Gabor Mizsei

Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions Two Years’ Follow-Up by High-Resolution Noninvasive Magnetic Resonance Imaging

Background—Statins are widely used to treat hypercholesterolemia and atherosclerotic disease. Noninvasive MRI allows serial monitoring of atherosclerotic plaque size changes. Our aim was to investigate the effects of lipid lowering with simvastatin on atherosclerotic lesions. Methods and Results—A total of 44 aortic and 32 carotid artery plaques were detected in 21 asymptomatic hypercholesterolemic patients at baseline. The effects of statin on these atherosclerotic lesions were evaluated as changes versus baseline in lumen area (LA), vessel wall thickness (VWT), and vessel wall area (VWA) by MRI. Maximal reduction of plasma total and LDL cholesterol by simvastatin (23% and 38% respectively;P <0.01 versus baseline) was achieved after ≈6 weeks of therapy and maintained thereafter throughout the study. Significant (P <0.01) reductions in maximal VWT and VWA at 12 months (10% and 11% for aortic and 8% and 11% for carotid plaques, respectively), without changes in LA, have been reported. Further decreases in VWT and VWA ranging from 12% to 20% were observed at 18 and 24 months. A slight but significant increase (ranging from 4% to 6%) in LA was seen in both carotid and aortic lesions at these later time points. Conclusion—The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.

In Vivo Noninvasive Detection and Age Definition of Arterial Thrombus by MRI

OBJECTIVES The purpose of this study was to evaluate the potential of magnetic resonance (MR) to detect arterial thrombotic obstruction and define thrombus age. BACKGROUND; Arterial thrombi underlie the clinical consequences of atherosclerosis and are not reliably detected by current noninvasive diagnostic techniques. METHODS Carotid thrombi were induced in swine (n = 7) by arterial injury. Serial high-resolution in vivo MR images were obtained using black-blood T1-weighted (T1W) and T2-weighted (T2W) sequences in a clinical 1.5T MR system at 6 h, 1 day and at 1, 2, 3, 6 and 9 weeks. At each time point one animal was sacrificed and the occluded carotid artery processed for histopathology. Thrombus signal intensity (SI) was normalized to that of the adjacent muscle. Thrombus age was assessed based on MR appearance by two blinded independent observers. RESULTS Thrombus appearance and relative SI revealed characteristic temporal changes in multicontrast-weighted MR images, reflecting histologic changes in the composition. Acute thrombus appeared very bright on the T2W images, facilitating the detection. Signal intensity was 197 +/- 25% at 6 h, peaking at 1 week (246 +/- 51%), reaching a plateau by 6 weeks (120 +/- 15%). At six weeks, complete thrombus organization was confirmed histologically. The T1W images had similar pattern with lower SI than T2W. Age definition using visual appearance was highly accurate (Pearsons chi-square with 4 df ranging from 96 to 132 and Cohens kappa at 0.81 to 0.94). Agreement between observers was substantial (Pearson chi-square with 4 df = 91.5, kappa = 0.79). CONCLUSIONS Magnetic resonance imaging is a promising tool to noninvasively detect arterial thrombosis. Measurement of SI and the characteristic visual appearance of the thrombus have the potential to define thrombus age.

Parallel and nonparallel simultaneous multislice black-blood double inversion recovery techniques for vessel wall imaging.

To reduce long examination times of black‐blood vessel wall imaging by acquiring multiple slices simultaneously and by using parallel acquisition techniques.

Comparison of gated and nongated fast multislice black‐blood carotid imaging using rapid extended coverage and inflow/outflow saturation techniques

To comparatively analyze two fast in vivo multislice black‐blood carotid artery vessel wall imaging techniques with and without cardiac gating.

Multislice dark-blood carotid artery wall imaging: A 1.5 T and 3.0 T comparison†

To compare two multislice turbo spin‐echo (TSE) carotid artery wall imaging techniques at 1.5 T and 3.0 T, and to investigate the feasibility of higher spatial resolution carotid artery wall imaging at 3.0 T.

Real time magnetic resonance guided endomyocardial local delivery

Objective: To investigate the feasibility of targeting various areas of left ventricle myocardium under real time magnetic resonance (MR) imaging with a customised injection catheter equipped with a miniaturised coil. Design: A needle injection catheter with a mounted resonant solenoid circuit (coil) at its tip was designed and constructed. A 1.5 T MR scanner with customised real time sequence combined with in-room scan running capabilities was used. With this system, various myocardial areas within the left ventricle were targeted and injected with a gadolinium-diethylenetriaminepentaacetic acid (DTPA) and Indian ink mixture. Results: Real time sequencing at 10 frames/s allowed clear visualisation of the moving catheter and its transit through the aorta into the ventricle, as well as targeting of all ventricle wall segments without further image enhancement techniques. All injections were visualised by real time MR imaging and verified by gross pathology. Conclusion: The tracking device allowed real time in vivo visualisation of catheters in the aorta and left ventricle as well as precise targeting of myocardial areas. The use of this real time catheter tracking may enable precise and adequate delivery of agents for tissue regeneration.

Fenofibrate induces plaque regression in hypercholesterolemic atherosclerotic rabbits: In vivo demonstration by high-resolution magnetic resource imaging

Introduction: Fenofibrate has shown to reduce major cardiovascular events and slow angiographic progression of coronary atherosclerosis. Its postulate mechanism of action is through adwation of peroxlsomal proliferator-activated receptor-alpha, a nuclear transcription factor that controls a van&y of cellular functions. We investigated the antiatherogenic effects of fenofibrate on previously established experimental atherosclerotic (AT) lesions. Method AT-lesions were induced in NZW rabbits (n=24) by a combination of double balloon-mjury and g-month hypercholesterolemlc (HC) diet. At the end of the AT-inductton period all rabbits underwent MRI and 7 of them were sacrificed, processed for histology, and served as AT-control. The remaining animals were randomized into 3 groups: [l] resuming standard chow (n=5), [2] HC-diet+placebo (n=6) and [3] HC-diet+fenofibrate (n=6). Rabbits underwent an additional MRI after 6 months of treatment, and were then sacrificed for histopathology. Results MRI showed that all groups had similar vessel wall area (VWA) at randomization. Significant increase in VWA was seen in the HC-diet+placebo group (15%*4%. p=O.O07 vs. baseline). In the group resuming standard chow, progression was abolished (2.5+3%, ~~0.37 vs. baseline). The fenofibrate group had significant plaque regression (11+4%, p=O.O41) despite maintalned HC-diet. Plasma lipid levels were normalized in standard chow group, whereas they remamed elevated m both, the HC-diet+placebo and HC-diet+fenofibrate groups. Hlstopathological analysis, to define vascular biology of the different treatment groups, IS under investigation. Conclusion Our data indicate that normalization of plasma lipid levels abolishes atherosclerosis progression. Fenofibrate elicits regression of atherosclerotic lesions independently of the plasma lipid levels. These observations support the lipid-Independent mechanism of action and the anti-atherogenic benefits of fenofibrate, supporting the potential antiatherogenic effect of PPAR-alpha agonists.