Reference Values for Water-Specific T1 of the Liver at 3 T: T2*-Compensation and the Confounding Effects of Fat.

BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Diffusion-weighted MR spectroscopy: Consensus, recommendations, and resources from acquisition to modeling.

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations. Despite its great potential, dMRS remains a challenging technique on all levels: from the data acquisition to the analysis, quantification, modeling, and interpretation of results. These challenges were the motivation behind the organization of the Lorentz Center workshop on "Best Practices & Tools for Diffusion MR Spectroscopy" held in Leiden, the Netherlands, in September 2021. During the workshop, the dMRS community established a set of recommendations to execute robust dMRS studies. This paper provides a description of the steps needed for acquiring, processing, fitting, and modeling dMRS data, and provides links to useful resources.

Longitudinal Functional Connectome in Pediatric Concussion: An Advancing Concussion Assessment in Pediatrics Study.

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents (n = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Tensor-valued diffusion MRI of human acute stroke.

PURPOSE: Tensor-valued diffusion encoding can disentangle orientation dispersion and subvoxel anisotropy, potentially offering insight into microstructural changes after cerebral ischemia. The purpose was to evaluate tensor-valued diffusion MRI in human acute ischemic stroke, assess potential confounders from diffusion time dependencies, and compare to Monte Carlo diffusion simulations of axon beading. METHODS: Linear (LTE) and spherical (STE) b-tensor encoding with inherently different effective diffusion times were acquired in 21 acute ischemic stroke patients between 3 and 57 h post-onset at 3 T in 2.5 min. In an additional 10 patients, STE with 2 LTE yielding different effective diffusion times were acquired for comparison. Diffusional variance decomposition (DIVIDE) was used to estimate microscopic anisotropy (µFA), as well as anisotropic, isotropic, and total diffusional variance (MKA , MKI , MKT ). DIVIDE parameters, and diffusion tensor imaging (DTI)-derived mean diffusivity and fractional anisotropy (FA) were compared in lesion versus contralateral white matter. Monte Carlo diffusion simulations of various cylindrical geometries for all b-tensor protocols were used to interpret parameter measurements. RESULTS: MD was ˜40% lower in lesions for all LTE/STE protocols. The DIVIDE parameters varied with effective diffusion time: higher µFA and MKA in lesion versus contralateral white matter for STE with longer effective diffusion time LTE, whereas the shorter effective diffusion time LTE protocol yielded lower µFA and MKA in lesions. Both protocols, regardless of diffusion time, were consistent with simulations of greater beading amplitude and intracellular volume fraction. CONCLUSION: DIVIDE parameters depend on diffusion time in acute stroke but consistently indicate neurite beading and larger intracellular volume fraction.

Cardiac Magnetic Resonance Imaging in Individuals With Prenatal Alcohol Exposure.

Background: Prenatal alcohol exposure (PAE) has teratogenic effects on numerous body systems including the heart. However, research magnetic resonance imaging (MRI) studies in humans with PAE have thus far been limited to the brain. This study aims to use MRI to examine heart structure and function, brain volumes, and body composition in children and adolescents with PAE. Methods: Heart, brain, and abdominal 3T MRI of 17 children, adolescents, and young adults with PAE and 53 unexposed controls was acquired to measure: (1) left ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, longitudinal strain, circumferential strain, and heart mass; (2) total brain, cerebellum, white matter, grey matter, caudate, thalamus, putamen, and globus pallidus volumes; and (3) subcutaneous fat, visceral fat, muscle fat, and muscle (body composition). Results: Cardiac MRI revealed no abnormalities in the PAE group on evaluation by a paediatric cardiologist and by statistical comparison with a control group. Cardiac parameters in both groups were in line with previous reports, including expected sex- and age-related differences. Cerebellum, caudate, and globus pallidus volumes were all smaller. Body mass index and subcutaneous fat percent were higher in females with PAE relative to control females, but lower in males with PAE relative to control males. Conclusions: Children with PAE did not have abnormalities in MRI-derived measures of cardiac structure or function despite smaller brain volumes and sex-specific differences in body composition relative to healthy controls.

Contexte: L'exposition prénatale à l'alcool (EPA) engendre des effets tératogènes dans de nombreux systèmes et organes du corps humain, notamment le cœur. Cependant, la recherche à l'aide de l'imagerie par résonance magnétique (IRM) chez des humains ayant des antécédents d'EPA s'est limitée aux effets sur le cerveau jusqu'à maintenant. Cette étude vise à utiliser l'IRM pour examiner la fonction et la structure du cœur, le volume de diverses parties du cerveau ainsi que la composition corporelle chez des enfants et des adolescents ayant des antécédents d'EPA. Méthodologie: Chez 17 enfants, adolescents et jeunes adultes ayant été exposés à l'alcool au stade prénatal et chez 53 personnes n'ayant pas d'antécédents d'EPA, des images du cœur, du cerveau et de l'abdomen ont été acquises par la technique d'IRM 3T afin de mesurer : i) la fraction d'éjection du ventricule gauche, le volume télédiastolique, le volume télésystolique, le volume de sang éjecté, le débit cardiaque, la déformation longitudinale, la déformation circonférentielle et la masse cardiaque; ii) les volumes du cerveau en entier, du cervelet, de la substance blanche, de la substance grise, du noyau caudé, du thalamus, du putamen et du globus pallidus; et iii) le pourcentage de tissu adipeux contenu sous la peau, dans les viscères et dans les muscles ainsi que le pourcentage de muscles (composition corporelle). Résultats: Les images obtenues par l'IRM cardiaque n'ont pas révélé d'anomalies chez le groupe ayant des antécédents d'EPA après évaluation par un cardiologue pédiatrique et comparaison statistique avec le groupe témoin. Les paramètres cardiaques mesurés chez les deux groupes reflétaient les données ayant été précédemment rapportées, y compris les attentes liées aux différences quant au sexe et à l'âge. Les volumes du cervelet, du noyau caudé et du globus pallidus étaient diminués chez les personnes ayant des antécédents d'EPA. Alors que l'indice de masse corporelle et le pourcentage de tissu adipeux sous-cutané étaient plus élevés chez les personnes de sexe féminin ayant des antécédents d'EPA que chez les personnes de sexe féminin appartenant au groupe témoin, ces mêmes paramètres se trouvaient diminués chez les personnes de sexe masculin ayant des antécédents d'EPA comparativement aux personnes de sexe masculin appartenant au groupe témoin. Conclusions: Chez les enfants ayant des antécédents d'EPA, les mesures de la fonction et de la structure cardiaques dérivées des données de l'IRM ne présentaient pas d'anomalies, bien qu'une diminution du volume de certaines parties du cerveau et des différences dans la composition corporelle propres au sexe aient été observées dans ce groupe comparativement aux personnes en santé appartenant au groupe témoin.

Characterization of white matter alterations using diffusion kurtosis imaging in patients with amyotrophic lateral sclerosis.

BACKGROUND: To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). METHODS: Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients. RESULTS: In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p < .017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p < .05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p < .01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. CONCLUSION: DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.

Longitudinal Gray Matter Trajectories in Pediatric Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI). METHODS: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction. RESULTS: Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]). DISCUSSION: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.

Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

OBJECTIVE: Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. METHODS: 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. RESULTS: There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. INTERPRETATION: These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

High-resolution diffusion tensor imaging and T2 mapping detect regional changes within the hippocampus in multiple sclerosis.

Hippocampus demyelinating lesions in multiple sclerosis (MS) have been frequently observed in ex vivo histopathological studies; however, they are difficult to image and quantify in vivo. Diffusion tensor imaging (DTI) and T2 mapping could potentially detect such regional in vivo changes if acquired with sufficient spatial resolution. The goal here was to evaluate whether there are focal hippocampal abnormalities in 43 MS patients (35 relapsing-remitting, eight secondary progressive) with and without cognitive impairment (CI) versus 43 controls using high-resolution 1 mm isotropic DTI, as well as complementary methods of T2-weighted and T2 mapping at 3 T. Abnormal hippocampus regions were identified voxel-by-voxel by using mean diffusivity (MD)/T2 thresholds and avoiding voxels attributed to cerebrospinal fluid. When compared with controls, averaged left/right whole hippocampus MD was higher in both MS groups, while lower fractional anisotropy (FA) and volume, and higher T2 relaxometry and T2-weighted signal values, were only significant in CI MS. The hippocampal MD and T2 images/maps were not uniformly affected and focal regions of elevated MD/T2 were evident in MS patients. Both CI and not CI MS groups showed greater proportional areas of the hippocampus with elevated MD, whereas only the CI group showed a greater proportional area of elevated T2 relaxation times or T2-weighted signal. Higher T2 relaxometry and T2-weighted signal values of elevated regions correlated with greater disability and whole hippocampus FA negatively correlated with physical fatigue. High-resolution hippocampus DTI and T2 mapping with less partial volume effects showed whole hippocampus abnormalities with regional elevations of MD/T2 in MS, which could be interpreted as potentially from demyelination, neuron loss, and/or inflammation, and which overall were more extensive in the hippocampus of patients with larger total brain lesion volumes and CI.

Motor cortex functional connectivity is associated with underlying neurochemistry in ALS.

OBJECTIVE: To identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS). METHODS: 52 patients with ALS and 52 healthy controls, matched for age and sex, were enrolled from 5 centres across Canada for the Canadian ALS Neuroimaging Consortium study. Resting-state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy data were acquired. Functional connectivity maps, diffusion metrics and neurometabolite ratios were obtained from the analyses of the acquired multimodal data. A clinical assessment of foot tapping (frequency) was performed to examine upper motor neuron function in all participants. RESULTS: Compared with healthy controls, the primary motor cortex in ALS showed reduced functional connectivity with sensory (T=5.21), frontal (T=3.70), temporal (T=3.80), putaminal (T=4.03) and adjacent motor (T=4.60) regions. In the primary motor cortex, N-acetyl aspartate (NAA, a neuronal marker) ratios and diffusion metrics (mean, axial and radial diffusivity, fractional anisotropy (FA)) were altered. Within the ALS cohort, foot tapping frequency correlated with NAA (r=0.347) and white matter FA (r=0.537). NAA levels showed associations with disturbed functional connectivity of the motor cortex. CONCLUSION: In vivo neurochemistry may represent an effective imaging marker of impaired motor cortex functional connectivity in ALS.

Longitudinal hippocampal diffusion-weighted imaging and T2 relaxometry demonstrate regional abnormalities which are stable and predict subfield pathology in temporal lobe epilepsy.

OBJECTIVE: High-resolution (1 mm isotropic) diffusion tensor imaging (DTI) of the hippocampus in temporal lobe epilepsy (TLE) patients has shown patterns of hippocampal subfield diffusion abnormalities, which were consistent with hippocampal sclerosis (HS) subtype on surgical histology. The objectives of this longitudinal imaging study were to determine the stability of focal hippocampus diffusion changes over time in TLE patients, compare diffusion and quantitative T2 abnormalities of the sclerotic hippocampus, and correlate presurgical mean diffusivity (MD) and T2 maps with postsurgical histology. METHODS: Nineteen TLE patients and 19 controls underwent two high-resolution (1 mm isotropic) DTI and 1.1 × 1.1 × 1 mm3  T2 relaxometry scans (in a subset of 16 TLE patients and 9 controls) of the hippocampus at 3T, with a 2.6 ± 0.8 year inter-scan interval. Within-participant hippocampal volume, MD and T2 were compared between the scans. Contralateral hippocampal changes 2.3 ± 1.0 years after surgery and ipsilateral preoperative MD maps versus postoperative subfield histopathology were evaluated in eight patients who underwent surgical resection of the hippocampus. RESULTS: Reduced volume and elevated MD and T2 of sclerotic hippocampi remained unchanged between longitudinal scans. Focal regions of elevated MD and T2 in bilateral hippocampi of HS TLE were detected consistently at both scans. Regions of high MD and T2 correlated and remained consistent over time. Volume, MD, and T2 remained unchanged in postoperative contralateral hippocampus. Regional elevations of MD identified subfield neuron loss on postsurgical histology with 88% sensitivity and 88% specificity. Focal T2 elevations identified subfield neuron loss with 75% sensitivity and 88% specificity. SIGNIFICANCE: Diffusion and T2 abnormalities in ipsilateral and contralateral hippocampi remained unchanged between the scans suggesting permanent microstructural alterations. MD and T2 demonstrated good sensitivity and specificity to detect hippocampal subfield neuron loss on postsurgical histology, supporting the potential that high-resolution hippocampal DTI and T2 could be used to diagnose HS subtype before surgery.

Quantitative Susceptibility Mapping Changes Relate to Gait Issues in Parkinson's Disease.

BACKGROUND: Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson's disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD. METHODS: This case-control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities. RESULTS: Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04). CONCLUSION: Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

A Normative Brain MRI Database of Neurotypical Participants from 5 to 90 Years of Age.

Brain magnetic resonance imaging (MRI) studies of clinical populations often require comparison to a normative 'control' cohort, usually of similar age/sex, scanned with the same protocol. The goal here was to create a normative brain MRI database of common quantitative methods to be used in comparisons with a variety of neurological disorders across the lifespan. 378 neurotypical controls (aged 5-90 years; median 31 years; 216 females, 162 males) completed brain MRI, cognitive testing, clinical assessment, and a demographics questionnaire. In addition, this large normative sample will yield novel insight into healthy brain development and aging.

Frontoparietal and temporal white matter diffusion MRI in children and youth with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with brain alterations and neurocognitive deficits, but relationships between brain alterations and neurocognitive deficits remain unclear. METHODS: Diffusion tensor imaging (DTI) data were obtained from 31 participants with PAE and 31 unexposed controls aged 7-15 years. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from the genu, body, and splenium of the corpus callosum (CC), bilateral cingulum, and inferior and superior longitudinal fasciculus (ILF, SLF). Participants completed language subtests from the NEPSY-II. Executive functioning was measured using the Behavior Rating Inventory of Executive Functioning (BRIEF-PR) and verbal learning was assessed using the California Verbal Learning Test-Children's Version (CVLT-C) only in children with PAE. Group differences in diffusion metrics and cognitive scores were tested. Principal component analysis was used to reduce redundancy in cognitive and behavior variables; associations between components and brain measures were then assessed. RESULTS: Children with PAE had lower MD in the right SLF compared with unexposed controls. FA was positively related to age in 6 of 9 tracts and MD negatively related to age in all tracts; there were no significant age-by-group interactions. Participants with PAE scored lower than unexposed peers on the NEPSY-II Comprehension of Instructions and Phonological Processing and above population norms (indicating worse performance) on the BRIEF-PR. Children with PAE had a negative association between a principal component closely associated with Speeded Naming and FA in the left SLF (PAE: p = 0.002) and left ILF (PAE: p = 0.002); unexposed controls showed no significant associations. CONCLUSION: We found widespread cognitive difficulties in children with PAE, but relatively limited differences in brain metrics and associations with age. Different brain-cognitive relationships were found in children with PAE compared with controls. Overall, the results provide additional evidence that PAE may lead to cognitive difficulties and disrupt typical brain-function relationships.

Multisite Harmonization of Structural DTI Networks in Children: An A-CAP Study.

The analysis of large, multisite neuroimaging datasets provides a promising means for robust characterization of brain networks that can reduce false positives and improve reproducibility. However, the use of different MRI scanners introduces variability to the data. Managing those sources of variability is increasingly important for the generation of accurate group-level inferences. ComBat is one of the most promising tools for multisite (multiscanner) harmonization of structural neuroimaging data, but no study has examined its application to graph theory metrics derived from the structural brain connectome. The present work evaluates the use of ComBat for multisite harmonization in the context of structural network analysis of diffusion-weighted scans from the Advancing Concussion Assessment in Pediatrics (A-CAP) study. Scans were acquired on six different scanners from 484 children aged 8.00-16.99 years [Mean = 12.37 ± 2.34 years; 289 (59.7%) Male] ~10 days following mild traumatic brain injury (n = 313) or orthopedic injury (n = 171). Whole brain deterministic diffusion tensor tractography was conducted and used to construct a 90 x 90 weighted (average fractional anisotropy) adjacency matrix for each scan. ComBat harmonization was applied separately at one of two different stages during data processing, either on the (i) weighted adjacency matrices (matrix harmonization) or (ii) global network metrics derived using unharmonized weighted adjacency matrices (parameter harmonization). Global network metrics based on unharmonized adjacency matrices and each harmonization approach were derived. Robust scanner effects were found for unharmonized metrics. Some scanner effects remained significant for matrix harmonized metrics, but effect sizes were less robust. Parameter harmonized metrics did not differ by scanner. Intraclass correlations (ICC) indicated good to excellent within-scanner consistency between metrics calculated before and after both harmonization approaches. Age correlated with unharmonized network metrics, but was more strongly correlated with network metrics based on both harmonization approaches. Parameter harmonization successfully controlled for scanner variability while preserving network topology and connectivity weights, indicating that harmonization of global network parameters based on unharmonized adjacency matrices may provide optimal results. The current work supports the use of ComBat for removing multiscanner effects on global network topology.

White Matter Diffusion Properties in Chronic Temporomandibular Disorders: An Exploratory Analysis.

Objective: To determine differences in diffusion metrics in key white matter (WM) tracts between women with chronic temporomandibular disorders (TMDs) and age- and sex-matched healthy controls. Design: Cross sectional study compared diffusion metrics between groups and explored their associations with clinical variables in subjects with TMDs. Methods: In a total of 33 subjects with TMDs and 33 healthy controls, we performed tractography to obtain diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) from the cingulum near the cingulate gyrus (CGC), the cingulum near the hippocampus (CGH), the fornix, the anterior limb of the internal capsule (ALIC), the posterior limb of the internal capsule (PLIC), and the uncinate fasciculus (UF). We compared diffusion metrics across groups and explored the relationships between diffusion metrics and clinical measures (pain chronicity and intensity, central sensitization, somatization, depression, orofacial behavior severity, jaw function limitations, disability, and interference due to pain) in subjects with TMDs. Results: We observed differences in diffusion metrics between groups, primarily in the right side of the brain, with the right CGC having lower FA and the right UF having lower FA and higher MD and RD in subjects with TMDs compared to healthy controls. No clinical measures were consistently associated with diffusion metrics in subjects with TMDs. Conclusion: The UF showed potential microstructural damage in subjects with TMDs, but further studies are needed to confirm any associations between diffusion changes and clinical measures.

Multisite reproducibility of quantitative susceptibility mapping and effective transverse relaxation rate in deep gray matter at 3 T using locally optimized sequences in 24 traveling heads.

Iron concentration in the human brain plays a crucial role in several neurodegenerative diseases and can be monitored noninvasively using quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2 *) mapping from multiecho T2 *-weighted images. Large population studies enable better understanding of pathologies and can benefit from pooling multisite data. However, reproducibility may be compromised between sites and studies using different hardware and sequence protocols. This work investigates QSM and R2 * reproducibility at 3 T using locally optimized sequences from three centers and two vendors, and investigates possible reduction of cross-site variability through postprocessing approaches. Twenty-four healthy subjects traveled between three sites and were scanned twice at each site. Scan-rescan measurements from seven deep gray matter regions were used for assessing within-site and cross-site reproducibility using intraclass correlation coefficient (ICC) and within-subject standard deviation (SDw) measures. In addition, multiple QSM and R2 * postprocessing options were investigated with the aim to minimize cross-site sequence-related variations, including: mask generation approach, echo-timing selection, harmonizing spatial resolution, field map estimation, susceptibility inversion method, and linear field correction for magnitude images. The same-subject cross-site region of interest measurements for QSM and R2 * were highly correlated (R2 ≥ 0.94) and reproducible (mean ICC of 0.89 and 0.82 for QSM and R2 *, respectively). The mean cross-site SDw was 4.16 parts per billion (ppb) for QSM and 1.27 s-1 for R2 *. For within-site measurements of QSM and R2 *, the mean ICC was 0.97 and 0.87 and mean SDw was 2.36 ppb and 0.97 s-1 , respectively. The precision level is regionally dependent and is reduced in the frontal lobe, near brain edges, and in white matter regions. Cross-site QSM variability (mean SDw) was reduced up to 46% through postprocessing approaches, such as masking out less reliable regions, matching available echo timings and spatial resolution, avoiding the use of the nonconsistent magnitude contrast between scans in field estimation, and minimizing streaking artifacts.

High-resolution diffusion tensor imaging identifies hippocampal volume loss without diffusion changes in individuals with prenatal alcohol exposure.

BACKGROUND: Magnetic resonance imaging (MRI) studies of prenatal alcohol exposure (PAE) commonly report reduced hippocampal volumes, which animal models suggest may result from microstructural changes that include cell loss and altered myelination. Diffusion tensor imaging (DTI) is sensitive to microstructural changes but has not yet been used to study the hippocampus in PAE. METHODS: Thirty-six healthy controls (19 females; 8 to 24 years) and 19 participants with PAE (8 females; 8 to 23 years) underwent high-resolution (1 mm isotropic) DTI, anatomical T1-weighted imaging, and cognitive testing. Whole-hippocampus, head, body, and tail subregions were manually segmented to yield DTI metrics (mean, axial, and radial diffusivities-MD, AD, and RD; fractional anisotropy-FA), volumes, and qualitative assessments of hippocampal morphology and digitations. Automated segmentation of T1-weighted images was used to corroborate manual whole-hippocampus volumes. RESULTS: Gross morphology and digitation counts were similar in both groups. Whole-hippocampus volumes were 18% smaller in the PAE than the control group on manually traced diffusion images, but automated T1-weighted image segmentations were not significantly different. Subregion segmentation on DTI revealed reduced volumes of the body and tail, but not the head. There were no significant differences in diffusion metrics between groups for any hippocampal region. Correlations between age and volume were not significant in either group, whereas negative correlations between age and whole-hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. There were no significant effects of sex, group by age, or group by sex for any hippocampal metric. In controls, seven positive linear correlations were found between hippocampal volume and cognition; five of these were left lateralized and included episodic and working memory, and two were right lateralized and included working memory and processing speed. In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory. CONCLUSIONS: Reductions of hippocampal volumes and altered relationships with memory suggest disrupted hippocampal development in PAE.

Lifespan Volume Trajectories From Non-harmonized T1-Weighted MRI Do Not Differ After Site Correction Based on Traveling Human Phantoms.

Multi-site imaging consortiums strive to increase participant numbers by pooling data across sites, but scanner related differences can bias results. This study combines data from three research MRI centers, including three different scanner models from two vendors, to examine non-harmonized T1-weighted brain imaging protocols in two cohorts. First, 23 human traveling phantoms were scanned twice each at all three sites (six scans per person; 138 scans total) to quantify within-participant variability of brain volumes (total brain, white matter, gray matter, lateral ventricles, thalamus, caudate, putamen and globus pallidus), and to calculate site-specific correction factors for each structure. Sample size calculations were used to determine the number of traveling phantoms needed to achieve effect sizes for observed differences to help guide future studies. Next, cross-sectional lifespan volume trajectories were examined in 856 healthy participants (5-91 years of age) scanned at these sites. Cross-sectional trajectories of volume versus age for each structure were then compared before and after application of traveling phantom based site-specific correction factors, as well as correction using the open-source method ComBat. Although small systematic differences between sites were observed in the traveling phantom analysis, correction for site using either method had little impact on the lifespan trajectories. Only white matter had small but significant differences in the intercept parameter after ComBat correction (but not traveling phantom based correction), while no other fits differed. This suggests that age-related changes over the lifespan outweigh systematic differences between scanners for volumetric analysis. This work will help guide pooling of multisite datasets as well as meta-analyses of data from non-harmonized protocols.