Diffusion Tensor Imaging Measures Research Articles

Detection of gray matter microstructural changes in Alzheimer\u2019s disease continuum using fiber orientation

BackgroundThis study aimed to investigate feasible gray matter microstructural biomarkers with high sensitivity for early Alzheimer’s disease (AD) detection. We propose a diffusion tensor imaging (DTI) measure, “radiality”, as an early AD biomarker. It is the dot product of the normal vector of the cortical surface and primary diffusion direction, which reflects the fiber orientation within the cortical column.MethodsWe analyzed neuroimages from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including images from 78 cognitively normal (CN), 50 early mild cognitive impairment (EMCI), 34 late mild cognitive impairment (LMCI), and 39 AD patients. We then evaluated the cortical thickness (CTh), mean diffusivity (MD), which are conventional AD magnetic resonance imaging (MRI) biomarkers, and the amount of accumulated amyloid and tau using positron emission tomography (PET). Radiality was projected on the gray matter surface to compare and validate the changes with different stages alongside other neuroimage biomarkers.ResultsThe results revealed decreased radiality primarily in the entorhinal, insula, frontal, and temporal cortex with further progression of disease. In particular, radiality could delineate the difference between the CN and EMCI groups, while the other biomarkers could not. We examined the relationship between radiality and other biomarkers to validate its pathological evidence in AD. Overall, radiality showed a high association with conventional biomarkers. Additional ROI analysis revealed the dynamics of AD-related changes as stages onward.ConclusionRadiality in cortical gray matter showed AD-specific changes and relevance with other conventional AD biomarkers with high sensitivity. Moreover, radiality could identify the group differences seen in EMCI, representative of changes in early AD, which supports its superiority in early diagnosis compared to that possible with conventional biomarkers. We provide evidence of structural changes with cognitive impairment and suggest radiality as a sensitive biomarker for identifying early AD.

Association of Speech Recognition Thresholds With Brain Volumes and White Matter Microstructure: The Rotterdam Study.

Brain volumetric declines may underlie the association between hearing loss and dementia. While much is known about the peripheral auditory function and brain volumetric declines, poorer central auditory speech processing may also be associated with decreases in brain volumes. Central auditory speech processing, measured by the speech recognition threshold (SRT) from the Digits-in-Noise task, and neuroimaging assessments (structural magnetic resonance imaging [MRI] and fractional anisotropy and mean diffusivity from diffusion tensor imaging), were assessed cross-sectionally in 2,368 Rotterdam Study participants aged 51.8 to 97.8 years. SRTs were defined continuously and categorically by degrees of auditory performance (normal, insufficient, and poor). Brain volumes from structural MRI were assessed on a global and lobar level, as well as for specific dementia-related structures (hippocampus, entorhinal cortex, parahippocampal gyrus). Multivariable linear regression models adjusted by age, age-squared, sex, educational level, alcohol consumption, intracranial volume (MRI only), cardiovascular risk factors (hypertension, diabetes, obesity, current smoking), and pure-tone average were used to determine associations between SRT and brain structure. Poorer central auditory speech processing was associated with larger parietal lobe volume (difference in mL per dB increase= 0.24, 95% CI: 0.05, 0.42), but not with diffusion tensor imaging measures. Degrees of auditory performance were not associated with brain volumes and white matter microstructure. Central auditory speech processing in the presence of both vascular burden and pure-tone average may not be related to brain volumes and white matter microstructure. Longitudinal follow-up is needed to explore these relationships thoroughly.

Twenty-first birthday drinking: Extreme-drinking episodes and white matter microstructural changes in the fornix and corpus callosum.

The 21st birthday celebration is characterized by extreme alcohol consumption. Accumulating evidence suggests that high-dose bingeing is related to structural brain changes and cognitive deficits. This is particularly problematic in the transition from adolescence to adulthood when the brain is still maturing, elevating the brain's sensitivity to the acute effects of alcohol intoxication. Heavy drinking is associated with reduced structural integrity in the hippocampus and corpus callosum and is accompanied by cognitive deficits. However, there is little research examining changes in the human brain related to discrete heavy-drinking episodes. The present study investigated whether alcohol exposure during a 21st birthday celebration would result in changes to white matter microstructure by utilizing diffusion tensor imaging measures and a quasi-experimental design. By examining structural changes in the brain from pre- to postcelebration within subjects (N = 49) prospectively, we were able to more directly observe brain changes following an extreme-drinking episode. Region of interest analyses demonstrated increased fractional anisotropy in the posterior fornix (p < .0001) and in the body of the corpus callosum (p = .0029) from pre- to postbirthday celebration. These results suggest acute white matter damage to the fornix and corpus callosum following an extreme-drinking episode, which is especially problematic during continued neurodevelopment. Therefore, 21st birthday drinking may be considered an important target event for preventing acute brain injury in young adults. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Correlations between DTI-derived metrics and MRS metabolites in tumour regions of glioblastoma: a pilot study.

IntroductionSpecific correlations among diffusion tensor imaging (DTI)-derived metrics and magnetic resonance spectroscopy (MRS) metabolite ratios in brains with glioblastoma are still not completely understood.Patients and methodsWe made retrospective cohort study. MRS ratios (choline-to-N-acetyl aspartate [Cho/NAA], lipids and lactate to creatine [LL/Cr], and myo-inositol/creatine [mI/Cr]) were correlated with eleven DTI biomarkers: mean diffusivity (MD), fractional anisotropy (FA), pure isotropic diffusion (p), pure anisotropic diffusion (q), the total magnitude of the diffusion tensor (L), linear tensor (Cl), planar tensor (Cp), spherical tensor (Cs), relative anisotropy (RA), axial diffusivity (AD) and radial diffusivity (RD) at the same regions: enhanced rim, peritumoral oedema and normal-appearing white matter. Correlational analyses of 546 MRS and DTI measurements used Spearman coefficient.ResultsAt the enhancing rim we found four significant correlations: FA ⇔ LL/Cr, Rs = -.364, p = .034; Cp ⇔ LL/Cr, Rs = .362, p = .035; q ⇔ LL/Cr, Rs = -.349, p = .035; RA ⇔ LL/Cr, Rs = -.357, p = .038. Another ten pairs of significant correlations were found in the peritumoral edema: AD ⇔ LL/Cr, AD ⇔ mI/Cr, MD ⇔ LL/Cr, MD ⇔ mI/Cr, p ⇔ LL/Cr, p ⇔ mI/ Cr, RD ⇔ mI/Cr, RD ⇔ mI/Cr, L ⇔ LL/Cr, L ⇔ mI/Cr.ConclusionsDTI and MRS biomarkers answer different questions; peritumoral oedema represents the biggest challenge with at least ten significant correlations between DTI and MRS that need additional studies. The fact that DTI and MRS measures are not specific of one histologic type of tumour broadens their application to a wider variety of intracranial pathologies.

Changes in structural and functional connectivity during two years of fingolimod therapy for multiple sclerosis

BackgroundFingolimod, an oral drug, has been reported to reduce relapse rate in multiple sclerosis (MS). However disease progression may still occur in spite of control of inflammation. Functional imbalances within and between cerebral networks associated with disruption of structural and functional network integrity, have been reported in MS. An effective therapy is expected to stabilize such functional network integrity. ObjectiveThe purpose of this study was to investigate changes in structural and resting-state functional connectivity of motor and cognitive networks, and associated changes in neurologic scores in MS, during 2 years of fingolimod therapy. MethodsTwenty five subjects with MS were recruited for this study. Subjects were scanned with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at 3 T with 6-month interval over a period of 2 years. Neurologic performance scores of motor and cognitive performances were also obtained. ResultsDTI measures worsened during the 1st year and then stabilized; any trend of stabilization of fcMRI was delayed until the 2nd year. While motor performance did not change, cognitive performance showed improvement. Several baseline DTI measures correlated with relevant neurologic scores. ConclusionInitial worsening of motor and cognitive network was reported after 1 year of treatment, but seems DTI and fcMRI measures seem to stabilize after around one year fingolimod therapy.

Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.

The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Median participant age was 30 years old and 29/30 were male. Participants' median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.

Association of Poorer Hearing With Longitudinal Change in Cerebral White Matter Microstructure

There is a dearth of studies that examine the association between poorer hearing and change in cerebral white matter (WM) microstructure. To examine the association of poorer hearing with baseline and change in WM microstructure among older adults. This was a prospective cohort study that evaluated speech-in-noise, pure-tone audiometry, and WM microstructure, as measured by mean diffusivity (MD) and fractional anisotropy (FA), both of which were evaluated by diffusion tensor imaging (DTI) in 17 WM regions. Data were collected between October 2012 and December 2018 and analyzed between March 2019 and August 2019 with a mean follow-up time of 1.7 years. The study evaluated responses to the Baltimore Longitudinal Study of Aging among 356 cognitively normal adults who had at least 1 hearing assessment and DTI session. Excluded were those with baseline cognitive impairment, stroke, head injuries, Parkinson disease, and/or bipolar disorder. Peripheral auditory function was measured by pure-tone average in the better-hearing ear. Central auditory function was measured by signal-to-noise ratio score from a speech-in-noise task and adjusted by pure-tone average. Linear mixed-effects models with random intercepts and slopes were used to examine the association of poorer peripheral and central auditory function with baseline and longitudinal DTI metrics in 17 WM regions, adjusting for baseline characteristics (age, sex, race, hypertension, elevated total cholesterol, and obesity). Of 356 cognitively normal adults included in the study, the mean (SD) age was 73.5 (8.8) years, and 204 (57.3%) were women. There were no baseline associations between hearing and DTI measures. Longitudinally, poorer peripheral hearing was associated with increases in MD in the inferior fronto-occipital fasciculus (β = 0.025; 95% CI, 0.008-0.042) and the body (β = 0.050; 95% CI, 0.015-0.085) of the corpus callosum, but there were no associations of peripheral hearing with FA changes in these tracts. Poorer central auditory function was associated with longitudinal MD increases (β = 0.031; 95% CI, 0.010-0.052) and FA declines (β = -1.624; 95% CI, -2.511 to -0.738) in the uncinate fasciculus. Findings of this cohort study suggest that poorer hearing is related to change in integrity of specific WM regions involved with auditory processing.

Multimodal principal component analysis to identify major features of white matter structure and links to reading.

The role of white matter in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age. Analysis was performed for nine reading-related tracts in 46 neurotypical 6-16 year olds. We identified three principal components (PCs) which explained 79.5% of variance in our dataset. PC1 probed tissue complexity, PC2 described myelin and axonal packing, while PC3 was related to axonal diameter. Mixed effects regression models did not identify any significant relationships between principal components and reading skill. Bayes factor analysis revealed that the absence of relationships was not due to low power. Increasing PC1 in the left arcuate fasciculus with age suggest increases in tissue complexity, while increases of PC2 in the bilateral arcuate, inferior longitudinal, inferior fronto-occipital fasciculi, and splenium suggest increases in myelin and axonal packing with age. Multimodal white matter imaging and PCA provide microstructurally informative, powerful principal components which can be used by future studies of development and cognition. Our findings suggest major features of white matter undergo development during childhood and adolescence, but changes are not linked to reading during this period in our typically-developing sample.

Diffusion Tensor Imaging in Contact and Non-Contact University-Level Sport Athletes.

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

The associations of BMI with mean diffusivity of basal ganglia among young adults with mild obesity and without obesity

Obesity causes a wide range of systemic diseases and is associated with mood and anxiety disorders. It is also associated with dopaminergic reward system function. However, the relationships between microstructural properties of the dopaminergic system and body mass index (BMI) have not been investigated. In this study, we investigated the associations of BMI with mean diffusivity (MD), diffusion tensor imaging measure in areas of the dopaminergic system (MDDS) in 435 healthy young adults with mild obesity and without obesity (BMI < 40). We detected the association between greater BMI and lower MD of the right globus pallidus and the right putamen. These results suggest that the property of the dopaminergic system is associated with BMI among young adults with mild obesity and without obesity.

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

ObjectivesTo assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist’s scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times.MethodsIn this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson’s correlation between visit 1 measurements and return to play times was assessed.ResultsThere were significant differences between visits in BAMIC scores (Z = − 2.088; p = 0.037), modified Peetrons (Z = − 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not.ConclusionsT2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring.Key Points• Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI.• Measurements of T2 and diffusion using MRI are not as good as a radiologist’s visual report at predicting return to play time after acute muscle tear.

Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

Magnetic resonance diffusion tensor imaging of cervical microstructure in normal early and late pregnancy in vivo

Cervical remodeling is an important aspect of birth timing. Before cervical ripening, the collagen fibers are arranged in a closely interweaved network, but during ripening, the fibers become disorganized and the cervix becomes more hydrated. To quantitatively measure cervical remodeling, we need a noninvasive method to monitor changes in cervical collagen fiber organization and hydration invivo. To use diffusion tensor imaging to image and quantify the spatial and temporal differences in cervical microstructure between normal early and late pregnancies. After institutional review board approval and consent, a group of healthy women in early pregnancy (22 patients at 12-14 weeks' gestation) and a group in late pregnancy (27 patients at 36-38 weeks' gestation) underwent magnetic resonance imaging on a Siemens MAGNETOM Vida 3 Tesla unit. Diffusion tensor imaging of the cervix in the axial plane was performed with a two-dimensional single-shot echo planar imaging diffusion-weighted sequence. In early and late pregnancy groups, the differences of the diffusion tensor imaging measures were compared between the subglandular zone and the outer stroma regions of the cervix. In addition, the diffusion tensor imaging measures were compared between the early and late pregnancy groups. Finally, for the late pregnancy group, the diffusion tensor imaging measures were compared between the primipara and multipara groups. Diffusion tensor imaging measures of microstructure significantly differed between the subglandular zone and outer stroma regions of the cervix in both early and late pregnancies. In the subglandular zone, fractional anisotropy was lower in the late pregnancy group than in the early pregnancy group (0.37 [0.34-0.42] vs 0.50 [0.43-0.58]; P<.0005), suggesting increased collagen fiber disorganization in this zone. In addition, mean diffusivity was higher in the late pregnancy group than in the early pregnancy group (1.84 [1.73-2.02] mm2/sec×10-3 vs 1.56 [1.42-1.69] mm2/sec×10-3; P=.001), suggesting increased hydration in the subglandular zone. In the outer stroma, neither fractional anisotropy (0.44 [0.40-0.50] vs 0.41 [0.37-0.43]; P=.095) nor mean diffusivity (2.09 [1.92-2.25] mm2/sec×10-3 vs 2.12 [2.04-2.24] mm2/sec×10-3; P=.269) significantly differed between early pregnancy and late pregnancy, suggesting insignificant temporal microstructural changes in this cervical zone. Diffusion tensor imaging measures did not significantly differ between cervixes from primiparous and multiparous women in late pregnancy. This invivo study demonstrates that diffusion tensor imaging can noninvasively quantify the microstructural differences in collagen fiber organization and hydration in cervical subregions between early pregnancy and late pregnancy.

Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI.

To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI. Patients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days, and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury. At enrollment, patients with TBI had increased serum NfL compared to controls (p < 0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls (p < 0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI. Serum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI. This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.

Using diffusion tensor imaging to detect cortical changes in fronto-temporal dementia subtypes

Fronto-temporal dementia (FTD) is a common type of presenile dementia, characterized by a heterogeneous clinical presentation that includes three main subtypes: behavioural-variant FTD, non-fluent/agrammatic variant primary progressive aphasia and semantic variant PPA. To better understand the FTD subtypes and develop more specific treatments, correct diagnosis is essential. This study aimed to test the discrimination power of a novel set of cortical Diffusion Tensor Imaging measures (DTI), on FTD subtypes. A total of 96 subjects with FTD and 84 healthy subjects (HS) were included in the study. A “selection cohort” was used to determine the set of features (measurements) and to use them to select the “best” machine learning classifier from a range of seven main models. The selected classifier was trained on a “training cohort” and tested on a third cohort (“test cohort”). The classifier was used to assess the classification power for binary (HS vs. FTD), and multiclass (HS and FTD subtypes) classification problems. In the binary classification, one of the new DTI features obtained the highest accuracy (85%) as a single feature, and when it was combined with other DTI features and two other common clinical measures (grey matter fraction and MMSE), obtained an accuracy of 88%. The new DTI features can distinguish between HS and FTD subgroups with an accuracy of 76%. These results suggest that DTI measures could support differential diagnosis in a clinical setting, potentially improve efficacy of new innovative drug treatments through effective patient selection, stratification and measurement of outcomes.

Hippocampal Plasticity After Acute Exercise In Older Adults: A Diffusion Tensor Imaging Study

PURPOSE: The hippocampus is a critical region for many cognitive and memory processes that experience structural and functional decline with age. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural MRI. Critically, microstructural alterations within the hippocampus over short time intervals have been associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. It is not yet known, however, if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise. METHODS: We used a within subject-design to determine if a 30-minute bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging (DTI) measures in healthy older adults (n=30) compared to a seated rest control condition. RESULTS: Following exercise there was significantly lower fractional anisotropy (FA) relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity (Dr). No significant differences in mean diffusivity (MD) or axial diffusivity (Da) were observed. Additionally, cerebral blood flow (CBF) data were obtained in a subset of participants (n=13). Differences in Dr within the bilateral hippocampus were significantly associated with differences in bilateral hippocampal perfusion. CONCLUSIONS: These findings suggest that a single session of exercise can lead to microstructural changes in the hippocampus of healthy older adults, and that these differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus, a region that is often susceptible to age and pathological-related cognitive decline.

Effect of age and neurofibromatosis type 1 status on white matter integrity in the optic radiations.

BackgroundAdults with neurofibromatosis type 1 (NF1) have decreased white matter integrity, but differences in children with NF1 have not been described. Defining normal values for diffusion tensor imaging (DTI) measures, especially in the optic radiations, is important to the development of DTI as a potential biomarker of visual acuity in children with optic pathway glioma. This study examines the effect of age and NF1 status on DTI measures in children.MethodsIn this retrospective study, MR imaging including DTI was conducted in 93 children (40 children with NF1 and 53 healthy controls) between 0 and 14 years of age. Regression models of age, sex, and NF1 status on DTI measures were evaluated, and tract-based spatial statistics (TBSS) compared DTI measures in age-matched NF1 to non-NF1 cohorts.ResultsFractional anisotropy, radial diffusivity, and mean diffusivity in white matter tracts of the optic radiations varied with age and were best modeled by a logarithmic function. Age-related DTI measure change was different in NF1 versus non-NF1 subjects. Normal values and 95% confidence intervals for age 0.5–12 years were derived for both groups. Differences in DTI measures between NF1 and non-NF1 groups at a range of ages were shown diffusely throughout the cerebral white matter using TBSS.ConclusionsChildren with NF1 demonstrate increased diffusion throughout the brain compared to children without NF1 suggesting a potentially altered developmental trajectory of optic radiation microstructure. Defining normal values for white matter integrity in children with NF1 may help target early intervention efforts in this vulnerable group.

Diffusion tensor imaging findings in children with sluggish cognitive tempo comorbid Attention Deficit Hyperactivity Disorder

Objective: The construct of Sluggish Cognitive Tempo (SCT) is characterized by daydreaming, mental confusion, staring blankly and hypoactivity. Our main goal was to explore neuropsychological differences in Attention Deficit Hyperactivity Disorder-Inattentive presentation (ADHD-IA) groups with and without SCT symptoms compared to healthy controls. After detecting specific neuropsychological differences, we examined white matter microstructure using Diffusion Tensor Imaging (DTI) data obtained from 3.0 Tesla MRI scans of the cases with SCT symptoms comparing to Typically Developing (TD) controls.Method: In this study, we included 24 cases in the ADHD-IA group with SCT symptoms, 57 cases in the ADHD-IA group without SCT symptoms and, 24 children in the TD group. We applied tract-based spatial statistics to the DTI measures for obtaining fractional anisotropy (FA), axial, radial and mean diffusivity (AD, RD, MD) to explore white matter differences for the whole brain.Results: Omission error scores and longer reaction time scores were specifically associated with inattention symptoms. Commission error scores were significantly and specifically related to SCT symptoms. Cases with SCT symptoms presented increased FA in the bilateral anterior and posterior limb of the internal capsule, bilateral cerebral peduncle, and the fornix than TD group.Conclusions: Neurobiological differences in ADHD cases are still relatively unexplored. We suggest that including an assessment for SCT in the neuropsychological and neuroimaging studies of ADHD may provide more consistent results.

Associations of Maternal Prenatal Drug Abuse With Measures of Newborn Brain Structure, Tissue Organization, and Metabolite Concentrations

Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children. To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain. For this cohort study, a volunteer sample of 210 illicit drug-using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York. Enrollment, scanning, and long-term follow-up occurred from September 2004 through February 2012, and image processing and statistical analyses continued through fall 2018. In addition to 26 participants with incomplete data, a total of 64 mothers were lost to follow-up during pregnancy, and 13 newborns were lost to follow-up at birth because of perinatal complications. Newborns were assigned to 1 of 4 primary exposure groups based on the history of most frequent maternal drug use: marijuana, cocaine, methadone maintenance, and/or heroin. Unexposed newborns were controls. Unsedated magnetic resonance imaging (MRI) of newborn brains was performed shortly after birth. Infant neurodevelopmental outcomes were assessed at age 12 months. MRI modalities included anatomical imaging, diffusion tensor imaging, T2 relaxometry, and magnetic resonance spectroscopic imaging. Infant neurodevelopmental outcomes included Bayley scales of infant development-III and Vineland Adaptive Behavior Scales. Statistical analyses were performed with results represented on the brain images. Of 118 mothers, 42 (35%) were in the control group (mean [SD] age, 25.9 [6.1] years), 29 (25%) were in the cocaine group (mean [SD] age, 29.0 [6.1] years), 29 (25%) were in the marijuana group (mean [SD] age, 24.3 [5.5] years), and 18 (15%) were in the methadone and/or heroin group (mean [SD] age, 30.9 [5.7] years). Not all newborns could be scanned successfully; therefore, usable MRIs were acquired for 118 newborns from predominantly minority groups and with economically disadvantaged mothers. Anatomic abnormalities were detected in similar locations across all 3 drug exposures and included smaller volumes in the dorsal, medial, and ventral surfaces of the frontal lobe and dose-related increases in volumes in the lateral temporal lobe, dorsal parietal lobe, and superior frontal gyrus. Dose-related increases in diffusion tensor measures of tissue organization, decreases in T2 relaxometry times, and increases in spectroscopy metabolite concentrations were similar across exposures. These associations of exposures with brain measures were similar to the associations of newborn age with brain measures. The anatomic and diffusion tensor imaging measures suppressively mediated the associations of prenatal exposure with poorer 12-month infant outcomes. The findings suggest that prenatal drug exposure is associated with measures of newborn brain tissue in patterns that may indicate that exposures accelerated normal fetal brain maturation, which in turn mediated the associations with poorer 12-month infant outcomes.

Stress-Induced Microstructural Alterations Correlate With the Cognitive Performance of Rats: A Longitudinal in vivo Diffusion Tensor Imaging Study.

Background: Stress-induced cellular changes in limbic brain structures contribute to the development of various psychopathologies. In vivo detection of these microstructural changes may help us to develop objective biomarkers for psychiatric disorders. Diffusion tensor imaging (DTI) is an advanced neuroimaging technique that enables the non-invasive examination of white matter integrity and provides insights into the microstructure of pathways connecting brain areas.Objective: Our aim was to examine the temporal dynamics of stress-induced structural changes with repeated in vivo DTI scans and correlate them with behavioral alterations.Methods: Out of 32 young adult male rats, 16 were exposed to daily immobilization stress for 3 weeks. Four DTI measurements were done: one before the stress exposure (baseline), two scans during the stress (acute and chronic phases), and a last one 2 weeks after the end of the stress protocol (recovery). We used a 4.7T small-animal MRI system and examined 18 gray and white matter structures calculating the following parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). T2-weighted images were used for volumetry. Cognitive performance and anxiety levels of the animals were assessed in the Morris water maze, novel object recognition, open field, and elevated plus maze tests.Results: Reduced FA and increased MD and RD values were found in the corpus callosum and external capsule of stressed rats. Stress increased RD in the anterior commissure and reduced MD and RD in the amygdala. We observed time-dependent changes in several DTI parameters as the rats matured, but we found no evidence of stress-induced volumetric alterations in the brains. Stressed rats displayed cognitive impairments and we found numerous correlations between the cognitive performance of the animals and between various DTI metrics of the inferior colliculus, corpus callosum, anterior commissure, and amygdala.Conclusions: Our data provide further support to the translational value of DTI studies and suggest that chronic stress exposure results in similar white matter microstructural alterations that have been documented in stress-related psychiatric disorders. These DTI findings imply microstructural abnormalities in the brain, which may underlie the cognitive deficits that are often present in stress-related mental disorders.