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Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain.

ABSTRACT: The postnatal period is a remarkably dynamic phase of brain growth and development characterized by large-scale macrostructural changes, as well as dramatic microstructural changes, including myelination and cortical layering. This crucial period of neurodevelopment is uniquely susceptible to a wide variety of insults that may lead to neurologic disease. MRI is an important tool for studying both normal and abnormal neurodevelopmental changes, and quantitative imaging strategies like diffusion tensor imaging (DTI) allow visualization of many of the complex microstructural changes that occur during postnatal life. Diffusion tensor magnetic resonance histology (DT-MRH) provides particularly unique insight into cytoarchitectural changes in the developing brain. In this study, we used DT-MRH to track microstructural changes in the rat brain throughout normal postnatal neurodevelopment. We provide examples of diffusion tensor parameter changes in both white matter and gray matter structures, and correlate these changes with changes in cytoarchitecture. Finally, we provide a comprehensive database of image sets as a foundation for future studies using DT-MRH to characterize abnormal neurodevelopment in rodent models of neurodevelopmental disease.

SUBMITTER: Calabrese E

PROVIDER: S-EPMC3690820 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain.

Calabrese Evan E Johnson G Allan GA

NeuroImage 20130503

The postnatal period is a remarkably dynamic phase of brain growth and development characterized by large-scale macrostructural changes, as well as dramatic microstructural changes, including myelination and cortical layering. This crucial period of neurodevelopment is uniquely susceptible to a wide variety of insults that may lead to neurologic disease. MRI is an important tool for studying both normal and abnormal neurodevelopmental changes, and quantitative imaging strategies like diffusion t ...[more]

PMID: 23648962

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Project description:BackgroundCardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function.ObjectivesThis study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM.MethodsIn vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients.ResultsIn swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001).ConclusionsMyocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

Project description:Diffusion tensor imaging (DTI) has emerged as a promising method for noninvasive quantification of myocardial microstructure. However, the origin and behavior of DTI measurements during myocardial normal development and remodeling remain poorly understood. In this work, conventional and bicompartmental DTI in addition to three-dimensional histological correlation were performed in a sheep model of myocardial development from third trimester to postnatal 5 months of age. Comparing the earliest time points in the third trimester with the postnatal 5 month group, the scalar transverse diffusivities preferentially increased in both left ventricle (LV) and right ventricle (RV): secondary eigenvalues D2 increased by 54% (LV) and 36% (RV), whereas tertiary eigenvalues D3 increased by 85% (LV) and 67% (RV). The longitudinal diffusivity D1 changes were small, which led to a decrease in fractional anisotropy by 41% (LV) and 33% (RV) in 5 month versus fetal hearts. Histological analysis suggested that myocardial development is associated with hyperplasia in the early stages of the third trimester followed by myocyte growth in the later stages up to 5 months of age (increased average myocyte width by 198%, myocyte length by 128%, and decreased nucleus density by 70% between preterm and postnatal 5 month hearts.) In a few histological samples (N = 6), correlations were observed between DTI longitudinal diffusivity and myocyte length (r = 0.86, P < 0.05), and transverse diffusivity and myocyte width (r = 0.96, P < 0.01). Linear regression analysis showed that transverse diffusivities are more affected by changes in myocyte size and nucleus density changes than longitudinal diffusivities, which is consistent with predictions of classical models of diffusion in porous media. Furthermore, primary and secondary DTI eigenvectors during development changed significantly. Collectively, the findings demonstrate a role for DTI to monitor and quantify myocardial development, and potentially cardiac disease. Copyright © 2016 John Wiley & Sons, Ltd.

Project description:PurposeTo develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues.Materials and methodsTwenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients' scans. Image processing at pixel resolution yielded parametric maps of three directional diffusion coefficients ?1, ?2, ?3, apparent diffusion coefficient (ADC), and fractional anisotropy (FA), as well as a ?1-vector map, and a main diffusion-direction map.ResultsDTI measurements of healthy pancreatic tissue at b-values 0,500 s/mm² yielded: ?1?=?(2.65±0.35)×10?³, ?2?=?(1.87±0.22)×10?³, ?3?=?(1.20±0.18)×10?³, ADC?=?(1.91±0.22)×10?³ (all in mm²/s units) and FA?=?0.38±0.06. Using b-values of 100,500 s/mm² led to a significant reduction in ?1, ?2, ?3 and ADC (p<.0001) and a significant increase (p<0.0001) in FA. The reduction in the diffusion coefficients suggested a contribution of a fast intra-voxel-incoherent-motion (IVIM) component at b?100 s/mm², which was confirmed by the multi-b DWI results. In PDACs, ?1, ?2, ?3 and ADC in both 0,500 s/mm² and 100,500 s/mm² b-values sets, as well as the reduction in these diffusion coefficients between the two sets, were significantly lower in comparison to the distal normal pancreatic tissue, suggesting higher cellularity and diminution of the fast-IVIM component in the cancer tissue.ConclusionDTI using two reference b-values 0 and 100 s/mm² enabled characterization of the water diffusion and anisotropy of the healthy pancreas, taking into account a contribution of IVIM. The reduction in the diffusion coefficients of PDAC, as compared to normal pancreatic tissue, and the smaller change in these coefficients in PDAC when the reference b-value was modified from 0 to 100 s/mm², helped identifying the presence of malignancy.

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.

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Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain.

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Diffusion tensor magnetic resonance histology reveals microstructural changes in the developing rat brain.

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