Biomedical subjects

Juan Gilberto S Aguinaldo

Publications and source records attributed to Juan Gilberto S Aguinaldo.

10 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

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

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

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↗

PubMed2003

Magnetic resonance microscopy quantifies the disease progression in Marfan syndrome mice.

PURPOSE: To use noninvasive magnetic resonance microscopy (MRM) to examine aneurysmal disease in the mouse model of Marfan syndrome (MFS). MATERIALS AND METHODS: A total of eight wild-type (WT) and MFS mice were imaged using MRM; four of them at three different time points over an 8-week period and the remaining animals were imaged at one time point. The maximal cross-sectional area of the aorta was measured by manual tracing and by automated means from combined cardiac and respiratory-gated bright-blood images. Relationships between aortic size and age and the differences between WT and mutant mice aortic size were established. RESULTS: Maximal cross-sectional aortic areas differed significantly (P < 0.05) between WT and mutant mice for all time points, with MFS mice having larger aortic size. There was a positive correlation between aortic size and age in MFS mice (r = 0.80) with a significant increase from the 14th to the 22nd week (P < 0.05). CONCLUSION: MRM detected the differences in aortic size between WT and mutant mice over time, demonstrating a potential for noninvasive technique for the assessment of potential therapies in MFS mice.

Analysis of Variance↗