Biomedical subjects

Gabor Mizsei

Publications and source records attributed to Gabor Mizsei.

10 recordsLinked to original sources

PubMed2006

Fenofibrate induces plaque regression in hypercholesterolemic atherosclerotic rabbits: in vivo demonstration by high-resolution MRI.

INTRODUCTION: Fenofibrate has shown to reduce major cardiovascular events and slow angiographic progression of coronary atherosclerosis. The postulated mechanism of action is via the activation of peroxisomal proliferator-activated receptor-alpha (PPAR-alpha), a nuclear transcription factor that controls a variety of cellular functions. We investigated the anti-atherogenic effects of fenofibrate on previously established experimental atherosclerotic lesions. METHOD: Atherosclerotic lesions were induced in the abdominal aorta of New Zealand white (NZW) rabbits (n=19) by a combination of a double-balloon injury and a 9-month hypercholesterolemic diet. The rabbits were randomized into placebo or fenofibrate group. The corresponding treatments were added to the hypercholesterolemic diet. All rabbits underwent MRI examination at randomization and after 6 months of treatment, and were then sacrificed for histopathology. RESULTS: LDL-cholesterol was similarly elevated at randomization and follow-up, and was not significantly modified by fenofibrate therapy. HDL-cholesterol decreased (-27+/-10%, p=0.04) in the placebo and increased (+36.8+/-2%, p=0.04) in the fenofibrate group. MRI showed comparable vessel wall area (VWA) at randomization in both groups. At 15months, a significant increase in VWA was seen in the placebo group (15+/-4%, p=0.007), while fenofibrate treatment was associated with a regression (-11+/-4%, p=0.041) of previously established lesions. Fenofibrate also decreased macrophage and increased smooth muscle cell/collagen content of atherosclerotic lesions. CONCLUSION: MRI measurements can, in conjunction with in vitro histological measurements, contribute to the understanding of the actions of pharmacologic agents in experimental models of atherosclerosis. Fenofibrate significantly regresses atherosclerotic lesions and induced changes in plaque composition associated with a more "stable" phenotype (reduced macrophages and increased SMC). These observations support the potential anti-atherogenic effects of PPAR-alpha agonists.

Animals↗

PubMed2006

Multislice dark-blood carotid artery wall imaging: a 1.5 T and 3.0 T comparison.

PURPOSE: 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. MATERIALS AND METHODS: Multislice proton density-weighted (PDW), T2-weighted (T2W), and T1-weighted (T1W) inflow/outflow saturation band (IOSB) and rapid extended coverage double inversion-recovery (REX-DIR) TSE carotid artery wall imaging was performed on six healthy volunteers at 1.5 T and 3.0 T using time-, coverage-, and spatial resolution-matched (0.47 x 0.47 x 3 mm3) imaging protocols. To investigate whether improved signal-to-noise ratio (SNR) at 3.0 T could allow for improved spatial resolution, higher spatial resolution imaging (0.31 x 0.31 x 3 mm3) was performed at 3.0 T. Carotid artery wall SNR, carotid lumen SNR, and wall-lumen contrast-to-noise ratio (CNR) were measured. RESULTS: Signal gain at 3.0 T relative to 1.5 T was observed for carotid artery wall SNR (223%) and wall-lumen CNR (255%) in all acquisitions (P < 0.025). IOSB and REX-DIR images were found to have different levels of SNR and CNR (P < 0.05) with IOSB values observed to be larger. Normalized to a common imaging time, the higher spatial resolution imaging at 3.0 T and the lower spatial resolution imaging at 1.5 T provided similar levels of wall-lumen CNR (P = NS). CONCLUSION: Multislice carotid wall imaging at 3.0 T with IOSB and REX-DIR benefits from improved SNR and CNR relative to 1.5 T, and allows for higher spatial resolution carotid artery wall imaging.

Adult↗

PubMed2005

Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging.

OBJECTIVES: This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI). BACKGROUND: Regression of atherosclerotic lesions by lipid-lowering therapy has been reported. METHODS: Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden. RESULTS: Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p < 0.001). Total cholesterol decreased by 26% versus 33% and LDL-C by 36% versus 46% in the conventional (20 mg) versus aggressive (80 mg) simvastatin groups, respectively. Although the simvastatin 80-mg group had significantly higher baseline TC and LDL-C levels, both groups reached similar absolute values after treatment. A significant reduction in VWA was already observed by 12 months. No difference on vascular effects was detected between the randomized doses. Post-hoc analysis showed that patients reaching mean on-treatment LDL-C < or = 100 mg/dl had larger decreases in plaque size. CONCLUSIONS: Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.

Adult↗

PubMed2005

Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging.

OBJECTIVE: Plaque rupture leading to thrombosis and occlusion is a major source of acute coronary syndromes. Methods for accurate detection of thrombosis in veins or arteries may expand our capacity to predict clinical complications and guide therapeutic decisions. We sought to demonstrate the feasibility of in vivo acute thrombus detection using a fibrin-targeted gadolinium based magnetic resonance contrast agent (EP-1242). METHODS: Carotid thrombosis was induced in 12 guinea pigs by external injury and blood stasis. MR images were obtained after thrombus formation pre- and post- EP-1242 injection, using a T1-weighted high-resolution fast spin-echo sequence. RESULTS: An occlusive fibrin-rich thrombus was achieved in all animals. Correlation for thrombus location was excellent between MRI and histology (R=0.94; P<0.001). Contrast-enhanced MRI significantly improved thrombus detection when compared to non contrast-enhanced MRI (100% versus 41.6%; p<0.001). In addition, thrombus signal intensity (SI) was significantly increased after injection (SI(30 min-post)=4.39+/-0.12 versus 1.0; p<0.001). Contrast-to-noise ratio (CNR) was 43.8+/-7.2, 30 min post-injection (P<0.001). No enhancement was seen in the uninjured control arteries. CONCLUSIONS: We demonstrate the feasibility of in vivo MRI for carotid thrombus detection using a novel fibrin-targeted contrast agent. This technique significantly improves detection of small size thrombi in an animal model of occlusive fibrin-rich thrombosis.

Acute Disease↗

PubMed2005

Comparison of gated and non-gated fast multislice black-blood carotid imaging using rapid extended coverage and inflow/outflow saturation techniques.

PURPOSE: To comparatively analyze two fast in vivo multislice black-blood carotid artery vessel wall imaging techniques with and without cardiac gating. MATERIALS AND METHODS: Eight subjects with carotid artery atherosclerosis, and four healthy subjects were studied using two black-blood multislice techniques: rapid extended coverage double inversion recovery (REX-DIR), and inflow/outflow saturation band (IOSB) rapid acquisition with relaxation enhancement (RARE) multislice acquisitions. Quantitative, qualitative, and morphometric analyses were performed on images. RESULTS: Gating produced significantly lower values for the REX-DIR sequence with respect to signal intensity in muscle and the carotid artery wall, whereas it had no effect on flow suppression compared to non-gated images. For the IOSB sequences, gating had no significant effect on signal intensity of muscle and the carotid artery wall, but worsened flow suppression. REX-DIR and IOSB sequences were statistically different with respect to signal intensity of muscle (with REX-DIR sequences having lower values), while no statistical significance was observed for flow suppression and wall delineation. A morphologic analysis of the vessel wall and lumen comparing REX-DIR gated, IOSB gated, REX-DIR non-gated, and IOSB non-gated sequences revealed no significant differences between the acquisition techniques tested. CONCLUSION: Non-gated sequences may be used instead of gated sequences in atherosclerotic vessel wall imaging without compromising image quality. This may shorten examination time and improve patient comfort.

Adolescent↗

PubMed2004

The selective peroxisomal proliferator-activated receptor-gamma agonist has an additive effect on plaque regression in combination with simvastatin in experimental atherosclerosis: in vivo study by high-resolution magnetic resonance imaging.

OBJECTIVES: We sought to investigate the anti-atherogenic effects of a selective peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) agonist and simvastatin, as well as their combination, over time, in a rabbit model of experimental atherosclerosis. BACKGROUND: The PPARs are nuclear transcription factors that control a variety of cellular functions, with the potential effects required to induce plaque regression and stabilization. METHODS: Atherosclerosis was induced in rabbits (n = 37) by the combination of double-balloon injury and a nine-month high-cholesterol (HC) diet. The rabbits were randomized into a continued HC diet, a normal chow (NC) diet, NC plus simvastatin, NC plus PPAR-gamma agonist, and NC plus simvastatin plus PPAR-gamma agonist. All rabbits underwent magnetic resonance imaging (MRI) at randomization and after six months of treatment and were then sacrificed for histopathologic study. RESULTS: All groups had a similar vessel wall area by MRI (8.45 +/- 0.65 mm(2), p = NS between groups) at randomization. Significant progression was seen in the HC diet group (15 +/- 4%, p < 0.01). In the NC and NC plus PPAR-gamma agonist groups, progression was abolished (-2.5 +/- 3% and -4.5 +/- 5%, respectively; p = NS). The NC plus simvastatin and NC plus simvastatin plus PPAR-gamma agonist groups had significant plaque regression (-12 +/- 4% [p < 0.05] and -22 +/- 4% [p < 0.01], respectively). Regression was independent of plasma lipid levels. All NC groups had similar lipid profiles at the end of treatment. Histopathologic analysis of the NC groups showed a decreased macrophage content and matrix metalloproteinase activity and an increased smooth muscle cell/collagen content of lesions. CONCLUSIONS: Our data indicate that normalization of plasma lipid levels abolishes progression of atherosclerosis. Simvastatin elicits regression of atherosclerotic lesions, and the combination simvastatin plus PPAR-gamma agonist has additive regression effects on plaque. This is paralleled by structural alterations in plaque composition, which may increase plaque stability. These observations support the beneficial effects of statins on atherosclerosis and show additional anti-atherogenic benefits of combining a PPAR-gamma agonist with simvastatin.

Animals↗

PubMed2004

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

PURPOSE: To reduce long examination times of black-blood vessel wall imaging by acquiring multiple slices simultaneously and by using parallel acquisition techniques. MATERIALS AND METHODS: DIR-rapid acquisition with relaxation enhancement (RARE) techniques imaging up to 10 simultaneous slices per acquisition with single and multiple 180 degrees -reinversion pulses were developed. A slab-selective reinversion multislice DIR-RARE sequence incorporating generalized autocalibrating partially parallel acquisitions (GRAPPA) imaging was implemented. Four-channel and eight-channel carotid coils were built to test these sequences. A total of 11 subjects were studied. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) efficiency factor (SEF, SNR/unit time/slice) were measured from aortic images of three healthy subjects to determine optimal MR parameters. The DIR-RARE-GRAPPA sequence was run on aortas and carotid arteries of the five remaining healthy subjects and three atherosclerotic patients with optimal parameters (acquisition times 12-21 seconds). RESULTS: SEFs of slab-selective protocols were significantly higher than those of slice-selective protocols, and SEFs of DIR-RARE-GRAPPA protocols were significantly higher than corresponding non-GRAPPA protocols (P < 0.05). CNR was not significantly different for all imaging protocols. The DIR-RARE-GRAPPA multislice sequence showed 8.35-fold time improvement vs. single-slice DIR-2RARE sequence. CONCLUSION: Future MRI atherosclerotic plaque studies can be performed in substantially shorter times using these methods.

Adult↗

PubMed2004

Rapid extended coverage simultaneous multisection black-blood vessel wall MR imaging.

A two-dimensional rapid extended coverage (REX) rapid acquisition with relaxation enhancement (RARE) pulse sequence for simultaneous multisection double inversion-recovery (DIR) black-blood vessel wall magnetic resonance (MR) imaging was developed. Aortic vessel wall MR imaging was performed in five healthy subjects (mean age, 33 years +/- 4 [SD]) and five patients with atherosclerotic disease (mean age, 67 years +/- 11.7). Shortening of blood inversion time and imaging of multiple sections after single DIR block resulted in simultaneous acquisition of up to 20 aortic wall sections in less than 1 minute (spatial resolution, 0.97 x 0.97 x 3 mm(3)). Higher signal-to-noise ratios per unit time per section (16.0 +/- 2.45 vs 7.5 +/- 1.10, P <.05), no significant changes in contrast-to-noise ratios (15.0 +/- 5.3 vs 20.1 +/- 3.9, P >.05), and 17-fold improvement in acquisition time compared with those at conventional single-section DIR RARE imaging was achieved. Use of the REX method significantly shortened aortic imaging acquisition times without degrading image quality.

Adult↗

PubMed2002

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 approximately 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.

Anticholesteremic Agents↗

PubMed2002

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 (Pearson's chi-square with 4 df ranging from 96 to 132 and Cohen's 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.

Age Factors↗