Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Contrast-free detection of myocardial fibrosis in hypertrophic cardiomyopathy patients with diffusion-weighted cardiovascular magnetic resonance.

BackgroundsPrevious studies have shown that diffusion-weighted cardiovascular magnetic resonance (DW-CMR) is highly sensitive to replacement fibrosis of chronic myocardial infarction. Despite this sensitivity to myocardial infarction, DW-CMR has not been established as a method to detect diffuse myocardial fibrosis. We propose the application of a recently developed DW-CMR technique to detect diffuse myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients and compare its performance with established CMR techniques.MethodsHCM patients (N = 23) were recruited and scanned with the following protocol: standard morphological localizers, DW-CMR, extracellular volume (ECV) CMR, and late gadolinium enhanced (LGE) imaging for reference. Apparent diffusion coefficient (ADC) and ECV maps were segmented into 6 American Heart Association (AHA) segments. Positive regions for myocardial fibrosis were defined as: ADC > 2.0 μm(2)/ms and ECV > 30%. Fibrotic and non-fibrotic mean ADC and ECV values were compared as well as ADC-derived and ECV-derived fibrosis burden. In addition, fibrosis regional detection was compared between ADC and ECV calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) using ECV as the gold-standard reference.ResultsADC (2.4 ± 0.2 μm(2)/ms) of fibrotic regions (ADC > 2.0 μm(2)/ms) was significantly (p < 0.01) higher than ADC (1.5 ± 0.2 μm(2)/ms) of non-fibrotic regions. Similarly, ECV (35 ± 4%) of fibrotic regions (ECV > 30%) was significantly (p < 0.01) higher than ECV (26 ± 2%) of non-fibrotic regions. In fibrotic regions defined by ECV, ADC (2.2 ± 0.3 μm(2)/ms) was again significantly (p < 0.05) higher than ADC (1.6 ± 0.3 μm(2)/ms) of non-fibrotic regions. In fibrotic regions defined by ADC criterion, ECV (34 ± 5%) was significantly (p < 0.01) higher than ECV (28 ± 3%) in non-fibrotic regions. ADC-derived and ECV-derived fibrosis burdens were in substantial agreement (intra-class correlation = 0.83). Regional detection between ADC and ECV of diffuse fibrosis yielded substantial agreement (κ = 0.66) with high sensitivity, specificity, PPV, NPV, and accuracy (0.80, 0.85, 0.81, 0.85, and 0.83, respectively).ConclusionDW-CMR is sensitive to diffuse myocardial fibrosis and is capable of characterizing the extent of fibrosis in HCM patients

Deep and superficial amygdala nuclei projections revealed in vivo by probabilistic tractography

Copyright © 2011 Society for Neuroscience and the authors. The The Journal of Neuroscience uses a Creative Commons Attribution-NonCommercial-ShareAlike licence: http://creativecommons.org/licenses/by-nc-sa/4.0/.Despite a homogenous macroscopic appearance on magnetic resonance images, subregions of the amygdala express distinct functional profiles as well as corresponding differences in connectivity. In particular, histological analysis shows stronger connections for superficial (i.e., centromedial and cortical), compared with deep (i.e., basolateral and other), amygdala nuclei to lateral orbitofrontal cortex and stronger connections of deep compared with superficial, nuclei to polymodal areas in the temporal pole. Here, we use diffusion weighted imaging with probabilistic tractography to investigate these connections in humans. We use a data-driven approach to segment the amygdala into two subregions using k-means clustering. The identified subregions are spatially contiguous and their location corresponds to deep and superficial nuclear groups. Quantification of the connection strength between these amygdala clusters and individual target regions corresponds to qualitative histological findings in non-human primates, indicating such findings can be extrapolated to humans. We propose that connectivity profiles provide a potentially powerful approach for in vivo amygdala parcellation and can serve as a guide in studies that exploit functional and anatomical neuroimaging.The Wellcome Trust, a Max Planck Research Award and Swiss National Science Foundation

Diffusion Tensor Imaging Correlates with Short-Term Myelopathy Outcome in Patients with Cervical Spondylotic Myelopathy

Objective To determine if spinal cord diffusion tensor imaging indexes correlate with short-term clinical outcome in patients undergoing elective cervical spine surgery for cervical spondylotic myelopathy (CSM). Methods A prospective consecutive cohort study was performed in patients undergoing elective cervical spine surgery for CSM. After obtaining informed consent, patients with CSM underwent preoperative T2-weighted magnetic resonance imaging and diffusion tensor imaging of the cervical spine. Fractional anisotropy (FA) values at the level of maximum cord compression and at the noncompressed C1-2 level were calculated on axial images. We recorded the modified Japanese Orthopaedic Association (mJOA) scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores for all patients preoperatively and 3 months postoperatively. Statistical analysis was performed to identify correlations between FA and clinical outcome scores. Results The study included 27 patients (mean age 54.5 years ± 1.9, 12 men). The mean postoperative changes in mJOA scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores were 0.9 ± 0.3, −6.0 ± 1.9, and 3.4 ± 1.9. The mean FA at the level of maximum compression was significantly lower than the mean FA at the C1-2 level (0.5 vs. 0.55, P = 0.01). FA was significantly correlated with change in mJOA scale score (Pearson r = −0.42, P = 0.02). FA was significantly correlated with the preoperative mJOA scale score (Pearson r = 0.65, P \u3c 0.001). Conclusions Preoperative FA at the level of maximum cord compression significantly correlates with the 3-month change in mJOA scale score among patients with CSM. FA was also significantly associated with preoperative mJOA scale score and is a potential biomarker for spinal cord dysfunction in CSM