Diffusion Tensor Imaging Measures Research Articles

Altered MRI Diffusion Properties of the White Matter Tracts Connecting Frontal and Thalamic Brain Regions in First-Episode, Drug-Naïve Patients With Postpartum Depression.

Although progress has been made in exploring postpartum depression (PPD), the involvement of cerebral structure connectivity in PPD patients keeps unclear. To explore structural connectivity alternations in mothers with PPD, diffusion tensor imaging (DTI) and automated fiber quantification (AFQ) were used to calculate brain white matter microstructure properties. Cross-sectional. A total of 51 women with first-episode, treatment-näive PPD, and 49 matched healthy postpartum women (HPW) controls. A 3.0 T; single-shot echo-planar imaging sequence. DTI measurements of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were obtained for 18 specific white matter tracts. The relationship between PDD symptoms, hormone levels, and postpartum days was also investigated. Two sample t test and Pearson's correlation analysis. The analysis was performed by using a permutation-based multiple-comparison correction approach, with the threshold of P < 0.05 (family wise error corrected [FWE-corrected]) separately across the four different outcome measures. Women with PPD showed significantly increased FA and AD in right anterior thalamic radiation (ATR) tract and significantly increased FA and significantly reduced RD in the cingulum tract, compared to women without PPD. The RD values of right cingulum were significantly positively correlated with postpartum days in HPW (r=0.39). There were no significant relationships between brain measures and hormone levels in either patients or controls. DTI measures have revealed altered integrity in the white matter of the cortical-thalamic circuits in women with PPD compared to HPW. Damage to these circuits may be a structural basis for the impaired emotional regulation and blunted mother-infant bonding in mothers with PPD and a potential target for the development of new treatments. 2 TECHNICAL EFFICACY: Stage 3.

Memory retrieval brain-behavior disconnection in mild traumatic brain injury: A magnetoencephalography and diffusion tensor imaging study.

Mild traumatic brain (mTBI) injury is often associated with long-term cognitive and behavioral complications, including an increased risk of memory impairment. Current research challenges include a lack of cross-modal convergence regarding the underlying neural-behavioral mechanisms of mTBI, which hinders therapeutics and outcome management for this frequently under-treated and vulnerable population. We used multi-modality imaging methods including magnetoencephalography (MEG) and diffusion tensor imaging (DTI) to investigate brain-behavior impairment in mTBI related to working memory. A total of 41 participants were recruited, including 23 patients with a first-time mTBI imaged within 3 months of injury (all male, age=29.9, SD=6.9), and 18 control participants (all male, age=27.3, SD=5.3). Whole-brain statistics revealed spatially concomitant functional-structural disruptions in brain-behavior interactions in working memory in the mTBI group compared with the control group. These disruptions are located in the hippocampal-prefrontal region and, additionally, in the amygdala (measured by MEG neural activation and DTI measures of fractional anisotropy in relation to working memory performance; p < .05, two-way ANCOVA, nonparametric permutations, corrected). Impaired brain-behavior connections found in the hippocampal-prefrontal and amygdala circuits indicate brain dysregulation of memory, which may leave mTBI patients vulnerable to increased environmental demands exerting memory resources, leading to related cognitive and emotional psychopathologies. The findings yield clinical implications and highlight a need for early rehabilitation after mTBI, including attention- and sensory-based behavioral exercises.

MRI diffusion tensor imaging scalar values in dogs with intervertebral disc herniation: A comparison between manual and semiautomated region of interest methods.

Magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) measures have been described as methods for quantifying spinal cord injury and predicting outcome in dogs with intervertebral disc herniation (IVDH); however, studies comparing methods for selecting regions of interest (ROIs) are currently lacking. The aims of this retrospective, methods comparison, observational study were to compare DTI measurements acquired using manual (mROI) versus semiautomated ROI (sROI) methods and to compare DTI measurements with patient outcomes. Magnetic resonance imaging scans that included DTI pulse sequences were retrieved for 65 dogs with confirmed IVDH. Regions of interest were placed at one vertebral length cranial and caudal to the region of spinal cord compression (RSCC) using the mROI and sROI methods. Scalar values based on the mROI and sROI methods were compared. There was a significant difference for all DTI measures (P<0.0001), where fractional anisotropy was higher (95% confidence interval [CI]: 0.15, 0.19) and mean diffusivity (MD; CI: -0.41, -0.35), axial diffusivity (AD; CI: -0.47, -0.36) and radial diffusivity (RD; CI: -0.36, -0.27) were lower for the mROI than for the sROI. For both the mROI and sROI, MD, AD, and RD were significantly lower (p<0.05) at the RSCC in paraplegic dogs that did not regain motor function. The findings indicated that DTI methods for quantifying SCI using open source software and ROI were feasible for use in dogs with IVDH; however, values based on sROI methods differed from values based on mROI methods. Some DTI measures based on both the mROI and sROI methods were predictive of poor patient outcome.

Bridging the gap between constrained spherical deconvolution and diffusional variance decomposition via tensor-valued diffusion MRI.

Diffusion tensor imaging (DTI) is widely used to extract valuable tissue measurements and white matter (WM) fiber orientations, even though its lack of specificity is now well-known, especially for WM fiber crossings. Models such as constrained spherical deconvolution (CSD) take advantage of high angular resolution diffusion imaging (HARDI) data to compute fiber orientation distribution functions (fODF) and tackle the orientational part of the DTI limitations. Furthermore, the recent introduction of tensor-valued diffusion MRI allows for diffusional variance decomposition (DIVIDE), enabling the computation of measures more specific to microstructure than DTI measures, such as microscopic fractional anisotropy (μFA). Recent work on making CSD compatible with tensor-valued diffusion MRI data opens the door for methods combining CSD and DIVIDE to get both fODFs and microstructure measures. However, the impacts of such atypical data on fODF reconstruction with CSD are yet to be fully known and understood. In this work, we use simulated data to explore the effects of various combinations of diffusion encodings on the angular resolution of extracted fOFDs and on the versatility of CSD in multiple realistic situations. We also compare the combinations with regards to their performance at producing accurate and precise μFA with DIVIDE, and present an optimized 10min protocol combining linear and spherical b-tensor encodings for both methods. We show that our proposed protocol enables the reconstruction of both fODFs and μFA on in vivo data.

Implicating Causal Brain Magnetic Resonance Imaging in Glaucoma Using Mendelian Randomization.

BackgroundGlaucoma is hypothesized to originate in the brain but manifests as an eye disease as it possesses the common features of neurodegeneration diseases. But there is no evidence to demonstrate the primary brain changes in glaucoma patients. In the present study, we have used Mendelian randomization (MR) to understand the causal effect of brain alterations on glaucoma.MethodsOur MR study was carried out using summary statistics from genome-wide associations for 110 diffusion tensor imaging (DTI) measurements of white matter (WM) tracts (17,706 individuals), 101 brain region-of-interest (ROI) volumes (19,629 individuals), and glaucoma (8,591 cases, 210,201 control subjects). The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method and verified by two other MR methods, including MR Egger, weighted median, and extensive sensitivity analyses.ResultsGenetic liability to fornix fractional anisotropy (FX.FA) (OR = 0.71, 95%CI = 0.56–0.88, P = 2.44 × 10–3), and uncinate fasciculus UNC.FA (OR = 0.65, 95%CI = 0.48–0.88, P = 5.57 × 10–3) was associated with a low risk of glaucoma. Besides, the right ventral diencephalon (OR = 1.72, 95%CI = 1.17–2.52, P = 5.64 × 10–3) and brain stem (OR = 1.35, 95%CI = 1.08–1.69, P = 8.94 × 10–3) were associated with the increased risk of glaucoma. No heterogeneity and pleiotropy were detected.ConclusionOur study suggests that the fornix and uncinate fasciculus degenerations and injures of the right ventral diencephalon and brain stem potentially increase the occurrence of glaucoma and reveal the existence of the brain-eye axis.

Magic angle effect on diffusion tensor imaging in ligament and brain

PurposeTo evaluate the magic angle effect on diffusion tensor imaging (DTI) measurements in rat ligaments and mouse brains. MethodsThree rat knee joints and three mouse brains were scanned at 9.4 T using a modified 3D diffusion-weighted spin echo pulse sequence with the isotropic spatial resolution of 45 μm. The b value was 1000 s/mm2 for rat knee and 4000 s/mm2 for mouse brain. DTI model was used to investigate the quantitative metrics at different orientations with respect to the main magnetic field. The collagen fiber structure of the ligament was validated with polarized light microscopy (PLM) imaging. ResultsThe signal intensity, signal-to-noise ratio (SNR), and DTI metrics in the ligament were strongly dependent on the collagen fiber orientation with respect to the main magnetic field from both simulation and actual MRI scans. The variation of fractional anisotropy (FA) was about ~32%, and the variation of mean diffusivity (MD) was ~11%. These findings were further validated with the numerical simulation at different SNRs (~10.0 to 86.0). Compared to the ligament, the DTI metrics showed little orientation dependence in mouse brains. ConclusionMagic angle effect plays an important role in DTI measurements in the highly ordered collagen-rich tissues, while MD showed less orientation dependence than FA.

Age-Dependent Association Between Cognitive Reserve Proxy and Longitudinal White Matter Microstructure in Older Adults.

ObjectiveThis study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship between the proxy CR composite score and white matter microstructure was modified by participant age, APOE-ε4 genetic status, and level of vascular risk.MethodsA sample of 192 non-demented (n = 166 cognitively normal, n = 26 mild cognitive impairment) older adults [mean age = 70.17 (SD = 8.5) years] from the BIOCARD study underwent longitudinal DTI (mean follow-up = 2.5 years, max = 4.7 years). White matter microstructure was quantified by fractional anisotropy (FA) and radial diffusivity (RD) values in global white matter tracts and medial temporal lobe (MTL) white matter tracts.ResultsUsing longitudinal linear mixed effect models, we found that FA decreased over time and RD increased over time in both the global and MTL DTI composites, but the rate of change in these DTI measures was not related to level of CR. However, there were significant interactions between the CR composite score and age for global RD in the full sample, and for global FA, global RD, and MTL RD among those with normal cognition. These interactions indicated that among participants with a lower baseline age, higher CR composite scores were associated with higher FA and lower RD values, while among participants with higher age at baseline, higher CR composite scores were associated with lower FA and higher RD values. Furthermore, these relationships were not modified by APOE-ε4 genotype or level of vascular risk.ConclusionThe association between level of CR and DTI measures differs by age, suggesting a possible neuroprotective effect of CR among late middle-aged adults that shifts to a compensatory effect among older adults.

Tract-Based Spatial Statistics Analysis of Diffusion Tensor Imaging in Older Adults After the PICMOR Intervention Program: A Pilot Study.

Diffusion tensor imaging (DTI) enables the investigation of white matter properties in vivo by applying a tensor model to the diffusion of water molecules in the brain. Using DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), an attempt has been made to detect age-related alterations in the white matter microstructure in aging research. However, the use of comprehensive DTI measures to examine the effects of cognitive intervention/training on white matter fiber health in older adults remains limited. Recently, we developed a cognitive intervention program called Photo-Integrated Conversation Moderated by Robots (PICMOR), which utilizes one of the most intellectual activities of daily life, conversations. To examine the effects of PICMOR on cognitive function in older adults, we conducted a randomized controlled trial and found that verbal fluency task scores were improved by this intervention. Based on these behavioral findings, we collected in this pilot study diffusion-weighted images from the participants to identify candidate structures for white matter microstructural changes induced by this intervention. The results from tract-based spatial statistics analyses showed that the intervention group, who participated in PICMOR-based conversations, had significantly higher FA values or lower MD, AD, or RD values across various fiber tracts, including the left anterior corona radiata, external capsule, and anterior limb of the internal capsule, compared to the control group, who participated in unstructured free conversations. Furthermore, a larger improvement in verbal fluency task scores throughout the intervention was associated with smaller AD values in clusters, including the left side of these frontal regions. The present findings suggest that left frontal white matter structures are candidates for the neural underpinnings responsible for the enhancement of verbal fluency. Although our findings are limited by the lack of comparable data at baseline, we successfully confirmed the hypothesized pattern of group differences in DTI indices after the intervention, which fits well with the results of other cognitive intervention studies. To confirm whether this pattern reflects intervention-induced white matter alterations, longitudinal data acquisition is needed in future research.

Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter

The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the “last-in-first-out”) concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.

Altered white matter microstructure and neurocognitive function of HIV-infected patients with low nadir CD4.

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects.

Lithium: more than a mood stabilizier

IntroductionBipolar disorder (BD) is characterized by episodic changes in affect, motivation, cognition and behavior. This severe mental disorder has a prevalence of at least 1% and a high heritability of 60%-80%. The pathophysiology is still poorly understood but evidence indicate that the disorder relates to disturbances in front-limbic networks relevant for emotion processing and regulation. New techniques have been used to study BD and showed aberrante white matter (WM) microstructure in the corpus callosum and from-limbic pathways. However, lithium, a mood stabilizier, it looks like has celular and neuromodulatory effects.ObjectivesThe authors elaborate a narrative literature review to identify the existing clinical evidence of lithium’s effect on the WM from BD patients.MethodsPubmed databased searched using the therms “bipolar disorder”, “white matter” and “lithium”.ResultsLithium is a bipolar medication that confers treatment and long-term prophylaxis and been reported as having neuroprotective effects.Studies that used new techniques such diffusion tensor imaging measures to assess white matter integrity reported a positive effect of lithium on the integrity of WM of BD patients and suggest that response to lithium treatment in BD patients is associated with normalization of WM microstructure in regions associated with emotion processing.ConclusionsLithium appears to positively influence the evolution of the white matter abnormalities described in BD patients however further investigation is required to strongly reinforce this potential and safety.DisclosureNo significant relationships.

18F-SynVesT-1 PET/MR Imaging of the Effect of Gut Microbiota on Synaptic Density and Neurite Microstructure: A Preclinical Pilot Study.

The gut microbiome profoundly influences brain structure and function. The gut microbiome is hypothesized to play a key role in the etiopathogenesis of neuropsychiatric and neurodegenerative illness; however, the contribution of an intact gut microbiome to quantitative neuroimaging parameters of brain microstructure and function remains unknown. Herein, we report the broad and significant influence of a functional gut microbiome on commonly employed neuroimaging measures of diffusion tensor imaging (DTI), neurite orientation dispersion and density (NODDI) imaging, and SV2A 18F-SynVesT-1 synaptic density PET imaging when compared to germ-free animals. In this pilot study, we demonstrate that mice, in the presence of a functional gut microbiome, possess higher neurite density and orientation dispersion and decreased synaptic density when compared to age- and sex-matched germ-free mice. Our results reveal the region-specific structural influences and synaptic changes in the brain arising from the presence of intestinal microbiota. Further, our study highlights important considerations for the development of quantitative neuroimaging biomarkers for precision imaging in neurologic and psychiatric illness.

Global changes in diffusion tensor imaging during acute ischemic stroke and post-stroke cognitive performance

Post-stroke cognitive impairment is related to the effects of the acute stroke and pre-stroke brain health. We tested whether diffusion tensor imaging (DTI) can detect acute, global effects of stroke and predict post-stroke cognitive performance. Patients with stroke or TIA enrolled in a prospective cohort study were included if they had 1) at least one DTI acquisition at acute presentation, 24 hours, 5 days, or 30 days, and 2) follow-up testing with the telephone Montreal Cognitive Assessment (T-MoCA) at 30 and/or 90 days. A whole brain, white-matter skeleton excluding the infarct was used to derive mean global DTI measures for mean diffusivity (MD), fractional anisotropy (FA), free water (FW), FW-corrected MD (MDtissue), and FW-corrected FA (FAtissue). In 74 patients with ischemic stroke or TIA, there was a transient 4.2% increase in mean global FW between acute presentation and 24 hours (p = 0.024) that returned to initial values by 30 days (p = 0.03). Each acute global DTI measure was associated with 30-day T-MoCA score (n = 61, p = 0.0011–0.0076). Acute global FW, MD, FA and FAtissue were also associated with 90-day T-MoCA (n = 56, p = 0.0034–0.049). Transient global FW elevation likely reflects stroke-related interstitial edema, whereas other global DTI measures are more representative of pre-stroke brain health.

Longitudinal changes of white matter microstructure following traumatic brain injury in U.S. military service members

The purpose of this study was to analyze quantitative diffusion tensor imaging measures across the spectrum of traumatic brain injury severity and evaluate their trajectories in military service members. Participants were 96 U.S. military service members and veterans who had sustained a mild traumatic brain injury [including complicated mild traumatic brain injury (n = 16) and uncomplicated mild traumatic brain injury (n = 68)], moderate-severe traumatic brain injury (n = 12), and controls (with or without orthopaedic injury, n = 39). All participants had been scanned at least twice, with some receiving up to five scans. Both whole brain voxel-wise analysis and tract-of-interest analysis were applied to assess the group differences of diffusion tensor imaging metrics, and their trajectories between time points of scans and days since injury. Linear mixed modelling was applied to evaluate cross-sectional and longitudinal diffusion tensor imaging metrics changes within and between groups using both tract-of-interest and voxel-wise analyses. Participants with moderate to severe traumatic brain injury had larger white matter disruption both in superficial subcortical and deep white matter, mainly over the anterior part of cerebrum, than those with mild traumatic brain injury, both complicated and uncomplicated, and there was no evidence of recovery over the period of follow-ups in moderate-severe traumatic brain injury, but deterioration was possible. Participants with mild traumatic brain injury had white matter microstructural changes, mainly in deep central white matter over the posterior part of cerebrum, with more spatial involvement in complicated mild traumatic brain injury than in uncomplicated mild traumatic brain injury and possible brain repair through neuroplasticity, e.g. astrocytosis with glial processes and glial scaring. Our results did not replicate 'V-shaped' trajectories in diffusion tensor imaging metrics, which were revealed in a previous study assessing the sub-acute stage of brain injury in service members and veterans following military combat concussion. In addition, non-traumatic brain injury controls, though not demonstrating any evidence of sustaining a traumatic brain injury, might have transient white matter changes with recovery afterward. Our results suggest that white matter integrity following a remote traumatic brain injury may change as a result of different underlying mechanisms at the microstructural level, which can have a significant consequence on the long-term well beings of service members and veterans. In conclusion, longitudinal diffusion tensor imaging improves our understanding of the mechanisms of white matter microstructural changes across the spectrum of traumatic brain injury severity. The quantitative metrics can be useful as guidelines in monitoring the long-term recovery.

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity. We used these measures of structural brain integrity to assess white matter changes, physical fitness, and cognition in a cross-sectional study of PLWH. Forty-four virologically well-controlled PLWH were recruited (average age of 56 years, a median recent CD4+ count of 682 cells/mm3). Diffusion tensor imaging -derived fractional anisotropy (FA) and diffusion basis spectrum imaging-derived axonal density were calculated. Cardiorespiratory fitness [maximal volume of oxygen consumption (VO2 max)] was measured by performing indirect calorimetry during exercise to volitional exhaustion. Cardiovascular risk was assessed by the Framingham risk score. Neuropsychological performance (NP) testing evaluated learning, memory, psychomotor/processing speed, and executive function. Partial correlations assessed the relationships among cardiorespiratory fitness, neuroimaging, NP, and HIV clinical metrics (CD4+ count and time since diagnosis). Higher VO2 max was associated with higher FA and higher axonal density in multiple white matter tracts, including the corticospinal tract and superior longitudinal fasciculus. Better NP in the motor/psychomotor domain was positively associated with FA and axonal density in diverse tracts including those associated with motor and visuospatial processing. However, higher VO2 max was not associated with NP or HIV clinical metrics. An active lifestyle promoting cardiorespiratory fitness may lead to better white matter integrity and decreased susceptibility to cognitive decline in virologically well-controlled PLWH.

Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure

High levels of prenatal alcohol exposure (PAE) are associated with widespread behavioral and cognitive problems as well as structural alterations of the brain. However, it remains unclear whether low levels of PAE affect brain structure and function, and prior studies generally have not had well-matched control populations (eg, for sociodemographic variables). To compare structural brain alterations and behavioral changes in children with lower levels of PAE with those of well-matched controls with no PAE. In this cross-sectional study, participants were selected from the Adolescent Brain Cognitive Development study. Children with PAE were compared with controls matched for age, sex, family income, maternal educational level, and caregiver status. Neither group had prenatal exposure to other adverse substances (eg, tobacco, cannabis, illicit drugs). Data were collected from September 1, 2016, to November 15, 2018, and analyzed from October 14, 2020, to February 14, 2022. Diffusion tensor imaging, resting-state functional magnetic resonance imaging (MRI), and Child Behavior Checklist (CBCL) administration. Fractional anisotropy (FA); mean, axial, and radial diffusivity from diffusion tensor imaging; brain functional signal variations from functional MRI; and several scores, including internalizing and externalizing behavior problems, from the CBCL. Spearman correlation coefficients between diffusion tensor imaging and functional MRI measures and the CBCL scores were calculated. A total of 270 children were included in the analysis (mean [SD] age, 9.86 [0.46] years; 141 female [52.2%] and 129 male [47.8%]), consisting of 135 children with PAE (mean [SD] age, 9.85 [0.65] years; 73 female [54.1%] and 62 male [45.9%]) (mean exposure, 1 drink/wk) and 135 unexposed controls (mean [SD] age, 9.87 [0.04] years; 68 female [50.4%] and 67 male [49.6%]). Children with PAE had lower mean (SD) FA in white matter of the left postcentral (0.35 [0.05] vs 0.36 [0.04]; mean difference, -0.02 [95% CI, -0.03 to -0.01]), left inferior parietal (0.31 [0.07] vs 0.33 [0.06]; mean difference, -0.03 [95% CI, -0.04 to -0.01]), left planum temporale (0.26 [0.04] vs 0.28 [0.03]; mean difference, -0.02 [95% CI, -0.03 to -0.01]), left inferior occipital (0.30 [0.07] vs 0.32 [0.05]; mean difference, -0.03 [95% CI, -0.04 to -0.01]), and right middle occipital (0.30 [0.04] vs 0.31 [0.04]; mean difference, -0.01 [95% CI, -0.02 to -0.01]) areas compared with controls, and higher FA in the gray matter of the putamen (0.22 [0.03] vs 0.21 [0.02]; mean difference, 0.01 [95% CI, 0.005-0.02]). Externalizing behavior scores were higher (worse) in children with PAE than in controls (mean [SD], 45.2 [9.0] vs 42.8 [9.0]; mean difference, 2.39 [95% CI, 0.30-4.47]). Several of these regions had significant group-behavior interactions, such that the higher FA was associated with less problematic behaviors in controls (ρ range, -0.24 to -0.08) but no associations were present in the PAE group (ρ range, 0.02-0.16). In this cross-sectional study, children with low levels of PAE had lower FA and more behavioral problems compared with a well-matched control group. These results suggest that PAE, even in small amounts, has a measurable effect on brain structure in children.

Track-weighted imaging analysis of white matter microstructures in healthy children: Sex and hemispheric differences.

Structural substrates of sex differences in human function and behavior have been elucidated in previous studies. Diffusion weighted magnetic resonance imaging (DW-MRI) is a widely used non-invasive imaging technique in studying human brain white matter structural organization. While many DW-MRI studies reporting sex differences in WM structure are based on diffusion tensor imaging (DTI) measures, tract specific microstructural differences require further investigation. In this study, we aim to investigate sex differences and sex-specific hemispheric differences in white matter microstructural development in healthy 8-year-old children based on novel track weighted imaging (TWI) analysis. Average pathlength map (APM) is a TWI contrast in which the average length of fibers passing through a voxel is utilized. In this study, we employed tract specific APM measures to evaluate sex differences in WM microstructural development. A total of 37 WM tracts were analyzed including 7 commissural tracts, 9 bilateral association tracts and 6 bilateral projection tracts. APM maps were generated for each tract. Tract-wise group tests were done using the mean values of APM maps. Sex differences were tested using general linear model based group comparisons. Age and total brain volume were included as covariates in the group analysis. Sex specific hemispheric differences were performed for the 15 bilateral tracts. One sample t-tests were done independently for left>right and right>left cases and the APM measures were controlled for age and total cerebral hemispheric volume. P-values<0.05 were considered significant after correcting for multiple comparisons accounting for the total number of tracts. Significant sex differences were revealed in APM measures between boys and girls in 11 WM tracts including rostral body of corpus callosum (CC), left inferior fronto-occipital fasciculus (IFOF), right cingulum, bilateral first and second segments of superior longitudinal fasciculus (SLF), right middle longitudinal fasciculus (MLF), bilateral fronto-pontine (FPT) and right parieto-occipital pontine tracts (POPT). The sex differences showed higher APM values for these 11 tracts in boys as compared to that of girls. In hemispheric differences analysis for both boys and girls, 2 tracts, arcuate fasciculus and optic radiation showed higher APM in left tracts as compared right; 5 tracts, IFOF, MLF, third segment of SLF, FPT and superior thalamic radiation showed higher APM in right tracts as compared to left. This indicates that boys and girls possess similar lateral asymmetries in these 7 tracts. Additionally, anterior thalamic radiation (ATR) showed higher APM in left tract and 4 tracts, first segment of SLF, POPT, inferior longitudinal fasciculus and cortico-spinal tract showed higher APM in right for boys. In girls, second segment of SLF and uncinate fasciculus showed higher APM in right hemisphere. These results indicate different lateral asymmetries between boys and girls for 7 tracts. Overall, boys showed higher average fiber length in most of the tracts, even after controlling for total brain volume.

Connecting macroscopic diffusion metrics of cardiac diffusion tensor imaging and microscopic myocardial structures based on simulation.

To investigate the relationship between microscopic myocardial structures and macroscopic measurements of diffusion tensor imaging (DTI), we proposed a cardiac DTI simulation method using the Bloch equationand the Monte Carlo random walk in a realistic myocardium model reconstructed from polarized light imaging (PLI) data of the entire human heart. To obtain a realistic simulation, with the constraints of prior knowledge pertaining to the maturational change of the myocardium structure, appropriate microstructure modeling parameters were iteratively determined by matching DTI simulations and real acquisitions of the same hearts in terms of helix angle, fractional anisotropy (FA) and mean diffusivity (MD) maps. Once a realistic simulation was obtained, we varied the extra-cellular volume (ECV) ratio, myocyte orientation heterogeneity and myocyte size, and explored the effects of microscopic changes in tissue structure on macroscopic diffusion metrics. The experimental results demonstrated the feasibility of simulating the DTI of the whole heart using PLI measurements. When varying ECV from 15% to 55%, mean FA decreased from 0.55 to 0.26, axial diffusivity increased by 0.6 μm2/ms, and radial diffusivity increased by 0.7 μm2/ms. When orientation heterogeneity was varied from 0 to 20∘, mean FA decreased from 0.4 to 0.3, axial diffusivity decreased by 0.08 μm2/ms, and radial diffusivity increased by 0.03 μm2/ms. When mean diameter of myocytes was varied from 6 μm to 10 μm, FA decreased from 0.67 to 0.46, axial and radial diffusivities increased by 0.05 and 0.2 μm2/ms, respectively.

Cumulative strain-based metrics for predicting subconcussive head impact exposure-related imaging changes in a cohort of American youth football players.

Youth football athletes are exposed to repetitive subconcussive head impacts during normal participation in the sport, and there is increasing concern about the long-term effects of these impacts. The objective of the current study was to determine if strain-based cumulative exposure measures are superior to kinematic-based exposure measures for predicting imaging changes in the brain. This prospective, longitudinal cohort study was conducted from 2012 to 2017 and assessed youth, male football athletes. Kinematic data were collected at all practices and games from enrolled athletes participating in local youth football organizations in Winston-Salem, North Carolina, and were used to calculate multiple risk-weighted cumulative exposure (RWE) kinematic metrics and 36 strain-based exposure metrics. Pre- and postseason imaging was performed at Wake Forest School of Medicine, and diffusion tensor imaging (DTI) measures, including fractional anisotropy (FA), and its components (CL, CP, and CS), and mean diffusivity (MD), were investigated. Included participants were youth football players ranging in age from 9 to 13 years. Exclusion criteria included any history of previous neurological illness, psychiatric illness, brain tumor, concussion within the past 6 months, and/or contraindication to MRI. A total of 95 male athletes (mean age 11.9 years [SD 1.0 years]) participated between 2012 and 2017, with some participating for multiple seasons, resulting in 116 unique athlete-seasons. Regression analysis revealed statistically significant linear relationships between the FA, linear coefficient (CL), and spherical coefficient (CS) and all strain exposure measures, and well as the planar coefficient (CP) and 8 strain measures. For the kinematic exposure measures, there were statistically significant relationships between FA and RWE linear (RWEL) and RWE combined probability (RWECP) as well as CS and RWEL. According to area under the receiver operating characteristic (ROC) curve (AUC) analysis, the best-performing metrics were all strain measures, and included metrics based on tensile, compressive, and shear strain. Using ROC curves and AUC analysis, all exposure metrics were ranked in order of performance, and the results demonstrated that all the strain-based metrics performed better than any of the kinematic metrics, indicating that strain-based metrics are better discriminators of imaging changes than kinematic-based measures. Studies relating the biomechanics of head impacts with brain imaging and cognitive function may allow equipment designers, care providers, and organizations to prevent, identify, and treat injuries in order to make football a safer activity.

Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.

Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.