Fractional Anisotropy Measures Research Articles

A site-wise reliability analysis of the ABCD diffusion fractional anisotropy and cortical thickness: impact of scanner platforms.

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce non-biological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation coefficients (ICC). We developed a site-wise adaptive ICC (AICC) to evaluate the reliability of imaging-derived phenotypes while accounting for ongoing brain development. AICC iteratively estimates the population-level age-related brain development trajectory using a weighted mixed model and updates age-corrected site-wise reliability until convergence. We evaluated the test-retest reliability of regional fractional anisotropy (FA) measures from diffusion tensor imaging and cortical thickness (CT) from structural MRI data for each site. The mean AICC for 20 FA tracts across sites was 0.61±0.19, lower than the mean AICC for CT in 34 regions across sites, 0.76±0.12. Remarkably, sites using Siemens scanners consistently showed significantly higher AICC values compared to those using GE/Philips scanners for both FA (AICC=0.71±0.12 vs 0.46±0.17, p<0.001) and CT (AICC=0.80±0.10 vs 0.69±0.11, p<0.001). These findings demonstrate site-and-scanner related variations in data quality and underscore the necessity for meticulous data curation in subsequent association analyses.

Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.

Estimating the prevalence of Non-Verbal Learning Disability (NVLD) from the ABCD sample.

Non-Verbal Learning Disability (NVLD) is a neurodevelopmental disorder characterized by deficits in processing visuospatial information but with age-appropriate verbal skills. This cognitive profile has been hypothesized to be associated with atypical white matter, but at the present there is a lack of evidence for this hypothesis. Currently, the condition is not characterized within the main diagnostic systems, in part because no clear set of criteria for characterizing the disorder exists. This report is the first attempt to estimate NVLD prevalence, using two sets of diagnostic criteria, in a large sample of over 11,000 children who were selected without regards to problems of specific nature, either psychological, neurological, physical and/or social. Furthermore, it examined the association between the profile of cognitive abilities and aspects of whole-brain white matter measures in children with and without symptoms associated with NVLD. Participants were drawn from the Adolescent Brain Cognitive Development (ABCD) study, a 10-year longitudinal study of 11,876 children in the U.S. The data used in the present study were drawn from the initial testing point at which the children were 9-10years old. Prevalence of NVLD based on two distinct sets of criteria, correlations between the measures used to create the criteria, correlations between criteria measures and measures of white matter integrity. The cognitive criteria included measures of visuospatial processing, reading, intelligence and social skills. By varying the cut-offs applied to social skills in conjunction with visuo-spatial difficulties, spared reading skills and intelligence scores, we calculated prevalence for two NVLD groups. White matter characteristics were measures of volume, fractional anisotropy and mean diffusivity. Based on the criteria used, the estimated prevalence of NVLD varied from 1 to 8%. Furthermore, children with NVLD showed a dissociation between measures of visuo-spatial processing not observed in non-NVLD children. At the neurological level, findings provide preliminary evidenceof associations between the cognitive profile of NVLD and abnormalities in white matters tracts. The present study documents that exists, within this large non-selected sample, a proportion of youth who show evidence of NVLD. Given those results, it appears essential to establish the best diagnostic criteria, to improve the treatment options and quality of life for children with this disorder.

Down-sampling in diffusion MRI: a bundle-specific DTI and NODDI study.

Multi-shell diffusion Magnetic Resonance Imaging (dMRI) data has been widely used to characterise white matter microstructure in several neurodegenerative diseases. The lack of standardised dMRI protocols often implies the acquisition of redundant measurements, resulting in prolonged acquisition times. In this study, we investigate the impact of the number of gradient directions on Diffusion Tensor Imaging (DTI) and on Neurite Orientation Dispersion and Density Imaging (NODDI) metrics. Data from 124 healthy controls collected in three different longitudinal studies were included. Using an in-house algorithm, we reduced the number of gradient directions in each data shell. We estimated DTI and NODDI measures on six white matter bundles clinically relevant for neurodegenerative diseases. Fractional Anisotropy (FA) measures on bundles where data were sampled at the 30% rate, showed a median L1 distance of up to 3.92% and a 95% CI of (1.74, 8.97)% when compared to those obtained at reference sampling. Mean Diffusivity (MD) reached up to 4.31% and a 95% CI of (1.60, 16.98)% on the same premises. At a sampling rate of 50%, we obtained a median of 3.90% and a 95% CI of (1.99, 16.65)% in FA, and 5.49% with a 95% CI of (2.14, 21.68)% in MD. The Intra-Cellular volume fraction (ICvf) median L1 distance was up to 2.83% with a 95% CI of (1.98, 4.82)% at a 30% sampling rate and 3.95% with a 95% CI of (2.39, 7.81)% at a 50% sampling rate. The volume difference of the reconstructed white matter at reference and 50% sampling reached a maximum of (2.09 ± 0.81)%. In conclusion, DTI and NODDI measures reported at reference sampling were comparable to those obtained when the number of dMRI volumes was reduced by up to 30%. Close to reference DTI and NODDI metrics were estimated with a significant reduction in acquisition time using three shells, respectively with: 4 directions at a b value of 700 s/mm2, 14 at 1000 s/mm2, and 32 at 2000 s/mm2. The study revealed aspects that can be important for large-scale clinical studies on bundle-specific diffusion MRI.

Effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on the balance and the white matter integrity in patients with relapsing-remitting multiple sclerosis: A long-term follow-up study

ObjectivesRepetitive Transcranial Magnetic Stimulation (rTMS) is considered as a safe and non-invasive developing technique used as a therapeutic method for patients with Relapsing-Remitting Multiple Sclerosis (RRMS) who suffer from disturbances in gait and balance. The aim of our study is to evaluate the long-term effect of high frequency rTMS as a therapeutic option for truncal ataxia in RRMS patients and to assess its impact on the integrity of the white matter (WMI), measured in the form of anisotropy metrics using diffusion tensor imaging (DTI). MethodsThe study was conducted in two phases: phase I; a randomized, single-blind, sham-controlled phase and phase II was a 12 months longitudinal open-label prospective phase. Phase I of the trial involved the randomization of 43 patients with RRMS and truncal ataxia to either real (n = 20) or sham (n = 19) rTMS (2 participants from each treatment group were excluded from the study; one developed a relapse before treatment, 2 declined to participate, and one did not show up). Phase II involved providing 12 actual treatments cycles to all patients; each cycle length is 4 weeks, repeated four times on a trimonthly basis, forming a total of 48 sessions. DTI was used for assessment of the WMI. All patients performed DTI 3 times: Imaging sessions were conducted at the screening visit, at the end of phase I, and after the last session in phase II for the first, second and third sessions respectively. A figure-of-8-shape coil, employing rTMS protocol and located over the cerebellum, was used. rTMS protocol is formed of 20 trains formed of 50 stimuli with 20 s apart (5 Hz of 80 % of resting Motor Threshold “MT”). The Berg Balance Scale (BBS), Time up and go (TUG) test, and 10-m walk test (10MWT) were first evaluated at the start of each cycle and just after the final rTMS session. ResultsThe genuine rTMS group's 10MWT, TUG, and BBS showed substantial improvement (p < 0.01), which is continued to be improved throughout the study Timeline, with a significant difference observed following the final rTMS session (P< 0.001). A longitudinal increase in FA was observed in both the Cerebello-Thalamo-Cortical (CTC) and Cortico-Ponto-Cerebellar (CPC) bilateral, as indicated by means of Fractional Anisotropy (FA) measures (p < 0.05). ConclusionIn ataxic RRMS patients, high frequency rTMS over the cerebellum has a long-term beneficial impact on both balance and WMI.

Association of Poor Oral Health With Neuroimaging Markers of White Matter Injury in Middle-Aged Participants in the UK Biobank.

Poor oral health is a modifiable risk factor that is associated with clinically observed cardiovascular disease. However, the relationship between oral and brain health is not well understood. We tested the hypothesis that poor oral health is associated with worse neuroimaging brain health profiles in middle-aged persons without stroke or dementia. We performed a 2-stage cross-sectional neuroimaging study using UK Biobank data. First, we tested for association between self-reported poor oral health and MRI neuroimaging markers of brain health. Second, we used Mendelian randomization (MR) analyses to test for association between genetically determined poor oral health and the same neuroimaging markers. Poor oral health was defined as the presence of dentures or loose teeth. As instruments for the MR analysis, we used 116 independent DNA sequence variants linked to increased composite risk of dentures or teeth that are decayed, missing, or filled. Neuroimaging markers of brain health included white matter hyperintensity (WMH) volume and aggregate measures of fractional anisotropy (FA) and mean diffusivity (MD), 2 metrics indicative of white matter tract disintegrity obtained through diffusion tensor imaging across 48 brain regions. We included 40,175 persons (mean age 55 years, female sex 53%) enrolled from 2006 to 2010, who underwent a dedicated research brain MRI between 2014 and 2016. Among participants, 5,470 (14%) had poor oral health. Poor oral health was associated with a 9% increase in WMH volume (β = 0.09, SD = 0.014, p < 0.001), 10% change in aggregate FA score (β = 0.10, SD = 0.013, p < 0.001), and 5% change in aggregate MD score (β = 0.05, SD = 0.013, p < 0.001). Genetically determined poor oral health was associated with a 30% increase in WMH volume (β = 0.30, SD = 0.06, p < 0.001), 43% change in aggregate FA score (β = 0.43, SD = 0.06, p < 0.001), and 10% change in aggregate MD score (β = 0.10, SD = 0.03, p < 0.01). Among middle age Britons without stroke or dementia, poor oral health was associated with worse neuroimaging brain health profiles. Genetic analyses confirmed these associations, supporting a potentially causal association. Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health.

Diffusion tensor imaging in pediatric patients with dystonia

Background: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia.Methods: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies.Results: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus.Conclusion: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

Severity of muscle impairment and its progression assessed using musculoskeletal magnetic resonance imaging and diffusion tension imaging in 78 boys with Duchenne muscular dystrophy: a retrospective study

PurposeDuchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. Current diagnostic tests like genetic testing, needle electromyography, and muscle biopsy are either not easily available or invasive, and they are impractical for assessing disease progression and treatment outcomes. Therefore, there is a need for a non-invasive and accurate investigative modality for DMD. In recent years, musculoskeletal magnetic resonance imaging (MRI-MSK) along with fractional anisotropy (FA) and diffusion tensor imaging (DTI) have become major non-invasive tools.Material and methodsT1-weighted MRI-MSK and FA measures of DTI of 78 DMD patients were retrospectively studied to identify the distinct pattern of muscle involvement and fatty infiltration as age and/or disease progresses. Correlation analysis was performed between MRI-MSK grade score vs. age, muscle strength, and Vignos scale. Spearman’s rank correlation coefficient was used.ResultsAs age increased, the MRI grade score and Vignos score increased. There was a statistically significant high positive correlation between MRI-MSK grade score and age, and low positive correlation with Vignos scores. With increasing age, the muscle strength on manual muscle testing (MMT) and FA value decreased. There was high negative correlation with muscle strength on MMT and low positive correlation between FA values and MMT score.ConclusionsOn T1-weighted MRI, a distinct pattern, extent, and distribution of lower limb muscle involvement can be seen. MRI-MSK grade score worsens with progressing age, reducing strength, and increasing functional impairment. FA alone may not be an accurate marker in assessing progression of DMD. MRI-MSK and other DTI measures should be further explored as diagnostic and prognostic tools for DMD.

Common neurobiological mechanisms underlying anosognosia and neuropsychiatric symptoms across the Alzheimer’s disease spectrum

AbstractBackgroundBoth loss of awareness for cognitive decline (a.k.a. anosognosia) and neuropsychiatric symptoms (NPS) are common symptoms in Alzheimer’s disease (AD) and have been associated with AD pathology. Recent studies have shown a co‐occurrence between these symptoms across the AD spectrum, suggesting shared underlying neurophysiological processes, especially within the default mode network (DMN). Here, we investigated the relationship between NPS and altered awareness and the structural integrity (as assessed with diffusion tensor imaging, DTI) of brain regions supporting the DMN in participants with and without amyloid pathology.MethodsThree‐hundred participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent an amyloid positron emission tomography (PET), using 18F‐AV45 (florbetapir), and were classified into two groups: amyloid‐positive (A+) and negative (A‐). Individual mean fractional anisotropy (FA) was calculated from tracts overlapping the DMN regions. An awareness index was computed using the discrepancy between Everyday Cognition questionnaire scores from participants and informants. The Neuropsychiatric Inventory Total Score was used to assess the informant‐reported NPS. We compared amyloid groups on demographics and our different measures of interest. Pearson correlations were used to determine associations between measures of interest in each amyloid group. A multivariate multiple regression (MMR) model was performed to determine whether structural brain integrity predicts altered awareness and NPS jointly.ResultsA+ participants were significantly older (74 ± 7 vs. 72 ± 7 for A‐), more impaired (CDR global), and showed lower awareness and diffusion, and greater NPS (all p&lt;0.001, see Table 1). Significant correlations were found between the FA, NPS, and awareness measures in A+ participants, with decreased FA associated with decreased awareness and more NPS. The MMR confirmed these associations between FA, awareness and NPS (p&lt;0.02, see Table 2). The Pillai test revealed that the DTI effect jointly contributed to both models. No significant relationships were observed in the A‐ group.ConclusionOur results show that, in amyloid‐positive individuals across the AD spectrum, decreased awareness and increased NPS were related to decreased structural integrity of the DMN. This supports the hypothesis of common neurobiological mechanisms underlying anosognosia and NPS in AD.

MRI of brachial plexus using diffusion tensor imaging: a pilot study for the use of resolve sequence surgical and radiologic anatomy.

Clinical exam is the goldstandard for surgical indication. ENMG and conventional MRI are insufficient to understand the highly variable clinical presentation of brachial plexus (BP) lesions. DTI is based on motion of water molecules and can explore nerve function. This pilot study of healthy subjects aimed to develop RESOLVE sequence for BP exploration using diffusion MRI. The main objective was to provide complete precise information from DTI cartography associated with anatomical data. Six healthy volunteers were scanned using 3T PRISMA scanner with anatomic 3D STIR SPACE and RESOLVE diffusion sequences. Diffusion parametric maps of fractional anisotropy (FA) were extracted from RESOLVE acquisitions. A reproducible method for roots volumes and angles measurements was created using 3DSlicer. ROI were segmented on Mean B0 sequences. FA measurements were obtained with ROI on Mean B0 sequences. RESOLVE sequence was adapted to the BP. Mean FA was 0.30. Angles measurements on 3D STIR SPACE sequences showed increasing values from proximal to distal roots with an 0.6 ICC. Volume measurements on anatomic sequences varied widely from one root to another but did not show any significant difference on laterality. A new and reproducible method for BP exploration was developed, using MRI RESOLVE DTI sequences. Complete mapping was obtained but a low resolution of track density imaging did not allow to exploit distal nerves. Deterministic tractography principal limit was the lack of resolution. Extraction of diffusion, volumetric and angular parameters of the plexus roots, and scripts creation for image processing was adapted to the healthy BP.

Evidence of Ongoing Cerebral Microstructural Reorganization in Children With Persisting Symptoms Following Mild Traumatic Brain Injury: A NODDI DTI Analysis.

Approximately 300-550 children per 100,000 sustain a mild traumatic brain injury (mTBI) each year, of whom ∼25-30% have long-term cognitive problems. Following mTBI, free water (FW) accumulation occurs in white matter (WM) tracts. Diffusion tensor imaging (DTI) can be used to investigate structural integrity following mTBI. Compared with conventional DTI, neurite orientation dispersion and density imaging (NODDI) orientation dispersion index (ODI) and fraction of isolated free water (FISO) metrics may allow a more advanced insight into microstructural damage following pediatric mTBI. In this longitudinal study, we used NODDI to explore whole-brain and tract-specific differences in ODI and FISO in children with persistent symptoms after mTBI (n = 80) and in children displaying clinical recovery (n = 32) at 1 and 2-3 months post-mTBI compared with healthy controls (HCs) (n = 21). Two-way repeated measures analysis of variance (ANOVA) and voxelwise two-sample t tests were conducted to compare whole-brain and tract-specific diffusion across groups. All results were corrected at positive false discovery rate (pFDR) <0.05. We also examined the association between NODDI metrics and clinical outcomes, using logistical regression to investigate the value of NODDI metrics in predicting future recovery from mTBI. Whole-brain ODI was significantly increased in symptomatic participants compared with HCs at both 1 and 2 months post-injury, where the uncinate fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF) were particularly implicated. Using region of interest (ROI) analysis in significant WM, bilateral IFOF and UF voxels, symptomatic participants had the highest ODI in all ROIs. ODI was lower in asymptomatic participants, and HCs had the lowest ODI in all ROIs. No changes in FISO were found across groups or over time. WM ODI was moderately correlated with a higher youth-reported post-concussion symptom inventory (PCSI) score. With 87% predictive power, ODI (1 month post-injury) and clinical predictors (age, sex, PCSI score, attention scores) were a more sensitive predictor of recovery at 2-3 months post-injury than fractional anisotropy (FA) and clinical predictors, or clinical predictors alone. FISO could not predict recovery at 2-3 months post-injury. Therefore, we found that ODI was significantly increased in symptomatic children following mTBI compared with HCs at 1 month post-injury, and progressively decreased over time alongside clinical recovery. We found no significant differences in FISO between groups or over time. WM ODI at 1 month was a more sensitive predictor of clinical recovery at 2-3 months post-injury than FA, FISO, or clinical measures alone. Our results show evidence of ongoing microstructural reorganization or neuroinflammation between 1 and 2-3 months post-injury, further supporting delayed return to play in children who remain symptomatic. We recommend future research examining the clinical utility of NODDI following mTBI to predict recovery or persistence of post-concussion symptoms and thereby inform management of mTBI.

Maternal Thyroid Function During Pregnancy and Offspring White Matter Microstructure in Early Adulthood: A Prospective Birth Cohort Study.

Background: The fetus is fully dependent on maternal thyroid hormones until mid-gestation and suboptimal maternal thyroid function has been associated with alterations in the neurodevelopment of the offspring. We used maternal free thyroxine (fT4) and thyrotropin (TSH) levels in early gestation to study the association of maternal thyroid function during early pregnancy and offspring brain white matter (WM) integrity in early adulthood. Methods: Our study population consisted of a total of 292 mother-child pairs. Maternal fT4 and TSH were used as predictors and offspring multimodal imaging measures of fractional anisotropy, mean diffusivity, and magnetization transfer ratio (FA, MD, and MTR) as dependent variables. First, as Global analysis, all analyzed 14 WM tracts were studied simultaneously using linear-mixed effect models. Second, if a global effect was detected, a post hoc Tract-wise analysis was carried out using linear models individually in each WM tract. Study population was stratified by sex. Results: We found a positive association between maternal fT4 and offspring Global FA in males when adjusted for all maternal and offspring covariates (n = 114; β = 0.154; confidence interval = 0.045-0.263; p = 0.006). The finding was observed to be driven by multiple WM tracts, of which three projection fiber tracts and the forceps minor survived correcting for multiple comparisons in Tract-wise analysis. Conclusions: Maternal thyroid function in early pregnancy was observed to be associated with WM microstructure in male offspring in early adulthood. Our results suggest that maternal fT4 levels in early pregnancy may modulate axonal characteristics, with a long-term effect on offspring WM development.

The potential of electromyography, diagnostic transcranial magnetic stimulation, and multiparametric magnetic resonance imaging in the combinatory assessment of facial nerve disorders: a literature review and clinical case series

Facial neuropathy (FN) is a complex multicausal problem that, with a seemingly obvious clinical picture, might be challenging to diagnose. Up to 5% of FN cases could be caused by neoplastic or otogenic processes, necessitating an interdisciplinary approach to its treatment by various specialties and in some cases a surgical intervention. In addition, in the early stages of FN, it is difficult to predict its outcomes. Therefore, beyond usual neurological exam and widely used electromyography (EMG), other additional diagnostic tools are used to ensure extended diagnosis, including cancer awareness.&#x0D; In this paper we have analyzed the principles, role and value of computed tomography, magnetic resonance imaging (MRI), diagnostic transcranial magnetic stimulation combined with EMG, and ultrasound assessment with a high-frequency linear transducer in acute FN. We present our own clinical cases of pediatric patients with FN, who were assessed with EMG and multiparametric MRI including diffusion tensor imaging. These cases illustrate both the abnormalities found in the typical course of Bell's palsy, as well as the abnormalities in neoplasm-associated FN that clinically fully mimic the Bell's palsy. Based on the world experience in multiparametric MRI, including the use of extended protocols in the Pediatric Research and Clinical Center for Infectious Diseases, in case of suspected FN, the most important are high-resolution structural submillimeter sequences based on the gradient echo (SSFP) and diffusion tensor imaging (DTI). Measurement and assessment of fractional anisotropy at the motor nuclei of the facial nerves in the pons look promising for further research. The paper is the first to describe a modified combination diagnostic approach to Bell's palsy with the use of diagnostic transcranial magnetic stimulation with round coil, supramaximal stimulation with identification of the motor evoked response threshold (minimal inducer power to register a reproducible evoked motor response of 50-100 mV in amplitude) in the occipito-parietal area of the ipsilateral muscle.

Double pulsed field gradient diffusion MRI to assess skeletal muscle microstructure.

Preliminary study to determine whether double pulsed field gradient (PFG) diffusion MRI is sensitive to key features of muscle microstructure related to function. The restricted diffusion profile of molecules in models of muscle microstructure derived from histology were systematically simulated using a numerical simulation approach. Diffusion tensor subspace imaging analysis of the diffusion signal was performed, and spherical anisotropy (SA) was calculated for each model. Linear regression was used to determine the predictive capacity of SA on the fiber area, fiber diameter, and surface area to volume ratio of the models. Additionally, a rat model of muscle hypertrophy was scanned using a single PFG and a double PFG pulse sequence, and the restricted diffusion measurements were compared with histological measurements of microstructure. Excellent agreement between SA and muscle fiber area (r2 = 0.71; p < 0.0001), fiber diameter (r2 = 0.83; p < 0.0001), and surface area to volume ratio (r2 = 0.97; p < 0.0001) in simulated models was found. In a scanned rat leg, the distribution of these microstructural features measured from histology was broad and demonstrated that there is a wide variance in the microstructural features observed, similar to the SA distributions. However, the distribution of fractional anisotropy measurements in the same tissue was narrow. This study demonstrates that SA-a scalar value from diffusion tensor subspace imaging analysis-is highly sensitive to muscle microstructural features predictive of function. Furthermore, these techniques and analysis tools can be translated to real experiments in skeletal muscle. The increased dynamic range of SA compared with fractional anisotropy in the same tissue suggests increased sensitivity to detecting changes in tissue microstructure.

Diffusion Tensor MR Imaging Evaluation in Children with Developmental Delay

Context: Developmental delay (DD) has a significant detrimental effect on the child’s quality of life. The critical time of diagnosis has a significant impact in preventing the decreased quality of life that the children with DD face, for which magnetic resonance imaging (MRI) with its new imaging techniques plays a pivotal role. Diffusion tensor imaging (DTI), a MRI technique, identifies microscopic features that are thought to be precursors to the ultimate stage of macroscopic tissue atrophy. Objectives: Spectrum of abnormal MRI brain findings was characterized, and role of DTI was evaluated in children with DD. Methods: Observational, descriptive study was performed on 80 children. Fifty cases of DD between the age of 1 month and 16 years, and 30 normal age-matched controls, underwent brain MRI with DTI for structural assessment of brain with measurement of fractional anisotropy (FA) of white matter tracts. “One sample t test” determined whether statistical significance existed between mean FA values of cases and controls. Results: Spectrum of hypoxic-ischemic insult and white matter abnormalities were the common findings seen in 21 (42%) and 19 (38%) children, respectively, amongst cases. On DTI, reduced FA was observed in white matter tracts of 24 (48%) children, most commonly in the corpus callosum of 13 (26%) children. Abnormal FA values in certain white matter tracts were observed in 6 (40%) out of 15 children with normal MRI brain. Conclusion: DTI exhibited the ability to pick up white matter tract abnormalities in the form of reduced FA values in children with DD, including some who showed structurally normal MRI.

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).

The additive value of diffusion tensor imaging in the determination of perianal fistula activity

BackgroundAlthough the activity of the perianal fistula has been evaluated before by MRI in the literature, limited diffusion tensor magnetic resonance imaging (DT-MRI) studies are reported to date. Our study aimed to elucidate the role of DT-MRI in evaluating the activity state of the perianal fistula and the prediction of postoperative complications. We reviewed the data of 30 patients diagnosed with perianal fistula and referred them for an MRI diffusion study before the surgical intervention. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were calculated for the fistulous area and the normal surrounding puborectalis as a control area.ResultsAccording to the presence of pus intraoperatively, patients were allocated into two groups: the active group (10 patients) and the inactive group (20 patients). FA and ADC measurements showed a significant decrease in association with the active disease when measured at the fistula site, and this was not observed in the normal surrounding tissues. The area under the curve (AUC) was 0.985 and 0.730 for the ADC and FA, respectively, when cutoff values of 1 × 10–3 mm2/s and 0.621 were applied, respectively. Adding the FA to the ADC increased the DT-MRI specificity to 95% in the determination of the active fistula. The combination between both FA and ADC increased the AUC to 0.785 with a sensitivity of 73.7% and specificity of 63.6% in the detection of postoperative complications.ConclusionsDT-MRI could be used as a reliable diagnostic tool to differentiate patients with active perianal fistula disease from inactive ones and to predict the postoperative outcome.

THE CONTRIBUTION OF DIFFUSION TENSOR IMAGING TO CONVENTIONAL MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF MULTIPLE SCLEROSIS PATIENTS

Aim: The aim of this study is to investigate whether anisotropic diffusion is superior to conventional magnetic resonance imaging for understanding the pathophysiology of multiple sclerosis (MS) disease by Fractional anisotropy (FA) measurements.&#x0D; Material and Methods: In our study, FA measurements were made from the plaque, the periplaque area, the normal appeared white matter contralateral to the plaque and normal appearing white matter areas in MS patients and from the normal white matter in the control group. 3D trography maps were made in all MS patients and it was evaluated whether white pathways were affected by MS disease.&#x0D; Results: When the degree of anisotropy was compared to the control group, the degree of plaques was found lowest. Increase was observed in periplaque, the normal appeared white matter contralateral to the plaque and normal appearing white matter, respectively. The active plaque FA value was found to be lower than the chronic plaque FA value, and the chronic plaque FA was found to be lower than the normal white matter FA value. It has been shown that plaques traced along axonal pathways in MS patients cause interruption in axonal pathways. &#x0D; Conclusion: Progressive decrease in anisotropy from normal appearing white matter to periplaque white matter and plaque level indicates myelin damage. This suggests that the white matter that appears normal on T2 images on conventional MR is not actually normal. Based on these results, it was thought that diffusion tensor imaging would be useful in evaluating the burden of disease in MS patients.

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats.

Studies on differences in brain structure and function according to sex are reported to contribute to differences in behavior and cognition. However, few studies have investigated brain structures or used tractography to investigate gender differences in pain sensitivity. The identification of tracts involved in sex-based structural differences that show pain sensitivity has remained elusive to date. Here, we attempted to demonstrate the sex differences in pain sensitivity and to clarify its relationship with brain structural connectivity. In this study, pain behavior test and brain diffusion tensor imaging (DTI) were performed in male and female rats and tractography was performed on the whole brain using fiber tracking software. We selected eight brain regions related to pain and performed a tractography analysis of these regions. Fractional anisotropy (FA) measurements using automated tractography revealed sex differences in the anterior cingulate cortex (ACC)-, prefrontal cortex (PFC)-, and ventral posterior thalamus-related brain connections. In addition, the results of the correlation analysis of pain sensitivity and DTI tractography showed differences in mean, axial, and radial diffusivities, as well as FA. This study revealed the potential of DTI for exploring circuits involved in pain sensitivity. The behavioral and functional relevance's of measures derived from DTI tractography is demonstrated by their relationship with pain sensitivity.

Unsupervised neurobiology-driven stratification of clinical heterogeneity in depression

IntroductionOne of the main obstacles in providing effective treatments for major depressive disorder (MDD) is clinical heterogeneity, whose neurobiological correlates are not clearly defined. A biologically meaningful stratification of depressed patients is needed to promote tailored diagnostic procedures.ObjectivesUsing structural data, we performed an unsupervised clustering to define clinically meaningful clusters of depressed patients.MethodsT1-weighted and diffusion tensor images were obtained from 102 MDD patients. In 64 patients, clinical symptoms, number of stressful life events, severity and exposure to adverse childhood experiences were evaluated using the Beck Depression Inventory (BDI), Schedule of Recent Experiences (SRE), Risky Family Questionnaire (RFQ), and Childhood Trauma Questionnaire (CTQ). Clustering analyses were performed with extracted tract-based fractional anisotropy (TBSS, FSL), cortical thickness, surface area, and regional measures of grey matter volumes (CAT12). Gaussian mixture model was implemented for clustering, considering Support Vector Machine (SVM) as classifier. A 10x2 repeated cross-validation with grid search was performed for hyperparameters tuning and clusters’ stability. The optimal number of clusters was determined by normalized stability, Akaike and Bayesian information criterion. Analyses were adjusted for total intracranial volume, age, and sex. The clinical relevance of the identified clusters was assessed through MANOVA, considering domains of clinical scales as dependent variables and clusters’ labels as fixed factors. Discriminant analysis was subsequently performed to assess the discriminative power of these variables.ResultsCross-validated clustering approach identified 2 highly stable clusters (normalized stability=0.316, AIC=-80292.48, BIC=351329.16). MANOVA showed a significant between-clusters difference in clinical scales scores (p=0.038). Discriminant analysis distinguished the two clusters with an accuracy of 78.1%, with BDI behavioural and CTQ minimisation/denial domains showing the highest discriminant values (0.325 and 0.313).ConclusionsOur results defined two biologically informed clusters of MDD patients associated with childhood trauma and specific clinical profiles, which may assist in targeting effective interventions and treatments.Disclosure of InterestNone Declared