Vitalii V. Itskovich

Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging

Background—MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non–lipid-rich plaques. Methods and Results—Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 μmol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (P<0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 hour: 164% [P<0.005]; 24 hours: 207% [P<0.001]). At 1 hour and 24 hours after injection, the contrast-to-noise ratio was higher with the use of IR-DIFF-TFL than with IR-TFL (1 hour: 13.0±7.7 versus −19.8±10.3 [P<0.001]; 24 hours: 15.2±5.9 versus 11.4±8.9, respectively [P=0.052]). There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (r2=0.87; P<0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques. Conclusions—Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.

Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): Sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T

Iron oxides are used for cell trafficking and identification of macrophages in plaque using MRI. Due to the negative contrast, differentiation between signal loss caused by iron and native low signal in tissue may be problematic. It is, therefore, preferable to achieve positive contrast. The purpose of this study was to test the efficacy of a new MRI sequence GRASP (GRe Acquisition for Superparamagnetic Particles) to generate a positive signal in phantoms containing iron. Membrane phantoms were constructed containing Ferumoxide at 7 concentrations. Standard GRE sequences were modified with user controlled z‐gradient rephasing (±100%). CNR values were determined as a function of echo time (TE) and % rephasing at 1.5T and 3T. T2* values were determined using multiple double‐echo GRE. The GRASP sequence generated positive signal enhancement in phantoms containing iron. For all rephasing values ≤30%, positive contrast was observed. The CNR generated at 1.5T was greater than the values at 3T for all concentrations tested. Correlation between CNR at 0% and 100% rephasing was observed at 1.5T(R = 0.84). Additionally, correlation between field change across the volume and CNR was observed. In conclusion, GRASP sequences may be used to generate positive signal enhancement in the presence of iron using MRI. Magn Reson Med, 2006.

Serial Studies of Mouse Atherosclerosis by In Vivo Magnetic Resonance Imaging Detect Lesion Regression After Correction of Dyslipidemia

Objective—We determined the effects of sustained normocholesterolemia on advanced mouse atherosclerosis and whether changes in plaque size and composition can be detected noninvasively by MRI. Methods and Results—Aortic arch segments containing advanced lesions from apolipoprotein E–deficient (apoE−/−) mice (total cholesterol 1281±97 mg/dL) were transplanted into syngeneic wild-type (WT; 111±11 mg/dL) or apoE−/− (702±74 mg/dL) recipient mice on chow diet. Mice underwent serial MRI at 3, 5, 7, and 9 weeks after transplantation. Compared with 3 weeks, correction of dyslipidemia in WT recipient mice resulted in a monotonic decrease (regression) in arterial wall volume, whereas in apoE−/− recipient mice, further plaque progression was noted (P<0.05). MRI and histological measurements were closely correlated (R=0.937). The lesional content of macrophages decreased >90% (P<0.001), and smooth muscle cells increased in the WT recipient mice. In vivo T1-, T2-, and proton density–weighted images of the mouse thoracic aorta differentiated intraplaque lipid and collagen. Conclusions—Plaque changes can be noninvasively monitored by serial in vivo MRI of a mouse regression model. Our ability to image the thoracic aorta and perform in vivo plaque characterization will further enhance atherosclerosis studies.

Quantification of human atherosclerotic plaques using spatially enhanced cluster analysis of multicontrast-weighted magnetic resonance images

One of the current limitations of magnetic resonance imaging (MRI) is the lack of an objective method to classify plaque components. Here we present a cluster analysis technique that can objectively quantify and classify MR images of atherosclerotic plaques. We obtained three‐dimensional (3D) images from 12 human coronary artery specimens on a 9.4T imaging system using multicontrast‐weighted fast spin‐echo (T1‐, proton density‐, and T2‐weighted) imaging with an isotropic voxel size of 39 μ. Spatially enhanced cluster analysis (SECA) was performed on multicontrast MR images, and the resulting segmentation was evaluated against histological tracings. To visualize the overall structure of plaques, the MR images were rendered in 3D. The specimens exhibited lesions of American Heart Association (AHA) plaque classification types I‐VI. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained from the cluster‐analyzed MR and histopathology images showed very good agreement for all AHA types (92%, Cohens κ = 0.89, P < 0.0001). All plaque types were identified and quantified by SECA with a high degree of correlation between cluster‐analyzed MR and manually traced histopathology data. MRI combined with SECA provides an objective method for atherosclerotic plaque component characterization and quantification. Magn Reson Med 52:515–523, 2004.

Mouse model of heterotopic aortic arch transplantation

BACKGROUND Syngeneic heterotopic transplantation of segments of descending thoracic aortas containing atherosclerotic lesions from hypercholesterolemic mice into normocholesterolemic recipients has been useful for studies on plaque regression and stabilization. Because lesion development is more rapid and exuberant in the aortic arch, a technique of transplantation of the mouse aortic arch was developed. MATERIALS AND METHODS C57BL/6, apoE-deficient (apoE-/-) (hypercholesterolemic) mice were fed a Western diet for 22 weeks and used as donors of aortic-arch segments containing atherosclerotic lesions. Twenty syngeneic transplants were performed on age-matched wild-type (normocholesterolemic) mice. Aortic arches containing atherosclerotic lesions were implanted on the abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Two weeks after transplantation, grafts were noninvasively imaged in vivo by magnetic resonance (MR) microscopy. Grafts harvested four weeks after transplantation were submitted for histological examination. RESULTS All recipients survived the entire follow-up period (1 month) without complications. Duration of recipient procedure ranged from 90 to 120 (mean, 105) min; aortic clamping time varied from 45 to 60 min. In vivo MR microscopy demonstrated patency of the grafts and wall thickening that corresponded to the preexisting atherosclerotic lesions. Histology confirmed patency and atherosclerotic thickening of the grafts, and showed no evidence of acute tissue damage. CONCLUSIONS Syngeneic transplantation of the aortic arch in mice represents a useful alternative model for studies on morphology, imaging, and mechanisms of atherosclerosis. The curvature of the aortic arch is preserved after implantation onto the abdominal aorta, providing clear landmarks for noninvasive assessment using MR.

Characterization of aortic root atherosclerosis in apoe knockout mice: High-resolution in vivo and ex vivo mrm with histological correlation

In vivo, cardiac‐gated, black‐blood, and ex vivo magnetic resonance microscopy (MRM) images of the aortic root, and histopathology data were obtained from 12 transgenic and wild‐type (WT) mice. MRM was performed using a black‐blood imaging spin‐echo sequence with upstream and downstream in‐flow saturation pulses to obtain aortic root images in three contrast techniques: proton density‐weighted (PDW), T1‐ (T1W), and T2‐weighted (T2W). Aortic wall thickness and area were measured and correlated with histopathology data (R > 0.90). Ex vivo lesion components (lipid core, fibrous tissue, and cell tissue) were identified and characterized by differing image contrast in PDW, T1W, and T2W MRM, and by histopathology. The differences between WT and transgenic mice for maximal wall thickness and area were statistically significant (P < 0.05). This study demonstrates the feasibility of in vivo murine aortic root lesion assessment and ex vivo plaque characterization by MRM. Magn Reson Med 49:381–385, 2003.

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.

Prenatal Detection of Embryo Resorption in Osteopontin-Deficient Mice Using Serial Noninvasive Magnetic Resonance Microscopy

Appropriate temporal and spatial expression of osteopontin (OPN) in the female genital tract may be critical for successful embryo implantation and maintenance of gestation. Traditionally, experimental assessments of reproductive success have been limited to ex vivo dissection at a single time point to determine embryo number and size and are inadequate for ongoing study of the effect(s) of genetic manipulation on any individual gestation. To investigate the role of OPN in the maintenance of gestation, we developed a noninvasive, in vivo method of pregnancy surveillance suitable for murine application using magnetic resonance microscopy (MRM). Gravid wild-type mice (n =7) and mice with targeted disruption of one or both OPN alleles (OPN−/−, n = 9; OPN+/−, n = 3) underwent MRM on postcoital days 10.5, 15.5, and 19.5. Prenatal MRM images were used to determine embryo numbers and sizes. There were no significant differences in embryo numbers determined independently by two blinded observers (mean difference between observers = 0.04 embryos; p = 0.87). There was a significant effect of genotype on embryo size, with OPN−/− embryos significantly smaller at all gestational ages. However, targeted disruption of one or more OPN alleles had no effect on embryo number at any gestational age. Thus, MRM may be a powerful noninvasive method for in vivo prenatal developmental study of genetically engineered mice.

Carotid Black Blood MRI Burden of Atherosclerotic Disease Assessment Correlates with Ultrasound Intima-Media Thickness

The aim of this study was to correlate carotid black blood MRI based measurements with those obtained by ultrasound intima-media thickness (IMT). Seventeen patients with intermediate to high Framingham cardiovascular risk score underwent both carotid ultrasound and rapid extended coverage double inversion recovery black blood carotid MRI. Overall, there was good correlation between wall area, wall thickness, and plaque index measured by MRI and the IMT measurements obtained from the ultrasound images (max r2 = 0.72, p < 0.05). Patients with mean IMT > or = 1.2 mm had significantly higher values of wall area, plaque index and wall thickness compared to patients with mean IMT < 1.2 mm. Vessel wall measurements assessed by black-blood MRI may be potentially used clinically to evaluate plaque progression and regression.