Alternation of psychological resilience may moderate mentalization toward mental health conditions from macro- and microstructure aspects.

OBJECTIVE: We aim to investigate the interplay between mentalization, brain microstructure, and psychological resilience as potential protective factors against mental illness. METHOD: Four hundred and twenty-six participants (mean age 40.12±16.95; 202 males, 224 females), without psychiatric or neurological history, completed assessments: Dissociative Process Scale (DPS), Peace of Mind (PoM), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Resilience Scale for Adults (RSA), and Magnetic Resonance Imaging (MRI) structures with selected regions of interest, and Diffusion Tensor Imaging (DTI) maps from various tracts in the right hemisphere and connection to the frontal areas, including anterior thalamic radiation (ATR), Cingulum (hippocampus) (CH), Corticospinal tract (CST), Superior longitudinal fasciculus (SLF), Inferior fronto-occipital fasciculus (IFOF), and Uncinate fasciculus (UF) were analyzed. RESULTS: Two clusters, representing hypomentalization (HypoM) and hypermentalization (HyperM), were identified based on DPS, CPSS, and RFQ responses. One-way ANOVA showed no significant age or gender differences between clusters. The HypoM group exhibited lower PoM scores, higher BDI and BAI scores, and lower RSA scores (ps< 0.05). Structural brain metric comparison showed significant differences in GMV in the right caudal middle frontal gyrus (rcMFG), right superior frontal gyrus (rsFG), and right frontal pole (rFP) between groups. In addition, the HyperM individuals with a higher risk of depression and a higher ratio of intrapersonal to interpersonal factors of resilience were found with reduced GMV on the rcMFG. Additionally, analyses of DTI metrics revealed significant differences between two groups in rATR and rSLF in terms of fractional anisotropy (FA) values; rATR, rCST, rUF, rSLF, rCH and rIFOF in terms of mean diffusivity (MD) values, and radial diffusivity (RD) (corrected p = 0.05). Moreover, the positive correlation between different domains of resilience and white matter (WM) integrity implied further enhancement of intrapersonal or interpersonal resilience factors that are different for people with different mentalization. CONCLUSIONS: The findings underscore the importance of considering both intrapersonal and interpersonal factors in understanding the interactions between psychological resilience and mental health conditions relevant to brain mechanisms.

Connectome alterations following perinatal deafness in the cat.

Following sensory deprivation, areas and networks in the brain may adapt and reorganize to compensate for the loss of input. These adaptations are manifestations of compensatory crossmodal plasticity, which has been documented in both human and animal models of deafness-including the domestic cat. Although there are abundant examples of structural plasticity in deaf felines from retrograde tracer-based studies, there is a lack of diffusion-based knowledge involving this model compared to the current breadth of human research. The purpose of this study was to explore white matter structural adaptations in the perinatally-deafened cat via tractography, increasing the methodological overlap between species. Plasticity was examined by identifying unique group connections and assessing altered connectional strength throughout the entirety of the brain. Results revealed a largely preserved connectome containing a limited number of group-specific or altered connections focused within and between sensory networks, which is generally corroborated by deaf feline anatomical tracer literature. Furthermore, five hubs of cortical plasticity and altered communication following perinatal deafness were observed. The limited differences found in the present study suggest that deafness-induced crossmodal plasticity is largely built upon intrinsic structural connections, with limited remodeling of underlying white matter.

Structural interhemispheric connectivity defects in mouse models of BBSOAS: Insights from high spatial resolution 3D white matter tractography.

White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.

Impact of truncating diffusion MRI scans on diffusional kurtosis imaging.

OBJECTIVE: Diffusional kurtosis imaging (DKI) extends diffusion tensor imaging (DTI), characterizing non-Gaussian diffusion effects but requires longer acquisition times. To ensure the robustness of DKI parameters, data acquisition ordering should be optimized allowing for scan interruptions or shortening. Three methodologies were used to examine how reduced diffusion MRI scans impact DKI histogram-metrics: 1) the electrostatic repulsion model (OptEEM); 2) spherical codes (OptSC); 3) random (RandomTRUNC). MATERIALS AND METHODS: Pre-acquired diffusion multi-shell data from 14 female healthy volunteers (29±5 years) were used to generate reordered data. For each strategy, subsets containing different amounts of the full dataset were generated. The subsampling effects were assessed on histogram-based DKI metrics from tract-based spatial statistics (TBSS) skeletonized maps. To evaluate each subsampling method on simulated data at different SNRs and the influence of subsampling on in vivo data, we used a 3-way and 2-way repeated measures ANOVA, respectively. RESULTS: Simulations showed that subsampling had different effects depending on DKI parameter, with fractional anisotropy the most stable (up to 5% error) and radial kurtosis the least stable (up to 26% error). RandomTRUNC performed the worst while the others showed comparable results. Furthermore, the impact of subsampling varied across distinct histogram characteristics, the peak value the least affected (OptEEM: up to 5% error; OptSC: up to 7% error) and peak height (OptEEM: up to 8% error; OptSC: up to 11% error) the most affected. CONCLUSION: The impact of truncation depends on specific histogram-based DKI metrics. The use of a strategy for optimizing the acquisition order is advisable to improve DKI robustness to exam interruptions.

Diagnostic efficacy of tract-specific diffusion tensor imaging in cervical spondylotic myelopathy with electrophysiological examination validation.

PURPOSE: This study aimed to investigate the effectiveness of tract-specific diffusion tensor imaging (DTI) metrics in identifying the responsible segments for neurological dysfunction in cervical spondylotic myelopathy (CSM). METHODS: The study encompassed nineteen participants diagnosed with CSM, including 10 males and 9 females. Additionally, a control group consisting of ten healthy caregivers (5 males and 5 females) were recruited with no symptoms and no compressions on magnetic resonance imaging (MRI). All participants underwent a comprehensive physical examination, MRI assessment, and DTI examination conducted by a senior chief physician. Several parameters were collected from the MR images, including the aspect ratio (defined as the anteroposterior diameter / the transverse diameter of the corresponding segment's spinal cord), transverse ratio (defined as the transverse diameter of the corresponding segment's spinal cord / the transverse diameter of the spinal cord at C2/3), and T2 high signal of the spinal cord. Furthermore, quantitative DTI metrics, such as axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA), were calculated using automatic region-of-interest (ROI) analysis for both whole spinal cord column and dorsal column. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic efficacy of the aspect ratio, transverse ratio, and DTI parameters. The area under the curve (AUC), sensitivity, and specificity were calculated. Intraoperative spinal cord electrophysiological examination was performed as the objective measure of spinal cord function during surgery. RESULTS: As determined by electrophysiological examination, neurological dysfunction was found in 2 patients due to C3/4 compression, in 10 patients due to C4/5 compression, in 6 patients due to C5/6 compression, and in 1 patient due to C6/7 compression. The modified Japanese Orthopedic Association scale (mJOA) was 12.71 ± 1.55 in the CSM group, with 4.87 ± 0.72 for sensory nerve function and 5.05 ± 1.35 for motor nerve function. For the control group, none of the volunteers had neurological dysfunction. T2 high signal was found at the most stenotic segment in 13 patients of the CSM group. Considering all the cervical segments, the aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) was more capable of determining the responsible segment than transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). AD, MD, and RD were significantly higher while FA was significantly lower in the responsible segment than in the irresponsible segment (P < 0.05). The AUC of DTI-Dorsal column parameters (AD, MD, RD, FA) was larger than the corresponding parameters of the DTI (Whole spinal cord). AD of DTI-Dorsal Column possessed the greatest efficacy (AUC = 0.823, sensitivity = 84.21%, specificity = 77.32%) to determine the responsible segment, larger than AD of DTI-Whole spinal cord (AUC = 0.822, P = 0.001, Sensitivity = 89.47%, Specificity = 77.32%), aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) and transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). Subgroup analysis revealed that the diagnostic efficacy of DTI and MRI parameters was influenced by cervical spine segment. CONCLUSIONS: When considering all cervical segments, AD from the DTI-Dorsal Column exhibited the most significant potential in identifying responsible segments. This potential was found to be superior to that of DTI-Whole spinal cord, aspect ratio, the most stenotic segment, T2 high signals, transverse ratio, motor nerve dysfunction, and sensory nerve dysfunction. The diagnostic effectiveness of both DTI and MRI parameters was notably influenced by the specific cervical spine segment.

Utility of diffusion tensor imaging and generalized q-sampling imaging for predicting short-term clinical effect of deep brain stimulation in Parkinson's disease.

PURPOSE: To assess whether diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI) metrics could preoperatively predict the clinical outcome of deep brain stimulation (DBS) in patients with Parkinson's disease (PD). METHODS: In this single-center retrospective study, from September 2021 to March 2023, preoperative DTI and GQI examinations of 44 patients who underwent DBS surgery, were analyzed. To evaluate motor functions, the Unified Parkinson's Disease Rating Scale (UPDRS) during on- and off-medication and Parkinson's Disease Questionnaire-39 (PDQ-39) scales were used before and three months after DBS surgery. The study population was divided into two groups according to the improvement rate of scales: ≥ 50% and < 50%. Five target regions, reported to be affected in PD, were investigated. The parameters having statistically significant difference were subjected to a receiver operating characteristic (ROC) analysis. RESULTS: Quantitative anisotropy (qa) values from globus pallidus externus, globus pallidus internus (qa_Gpi), and substantia nigra exhibited significant distributional difference between groups in terms of the improvement rate of UPDRS-3 scale during on-medication (p = 0.003, p = 0.0003, and p = 0.0008, respectively). In ROC analysis, the best parameter in predicting DBS response included qa_Gpi with a cut-off value of 0.01370 achieved an area under the ROC curve, accuracy, sensitivity, and specificity of 0.810, 73%, 62.5%, and 85%, respectively. Optimal cut-off values of ≥ 0.01864 and ≤ 0.01162 yielded a sensitivity and specificity of 100%, respectively. CONCLUSION: The imaging parameters acquired from GQI, particularly qa_Gpi, may have the ability to non-invasively predict the clinical outcome of DBS surgery.

An integration of neuroimaging and serum proteomics analysis suggests immune and inflammation are associated with white matter microstructure changes in cerebral small vessel disease with depressive symptoms.

INTRODUCTION: Depressive symptoms are a common concomitant of cerebral small vessel disease (CSVD), of which pathogenesis requires more study. White matter microstructural abnormalities and proteomic alternation have been widely reported regarding depression in the elderly with CSVD. Exploring the relationship between cerebral white matter microstructural alterations and serum proteins may complete the explanation of molecular mechanisms for the findings from neuroimaging research of CSVD combined with depressive symptoms. METHODS: An untargeted proteomics approach based on mass spectrometry was used to obtain serum proteomic profiles, which were clustered into co-expression protein modules. White matter microstructural integrity was measured using the FMRIB Software Library (FSL) and MATLAB to analyze diffusion tensor imaging (DTI) data and calculate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for 50 regions of interest (ROI). Integrating the proteome with the DTI results, weighted gene co-expression analysis (WGCNA) was used to identify protein modules related to white matter microstructural alterations, and the proteins of the corresponding modules were analyzed for functional enrichment through bioinformatics techniques. RESULTS: DTI measurements were analCerebral small vessel disease (CSVD); Depression; Diffusion tensor imaging (DTI); Proteomics; Inflammationyzed between individuals with CSVD and depressive symptoms (CSVD+D) (n = 24) and those without depressive symptoms (CSVD-D) (n = 35). Results showed an overall increase in MD, AD, and RD within the left hemisphere of the CSVD+D group, suggesting widespread loss of white matter integrity and axonal demyelination, including left superior longitudinal fasciculus (SLF), left posterior corona radiata (PCR) and right external capsule (EC). We identified two protein modules associated with DTI diffusivity, and functional enrichment analyses revealed that complement and coagulation cascades and immune responses participate in the alternation of white matter microstructure in the CSVD+D group. CONCLUSION: The results suggested immune- and inflammation-related mechanism was associated with white matter microstructure changes in CSVD with depressive symptoms.

Alteration of fractional anisotropy in preterm-born individuals: a systematic review and meta-analysis.

BACKGROUD: Neurological disorders are common in preterm (PT) born individuals. Diffusion tensor imaging (DTI) studies using tract-based spatial statistics (TBSS) effectively detect microstructural white matter (WM) abnormalities in the brain. We conducted this systematic review to integrate the findings of TBSS studies to determine the most consistent WM alterations in PT born individuals. METHODS: PubMed, Embase, Web of Science and Science Direct were searched. DTI studies using TBSS in PT born individuals were screened up to October 2022. The systematic review included studies reporting alterations in FA values for the entire brain in a stereotactic space, with three coordinates (x, y, z), according to the seed-based d mapping method. RESULTS: The search strategy identified seventeen studies that fulfilled our inclusion criteria, with a total of 911 PT-born individuals and 563 matched controls were analysed. Of the seventeen studies, eight were dedicated to 650 adults, five to 411 children and four to 413 infants. Ten studies recruited 812 individuals born very prematurely (GA <29 weeks), six studies recruited 386 moderately premature individuals (GA = 29-32 weeks) and one study recruited 276 individuals born late prematurely (GA >32 weeks). This meta-analysis of six studies including 388 individuals highlighted four brain regions in which fractional anisotropy (FA) was lower in PT group than in people born at term. The quantitative meta-analysis found that the most robust WM alterations were located in the corpus callosum (CC), the bilateral thalamus and the left superior longitudinal fasciculus (SLF) II. Significant changes in FA reflect WM abnormalities in PT born individuals from infant to young adulthood. CONCLUSIONS: Significant changes in FA reflect WM abnormalities in individuals born PT from infancy to young adulthood. The abnormal development of the CC, bilateral thalamus and left SLF may play a vital role in the neurodevelopment of PT individuals.

Neurological disorders are prevalent in preterm (PT) born individuals. The use of tract-based spatial statistics (TBSS) in diffusion tensor imaging (DTI) studies has proven effective in detecting microstructural abnormalities of the white matter (WM) of the brain. In order to determine the most consistent alterations in WM among those born prematurely, we have screened DTI studies using TBSS in this PT born population up until October 2022. The meta-analysis identified four brain regions where fractional anisotropy (FA) was lower in the PT group than in those born at term. The quantitative meta-analysis identified the corpus callosum, the bilateral thalamus and the left superior longitudinal fasciculus II. As the most robust WM alterations. Various studies have demonstrated the links between PT birth, intelligence quotient, gestational age and subject age.

A case study of left visual neglect after right pontine lesion: pathophysiological evidence for the infratentorial involvement in human visual attention.

Hemispatial neglect, the inability to attend to the contralesional side of space, is the most common disturbance of visuospatial attention. Both hemispatial neglect and visuospatial attention are typically associated with extended cortical networks. Nevertheless, recent accounts challenge this so-called corticocentric view and postulate the participation of structures well beyond the telencephalic cortex, in particular advocating the role of the brainstem. However, to the best of our knowledge, hemispatial neglect after a brainstem lesion has not yet been described. We describe, for the first time in a human, the occurrence and remission of contralesional visual hemispatial neglect after a focal lesion in the right pons. Hemispatial neglect was assessed by means of video-oculography during free visual exploration, a very sensitive and established method, and its remission was followed up until 3 wk after stroke. Moreover, by means of a lesion-deficit approach complemented by imaging, we identify a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons. Our findings offer, for the first time in a human, causal, lesion-based support for recent seminal accounts postulating the role of infratentorial structures participating in the activity of cerebral cortical attentional networks mediating attentional processes.NEW & NOTEWORTHY Visuospatial attention and its most common disturbance, hemispatial neglect, are typically associated with extended cortical networks. However, recent accounts challenge this corticocentric view and advocate the role of infratentorial structures. We describe, for the first time in a human, the occurrence of contralesional visual hemispatial neglect after a focal lesion in the right pons. We provide causal, lesion-based evidence for a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons.

Magnetic resonance and diffusion tensor imaging of the adolescent rabbit growth plate of the knee.

PURPOSE: To assess the ability of MRI-DTI to evaluate growth plate morphology and activity compared with that of histomorphometry and micro-CT in rabbits. METHODS: The hind limbs of female rabbits aged 16, 20, and 24 wk (n = 4 per age group) were studied using a 9.4T MRI scanner with a multi-gradient echo 3D sequence and DTI in 14 directions (b-value = 984 s/mm2 ). After MRI, the right and left hind limb were processed for histological analysis and micro-CT, respectively. The Wilcoxon signed-rank test was used to evaluate the height and volume of the growth plate. Intraclass correlation and Pearson correlation coefficient were used to evaluate the association between DTI metrics and age. RESULTS: The growth plate height and volume were similar for all modalities at each time point and age. Age was correlated with all tractography and DTI metrics in both the femur and tibia. A correlation was also observed between all the metrics at both sites. Tract number and volume declined with age; however, tract length did not show any changes. The fractional anisotropy color map showed lateral diffusion centrally in the growth plate and perpendicular diffusion in the hypertrophic zone, as verified by histology and micro-CT. CONCLUSION: MRI-DTI may be useful for evaluating the growth plates.

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

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

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 µm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Exploring Radial Asymmetry in MR Diffusion Tensor Imaging and Its Impact on the Interpretation of Glymphatic Mechanisms.

BACKGROUND: Diffusion imaging holds great potential for the non-invasive assessment of the glymphatic system in humans. One technique, diffusion tensor imaging along the perivascular space (DTI-ALPS), has introduced the ALPS-index, a novel metric for evaluating diffusivity within the perivascular space. However, it still needs to be established whether the observed reduction in the ALPS-index reflects axonal changes, a common occurrence in neurodegenerative diseases. PURPOSE: To determine whether axonal alterations can influence change in the ALPS-index. STUDY TYPE: Retrospective. POPULATION: 100 participants (78 cognitively normal and 22 with mild cognitive impairments) aged 50-90 years old. FIELD STRENGTH/SEQUENCE: 3T; diffusion-weighted single-shot spin-echo echo-planar imaging sequence, T1-weighted images (MP-RAGE). ASSESSMENT: The ratio of two radial diffusivities of the diffusion tensor (i.e., λ2/λ3) across major white matter tracts with distinct venous/perivenous anatomy that fulfill (ALPS-tracts) and do not fulfill (control tracts) ALPS-index anatomical assumptions were analyzed. STATISTICAL TESTS: To investigate the correlation between λ2/λ3 and age/cognitive function (RAVLT) while accounting for the effect of age, linear regression was implemented to remove the age effect from each variable. Pearson correlation analysis was conducted on the residuals obtained from the linear regression. Statistical significance was set at p < 0.05. RESULTS: λ2 was ~50% higher than λ3 and demonstrated a consistent pattern across both ALPS and control tracts. Additionally, in both ALPS and control tracts a reduction in the λ2/λ3 ratio was observed with advancing age (r = -0.39, r = -0.29, association and forceps tract, respectively) and decreased memory function (r = 0.24, r = 0.27, association and forceps tract, respectively). DATA CONCLUSIONS: The results unveil a widespread radial asymmetry of white matter tracts that changes with aging and neurodegeration. These findings highlight that the ALPS-index may not solely reflect changes in the diffusivity of the perivascular space but may also incorporate axonal contributions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

The association between white matter tract structural connectivity and information processing speed in relapsing-remitting multiple sclerosis.

BACKGROUND: Information processing speed (IPS) deterioration is common in relapsing-remitting multiple sclerosis (RRMS) patients [1] and might severely affect quality of life and occupational activity. However, understanding of its neural substrate is not fully elucidated. We aimed to investigate the associations between MRI-derived metrics of neuroanatomical structures, including the tracts, and IPS. METHODS: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Color Trails Test (CTT) were used to evaluate IPS in 73 RRMS consecutive patients, all undergoing only interferon beta (IFN-ß) therapy during the study. At the same time, 1.5T MRI including diffusion tensor imaging (DTI) data was acquired for each recruited subject. We analyzed volumetric and diffusion MRI measures (FreeSurfer 6.0) including normalized brain volume (NBV), cortical thickness (thk), white matter hypointensities (WMH), volume (vol), diffusion parameters: mean (MD), radial (RD), axial (AD) diffusivities, and fractional anisotropy (FA) of 18 major white-matter (WM) tracts. Multiple linear regression model with interaction resulted in distinguishing the neural substrate of IPS deficit in the IPS impaired subgroup of patients. RESULTS: The most significant tract abnormalities contributing to IPS deficit were right inferior longitudinal fasciculus (R ILF) FA, forceps major (FMAJ) FA, forceps minor (FMIN) FA, R uncinate fasciculus (UNC) AD, R corticospinal tract (CST) FA, and left superior longitudinal fasciculus FA (L SLFT). Among volumetric MRI metrics, IPS deficit was associated with L and R thalamic vol. and cortical thickness of insular regions. CONCLUSION: In this study, we showed that disconnection of the selected WM tracts, in addition to cortical and deep gray matter (GM) atrophy, might underlie IPS deficit in RRMS patients but more extensive studies are needed for precise associations.

Effects of anesthesia exposure on postnatal maturation of white matter in rhesus monkeys.

There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2 weeks to 36 months to assess postnatal white matter (WM) maturation. We investigated the longitudinal relationships between each DTI property and anesthesia exposure, taking age, sex, and weight of the monkeys into consideration. Quantification of anesthesia exposure was normalized to account for variation in exposures. Segmented linear regression with two knots provided the best model for quantifying WM DTI properties across brain development as well as the summative effect of anesthesia exposure. The resulting model revealed statistically significant age and anesthesia effects in most WM tracts. Our analysis indicated there were major effects on WM associated with low levels of anesthesia even when repeated as few as three times. Fractional anisotropy values were reduced across several WM tracts in the brain, indicating that anesthesia exposure may delay WM maturation, and highlight the potential clinical concerns with even a few exposures in young children.

Assessing traffic-related air pollution-induced fiber-specific white matter degradation associated with motor performance declines in aged rats.

Fine particulate matter (PM2.5) is thought to exacerbate Parkinson's disease (PD) in the elderly, and early detection of PD progression may prevent further irreversible damage. Therefore, we used diffusion tensor imaging (DTI) for probing microstructural changes after late-life chronic traffic-related PM2.5 exposure. Herein, 1.5-year-old Fischer 344 rats were exposed to clean air (control), high-efficiency particulate air (HEPA)-filtered ambient air (HEPA group), and ambient traffic-related PM2.5 (PM2.5 group, 9.933 ± 1.021 µg/m3) for 3 months. Rotarod test, DTI tractographic analysis, and immunohistochemistry were performed in the end of study period. Aged rats exposed to PM2.5 exhibited motor impairment with decreased fractional anisotropy and tyrosine hydroxylase expression in olfactory and nigrostriatal circuits, indicating disrupted white matter integrity and dopaminergic (DA) neuronal loss. Additionally, increased radial diffusivity and lower expression of myelin basic protein in PM2.5 group suggested ageing progression of demyelination exacerbated by PM2.5 exposure. Significant production of tumor necrosis factor-α was also observed after PM2.5 exposure, revealing potential inflammation of injury to multiple fiber tracts of DA pathways. Microstructural changes demonstrated potential links between PM2.5-induced inflammatory white matter demyelination and behavioral performance, with indication of pre-manifestation of DTI-based biomarkers for early detection of PD progression in the elderly.

Fiber tracing and microstructural characterization among audiovisual integration brain regions in neonates compared with young adults.

Audiovisual integration has been related with cognitive-processing and behavioral advantages, as well as with various socio-cognitive disorders. While some studies have identified brain regions instantiating this ability shortly after birth, little is known about the structural pathways connecting them. The goal of the present study was to reconstruct fiber tracts linking AVI regions in the newborn in-vivo brain and assess their adult-likeness by comparing them with analogous fiber tracts of young adults. We performed probabilistic tractography and compared connective probabilities between a sample of term-born neonates (N = 311; the Developing Human Connectome Project (dHCP, http://www.developingconnectome.org) and young adults (N = 311 The Human Connectome Project; https://www.humanconnectome.org/) by means of a classification algorithm. Furthermore, we computed Dice coefficients to assess between-group spatial similarity of the reconstructed fibers and used diffusion metrics to characterize neonates' AVI brain network in terms of microstructural properties, interhemispheric differences and the association with perinatal covariates and biological sex. Overall, our results indicate that the AVI fiber bundles were successfully reconstructed in a vast majority of neonates, similarly to adults. Connective probability distributional similarities and spatial overlaps of AVI fibers between the two groups differed across the reconstructed fibers. There was a rank-order correspondence of the fibers' connective strengths across the groups. Additionally, the study revealed patterns of diffusion metrics in line with early white matter developmental trajectories and a developmental advantage for females. Altogether, these findings deliver evidence of meaningful structural connections among AVI regions in the newborn in-vivo brain.

HIV peripheral neuropathy-related degeneration of white matter tracts to sensorimotor cortex.

Human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) affects up to 50% of people with HIV and is associated with depression, unemployment, and generally worsened quality of life. Previous work on the cortical mechanism of HIV neuropathy found decreased gray matter volume in the bilateral midbrain, thalamus, and posterior cingulate cortex, but structural connectivity in this context remains under-studied. Here we examine alterations in white matter microstructure using diffusion imaging, hypothesizing that cortical white matter degeneration would be observed in continuation of the peripheral white matter atrophy previously observed in HIV-DSP. Male HIV seropositive patients (n = 57) experiencing varying degrees of HIV neuropathy underwent single-shell diffusion tensor imaging with 51 sampling directions. The scans were pooled using tractography and connectometry to create a quantitative map of white matter tract integrity, measured in generalized fractional anisotropy (GFA). The relationship between GFA and neuropathy severity was evaluated with linear regression. Correction for multiple comparisons was done using false discovery rate (FDR), a statistical method commonly used in genomics and imaging to minimize false positives when thousands of individual comparisons are made. Neuropathy severity was associated with decreased GFA along thalamocortical radiations leading along the lateral thalamus to sensorimotor cortex, with r = -0.405 (p < 0.001; FDR), as well as with the superior bilateral cingulum (r = -0.346 (p < 0.05; FDR)). Among a population of HIV neuropathy patients, greater neuropathy severity was correlated with lower white matter integrity running from midbrain to somatosensory cortex. This suggests ascending deafferentation extending from damaged peripheral nerves further downstream than seen previously, into the axons of third-order neurons. There is also evidence of cingulum degeneration, implying some more complex mechanism beyond the ascending atrophy observed here.

Diffusion Tensor Imaging of the Dentate Nucleus After Repeated Administration of Gadobutrol in Children.

This study aimed to investigate possible signal changes in the dentate nucleus (DN) on diffusion tensor imaging (DTI) after administration of gadobutrol in a pediatric cohort. Total of 50 pediatric patients (mean age: 6.2 ± 4.3 years) with normal renal function exposed exclusively to the macrocyclic GBCA (mcGBCA) gadobutrol and 50 age- and sex-matched control patients with nonpathological neuroimaging findings (and no GBCA administration). Mean diffusivity (MD) and fractional anisotropy (FA) values were determined in the DN. A paired t test was performed to compare FA, MD values, and DN-to-middle cerebral peduncle (MCP) T1WI SI ratios between children exposed to gadobutrol and controls. Pearson correlation analysis was conducted to determine any correlation between FA and MD values as well as T1WI SI ratios and confounding parameters. The mean FA values of DN was significantly lower in children with mcGBCA than in the control group (p < 0.001; non-GBCA group, 0.299 ± 0.03; mcGBCA group, 0.254 ± 0.05), but no significant difference of the T1WI SI ratio was noted between the mcGBCA group (0.946 ± 0.06) and the control group (0.963 ± 0.05; p = 0.336). There was also a significant MD value difference between mcGBCA group and control group (p < 0.001; non-GBCA group, 0.152 ± 0.02 × 10-3 mm2/s; mcGBCA group, 0.173 ± 0.03 × 10-3 mm2/s). A significant correlation was identified between FA/MD values and the number of mcGBCA administration (FA; correlation coefficient = - 0.355, p = 0.011 and MD; correlation coefficient = 0.334, p = 0.018). The administration of the gadobutrol was associated with higher MD and lower FA values in DN suggesting a difference in cerebellar tissue integrity between children exposed to mcGBCAs and control group.

White matter brain changes in chronic pancreatitis: A 7-year longitudinal follow-up study.

BACKGROUND/OBJECTIVES: The progression of cerebral white matter changes over time has not been explored in chronic pancreatitis (CP). We aimed to characterize such alterations in individuals with CP at baseline and after 7-years as compared with controls and to explore associations to risk factors and clinical parameters. METHODS: Diffusion tensor imaging was used to evaluate 20 individuals with CP and 13 healthy controls at baseline and after 7-years (CP: n = 9, controls: n = 11). Tract-based spatial statistics were used to assess whole-brain white matter structure, extract significant fractional anisotropy (FA) clusters between groups, mean FA skeleton, mean FA and mean diffusivity (MD). FA of the extracted significant clusters between groups were used for regression analyses with risk factors and clinical parameters, including duration of CP, smoking, and diabetes. RESULTS: At baseline, widespread reductions in FA were found in CP compared to controls involving corpus callosum, the anterior, posterior thalamic radiation, and superior and posterior corona radiata (cluster volume: 49,431 mm3, all P < 0.05). At baseline, also the mean FA (P = 0.004) and FA skeleton (P = 0.002) were reduced in CP compared to controls. FA of the extracted significant cluster was associated with the daily tobacco use (P = 0.001) and duration of CP (P = 0.010). At follow-up, the whole-brain FA skeleton was reduced by 1.7% for both CP individuals and controls (P = 0.878). CONCLUSION: Individuals with CP had widespread cerebral white matter alterations at baseline that can likely be explained by the CP disease and exposure to toxic substances. Otherwise, further progression resembles that in healthy controls.