Biomedical subjects

Venkatesh Mani

Publications and source records attributed to Venkatesh Mani.

13 recordsLinked to original sources

PubMed2007

Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI.

We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.

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↗

PubMed2006

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. T(2)* values were determined using multiple double-echo GRE. The GRASP sequence generated positive signal enhancement in phantoms containing iron. For all rephasing values <or=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.

Artifacts↗

PubMed2006

MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor.

The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.

Animals↗

PubMed2006

Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP.

In vivo markers that allow for detection of ferritin within atheromatous plaque may be useful for identifying iron-catalyzed hydroxyl-radical formation and subsequent lipid peroxidation. Recently, a positive contrast MR technique--GRadient echo Acquisition for Superparamagnetic particles/suscePtibility (GRASP)--was used to identify the presence of magnetic entities in phantom models. The aim of the current study was to determine the feasibility of using GRASP in conjunction with conventional T(2) (*)-weighted (T(2) (*)W) gradient-echo (GRE) sequences for identifying ferritin/hemosiderin deposition using in vitro and in vivo models of thrombus. In vitro thrombi were prepared by incubating blood with ferritin. MRI was performed using conventional GRE sequences and GRASP. The results indicate that GRASP was able to verify ferritin deposition in in vitro thrombi. In vivo thrombi were created using a crush injury model in rabbits. The signal enhancement obtained using conventional GRE sequences and GRASP was compared with the location of iron deposition by histology. In all of the animals the GRASP signal correlated with signal loss by conventional GRE, and ferritin/hemosiderin deposition by histology. GRASP sequences in combination with conventional GRE sequences may be used to detect the presence of ferritin deposition in in vitro thrombi and in vivo crush-injured rabbit carotid arteries.

Animals↗

PubMed2006

Gadolinium mixed-micelles: effect of the amphiphile on in vitro and in vivo efficacy in apolipoprotein E knockout mouse models of atherosclerosis.

Gadolinium (Gd) micelles are nanoparticles that incorporate phospholipids, surfactants, and lipophilic Gd complexes. Preliminary studies have shown that lipid-based nanoparticles may penetrate atherosclerotic plaque. The aim of the current study was to prepare, characterize, and evaluate in vivo the efficacy of two Gd micelle formulations using apolipoprotein E knockout (ApoE(-/-)) mouse models of atherosclerosis. Gd micelles were prepared using two different amphiphiles but similar GdDTPA lipids, surfactants, and fluorescent labels. The results indicate that the choice of amphiphile may affect the particle size, relaxivity, and blood clearance in wild-type mice (WT). However, the in vivo MR efficacy, with respect to uptake in the vessel wall of ApoE(-/-) mice, was not affected by the amphiphile used. Significant wall enhancement of ApoE(-/-) mice was observed following administration of 0.015 and 0.038 mmol Gd/kg of both micelle formulations. No significant enhancement of the vessel wall of WT mice was observed for any of the dosages or formulations tested. Additionally, liver uptake 24 hr post-injection (p.i.) was not influenced by the choice of amphiphile. The results of this study strongly suggest that liver uptake and wall enhancement may be regulated by the surface properties of the micelle and not by other factors, such as micelle size.

Animals↗

PubMed2006

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.

Aged↗

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

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 T(1)-, T(2)-, 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. Serial in vivo MRI of mouse arterial plaque after correction of dyslipidemia revealed a monotonic decrease in lesion size (regression) and changes in lesion composition consistent with a stable plaque phenotype. Serial in vivo MRI will enhance studies of plaque regression in animal models in response to therapeutic interventions.

Animals↗

PubMed2004

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 micromol/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.

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

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 micro. 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%, Cohen's kappa = 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.

Analysis of Variance↗

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↗