Michael V. McConnell, MD, MSEE

View details for PubMedID 24172077

View details for DOI 10.1016/j.jacc.2013.02.002

View details for PubMedID 24556329

Abstract

Transthoracic echocardiographic (TTE) imaging is the mainstay of clinical practice for evaluating right ventricular (RV) size and function, but its accuracy in patients with pulmonary hypertension has not been well validated.Magnetic resonance imaging (MRI) and TTE images were retrospectively reviewed in 40 consecutive patients with pulmonary hypertension. RV and left ventricular volumes and ejection fractions were calculated using MRI. TTE areas and indices of RV ejection fraction (RVEF) were compared.The average age was 42 ± 12 years, with a majority of women (85%). There was a wide range of mean pulmonary arterial pressures (27-81 mm Hg) and RV end-diastolic volumes (111-576 mL), RVEFs (8%-67 %), and left ventricular ejection fractions (26%-72%) by MRI. There was a strong association between TTE and MRI-derived parameters: RV end-diastolic area (by TTE imaging) and RV end-diastolic volume (by MRI), R(2) = 0.78 (P < .001); RV fractional area change by TTE imaging and RVEF by MRI, R(2) = 0.76 (P < .001); and tricuspid annular plane systolic excursion by TTE imaging and RVEF by MRI, R(2) = 0.64 (P < .001). By receiver operating characteristic curve analysis, an RV fractional area change < 25% provided excellent discrimination of moderate systolic dysfunction (RVEF < 35%), with an area under the curve of 0.97 (P < .001). An RV end-diastolic area index of 18 cm(2)/m(2) provided excellent discrimination for moderate RV enlargement (area under the curve, 0.89; P < .001).Echocardiographic estimates of RV volume (by RV end-diastolic area) and function (by RV fractional area change and tricuspid annular plane systolic excursion) offer good approximations of RV size and function in patients with pulmonary hypertension and allow the accurate discrimination of normal from abnormal.

View details for DOI 10.1016/j.echo.2013.12.011

View details for PubMedID 24444659

Abstract

Continuous monitoring of in vivo biological processes and their evolution at the cellular level would enable major advances in our understanding of biology and disease. As a stepping stone towards chronic cellular monitoring, we demonstrate massively parallel fabrication and delivery of 3D multilayer micro-Tags (μTags) into living cells. Both 10 μm × 10 μm × 1.5 μm and 18 μm × 7 μm × 1.5 μm devices containing inductive and capacitive structures were designed and fabricated as potential passive radio-frequency identification tags. We show cellular internalization and persistence of μTags over a 5-day period. Our results represent a promising advance in technologies for studying biology and disease at the cellular level.

View details for DOI 10.1038/srep02295

View details for Web of Science ID 000322308900002

View details for PubMedID 23887586

Abstract

Noninvasive visualization of the coronary arteries in vivo is one of the most important goals in cardiovascular imaging. Compared to other paradigms for coronary MR angiography, a free-breathing three-dimensional whole-heart iso-resolution approach simplifies prescription effort, requires less patient cooperation, reduces overall exam time, and supports retrospective reformats at arbitrary planes. However, this approach requires a long continuous acquisition and must account for respiratory and cardiac motion throughout the scan. In this work, a new free-breathing coronary MR angiography technique that reduces scan time and improves robustness to motion is developed. Data acquisition is accomplished using a three-dimensional cones non-Cartesian trajectory, which can reduce the number of readouts 3-fold or more compared to conventional three-dimensional Cartesian encoding and provides greater robustness to motion/flow effects. To further enhance robustness to motion, two-dimensional navigator images are acquired to directly track respiration-induced displacement of the heart and enable retrospective compensation of all acquired data (none discarded) for image reconstruction. In addition, multiple cardiac phases are imaged to support retrospective selection of the best phase(s) for visualizing each coronary segment. Experimental results demonstrate that whole-heart coronary angiograms can be obtained rapidly and robustly with this proposed technique.

View details for DOI 10.1002/mrm.24342

View details for Web of Science ID 000316629300020

Abstract

Patients with a myocardial bridge (MB) and no significant obstructive coronary artery disease (CAD) may experience angina presumably from ischemia, but noninvasive assessment has been limited and the underlying mechanism poorly understood. This study seeks to correlate a novel exercise echocardiography (EE) finding for MBs with invasive structural and hemodynamic measurements.Eighteen patients with angina and an EE pattern of focal end-systolic to early-diastolic buckling in the septum with apical sparing were prospectively enrolled for invasive assessment. This included coronary angiography, left anterior descending artery (LAD) intravascular ultrasound (IVUS), and intracoronary pressure and Doppler measurements at rest and during dobutamine stress. All patients were found to have an LAD MB on IVUS. The ratios of diastolic intracoronary pressure divided by aortic pressure at rest (Pd/Pa) and during dobutamine stress (diastolic fractional flow reserve [dFFR]) and peak Doppler flow velocity recordings at rest and with stress were successfully performed in 14 patients. All had abnormal dFFR (?0.75) at stress within the bridge, distally or in both positions, and on average showed a more than doubling in peak Doppler flow velocity inside the MB at stress. Seventy-five percent of patients had normalization of dFFR distal to the MB, with partial pressure recovery and a decrease in peak Doppler flow velocity.A distinctive septal wall motion abnormality with apical sparing on EE is associated with a documented MB by IVUS and a decreased dFFR. We posit that the septal wall motion abnormality on EE is due to dynamic ischemia local to the compressed segment of the LAD from the increase in velocity and decrease in perfusion pressure, consistent with the Venturi effect.

View details for DOI 10.1161/JAHA.113.000097

View details for PubMedID 23591827

Abstract

Three-dimensional cardiac magnetic resonance perfusion imaging is promising for the precise sizing of defects and for providing high perfusion contrast, but remains an experimental approach primarily due to the need for large-dimensional encoding, which, for traditional 3DFT imaging, requires either impractical acceleration factors or sacrifices in spatial resolution. We demonstrated the feasibility of rapid three-dimensional cardiac magnetic resonance perfusion imaging using a stack-of-spirals acquisition accelerated by non-Cartesian k-t SENSE, which enables entire myocardial coverage with an in-plane resolution of 2.4 mm. The optimal undersampling pattern was used to achieve the largest separation between true and aliased signals, which is a prerequisite for k-t SENSE reconstruction. Flip angle and saturation recovery time were chosen to ensure negligible magnetization variation during the transient data acquisition. We compared the proposed three-dimensional perfusion method with the standard 2DFT approach by consecutively acquiring both data during each R-R interval in cardiac patients. The mean and standard deviation of the correlation coefficients between time intensity curves of three-dimensional versus 2DFT were 0.94 and 0.06 across seven subjects. The linear correlation between the two sets of upslope values was significant (r = 0.78, P < 0.05).

View details for DOI 10.1002/mrm.24303

View details for Web of Science ID 000315331300026

View details for PubMedID 22556062

View details for PubMedID 23769491

Abstract

Macrophages are critical contributors to atherosclerosis. Single-walled carbon nanotubes (SWNTs) show promising properties for cellular imaging and thermal therapy, which may have application to vascular macrophages.In vitro uptake and photothermal destruction of mouse macrophage cells (RAW264.7) were performed with SWNTs (14.7 nmol/L) exposed to an 808-nm light source. SWNTs were taken up by 94 ± 6% of macrophages, and light exposure induced 93 ± 3% cell death. In vivo vascular macrophage uptake and ablation were then investigated in carotid-ligated FVB mice (n=33) after induction of hyperlipidemia and diabetes. Two weeks postligation, near-infrared fluorescence (NIRF) carotid imaging (n=12) was performed with SWNT-Cy5.5 (8 nmol of Cy5.5) given via the tail vein. Photothermal heating and macrophage apoptosis were evaluated on freshly excised carotid arteries (n=21). NIRF of SWNTs showed higher signal intensity in ligated carotids compared with sham, confirmed by both in situ and ex vivo NIRF imaging (P<0.05, ligation versus sham). Immunofluorescence staining showed colocalization of SWNT-Cy5.5 and macrophages in atherosclerotic lesions. Light (808 nm) exposure of freshly excised carotids showed heating and induction of macrophage apoptosis in ligated left carotid arteries with SWNTs, but not in control groups without SWNTs or without light exposure.Carbon nanotubes accumulate in atherosclerotic macrophages in vivo and provide a multifunctional platform for imaging and photothermal therapy of vascular inflammation.

View details for DOI 10.1161/JAHA.112.002568

View details for PubMedID 23316318

View details for DOI 10.1161/CIRCGENETICS.112.962746

View details for Web of Science ID 000309884900017

View details for PubMedID 22715281

Abstract

Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n?=?16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88?±?0.30 vs. 1.17?±?0.10, p?=?0.04; AAA: 2.59?±?0.24 vs. 1.82?±?0.16, p?=?0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

View details for DOI 10.1007/s11307-011-0495-1

View details for Web of Science ID 000303884400006

View details for PubMedID 21638084

Abstract

Listeriosis is one of the most lethal bacterial diseases for fetuses and infants. However, pregnant women who get infected with Listeria may experience only mild symptoms, making the diagnosis difficult, even when the fetus is fatally infected.To reveal features of this infection, we conducted a multimodality imaging study of Listeria-induced miscarriage, using a pregnant mouse model. In this model, fetal morbidity and mortality can be observed in utero, noninvasively, and the timing and extent of infection can be carefully controlled. By employing in vivo bioluminescence imaging (BLI), perinatal infections were localized over time such that a correlation of infection to outcome could be determined without the need to kill the animal subject. The morbidity and viability of fetuses were assessed with ultrasound, and fetal morphology was imaged using magnetic resonance imaging (MRI).The ultrasound revealed sustained fetal bradycardia, the slowing of the fetal heartbeat, in infected fetuses, with an association between slowed fetal heart rate and strong bioluminescent signal.Uninfected fetuses showing no bioluminescent signal in the same uterine horn exhibited normal heartbeats. Thus, fetal bradycardia during infection was localized to the infected fetus and was not systemic or disseminated.

View details for DOI 10.1038/pr.2012.2

View details for Web of Science ID 000303373300003

View details for PubMedID 22314663

Abstract

Macrophage infiltration is a prominent feature of abdominal aortic aneurysm (AAA) progression. We used a combined imaging approach with bioluminescence (BLI) and magnetic resonance imaging (MRI) to study macrophage homing and accumulation in experimental AAA disease. Murine AAAs were created via intra-aortic infusion of porcine pancreatic elastase. Mice were imaged over 14 days after injection of prepared peritoneal macrophages. For BLI, macrophages were from transgenic mice expressing luciferase. For MRI, macrophages were labeled with iron oxide particles. Macrophage accumulation during aneurysm progression was observed by in situ BLI and by in vivo 7T MRI. Mice were sacrificed after imaging for histologic analysis. In situ BLI (n ?=? 32) demonstrated high signal in the AAA by days 7 and 14, which correlated significantly with macrophage number and aortic diameter. In vivo 7T MRI (n ?=? 13) at day 14 demonstrated T?* signal loss in the AAA and not in sham mice. Immunohistochemistry and Prussian blue staining confirmed the presence of injected macrophages in the AAA. BLI and MRI provide complementary approaches to track macrophage homing and accumulation in experimental AAAs. Similar dual imaging strategies may aid the study of AAA biology and the evaluation of novel therapies.

View details for DOI 10.2310/7290.2011.00033

View details for Web of Science ID 000307645900004

View details for PubMedID 22469240

Abstract

Identification and treatment of abdominal aortic aneurysm (AAA) remains among the most prominent challenges in vascular medicine. MicroRNAs are crucial regulators of cardiovascular pathology and represent possible targets for the inhibition of AAA expansion. We identified microRNA-21 (miR-21) as a key modulator of proliferation and apoptosis of vascular wall smooth muscle cells during development of AAA in two established murine models. In both models (AAA induced by porcine pancreatic elastase or infusion of angiotensin II), miR-21 expression increased as AAA developed. Lentiviral overexpression of miR-21 induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion. miR-21 overexpression substantially decreased expression of the phosphatase and tensin homolog (PTEN) protein, leading to increased phosphorylation and activation of AKT, a component of a pro-proliferative and antiapoptotic pathway. Systemic injection of a locked nucleic acid-modified antagomir targeting miR-21 diminished the pro-proliferative impact of down-regulated PTEN, leading to a marked increase in the size of AAA. Similar results were seen in mice with AAA augmented by nicotine and in human aortic tissue samples from patients undergoing surgical repair of AAA (with more pronounced effects observed in smokers). Modulation of miR-21 expression shows potential as a new therapeutic option to limit AAA expansion and vascular disease progression.

View details for DOI 10.1126/scitranslmed.3003441

View details for Web of Science ID 000300952100004

View details for PubMedID 22357537

Abstract

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe-/- mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti-miR-29b greatly increased collagen expression, leading to an early fibrotic response in the abdominal aortic wall and resulting in a significant reduction in AAA progression over time in both models. In contrast, overexpression of miR-29b using a lentiviral vector led to augmented AAA expansion and significant increase of aortic rupture rate. Cell culture studies identified aortic fibroblasts as the likely vascular cell type mediating the profibrotic effects of miR-29b modulation. A similar pattern of reduced miR-29b expression and increased target gene expression was observed in human AAA tissue samples compared with that in organ donor controls. These data suggest that therapeutic manipulation of miR-29b and its target genes holds promise for limiting AAA disease progression and protecting from rupture.

View details for DOI 10.1172/JCI61598

View details for Web of Science ID 000299765800016

View details for PubMedID 22269326

Abstract

Inflammation plays a critical role in atherosclerosis and is associated with upregulation of inducible nitric oxide synthase (iNOS). We studied bioluminescence imaging (BLI) to track iNOS gene expression in a murine model of vascular inflammation.Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in 18 iNOS-luc reporter mice. In vivo iNOS expression was imaged serially by BLI over 14 days, followed by in situ BLI and histology.BLI signal from ligated carotids increased over 14 days (9.7 ± 4.4 × 10(3 ) vs. 4.4 ± 1.7 × 10(3) photons/s/cm(2)/sr at baseline, p < 0.001 vs. baseline, p < 0.05 vs. sham controls). Histology confirmed substantial macrophage infiltration, with iNOS and luciferase expression, only in ligated left carotid arteries and not controls.BLI allows in vivo detection of iNOS expression in murine carotid lesions and may provide a valuable approach for monitoring vascular gene expression and inflammation in small animal models.

View details for DOI 10.1007/s11307-010-0451-5

View details for Web of Science ID 000296794400002

View details for PubMedID 21057879

Abstract

Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement.The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

View details for DOI 10.1161/CIRCIMAGING.110.960591

View details for Web of Science ID 000295030600017

View details for PubMedID 21719779

Abstract

The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, in silico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms.

View details for DOI 10.1007/s10439-011-0284-7

View details for Web of Science ID 000291479600010

View details for PubMedID 21404126

Abstract

We investigated the association between physical activity and coronary vasodilation to nitroglycerin (NTG) in the ADVANCE (Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology) cohort of older healthy subjects.Physical activity may exert its beneficial effects by augmenting coronary responsiveness to nitric oxide. The relationship between physical activity and coronary vasodilatory response to NTG, an exogenous nitric oxide donor, has not been studied in a community-based population with typical activity levels.In 212 older adults (ages 60 to 72 years) without cardiovascular disease, we measured the coronary vasodilatory response to NTG using magnetic resonance angiography and physical activity using the Stanford Seven-Day Physical Activity Recall Questionnaire. The primary predictor measure was total physical activity (kcal/kg/day). The primary outcome measure was coronary vasodilatory response (percent increase of cross-sectional area post-NTG).Coronary vasodilation was 27.6% in more active subjects (>35 kcal/kg/day, e.g., 1 h of walking per day) compared to 18.9% in less active subjects (p=0.03). Regression analysis showed a significant positive correlation between coronary vasodilation and physical activity (p=0.003), with a slope (beta) of 1.2% per kcal/kg/day. This finding remained significant after adjustment for cardiac risk factors, coronary calcium, the use of vasoactive or statin medications, and analysis of physical activity by quintiles (p < 0.05). Coronary vasodilation was also associated with physical activity intensity (p = 0.03).In an asymptomatic, community-based cohort of older adults, increased coronary vasodilatory response was independently associated with greater physical activity, supporting the benefits of exercise on the order of 1 h of walking per day.

View details for DOI 10.1016/j.jcmg.2011.05.001

View details for Web of Science ID 000292042900009

View details for PubMedID 21679897

Abstract

Cage-like protein nanoparticles are promising platforms for cell- and tissue-specific targeted delivery of imaging and therapeutic agents. Here, we have successfully modified the 12 nm small heat shock protein from Methanococcus jannaschii (MjHsp) to detect atherosclerotic plaque lesions in a mouse model system. As macrophages are centrally involved in the initiation and progression of atherosclerosis, targeted imaging of macrophages is valuable to assess the biologic status of the blood vessel wall. LyP-1, a nine residue peptide, has been shown to target tumor-associated macrophages. Thus, LyP-1 was genetically incorporated onto the exterior surface of MjHsp, while a fluorescent molecule (Cy5.5) was conjugated on the interior cavity. This bioengineered protein cage, LyP-Hsp, exhibited enhanced affinity to macrophage in vitro. Furthermore, in vivo injection of LyP-Hsp allowed visualization of macrophage-rich murine carotid lesions by in situ and ex vivo fluorescence imaging. These results demonstrate the potential of LyP-1-conjugated protein cages as nanoscale platforms for delivery of imaging agents for the diagnosis of atherosclerosis.

View details for DOI 10.1021/nn102863y

View details for Web of Science ID 000289742100011

View details for PubMedID 21391720

Abstract

The purpose of this study is to validate numerical simulations of flow and pressure in an abdominal aortic aneurysm (AAA) using phase-contrast magnetic resonance imaging (PCMRI) and an in vitro phantom under physiological flow and pressure conditions. We constructed a two-outlet physical flow phantom based on patient imaging data of an AAA and developed a physical Windkessel model to use as outlet boundary conditions. We then acquired PCMRI data in the phantom while it operated under conditions mimicking a resting and a light exercise physiological state. Next, we performed in silico numerical simulations and compared experimentally measured velocities, flows, and pressures in the in vitro phantom to those computed in the in silico simulations. There was a high degree of agreement in all of the pressure and flow waveform shapes and magnitudes between the experimental measurements and simulated results. The average pressures and flow split difference between experiment and simulation were all within 2%. Velocity patterns showed good agreement between experimental measurements and simulated results, especially in the case of whole-cycle averaged comparisons. We demonstrated methods to perform in vitro phantom experiments with physiological flows and pressures, showing good agreement between numerically simulated and experimentally measured velocity fields and pressure waveforms in a complex patient-specific AAA geometry.

View details for DOI 10.1115/1.4003526

View details for Web of Science ID 000288706600004

View details for PubMedID 21428677

Abstract

Atherosclerosis is a leading cause of death worldwide. Macrophages are key components of vascular inflammation, which contributes to the development and complications of atherosclerosis. Ferritin, an iron storage and transport protein, has been found to accumulate in macrophages in human atherosclerotic plaques. We hypothesized that ferritin could serve as an intrinsic nano-platform to target delivery of imaging agents to vascular macrophages to detect high-risk atherosclerotic plaques. Here we show that engineered human ferritin protein cages, either conjugated to the fluorescent Cy5.5 molecule or encapsulating a magnetite nanoparticle, are taken up in vivo by macrophages in murine atherosclerotic carotid arteries and can be imaged by fluorescence and magnetic resonance imaging. These results indicate that human ferritin can serve as a nanoparticle platform to image vascular inflammation in vivo.

View details for DOI 10.1016/j.biomaterials.2010.09.029

View details for Web of Science ID 000287073000020

View details for PubMedID 21074263

Abstract

FeCo/graphitic-carbon nanocrystals (FeCo/GC) are biocompatible, high-relaxivity, multi-functional nanoparticles. Macrophages represent important cellular imaging targets for assessing vascular inflammation. We evaluated FeCo/GC for vascular macrophage uptake and imaging in vivo using fluorescence and MRI.Hyperlipidemic and diabetic mice underwent carotid ligation to produce a macrophage-rich vascular lesion. In situ and ex vivo fluorescence imaging were performed at 48 hours after intravenous injection of FeCo/GC conjugated to Cy5.5 (n?=?8, 8 nmol of Cy5.5/mouse). Significant fluorescence signal from FeCo/GC-Cy5.5 was present in the ligated left carotid arteries, but not in the control (non-ligated) right carotid arteries or sham-operated carotid arteries (p?=?0.03 for ligated vs. non-ligated). Serial in vivo 3T MRI was performed at 48 and 72 hours after intravenous FeCo/GC (n?=?6, 270 µg Fe/mouse). Significant T2* signal loss from FeCo/GC was seen in ligated left carotid arteries, not in non-ligated controls (p?=?0.03). Immunofluorescence staining showed colocalization of FeCo/GC and macrophages in ligated carotid arteries.FeCo/GC accumulates in vascular macrophages in vivo, allowing fluorescence and MR imaging. This multi-functional high-relaxivity nanoparticle platform provides a promising approach for cellular imaging of vascular inflammation.

View details for DOI 10.1371/journal.pone.0014523

View details for Web of Science ID 000286516500005

View details for PubMedID 21264237

Abstract

The aim of this study was to definitively assess the validity of noninvasive high-frequency ultrasound (US) measurements of aortic luminal diameter (ALD) in a murine model of elastase-induced abdominal aortic aneurysm in comparison with in situ video microscopy (VM).C57BL/6 mice underwent transient perfusion of the aorta with either elastase (n = 20: Elastase group) or saline (n = 10: Sham). Unoperated mice (n = 10) were also studied.ALD measurements by US had excellent linear correlation and absolute agreement with that by VM in both Control (unoperated or sham-operated mice) and elastase groups (r = 0.96, intraclass correlation coefficient (ICC) = 0.88 and r = 0.93, ICC = 0.92, resp.). Bland-Altman analysis of US compared with VM measurements in both groups indicated good agreement, however US measurements were slightly but significantly higher than VM measurements in the control group (mean bias 0.039?mm, P < .05). Linear regression analysis revealed excellent correlation between US and VM measurements in both groups. (R² = 0.91 in Control group, R² = 0.85 in elastase group.) The reliability of US measurements was also confirmed by ex vivo histological measurements.High-frequency US provides reliable ALD measurements in developing murine abdominal aortic aneurysms.

View details for DOI 10.1155/2011/252141

View details for Web of Science ID 000289091200001

View details for PubMedID 21331328

Abstract

Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.

View details for DOI 10.1186/1532-429X-12-75

View details for Web of Science ID 000286371000001

View details for PubMedID 21192815

Abstract

Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin.Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.

View details for DOI 10.1186/1532-429X-12-50

View details for Web of Science ID 000282342300001

View details for PubMedID 20815898

Abstract

Magnetic resonance thermometry using the proton resonance frequency (PRF) shift is a promising technique for guiding thermal ablation. For temperature monitoring in moving organs, such as the liver and the heart, problems with motion must be addressed. Multi-baseline subtraction techniques have been proposed, which use a library of baseline images covering the respiratory and cardiac cycle. However, main field shifts due to lung and diaphragm motion can cause large inaccuracies in multi-baseline subtraction. Referenceless thermometry methods based on polynomial phase regression are immune to motion and susceptibility shifts. While referenceless methods can accurately estimate temperature within the organ, in general, the background phase at organ/tissue interfaces requires large polynomial orders to fit, leading to increased danger that the heated region itself will be fitted by the polynomial and thermal dose will be underestimated. In this paper, a hybrid method for PRF thermometry in moving organs is presented that combines the strengths of referenceless and multi-baseline thermometry.The hybrid image model assumes that three sources contribute to image phase during thermal treatment: Background anatomical phase, spatially smooth phase deviations, and focal, heat-induced phase shifts. The new model and temperature estimation algorithm were tested in the heart and liver of normal volunteers, in a moving phantom HIFU heating experiment, and in numerical simulations of thermal ablation. The results were compared to multi-baseline and referenceless methods alone.The hybrid method allows for in vivo temperature estimation in the liver and the heart with lower temperature uncertainty compared to multi-baseline and referenceless methods. The moving phantom HIFU experiment showed that the method accurately estimates temperature during motion in the presence of smooth main field shifts. Numerical simulations illustrated the method's sensitivity to algorithm parameters and hot spot features.This new hybrid method for MR thermometry in moving organs combines the strengths of both multi-baseline subtraction and referenceless thermometry and overcomes their fundamental weaknesses.

View details for DOI 10.1118/1.3475943

View details for Web of Science ID 000281906000053

View details for PubMedID 20964221

Abstract

This study evaluates how characterization of tissue heterogeneity of myocardial infarction by cardiovascular magnetic resonance (CMR) is associated with cardiovascular events (CVE) in patients with ischemic cardiomyopathy (ICM).Prior studies demonstrated that the quantification of myocardial scar volume by CMR is superior to left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction (LVEF) in predicting future CVE in ICM patients. Evaluation of infarct heterogeneity by measuring infarct core and border zones through CMR might have a higher association with CVE.Seventy patients (mean LVEF: 25 +/- 11%) considered for revascularization or medical management +/- implantable cardiac defibrillator were enrolled. A 1.5-T GE MRI (Signa, GE Healthcare, Milwaukee, Wisconsin) was used to acquire cine and delayed enhancement images. The patients' core and border zones of infarcted myocardium were analyzed and followed for CVE.Larger infarct border zone and its percentage of myocardium were found in the 29 patients (41%) who had CVE (median 13.3 g [interquartile range (IQR) 8.4 to 25.1 g] vs. 8.0 g [IQR 3.0 to 14.5 g], p = 0.02 and 7.8% [IQR 4.9% to 17.0%] vs. 4.1% [IQR 1.9% to 9.3%], p = 0.02, respectively). The core infarct zone and its percentage of myocardium, left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF were not statistically significant. Sub-analysis of the medical management and revascularization patients with CVE demonstrated that the medically managed patients had a larger border zone, whereas there was no difference between border and core zones in the revascularization group (p < 0.05).Quantification of core and border zones and their percentages of myocardium through CMR is associated with future CVE and might assist in the management of patients with ICM.

View details for DOI 10.1016/j.jacc.2010.01.052

View details for Web of Science ID 000278565200012

View details for PubMedID 20538171

Abstract

Paradoxical embolization can occur when a right-to-left shunt allows a venous thromboembolus to escape filtration by the lungs. Venous collateral pathways draining into the left heart incited by superior vena cava obstruction are a rare acquired right-to-left shunt. Herein, the authors report on a case of transient ischemic attack in a patient with vena caval occlusion secondary to histoplasmosis-related fibrosing mediastinitis, with subclavian vein thrombosis and a right-to-left extracardiac shunt diagnosed with echocardiography. Despite the complexity of the collateral network, this shunt was successfully eradicated with coil embolization.

View details for DOI 10.1016/j.jvir.2009.09.022

View details for Web of Science ID 000277367500017

View details for PubMedID 20123198

Abstract

FeCo-graphitic carbon shell nanocrystals are a novel MRI contrast agent with unprecedented high per-metal-atom-basis relaxivity (r(1) = 97 mM(-1) sec(-1), r(2) = 400 mM(-1) sec(-1)) and multifunctional capabilities. While the conventional gadolinium-based contrast-enhanced angiographic magnetic MRI has proven useful for diagnosis of vascular diseases, its short circulation time and relatively low sensitivity render high-resolution MRI of morphologically small vascular structures such as those involved in collateral, arteriogenic, and angiogenic vessel formation challenging. Here, by combining FeCo-graphitic carbon shell nanocrystals with high-resolution MRI technique, we demonstrate that such microvessels down to approximately 100 mum can be monitored in high contrast and noninvasively using a conventional 1.5-T clinical MRI system, achieving a diagnostic imaging standard approximating that of the more invasive X-ray angiography. Preliminary in vitro and in vivo toxicity study results also show no sign of toxicity.

View details for DOI 10.1002/mrm.22132

View details for Web of Science ID 000272067600017

View details for PubMedID 19859938

View details for DOI 10.1056/NEJMicm0802946

View details for PubMedID 19864670

Abstract

Mural inflammation and neovascularization are characteristic pathological features of abdominal aortic aneurysm (AAA) disease. Vascular endothelial growth factor receptor (VEGFR) expression may also mediate AAA growth and rupture. We examined VEGFR expression as a function of AAA disease progression in the Apolipoprotein E-deficient (Apo E(-/-)) murine AAA model.Apo E(-/-) mice maintained on a high-fat diet underwent continuous infusion with angiotensin II at 1000 ng/kg/min (Ang II) or vehicle (Control) via subcutaneous osmotic pump. Serial transabdominal ultrasound measurements of abdominal aortic diameter were recorded (n=16 mice, 3 to 4 time points per mouse) for up to 28 days. Near-infrared receptor fluorescent (NIRF) imaging was performed on Ang II mice (n=9) and Controls (n=5) with scVEGF/Cy, a single-chain VEGF homo-dimer labeled with Cy 5.5 fluorescent tracer (7 to 18 microg/mouse IV). NIRF with inactivated single chain VEGF/Cy tracer (scVEGF/In, 18 microg/mouse IV) was performed on 2 additional Ang II mice to control for nonreceptor-mediated tracer binding and uptake. After image acquisition and sacrifice, aortae were harvested for analysis. An additional AAA mouse cohort received either an oral angiogenesis inhibitor or suitable negative or positive controls to clarify the significance of angiogenesis in experimental aneurysm progression. Aneurysms developed in the suprarenal aortic segment of all Ang II mice. Significantly greater fluorescent signal was obtained from aneurysmal aorta as compared to remote, uninvolved aortic segments in Ang II scVEGF/Cy mice or AAA in scVEGF/In mice or suprarenal aortic segments in Control mice. Signal intensity increased in a diameter-dependent fashion in aneurysmal segments. Immunostaining confirmed mural VEGFR-2 expression in medial smooth muscle cells. Treatment with an angiogenesis inhibitor attenuated AAA formation while decreasing mural macrophage infiltration and CD-31(+) cell density.Mural VEGFR expression, as determined by scVEGF/Cy fluorescent imaging and VEGFR-2 immunostaining, increases in experimental AAAs in a diameter-dependent fashion. Angiogenesis inhibition limits AAA progression. Clinical VEGFR expression imaging strategies, if feasible, may improve real-time monitoring of AAA disease progression and response to suppressive strategies.

View details for DOI 10.1161/ATVBAHA.109.187757

View details for Web of Science ID 000269848600010

View details for PubMedID 19574559

View details for DOI 10.1016/j.ijcard.2007.08.113

View details for Web of Science ID 000263950100046

View details for PubMedID 18164082

Abstract

These reporting guidelines are recommended by the Society for Cardiovascular Magnetic Resonance (SCMR) to provide a framework for healthcare delivery systems to disseminate cardiac and vascular imaging findings related to the performance of cardiovascular magnetic resonance (CMR) examinations.

View details for DOI 10.1186/1532-429X-11-5

View details for Web of Science ID 000266105700001

View details for PubMedID 19257889

Abstract

Macrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)-iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R(2) relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn-iron oxide contrast agent to assess inflammatory disease status such as macrophage-rich atherosclerotic plaques in vivo.

View details for DOI 10.1002/mrm.21761

View details for Web of Science ID 000260341700008

View details for PubMedID 18956458

Abstract

Mouse embryonic stem cells have demonstrated potential to restore infarcted myocardium after acute myocardial infarction. Although the underlying mechanism remains controversial, magnetic resonance imaging has provided reliable in vivo assessment of functional recovery after cellular transplants. Multimodal comparison of the restorative effects of mouse embryonic stem cells and mouse embryonic fibroblasts was performed to validate magnetic resonance imaging data and provide mechanistic insight.SCID-beige mice (n = 55) underwent coronary artery ligation followed by injection of 2.5 x 10(5) mouse embryonic stem cells, 2.5 x 10(5) mouse embryonic fibroblasts, or normal saline solution. In vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells was evaluated by (1) in vivo pressure-volume loops, (2) in vivo bioluminescence imaging, and (3) ex vivo TaqMan (Roche Molecular Diagnostics, Pleasanton, Calif) polymerase chain reaction and immunohistologic examination.In vivo magnetic resonance imaging demonstrated significant improvement in left ventricular ejection fraction at 1 week in the mouse embryonic stem cell group. This finding was validated with (1) pressure-volume loop analysis demonstrating significantly improved systolic and diastolic functions, (2) bioluminescence imaging and polymerase chain reaction showing superior posttransplant survival of mouse embryonic stem cells, (3) immunohistologic identification of cardiac phenotype within engrafted mouse embryonic stem cells, and (4) polymerase chain reaction measuring increased expressions of angiogenic and antiapoptotic genes and decreased expressions of antifibrotic genes.This study validates in vivo magnetic resonance imaging as an effective means of evaluating the restorative potential of mouse embryonic stem cells.

View details for DOI 10.1016/j.jtcvs.2007.12.053

View details for Web of Science ID 000260314800033

View details for PubMedID 18954646

Abstract

Impaired coronary vasodilation to both endothelial-dependent and endothelial-independent stimuli have been associated with atherosclerosis. Direct measurement of coronary vasodilation using x-ray angiography or intravascular ultrasound is invasive and, thus, not appropriate for asymptomatic patients or for serial follow-up. In this study, high-resolution coronary cardiovascular magnetic resonance (CMR) was used to investigate the vasodilatory response to nitroglycerine (NTG) of asymptomatic patients at high risk for CAD.A total of 46 asymptomatic subjects were studied: 13 high-risk patients [8 with diabetes mellitus (DM), 5 with end stage renal disease (ESRD)] and 33 age-matched controls. Long-axis and cross-sectional coronary artery images were acquired pre- and 5 minutes post-sublingual NTG using a sub-mm-resolution multi-slice spiral coronary CMR sequence. Coronary cross sectional area (CSA) was measured on pre- and post-NTG images and % coronary vasodilation was calculated.Patients with DM and ESRD had impaired coronary vasodilation to NTG compared to age-matched controls (17.8 +/- 7.3% vs. 25.6 +/- 7.1%, p = 0.002). This remained significant for ESRD patients alone (14.8 +/- 7.7% vs. 25.6 +/- 7.1%; p = 0.003) and for DM patients alone (19.8 +/- 6.3% vs. 25.6 +/- 7.1%; p = 0.049), with a non-significant trend toward greater impairment in the ESRD vs. DM patients (14.8 +/- 7.7% vs. 19.8 +/- 6.3%; p = 0.23).Noninvasive coronary CMR demonstrates impairment of coronary vasodilation to NTG in high-risk patients with DM and ESRD. This may provide a functional indicator of subclinical atherosclerosis and warrants clinical follow up to determine prognostic significance.

View details for DOI 10.1186/1532-429X-10-28

View details for Web of Science ID 000258405900001

View details for PubMedID 18513419

Abstract

Cardiovascular magnetic resonance (CMR) can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM).We consecutively studied 86 patients with ICM (LVEF < 50%, mean LVEF: 26 +/- 12%) with CMR before revascularization or medication therapy +/- implantable cardiac defibrillator, determined the amount of myocardial scar, and followed for development of cardiovascular events. Thirty-three patients (38%) had cardiovascular events (mean follow-up: 20 +/- 16 months). Patients who developed cardiovascular events had larger scar volume and scar percentage of the myocardium than those who did not develop cardiovascular events (16.8 +/- 12.4 cm3 vs. 11.7 +/- 12.6 cm3, p = 0.023 and 10.2 +/- 6.9% vs. 7.2 +/- 6.7%, p = 0.037, respectively). There were no significant differences in LVEDV, LVESV and LVEF between the patients with and without cardiovascular events (231 +/- 76 ml vs. 230 +/- 88 ml; 180 +/- 73 ml vs. 175 +/- 90 ml; and 25 +/- 10% vs. 27 +/- 13%, respectively).Quantification of the scar volume and scar percentage by CMR is superior to LVEDV, LVESV, and LVEF in prognosticating the future likelihood of the development of cardiovascular events in patients with ICM.

View details for DOI 10.1186/1532-429X-10-17

View details for Web of Science ID 000257207000002

View details for PubMedID 18400089

Abstract

This study evaluated the hypothesis that impaired nitroglycerin (NTG)-induced coronary vasodilation is associated with advanced coronary atherosclerosis in asymptomatic older patients.Atherosclerosis is associated with both structural and functional abnormalities of the vessel wall. Noninvasive functional measures of subclinical coronary atherosclerosis may help characterize high-risk subjects and guide preventive therapy.A total of 236 older patients (age 60 to 72 years, 33% female) without a history of cardiovascular disease were studied. Nitroglycerin-induced coronary vasodilation was measured by magnetic resonance angiography (MRA). Cross-sectional images of the right coronary artery were acquired before and 5 min after 0.4-mg sublingual NTG using a gated, breath-held spiral coronary MRA sequence (0.7-mm resolution). Quantitative analysis of the increase in cross-sectional area was performed in the 90% of patients (n = 212) with adequate image quality. Quantitation of coronary artery calcification (CAC) was performed by multidetector computed tomography using the Agatston method.Forty patients (19%) had advanced CAC (> or =400). Coronary vasodilation to NTG was significantly impaired (p = 0.02) in patients with advanced CAC (median [interquartile range] = 15.9% [4.2% to 28.0%] vs. 21.5% [9.6% to 36.6%] for CAC <400). Importantly, NTG-induced coronary vasodilation remained independently associated with advanced CAC after multivariate analysis incorporating risk factors (p = 0.02) and other potential confounders (p = 0.04). There was no significant difference in coronary vasodilation between men and women, but few women (n = 3) had advanced CAC.Impaired NTG-induced coronary vasodilation by MRA is associated with advanced coronary atherosclerosis in a community-based cohort of older asymptomatic subjects. Coronary MRA may provide a noninvasive functional assessment of subclinical coronary atherosclerosis.

View details for DOI 10.1016/j.jcmg.2007.12.001

View details for Web of Science ID 000207649700007

View details for PubMedID 19356424

Abstract

Nanocrystals with advanced magnetic or optical properties have been actively pursued for potential biological applications, including integrated imaging, diagnosis and therapy. Among various magnetic nanocrystals, FeCo has superior magnetic properties, but it has yet to be explored owing to the problems of easy oxidation and potential toxicity. Previously, FeCo nanocrystals with multilayered graphitic carbon, pyrolytic carbon or inert metals have been obtained, but not in the single-shelled, discrete, chemically functionalized and water-soluble forms desired for biological applications. Here, we present a scalable chemical vapour deposition method to synthesize FeCo/single-graphitic-shell nanocrystals that are soluble and stable in water solutions. We explore the multiple functionalities of these core-shell materials by characterizing the magnetic properties of the FeCo core and near-infrared optical absorbance of the single-layered graphitic shell. The nanocrystals exhibit ultra-high saturation magnetization, r1 and r2 relaxivities and high optical absorbance in the near-infrared region. Mesenchymal stem cells are able to internalize these nanoparticles, showing high negative-contrast enhancement in magnetic-resonance imaging (MRI). Preliminary in vivo experiments achieve long-lasting positive-contrast enhancement for vascular MRI in rabbits. These results point to the potential of using these nanocrystals for integrated diagnosis and therapeutic (photothermal-ablation) applications.

View details for DOI 10.1038/nmat1775

View details for Web of Science ID 000242478600021

View details for PubMedID 17115025

View details for DOI 10.1161/CIRCULATIONAHA.104.532481

View details for Web of Science ID 000238033400019

View details for PubMedID 16754807

Abstract

To compare black-blood multicontrast carotid imaging at 3T and 1.5T and assess compatibility between morphological measurements of carotid arteries at 1.5T and 3T.Five healthy subjects and two atherosclerosis patients were scanned in 1.5T and 3T scanners with a similar protocol providing transverse T1-, T2-, and proton density (PD)-weighted black-blood images using a fast spin-echo sequence with single- (T1-weighted) or multislice (PD-/T2-weighted) double inversion recovery (DIR) preparation. Wall and lumen signal-to-noise ratio (SNR) and wall/lumen contrast-to-noise ratio (CNR) were compared in 44 artery cross-sections by paired t-test. Interscanner variability of the lumen area (LA), wall area (WA), and mean wall thickness (MWT) was assessed using Bland-Altman analysis.Wall SNR and lumen/wall CNR significantly increased (P < 0.0001) at 3T with a 1.5-fold gain for T1-weighted images and a 1.7/1.8-fold gain for PD-/T2-weighted images. Lumen SNR did not differ for single-slice DIR T1-weighted images (P = 0.2), but was larger at 3T for multislice DIR PD-/T2-weighted images (P = 0.01/0.03). The LA, WA, and MWT demonstrated good agreement with no significant bias (P 0.5), a coefficient of variation (CV) of < 10%, and intraclass correlation coefficient (ICC) of > 0.95.This study demonstrated significant improvement in SNR, CNR, and image quality for high- resolution black-blood imaging of carotid arteries at 3T. Morphologic measurements are compatible between 1.5T and 3T.

View details for DOI 10.1002/jmri.20562

View details for Web of Science ID 000237124800011

View details for PubMedID 16555259

Abstract

Cell therapy has demonstrated the potential to restore injured myocardium. A reliable in vivo imaging method to localize transplanted cells and monitor their restorative effects will enable a systematic investigation of this therapeutic modality. The dual MRI capability of imaging both magnetically labeled mouse embryonic stem cells (mESC) and their restorative effects on cardiac function in a murine model of acute myocardial infarction is demonstrated. Serial in vivo MR detection of transplanted mESC and monitoring of the mESC-treated myocardium was conducted over a 4-week period using a 1.5 T clinical scanner. During the 4-week duration, the mESC-treated myocardium demonstrated sustained improvement of the left ventricular (LV) ejection fraction and conservation of LV mass. Furthermore, no significant difference of their restorative effects on the cardiac function was created by the magnetic labeling of mESC. Thus, in vivo MRI enables simultaneous detection of transplanted mESC and their therapeutic effect on the injured myocardium.

View details for DOI 10.1002/mrm.20702

View details for Web of Science ID 000234342800025

View details for PubMedID 16315206

Abstract

CMR is valuable in the evaluation of congenital heart disease (CHD). Traditional flow imaging sequences involve cardiac and respiratory gating, increasing scan time and susceptibility to arrhythmias. We studied a real-time color-flow CMR system for the detection of flow abnormalities in 13 adults with CHD. All 16 congenital flow abnormalities previously detected by echocardiography were visualized using color-flow CMR, including atrial septal defects (n = 4), ventricular septal defects (n = 9), aortic coarctation (n = 1), Blalock-Taussig shunt (n = 1) and Fontan shunt (n = 1). Real-time color-flow CMR can identify intra- and extra-cardiac flow abnormalities in adults with congenital heart disease.

View details for DOI 10.1080/10976640600777728

View details for Web of Science ID 000241485600007

View details for PubMedID 17060103

Abstract

We assessed whether cardiovascular magnetic resonance imaging (CMR) of peri-infarct ischemia provides prognostic information in severe ischemic cardiomyopathy (ICM) patients referred for revascularization.Twenty-one patients with severe ICM were recruited prospectively for combined stress adenosine perfusion, late gadolinium enhancement, and rest perfusion studies. The patients were followed for in-hospital and post-discharge cardiovascular events.During 12+/- 9.8 months follow-up, 67% of the patients with peri-infarct ischemia and 13% of the patients without peri-infarct ischemia had cardiovascular events (p = 0.03). CONCLUSION. In severe ICM patients, the presence of peri-infarct ischemia was associated with a higher incidence of cardiovascular events.

View details for DOI 10.1080/10976640600737615

View details for Web of Science ID 000241485600002

View details for PubMedID 17060098

Abstract

To study the feasibility of a combined high spatial and temporal resolution real-time spiral MRI sequence for guiding coronary-sized vascular interventions.Eight New Zealand White rabbits (four normal and four with a surgically-created stenosis in the abdominal aorta) were studied. A real-time interactive spiral MRI sequence combining 1.1 x 1.1 mm(2) in-plane resolution and 189-msec total image acquisition time was used to image all phases of an interventional procedure (i.e., guidewire placement, balloon angioplasty, and stenting) in the rabbit aorta using coronary-sized devices on a 1.5 T MRI system.Real-time spiral MRI identified all rabbit aortic stenoses and provided high-temporal-resolution visualization of guide-wires crossing the stenoses in all animals. Angioplasty balloon dilatation and deployment of coronary-sized copper stents in the rabbit aorta were also successfully imaged by real-time spiral MRI.Combining high spatial and temporal resolution with spiral MRI allows real-time MR-guided vascular intervention using coronary-sized devices in a rabbit model. This is a promising approach for guiding coronary interventions.

View details for DOI 10.1002/jmri.20409

View details for Web of Science ID 000233096000015

Abstract

Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.

View details for DOI 10.1002/mrm.20477

View details for Web of Science ID 000228796900002

View details for PubMedID 15844142

Abstract

The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation.Coronary vasodilation plays a vital role in the human coronary circulation. Previous studies of epicardial coronary vasodilation have used invasive coronary angiography. Coronary MRA may provide an alternative noninvasive method to directly assess changes in coronary size.Thirty-two subjects were studied: 12 patients (age 55 +/- 18 years) and 20 healthy subjects (age 34 +/- 4 years). High-resolution multi-slice spiral coronary MRA (in-plane resolution of 0.52 to 0.75 mm) was performed before and after sublingual nitroglycerin (NTG). Quantitative analysis of coronary vasodilation was performed on cross-sectional images of the right coronary artery (RCA). A time-course analysis of coronary vasodilation was performed in a subset of eight subjects for 30 min after NTG. Signal-to-noise ratio was also measured on the in-plane RCA images.Coronary MRA demonstrated a 23% increase in cross-sectional area after NTG (16.9 +/- 7.8 mm2 to 20.8 +/- 8.9 mm2, p <0.0001), with significant vasodilation between 3 and 15 min after NTG on time-course analysis. The MRA measurements had low interobserver variability (< or =5%) and good correlation with X-ray angiography (r=0.98). The magnitude of vasodilation correlated with baseline cross-sectional area (r=0.52, p=0.03) and age (r=0.40, p=0.019). Post-NTG images also demonstrated a 31% improvement in coronary signal-to-noise ratio (p = 0.002).Nitroglycerin-enhanced coronary MRA can noninvasively measure coronary artery vasodilation and is a promising noninvasive technique to study coronary vasomotor function.

View details for DOI 10.1016/j.jacc.2004.09.057

View details for Web of Science ID 000226012600020

View details for PubMedID 15629383

Abstract

A dynamic real-time (dRT) architecture has been developed to address limitations in magnetic resonance coronary angiography (MRCA). A prospective clinical trial of 45 patients suspected of coronary artery disease was conducted to determine clinical utility of this integrated real-time system.Clinical implementation of MRCA is not performed routinely today. However, improved anatomic coverage, image quality, and scan flexibility may enhance its clinical utility. A novel real-time architecture addresses these challenges through instantaneous reconfiguration between real-time (RT) and high-resolution (HR) imaging sequences with dynamic selection of the desired element on a custom-designed receiver coil.A total of 45 subjects were recruited consecutively to evaluate scan time, anatomic coverage, image quality, and detection of coronary lesions. Using a modern PC, the dRT switches from RT to gated HR imaging sequence in one repetition time (39 ms). Magnetic resonance imaging (MRI) scanning was performed using a custom-designed coronary coil consisting of two four-inch phase-array circular elements enabled with real-time selection of the desired coil element.All studies were completed in less than 45 minutes and required a mean of 12 breath holds (16 heartbeats). Of the total number of coronary segments, 91% (357/394) were visualized. Excellent or good image quality was achieved in 86% of the segments. Blinded analysis of the coronary arteries revealed sensitivity of 93% and specificity of 88% in the detection of coronary stenoses.The integrated environment of dRT provides a rapid and flexible scan protocol for MRCA while achieving wide anatomical coverage, high image quality, and reliable detection of coronary stenosis in short scan time.

View details for DOI 10.1016/j.JCMR.20036192

View details for Web of Science ID 000226039200015

View details for PubMedID 15646892

Abstract

MR coronary angiography (MRCA) has been demonstrated successfully at 3 Tesla (T). However, the advantages remain unclear. No systematic comparison of MRCA between 1.5 T and 3 T has been performed. Therefore, anatomic coverage, image quality, signal-to-noise ratio (SNR), contrast-to-noise ration (CNR), and susceptibility artifacts were compared in 23 subjects.Identical real-time (RT) and high-resolution (HR) sequences were implemented on the GE 1.5 T (Signa Twinspeed) and 3.0 T (Signa VH/i) whole body systems (GE, Milwaukee, WI). Both scanners were equipped with high-performance gradient systems capable of 40 mT/m peak amplitude and 150 mT/m/ms slew rate. Real-time localization of the coronary arteries was followed by a cardiac-gated, breath-hold HR sequence. Twenty-three subjects were recruited consecutively and underwent both 3 T and 1.5 T MRCA within one week. Coronary coverage based on the number of coronary segments visualized, image quality using a grading scale, SNR, CNR, and presence of susceptibility artifacts were analyzed. A significant improvement in SNR (47%), CNR (30%), and image quality were seen in 3 T. However, a significant increase in susceptibility artifacts was also noted.MRCA at 3 T significantly improves SNR, CNR, and image quality at the expense of susceptibility artifacts. Further optimization of the imaging parameters at 3 T may facilitate clinical implementation of MRCA.

View details for DOI 10.1081/JCMR.20036180

View details for Web of Science ID 000226039200014

View details for PubMedID 15646891

Abstract

Previously published reports show that there is significant intraobserver, interobserver, and interinstitutional variability in the determination of left ventricular (LV) ejection fraction (EF) by echocardiography. With the increased deployment of echocardiography (eg, handheld devices), there exists a need for developing a simple, intuitive approach for evaluating LVEF that allows a wider range of physicians to accurately and rapidly determine LVEF.We sought to create a system for assessing LVEF that relies on recognition and matching of patterns, rather than on mathematic calculations and geometric assumptions.A library of videoclips of cardiac function was compiled from 54 patients who spanned the spectrum of LVEF. LVEFs were calculated for these patients using standard echocardiographic methods, with further validation of a subsample using cardiac magnetic resonance imaging measurement of LVEF. The library of images was used to create a software tool for assessing LVEF on the basis of a "template-matching" approach. The software tool was then tested on medical students (N=13) to determine whether it enabled relatively untrained individuals to make accurate LVEF estimates.Using a template-matching approach for interpretation of echocardiograms, medical students were able to accurately estimate LVEF after only a limited introduction to echocardiography. Their LVEF estimates showed good correlation and agreement with gold standard (r = 0.88, standard square of the estimate = 6.0, limits of agreement = +12.0%, -15.6%).A new visual approach for assessing cardiac function using template matching can accurately estimate LVEF. With minimal training, medical students can make LVEF estimates that correlate well with gold standard. The application of this new approach includes allowing for the interpretation of LVEF from echocardiograms to be performed by a broader spectrum of physicians.

View details for DOI 10.1067/S0894-7317(03)00400-0

View details for Web of Science ID 000184604400007

View details for PubMedID 12878991

Abstract

A spiral high-resolution coronary artery imaging sequence (SH) interfaced with real-time localization system (RT) has been developed. A clinical study of 40 patients suspected of coronary artery disease (CAD) was conducted. Segmented k-space acquisition techniques have dominated magnetic resonance coronary angiography (MRCA) over the last decade. Although a recent multicenter trial using this technique demonstrated encouraging results, the technique was hampered by low specificity. Spiral k-space acquisition had demonstrated several advantages for MRCA. Therefore, a first clinical trial implementing spiral high-resolution coronary imaging sequence with real-time localization (SH-RT) was performed.A clinical study of 40 patients suspected of CAD undergoing X-ray angiography was conducted to analyze the clinical reliability of this novel imaging system. The SH-RT had been designed to exploit the unique capability of two imaging sequences. The RT allowed a rapid localization of the coronary arteries. Then SH achieved multislice acquisition during a short breath-hold with submillimeter resolution. The MRCA data were analyzed for scan time, anatomic coverage, image quality, and accuracy in detecting CAD. In 40 subjects, SH achieved 0.7 to 0.9 mm resolution with 14-heartbeat breath-holds. Excellent or good image quality was achieved in 78% (263/337) of the coronary segments. Blinded consensus reading among three observers generated sensitivity of 76% and specificity of 91% in the detection of CAD compared with X-ray angiography. The MRCA imaging sequence implementing a novel spiral k-space acquisition technique enabled rapid and reliable imaging of the CAD in submillimeter resolution with short breath-holds.

View details for DOI 10.1016/S0735-1097(03)00079-2

View details for Web of Science ID 000181968900011

View details for PubMedID 12679213

Abstract

Magnetic resonance coronary angiography (MRCA) has witnessed tremendous technical advances over the past decade. Although high-quality images of the coronary arteries have been demonstrated, this imaging modality is not performed routinely today. The fundamental properties of the coronary arteries deterring noninvasive imaging are well known. This article provides an overview of the developmental efforts to overcome these challenges, and highlights key technical and clinical advances. The future prospect of MRCA depends on clinical implementation of the technique. In order to meet this challenge, the following issues must be addressed: contrast- and signal-to-noise ratio, temporal and spatial resolution, and scan protocol.

View details for PubMedID 12493161

Abstract

Hibernating myocardium refers to regions of impaired left ventricular function at rest due to coronary artery disease that is reversible with revascularization. The accurate identification and assessment of myocardial viability is a critical aspect of the management of the patient with coronary artery disease and left ventricular dysfunction. Several non-invasive methods exist to assist the clinician in distinguishing those patients with significant regions of hibernating myocardium from those who have non-viable scar. This is important not only to identify those patients who would most benefit from percutaneous intervention or surgery, but also to spare the latter group from the morbidity and mortality associated with a revascularization procedure that would provide little benefit. While nuclear medicine imaging is the most widely used means for evaluating myocardial viability, alternative modalities have emerged and have gained increasing acceptance in recent years. This article will review the echocardiographic and magnetic resonance imaging (MRI) methods that are currently available or under investigation to assess myocardial viability. These techniques include rest and stress echocardiography, myocardial contrast echocardiography, stress MRI, contrast-enhanced MRI and magnetic resonance spectroscopy (MRS).

View details for Web of Science ID 000175245600006

View details for PubMedID 11930186

Abstract

The Magnetic resonance imaging (MRI) is an emerging technology for catheter-based imaging and interventions. Real-time MRI is a promising methodfor overcoming catheter and physiologic motion for intravascular imaging.All imaging was performed on a 1.5 T Signa MRI scanner with high-speed gradients. Multiple catheter coils were designed and constructed, including low-profile, stub-matched coils. Coil sensitivity patterns and SNR measurements were compared. Real-time imaging was performed with an interleaved spiral sequence using a dedicated workstation, providing real-time data acquisition, image reconstruction and interactive control and display. Real-time "black-blood" imaging was achieved through incorporation of off-slice saturation pulses. The imaging sequence was tested in a continuous flow phantom and then in vivo in the rabbit aorta using a 2 mm catheter coil.The real-time intravascular imaging sequence achieved 120-440 micron resolution at up to 16 frames per second. Low-profile stub-tuned catheter coils achieved similar SNR to larger traditional coil designs. In the phantom experiments, addition of real-time black-blood saturation pulses effectively suppressed the flow signal and allowed visualization of the phantom wall. In vivo experiments clearly showed real-time intravascular imaging of the rabbit aortic wall with minimal motion artifacts and effective blood signal suppression.Real-time imaging with low-profile coil designs provides significant enhancements to intravascular MRI.

View details for Web of Science ID 000176057200005

View details for PubMedID 12074137

View details for Web of Science ID 000173023400005

View details for PubMedID 11811327

Abstract

Conventional cardiovascular imaging, with a focus on identifying flow-limiting stenoses, does not directly image the atherosclerotic lesion. Recent clinical and pathobiologic data indicate that stenosis severity does not dictate cardiovascular risk and that there are functional, structural, and biologic features of atherosclerosis that are associated with cardiovascular events. Imaging technologies, such as ultrasound, light, x-ray, magnetic resonance, and targeted contrast agents, have been developed to characterize directly the atherosclerotic vessel wall. They provide promising approaches to predict cardiovascular risk and facilitate further study of the mechanisms of atherosclerosis progression and its response to therapy.

View details for PubMedID 10953263

Abstract

Though rare, anomalous coronary artery disease is a well-known cause of myocardial ischemia and sudden death among children and young adults. The projectional nature of conventional x-ray angiography often leads to difficulty in the definition of anomalous vessels. Studies have now documented the high accuracy of coronary magnetic resonance angiography (MRA) for the noninvasive detection and definition of anomalous coronary arteries among patients with suspected anomalous coronary arteries of congenital conditions associated with anomalous coronary arteries. With increasing clinical experience, coronary MRA will likely emerge as the gold standard for the diagnosis of this condition.

View details for Web of Science ID 000165077200009

View details for PubMedID 11545120

Abstract

For free-breathing, high-resolution, three-dimensional coronary magnetic resonance angiography (MRA), the use of intravascular contrast agents may be helpful for contrast enhancement between coronary blood and myocardium. In six patients, 0.1 mmol/kg of the intravascular contrast agent MS-325/AngioMARK was given intravenously followed by double-oblique, free-breathing, three-dimensional inversion-recovery coronary MRA with real-time navigator gating and motion correction. Contrast-enhanced, three-dimensional coronary MRA images were compared with images obtained with a T2 prepulse (T2Prep) without exogenous contrast. The contrast-enhanced images demonstrated a 69% improvement in the contrast-to-noise ratio (6.6 +/- 1.1 vs. 11.1 +/- 2.5; P < 0.01) compared with the T2Prep approach. By using the intravascular agent, extensive portions (> 80 mm) of the native left and right coronary system could be displayed consistently with sub-millimeter in-plane resolution. The intravascular contrast agent, MS-325/AngioMARK, leads to a considerable enhancement of the blood/muscle contrast for coronary MRA compared with T2Prep techniques. The clinical value of the agent remains to be defined in a larger patient series. J. Magn. Reson. Imaging 1999;10:790-799.

View details for Web of Science ID 000087572100025

View details for PubMedID 10548790

Abstract

Direct imaging of the atherosclerotic plaque, rather than the angiographic lumen, may provide greater insight into the response of atherosclerosis to cholesterol-lowering therapy. Aortic plaque was studied in vivo by MRI in rabbits undergoing dietary cholesterol intervention. Thirty-one rabbits underwent aortic balloon injury and high-cholesterol diet for 4 months and then were assigned to low-cholesterol versus continued high-cholesterol diet for up to an additional 16 months. High-resolution (310 micrometer) fast spin-echo MRI of the abdominal aorta was performed at 4, 12, and 20 months and compared with histology. MRI demonstrated a significant reduction in % area stenosis in rabbits placed on low-cholesterol diet (44.6+/-2. 1% at 20 months versus 55.8+/-1.5% at 4 months, P=0.0002). In contrast, % area stenosis increased in rabbits maintained on high-cholesterol diet (69.8+/-3.8% at 20 months versus 55.8+/-1.5% at 4 months, P=0.001). Similarly, plaque thickness decreased significantly in the low-cholesterol group (0.60+/-0.05 mm at 20 months versus 0.85+/-0.06 mm at 4 months, P=0.006), with a trend toward increase in the high-cholesterol group (1.02+/-0.08 mm at 20 months versus 0.85+/-0.06 mm at 4 months, P=0.1). Thus, in rabbits undergoing dietary cholesterol lowering, MRI detected regression of aortic atherosclerotic plaque in vivo. Plaque progression was seen with maintenance of high-cholesterol diet. MRI is a promising noninvasive technology for directly imaging atherosclerosis and its response to therapeutic interventions.

View details for Web of Science ID 000082104500019

View details for PubMedID 10446077

Abstract

Abnormalities in right ventricular regional and global function can occur in the setting of acute pulmonary embolism. Treatment of acute pulmonary embolism with thrombolysis is associated with significant improvement in regional and global right ventricular function.

View details for Web of Science ID 000078930900036

View details for PubMedID 10080447

Abstract

There is substantial epidemiologic data, but limited experimental data, supporting the mortality benefit of low-dose alcohol consumption. A regimen of a single, daily alcoholic beverage was sufficient to increase both high-density lipoprotein (HDL) (4.4%, p = 0.03) and HDL2 (7.7%, p = 0.04) in men and women, but did not significantly affect hemostatic markers of cardiovascular risk.

View details for Web of Science ID A1997YD11600024

View details for PubMedID 9359559

Abstract

To determine the potential benefit of prospective navigator correction of image position for coronary magnetic resonance (MR) angiography.Two-dimensional MR angiograms were obtained with free breathing in 12 adult subjects. Navigator gating was used with and without prospective correction and with gating windows set at 3, 5, and 7 mm. MR angiograms were compared with those obtained with conventional, end-expiratory breath holding.Navigator gating with correction resulted in image quality equivalent to that obtained with breath holding, even with the 7-mm gating window. In contrast, navigator gating without correction allowed only maintenance of image quality similar to that obtained with breath holding for the 3- and 5-mm windows and resulted in decreased image quality with the 7-mm window (P < .05). Use of navigator gating with correction and the 7-mm window resulted in a 28% decrease in imaging time compared with breath holding and a 33% decrease compared with the 3-mm gating window (P < .05 for both comparisons).Prospective, adaptive navigator correction of image position for free-breathing coronary MR angiography is a promising, novel approach to compensate for respiratory motion.

View details for Web of Science ID A1997XA57800026

View details for PubMedID 9169696

Abstract

Currently, breath-holding during MR coronary angiography is used to minimize respiratory motion. This technique requires patient cooperation and is associated with slice registration errors. The goal of this study was to evaluate alternative non-breath-hold techniques for MR coronary angiography during free breathing.Subjects underwent MR coronary angiography using an ECG-gated, fat-suppressed, segmented K-space, gradient-echo sequence. Images were obtained during free breathing using both real-time navigator gating and respiratory bellows gating. These were compared with images obtained during conventional breath-holding. The optimal navigator location (diaphragmatic or cardiac) was also studied. Image quality, registration error, and scan time were measured for all scans.Navigator gating for MR coronary angiography during free breathing resulted in image quality equivalent to that obtained during breath-holding and was superior to that obtained with respiratory bellows gating (p < .04). Also, navigator gating reduced registration errors by 75% compared with breath-holding (p < .01) and did not increase scan time. No significant differences in the parameters measured were observed among the different navigator locations.Real-time navigator gating for MR coronary angiography during free breathing achieved image quality and scan time equivalent to breath-holding. Navigator gating also significantly reduced registration error. Compared with breath-holding and respiratory bellows gating, navigator gating during free breathing is a more optimal approach for suppression of respiratory motion during MR coronary angiography.

View details for Web of Science ID A1997WV56800051

View details for PubMedID 9129447

Abstract

Current MR coronary angiography (MRCA) methods use breath-holding to minimize respiratory motion. A major limitation to this technique is misregistration between imaging slices due to breath-hold variability. Prospective adaptive correction of image location using real-time navigator measurement of diaphragm position is a potential method for improving slice registration in breath-hold MRCA. Ten subjects underwent MRCA using an ECG-gated, fat-suppressed, segmented k-space, gradient-echo sequence. Transverse and coronal images were acquired using standard breath-holding with and without prospective navigator correction. Breath-hold MRCA with prospective navigator correction resulted in a 47% reduction in craniocaudal slice registration error compared to standard breath-holding (0.9 +/- 0.2 mm versus 1.7 +/- 0.4 mm, P = 0.04). Prospective adaptive navigator correction of image location significantly improves slice registration for breath-hold MRCA and is a promising motion correction technique for cardiac MR.

View details for Web of Science ID A1997VZ62900020

View details for PubMedID 8978644

Abstract

Numerous trials have demonstrated that cholesterol-lowering therapy leads to marked reductions in cardiovascular and overall mortality and in the need for coronary revascularization. Angiographic regression trials have shown that cholesterol lowering can reduce progression and, in some instances, achieve regression of coronary atherosclerotic lesions. However, recent studies have contradicted the traditional view that the clinical course of coronary artery disease is closely linked to the severity of coronary artery stenosis. It is now apparent that stenoses responsible for myocardial infarction or unstable angina are typically mild rather than severe. These observations suggest that regression may not be the principal mechanism by which cholesterol lowering affects cardiovascular risk. Two mechanisms---plaque stabilization and improved endothelial function-have been examined in this regard. Basic studies suggest that cholesterol lowering favorably alters those features of atherosclerosis that promote plaque stability. Recent clinical studies have clearly established that aggressive lipid-lowering therapy improves endothelial function and reduces myocardial ischemia in patients with hypercholesterolemia.

View details for PubMedID 8900332

Abstract

This study analyzed the regional pattern of right ventricular (RV) dysfunction on transthoracic echocardiograms in patients with and without acute pulmonary embolism. Quantitative (centerline) and qualitative (wall motion score) analyses of segmental RV free wall motion were performed on a "training" cohort of 41 patients (group 1), including 14 patients with acute pulmonary embolism, 9 patients with primary pulmonary hypertension, and 18 normal subjects. Patients with acute pulmonary embolism had a distinct regional pattern of RV dysfunction, with akinesia of the mid-free wall (centerline excursion: -0.2 +/- 0.8 mm, p = 0.0001 vs normal) but normal motion at the apex (centerline excursion: 5.7 +/- 0.8 mm, p = NS vs normal). In contrast, patients with primary pulmonary hypertension had abnormal wall motion in all regions (p <0.03 vs normal). This echocardiographic finding of normal wall motion at the apex and abnormal wall motion in the mid-free wall in acute pulmonary embolism was then tested in a "validation" cohort of 85 patients (group 2), consisting of hospitalized patients with RV dysfunction from any cause, including 13 patients with acute pulmonary embolism. The finding had a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism, with a positive predictive value of 71% and a negative predictive value of 96%. Thus, a distinct echocardiographic pattern of regional RV dysfunction, in which the apex is spared occurs in acute pulmonary embolism. This finding should raise the level of clinical suspicion for the diagnosis of acute pulmonary embolism.

View details for Web of Science ID A1996VD82700016

View details for PubMedID 8752195

Abstract

Anomalous coronary arteries are a rare but recognized cause of myocardial ischemia and sudden death. Identification currently requires x-ray angiography, which may have difficulty defining the three-dimensional course of the anomalous vessel. Magnetic resonance coronary angiography (MRCA) has been shown to image coronary artery anatomy noninvasively. We hypothesize that MRCA may be useful in the identification of anomalous coronary arteries and their anatomic course.Sixteen patients (9 men, 7 women, age 44 to 81 years) with anomalous aortic origins of the coronary arteries by conventional x-ray angiography underwent MRCA. Multiple images of the major epicardial coronary arteries were obtained by use of a breathhold, fat-suppressed, segmented-k space, gradient-echo technique by investigators blinded to all patient data. Anomalous coronary artery pathology, by x-ray angiography, included right-sided left main coronary artery (n = 3), right-sided left circumflex artery (n = 6), separate left-sided left anterior descending and left circumflex arteries (n = 2), left-sided right coronary artery (n = 4), and an anteriorly displaced right coronary artery (n = 1). MRCA correctly identified the anomalous coronary vessel(s) in 14 of 15 patients. In 1 patient, the anomalous vessel was incorrectly identified, and in 2 patients the course of the anomalous vessel was not clearly seen; one of these was a nondominant, anomalous right coronary artery.MRCA is a useful technique for the noninvasive identification of anomalous coronary arteries and their anatomic course.

View details for Web of Science ID A1995TG29200004

View details for PubMedID 7586298

Abstract

MRC OX35, an anti-CD4 mAb, was used to treat high responder Wistar Furth (W/F) (RT1u) and low responder DA (RT1a) rats which had been grafted with directly vascularized hearts from PVG (RT1c) rats across a full MHC plus non-MHC incompatibility. Four doses of mAb at 7 mg/kg given in the first 2 wk postgrafting induced indefinite graft survival (greater than 150 days) in DA hosts, but only delayed rejection to 18 to 42 days in W/F as compared to rejection times of 6 to 8 days in untreated rats. The extension of MRC OX35 treatment to 6 wk in W/F rats induced indefinite graft survival in three of six rats. During treatment MRC OX35 therapy only partially depleted CD4+ cells, and all circulating CD4+ cells were coated with MRC OX35. The capacity of naive CD4+ and CD8+ cells from W/F and DA to be activated to PVG alloantigen was compared both in vitro in an MLC assay and in vivo by an adoptive transfer assay of their capacity to restore rejection of PVG heart grafts in irradiated syngeneic hosts. CD4+ cells from both W/F and DA proliferated in MLC and restored graft rejection. W/F CD8+ cells both proliferated in MLC and restored rejection, but DA CD8+ cells neither proliferated nor reconstituted rejection. Examination of lymphocytes from MRC OX35 treated hosts with long-surviving grafts showed that they were neither depleted of CD4+ T cells nor did they lack the capacity to proliferate to PVG Ag in MLC, this response being similar to that to third-party Ag or by naive lymphocytes. Compared to first-set rejection, PVG skin graft rejection was delayed 2 to 3 days in W/F and 10 to 12 days in DA rats with long-surviving grafts after MRC OX35 therapy, whereas they rejected third-party skin grafts in first-set tempo. These studies show that differences in graft survival in anti-CD4 treated low and high responder strains may be due to the inherent capacity of CD8+ cells to be activated to effect rejection independent of CD4+ cells in W/F but not in DA. In those hosts that accept grafts, there is no evidence of clonal deletion, but there appears to be a form of unresponsiveness akin to that induced in adult rats by other immunosuppressive therapies that protects the graft from rejection.

View details for Web of Science ID A1989AW84000008

View details for PubMedID 2572644

View details for Web of Science ID A1989U239800025

View details for PubMedID 2496503

Abstract

Dual-chamber pacemakers interact with cardiac rhythms in complex ways. The resultant surface electrocardiograms (ECGs) are often very difficult to interpret. A simple and automatic diagnostic diagram is described that graphically illustrates pacemaker-heart interactions. Pacemaker operation is explained by a continuous series of lines and symbols that interconnect any sequence of paced and sensed events in both chambers. Fixed, programmable, and adaptive pacemaker timing intervals are all shown in a simple format. The pacemaker diagnostic diagram is plotted directly below the ECG to help users interpret the paced cardiac rhythm. The pacemaker diagnostic diagram is generated by software in a pacemaker programmer from: (1) telemetered real-time event markers; (2) fixed and programmable timing parameters (lower rate, AV interval, etc.); (3) pacemaker conditional logic. If this computer analysis of the telemetered event markers is not consistent with normal pacemaker operation, a specific error-message is printed. The pacemaker diagnostic diagram should be useful for instruction, pacemaker follow-up, and troubleshooting.

View details for Web of Science ID A1985AQP1600010

View details for PubMedID 2414751