Dr. Jeremy Heit is a neurointerventional surgeon (neurointerventional radiologist) who specializes in treating stroke, brain aneurysms, brain arteriovenous malformations, brain and spinal dural arteriovenous fistulae, carotid artery stenosis, vertebral body compression fractures, and congenital vascular malformations. Dr. Heit treats all of these conditions using minimally-invasive, image-guided procedures and state-of-the-art technology.

Clinical Focus

  • Interventional Neuroradiology
  • Neurointerventional Surgery
  • Neuroradiology
  • Diagnostic Radiology
  • Stroke
  • Cerebral Aneurysms
  • Dural Arteriovenous Fistula
  • Cerebral Arteriovenous Malformation (AVM)

Academic Appointments

  • Clinical Assistant Professor, Radiology
  • Clinical Assistant Professor (By courtesy), Neurosurgery

Honors & Awards

  • Valedictorian, Regis Jesuit High School, Aurora, CO (5/1996)
  • Boettcher Foundation Scholar, Full Academic Scholarship to the University of Colorado at Boulder, Boettcher Foundation (8/1996 – 5/2000)
  • Beta Kappa Honor Society, Phi Beta Kappa (4/1997 – present)
  • Summa Cum Laude, Department of Biochemisty, University of Colorado at Boulder (5/2000)
  • Graduation with Distinction in Molecular, Cellular and Developmental Biology, University of Colorado at Boulder (5/2000)
  • Department of Biochemistry Outstanding Graduating Senior Award, University of Colorado at Boulder (5/2000)
  • Medical Scientist dual MD/PhD Training Program, Stanford University School of Medicine (8/2000 – 6/2008)
  • Chief Resident in Radiology, Massachusetts General Hospital, Boston, MA (3/2011 – 2/2102)
  • Roentgen Resident/Fellow Research Award, RSNA Research and Education Foundation, Radiological Society of North America (5/2011)

Boards, Advisory Committees, Professional Organizations

  • Research Committee, American Society of Neuroradiology (2012 - Present)

Professional Education

  • Internship:Brigham and Women's Hospital Internal Medicine ResidencyMA
  • Board Certification: Diagnostic Radiology, American Board of Radiology (2013)
  • Fellowship:Stanford University Hospital and ClinicsCA
  • Residency:Massachusetts General HospitalMA
  • Medical Education:Stanford University Medical School (2008) CA
  • PhD, Stanford University Medical School, Developmental Biology (2007)
  • BA, University of Colorado at Boulder, Biochemistry, Summa Cum Laude, and Molecular, Cellular, and Developmental Biology (2000)


All Publications

  • 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


    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 DOI 10.1177/0271678X17721830

    View details for Web of Science ID 000443291300002

    View details for PubMedID 28816594

    View details for PubMedCentralID PMC6125970

  • 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


    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: Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.022147

    View details for PubMedID 29986935

  • 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


    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 DOI 10.1016/j.clinimag.2018.02.014

    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


    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 number, NCT02586415 .).

    View details for DOI 10.1056/NEJMoa1713973

    View details for PubMedID 29364767

  • 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


    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 DOI 10.1136/neurintsurg-2017-013256

    View details for PubMedID 28768818

  • 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


    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 DOI 10.1161/STROKEAHA.118.021402

    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


    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 (κ=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%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=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 DOI 10.1136/neurintsurg-2018-013784

    View details for PubMedID 29555872

  • 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 DOI 10.1053/

    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


    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 DOI 10.1177/1591019917737734

    View details for PubMedID 29125024

    View details for PubMedCentralID PMC5772540

  • 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


    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


    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


     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


    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

  • 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

  • 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


    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

  • 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)


    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

    View details for PubMedCentralID PMC5392038

  • 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


    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

  • 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-?


    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

  • 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


    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 DOI 10.1177/1591019917722514

    View details for PubMedID 28758549

    View details for PubMedCentralID PMC5814067

  • 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


    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 (κ = .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 DOI 10.1111/jon.12487

    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

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


    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

  • 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 Web of Science ID 000389606200014

    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


    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
  • 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


    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


    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)


    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


    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 κ = 0.82) and interobserver (weighted κ = 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 Web of Science ID 000378658500028

    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


    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 Web of Science ID 000375049700044

    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
  • 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

  • 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


    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 DOI 10.3174/ajnr.A4503

    View details for PubMedID 26338924

  • 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


    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

  • 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

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


    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


    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


    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


    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 Web of Science ID 000346242600015

    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


    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-?


    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: .

    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


    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-?


    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

    View details for PubMedCentralID PMC4278086

  • 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


    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


    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


    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 < 0.0001). Patients who expired had an average rate of ICH expansion of 2.8 ml/h compared to 0.2 ml/h in survivors. Spot sign score on presentation to the ED correlated with the average rate of hematoma expansion. Average rate of hematoma expansion predicts mortality in spontaneous ICH. Spot sign score on presentation correlates with rate of expansion, supporting the hypothesis that high spot sign scores likely reflect active bleeding in acute ICH.

    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


    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 Web of Science ID 000263075000012

    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


    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 Web of Science ID 000250583900043

    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


    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 Web of Science ID 000250250100008

    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


    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 Web of Science ID 000240622000048

    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


    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 Web of Science ID 000237920800038

    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


    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 Web of Science ID 000242325100014

    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


    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 Web of Science ID 000226386200003

    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


    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


    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 Web of Science ID 000179783400052

    View details for PubMedID 12441403