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Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcA? Mouse Model of Cerebral Amyloidosis.

ABSTRACT: Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcA? mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates [Formula: see text] obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV([Formula: see text])]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV([Formula: see text]), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV([Formula: see text]) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24-month old mice were significantly associated with genotype. In those regions Q-values were reduced between 11 and 26% in arcA? mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a reduction of microvessel density in the old arcA? mice. We further demonstrated a region-specific association between parenchymal and vascular deposition of ?-amyloid and decreased vascular density, without a correlation with the amount of A? deposition. We found that Q mapping was more suitable than the hemodynamic read-outs to detect amyloid-related degeneration of the cerebral microvasculature.

SUBMITTER: Ielacqua GD

PROVIDER: S-EPMC4717293 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis.

Ielacqua Giovanna D GD Schlegel Felix F Füchtemeier Martina M Xandry Jael J Rudin Markus M Klohs Jan J

Frontiers in aging neuroscience 20160119

Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAβ mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the bra ...[more]

PMID: 26834622

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Project description:Background Cardiac amyloidosis (CA) is a disease of interstitial myocardial infiltration, usually by light chains or transthyretin. We used diffusion tensor cardiovascular magnetic resonance (DT-CMR) to noninvasively assess the effects of amyloid infiltration on the cardiac microstructure. Methods DT-CMR was performed at diastole and systole in 20 CA, 11 hypertrophic cardiomyopathy, and 10 control subjects with calculation of mean diffusivity, fractional anisotropy, and sheetlet orientation (secondary eigenvector angle). Results Mean diffusivity was elevated and fractional anisotropy reduced in CA compared with both controls and hypertrophic cardiomyopathy (P<0.001). In CA, mean diffusivity was correlated with extracellular volume (r=0.68, P=0.004), and fractional anisotropy was inversely correlated with circumferential strain (r=-0.65, P=0.02). In CA, diastolic secondary eigenvector angle was elevated, and secondary eigenvector angle mobility was reduced compared with controls (both P<0.001). Diastolic secondary eigenvector angle was correlated with amyloid burden measured by extracellular volume in transthyretin, but not light chain amyloidosis. Conclusions DT-CMR can characterize the microstructural effects of amyloid infiltration and is a contrast-free method to identify the location and extent of the expanded disorganized myocardium. The diffusion biomarkers mean diffusivity and fractional anisotropy effectively discriminate CA from hypertrophic cardiomyopathy. DT-CMR demonstrated that failure of sheetlet relaxation in diastole correlated with extracellular volume in transthyretin, but not light chain amyloidosis. This indicates that different mechanisms may be responsible for impaired contractility in CA, with an amyloid burden effect in transthyretin, but an idiosyncratic effect in light chain amyloidosis. Consequently, DT-CMR offers a contrast-free tool to identify novel pathophysiology, improve diagnostics, and monitor disease through noninvasive microstructural assessment.

Project description:BackgroundIn-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls.MethodsTen patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A).ResultsMD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10- 3 vs 1.41 ± 0.07 10- 3 mm2/s, p < 0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p < 0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p < 0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p < 0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001).ConclusionCMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA.

Dataset Information

Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcA? Mouse Model of Cerebral Amyloidosis.

Publications

Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis.

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