Changes In Microstructural Integrity Research Articles

Diffusion tensor imaging analysis of rheumatoid arthritis patients with neuropsychiatric features to determine the alteration of white matter integrity due to vascular events.

The pathophysiology of neuropsychiatric manifestations in rheumatoid arthritis is not well known. The magnetic resonance imaging of the brain in rheumatoid arthritis demonstrates non-specific findings, and in the majority of cases, magnetic resonance imaging fails to detect an abnormality, even in rheumatoid arthritis patients with neuropsychiatric manifestations. Therefore, we aimed to assess microstructural integrity changes of white matter in patients with rheumatoid arthritis by using different diffusion tensor imaging parameters. Eighteen rheumatoid arthritis patients (10 with neuropsychiatric symptoms and 8 without any neuropsychiatric symptoms) and 14 controls were included. The volume of the T2 hyperintense lesions was assessed. Different diffusion tensor imaging parameters such as fractional anisotropy, apparent diffusion coefficient, trace, axial diffusivity, and radial diffusivity were obtained from six different regions of white matter. Inter group significant difference was determined by one-way analysis of variance followed by Tukey's post hoc test. The accuracy of diffusion tensor imaging matrices was evaluated from the receiver operating characteristic curve. No significant difference in lesions' volume was detected between rheumatoid arthritis patients with or without neuropsychiatric symptoms. There was an increased apparent diffusion coefficient and radial diffusivity (p < 0.05) as well as decreased fractional anisotropy and axial diffusivity (p < 0.5) in rheumatoid arthritis patients with neuropsychiatric symptoms compared to controls. Moreover, the apparent diffusion coefficient (p < .05) was increased in both positive and negative MRI of patients with neuropsychiatric features compared to the control group. The sensitivity and specificity of the apparent diffusion coefficient parameters was 73% and 72%, respectively. The various anisotropic metrics were altered in rheumatoid arthritis patients with neuropsychiatric symptoms by using diffusion tensor imaging analysis, representing that central nervous system vasculitis leads to tissue hypoxia resulting in vasogenic edema. This may lead to axonal and myelin degeneration of white matter fibers and neuronal cell disruption. Key Points • Our study confirms that neurovascular events are not uncommon in RA patients with NP features. Diffusion tensor imaging (DTI) is superior to conventional MRI scan for RA patients with NP features because it distinguishes between gray and white matter structures. • RA patients with NP features are more likely to have microstructural changes detected by DTI than by DWI, and it can provide comprehensive anatomical layouts describing regional disparities in neurodegeneration. • DTI's quantitative association of NP symptoms in a large patient cohort is an important study scope.

FV 17 Wallerian degeneration of descending fiber tracts explains motor impairment after stroke

Introduction: Structural changes post-stroke have frequently been assessed using diffusion tensor imaging (DTI). While the microstructural integrity of various parts of the corticospinal tract (CST) has been linked to motor impairment 1 , it remains unclear whether the reduction in anisotropy can be attributed to descending or crossing fibers within the CST. To address this question, we used diffusion spectrum imaging (DSI), an advanced imaging approach that overcomes the shortcomings of DTI, and delineated the influence of CST-inherent crossing and descending fibers. Patients and Methods: DSI scans of 25 chronic stroke patients (mean age=66.7, sd=11.2) and 22 age-matched controls were corrected for motion-and distortion artifacts, reconstructed, and normalized using QSIPrep 2 . Lesion and individual white matter (WM) masks were applied to the resulting generalized fractional anisotropy (gfa)-maps, focusing the analysis on secondary degeneration in WM-tracts. A deterministic mask containing the number of trackable directions per voxel 3 was applied to compartmentalize whole-brain gfa-values. Compartment-wise mean gfa was extracted from motor tracts as defined in the HCP tractography atlas 4 . Using these values, we tested for differences between patients and controls and for an association with upper and lower limb motor impairment. Results: Patients featured reduced gfa-values within the affected CST compared to age-matched controls (t(45)=-3.35, p=.002). This difference was mainly attributable to voxels containing only one fiber direction (t(45)=-3.92, p<.001), i.e., descending fibers, while voxels containing two directions, i.e., crossing fibers, showed no difference (p>0.4). Mean gfa of the affected CST significantly explained upper limb impairment (R 2 =0.30, p=.005), especially for patients suffering from persistent motor deficits (R 2 =0.43, p=.01). This association was driven by unidirectional (R 2 =0.26, p=.009) and not multidirectional voxels (p>0.3). Mean-gfa within the rubrospinal tract was related to persisting lower limb deficits. Conclusion: Anisotropy measures of the CST derived from DSI were significantly reduced and explained upper limb motor impairment in chronic stroke patients. These findings were driven by voxels containing a single fiber direction suggesting that changes in microstructural integrity of motor pathways assessed via diffusion imaging originate from Wallerian degeneration of descending fibers. In non-fully recovered stroke patients with CST damage, extrapyramidal pathways such as the rubrospinal tract may contribute to leg movements, potentially reflecting a compensatory mechanism after CST damage. Our findings underline the potential of DSI to predict motor outcome, especially when focusing the analysis on descending fibers via compartmentalization. References 1 Koch et al., 2016, Annals Clin Transl Neurol. 2 Cieslak et al., 2021, Nature Methods. 3 Volz et al., 2018, Brain Struct Funct. 4 Yeh et al., 2018, NeuroImage.

Magnetisation transfer imaging revealed microstructural changes related to apathy symptoms after ischaemic stroke.

Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p=0.003). These associations were independent of depressive symptoms. Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

Diffusion tensor imaging analysis in scrub typhus meningoencephalitis to determine the alteration of microstructural subcortical white-matter integrity.

Magnetic resonance imaging (MRI) of the brain in scrub typhus meningoencephalitis is non-specific, and in the majority of the cases, conventional MRI fails to detect any abnormality. However, autopsy reports depict central nervous system involvement in almost all patients. There is therefore a need for research on the quantitative assessment of brain parenchyma that can detect microstructural abnormalities. The study aimed to assess the microstructural integrity changes of scrub typhus meningoencephalitis by using different diffusion tensor imaging (DTI) parameters. This was a retrospective analysis of scrub typhus meningoencephalitis. Seven patients and seven age- and sex-matched healthy controls were included. Different DTI parameters such as apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), trace, volume ratio (VR) and geodesic anisotropy (GA) were obtained from six different regions of subcortical white matter at the level of the centrum semiovale. Intergroup significant difference was determined by one-way analysis of variance followed by Tukey's post hoc test. Receiver operating characteristic curves were constructed to determine the accuracy of the DTI matrices. There was a significant decrease in FA, RA and GA as well as an increase in ADC and VR in the subcortical white matter in patients with scrub typhus meningoencephalitis compared to controls (p < 0.001). The maximum sensitivity of the DTI parameters was 85.7%, and the maximum specificity was 81%. There was an alteration of subcortical white-matter integrity in scrub typhus meningoencephalitis that represents the axonal degeneration, myelin breakdown and neuronal degeneration. DTI may be a useful tool to detect white-matter abnormalities in scrub typhus meningoencephalitis in clinical practice, particularly in patients with negative conventional MRI.

Endovascular stroke treatment using balloon guide catheters may reduce penumbral tissue damage and improve long-term outcome

ObjectivesDuring mechanical recanalization of large vessel occlusions (LVO), the use of proximal flow arrest with balloon guide catheters (BGC) was shown to be associated with better angiographic and even clinical outcome. The aim of the study was to analyze the impact of BGC use on microstructural alterations in the salvaged penumbra.MethodsAll patients who underwent mechanical recanalization of LVO of the anterior circulation were reviewed within a prospective stroke registry of a single comprehensive stroke center. Fifty-two patients received an admission CT perfusion together with post-interventional diffusion tensor imaging. Technical details such as BGC usage were correlated with microstructural integrity changes of the salvaged gray matter through the mean diffusivity (MD) index. Moderation analysis was performed to test the interaction of BGC on the correlation between angiographic and clinical outcomes.ResultsFor all patients with complete reperfusion, microstructural integrity changes with lowered MD index were found within the salvaged penumbra for cases of non-BGC usage (mean − 0.02) compared to cases with BGC usage (0.01, p = 0.04). The importance of complete reperfusion for good clinical outcome is predominantly based on patients treated with BGC (effect 2.78, p = 0.01 vs. for non-BGC: 0.3, p = 0.71).ConclusionsThe lowered MD index early after mechanical recanalization without BGC usage can be interpreted as microstructural ischemic damage of the salvaged penumbra. It was shown that achieving complete reperfusion in a setting of BGC usage with proximal flow arrest minimizes penumbral damage and improves long-term outcomes.Key Points• Microstructural ischemic damage can be reduced by using proximal flow arrest during endovascular treatment with balloon guide catheter.• Complete reperfusion in a setting of balloon guide catheter minimizes penumbral damage and improves long-term outcome.

T2 heterogeneity: a novel marker of microstructural integrity associated with cognitive decline in people with mild cognitive impairment

BackgroundEarly Alzheimer’s disease (AD) diagnosis is vital for development of disease-modifying therapies. Prior to significant brain tissue atrophy, several microstructural changes take place as a result of Alzheimer’s pathology. These include deposition of amyloid, tau and iron, as well as altered water homeostasis in tissue and some cell death. T2 relaxation time, a quantitative MRI measure, is sensitive to these changes and may be a useful non-invasive, early marker of tissue integrity which could predict conversion to dementia. We propose that different microstructural changes affect T2 in opposing ways, such that average ‘midpoint’ measures of T2 are less sensitive than measuring distribution width (heterogeneity). T2 heterogeneity in the brain may present a sensitive early marker of AD pathology.MethodsIn this cohort study, we tested 97 healthy older controls, 49 people with mild cognitive impairment (MCI) and 10 with a clinical diagnosis of AD. All participants underwent structural MRI including a multi-echo sequence for quantitative T2 assessment. Cognitive change over 1 year was assessed in 20 participants with MCI. T2 distributions were modelled in the hippocampus and thalamus using log-logistic distribution giving measures of log-median value (midpoint; T2μ) and distribution width (heterogeneity; T2σ).ResultsWe show an increase in T2 heterogeneity (T2σ; p < .0001) in MCI compared to healthy controls, which was not seen with midpoint (T2μ; p = .149) in the hippocampus and thalamus. Hippocampal T2 heterogeneity predicted cognitive decline over 1 year in MCI participants (p = .018), but midpoint (p = .132) and volume (p = .315) did not. Age affects T2, but the effects described here are significant even after correcting for age.ConclusionsWe show that T2 heterogeneity can identify subtle changes in microstructural integrity of brain tissue in MCI and predict cognitive decline over a year. We describe a new model that considers the competing effects of factors that both increase and decrease T2. These two opposing forces suggest that previous conclusions based on T2 midpoint may have obscured the true potential of T2 as a marker of subtle neuropathology. We propose that T2 heterogeneity reflects microstructural integrity with potential to be a widely used early biomarker of conditions such as AD.

Assessing changes in microstructural integrity of white matter tracts in children with leukaemia following exposure to chemotherapy.

Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage. To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy. Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points. Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment. The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

Diffusion tensor imaging of lumbar spinal nerves reveals changes in microstructural integrity following decompression surgery associated with improvements in clinical symptoms: A case report

The outcomes from spinal nerve decompression surgery are highly variable with a sizable proportion of elderly foraminal stenosis patients not regaining good pain relief. A better understanding of nerve root compression before and following decompression surgery and whether these changes are mirrored by improvements in symptoms may help to improve clinical decision-making processes. This case study used a combination of diffusion tensor imaging (DTI), clinical questionnaires and motor neurophysiology assessments before and up to 3 months following spinal decompression surgery. In this case report, a 70-year-old women with compression of the left L5 spinal nerve root in the L5-S1 exit foramina was recruited to the study. At 3 months following surgery, DTI revealed marked improvements in left L5 microstructural integrity to a similar level to that seen in the intact right L5 nerve root. This was accompanied by a gradual improvement in pain-related symptoms, mood and disability score by 3 months. Using this novel multimodal approach, it may be possible to track concurrent improvements in pain-related symptoms, function and microstructural integrity of compressed nerves in elderly foraminal stenosis patients undergoing decompression surgery.

Microstructural Integrity of Salvaged Penumbra after Mechanical Thrombectomy.

There are sparse data on the microstructural integrity of salvaged penumbral tissue after mechanical thrombectomy of large-vessel occlusions. The aim of the study was to analyze possible microstructural alteration in the penumbra and their association with clinical symptoms as well as angiographic reperfusion success in patients undergoing mechanical thrombectomy. All patients who underwent mechanical thrombectomy for large-vessel occlusions in the anterior circulation and who received an admission CT perfusion together with postinterventional DTIs were included (n = 65). Angiographic reperfusion success by means of modified Thrombolysis in Cerebral Infarction (mTICI) scale and clinical outcome were recorded. Microstructural integrity was assessed by DTI evaluating the mean diffusivity index within the salvaged gray matter of the former penumbra. The mean diffusivity index was higher in completely recanalized patients (mTICI 3: -0.001 ± 0.034 versus mTICI <3: -0.030 ± 0.055, P = .03). There was a positive correlation between the mean diffusivity index and NIHSS score improvement (r = 0.49, P = .003) and the mean diffusivity index was associated with midterm functional outcome (r = -0.37, P = .04) after adjustment for confounders. In mediation analysis, the mean diffusivity index and infarction growth mediated the association between reperfusion success and clinical outcomes. The macroscopic salvaged penumbra included areas of microstructural integrity changes, most likely related to the initial hypoperfusion. These abnormalities were found early after mechanical thrombectomy, were dependent on angiographic results, and correlated with the clinical outcome. When confirmed, these findings prompt the evaluation of therapies for protection of the penumbral tissue integrity.

Increased sensitivity to traumatic axonal injury on postconcussion diffusion tensor imaging scans in National Football League players by using premorbid baseline scans.

Statistical challenges exist when using diffusion tensor imaging (DTI) to assess traumatic axonal injury (TAI) in individual concussed athletes. The authors examined active professional American football players over a 6-year time period to study potential TAI after concussion and assess optimal methods to analyze DTI at the individual level. Active American professional football players recruited prospectively were assessed with DTI, conventional MRI, and standard clinical workup. Subjects underwent an optional preseason baseline scan and were asked to undergo a scan within 5 days of concussion during gameplay. DTI from 25 age- and sex-matched controls were obtained. Both semiautomated region-of-interest analysis and fully automated tract-based spatial statistics (TBSS) were used to examine DTI at individual and group levels. Statistical differences were assessed comparing individual DTI data to baseline imaging versus a normative database. Group-level comparisons were also performed to determine if longer exposure to professional-level play or prior concussion cause white matter microstructural integrity changes. Forty-nine active professional football players were recruited into the study. Of the 49 players, 7 were assessed at baseline during the preseason and after acute concussion. An additional 18 players were assessed after acute concussion only. An additional 24 players had only preseason baseline assessments. The results suggest DTI is more sensitive to suspected TAI than conventional MRI, given that 4 players demonstrated decreased fractional anisotropy (FA) in multiple tracts despite normal conventional MRI. Furthermore, the data suggest individual assessment of DTI data using baseline premorbid imaging is more sensitive than typical methods of comparing data to a normative control group. Among all subjects with baseline data, 1 reduced FA tract (± 2.5 standard deviations) was found using the typical normative database reference versus 10 statistically significant (p < 0.05) reduced FA tracts when referencing internal control baseline data. All group-level comparisons were statistically insignificant (p > 0.05). Baseline premorbid DTI data for individual DTI analysis provides increased statistical sensitivity. Specificity using baseline imaging also increases because numerous potential etiologies for reduced FA may exist prior to a concussion. These data suggest that there is a high potential for false-positive and false-negative assessment of DTI data using typical methods of comparing an individual to normative groups given the variability of FA values in the normal population.

Chlorophyll degradation and carotenoid biosynthetic pathways: Gene expression and pigment content in broccoli during yellowing

Broccoli undergoes yellowing in unfavorable conditions, thereby diminishing the sensory quality and commodity value. This study aimed to investigate systematically cellular and/or biomolecular changes involved in broccoli yellowing by analyzing changes in microstructural integrity, pigment content, and gene expression. On day-5 of storage at 20 °C, the buds turned yellow without blooming and showed structural damage; ultrastructural analysis revealed plastid transformation and abnormal chloroplast development. Genes regulating pigment content and chloroplast structure directly were identified. More specifically, BoCAO and BoNYC1 regulated chlorophyll turnover, affecting chlorophyll a and b contents. Changes in the β-cryptoxanthin content were influenced by the combined action of up- (BoHYD) and downstream (BoZEP) genes. BoZEP and BoVDE were activated after cold-temperature induction. High BoHO1 expression delayed yellowing at low temperature, inducing BoZEP expression. Color intensity correlated significantly with the chlorophyll b, β-cryptoxanthin, and β-carotene contents, which were associated with increased yellowing of plant tissues.

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients.

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.

Novel strain analysis informs about injury susceptibility of the corpus callosum to repeated impacts.

Increasing evidence for the cumulative effects of head trauma on structural integrity of the brain has emphasized the need to understand the relationship between tissue mechanic properties and injury susceptibility. Here, diffusion tensor imaging, helmet accelerometers and amplified magnetic resonance imaging were combined to gather insight about the region-specific vulnerability of the corpus callosum to microstructural changes in white-matter integrity upon exposure to sub-concussive impacts. A total of 33 male Canadian football players (meanage = 20.3 ± 1.4 years) were assessed at three time points during a football season (baseline pre-season, mid-season and post-season). The athletes were split into a LOW (N = 16) and HIGH (N = 17) exposure group based on the frequency of sub-concussive impacts sustained on a per-session basis, measured using the helmet-mounted accelerometers. Longitudinal decreases in fractional anisotropy were observed in anterior and posterior regions of the corpus callosum (average cluster size = 40.0 ± 4.4 voxels; P < 0.05, corrected) for athletes from the HIGH exposure group. These results suggest that the white-matter tract may be vulnerable to repetitive sub-concussive collisions sustained over the course of a football season. Using these findings as a basis for further investigation, a novel exploratory analysis of strain derived from sub-voxel motion of brain tissues in response to cardiac impulses was developed using amplified magnetic resonance imaging. This approach revealed specific differences in strain (and thus possibly stiffness) along the white-matter tract (P < 0.0001) suggesting a possible signature relationship between changes in white-matter integrity and tissue mechanical properties. In light of these findings, additional information about the viscoelastic behaviour of white-matter tissues may be imperative in elucidating the mechanisms responsible for region-specific differences in injury susceptibility observed, for instance, through changes in microstructural integrity following exposure to sub-concussive head impacts.

Corpus callosum diffusion abnormalities in refractory epilepsy associated with hippocampal sclerosis

ObjectivesTo detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics. MethodsFourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics. ResultsHS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings. ConclusionsThis is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC.

In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle.

Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non-surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.

Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts.

To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts. Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. We found focal cortical thinning specifically in areas connected to acute infarcts (p < 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (ρ = -0.39, p = 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter. These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke.

Successful tactile based visual sensory substitution use functions independently of visual pathway integrity.

Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort).Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS).Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ≤ 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort.Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients.

Basal forebrain atrophy predicts clinical progression in the nondemented elderly

hippocampal and sub-hippocampal volumes were not statistically significant. In contrast, despite the small sample sizes, the mild AD group exhibited significantly greater WM microstructural integrity changes in the medial temporal lobe structures, compared to aMCI group at p < 0.05. These findings suggest that the white matter integrity changes in the medial temporal lobe may be a more robust early biomarker than cortical volume changes to distinguish mild AD from aMCI.

White matter abnormalities of fronto-striato-thalamic circuitry in obsessive–compulsive disorder: A study using diffusion spectrum imaging tractography

Previous studies have reported white matter abnormalities in patients with obsessive–compulsive disorder (OCD). This study aimed to further explore white matter abnormalities in OCD patients through diffusion spectrum imaging (DSI) and tractography of the two white matter tracts which most probably play an important role in OCD neuropathology: the anterior segment of cingulum bundles (ACB) and the anterior thalamic radiations (ATR). Twelve right-handed, medicated adult patients with OCD and 12 matched controls underwent DSI on a 3 tesla magnetic resonance imaging (MRI) system. Tractography based on DSI data was reconstructed to define the ACB and ATR. Mean generalized fractional anisotropy (GFA) was calculated for each targeted tract and was used to analyze local changes in microstructural integrity along individual tracts. There was a significantly lower mean GFA in both the right ATR and left ACB in OCD subjects compared to controls. OCD subjects also demonstrated decreased left-lateralized asymmetry of the ACB when compared to controls. Furthermore, the mean GFA of the left ACB positively correlated with OCD subjects’ obsessive subscores on the Yale–Brown Obsessive–Compulsive scale. This study supports the white matter abnormalities in the ACB and ATR of OCD subjects, which corroborates neurobiological models that posit a defect in fronto-striato-thalamic circuitry in OCD.