Changes In Mean Diffusivity Research Articles

Mechanisms of central brain atrophy in multiple sclerosis

Background: Change in ventricular volume has been suggested as surrogate measure of central brain atrophy (CBA) applicable to the everyday management of multiple sclerosis (MS) patients. Objectives: We investigated the contribution of inflammatory activity (including the severity of lesional tissue damage) to CBA. Methods: Fifty patients with relapsing–remitting multiple sclerosis (RRMS) were enrolled. Lesional activity during 4 years of follow-up was analysed using custom-build software, which segmented expanding part of the chronic lesions, new confluent lesions and new free-standing lesions. The degree of lesional tissue damage was assessed by change in mean diffusivity (MD). Volumetric change of lateral ventricles was used to measure CBA. Results: During follow-up, ventricles expanded on average by 12.6% ± 13.7% (mean ± SD). There was a significant increase of total lesion volume, 69.3% of which was due to expansion of chronic lesions. Correlation between volume of combined lesional activity and CBA (r2 = 0.67) increased when lesion volume was adjusted by the degree of tissue damage severity (r2 = 0.81). Regression analysis explained 90% of CBA variability, revealing that chronic lesion expansion was by far the largest contributor to ventricular enlargement. Discussion: CBA is almost entirely explained by the combination of the volume and severity of lesional activity. The expansion of chronic lesions plays a central role in this process.

Genetic and Environmental Influences on Structural and Diffusion-Based Alzheimer’s Disease Neuroimaging Signatures Across Midlife and Early Old Age

BackgroundComposite scores of magnetic resonance imaging–derived metrics in brain regions associated with Alzheimer’s disease (AD), commonly termed AD signatures, have been developed to distinguish early AD–related atrophy from normal age–associated changes. Diffusion-based gray matter signatures may be more sensitive to early AD–related changes compared with thickness/volume-based signatures, demonstrating their potential clinical utility. The timing of early (i.e., midlife) changes in AD signatures from different modalities and whether diffusion- and thickness/volume-based signatures each capture unique AD-related phenotypic or genetic information remains unknown. MethodsOur validated thickness/volume signature, our novel mean diffusivity (MD) signature, and a magnetic resonance imaging–derived measure of brain age were used in biometrical analyses to examine genetic and environmental influences on the measures as well as phenotypic and genetic relationships between measures over 12 years. Participants were 736 men from 3 waves of the Vietnam Era Twin Study of Aging (VETSA) (baseline/wave 1: mean age [years] = 56.1, SD = 2.6, range = 51.1–60.2). Subsequent waves occurred at approximately 5.7-year intervals. ResultsMD and thickness/volume signatures were highly heritable (56%–72%). Baseline MD signatures predicted thickness/volume signatures over a decade later, but baseline thickness/volume signatures showed a significantly weaker relationship with future MD signatures. AD signatures and brain age were correlated, but each measure captured unique phenotypic and genetic variance. ConclusionsCortical MD and thickness/volume AD signatures are heritable, and each signature captures unique variance that is also not explained by brain age. Moreover, results are in line with changes in MD emerging before changes in cortical thickness, underscoring the utility of MD as a very early predictor of AD risk.

Microstructural Gray Matter Integrity Deteriorates After an Ischemic Stroke and Is Associated with Processing Speed.

Microstructural changes after an ischemic stroke (IS) have mainly been described in white matter. Data evaluating microstructural changes in gray matter (GM) remain scarce. The aim of the present study was to evaluate the integrity of GM on longitudinal data using mean diffusivity (MD), and its influence on post-IS cognitive performances. A prospective study was conducted, including supra-tentorial IS patients without pre-stroke disability. A cognitive assessment was performed at baseline and 1year, including a Montreal Cognitive Assessment, an Isaacs set test, and a Zazzo cancelation task (ZCT): completion time and number of errors. A 3-T brain MRI was performed at the same two time-points, including diffusion tensor imaging for the assessment of GM MD. GM volume was also computed, and changes in GM volume and GM MD were evaluated, followed by the assessment of the relationship between these structural changes and changes in cognitive performances. One hundred and four patients were included (age 68.5 ± 21.5, 38.5% female). While no GM volume loss was observed, GM MD increased between baseline and 1year. The increase of GM MD in left fronto-temporal regions (dorsolateral prefrontal cortex, superior and medial temporal gyrus, p < 0.05, Threshold-Free Cluster Enhancement, 5000 permutations) was associated with an increase time to complete ZCT, regardless of demographic confounders, IS volume and location, GM, and white matter hyperintensity volume. GM integrity deterioration was thus associated with processing speed slowdown, and appears to be a biomarker of cognitive frailty. This broadens the knowledge of post-IS cognitive impairment mechanisms.

Modulation of network centrality and gray matter microstructure using multi-session brain stimulation and memory training.

Neural mechanisms of behavioral improvement induced by repeated transcranial direct current stimulation (tDCS) combined with cognitive training are yet unclear. Previously, we reported behavioral effects of a 3‐day visuospatial memory training with concurrent anodal tDCS over the right temporoparietal cortex in older adults. To investigate intervention‐induced neural alterations we here used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) datasets available from 35 participants of this previous study, acquired before and after the intervention. To delineate changes in whole‐brain functional network architecture, we employed eigenvector centrality mapping. Gray matter alterations were analyzed using DTI‐derived mean diffusivity (MD). Network centrality in the bilateral posterior temporooccipital cortex was reduced after anodal compared to sham stimulation. This focal effect is indicative of decreased functional connectivity of the brain region underneath the anodal electrode and its left‐hemispheric homolog with other “relevant” (i.e., highly connected) brain regions, thereby providing evidence for reorganizational processes within the brain's network architecture. Examining local MD changes in these clusters, an interaction between stimulation condition and training success indicated a decrease of MD in the right (stimulated) temporooccipital cluster in individuals who showed superior behavioral training benefits. Using a data‐driven whole‐brain network approach, we provide evidence for targeted neuromodulatory effects of a combined tDCS‐and‐training intervention. We show for the first time that gray matter alterations of microstructure (assessed by DTI‐derived MD) may be involved in tDCS‐enhanced cognitive training. Increased knowledge on how combined interventions modulate neural networks in older adults, will help the development of specific therapeutic interventions against age‐associated cognitive decline.

White matter alterations in heart-kidney imbalance insomnia and Jiao-Tai-Wan treatment: A diffusion-tensor imaging study

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

Diffusion tensor imaging in glioblastoma patients treated with volumetric modulated arc radiotherapy: a longitudinal study

Background Chemo- and radiotherapy (RT) is standard treatment for patients with high-grade glioma, but may cause side-effects on the patient’s cognitive function. Aim Use of diffusion tensor imaging (DTI) to investigate the longitudinal changes in normal-appearing brain tissue in glioblastoma patients undergoing modern arc-based RT with volumetric modulated arc therapy (VMAT) or helical tomotherapy. Materials and methods The study included 27 patients newly diagnosed with glioblastoma and planned for VMAT or tomotherapy. All subjects underwent magnetic resonance imaging at the start of RT and at week 3, 6, 15, and 26. Fourteen subjects were additionally imaged at week 52. The DTI data were co-registered to the dose distribution maps. Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were assessed in the corpus callosum, the centrum semiovale, the hippocampus, and the amygdala. Results Significant longitudinal changes in FA, MD, and RD were mainly found in the corpus callosum. In the other examined brain structures, only sparse and transient changes were seen. No consistent correlations were found between biodose, age, or gender and changes in DTI parameters. Conclusion Longitudinal changes in MD, FA, and RD were observed but only in a limited number of brain structures and the changes were smaller than expected from literature. The results suggest that modern, arc-based RT may have less negative effect on normal-appearing parts of the brain tissue up to 12 months after radiotherapy.

Altered diffusivity of the subarachnoid cisterns in the rat brain following neurological disorders

BackgroundAlthough changes in diffusion characteristics of the brain parenchyma in neurological disorders are widely studied and used in clinical practice, the change in diffusivity in the cerebrospinal fluid (CSF) system is rarely reported. In this study, free water diffusion in the subarachnoid cisterns and ventricles of the rat brain was examined using diffusion magnetic resonance imaging (MRI), and the effects of neurological disorders on diffusivity in CSF system were investigated. MethodsDiffusion MRI and T2-weighted images were obtained in the intact rats, 24 h after ischemic stroke, and 50 days after mild traumatic brain injury (mTBI). We conducted the assessment of diffusivity in the rat brain in the subarachnoid cisterns around the midbrain, as well as the lateral ventricles. One-way ANOVA and Kruskal–Wallis test were used to evaluate the change in mean diffusivity (MD) and MD histogram, respectively, in CSF system following different neurological disease. ResultsA significant decrease in the mean MD value of the subarachnoid cisterns was observed in the stroke rats compared with the intact and mTBI rats (p < 0.005). In addition, the skewness (p < 0.002), maximum MD (p < 0.002), and MD percentiles (p < 0.002) in the stroke rats differed significantly from those in the intact and mTBI rats. By contrast, no difference was observed in the mean MD value of the lateral ventricles among three groups of rats. We proposed that the assessment of the subarachnoid cisterns, rather than the lateral ventricles, in the rat brain would be useful in providing diffusion information in the CSF system. ConclusionsAlterations in MD parameters of the subarachnoid cisterns after stroke provide evidence that brain injury may alter the characteristics of free water diffusion not only in the brain parenchyma but also in the CSF system.

Plasma phosphorylated-tau181 levels reflect white matter microstructural changes across Alzheimer's disease progression.

Alzheimer's Disease (AD) is characterized by cognitive impairments that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181) has recently emerged as a new sensitive tool for the diagnosis of AD patients. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We obtained data from a large prospective cohort of elderly individuals participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI), which included baseline measurements of plasma P-tau181 and imaging findings. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) was included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging. The analysis revealed that the plasma level of P-tau181 has a positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC, and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.

Spermidine supplementation and diffusion weighted imaging in subjective cognitive decline

AbstractBackgroundSubjective Cognitive Decline (SCD) may represent an early, pre‐clinical manifestation of Alzheimer’s disease (Jessen et al., 2014), possibly accompanied by detrimental changes in white matter (WM) microstructure (Brueggen et al., 2019). Neuroprotective effects of increased external supply of spermidine were demonstrated in aged animal models (Madeo et al., 2018). This study investigated the effects of a 12‐month spermidine‐rich dietary supplementation on diffusion weighted imaging (DWI) parameters of central WM tracts in older persons with SCD.MethodThe monocentre, randomised, double‐blind, placebo‐controlled phase IIb SmartAge trial (clinicaltrial.gov: NCT03094546, Wirth et al., 2019) investigates the effects of a 12‐month dietary spermidine supplementation in SCD. Baseline and follow‐up DWI data were available for 72 SCDs (mean age 69±5 years; 38 placebo, 34 spermidine). Fractional anisotropy (FA) and mean diffusivity (MD) of central WM tracts were obtained through Tract Based Spatial Statistics. The interaction effect of intervention group and time was examined through analysis of variance. Exploratory analyses of within‐group changes from baseline to follow‐up were conducted using paired t‐tests. Correction for voxelwise multiple testing was applied.ResultNo statistically significant interaction effect of time and intervention group (spermidine vs. placebo) was present for FA and MD in central WM tracts. Exploratory within‐group analyses in the placebo group revealed a decrease of FA in areas comprising tracts within the limbic system and the MTL (right more than left), and an increase of FA in a small region of the right occipital lobe. Widespread increases of MD in the placebo group were observed in the right hemisphere and to a lesser extent in central regions of the left hemisphere. Within the spermidine group, no significant changes in FA or MD were present.ConclusionWhile our analyses did not show an interaction effect, we found detrimental within‐group changes in FA and MD from baseline to follow‐up in the placebo group but not in the spermidine group. Our findings thus suggest a potential beneficial influence of dietary spermidine supplementation on WM microstructure in SCD, to be followed up in future larger and longer‐lasting intervention studies.

Neuroanatomical substrates of attention processing speed in early dementia with Lewy bodies (DLB): A white‐matter voxel‐based morphometry and diffusion tensor imaging study

AbstractBackgroundBased on a previous study (Botzung et al., 2019) that revealed the importance of grey matter (GM) integrity in the striatum for attention processing speed, the purpose of this study was now to examine, in early DLB patients, the relationship between impaired attentional speed performances and white matter changes.MethodWe administered the Trail Making Test A (TMTA) to 73 prodromal to moderate DLB patients (mean MMSE = 26.4) and 30 control subjects (mean MMSE = 28.9) to assess attention processing speed. Three‐dimensional (3D) MRI and Diffusion‐weighted images (DTI) were acquired for all participants and correlational analyses were performed in the patient group using WM‐VBM, fractional anisotropy (FA) and mean diffusivity (MD).ResultBehavioral results showed significantly impaired performances in patients in comparison to control subjects (p = .004). In addition, correlational analyses using WM‐VBM revealed negative WM correlations in the anterior corpus callosum and in the anterior cingulum (p &lt; .05 FDR). Using DTI (p &lt; .05 FDR), correlated with TMTA scores, we found reduced FA in bilateral frontal and posterior regions, and increased MD in bilateral anterior and posterior networks.ConclusionWM‐VBM analysis revealed the involvement of anterior corpus callosum and cingulum, which could indicate a disruption of the loops connecting striatal regions and the prefrontal cortex. Changes in both FA and MD also correlate with impaired attentional speed: further DTI analyses are still ongoing to question the degree of which white matter tracts are disrupted between the striatum and cortical anterior and posterior networks, respectively.

Reduced diffusion in white matter after radiotherapy with photons and protons

Background and purposeRadio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation. Materials and methods70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions. ResultsWe observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: −7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly. ConclusionsIrradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography.

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract‐based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super‐resolution algorithm and DTI images processed with a motion‐tracked slice‐to‐volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor‐to‐tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto‐occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within‐tract changes. We found tract‐specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within‐tract developmental trajectories for the CST, IFOF, and forceps major.

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

Diffusion MRI of the infant brain reveals unique asymmetry patterns during the first-half-year of development

The human brain demonstrates anatomical and functional lateralization/asymmetry between the left and right hemispheres, and such asymmetry is known to start from the early age of life. However, how the asymmetry changes with brain development during infancy remained unknown. In this study, we aimed to systematically investigate the spatiotemporal pattern of brain asymmetry in healthy preterm-born infants during the first-half-year of development, using high angular resolution diffusion MRI.Sixty-five healthy preterm-born infants (gestational age between 25.3–36.6 weeks) were scanned with postmenstrual age (PMA) ranging from term-equivalent age (TEA) to 6-months. At the regional level, we performed a region-of-interest-based analysis by segmenting the brain into 63 symmetrical pairs of regions, based on which the laterality index was assessed and correlated with PMA. At the voxel level, we performed a fixel-based analysis of each fiber component between the native and left-right flipped data, separately in TEA-1 month, 1–3 months, and 3–6 months groups.The infant brains demonstrated extensive regions with structural asymmetry during their first half-of-year of life. A distinct central-peripheral asymmetry pattern was observed in mean diffusivity, namely, leftward lateralization in the neocortex and rightward asymmetry in the deep brain regions. Besides, the posterior brain demonstrated a higher lateralization index compared with the anterior brain in all metrics, which is congruent with the brain developmental pattern from caudal to rostral. Regionally, language processing regions showed a rightward asymmetry, while visuospatial processing regions exhibited leftward lateralization in fractional anisotropy, fibre density, and fibre cross-section measurements, and most white matter regions were lateralized to the left in these measurements. The laterality index of several regions (12 out 63) demonstrated significant developmental changes in mean diffusivity. At the fixel level, the fiber cross-section of inferior fronto-occipital fasciculus showed significant leftward asymmetry and the extent of asymmetry increased with PMA.In summary, the results revealed unique spatiotemporal patterns of macro- and micro-structural asymmetry in early life, which dynamically changed with age. These findings may contribute to the understanding of brain development during infancy.

Effect of Aerobic Exercise on White Matter Tract Microstructure in Young and Middle-Aged Healthy Adults

Recent evidence suggests that being physically active can mitigate age-related white matter (WM) changes. In a randomized clinical trial, the effect of 6-month aerobic exercise (AE) or stretching/toning interventions on measures of WM microstructure (WMM) was assessed in a sample of 74 adults aged 20–67 years. Major WM pathways were reconstructed. No significant group-level change in WM tract microstructure following an AE training was observed. Without adjustment for multiple comparisons, an increase in fractional anisotropy (FA) and a decrease in mean diffusivity (MD) of the uncinate fasciculus were observed post-intervention in the AE group in comparison with the stretching group. In the AE group, a significant increase in cardiorespiratory fitness was measured but did not correlate with FA and MD change. The present results of this study are in accordance with similar studies in healthy adults that did not show significant benefit on WMM after participating in an AE program.Clinical Trial Registration: Clinicaltrials.gov identifier, NCT01179958.

MACHINE LEARNING CLASSIFICATION OF VERIFIED HEAD IMPACT EXPOSURE REVEALS ASSOCIATIONS WITH LONGITUDINAL WHITE MATTER CHANGES IN FEMALE HIGH SCHOOL SOCCER PLAYERS

Background:Longitudinal changes in white matter (WM) integrity have been reported following cumulative exposure to sub-concussive head impacts (SCI) incurred during sports. SCI exposure is typically quantified using accelerometers that use an arbitrary g-force threshold for impact detection; however, this approach does not differentiate true impacts from non-physiological events, such as high-frequency cutaneous vibrations. This leads to a high false positive rate and the tendency to overestimate SCI exposure.Hypothesis/Purpose:To examine whether machine learning classification trained on video-verified impacts can produce more accurate quantification of SCI exposure and whether this can reveal associations between cumulative exposure and diffusion tensor imaging (DTI)-measured longitudinal WM changes in athletes.Methods:Pre- and post-season brain MRI scans were collected from 46 female high school soccer athletes. Athletes’ SCI exposure was recorded during their competitive season using head-mounted accelerometers. 24 athletes were assigned to a “Treatment Group” (TG) and were also video recorded during 17 of their games, while the remaining 22 athletes were assigned to a “Control Group” (CG) and were unrecorded. The TG video was used to verify whether the sensor-recorded impacts during those games were true head impacts or false positives. This dataset, along with the corresponding true/false labels, was used to train a machine learning classifier to learn a mapping between the accelerometer data and their respective labels. The trained model was then used to classify and filter the impacts recorded for the CG athletes by removing their predicted false positives. The CG athletes’ SCI exposure in both the unfiltered and filtered conditions was correlated with their pre- to post-season changes in DTI measures of mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA).Results:During the TG athletes’ 17 video-recorded games, 5146 impacts were recorded and 1128 were confirmed as true positives (22.0% accuracy). After training the machine learning classifier, the model was able to achieve 83.5% accuracy on this dataset. Associating the CG athletes’ unfiltered SCI exposure to pre- to post-season WM changes revealed no significant associations based on voxel-wise analysis over the whole brain WM network; however, after removing predicted false positives, the filtered SCI exposure revealed significant associations with changes in MD, RD, and FA (all p < 0.05).Conclusion:Machine learning classification of sensor-recorded SCI exposure exhibits superior accuracy and sensitivity to threshold-based detection used in standard accelerometry. Accurate quantification of SCI exposure also reveals associations with longitudinal WM changes.Figure 1:Season-long head impact exposure for the Treatment (TG) and Control (CG) groups. The unfiltered exposure (dark blue) represents the impacts recorded using standard accelerometry (using threshold-based detection). A subset of the TG impacts was video-recorded (red), with 22.0% of them being verified as true positives (orange). The CG impacts were predicted using a machine learning classifier trained on the TG video-verified subset as either true (green) or false positives (light blue).Figure 2:WM regions with significant longitudinal changes associated with filtered SCI exposure. Pre- to post-season reductions were found in mean diffusivity (red; A) and radial diffusivity (red; B), and significant increases were found in fractional anisotropy (blue; C) in the 22 CG athletes. The significant regions were overlaid onto the white matter skeleton (green) and standard T1-weighted image (gray).

Differentiating Glioblastomas from Solitary Brain Metastases: An Update on the Current Literature of Advanced Imaging Modalities.

Simple SummaryThe process of differentiating glioblastomas from solitary brain metastases is often difficult using traditional magnetic resonance imaging alone. In the past two decades, much progress has been made in devising advanced imaging modalities for the purpose of ascertaining more data on these intracranial tumors to help neuroradiologists in differentiating the two pathologies. In addition to the data provided by dynamic susceptibility contrast imaging and magnetic resonance spectroscopy, more innovative modalities now include diffusion tensor imaging and neurite orientation dispersion and density imaging. Radiomic analysis protocols and machine learning algorithms are being continually optimized to increase the accuracy of diagnosis by utilizing multiple different imaging protocols per patient. In this review, we provide an update on these advanced imaging modalities by reviewing the most up-to-date and current evidence.Differentiating between glioblastomas and solitary brain metastases proves to be a challenging diagnosis for neuroradiologists, as both present with imaging patterns consisting of peritumoral hyperintensities with similar intratumoral texture on traditional magnetic resonance imaging sequences. Early diagnosis is paramount, as each pathology has completely different methods of clinical assessment. In the past decade, recent developments in advanced imaging modalities enabled providers to acquire a more accurate diagnosis earlier in the patient’s clinical assessment, thus optimizing clinical outcome. Dynamic susceptibility contrast has been optimized for detecting relative cerebral blood flow and relative cerebral blood volume. Diffusion tensor imaging can be used to detect changes in mean diffusivity. Neurite orientation dispersion and density imaging is an innovative modality detecting changes in intracellular volume fraction, isotropic volume fraction, and extracellular volume fraction. Magnetic resonance spectroscopy is able to assist by providing a metabolic descriptor while detecting variable ratios of choline/N-acetylaspartate, choline/creatine, and N-acetylaspartate/creatine. Finally, radiomics and machine learning algorithms have been devised to assist in improving diagnostic accuracy while often utilizing more than one advanced imaging protocol per patient. In this review, we provide an update on all the current evidence regarding the identification and differentiation of glioblastomas from solitary brain metastases.

Exercise-induced fluid shifts are distinct to exercise mode and intensity: a comparison of blood flow-restricted and free-flow resistance exercise.

MRI can provide fundamental tools in decoding physiological stressors stimulated by training paradigms. Acute physiological changes induced by three diverse exercise protocols known to elicit similar levels of muscle hypertrophy were evaluated using muscle functional magnetic resonance imaging (mfMRI). The study was a cross-over study with participants (n = 10) performing three acute unilateral knee extensor exercise protocols to failure and a work matched control exercise protocol. Participants were scanned after each exercise protocol; 70% 1 repetition maximum (RM) (FF70); 20% 1RM (FF20); 20% 1RM with blood flow restriction (BFR20); free-flow (FF) control work matched to BFR20 (FF20WM). Post exercise mfMRI scans were used to obtain interleaved measures of muscle R2 (indicator of edema), R2' (indicator of deoxyhemoglobin), muscle cross sectional area (CSA) blood flow, and diffusion. Both BFR20 and FF20 exercise resulted in a larger acute decrease in R2, decrease in R2', and expansion of the extracellular compartment with slower rates of recovery. BFR20 caused greater acute increases in muscle CSA than FF20WM and FF70. Only BFR20 caused acute increases in intracellular volume. Postexercise muscle blood flow was higher after FF70 and FF20 exercise than BFR20. Acute changes in mean diffusivity were similar across all exercise protocols. This study was able to differentiate the acute physiological responses between anabolic exercise protocols. Low-load exercise protocols, known to have relatively higher energy contributions from glycolysis at task failure, elicited a higher mfMRI response. Noninvasive mfMRI represents a promising tool for decoding mechanisms of anabolic adaptation in muscle.NEW & NOTEWORTHY Using muscle functional MRI (mfMRI), this study was able to differentiate the acute physiological responses following three established hypertrophic resistance exercise strategies. Low-load exercise protocols performed to failure, with or without blood flow restriction, resulted in larger changes in R2 (i.e. greater T2-shifts) with a slow rate of return to baseline indicative of myocellular fluid shifts. These data were cross evaluated with interleaved measures of macrovascular blood flow, water diffusion, muscle cross sectional area (i.e. acute macroscopic muscle swelling), and intracellular water fraction measured using MRI.

Abstract P58: Motor Recovery After Chronic Stroke Correlates With Diffusion Tensor Measures of Ipsilesional Cerebral and Cerebellar White Matter Integrity

Introduction: We aimed to determine whether white matter (WM) tract integrity improved after a brain-computer interface (BCI) rehabilitation program for chronic stroke patients with upper extremity weakness. Mean diffusivity (MD) was calculated from diffusion tensor imaging (DTI) and is an indication of the integrity of axons and myelination in WM. MD is a biomarker in subacute stroke for post-stroke motor deficits and recovery. Methods: DTI scans were performed with 9 chronic hemiplegic stroke patients within 2 weeks of initiation and completion of a 12-week BCI rehabilitation program. All patients were a minimum of 6 months post-stroke. MD was then calculated using DSI-Studio for WM tracts in each patient at both pre- and post-therapy time points. Motor function was evaluated at these time points using the upper extremity portion of the Fugl-Meyer Assessment (UEFM). Voxelwise statistical analysis comparing pre- and post-intervention MD values was carried out using tract-based spatial statistics (TBSS). Relationships between MD measures in regions of interest and changes in motor function were estimated with Spearman correlations. Results: Voxelwise analysis using TBSS showed no significant group-level change in MD of WM tracts throughout the brain after completing BCI rehabilitation. However, the change in MD in ipsilesional cerebral WM was positively correlated with UEFM change (Spearman’s rho = 0.75, p = 0.02) as was the pre-BCI MD in the ipsilesional cerebellar WM (rho = 0.78, p = 0.01). The correlations between contralesional MD measures and UEFM change were not statistically significant. Conclusion: Correlation between changes in mean diffusivity of ipsilesional cerebral white matter and motor improvement in chronic stroke supports the literature that recovery may be mediated by axonal remyelination and regeneration. Furthermore, we find that pre-therapy, ipsilesional cerebellar white matter MD correlates with motor recovery and as such may serve as a predictive measure of the effectiveness of BCI therapy for patients.

Abstract P200: Transcranial Direct Current Stimulation in Post-Stroke Chronic Aphasia: A Double Blind Randomized Controlled Study

Background: There is growing evidence even amongst those with chronic aphasia that transcranial direct current stimulation (tDCS) combined with behavioral speech therapy could boost language. However, current findings do not allow making strong recommendations for using tDCS in order to improve language in post-stroke aphasia. The efficacy of tDCS therefore still needs to be established using double-blind controlled randomized trials in large samples. Intervention: In this ongoing double-blind randomized placebo controlled trial study, participants were randomly assigned either to the tDCS group or to the sham group. Both groups had five consecutive days of 20 minutes session, using a FDA approved tDCS device (soterixmedical.com). Behavioral and neuroimaging data were performed the week before/after tDCS/sham intervention and again 3 months following treatment. Participants: 42 post-stroke patients with chronic aphasia (32 males; age: 61±11y; 0.9-18years post-injury; 32 ischemic stroke; 19 non-fluent aphasia). Eighteen patients were in the tDCS group. Main Outcome Measures: The Western Aphasia Battery-Revised (WAB-R), Communication Outcomes after Stroke, patient and family report (COAST). MRI Diffusion Tensor Imaging data (64 dir) were also collected. Statistical Analyses: Anova with repeated measures was used on the behavioral outcome measures with aphasia severity, age and time since injury as covariates in SPSS. The average fractional anisotropy (FA) and mean diffusivity (MD) were extracted per ROI from each participant and timepoint. Main Results: a) Behavioral. Groups differed, pre/post intervention, on the WAB-R total score, for the Auditory-Verbal Comprehension and Repetition subscores; b) Neuroimaging. Change in Spontaneous Speech and Auditory Verbal Comprehension negatively correlated with change in mean MD and FA, respectively, in Superior Cerebellar Peduncle for tDCS, but not sham. Conclusion: Our preliminary findings show a higher improvement in language functions (for both receptive and expressive language skills) in response to treatment (vs. sham). Neuroplasticity was observed in superior cerebellar peduncle in response to tDCS mediated language improvement.