Diffusion Tensor Imaging Fractional Anisotropy Research Articles

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis. To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). This case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age. Remote history of mTBI. White matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed. A total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P < .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = -0.029, Cohen d = 0.66; P < .001), ODI of the left posterior thalamic radiation (β = -0.006, Cohen d = 0.55; P < .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P < .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10-3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10-4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10-3; P = .02). In this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.

178 Brains on the Pitch: Investigating the Neurophysiological and Neurocognitive Effects of Repetitive Head Impacts in Adolescent Female Soccer Players During a Single Season

INTRODUCTION: Repetitive exposure to head impact in contact sports has raised concerns for potential long-term structural and functional neurologic effects. This relationship has been minimally explored in female athletes, with conflicting results arising from the limited reports on this topic. METHODS: Prospective cohort design with pre- and post-season assessments of neurocognitive function, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). Neurocognitive battery evaluated processing speed, memory, and executive function domains via computerized (ImPACT) and paper-and-pencil testing. TMS assessments included motor evoked potential onset; interhemispheric conduction times; intercortical and intracortical inhibition. DTI measures included fractional anisotropy (FA) for white matter tracts of interest, including: posterior limb of internal capsule; cortical spinal tract; corpus callosum - selected for common involvement in traumatic brain injury within other studies. RESULTS: One player was officially diagnosed with concussion and was included in analysis. Neurocognitive performance was intact relative to same aged peers, and there were no significant differences over the season based on mean reliable change indices (-0.79-0.93). Paired t-test analysis indicated that the TMS measures were not significantly different between the two timepoints. Furthermore, DTI FA values and TMS measures were not notably different pre- versus postseason. CONCLUSIONS: In this cohort of high school female athletes, we did not observe significant anatomic, physiologic, or functional effects from repetitive head impacts. Our findings contradict previous studies that showed significant neurophysiologic and neurocognitive changes, even in the absence of clinically-observed concussion. Further research is needed to fully understand the long-term consequences of repetitive head impacts in female athletes and to develop effective strategies for mitigating potential risks.

Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8–23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10–6–0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10–4–0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury.

Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.

Microstructure abnormalities of the diffusion quantities in children with attention-deficit/hyperactivity disorder: an AFQ and TBSS study.

To explore the specific alterations of white matter microstructure in children with attention-deficit/hyperactivity disorder (ADHD) by automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS), and to analyze the correlation between white matter abnormality and impairment of executive function. In this prospective study, a total of twenty-seven patients diagnosed with ADHD (20 males, 7 females; mean age of 8.89 ± 1.67 years) and twenty-two healthy control (HC) individuals (11 males, 11 females, mean age of 9.82 ± 2.13 years) were included. All participants were scanned with diffusion kurtosis imaging (DKI) and assessed for executive functions. AFQ and TBSS analysis methods were used to investigate the white matter fiber impairment of ADHD patients, respectively. Axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) of 17 fiber properties were calculated using the AFQ. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MDDKI), axial diffusivity (ADDKI), radial diffusivity (RDDKI) and fractional anisotropy (FADKI) of DKI and AD, RD, MD, and FA of diffusion tensor imaging (DTI) assessed the integrity of the white matter based on TBSS. Partial correlation analyses were conducted to evaluate the correlation between white matter abnormalities and clinical test scores in ADHD while taking age, gender, and education years into account. The analyses were all family-wise error rate (FWE) corrected. ADHD patients performed worse on the Behavior Rating Inventory of Executive Function (BRIEF) test (p < 0.05). Minor variances existed in gender and age between ADHD and HC, but these variances did not yield statistically significant distinctions. There were no significant differences in TBSS for DKI and DTI parameters (p > 0.05, TFCE-corrected). Compared to HC volunteers, the mean AD value of right cingulum bundle (CB_R) fiber tract showed a significantly higher level in ADHD patients following the correction of FWE. As a result of the point-wise comparison between groups, significant alterations (FWE correction, p < 0.05) were mainly located in AD (nodes 36-38, nodes 83-97) and MD (nodes 92-95) of CB_R. There was no significant correlation between white matter diffusion parameters and clinical test scores in ADHD while taking age, gender, and education years into account. The AFQ method can detect ADHD white matter abnormalities in a specific location with greater sensitivity, and the CB_R played a critical role. Our findings may be helpful in further studying the relationship between focal white matter abnormalities and ADHD.

Magnetic resonance imaging parameters on lacrimal gland in thyroid eye disease: a systematic review and meta-analysis

BackgroundThyroid eye disease is an extrathyroidal manifestation of Graves’ disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction.MethodsUp to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient).ResultsThyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively.ConclusionsMagnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.

Generalized q‐sampling imaging‐based fiber tracking measures of white matter tracts in cognitive impairment

AbstractBackgroundDiffusion magnetic resonance imaging (dMRI) is a non‐invasive technique for exploring white matter fiber organization of the brain. As traditional diffusion tensor imaging (DTI) methods may provide inaccurate descriptions of local crossing and diverging fibers, we examined generalized q‐sampling imaging (GQI), a novel method providing better directional and quantitative information using dMRI data from community‐dwelling older adults.MethodWe examined baseline dMRI data from 227 adults aged 71±8 on average from the Wake Forest Alzheimer’s Disease Research Center’s Clinical Core, who had baseline and year‐1 follow‐up global Clinical Dementia Rating (CDR) score of 0 (indicates normal cognitive function) and 0.5 (akin to MCI). The primary outcome measure was cognitive migration status determined by CDR increase/decrease between baseline and follow‐up (mean difference = 13.9 months), shown in Figure. We performed atlas‐based fiber tracking analysis using GQ in DSI Studio to generate normalized quantitative anisotropy (NQA), DTI fractional anisotropy (DTI_FA) and restricted diffusion (RDI) measures in several AD‐related white matter (WM) tracts: Corpus Callosum (CC), Fornix, Cingulum bundle/Parahippocampal tracts (see Table 2: CFP; CP; CPP), Uncinate Fasciculus (UF), Superior Longitudinal Fasciculus (SLF) and Inferior Fronto‐Occipital Fasciculus (IFOF). We performed multinomial logistic regression (MLR) models adjusted for age, sex, and education, using cognitive migration status as the outcome and standardized GQI‐based diffusion indices sNQA, sRDI, and sDTI_FA as predictors.Result Table 1 lists the baseline demographics and biomarker characteristics for cognitive migration groups. MLR results in Table 2 show significant associations between diffusion indices and tracts for outcome 4 (Reversion) in reference to outcome 1 (stability of normal cognition). Decrease in sNQA in bilateral CP and right Fornix was significantly associated with higher odds of Reversion relative to the reference. Increase in sDTI_FA in left IFOF was associated with higher odds of reversion relative to reference. Decrease in sRDI in bilateral CFP, CPP, Fornix and UF and right CP was associated with higher reversion relative to reference.ConclusionIn early trajectories of cognitive impairment, RDI may be a sensitive diffusion marker for cognitive reversion in several AD‐related WM tracts. Future work will validate these markers in other cognitive migration groups (negative migration and MCI stability).

672 Diffusion Basis Spectrum Imaging Provides Insights into Cervical Spondylotic Myelopathy Pathology

INTRODUCTION: Diffusion basis spectrum imaging (DBSI) is a non-invasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. METHODS: A single-center prospective cohort study enrolled fifty CSM patients and twenty controls from 2018-2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging (DTI) and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and non-restricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury via intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using mJOA classifications. Imaging parameters were compared among patient groups using independent-samples t-tests and ANOVA. RESULTS: Twenty controls, 27 mild (mJOA 15-17), 12 moderate (12-14) and 11 severe (0-11) CSM patients were enrolled. All patient-reported outcome measures were worse in CSM patients (all p &lt; 0.001). DTI and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and CSM patients (p &lt; 0.05). DBSI fiber fraction, restricted fraction, and non-restricted fraction were significantly different between groups (p &lt; 0.01). DBSI intra-axonal axial diffusivity was lower in mild compared to moderate (mean difference [95% CI]: 1.1 [0.3, 2.1], p &lt; 0.01) and severe (1.9 [1.3, 2.4], p &lt; 0.001) CSM. CONCLUSIONS: DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.

Posterior white matter integrity and self-reported posterior cortical symptoms using the Colorado Posterior Cortical Questionnaire.

The Colorado Posterior Cortical Questionnaire (CPC-Q) is a self-report, 15-item screening questionnaire for posterior cortical symptoms, including visuospatial and visuoperceptual difficulties. Changes in white matter connectivity may precede obvious gray matter atrophy in neurodegenerative conditions, especially posterior cortical atrophy. Integration of CPC-Q scores and measures of white matter integrity could contribute to earlier detection of posterior cortical syndromes. We investigated the relationships between posterior cortical symptoms as captured by the CPC-Q and diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions of interest localized to posterior brain regions (posterior thalamic radiations, splenium of corpus callosum, tapetum). Comparisons were also made by diagnostic group [healthy older adult (n = 31), amnestic Alzheimer's disease (AD, n = 18), and posterior cortical atrophy (PCA, n = 9)] and by SENAS battery visuospatial composite score quartile. Exploratory comparisons of all available individual white matter region DTI FA to CPC-Q, as well as comparisons of DTI FA between diagnostic groups and visuospatial quartiles, were also made. CPC-Q score was correlated with the average DTI FA for the averaged posterior white matter regions of interest (r = -0.31, p = 0.02). Posterior thalamic radiation DTI FA was most strongly associated with CPC-Q (r = -0.34, p = 0.01) and visuospatial composite (r = 0.58, p < 0.01) scores and differed between the PCA and AD groups and the lower and higher visuospatial quartiles. The DTI FA of body and splenium of the corpus callosum also demonstrated this pattern but not the DTI FA of the tapetum. The integrity of posterior white matter tracts is associated with scores on the CPC-Q, adding to the validation evidence for this new questionnaire. White matter regions that may be related to posterior cortical symptoms detected by the CPC-Q, and distinct from those affected in amnestic syndromes, include the posterior thalamic radiations and body and splenium of the corpus callosum. These findings are in line with previous neuroimaging studies of PCA and support continued research on white matter in posterior cortical dysfunction.

Variation in Diffusion Tensor Imaging Parameters in the Cervical and Thoracic Spinal Cord (C1-C5 and C6-T2) Segments of Normal Beagle Dogs.

This study aimed to determine the characteristics and reference values of each vertebra in the cervicothoracic region by performing diffusion tensor imaging (DTI) scans and analyzing DTI parameters in normal Beagle dogs. In five adult Beagles under anesthetic maintenance, DTI was performed using a 1.5-T magnetic resonance imaging (MRI) scanner. Axial DTI was performed using three overlapping slabs to cover the cervical and thoracic spinal cords. After post-processing, DTI parameters were calculated along the entire spinal cord. Among DTI parameters, fractional anisotropy, relative anisotropy, and axonal diffusivity significantly decreased in the caudal direction. However, the apparent diffusion coefficient, radial diffusivity, and mean diffusivity values were not significantly correlated with vertebral levels. We provide evidence for the existence of segment-dependent DTI parameters in the canine cervical spinal cord. Therefore, comparisons of DTI parameters between lesions at different vertebral levels should be avoided unless normative data are available. Furthermore, the DTI data obtained in this study may contribute to the development of a clinical reference for spinal cord evaluation in dogs using DTI parameters.

Effects of Dementia and MCI on Diffusion Tensor Metrics Using the Updated ADNI3 DTI Preprocessing Pipeline

AbstractBackgroundDiffusion magnetic resonance imaging (dMRI) provides insight into white matter (WM) microstructural changes in Alzheimer’s disease and mild cognitive impairment (MCI). The Alzheimer’s Disease Neuroimaging Initiative’s (ADNI) has currently extended its ADNI3 imaging protocol to include dMRI from Siemens, Philips and General Electric (GE) scanners, resulting in seven vendor‐specific dMRI acquisition protocols (Table1). Here we present the updated ADNI3 preprocessing pipeline1 (Figure1) for diffusion tensor imaging (DTI) metrics made available via ADNI’s database, and evaluate their utility for detecting WM differences associated with clinical impairment.MethodRaw dMRI downloaded from ADNI are first denoised using DiPy’s principal component analysis (PCA) denoising algorithms: local PCA for zero‐padded k‐space data (GE), or Marchenko‐Pastur PCA for data with the original acquisition matrix (Siemens/Philips). dMRI are then corrected for Gibbs ringing, eddy currents using FSL’s eddy_cuda with repol outlier estimation and slice‐to‐volume correction, intensity inhomogeneity with ANTS N4, and echo‐planar imaging distortions with a three‐channel non‐linear registration of the subject‐level preprocessed average B0 image to the subject’s skull‐stripped T1‐weighted MRI. Bias field correction is applied again to dMRI with FSL‐FAST. DTI fractional anisotropy (FA), axial, mean and radial diffusivity (AxD, MD, RD) are estimated with FSL’s dtifit, using weighted least squares. The JHU ICBM‐DTI‐81 atlas FA is warped to subject‐level FA maps using ANTS, and the transformations are applied to atlas labels. Subject‐level mean and robust mean (using M‐estimator from R’s ‘WRS2’ package) of DTI metrics within 73 WM regions of interest (ROIs; Table2) are extracted. Here, we fit linear mixed effects models of diagnosis (N=733) and clinical dementia rating (CDR‐sob; N=682; Table3) in 28 of the 73 available ROIs, covarying for age, sex, age*sex, and including nested protocol|site variables as random effects; multiple comparisons were corrected for using false discovery rate (q=0.05).ResultLower anisotropy and greater diffusivity were associated with greater impairment, particularly in the hippocampal cingulum (Figure2). Results from mean and robust mean metrics were comparable. Overall, our results follow previous work2,3 using publicly available ADNI dMRI.ConclusionSubject‐level ADNI3 dMRI measures, sensitive to clinical indices of impairment as presented here, are available at https://ida.loni.usc.edu/.

Generalized q‐sampling imaging‐based fiber tracking measures of white matter tracts in cognitive impairment

AbstractBackgroundDiffusion magnetic resonance imaging (dMRI) is a non‐invasive technique for exploring white matter fiber organization of the brain. As traditional diffusion tensor imaging (DTI) methods may provide inaccurate descriptions of local crossing, kissing and diverging fibers, we examined generalized q‐sampling imaging (GQI), a novel method providing better directional and quantitative information using dMRI data from community‐dwelling older adults.MethodWe examined baseline dMRI data from 227 adults aged 71±8 on average from the Wake Forest Alzheimer’s Disease Research Center’s Clinical Core, who had baseline and year‐1 follow‐up global Clinical Dementia Rating (CDR) score of 0 (indicates normal cognitive function) and 0.5 (akin to mild cognitive impairment [MCI]). The primary outcome measure was cognitive migration status determined by CDR increase/decrease between baseline and follow‐up (mean difference=13.9 months), shown in Figure. We performed atlas‐based fiber tracking analysis using GQI in DSI Studio to generate normalized quantitative anisotropy (NQA), DTI fractional anisotropy (DTI_FA) and restricted diffusion (RDI) measures in several AD‐related white matter (WM) tracts: Corpus Callosum (CC), Fornix, Cingulum bundle/Parahippocampal tracts (CFP; CP; CPP), Uncinate Fasciculus (UF), Superior Longitudinal Fasciculus (SLF) and Inferior Fronto‐Occipital Fasciculus (IFOF). We performed multinomial logistic regression (MLR) models adjusted for age, sex, and education, using cognitive migration status as the outcome, and standardized GQI‐based diffusion indices sNQA, sRDI, and sDTI_FA as predictors.ResultTable 1 lists the baseline demographics and biomarker characteristics for cognitive migration groups. MLR results in Table 2 show significant associations between diffusion indices and tracts for outcome 4 (Reversion) in reference to outcome 1 (stability of normal cognition). Decrease in sNQA in bilateral CP and right Fornix was significantly associated with higher odds of Reversion relative to the reference. Increase in sDTI_FA in left IFOF was associated with higher odds of reversion relative to reference. Decrease in sRDI in bilateral CFP, CPP, Fornix and UF and right CP was associated with higher reversion relative to reference.ConclusionIn early trajectories of cognitive impairment, RDI may be a sensitive diffusion marker for cognitive reversion in several AD‐related WM tracts. Future work will validate these markers in other cognitive migration groups (negative migration and MCI stability).

The regional relationship between CSF VEGF and white matter microstructural integrity in older adults: A voxelwise DTI study

AbstractBackgroundBoth white matter (WM) micro‐ and macro‐ structural abnormalities occur in Alzheimer’s disease (AD) with micro‐structural abnormalities likely preceding macrostructural changes in the AD cascade. Diffusion tensor imaging (DTI) fractional anisotropy (FA) ‐ which is sensitive to factors such as myelination, fiber coherence, and fiber density‐ within an MRI voxel may be used to detect AD‐specific deficits. However, mechanisms driving loss of WM microstructural integrity in AD are poorly understood. Vascular endothelial growth factor (VEGF) is a multi‐function vascular protein linked to early AD brain and cognition biomarkers. VEGF provides neurotrophic support via glia and is also secreted by glial cells essential for maintaining myelin. However, in humans, the relationship between VEGF and WM microstructural integrity has yet to be mapped. We evaluated whether cerebrospinal fluid (CSF) VEGF levels were associated with voxelwise WM FA in older adults without dementia.MethodWe evaluated 72 older adults without dementia from the USC Alzheimer’s Disease Research Center (ADRC) (mean age 65.7; 47‐82 years old) with a clinical dementia rating (CDR) score of 0 (n=56) or 0.5 (n=16) who had both CSF VEGF‐A levels and a 3 T diffusion MRI scan (64‐direction (b=1000 s/mm2) DWI volumes). MRI scans were pre‐processed to reduce artifacts related to motion, distortion, eddy currents, bias field, and susceptibility artifacts. Tract‐based spatial statistics, using FSL software, was implemented to derive skeletonized FA maps along WM tracts. The association between VEGF and voxelwise FA WM integrity was evaluated using FSL’s general linear model tool. We covaried for age, sex, and CDR. FA significance cluster maps were corrected for voxelwise multiple comparisons.ResultHigher CSF VEGF levels were associated with lower DTI FA, indicative of poorer WM microstructural integrity, in the left and right superior longitudinal fasciculus, left anterior thalamic radiation, and left inferior frontal occipital fasciculus (p&lt;0.05) (Figure 1).ConclusionThese results demonstrate for the first time in humans that VEGF levels are related to WM microstructure in older adults without dementia, primarily in long range association fibers connecting temporal, parietal, and frontal lobes. These pathways are essential for memory, language, attention and emotional control.

Utility of diffusion tensor imaging in differentiating benign from malignant hepatic focal lesions.

To assess the diagnostic accuracy of diffusion tensor imaging (DTI) in the characterization of hepatic focal lesions (HFLs) and compare it to diffusion-weighted imaging (DWI). Prospective analysis was done for 49 patients (23 male and 26 female) with 74 HFLs who underwent dynamic MRI, DWI, and DTI. Apparent diffusion coefficient (ADC) values from DWI, fractional anisotropy (FA) values, and mean diffusivity (MD) values from DTI were measured by two independent radiologists. HFLs were classified into benign and malignant HFLs; the latter were subdivided into HCC and non-HCC lesions. Binary logistic regression was performed to analyze the associations between the DTI parameters and the distinction of malignant lesions. The ADC, MD, and FA at cutoff values of ≤ 1.17 × 10-3 mm2/s, ≤ 1.71 × 10-3 mm2/s, and > 0.29, respectively, are excellent discriminators for differentiating malignant and benign HFLs. The mean ADC and MD values of hemangiomas were significantly higher than HCC and non-HCC malignant lesions. In contrast, the mean FA values of hemangiomas were significantly lower than those of non-HCC malignant lesions and HCCs. The ADC and MD were very good discriminators at cutoff values of > 1.03 × 10-3 mm2/s and > 1.12 × 10-3 mm2/s, respectively. The FA at a cutoff value > 0.38 is an excellent discriminator for HCC versus non-HCC malignant lesions. Only FA value > 0.38 was a statistically significant independent predictor of HCC versus non-HCC lesions among the three parameters. There was an excellent inter-observer agreement with ICC > 0.9. MD and FA of DTI are non-invasive, very good, and excellent discriminators superior to ADC measured by DWI for the differentiation of HFLs. • The ADC, MD, and FA at cutoff values of ≤ 1.17 × 10-3 mm2/s, ≤ 1.71 × 10-3 mm2/s, and > 0.29, respectively, are excellent discriminators for differentiating malignant and benign HFLs. • The mean ADC and MD values of hemangiomas were significantly higher than those of HCC and non-HCC malignant lesions. In contrast, the mean FA values of hemangiomas were significantly lower than those of non-HCC malignant lesions and HCCs, respectively. • Multivariate regression analysis revealed that only FA value > 0.38 was a statistically significant independent predictor of HCC vs. non-HCC lesions. A lesion with FA > 0.38 has 34 times higher odds of being HCC rather than non-HCC lesions.

Utility of Diffusion Basis Spectrum Imaging in Quantifying Baseline Disease Severity and Prognosis of Cervical Spondylotic Myelopathy.

Prospective cohort study. The aim was to assess the association between diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) measures and cervical spondylotic myelopathy (CSM) clinical assessments at baseline and two-year follow-up. Despite advancements in diffusion-weighted imaging, few studies have examined associations between diffusion magnetic resonance imaging (MRI) markers and CSM-specific clinical domains at baseline and long-term follow-up. A single-center prospective cohort study enrolled 50 CSM patients who underwent surgical decompression and 20 controls from 2018 to 2020. At initial evaluation, all patients underwent diffusion-weighted MRI acquisition, followed by DTI and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. To improve estimations of intra-axonal anisotropic diffusion, DBSI measures intra-/extra-axonal fraction and intra-axonal axial diffusivity. DBSI also evaluates extra-axonal isotropic diffusion by restricted and nonrestricted fraction. Clinical assessments were performed at baseline and two-year follow-up and included the modified Japanese Orthopedic Association (mJOA); 36-Item Short Form Survey physical component summary (SF-36 PCS); SF-36 mental component summary; neck disability index; myelopathy disability index; and disability of the arm, shoulder, and hand. Pearson correlation coefficients were computed to compare associations between DTI/DBSI and clinical measures. A False Discovery Rate correction was applied for multiple comparisons testing. At baseline presentation, of 36 correlations analyzed between DTI metrics and CSM clinical measures, only DTI fractional anisotropy showed a positive correlation with SF-36 PCS ( r =0.36, P =0.02). In comparison, there were 30/81 (37%) significant correlations among DBSI and clinical measures. Increased DBSI axial diffusivity, intra-axonal axial diffusivity, intra-axonal fraction, restricted fraction, and extra-axonal anisotropic fraction were associated with worse clinical presentation (decreased mJOA; SF-36 PCS/mental component summary; and increased neck disability index; myelopathy disability index; disability of the arm, shoulder, and hand). At latest follow-up, increased preoperative DBSI intra-axonal axial diffusivity and extra-axonal anisotropic fraction were significantly correlated with improved mJOA. This findings demonstrate that DBSI measures may reflect baseline disease burden and long-term prognosis of CSM as compared with DTI. With further validation, DBSI may serve as a noninvasive biomarker following decompressive surgery. 3.

Physical Frailty and Brain White Matter Abnormalities: The Atherosclerosis Risk in Communities Study.

Physical frailty is associated with increased risk for dementia and other neurologic sequelae. However, the neurobiological changes underlying frailty and frailty risk remain unknown. We examined the association of cerebral white matter structure with current and future frailty. Atherosclerosis Risk in Communities Study Neurocognitive Study participants who underwent 3T brain MRI were included. Frailty status was classified according to the Fried criteria. Cerebral white matter integrity was defined using white matter hyperintensity (WMH) volume and microstructure, measured using diffusion tensor imaging fractional anisotropy (FA) and mean diffusivity (MD). Multivariable linear regression was used to relate baseline frailty to white matter structure; multivariable logistic regression was used to relate baseline white matter to frailty risk among participants nonfrail at baseline. In the cross-sectional analysis (N = 1 754; mean age: 76 years), frailty was associated with greater WMH volume, lower FA, and greater MD. These associations remained consistent after excluding participants with a history of stroke or dementia. Among participants nonfrail at baseline who completed follow-up frailty assessment (N = 1 379; 6.6-year follow-up period), each standard deviation increase in WMH volume was associated with 1.46 higher odds of frailty at follow-up. Composite FA and MD measures were not associated with future frailty; however, secondary analyses found several significant white matter tract-specific associations with frailty risk. The current study demonstrates a robust association of WMH volume with current and future frailty. Although measures of white matter microstructure were altered in frail individuals, these measures were not generally associated with progression from nonfrail to frail status.

Functional, but minimal microstructural brain changes present in aging Canadian football league players years after retirement

This brain imaging study examined subjects with a history of repetitive concussive and sub-concussive impacts sustained over the course of their careers in the Canadian Football League (CFL). We hypothesized that microstructural and functional abnormalities, assessed using diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (rsfMRI) respectively, would be present in these retired athletes, that are not present in matched controls. Seventeen aging, retired CFL players (aged 58.5±6.2y, ranged 45–66) completed three neuropsychological tests, and had anatomical, diffusion and functional MRI scans performed. Healthy age- and sex-matched control data (n = 2117) were used to develop a subject-specific and region-wise Z-scoring approach. Regional DTI fractional anisotropy (FA) and rsfMRI signal complexity (fractal dimension; FD) Z-score data was further analyzed as a subject-specific total, left, and right injury burden (IB) value for each MRI metric. Microstructural abnormality was detected in 6 of 17 subjects based on DTI FA. The rsfMRI data showed 4 subjects with higher total FDIB, and several regions had Z-score outliers detected in multiple subjects. The right pre-motor cortex, right hippocampus dentate gyrus, and right visual cortex were the most abnormally functioning grey matter brain regions. Total FAIB was negatively correlated with career length, social functioning, and significantly with emotional well-being, and positively correlated with physical health. Total FDIB was negatively correlated with energy and fatigue and general health, and positively correlated with age, career length, and education. This study provides evidence of brain changes years after professional athletes have retired.

Diffusion Tensor Imaging Observation of Frontal Lobe Multidirectional Transcranial Direct Current Stimulation in Stroke Patients with Memory Impairment.

Stroke is a group of diseases caused by the sudden rupture or blockage of blood vessels in the brain that prevent blood from flowing into the brain, resulting in brain tissue damage and dysfunction. Stroke has the characteristics of high morbidity, high disability, and high mortality. To investigate the effect of multidirectional transcranial direct current stimulation (tDCS) of the prefrontal lobe in stroke memory disorder. We evaluated 60 patients with poststroke memory impairment who underwent magnetic resonance diffusion tensor imaging (DTI) during their admission to our hospital between January 2018 and December 2020. The patients were divided into the prefrontal group (n = 15), dorsolateral group (n = 15), prefrontal + dorsolateral group (n = 15), and pseudostimulation group (n = 15). Assessments using the Rivermead Behavioral Memory Test (RBMT), Montreal Cognitive Assessment Scale (MoCA), Lovingston Occupational Therapy Cognitive Scale (LOTCA), and frontal lobe fractional anisotropy (FA) were performed before and after treatment. The RBMT, MoCA, and LOTCA scores in the prefrontal + dorsolateral group were significantly higher than those in the dorsolateral, prefrontal, and sham groups (all P < 0.05). The posttreatment FA value of the frontal lobe was significantly higher in the prefrontal + dorsolateral group than in the dorsolateral, prefrontal, and sham stimulation groups (all P < 0.05). The FA value of the frontal lobe was significantly lower in patients with severe memory impairment than in patients with mild-moderate memory impairment (P < 0.05). The area under the receiver operating characteristic curve was 0.801 (95% CI: 0.678–0.925, P < 0.05), and the optimal cut-off value was 0.34, with a sensitivity and specificity of 81.60% and 72.70%, respectively. Prefrontal lobe + dorsolateral tDCS is beneficial in the treatment of post-stroke memory impairment. The DTI FA value can be useful in determining the degree of memory impairment.

White Matter Abnormalities and Cognitive Deficit After Mild Traumatic Brain Injury: Comparing DTI, DKI, and NODDI.

White matter (WM) disruption is an important determinant of cognitive impairment after mild traumatic brain injury (mTBI), but traditional diffusion tensor imaging (DTI) shows some limitations in assessing WM damage. Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) show advantages over DTI in this respect. Therefore, we used these three diffusion models to investigate complex WM changes in the acute stage after mTBI. From 32 mTBI patients and 31 age-, sex-, and education-matched healthy controls, we calculated eight diffusion metrics based on DTI (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), DKI (mean kurtosis), and NODDI (orientation dispersion index, volume fraction of intracellular water (Vic), and volume fraction of the isotropic diffusion compartment). We used tract-based spatial statistics to identify group differences at the voxel level, and we then assessed the correlation between diffusion metrics and cognitive function. We also performed subgroup comparisons based on loss of consciousness. Patients showed WM abnormalities and cognitive deficit. And these two changes showed positive correlation. The correlation between Vic of the splenium of the corpus callosum and Digit Symbol Substitution Test scores showed the smallest p-value (p = 0.000, r = 0.481). We concluded that WM changes, especially in the splenium of the corpus callosum, correlate to cognitive deficit in this study. Furthermore, the high voxel count of NODDI results and the consistency of mean kurtosis and the volume fraction of intracellular water in previous studies and our study showed the functional complementarity of DKI and NODDI to DTI.

Abstract WMP82: Diffusion Tensor Imaging Is Independently Associated With Mobility After Intracerebral Hemorrhage

Background: Intracerebral hemorrhage (ICH) patients may appear disabled despite intact cortical spinal tracts (CST). ICH lesions may also vary in volume and location relative to the CST with differential impacts on motor outcome. In this study, we evaluated whether diffusion tensor imaging (DTI) integrity of CST fiber tracking associates with mobility three months post ICH. Methods: The Recovery and Outcomes from StrokE (ROSE) Study is a prospective, multi-center study of ICH serially assessed with motor, cognitive, and functional outcomes and MRI/DTI. Outcome data were collected by hospital chart review and interview/exam. Acute MRI images were analyzed by a central neuroimaging core for ICH location, size, intraventricular hemorrhage, and fractional anisotropy (FA) derived from DTI of the CST. Mobility was assessed at 3-month follow-up using the Barthel Mobility Index. We computed single variable logistic regression analyses (outcome = Barthel mobility at 3 months). We also computed a stepwise logistic model, with and without age, sex, and race, including variables that met P&lt;0.1 to best fit. Results: There were 76 ICH patients with DTI FA data available for analysis; 61 with complete data for the multivariate model. Poor mobility after ICH (N = 21; 27.6%) was associated with ICH volume, presence of IVH, Glasgow coma score, ipsilesional CST FA, ipsilesional CP FA and CP FA asymmetry index (Table 1). The multivariate model that adjusted for age, sex, and race identified ipsilesional CP FA, admission GCS and presence of IVH as associated with poor mobility at 3 months; notably, log ICH volume was not associated after controlling for CST injury (Table 1). Conclusions: The presence of IVH and the GCS score at baseline were associated with poor mobility. In addition, the CP FA asymmetry index was independently associated with poor mobility even after accounting for log ICH volume, suggesting that DTI is informative of outcome beyond classic ICH outcome predictors.