High-resolution Structural Imaging Research Articles

Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis.

Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD. A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients' perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets. Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS. This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

Association of neurostructural biomarkers with secondary attention-deficit/hyperactivity disorder (ADHD) symptom severity in children with traumatic brain injury: a prospective cohort study.

Despite a well-established link between childhood traumatic brain injury (TBI) and elevated secondary attention-deficit/hyperactivity disorder (s-ADHD) symptomology, the neurostructural correlates of these symptoms are largely unknown. Based on the influential 'triple-network model' of ADHD, this prospective longitudinal investigation aimed to (i) assess the effect of childhood TBI on brain morphometry of higher-order cognitive networks proposed to play a key role in ADHD pathophysiology, including the default-mode network (DMN), salience network (SN) and central executive network (CEN); and (ii) assess the independent prognostic value of DMN, SN and CEN morphometry in predicting s-ADHD symptom severity after childhood TBI. The study sample comprised 155 participants, including 112 children with medically confirmed mild-severe TBI ascertained from consecutive hospital admissions, and 43 typically developing (TD) children matched for age, sex and socio-economic status. High-resolution structural brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 103 children with TBI and 34 TD children. Parents completed well-validated measures of ADHD symptom severity at 12-months post injury. Relative to TD children and those with milder levels of TBI severity (mild, complicated mild, moderate), children with severe TBI showed altered brain morphometry within large-scale, higher-order cognitive networks, including significantly diminished grey matter volumes within the DMN, SN and CEN. When compared with the TD group, the TBI group showed significantly higher ADHD symptomatology and higher rates of clinically elevated symptoms. In multivariable models adjusted for other well-established risk factors, altered DMN morphometry independently predicted higher s-ADHD symptomatology at 12-months post-injury, whilst SN and CEN morphometry were not significant independent predictors. Our prospective study findings suggest that neurostructural alterations within higher-order cognitive circuitry may represent a prospective risk factor for s-ADHD symptomatology at 12-months post-injury in children with TBI. High-resolution structural brain MRI has potential to provide early prognostic biomarkers that may help early identification of high-risk children with TBI who are likely to benefit from early surveillance and preventive measures to optimise long-term neuropsychiatric outcomes.

The instant impact of a single hemodialysis session on brain morphological measurements in patients with end-stage renal disease.

ObjectiveTo investigate the instant impact of hemodialysis (HD) on the cerebral morphological measurements of patients with end-stage renal disease (ESRD).Materials and methodsTwenty-five patients undergoing maintenance HD and twenty-eight age-, sex-, and education-matched healthy control (HC) were included. The HD group and HC group had 3D high-resolution structural magnetic resonance imaging (MRI) scans twice and once, respectively. Both groups underwent neuropsychologic tests. The morphological measurements of structural MRI were measured using CAT12 and these measures were compared among three groups. The relationship between morphological measures and clinical parameters and neuropsychological tests were investigated through multiple regression analysis.ResultsCompared to the HC group, the cortical thickness before HD significantly decreased in the bilateral temporal lobe and significantly decreased in the left superior temporal gyrus after HD. The cortical thickness significantly increased in the bilateral temporal lobe, frontal lobe and occipital lobe after HD compared to before HD. The sulcus depth in the bilateral insula, frontal lobe, and parietal lobe after HD significantly increased compared to before HD. No significant differences in sulcus depth between HD and HC were detected. After HD, the cortical thickness of the right parsopercularis was positively correlated with the number connection test-A. Cortical thickness in multiple regions were positively correlated with blood flow velocity and cortical thickness in the left parahippocampal gyrus was negatively correlated with ultrafiltration volume. Patients showed better performance in the digit symbol test and line tracing test after HD compared to before HD, but there were no significant differences in the comparison of neuropsychologic tests between patients and HC.ConclusionThe instant morphological changes were captured during a single hemodialysis in HD patients. There was an association between these instant changes in the brain and clinical parameters and neuropsychologic tests. This work implied the instant impact of a single hemodialysis impact on the brain in HD patients.

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline.

ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

The association between ballroom dance training and empathic concern: Behavioral and brain evidence.

Dance is unique in that it is a sport and an art simultaneously. Beyond improving sensorimotor functions, dance training could benefit high-level emotional and cognitive functions. Duo dances also confer the possibility for dancers to develop the abilities to recognize, understand, and share the thoughts and feelings of their dance partners during the long-term dance training. To test this possibility, we collected high-resolution structural and resting-state functional magnetic resonance imaging (MRI) data from 43 expert-level ballroom dancers (a model of long-term exposure to duo dance training) and 40 age-matched and sex-matched nondancers, and measured their empathic ability using a self-report trait empathy scale. We found that ballroom dancers showed higher scores of empathic concern (EC) than controls. The EC scores were positively correlated with years with dance partners but negatively correlated with the number of dance partners for ballroom dancers. These behavioral results were supported by the structural and functional MRI data. Structurally, we observed that the gray matter volumes in the subgenual anterior cingulate cortex (ACC) and EC scores were positively correlated. Functionally, the connectivity between ACC and occipital gyrus was positively correlated with both EC scores and years with dance partners. In addition, the relationship between years with dance partners and EC scores was indirect-only mediated by the ACC-occipital gyrus functional connectivity. Therefore, our findings provided solid evidence for the close link between long-term ballroom dance training and empathy, which deepens our understanding of the neural mechanisms underlying this phenomenon.

Potential of Phase-Amplitude-Based Multi-Scale Full Waveform Inversion with Total-Variation Regularization for Seismic Imaging of Deep-Seated Ores

As the demand for ore resources increases, the target for mineral exploration gradually shifts from shallow to deep parts of the Earth (&gt;1 km). However, for the ore-hosting strata, it is difficult to obtain high-resolution images by using the electromagnetic method. Seismic full waveform inversion (FWI) is an optimization algorithm which aims at minimizing the prestack seismic data residual between synthetic and observed data. In this case, FWI provides an effective way to achieve high-resolution imaging of subsurface structures. However, acquired seismic data usually lack low frequencies, resulting in severe cycle skipping of FWI, when the initial velocity model is far away from the true one. Phase information in the seismic data provides the kinematic characteristics of waves and has a quasi-linearly relationship with subsurface structures. In this article, we propose to use a phase-amplitude-based full waveform inversion with total-variation regularization (TV-PAFWI) to invert the deep-seated ores. The ore-hosting velocity model test results demonstrate that the TV-PAFWI is suitable for high-resolution velocity model building, especially for deep-seated ores.

PLACENTAL HISTOPATHOLOGY CORRELATION WITH ANTENATAL UMBILICAL AND UTERINE ARTERY DOPPLER

Defective placentation results in a host of pregnancy complications like fetal loss, preeclampsia, and fetal growth restriction and abruptio placentae. There have been recent major advances in obstetric ultrasound such as high-resolution antenatal structural imaging, determination of maternal and fetal blood ow parameters and 3D and 4D ultrasound, which have revolutionised the obstetric care by antenatal diagnosis of placental pathology and its effect on the fetuses. The aim of this study is to correlate placental pathology ndings to antenatal Doppler and ultrasonogram and fetal outcome. : All placental specimens received in the department of Pathology, Karnataka Institute of MedicalMETHODS sciences, Hubballi from October 2017 to March 2019 were collected after taking an informed consent. All the casesINCLUSION CRITERIA: with antenatal Doppler and ultrasonogram details, irrespective of the gestational age and fetal outcome. UnbookedEXCLUSION CRITERIA: cases and cases without clinical history and image ndings. 115 cases Gross examination was done and sections were takenSAMPLE SIZE: from parenchyma, umbilical cord and the membranes according to Amsterdam guidelines for microscopic examination. The resultant microscopic ndings were correlated with antenatal Doppler and ultrasonogram. 115 of the 539 cases included in this study had Doppler data,RESULTS: among them, 19 cases showed abnormal Doppler. Placentae with abnormal Doppler ndings showed increased syncytial knots, poor vasculo- syncytial membrane, villous crowding and infarct (p&lt;0.05) and were associated with increased fetal death and growth restriction. CONCLUSION: Placental study correlated with the Doppler ndings and was instrumental in reaching a specic diagnosis in inconclusive cases.

Morphological Changes of Frontal Areas in Male Individuals With HIV: A Deformation-Based Morphometry Analysis.

ObjectivePrevious studies on HIV-infected (HIV+) individuals have revealed brain structural alterations underlying HIV-associated neurocognitive disorders. Most studies have adopted the widely used voxel-based morphological analysis of T1-weighted images or tracked-based analysis of diffusion tensor images. In this study, we investigated the HIV-related morphological changes using the deformation-based morphometry (DBM) analysis of T1-weighted images, which is another useful tool with high regional sensitivity.Materials and MethodsA total of 157 HIV+ (34.7 ± 8.5 years old) and 110 age-matched HIV-uninfected (HIV-) (33.7 ± 10.1 years old) men were recruited. All participants underwent neurocognitive assessments and brain scans, including high-resolution structural imaging and resting-state functional imaging. Structural alterations in HIV+ individuals were analyzed using DBM. Functional brain networks connected to the deformed regions were further investigated in a seed-based connectivity analysis. The correlations between imaging and cognitive or clinical measures were examined.ResultsThe DBM analysis revealed decreased values (i.e., tissue atrophy) in the bilateral frontal regions in the HIV+ group, including bilateral superior frontal gyrus, left middle frontal gyrus, and their neighboring white matter tract, superior corona radiata. The functional connectivity between the right superior frontal gyrus and the right inferior temporal region was enhanced in the HIV+ group, the connectivity strength of which was significantly correlated with the global deficit scores (r = 0.214, P = 0.034), and deficits in learning (r = 0.246, P = 0.014) and recall (r = 0.218, P = 0.031). Increased DBM indexes (i.e., tissue enlargement) of the right cerebellum were also observed in the HIV+ group.ConclusionThe current study revealed both gray and white matter volume changes in frontal regions and cerebellum in HIV+ individuals using DBM, complementing previous voxel-based morphological studies. Structural alterations were not limited to the local regions but were accompanied by disrupted functional connectivity between them and other relevant regions. Disruptions in neural networks were associated with cognitive performance, which may be related to HIV-associated neurocognitive disorders.

Exploring Honeybee Abdominal Anatomy through Micro-CT and Novel Multi-Staining Approaches.

Simple SummaryApis mellifera or western honeybees are insects belonging to the Order Hymenoptera and the most important pollinators worldwide with great implications in natural biodiversity and agriculture due to their importance in pollination and honey production. The characterization of honeybee anatomy with precise tools will allow a better comprehension of the physiology of these insects under different biological conditions. Here, we employed Micro-computed tomography and novel staining methods to define the morphoanatomical characteristics of the worker honeybee abdomen. We defined the 3D and 2Ds structures of the midgut and hindgut and discovered a new cell type called ventricular telocyte, with possible roles in honeybee epithelium maintenance. Overall, we propose that this method will be useful for further investigation of the structure of the honeybee abdomen under a wide variety of environmental conditions.Continuous improvements in morphological and histochemical analyses of Apis mellifera could improve our understanding of the anatomy and physiology of these insects at both the cellular and tissue level. In this work, two different approaches have been performed to add new data on the abdomen of worker bees: (i) Micro-computed tomography (Micro-CT), which allows the identification of small-scale structures (micrometers) with adequate/optimal resolution and avoids sample damage and, (ii) histochemical multi-staining with Periodic Acid-Schiff-Alcian blue, Lactophenol-Saphranin O and pentachrome staining to precisely characterize the histological structures of the midgut and hindgut. Micro-CT allowed high-resolution imaging of anatomical structures of the honeybee abdomen with particular emphasis on the proventriculus and pyloric valves, as well as the connection of the sting apparatus with the terminal abdominal ganglia. Furthermore, the histochemical analyses have allowed for the first-time description of ventricular telocytes in honeybees, a cell type located underneath the midgut epithelium characterized by thin and long cytoplasmic projections called telopodes. Overall, the analysis of these images could help the detailed anatomical description of the cryptic structures of honeybees and also the characterization of changes due to abiotic or biotic stress conditions.

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models.

Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.

Neonatal Pain, Opioid, and Anesthetic Exposure; What Remains in the Human Brain After the Wheels of Time?

ObjectiveTo evaluate possible negative long-term effects of neonatal exposure to pain, opioids and anesthetics in children and adolescents.Study DesignWe studied five unique groups of children recruited from well-documented neonatal cohorts with a history of neonatal exposure to pain, opioids or anesthetics at different points along the continuum from no pain to intense pain and from no opioid exposure to very high opioid exposure in the presence or absence of anesthetics. We evaluated children who underwent major surgery (group 1 and 2), extracorporeal membrane oxygenation (group 3), preterm birth (group 4) and prenatal opioid exposure (group 5) in comparison to healthy controls. Neuropsychological functioning, thermal detection and pain thresholds and high-resolution structural and task-based functional magnetic resonance imaging during pain were assessed. In total 94 cases were included and compared to their own control groups.ResultsChildren and adolescents in groups 3 and 5 showed worse neuropsychological functioning after high opioid exposure. A thicker cortex was found in group 1 (pain, opioid and anesthetic exposure) in only the left rostral-middle-frontal-cortex compared to controls. We found no differences in other brain volumes, pain thresholds or brain activity during pain in pain related brain regions between the other groups and their controls.ConclusionsNo major effects of neonatal pain, opioid or anesthetic exposure were observed in humans 8–19 years after exposure in early life, apart from neuropsychological effects in the groups with the highest opioid exposure that warrants further investigation. Studies with larger sample sizes are needed to confirm our findings and test for less pronounced differences between exposed and unexposed children.

Grey Matter Hypertrophy and Atrophy in Early-Blind Adolescents: A Surface-Based Morphometric Study.

Objective This study is aimed at exploring the regional changes in brain cortical morphology (thickness, volume, and surface area) in the early-blind adolescents (EBAs) by using the surface-based morphometric (SBM) method. Methods High-resolution structural T1-weighted images (T1WI) of 23 early-blind adolescents (EBAs) and 21 age- and gender-matched normal-sighted controls (NSCs) were acquired. Structural indices, including cortical thickness (CT), cortical volume (CV), and surface area (SA), were analyzed by using FreeSurfer software, and the correlations between structural indices and the blindness duration were computed by Pearson correlation analysis. Results Compared to controls, EBAs had significantly reduced CV and SA mainly in the primary visual cortex (V1) and decreased CV in the left vision-related cortices (r-MFC). There were no regions that EBAs had a significantly larger CV or SA than NSCs. EBAs had significantly increased CT in the V1 and strongly involved the visual cortex (right lateral occipital gyrus, LOG.R) and the left superior temporal gyrus (STG.L), while it had decreased CT in the left superior parietal lobule (SPL.L) and the right lingual gyrus (LING.R). Additionally, no correlation was found between cortical morphometric measures and clinical variables in the EBA group. Conclusions SBM is a useful method for detecting human brain structural abnormalities in blindness. The results showed that these structural abnormalities in the visual cortex and visual-related areas outside the occipital cortex in the EBAs not only may be influenced by neurodevelopment, degeneration, plasticity, and so on but also involved the interaction of these factors after the early visual deprivation.

Implementation of tissue clearing and 3‐dimensional volumetric imaging approaches for visualization of anatomical structures in autonomic nuclei

Alterations within central nervous system (CNS) autonomic nuclei contribute to a wide array of diseases. In this context, significant advancements have been made into disease‐related molecular mechanisms in autonomic brain regions. While helpful, it is important to consider that information processing within the CNS occurs through dynamic micro‐architectural structural interactions, such astrocyte‐neuron synaptic connections. However the traditional method for evaluating CNS morphology and synaptic contacts between cells is performed with immunohistochemistry on thin brain sections. An inherent limitation of this approach is not only the narrow 2‐dimensional field of view, but also the lack of optical transparency that minimizes high‐resolution imaging of anatomical structures and cell‐cell interactions. To overcome these limitations, here we sought to optimize tissue clearing approaches combined with 3D volumetric imaging for autonomic CNS nuclei. We focused our initial efforts on the forebrain subfornical organ (SFO), a region lacking a blood‐brain‐barrier, given: 1 Alterations in the SFO have been described to contribute to numerous disease conditions; and 2 The SFO represents a unique technical challenge for 3D imaging due to the complexity of cellular processes and surrounding lateral ventricle space. As a first step, we used a “passive” CLARITY tissue approach in 8‐week‐old C57Bl/6J male mice. Mice were transcardially perfused with an acrylamide‐based hydrogel in standard fixative. Subsequently, a brain section encompassing the entire SFO (~1mm) was obtained, and a series of thermal diffusion steps was performed to place existing protein structures in a “scaffold” and remove the lipid contents ‐ rendering the tissue transparent. Whole‐mount immunohistochemistry for astrocytes was then conducted using GFAP and DAPI as a nuclei marker, followed by 3D volumetric multiphoton imaging to acquire high‐resolution visualization of the entire SFO in three planes (Figure top). In brief, this approach proved to be a significant advancement beyond standard 2D histology, and 3D visualization of intricate astrocyte processes throughout the whole SFO was possible. However, a major limitation was the extensive amount of time required to process a single sample; 2 weeks for tissue clearing and 2 weeks for primary and secondary antibody incubation. Based on this, we adapted our protocol to an “active” CLARITY approach and employed electrophoretic‐based clearing of large brain sections (n=5), which resulted in a reduction in clearing time from 2 weeks to 4 hours. It was also readily apparent that this approach rendered the tissue more transparent than passive clearing, allowing for greater visualization of astrocyte processes (Figure middle). Preliminary analysis with IMARIS software to analyze astrocyte surface area and dendritic processing (Figure bottom) revealed highly complex SFO astrocytic structures with some dendrites extending from soma at the lateral ventricle throughout and surrounding nearly the entire SFO; these processes are not visualized with standard histology. Collectively, these approaches highlight the utility of tissue‐based clearing for 3D visualization of anatomical structures within autonomic nuclei and provide a framework to understand structure‐function relationships within these brain regions in the regulation of physiological and pathophysiological conditions.

Loss of superiority illusion in bipolar depressive disorder: A combined functional and structural MRI study

Superiority illusion (SI) is a positive cognitive bias related to self, manifested as overestimated self-appraisal. Negative self-schema is a core feature of the cognitive model of depression, including bipolar depressive disorder (BDD). However, only little research has explored the impaired self-processing in BDD. The potential alteration of positive self-bias and the corresponding neural mechanism in BDD remains unclear. This study aimed to investigate the underlying neural mechanism of self-processing in BDD combining task-related functional magnetic resonance imaging and high-resolution T1 structural imaging. Forty-three BDD and forty-eight healthy controls were recruited and underwent a self-related task, where participants were required to evaluate how they compared with their average peers on a serial of positive and negative traits. We defined the ratio of neural activation and gray matter volume (GMV) in a region as the functional–structural coupling index to detect the changes of brain image in BDD. Furthermore, we used moderation analysis to explore the relationship among functional–structural coupling, behavioral scores and depression symptoms. BDD exhibited decreased task activation, GMV, and functional–structural coupling in bilateral anterior insula (AI) and inferior parietal lobule (IPL). The associations between functional–structural coupling in the right AI, IPL and negative trait self-rating scores were moderated by depressive symptom severity. The study revealed disturbed self-related processing and provided new evidences to neuropsychological dysfunction in BDD.

Association between stressful life events and grey matter volume in the medial prefrontal cortex: A 2‐year longitudinal study

Stressful life events (SLEs) in adulthood are a risk factor for various disorders such as depression, cancer or infections. Part of this risk is mediated through pathways altering brain physiology and structure. There is a lack of longitudinal studies examining associations between SLEs and brain structural changes. High‐resolution structural magnetic resonance imaging data of 212 healthy subjects were acquired at baseline and after 2 years. Voxel‐based morphometry was used to identify associations between SLEs using the Life Events Questionnaire and grey matter volume (GMV) changes during the 2‐year period in an ROI approach. Furthermore, we assessed adverse childhood experiences as a possible moderator of SLEs‐GMV change associations. SLEs were negatively associated with GMV changes in the left medial prefrontal cortex. This association was stronger when subjects had experienced adverse childhood experiences. The medial prefrontal cortex has previously been associated with stress‐related disorders. The present findings represent a potential neural basis of the diathesis‐stress model of various disorders.

P 39 MRI-based geometric modeling for transcranial current stimulation in mild cognitive impairment converters

Question: Transcranial direct current stimulation (tDCS) is a fast-growing field in rehabilitation medicine. However, the stimulation-induced E-field may be uneven on the highly folded cortical surface and thus leads to heterogeneous results in clinical trials. This challenge has been addressed by the analytical methods applicable to quantitatively measure the geometric features derived from the high-resolution structural magnetic resonance imaging (MRI). As a set of novel geometric measures, the geometric features of the folded cortex could be decomposed into scalp-to-cortex distance (SCD), cortical thickness and gyrification. Beyond MRI-based measures, learnings from computational geometric models will be beneficial as this field embraces biophysics and engineering. This study aimed to examine and quantify the cortical morphometry of bilateral dorsolateral prefrontal cortex (DLPFC) and its impact on the E-field during pathological ageing. Methods: Baseline, 1-year and 3-year follow-up structural magnetic resonance imaging scans from normal ageing (NA) adults (n = 32), and mild cognitive impairment (MCI) converters (n = 22) were drawn from the Open Access Series of Imaging Studies (OASIS-2). The quantitative measures of region-specific morphometry included gyrification, cortical thickness (mm), surface area (mm2) and volume (mm3). Head model was developed to simulate the impact of morphometric changes on the E-field induced by tDCS. Results: Ageing had a nonlinear effect on the changes of volume and cortical thickness in the bilateral DLPFC. A pronounced ageing-related reduction was found in the gyrification of left DLPFC in MCI converters, which could predict the global cognition decline at the 3-year follow-up. Along with the reduced gyrification in left DLPFC, the E-field intensity of tDCS model was consequently decreased in MCI converters. Conclusions: Ageing has a prominent effect on region-specific cortical morphometry that leads to decreased E-field intensity in old adults with cognitive impairments. Our findings have important implications for conducting the transcranial brain stimulation in individuals with brain atrophy, such as Alzheimer’s Disease.

High-resolution three-dimensional blood flow tomography in the subdiffuse regime using laser speckle contrast imaging.

Significance: Visualizing high-resolution hemodynamics in cerebral tissue over a large field of view (FOV), provides important information in studying disease states affecting the brain. Current state-of-the-art optical blood flow imaging techniques either lack spatial resolution or are too slow to provide high temporal resolution reconstruction of flow map over a large FOV.Aim: We present a high spatial resolution computational optical imaging technique based on principles of laser speckle contrast imaging (LSCI) for reconstructing the blood flow maps in complex tissue over a large FOV provided that the three-dimensional (3D) vascular structure is known or assumed.Approach: Our proposed method uses a perturbation Monte Carlo simulation of the high-resolution 3D geometry for both accurately deriving the speckle contrast forward model and calculating the Jacobian matrix used in our reconstruction algorithm to achieve high resolution. Given the convex nature of our highly nonlinear problem, we implemented a mini-batch gradient descent with an adaptive learning rate optimization method to iteratively reconstruct the blood flow map. Specifically, we implemented advanced optimization techniques combined with efficient parallelization and vectorization of the forward and derivative calculations to make reconstruction of the blood flow map feasible with reconstruction times on the order of tens of minutes.Results: We tested our reconstruction algorithm through simulation of both a flow phantom model as well as an anatomically correct murine cerebral tissue and vasculature captured via two-photon microscopy. Additionally, we performed a noise study, examining the robustness of our inverse model in presence of 0.1% and 1% additive noise. In all cases, the blood flow reconstruction error was for most of the vasculature, except for the peripheral vasculature which suffered from insufficient photon sampling. Descending vasculature and deeper structures showed slightly higher sensitivity to noise compared with vasculature with a horizontal orientation at the more superficial layers. Our results show high-resolution reconstruction of the blood flow map in tissue down to and beyond.Conclusions: We have demonstrated a high-resolution computational imaging technique for visualizing blood flow map in complex tissue over a large FOV. Once a high-resolution structural image is captured, our reconstruction algorithm only requires a few LSCI images captured through a camera to reconstruct the blood flow map computationally at a high resolution. We note that the combination of high temporal and spatial resolution of our reconstruction algorithm makes the solution well-suited for applications involving fast monitoring of flow dynamics over a large FOV, such as in functional neural imaging.

Changes in Hippocampus and Amygdala Volume with Hypoxic Stress Related to Cardiorespiratory Fitness under a High-Altitude Environment.

The morphology of the hippocampus and amygdala can be significantly affected by a long-term hypoxia-induced inflammatory response. Cardiorespiratory fitness (CRF) has a significant effect on the neuroplasticity of the hippocampus and amygdala by countering inflammation. However, the role of CRF is still largely unclear at high altitudes. Here, we investigated brain limbic volumes in participants who had experienced long-term hypoxia exposure in Tibet (3680 m), utilizing high-resolution structural images to allow the segmentation of the hippocampus and amygdala into their constituent substructures. We recruited a total of 48 participants (48 males; aged = 20.92 ± 1.03 years) to undergo a structural 3T MRI, and the levels of maximal oxygen uptake (VO2max) were measured using a cardiorespiratory function test. Inflammatory biomarkers were also collected. The participants were divided into two groups according to the levels of median VO2max, and the analysis showed that the morphological indexes of subfields of the hippocampus and amygdala of the lower CRF group were decreased when compared with the higher CRF group. Furthermore, the multiple linear regression analysis showed that there was a higher association with inflammatory factors in the lower CRF group than that in the higher CRF group. This study suggested a significant association of CRF with hippocampus and amygdala volume, which may be related to hypoxic stress in high-altitude environments. A better CRF reduced physiological stress and a decrease in the inflammatory response was observed, which may be related to the increased oxygen transport capacity of the body.

Improving Imaging of the Brainstem and Cerebellum in Autistic Children: Transformation-Based High-Resolution Diffusion MRI (TiDi-Fused) in the Human Brainstem.

Diffusion-weighted magnetic resonance imaging (dMRI) of the brainstem is technically challenging, especially in young autistic children as nearby tissue-air interfaces and motion (voluntary and physiological) can lead to artifacts. This limits the availability of high-resolution images, which are desirable for improving the ability to study brainstem structures. Furthermore, inherently low signal-to-noise ratios, geometric distortions, and sensitivity to motion not related to molecular diffusion have resulted in limited techniques for high-resolution data acquisition compared to other modalities such as T1-weighted imaging. Here, we implement a method for achieving increased apparent spatial resolution in pediatric dMRI that hinges on accurate geometric distortion correction and on high fidelity within subject image registration between dMRI and magnetization prepared rapid acquisition gradient echo (MPnRAGE) images. We call this post-processing pipeline T1 weighted-diffusion fused, or “TiDi-Fused”. Data used in this work consists of dMRI data (2.4 mm resolution, corrected using FSL’s Topup) and T1-weighted (T1w) MPnRAGE anatomical data (1 mm resolution) acquired from 128 autistic and non-autistic children (ages 6–10 years old). Accurate correction of geometric distortion permitted for a further increase in apparent resolution of the dMRI scan via boundary-based registration to the MPnRAGE T1w. Estimation of fiber orientation distributions and further analyses were carried out in the T1w space. Data processed with the TiDi-Fused method were qualitatively and quantitatively compared to data processed with conventional dMRI processing methods. Results show the advantages of the TiDi-Fused pipeline including sharper brainstem gray-white matter tissue contrast, improved inter-subject spatial alignment for group analyses of dMRI based measures, accurate spatial alignment with histology-based imaging of the brainstem, reduced variability in brainstem-cerebellar white matter tracts, and more robust biologically plausible relationships between age and brainstem-cerebellar white matter tracts. Overall, this work identifies a promising pipeline for achieving high-resolution imaging of brainstem structures in pediatric and clinical populations who may not be able to endure long scan times. This pipeline may serve as a gateway for feasibly elucidating brainstem contributions to autism and other conditions.

Polarization Sensitive Photothermal Mid-Infrared Spectroscopic Imaging of Human Bone Marrow Tissue.

Collagen quantity and integrity play an important role in understanding diseases such as myelofibrosis (MF). Label-free mid-infrared spectroscopic imaging (MIRSI) has the potential to quantify collagen while minimizing the subjective variance observed with conventional histopathology. Infrared (IR) spectroscopy with polarization sensitivity provides chemical information while also estimating tissue dichroism. This can potentially aid MF grading by revealing the structure and orientation of collagen fibers. Simultaneous measurement of collagen structure and biochemical properties can translate clinically into improved diagnosis and enhance our understanding of disease progression. In this paper, we present the first report of polarization-dependent spectroscopic variations in collagen from human bone marrow samples. We build on prior work with animal models and extend it to human clinical biopsies with a practical method for high-resolution chemical and structural imaging of bone marrow on clinical glass slides. This is done using a new polarization-sensitive photothermal mid-infrared spectroscopic imaging scheme that enables sample and source independent polarization control. This technology provides 0.5µm spatial resolution, enabling the identification of thin (≈1µm) collagen fibers that were not separable using Fourier Transform Infrared (FT-IR) imaging in the fingerprint region at diffraction-limited resolution ( ≈ 5µm). Finally, we propose quantitative metrics to identify fiber orientation from discrete band images (amide I and amide II) measured under three polarizations. Previous studies have used a pair of orthogonal polarization measurements, which is insufficient for clinical samples since human bone biopsies contain collagen fibers with multiple orientations. Here, we address this challenge and demonstrate that three polarization measurements are necessary to resolve orientation ambiguity in clinical bone marrow samples. This is also the first study to demonstrate the ability to spectroscopically identify thin collagen fibers (≈1µm diameter) and their orientations, which is critical for accurate grading of human bone marrow fibrosis.