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Human Brain Mapping Jun 2024Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS)...
Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.
Topics: Humans; Female; Male; Adult; Middle Aged; Brain; Multiple Sclerosis; Diffusion Magnetic Resonance Imaging; Water; Cognitive Dysfunction; Parenchymal Tissue; White Matter; Gray Matter; Processing Speed
PubMed: 38895882
DOI: 10.1002/hbm.26761 -
BioRxiv : the Preprint Server For... Jun 2024In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the...
In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.
PubMed: 38895425
DOI: 10.1101/2024.06.05.597426 -
American Journal of Veterinary Research Jun 2024The objective of this study was to optimize an MRI-based diffusion tensor imaging (DTI) protocol for imaging the plantar nerves at the level of the tarsus in normal...
OBJECTIVE
The objective of this study was to optimize an MRI-based diffusion tensor imaging (DTI) protocol for imaging the plantar nerves at the level of the tarsus in normal equine limbs.
SAMPLE
12 pelvic cadaver limbs from horses without evidence of proximal suspensory pathology were imaged with a 3T MRI system.
METHODS
For diffusion-weighted imaging, b values of 600, 800, and 1,000 s/mm2 were tested. Data were processed with DSI Studio. Cross-sectional areas of the medial and lateral plantar nerve along the plantar tarsus were recorded. The length and number of fiber tracts, signal-to-noise ratio, and DTI variables were recorded.
RESULTS
At the level of interest, the mean cross-sectional areas of the plantar nerves ranged from 5.03 to 7.42 mm2. The DTI maps consistently generated tracts in the region of the lateral and medial plantar nerves with DTI values in the range of values reported for peripheral nerves in humans. Our findings demonstrate that DTI of the medial and lateral plantar nerves can be performed successfully and used to generate quantitative parameters including fractional anisotropy and mean, axial, and radial diffusivity.
CLINICAL RELEVANCE
Quantitative data generated with this imaging technique can be used to noninvasively characterize the microstructural integrity of neural tissue with possible applications in the evaluation of pathologic changes to the plantar tarsal and metatarsal nerves of horses with proximal suspensory desmopathy.
PubMed: 38889743
DOI: 10.2460/ajvr.24.03.0092 -
NeuroImage. Clinical Jun 2024The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA)...
OBJECTIVE
The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS.
METHODS
The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses.
RESULTS
FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts.
CONCLUSIONS
Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.
PubMed: 38889523
DOI: 10.1016/j.nicl.2024.103633 -
JU Open Plus Jan 2024To correlate clinical and urodynamics parameters in Multiple Sclerosis patients (MS) presenting Lower Urinary Tract Symptoms (LUTS) with both Expanded Disability Status...
PURPOSE
To correlate clinical and urodynamics parameters in Multiple Sclerosis patients (MS) presenting Lower Urinary Tract Symptoms (LUTS) with both Expanded Disability Status Scale (EDSS) and changes in white matter integrity as seen on Diffusion Tensor Images (DTI). LUTS worsen throughout MS, as does lesion burden. We investigated which symptoms correlated best with structural changes in white matter structure.
MATERIALS AND METHODS
Ten adult women >18 years were recruited with stable MS for ≥3 months and voiding dysfunction defined as %PVR/BV > 20%. Patients participated in a clinical Urodynamic Study (UDS) and completed several questionnaires (i.e., HAM, AUASS, NBS-QoL). DTI images were acquired using a 7-Tesla Siemens MAGNETOM Terra MRI scanner. DTI maps were constructed, and individual patients were co-registered with the ICBM-DTI-81 white matter atlas to extract fractional anisotropy (FA) and mean diffusivity (MD). Pearson's correlation test was performed between each WMT and clinical parameters and between clinical parameters and the EDSS score as well. P-values < 0.05 were considered significant.
RESULTS
Of the clinical parameters, %PVR/BV obtained from the average of multiple un-instrumented uroflow assessments had significant correlations to the greatest number of WMTs. Furthermore, we observed that in all recorded clinical parameters, %PVR/BV was the only significant parameter correlated to the EDSS score.
CONCLUSION
This study demonstrates that %PVR/BV can be used as an objective parameter to gauge WMT changes and disease progression in MS patients. Future studies are needed to refine this model.
PubMed: 38883864
DOI: 10.1097/ju9.0000000000000087 -
Frontiers in Neurology 2024Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic...
BACKGROUND
Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration.
METHODS
Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA.
RESULTS
Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex ( = 0.400, = 0.005).
CONCLUSION
Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.
PubMed: 38882690
DOI: 10.3389/fneur.2024.1360424 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in...
Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.
Topics: Humans; Male; Transcranial Magnetic Stimulation; Stroke; Motor Cortex; Middle Aged; Aged; Pyramidal Tracts; Stroke Rehabilitation; Evoked Potentials, Motor
PubMed: 38879808
DOI: 10.1093/cercor/bhae251 -
NeuroImage. Clinical Jun 2024The COVID-19 pandemic has affected millions worldwide, causing mortality and multi-organ morbidity. Neurological complications have been recognized. This study aimed to...
INTRODUCTION
The COVID-19 pandemic has affected millions worldwide, causing mortality and multi-organ morbidity. Neurological complications have been recognized. This study aimed to assess brain structural, microstructural, and connectivity alterations in patients with COVID-19-related olfactory or cognitive impairment using post-acute (time from onset: 264[208-313] days) multi-directional diffusion-weighted MRI (DW-MRI).
METHODS
The study included 16 COVID-19 patients with cognitive impairment (COVID-CM), 35 COVID-19 patients with olfactory disorder (COVID-OD), and 14 controls. A state-of-the-art processing pipeline was developed for DW-MRI pre-processing, mean diffusivity and fractional anisotropy computation, fiber density and cross-section analysis, and tractography of white-matter bundles. Brain parcellation required for probing network connectivity, region-specific microstructure and volume, and cortical thickness was based on T1-weighted scans and anatomical atlases.
RESULTS
Compared to controls, COVID-CM patients showed overall gray matter atrophy (age and sex corrected p = 0.004), and both COVID-19 patient groups showed regional atrophy and cortical thinning. Both groups presented an increase in gray matter mean diffusivity (corrected p = 0.001), decrease in white matter fiber density and cross-section (corrected p < 0.05), , and COVID-CM patients also displayed an overall increased diffusivity (p = 0.022) and decreased anisotropy (corrected p = 0.038) in white matter. Graph-based analysis revealed reduced network modularity, with an extensive pattern of connectivity increase, in conjunction with a localized reduction in a few connections, mainly located in the left hemisphere. The left cingulate, anterior cingulate, and insula were primarily involved.
CONCLUSION
Expanding upon previous findings, this study further investigated significant alterations in brain morphology, microstructure, and connectivity in COVID-19 patients with olfactory or cognitive disfunction. These findings suggest underlying neurodegeneration, neuroinflammation, and concomitant compensatory mechanisms. Future longitudinal studies are required to monitor the alterations over time and assess their transient or permanent nature.
PubMed: 38878591
DOI: 10.1016/j.nicl.2024.103631 -
Journal of Neurotrauma Jun 2024Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined...
Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. Here, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube (BST-I) to investigate whole-brain DTI changes in the acute-phase of bmTBI at 1, 3, 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy (TEM) and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days after injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days after injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.
PubMed: 38877821
DOI: 10.1089/neu.2023.0435 -
Sports Health Jun 2024The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We...
BACKGROUND
The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We performed Mendelian randomization (MR) analysis to identify the causal effects of ligamentous knee injuries on the CST.
HYPOTHESIS
Ligamentous knee injuries impair CST microstructure (ie, by reducing fractional anisotropy [FA] and increasing mean diffusivity [MD]).
STUDY DESIGN
MR analysis.
LEVEL OF EVIDENCE
Level 2.
METHODS
MR uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Summary data for ligamentous injuries in knee and CST structure were obtained from genome-wide association study datasets. Significant and independent (5 × 10; < 0.001; 10,000 kb) single-nucleotide polymorphisms were extracted for MR analysis. Three methods for MR analysis were used (hypothesis-driven 1-tailed inverse variance weighted, MR-Egger, and weighted median), and sensitivity analyses were conducted to test reliability and stability.
RESULTS
Results from 3 MR methods consistently demonstrated that ligamentous knee injuries increased MD of the right CST (β, 0.063; 90% CI, 0.003-0.123; = 0.04), and weak statistical significance suggested increased MD of the left CST (β, 0.060; 90% CI, -0.002 to -0.121; = 0.05). However, no significant causal relationships were observed in CST FA, and no significant pleiotropy or heterogeneity was observed. Sensitivity analysis utilizing 2-tailed tests had no significant associations between ligamentous knee injuries and changes in CST structure.
CONCLUSION
There is statistically weak genetic evidence that corticospinal pathway abnormalities may evolve after ligamentous knee injuries, which manifests as abnormally organized neurites.
CLINICAL RELEVANCE
Ligamentous knee injuries require attention not only to damage to the structure of the knee joint itself but also to the process of maladaptive neuroplasticity that leads to structural and functional changes of the CST; novel interventions that target the corticospinal pathway may provide subsequent treatment of ligamentous knee injuries.
PubMed: 38877724
DOI: 10.1177/19417381241255342