Dissecting whole-brain conduction delays through MRI microstructural measures.
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ABSTRACT:
SUBMITTER: Mancini M
PROVIDER: S-EPMC8448685 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Improved understanding of neuroimaging signal changes and their relation to patient outcomes after ischemic stroke is needed to improve ability to predict motor improvement and make therapy recommendations. The posterior limb of the internal capsule (PLIC) is a hub of afferent and efferent motor signaling and this work proposes new, image-based methods for prognosis based on interhemispheric differences in the PLIC. In this work, nine acute supratentorial ischemic stroke patients with motor impairment received a baseline, 203-direction diffusion brain MRI and a clinical assessment 3-12 days post-stroke and were compared to nine age-matched healthy controls. Asymmetries based on the mean and Kullback-Leibler divergence in the ipsilesional and contralesional PLIC were calculated for diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI) measures from the baseline MRI. Predictions of upper extremity Fugl-Meyer (FM) scores at 5-weeks follow-up from baseline measures of PLIC asymmetry in diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI) models were evaluated. For the stroke participants, the baseline asymmetry measures in the PLIC for the orientation dispersion index of the neurite orientation dispersion and density imaging (NODDI) model were highly correlated with upper extremity FM outcomes (r 2 = 0.83). Use of DSI and the NODDI orientation dispersion index parameter shows promise of being more predictive of stroke recovery and to help better understand white matter changes in stroke, beyond DTI measures. The new finding that baseline interhemispheric differences in the PLIC calculated from the orientation dispersion index of the NODDI model are highly correlated with upper extremity functional outcomes may lead to improved image-based motor-outcome prediction after middle cerebral artery ischemic stroke.
| S-EPMC6387951 | biostudies-literature
Project description:Background and significanceThe specialized conduction system (SCS) of the heart was extensively studied to understand the synchronization of atrial and ventricular contractions, the large atrial to His bundle (A-H) delay through the atrioventricular node (AVN), and delays between Purkinje (P) and ventricular (V) depolarization at distinct junctions (J), PVJs. Here, we use optical mapping of perfused rabbit hearts to revisit the mechanism that explains A-H delay and the role of a passive electrotonic step-delay at the boundary between atria and the AVN. We further visualize how the P anatomy controls papillary activation and valve closure before ventricular activation.MethodsRabbit hearts were perfused with a bolus (100-200 µl) of a voltage-sensitive dye (di4ANEPPS), blebbistatin (10-20 µM for 20 min) then the right atrial appendage and ventricular free-wall were cut to expose the AVN, P fibers (PFs), the septum, papillary muscles, and the endocardium. Fluorescence images were focused on a CMOS camera (SciMedia) captured at 1K-5 K frames/s from 100 × 100 pixels.ResultsAP propagation across the AVN-His (A-H) exhibits distinct patterns of delay and conduction blocks during S1-S2 stimulation. Refractory periods were 81 ± 9, 90 ± 21, 185 ± 15 ms for Atrial, AVN, and His, respectively. A large delay (>40 ms) occurs between atrial and AVN activation that increased during rapid atrial pacing contributing to the development of Wenckebach periodicity followed by delays within the AVN through slow or blocked conduction. The temporal resolution of the camera allowed us to identify PVJs by detecting doublets of AP upstrokes. PVJ delays were heterogeneous, fastest in PVJ that immediately trigger ventricular APs (3.4 ± 0.8 ms) and slow in regions where PF appear insulated from the neighboring ventricular myocytes (7.8 ± 2.4 ms). Insulated PF along papillary muscles conducted APs (>2 m/s), then triggered papillary muscle APs (<1 m/s), followed by APs firing of septum and endocardium. The anatomy of PFs and PVJs produced activation patterns that control the sequence of contractions ensuring that papillary contractions close the tricuspid valve 2-5 ms before right ventricular contractions.ConclusionsThe specialized conduction system can be accessed optically to investigate the electrical properties of the AVN, PVJ and activation patterns in physiological and pathological conditions.
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Project description:Phantoms, both numerical (software) and physical (hardware), can serve as a gold standard for the validation of MRI methods probing the brain microstructure. This review aims to provide guidelines on how to build, implement, or choose the right phantom for a particular application, along with an overview of the current state-of-the-art of phantoms dedicated to study brain microstructure with MRI. For physical phantoms, we discuss the essential requirements and relevant characteristics of both the (NMR visible) liquid and (NMR invisible) phantom materials that induce relevant microstructural features detectable via MRI, based on diffusion, intra-voxel incoherent motion, magnetization transfer or magnetic susceptibility weighted contrast. In particular, for diffusion MRI, many useful phantoms have been proposed, ranging from simple liquids to advanced biomimetic phantoms consisting of hollow or plain microfibers and capillaries. For numerical phantoms, the focus is on Monte Carlo simulations of random walk, for which the basic principles, along with useful criteria to check and potential pitfalls are reviewed, in addition to a literature overview highlighting recent advances. While many phantoms exist already, the current review aims to stimulate further research in the field and to address remaining needs.
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Project description:Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy.
| S-EPMC3738303 | biostudies-literature
Project description:Cognitive function relies on both molecular levels and cellular structures. However, systematic relationships between these two components of cognitive function, and their joint contribution to disease, are largely unknown. We utilize postmortem neuroimaging in tandem with gene expression and DNA methylation, from 222 deeply-phenotyped persons in a longitudinal aging cohort. Expression of hundreds of genes and methylation at thousands of loci are related to the microstructure of extensive regions of this same set of brains, as assessed by MRI. The genes linked to brain microstructure perform functions related to cell motility, transcriptional regulation and nuclear processes, and are selectively associated with Alzheimer's phenotypes. Similar methodology can be applied to other diseases to identify their joint molecular and structural basis, or to infer molecular levels in the brain on the basis of neuroimaging for precision medicine applications.
| S-EPMC6309607 | biostudies-literature
Project description:BackgroundAmyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains.ResultsThe article delineates a universal whole brain sampling strategy of pathologically relevant grey matter (cortical and subcortical) and white matter tracts of interest suitable for histological evaluation and direct correlation with MRI. A standardised systematic sampling strategy that was compatible with co-registration of images across modalities was established for regions representing phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) patterns that were topographically recognisable with defined neuroanatomical landmarks. Moreover, tractography-guided sampling facilitated accurate delineation of white matter tracts of interest. A digital photography pipeline at various stages of sampling and histological processing was established to account for structural deformations that might impact alignment and registration of histological images to MRI volumes. Combined with quantitative digital histology image analysis, the proposed sampling strategy is suitable for routine implementation in a high-throughput manner for acquisition of large-scale histology datasets. Proof of concept was determined in the spinal cord of an ALS patient where multiple MRI modalities (T1, T2, FA and MD) demonstrated sensitivity to axonal degeneration and associated heightened inflammatory changes in the lateral corticospinal tract. Furthermore, qualitative comparison of R2* and susceptibility maps in the motor cortex of 2 ALS patients demonstrated varying degrees of hyperintense signal changes compared to a control. Upon histological evaluation of the same region, intensity of signal changes in both modalities appeared to correspond primarily to the degree of microglial activation.ConclusionThe proposed post mortem whole brain sampling methodology enables the accurate intraindividual study of pathological propagation and comparison with quantitative MRI data, to more fully understand the relationship of imaging signal changes with underlying pathophysiology in ALS.
| S-EPMC5848544 | biostudies-literature
Project description:ObjectiveTo identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).DesignCross-sectional brain Magnetic Resonance I (MRI) study.SettingCommunity based cohort in three U.S. sites.ParticipantsA Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.Primary and secondary outcomes3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.ResultsAdjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).ConclusionIn middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.
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Project description:Our study explores the potential of conventional and advanced diffusion MRI techniques including diffusion tensor imaging (DTI), and single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD) to investigate complex microstructural changes following severe traumatic brain injury in rats at a chronic phase. Rat brains after sham-operation or lateral fluid percussion (LFP) injury were scanned ex vivo in a 9.4 T scanner. Our region-of-interest-based approach of tensor-, and SS3T-CSD derived fixel-, 3-tissue signal fraction maps were sensitive to changes in both white matter (WM) and grey matter (GM) areas. Tensor-based measures, such as fractional anisotropy (FA) and radial diffusivity (RD), detected more changes in WM and GM areas as compared to fixel-based measures including apparent fiber density (AFD), peak FOD amplitude and primary fiber bundle density, while 3-tissue signal fraction maps revealed distinct changes in WM, GM, and phosphate-buffered saline (PBS) fractions highlighting the complex tissue microstructural alterations post-trauma. Track-weighted imaging demonstrated changes in track morphology including reduced curvature and average pathlength distal from the primary lesion in severe TBI rats. In histological analysis, changes in the diffusion MRI measures could be associated to decreased myelin density, loss of myelinated axons, and increased cellularity, revealing progressive microstructural alterations in these brain areas five months after injury. Overall, this study highlights the use of combined conventional and advanced diffusion MRI measures to obtain more precise insights into the complex tissue microstructural alterations in chronic phase of severe brain injury.
| S-EPMC9908904 | biostudies-literature
Project description:One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations.Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images.Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r2>0.69; P<0.00001). They were associated with age (r2>0.29; P<0.00001) and differed by cognitive status (?2>26.48, P<0.00001). T2-FLAIR revealed a greater level of periventricular (?2=29.09) and deep white matter (?2=26.65, P<0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI (P<0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE.The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.
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Project description:Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.
| S-EPMC1895920 | biostudies-literature