careful evaluation of all potential therapeutic options. The fistula herein most likely occurred secondary to recanalization of a previously thrombosed vein of Trolard. This case demonstrates the possibility of arteriovenous fistula formation as a potential sequela of revascularization bypass surgery and lends support to the previously described traumatic etiology of fistula formation.

  View details for DOI 10.1227/NEU.0000000000000558

  View details for PubMedID 25251198

• Imaging selection for reperfusion therapy in acute ischemic stroke. Current treatment options in neurology Heit, J. J., Wintermark, M. 2015; 17 (2): 332-?

  Abstract

  Neuroimaging is essential in the evaluation of the acute stroke patient. Computed tomography (CT) or magnetic resonance imaging (MRI) should be used to confirm the diagnosis of acute stroke, exclude stroke mimics, and triage patients for intravenous tissue plasminogen activator and endovascular revascularization therapies. Advanced neuroimaging techniques, including CT-angiography, MR-angiography, CT-perfusion, and MR-perfusion should be used to further inform acute stroke treatment decisions. Patients considered for endovascular stroke therapy should have (1) a vascular occlusion that can be reached by an endovascular approach; (2) a small area of core cerebral infarction; and (3) viable tissue at risk of infarction if prompt revascularization is not achieved (penumbra).

  View details for DOI 10.1007/s11940-014-0332-3

  View details for PubMedID 25619536

• Imaging selection for reperfusion therapy in acute ischemic stroke. Current treatment options in neurology Heit, J. J., Wintermark, M. 2015; 17 (2): 332-?

  View details for DOI 10.1007/s11940-014-0332-3

  View details for PubMedID 25619536

• Persistent trigeminal artery supply to an intrinsic trigeminal nerve arteriovenous malformation: A rare cause of trigeminal neuralgia. Journal of clinical neuroscience Choudhri, O., Heit, J. J., Feroze, A. H., Chang, S. D., Dodd, R. L., Steinberg, G. K. 2015; 22 (2): 409-412

  Abstract

  Infratentorial arteriovenous malformations (AVM) associated with the trigeminal nerve root entry zone are a known cause of secondary trigeminal neuralgia (TN). The treatment of both TN and AVM can be challenging, especially if the AVM is embedded within the trigeminal nerve. A persistent trigeminal artery (PTA) can rarely supply these intrinsic trigeminal nerve AVM. We present a 64-year-old man with TN from a right trigeminal nerve AVM supplied by a PTA variant. The patient underwent microvascular decompression and a partial resection of the AVM with relief of facial pain symptoms. His residual AVM was subsequently treated with CyberKnife radiosurgery (Accuray, Sunnyvale, CA, USA). A multimodality approach may be required for the treatment of trigeminal nerve associated PTA AVM and important anatomic patterns need to be recognized before any treatment. Herein, we report to our knowledge the third documented patient with a posterior fossa AVM supplied by a PTA and the first PTA AVM presenting as facial pain.

  View details for DOI 10.1016/j.jocn.2014.06.007

  View details for PubMedID 25070632

• Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm. BMJ case reports Khatibi, K., Heit, J. J., Telischak, N. A., Elbers, J. M., Do, H. M. 2015; 2015

  Abstract

  A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  View details for DOI 10.1136/bcr-2015-011753

  View details for PubMedID 26109622

• Cerebral angioplasty using the Scepter XC dual lumen balloon for the treatment of vasospasm following intracranial aneurysm rupture JOURNAL OF NEUROINTERVENTIONAL SURGERY Heit, J. J., Choudhri, O., Marks, M. P., Dodd, R. L., Do, H. M. 2015; 7 (1): 56-61

  Abstract

  Cerebral vasospasm following subarachnoid hemorrhage (SAH) results in significant morbidity and mortality. Intra-arterial administration of calcium channel blockers or intracranial angioplasty may be performed when non-invasive medical management fails to prevent neurologic deterioration. Technical improvements in balloon catheters are expected to improve the success and safety of cerebral angioplasty.To describe our initial experience with the new Scepter XC balloon catheter in cerebral vasospasm treatment following SAH.All patients who underwent cerebral angioplasty using the Scepter XC balloon for the treatment of medically refractory cerebral vasospasm after SAH were identified. Patient demographic information, procedural details, and outcome were obtained from electronic medical records.Five consecutive patients undergoing vasospasm treatment with cerebral angioplasty using the Scepter XC were identified. All treated patients had medically refractory vasospasm that was moderate or severe. Angioplasty of the supraclinoid internal carotid artery, the A1 and A2 segments of the anterior cerebral artery, the M1 and M2 segments of the middle cerebral artery, the V4 segment of the vertebral artery, and the basilar artery was performed. All angioplasty procedures were technically successful, and the degree of vasospasm improved significantly following angioplasty. There were no complications related to the cerebral angioplasty procedures.The Scepter XC balloon catheter is safe and effective in the treatment of cerebral vasospasm following SAH. The excellent trackability and stability of the balloon catheter and the extra compliant design of the balloon represent technical advancements in the endovascular armamentarium in the treatment of cerebral vasospasm.

  View details for DOI 10.1136/neurintsurg-2013-011043

  View details for PubMedID 24385556

• Unruptured intracranial aneurysms conservatively followed with serial CT angiography: could morphology and growth predict rupture? JOURNAL OF NEUROINTERVENTIONAL SURGERY Mehan, W. A., Romero, J. M., Hirsch, J. A., Sabbag, D. J., Gonzalez, R. G., Heit, J. J., Schaefer, P. W. 2014; 6 (10): 761-766

  Abstract

  Despite several landmark studies, the natural history of unruptured intracranial aneurysms (UIA) remains uncertain. Our aim was to identify or confirm factors predictive of rupture of UIA being observed conservatively with serial CT angiography (CTA) in a North American patient population.We performed a retrospective review of patients with UIA being followed with serial CTA studies from 1999 to 2010. The following features for each aneurysm were cataloged from the official radiologic reports and CTA images: maximum diameter, growth between follow-up studies, location, multiplicity, wall calcification, intraluminal thrombus and morphology. Univariate logistic regression analysis of the potential independent risk factors for aneurysm rupture was performed. Statistically significant risk factors from the univariate analysis were then entered into a multivariate logistic regression analysis.152 patients with a total of 180 UIA had at least two CTA studies. Six aneurysms in six different patients ruptured during the CTA follow-up period for an overall rupture rate of 3.3% and an annual rupture rate of 0.97%. All ruptured aneurysms were ?9?mm. In the univariate analysis, the statistically significant predictors of aneurysm rupture were aneurysm size (p=0.003), aneurysm growth (p<0.0001) and aneurysm multilobulation (p=0.001). The risk factors that remained significant following the multivariate analysis were growth (OR 55.9; 95% CI 4.47 to 700.08; p=0.002) and multilobulation (OR 17.4; 95% CI 1.52 to 198.4; p=0.022).Aneurysm morphology and interval growth are characteristics predictive of a higher risk of subsequent rupture during conservative CTA follow-up.

  View details for DOI 10.1136/neurintsurg-2013-010944

  View details for Web of Science ID 000344939800014

  View details for PubMedID 24275611

• Endovascular reconstruction of enlarging traumatic internal carotid artery pseudoaneurysm. Neurosurgical focus Choudhri, O., Heit, J., Do, H. M. 2014; 37 (1): 1-?

  Abstract

  Traumatic dissecting pseudoaneurysms of the cervical and petrous internal carotid artery are often a result of blunt or penetrating trauma. These patients are at high risk for thromboembolic complications and are managed with antiplatelet agents. Patients who develop neurologic symptoms while on antiplatelet agents, or have interval enlargement of their pseudoaneurysms, may require repair of the vessel. We describe a case in which we performed an endovascular repair of an enlarging distal cervical internal carotid artery pseudoaneurysm, with placement of a covered stent. The video can be found here: http://youtu.be/uCypcsBvOZ4 .

  View details for DOI 10.3171/2014.V2.FOCUS14185

  View details for PubMedID 24983722

• E-013 endovascular management of pseudoaneurysms secondary to external ventricular drain placement: single center experience. Journal of neurointerventional surgery Choudhri, O., Gupta, M., Heit, J., Feroze, A., Do, H. 2014; 6: A43-4

  Abstract

  Placement of external ventricular drains is a common, life-saving neurosurgical procedure indicated across a variety of settings. While advances have made the procedure quite safe, the potential for iatrogenic morbidity and mortality continues. Herein, we document our experience with the endovascular management of three pseudoaneurysms associated with EVD placement.We performed a retrospective analysis to identify all EVDs placed from 2008 through 2013 at our institution,. In instances of EVD-associated cerebrovascular injury, all admission and subsequent radiographic studies were reviewed, including cerebral angiograms and computed tomography (CT) scans. Angiograms were reviewed to record the extent of vascular injury and angiographic outcomes after treatment.One female and two male patients (40-75 years) were found to have developed vascular injuries associated with EVD placement. Three pseudoaneurysms, namely of the posterior communicating artery (PCOM), pericallosal artery branch and the middle meningeal artery, were treated by coil and/or glue embolization.Although EVD-associated cerebrovascular injury remains a rare phenomenon, such procedures are not entirely benign. Endovascular repair for such lesions proves a viable, effective option.arteriovenous fistula (AVF), computed tomography (CT), external ventricular drain (EVD), posterior communicating artery (PCOM), posterior cerebral artery (PCA) DISCLOSURES: O. Choudhri: None. M. Gupta: None. J. Heit: None. A. Feroze: None. H. Do: None.

  View details for DOI 10.1136/neurintsurg-2014-011343.80

  View details for PubMedID 25064928

• Endovascular management of external ventricular drain-associated cerebrovascular injuries. Surgical neurology international Choudhri, O., Gupta, M., Feroze, A. H., Heit, J. J., Do, H. M. 2014; 5: 167-?

  Abstract

  Placement of external ventricular drains (EVDs) is a common, life-saving neurosurgical procedure indicated across a variety of settings. While advances have made the procedure quite safe, the potential for iatrogenic morbidity and mortality continues. We document our experience with the endovascular management of three pseudoaneurysms associated with EVD placement and discuss the endovascular treatment options for EVD-associated cerebrovascular injury.We performed a retrospective analysis to identify all EVDs placed from 2008 through 2013 at our institution. In instances of EVD-associated cerebrovascular injury, all admission and subsequent radiographic studies were reviewed, including cerebral angiograms and computed tomography (CT) scans where available. Angiograms were reviewed to record the extent of vascular injury and outcomes after treatment.One female and two male patients (age range, 40-75 years) were found to have developed vascular injuries associated with EVD placement. Three pseudoaneurysms, of the posterior communicating artery (PCOM), pericallosal artery branch, and the middle meningeal artery, respectively, were treated by coil and/or glue embolization.Although EVD-associated cerebrovascular injury remains a rare phenomenon, such procedures are not entirely benign. Endovascular repair for such lesions proves a viable, effective option.

  View details for DOI 10.4103/2152-7806.145930

  View details for PubMedID 25558425

• Prospective Validation of the Computed Tomographic Angiography Spot Sign Score for Intracerebral Hemorrhage STROKE Romero, J. M., Brouwers, H. B., Lu, J., Almandoz, J. E., Kelly, H., Heit, J., Goldstein, J., Rosand, J., Gonzalez, R. G. 2013; 44 (11): 3097-3102

  Abstract

  Intracerebral hemorrhage (ICH) results in high mortality and morbidity for patients. Previous retrospective studies correlated the spot sign score (SSSc) with ICH expansion, mortality, and clinical outcome among ICH survivors. We performed a prospective study to validate the SSSc for the prediction of ICH expansion, mortality, and clinical outcome among survivors.We prospectively included consecutive patients with primary ICH presenting to a single institution for a 1.5-year period. All patients underwent baseline noncontrast computed tomography (CT) and multidetector CT angiography performed within 24 hours of admission and a follow-up noncontrast CT within 48 hours after the initial CT. The ICH volume was calculated on the noncontrast CT images using semiautomated software. The SSSc was calculated on the multidetector CT angiographic source images. We assessed in-hospital mortality and modified Rankin Scale at discharge and at 3 months among survivors. A multivariate logistic regression analysis was performed to determine independent predictors of hematoma expansion, in-hospital mortality, and poor clinical outcome.A total of 131 patients met the inclusion criteria. Of the 131 patients, a spot sign was detected in 31 patients (24%). In a multivariate analysis, the SSSc predicted significant hematoma expansion (odds ratio, 3.1; 95% confidence interval, 1.77-5.39; P?0.0001), in-hospital mortality (odds ratio, 4.1; 95% confidence interval, 2.11-7.94; P?0.0001), and poor clinical outcome (odds ratio, 3; 95% confidence interval, 1.4-4.42; P=0.004). In addition, the SSSc was an accurate grading scale for ICH expansion, modified Rankin Scale at discharge, and in-hospital mortality.The SSSc demonstrated a strong stepwise correlation with hematoma expansion and clinical outcome in patients with primary ICH.

  View details for DOI 10.1161/STROKEAHA.113.002752

  View details for Web of Science ID 000325987300038

  View details for PubMedID 24021687

• Impact of online education on intern behaviour around joint commission national patient safety goals: a randomised trial BMJ QUALITY & SAFETY Shaw, T. J., Pernar, L. I., Peyre, S. E., Helfrick, J. F., Vogelgesang, K. R., Graydon-Baker, E., Chretien, Y., Brown, E. J., Nicholson, J. C., Heit, J. J., Co, J. P., Gandhi, T. 2012; 21 (10): 819-825

  Abstract

  To compare the effectiveness of two types of online learning methodologies for improving the patient-safety behaviours mandated in the Joint Commission National Patient Safety Goals (NPSG).This randomised controlled trial was conducted in 2010 at Massachusetts General Hospital and Brigham and Women's Hospital (BWH) in Boston USA. Incoming interns were randomised to either receive an online Spaced Education (SE) programme consisting of cases and questions that reinforce over time, or a programme consisting of an online slide show followed by a quiz (SQ). The outcome measures included NPSG-knowledge improvement, NPSG-compliant behaviours in a simulation scenario, self-reported confidence in safety and quality, programme acceptability and programme relevance.Both online learning programmes improved knowledge retention. On four out of seven survey items measuring satisfaction and self-reported confidence, the proportion of SE interns responding positively was significantly higher (p<0.05) than the fraction of SQ interns. SE interns demonstrated a mean 4.79 (36.6%) NPSG-compliant behaviours (out of 13 total), while SQ interns completed a mean 4.17 (32.0%) (p=0.09). Among those in surgical fields, SE interns demonstrated a mean 5.67 (43.6%) NPSG-compliant behaviours, while SQ interns completed a mean 2.33 (17.9%) (p=0.015). Focus group data indicates that SE was more contextually relevant than SQ, and significantly more engaging.While both online methodologies improved knowledge surrounding the NPSG, SE was more contextually relevant to trainees and was engaging. SE impacted more significantly on both self-reported confidence and the behaviour of surgical residents in a simulated scenario.

  View details for DOI 10.1136/bmjqs-2011-000702

  View details for Web of Science ID 000309513900003

  View details for PubMedID 22706930

• Spot sign score predicts rapid bleeding in spontaneous intracerebral hemorrhage. Emergency radiology Romero, J. M., Heit, J. J., Delgado Almandoz, J. E., Goldstein, J. N., Lu, J., Halpern, E., Greenberg, S. M., Rosand, J., Gonzalez, R. G. 2012; 19 (3): 195-202

  Abstract

  This study was conducted to determine whether spot sign score correlates with average rate of hematoma expansion and whether average rate of expansion predicts in-hospital mortality and clinical outcome in spontaneous intracerebral hemorrhage (ICH). The study included 367 patients presenting to the Emergency Department (ED) from January 1, 2000 to December 31, 2008 with nontraumatic ICH. All received noncontrast computed tomography (NCCT) of the head and multidetector CT angiography (MDCTA) on presentation to the ED and a follow-up NCCT within 48 h. Imaging was used to determine the hematoma location and volume, average rate of expansion, and spot sign score. Primary outcome measures included in-hospital mortality and clinical outcome based on modified Rankin Scale at 3 months or at discharge. Regression analysis was performed to correlate spot sign score and average rate of hematoma expansion. ICH expansion was identified in 194 of 367 patients (53%). In a multivariate analysis, rate of ICH expansion predicted mortality (hazard ratio 1.1, CI 1.08-1.12, p?

  View details for DOI 10.1007/s10140-012-1020-9

  View details for PubMedID 22271362

• Safety and Efficacy of Percutaneous Fiducial Marker Implantation for Image-guided Radiation Therapy JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kothary, N., Heit, J. J., Louie, J. D., Kuo, W. T., Loo, B. W., Koong, A., Chang, D. T., Hovsepian, D., Sze, D. Y., Hofmann, L. V. 2009; 20 (2): 235-239

  Abstract

  To evaluate the safety and technical success rate of percutaneous fiducial marker implantation in preparation for image-guided radiation therapy.From January 2003 to January 2008, we retrospectively reviewed 139 percutaneous fiducial marker implantations in 132 patients. Of the 139 implantations, 44 were in the lung, 61 were in the pancreas, and 34 were in the liver. Procedure-related major and minor complications were documented. Technical success was defined as implantation enabling adequate treatment planning and computed tomographic simulation.The major and minor complication rates were 5% and 17.3%, respectively. Pneumothorax after lung implantation was the most common complication. Pneumothoraces were seen in 20 of the 44 lung implantations (45%); a chest tube was required in only seven of the 44 lung transplantations (16%). Of the 139 implantations, 133 were successful; in six implantations (4.3%) the fiducial markers migrated and required additional procedures or alternate methods of implantation.Percutaneous implantation of fiducial marker is a safe and effective procedure with risks that are similar to those of conventional percutaneous organ biopsy.

  View details for DOI 10.1016/j.jvir.2008.09.026

  View details for PubMedID 19019700

• Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus SCIENCE Karnik, S. K., Chen, H., McLean, G. W., Heit, J. J., Gu, X., Zhang, A. Y., Fontaine, M., Yen, M. H., Kim, S. K. 2007; 318 (5851): 806-809

  Abstract

  During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.

  View details for DOI 10.1126/science.1146812

  View details for PubMedID 17975067

• Calcineurin/NFAT signaling in the beta-cell: from diabetes to new therapeutics BIOESSAYS Heit, J. J. 2007; 29 (10): 1011-1021

  Abstract

  Pancreatic beta-cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in beta-cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential beta-cell factors have been identified that are required for normal beta-cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that control expression of MODY and other factors continue to be revealed. Post-transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T-cells (NFAT) may be required for beta-cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the beta-cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed.

  View details for DOI 10.1002/bies.20644

  View details for PubMedID 17876792

• Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function NATURE Heit, J. J., Apelqvist, A. A., Gu, X., Winslow, M. M., Neilson, J. R., Crabtree, G. R., Kim, S. K. 2006; 443 (7109): 345-349

  Abstract

  The growth and function of organs such as pancreatic islets adapt to meet physiological challenges and maintain metabolic balance, but the mechanisms controlling these facultative responses are unclear. Diabetes in patients treated with calcineurin inhibitors such as cyclosporin A indicates that calcineurin/nuclear factor of activated T-cells (NFAT) signalling might control adaptive islet responses, but the roles of this pathway in beta-cells in vivo are not understood. Here we show that mice with a beta-cell-specific deletion of the calcineurin phosphatase regulatory subunit, calcineurin b1 (Cnb1), develop age-dependent diabetes characterized by decreased beta-cell proliferation and mass, reduced pancreatic insulin content and hypoinsulinaemia. Moreover, beta-cells lacking Cnb1 have a reduced expression of established regulators of beta-cell proliferation. Conditional expression of active NFATc1 in Cnb1-deficient beta-cells rescues these defects and prevents diabetes. In normal adult beta-cells, conditional NFAT activation promotes the expression of cell-cycle regulators and increases beta-cell proliferation and mass, resulting in hyperinsulinaemia. Conditional NFAT activation also induces the expression of genes critical for beta-cell endocrine function, including all six genes mutated in hereditary forms of monogenic type 2 diabetes. Thus, calcineurin/NFAT signalling regulates multiple factors that control growth and hallmark beta-cell functions, revealing unique models for the pathogenesis and therapy of diabetes.

  View details for DOI 10.1038/nature05097

  View details for PubMedID 16988714

• NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21 NATURE Arron, J. R., Winslow, M. M., Polleri, A., Chang, C., Wu, H., Gao, X., Neilson, J. R., Chen, L., Heit, J. J., Kim, S. K., Yamasaki, N., Miyakawa, T., Francke, U., Graef, I. A., Crabtree, G. R. 2006; 441 (7093): 595-600

  Abstract

  Trisomy 21 results in Down's syndrome, but little is known about how a 1.5-fold increase in gene dosage produces the pleiotropic phenotypes of Down's syndrome. Here we report that two genes, DSCR1 and DYRK1A , lie within the critical region of human chromosome 21 and act synergistically to prevent nuclear occupancy of NFATc transcription factors, which are regulators of vertebrate development. We use mathematical modelling to predict that autoregulation within the pathway accentuates the effects of trisomy of DSCR1 and DYRK1A, leading to failure to activate NFATc target genes under specific conditions. Our observations of calcineurin-and Nfatc-deficient mice, Dscr1- and Dyrk1a-overexpressing mice, mouse models of Down's syndrome and human trisomy 21 are consistent with these predictions. We suggest that the 1.5-fold increase in dosage of DSCR1 and DYRK1A cooperatively destabilizes a regulatory circuit, leading to reduced NFATc activity and many of the features of Down's syndrome. More generally, these observations suggest that the destabilization of regulatory circuits can underlie human disease.

  View details for DOI 10.1038/nature04678

  View details for PubMedID 16554754

• Intrinsic regulators of pancreatic beta-cell proliferation ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY Heit, J. J., Karnik, S. K., Kim, S. K. 2006; 22: 311-338

  Abstract

  Once thought incapable of significant proliferation, the pancreatic beta-cell has recently been shown to harbor immense powers of self-renewal. Pancreatic beta-cells, the sole source of insulin in vertebrate animals, can grow facultatively to a degree unmatched by other organs in experimental animals. beta-cell growth matches changes in systemic insulin demand, which increase during common physiologic states such as aging, obesity, and pregnancy. Compensatory changes in beta-cell mass are controlled by beta-cell proliferation. Here we review recent advances in our understanding of the intrinsic factors and mechanisms that control beta-cell cycle progression. Dysregulation of beta-cell proliferation is emerging as a fundamental feature in the pathogenesis of human disease states such as cancer and diabetes mellitus. New experimental observations and studies of these diseases suggest that beta-cell fate and expansion are coordinately regulated. We speculate on how these advances may accelerate the discovery of new strategies for the treatment of diseases characterized by a deficiency or excess of beta-cells.

  View details for DOI 10.1146/annurev.cellbio.22.010305.104425

  View details for PubMedID 16824015

• Embryonic stem cells and islet replacement in diabetes mellitus PEDIATRIC DIABETES Heit, J. J., Kim, S. K. 2004; 5: 5-15

  Abstract

  Transplantation of functional islets of Langerhans may emerge as a useful therapy for some patients with type 1 diabetes mellitus (DM), but donor islet shortages motivate the search for new sources of transplantable islets. Pluripotent embryonic stem (ES) cells are expandable in culture and have the potential to give rise to all cell types in the body. The recent isolation of pluripotent ES cells from humans has generated excitement over the possibility of engineering glucose-responsive islet replacement tissue from these cells in large quantities. In this study, we review the recent advances in generating insulin-producing cells (IPC) from mouse and human ES (hES) cells.

  View details for PubMedID 15601369

• N-terminal domain of yeast telomerase reverse transcriptase: Recruitment of Est3p to the telomerase complex MOLECULAR BIOLOGY OF THE CELL Friedman, K. L., Heit, J. J., Long, D. M., Cech, T. R. 2003; 14 (1): 1-13

  Abstract

  Telomerase is a reverse transcriptase that maintains chromosome ends. The N-terminal half of the catalytic protein subunit (TERT) contains three functional domains (I, II, and III) that are conserved among TERTs but not found in other reverse transcriptases. Guided by an amino acid sequence alignment of nine TERT proteins, mutations were introduced into yeast TERT (Est2p). In support of the proposed alignment, mutation of virtually all conserved residues resulted in loss-of-function or temperature sensitivity, accompanied by telomere shortening. Overexpression of telomerase component Est3p led to allele-specific suppression of the temperature-sensitive mutations in region I, suggesting that Est3p interacts with this protein domain. As predicted by the genetic results, a lethal mutation in region I resulted in loss of Est3p from the telomerase complex. We conclude that Est2p region I is required for the recruitment of Est3p to yeast telomerase. Given the phylogenetic conservation of region I of TERT, this protein domain may provide the equivalent function in all telomerases.

  View details for DOI 10.1091/mbc.E02-06-0327

  View details for Web of Science ID 000180497300002

  View details for PubMedID 12529422

• Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hori, Y., Rulifson, I. C., Tsai, B. C., Heit, J. J., Cahoy, J. D., Kim, S. K. 2002; 99 (25): 16105-16110

  Abstract

  The use of embryonic stem cells for cell-replacement therapy in diseases like diabetes mellitus requires methods to control the development of multipotent cells. We report that treatment of mouse embryonic stem cells with inhibitors of phosphoinositide 3-kinase, an essential intracellular signaling regulator, produced cells that resembled pancreatic beta cells in several ways. These cells aggregated in structures similar, but not identical, to pancreatic islets of Langerhans, produced insulin at levels far greater than previously reported, and displayed glucose-dependent insulin release in vitro. Transplantation of these cell aggregates increased circulating insulin levels, reduced weight loss, improved glycemic control, and completely rescued survival in mice with diabetes mellitus. Graft removal resulted in rapid relapse and death. Graft analysis revealed that transplanted insulin-producing cells remained differentiated, enlarged, and did not form detectable tumors. These results provide evidence that embryonic stem cells can serve as the source of insulin-producing replacement tissue in an experimental model of diabetes mellitus. Strategies for producing cells that can replace islet functions described here can be adapted for similar uses with human cells.

  View details for DOI 10.1073/pnas.252618999

  View details for PubMedID 12441403