Diffusion Tensor Imaging Changes Research Articles

White Matter Microstructure Changes Revealed by Diffusion Kurtosis and Diffusion Tensor Imaging in Mutant Huntingtin Gene Carriers.

Diffusion magnetic resonance imaging (dMRI) has revealed microstructural changes in white matter (WM) in Huntington's disease (HD). To compare the validities of different dMRI, i.e., diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in HD. 22 mutant huntingtin (mHTT) carriers and 14 controls were enrolled. Clinical assessments and dMRI were conducted. Based on CAG-Age Product (CAP) score, mHTT carriers were categorized into high CAP (hCAP) and medium and low CAP (m& lCAP) groups. Spearman analyses were used to explore correlations between imaging parameters in brain regions and clinical assessments. Receiver operating characteristic (ROC) was used to distinguish mHTT carriers from control, and define the HD patients at advanced stage. Compared to controls, mHTT carriers exhibited WM changes in DKI and DTI. There were 22 more regions showing significant differences in HD detected by MK than FA. Only MK in five brain regions showed significantly difference between any two group, and negatively correlated with the disease burden (r = -0.80 to -0.71). ROC analysis revealed that MK was more sensitive and FA was more specific, while Youden index showed that the integration of FA and MK gave rise to higher authenticities, in distinguishing m& lCAP from controls (Youden Index = 0.786), and discerning different phase of HD (Youden Index = 0.804). Microstructural changes in WM occur at early stage of HD and deteriorate over the disease progression. Integrating DKI and DTI would provide the best accuracies for differentiating early HD from control and identifying advanced HD.

Diffusion decrease in normal-appearing white matter structures following photon or proton irradiation indicates differences in regional radiosensitivity

PurposeRadio(chemo)therapy (RCT) as part of the standard treatment of glioma patients, inevitably leads to radiation exposure of the tumor-surrounding normal-appearing (NA) tissues. The effect of radiotherapy on the brain microstructure can be assessed by magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI). The aim of this study was to analyze regional DTI changes of white matter (WM) structures and to determine their dose- and time-dependency. MethodsAs part of a longitudinal prospective clinical study (NCT02824731), MRI data of 23 glioma patients treated with proton or photon beam therapy were acquired at three-monthly intervals until 36 months following irradiation. Mean, radial and axial diffusivity (MD, RD, AD) as well as fractional anisotropy (FA) were investigated in the NA tissue of 15 WM structures and their dependence on radiation dose, follow-up time and distance to the clinical target volume (CTV) was analyzed in a multivariate linear regression model. Due to the small and non-comparable patient numbers for proton and photon beam irradiation, a separate assessment of the findings per treatment modality was not performed. ResultsFour WM structures (i.e., internal capsule, corona radiata, posterior thalamic radiation, and superior longitudinal fasciculus) showed statistically significantly decreased RD and MD after RT, whereas AD decrease and FA increase occurred less frequently. The posterior thalamic radiation showed the most pronounced changes after RCT [i.e., ΔRD = −8.51 % (p = 0.012), ΔMD = −6.14 % (p = 0.012)]. The DTI changes depended significantly on mean dose and time. ConclusionSignificant changes in DTI for WM substructures were found even at low radiation doses. These findings may prompt new radiation dose constraints sparing the vulnerable structures from damage and subsequent side-effects.

Comparative utility of MRI and EEG for early detection of cortical dysmaturation after postnatal systemic inflammation in the neonatal rat

BackgroundExposure to postnatal systemic inflammation is associated with increased risk of brain injury in preterm infants, leading to impaired maturation of the cerebral cortex and adverse neurodevelopmental outcomes. However, the optimal method for identifying cortical dysmaturation is unclear. Herein, we compared the utility of electroencephalography (EEG), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) at different recovery times after systemic inflammation in newborn rats. MethodsSprague Dawley rat pups of both sexes received single-daily lipopolysaccharide (LPS; 0.3 mg/kg i.p.; n = 51) or saline (n = 55) injections on postnatal days (P)1, 2, and 3. A subset of these animals were implanted with EEG electrodes. Cortical EEG was recorded for 30 min from unanesthetized, unrestrained pups at P7, P14, and P21, and in separate groups, brain tissues were collected at these ages for ex-vivo MRI analysis (9.4 T) and Golgi–Cox staining (to assess neuronal morphology) in the motor cortex. ResultsPostnatal inflammation was associated with reduced cortical pyramidal neuron arborization from P7, P14, and P21. These changes were associated with dysmature EEG features (e.g., persistence of delta waveforms, higher EEG amplitude, reduced spectral edge frequency) at P7 and P14, and higher EEG power in the theta and alpha ranges at P21. By contrast, there were no changes in cortical DTI or NODDI in LPS rats at P7 or P14, while there was an increase in cortical fractional anisotropy (FA) and decrease in orientation dispersion index (ODI) at P21. ConclusionsEEG may be useful for identifying the early evolution of impaired cortical development after early life postnatal systemic inflammation, while DTI and NODDI seem to be more suited to assessing established cortical changes.

The Injury Progression in Acute Blast-Induced Mild Traumatic Brain Injury in Rats Reflected by Diffusion Tensor Imaging and Immunohistochemical Examination.

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.

Study protocol for "Psilocybin in patients with fibromyalgia: brain biomarkers of action".

Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI). Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity - plus event-related potential functional plasticity markers, captured via EEG. The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT.

Presence of Auditory Pathway Abnormalities in Children With Neurofibromatosis Type 1 With Brainstem Focal Areas of Abnormal Signal Intensity: Diffusion Tensor Imaging Features.

Background: To investigate whether there is a difference in mean diffusivity (MD) and fractional anisotropy (FA) values in the auditory pathways of neurofibromatosis type 1 patients with and without focal areas of abnormal signal intensity (FASI) compared to healthy controls by using diffusion tensor imaging (DTI). Methods: Patients were classified as group 1 with focal areas of abnormal signal intensity in the brainstem, group 2 without focal areas of abnormal signal intensity, and healthy control group 3 according to the MRI findings. Mean diffusivity and fractional anisotropy values of lateral lemniscus, inferior colliculus, corpus geniculatum mediale, Heschl gyrus, and brainstem were compared between groups. The correlation between mean diffusivity and fractional anisotropy values of auditory pathways and age was investigated. Results: There was a significant difference between group 1 and group 2 in terms of mean diffusivity and fractional anisotropy values at lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl gyrus. Increased mean diffusivity and decreased fractional anisotropy values at brainstem were found in group 1. There was a significant difference between group 1 and group 3 in terms of mean diffusivity values at all auditory pathways. Fractional anisotropy values obtained from lateral lemniscus, inferior colliculus, and Heschl gyrus decreased in group 1 compared with group 3. There was a negative correlation between mean diffusivity values and positive correlation between fractional anisotropy values at lateral lemniscus, inferior colliculus, Heschl gyrus, and age. Conclusions: Our diffusion tensor imaging findings show that the neuronal integrity of the auditory pathways is affected in neurofibromatosis type 1 patients with brainstem focal areas of abnormal signal intensity. We think that the disappearance of brainstem focal areas of abnormal signal intensity associated with myelin repair and the regression of diffusion tensor imaging changes in the auditory pathways occur simultaneously with advancing age in patients with neurofibromatosis type 1.

Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination.

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture.

Microstructure white matter changes and serum GFAP among different phenotypes of multiple sclerosis

Background. Multiple sclerosis (MS) is an autoimmune disease that targets the central nervous system (CNS). A patient’s degree of demyelination and axonal degeneration can only be roughly estimated based on clinical symptoms, neurochemical analysis or standard clinical MRI. Magnetic resonance diffusion tensor imaging (DTI) may provide more information on MS pathology than T1- and T2-weighted MRI alone. Glial fibrillary acidic protein (GFAP) uniquely found in astrocytes in the (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP is postulated to be a biomarker of astrocytic damage and reactive astrogliosis. Methods. A total of 60 patients with MS was categorized into three equal groups according to The Multiple Sclerosis Progression Discussion Tool (MSProDiscuss tool): RRMS, SPMS, RRMS with high risk to become SPMS and 20 healthy controls. Baseline clinical characteristics and detailed medical and neurological history were taken into consideration, as well as time of onset of MS, delay in diagnosis, initial symptoms, relapses features and behavior, EDSS and disease modifying therapy. They were subjected to DTI-MRI and blood sampling for GFAP. Results. DTI was able to differentiate between different MS phenotypes and was able to detect progression when we evaluated DTI changes in NAWM in different brain areas as low FA and high MD were associated with progression and increasing disability (p value =0.001). Serum GFAP differs significantly between patients with SPMS or patients in transition, also, it was higher in patients in transition than RRMS or control group (P value <0.001). There was a significant correlation between serum GFAP and DTI changes in NAWM as higher titres of GFAP were associated with lower FA and higher MD values in NAWM of frontal, temporal lobes, and CC body. Conclusion. Serum GFAP in addition to DTI measurable microdamage in NAWM can give us a wide scope of view about potential progression in MS pathology and related astrocytopathy.

Temporal Alterations in White Matter in An App Knock-In Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used the AppNL-G-F/NL-G-F knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein (APP) gene with three familial AD mutations. We performed in vivo diffusion tensor imaging (DTI) to study how the structural properties of the brain change across age in the context of AD. In late age APPKI mice, we observed reduced fractional anisotropy (FA), a proxy of WM integrity, in multiple brain regions, including the hippocampus, anterior commissure (AC), neocortex, and hypothalamus. At the cellular level, we observed greater numbers of oligodendrocytes in middle age (prior to observations in DTI) in both the AC, a major interhemispheric WM tract, and the hippocampus, which is involved in memory and heavily affected in AD, prior to observations in DTI. Proteomics analysis of the hippocampus also revealed altered expression of oligodendrocyte-related proteins with age and in APPKI mice. Together, these results help to improve our understanding of the development of AD pathology with age, and imply that middle age may be an important temporal window for potential therapeutic intervention.

Diffusion tensor-based analysis of white matter in dogs with idiopathic epilepsy.

The understanding of epileptic seizure pathogenesis has evolved over time, and it is now generally accepted that not only are cortical and subcortical areas involved but also the connection of these regions in the white matter (WM). Recent human neuroimaging studies confirmed the involvement of the WM in several epilepsy syndromes. Neuroimaging studies investigating WM integrity with diffusion tensor imaging (DTI) in canine idiopathic epilepsy are lacking. This study aimed to test the hypothesis that WM diffusion changes can be found in dogs affected by idiopathic epilepsy. Twenty-six dogs with idiopathic epilepsy (15 Border Collies and 11 Greater Swiss Mountain dogs) and 24 healthy controls (11 Beagle dogs, 5 Border Collies, and 8 Greater Swiss Mountain dogs) were prospectively enrolled. Most dogs with idiopathic epilepsy (17/26) were enrolled within 3 months after seizure onset. Diffusion tensor imaging of the brain with 32 diffusion directions (low b value = 0 s/mm2; maximal b value = 800 s/mm2) was performed in a 3 Tesla scanner. Tract-based spatial statistics (TBSS), a voxel-based approach, was used to investigate changes in fractional anisotropy (FA) and mean diffusivity (MD) in the idiopathic epilepsy group compared to the healthy control group. Additionally, FA and MD were investigated in the region of corpus callosum and cingulate white matter in both groups. We observed subtle changes in WM DTI between the idiopathic epilepsy group and the healthy control group limited to cingulate WM, with a significantly lower FA in the idiopathic epilepsy group compared to the healthy control group in the region of interest (ROI) approach (p = 0.027). No significant changes were found between the idiopathic epilepsy group and the healthy control group in the TBSS analysis and in the corpus callosum in the ROI approach. This study supports the cingulate area as a target structure in canine epilepsy. The subtle changes only might be explained by the short duration of epilepsy, small sample sizes, and the higher variability in canine brain anatomy. Furthermore, all included dogs showed generalized tonic-clonic seizures, possibly affected by generalized epilepsy syndrome, which are also associated with less pronounced DTI changes in humans than focal epilepsy syndromes.

Characterizing Typhoon-related Posttraumatic Stress Disorder Based on Multimodal Fusion of Structural, Diffusion, and Functional Magnetic Resonance Imaging

Diagnosing posttraumatic stress disorder (PTSD) using only single-modality images is controversial. We aimed to use multimodal magnetic resonance imaging (MRI) combining structural, diffusion, and functional MRI to possibly provide a more comprehensive viewpoint on the decisive characteristics of PTSD patients. Typhoon-exposed individuals with (n = 26) and without PTSD (n = 32) and healthy volunteers (n = 30) were enrolled. Five MRI features from three modalities, including two resting-state functional MRI (rs-fMRI) features (amplitude of low-frequency fluctuation, ALFF; and regional homogeneity, ReHo), one structural MRI feature (gray matter density, GM), and two diffusion tensor imaging (DTI) features (fractional anisotropy, FA; and mean diffusivity, MD) were investigated simultaneously with a multimodal canonical correlation analysis + joint independent component analysis model to identify abnormalities in the PTSD brain. We identified statistical differences between PTSD patients and healthy controls in terms of 1 rs-fMRI (ALFF, ReHo) alterations in the superior frontal gyrus, precuneus, inferior parietal lobule (IPL), anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC), 2 DTI (FA, MD) changes in the pons, genu, and splenium of the corpus callosum, and 3 Structural MRI abnormalities in the precuneus, IPL, ACC, and PCC. A novel ReHo component was found to distinguish PTSD and trauma-exposed controls, including the precuneus, IPL, middle frontal gyrus, middle occipital gyrus, and cerebellum. This study reveals that PTSD individuals exhibit intertwined functional and structural anomalies within the default mode network. Some alterations within this network may serve as a potential marker to distinguish between PTSD patients and trauma-exposed controls.

Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS

PurposeTo investigate how the microstructural neural integrity of cortico-thalamic-striatal (CTS) tracts correlate with fatigue and disability over time. The primary outcome was diffusion tensor imaging (DTI) metrics change over time, and the secondary outcome was correlations with fatigue and disability in people with RRMS (pw-RRMS). Methods76 clinically stable pw-RRMS and 43 matched healthy controls (HCs). The pw-RRMS cohort consisted of three different treatment subgroups. All participants underwent disability, cognitive, fatigue and mental health assessments. Structural and diffusion scans were performed at baseline (BL) and 2-year follow-up (2-YFU) for all participants. Fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD, AD) of normal-appearing white matter (NAWM) and white matter lesion (WML) in nine tracts-of-interests (TOIs) were estimated using our MRtrix3 in-house pipeline. ResultsWe found significant BL and 2-YFU differences in most diffusion metrics in TOIs in pw-RRMS compared to HCs (pFDR ≤ 0.001; false-detection-rate (FDR)-corrected). There was a significant decrease in WML diffusivities and an increase in FA over the follow-up period in most TOIs (pFDR ≤ 0.001). Additionally, there were no differences in DTI parameters across treatment groups. AD and MD were positively correlated with fatigue scores (r ≤ 0.33, p ≤ 0.01) in NAWM-TOIs, while disability (EDSS) was negatively correlated with FA in most NAWM-TOIs (|r|≤0.31, p ≤ 0.01) at both time points. Disability scores correlated with all diffusivity parameters (r ≤ 0.29, p ≤ 0.01) in most WML-TOIs at both time points. ConclusionStatistically significant changes in diffusion metrics in WML might be indicative of integrity improvement over two years in CTS tracts in clinically stable pw-RRMS. This finding represents structural changes within lesioned tracts. Measuring diffusivity in pw-RRMS affected tracts might be a relevant measure for future remyelination clinical trials.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents. Awake male and female Sprague Dawley rats (postnatal Day 35) received 140 closed-head impacts over the course of a week. Impacted and sham-impacted animals were restrained in a plastic cone, and unrestrained control animals were included to account for effects of restraint and normal development. Animals (n = 43) underwent repeated diffusion tensor imaging prior to and over 1 month following the final impact. A separate cohort (n = 53) was assessed behaviourally for fine motor control, emotional-affective behaviour and memory at acute and chronic time points. Histological and immunohistochemical analyses, which were exploratory in nature due to smaller sample sizes, were completed at 1 month following the final impact. All animals tolerated the protocol with no overt changes in behaviour or stigmata of traumatic brain injury, such as alteration of consciousness, intracranial haemorrhage or skull fracture. We detected longitudinal, sex-dependent diffusion tensor imaging changes (fractional anisotropy and axial diffusivity decline) in corpus callosum and external capsule of repetitive subconcussive head impact animals, which diverged from both sham and control. Compared to sham animals, repetitive subconcussive head impact animals exhibited acute but transient mild motor deficits. Repetitive subconcussive head impact animals also exhibited chronic anxiety and spatial memory impairment that differed from the control animals, but these effects were not different from those seen in the sham condition. We observed trends in the data for thinning of the corpus callosum as well as regions with elevated Iba-1 in the corpus callosum and cerebral white matter among repetitive subconcussive head impact animals. While replication with larger study samples is needed, our findings suggest that subconcussive head impacts cause microstructural tissue changes in the developing rat brain, which are detectable with diffusion tensor imaging, with suggestion of correlates in tissue pathology and behaviour. The results point to potential mechanisms underpinning consequences of subconcussive head impacts that have been described in humans. The congruence of our imaging findings with human subconcussive head impacts suggests that neuroimaging could serve as a translational bridge to advance study of injury mechanisms and development of interventions.

White matter microstructure and connectivity changes after surgery in male adults with obstructive sleep apnea: recovery or reorganization?

Obstructive sleep apnea (OSA) is a prevalent clinical problem significantly affecting cognitive functions. Surgical treatment is recommended for those unable to use continuous positive airway pressure. We aimed to investigate the therapeutic effect of upper airway surgery on the white matter (WM) microstructure and brain connectivity in patients with OSA. Twenty-one male patients with moderate-to-severe OSA were recruited for multi-level upper airway surgery. Overnight polysomnography (PSG), neuropsychiatric tests, and brain MRI scans were acquired before and 6.1 ± 0.8 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group. We calculated the longitudinal changes of diffusion tensor imaging (DTI) parameters, including fractional anisotropy (ΔFA) and mean/axial/radial diffusivity (ΔMD/AD/RD). We also assessed changes in network properties based on graph theory. Surgically treated patients showed improvement in PSG parameters and verbal memory after surgery. Globally, ΔFA was significantly higher and ΔRD was lower in the surgery group than in the untreated group. Especially ΔFA of the tracts involved in the limbic system was higher after surgery. In network analysis, higher Δbetweenness and lower Δclustering coefficients were observed in the surgical group than in the untreated group. Finally, the improvement of verbal memory after surgery positively correlated with ΔFA in superior thalamic radiation (p = 0.021), fronto aslant tracts (p = 0.027), and forceps minor tracts (p = 0.032). Surgical treatment of OSA can alleviate alterations in WM integrity and disruptions in local networks, particularly for the tracts involved in the limbic system. These findings may further explain the cognitive improvement observed after the treatment of OSA.

Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years.

Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years. Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time. MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores. Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

Characterization of white matter alterations using diffusion kurtosis imaging in patients with amyotrophic lateral sclerosis.

To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients. In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p<.017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p<.05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p<.01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.

Effect of HD-tDCS on white matter integrity and associated cognitive function in chronic schizophrenia: A double-blind, sham-controlled randomized trial

Schizophrenia is a disabling major mental disorder, which includes critical deficits in cognitive function, for which no effective intervention currently exists. The aim of our double-blind, randomized, sham-controlled trial was to evaluate the effects of high-definition transcranial direct current stimulation (HD-tDCS) on the cognitive deficits in schizophrenia. This study sample consisted of 56 individuals with chronic schizophrenia, randomly allocated to either the active stimulation or sham group. The treatment consisted of ten consecutive days of HD-tDCS, 20 min/day, applied over the left dorsolateral prefrontal lobe. Changes in clinical outcomes, cognitive assessments, and diffusion tensor imaging were evaluated pre- to post-intervention. Matched-healthy controls (HCs) were included to identify white matter changes in patients with schizophrenia before treatment. Compared to HCs, schizophrenia was associated with reduced integrity of the white matter tracts of the corpus callosum and corona radiata. HD-tDCS enhanced integrity in the corpus callosum and anterior and superior corona radiata, which was associated with the change in cognitive performance. HD-tDCS offers a potential approach to improve cognition deficits in schizophrenia through a modulatory effect on white matter tracts. Given the lack of approved treatments for cognitive deficits, these findings are clinically relevant.

A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age

Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions.

Association between Diffusion Tensor Imaging, inflammation and immunological alterations in unipolar and bipolar depression: a review

IntroductionMajor Depressive Disorder (MDD) and Bipolar Disorder Depression (BDD) are common psychiatric illnesses characterized by structural and functional brain alterations and signs of neuroinflammation. In line with the neuroinflammatory pathogenesis of depressive syndromes (Mechawar N, Savitz J. Neuropathology of mood disorders: do we see the stigmata of inflammation? Transl Psychiatry. 2016;6(11):e946), recent studies have demonstrated how white matter (WM) microstructural impairments detected by Diffusion Tensor Imaging (DTI) are correlated to peripheral immunomarkers in depressed patients.ObjectivesIn this context, the aim of our review is to report an updated overview of the evidence on the correlation between the blood immuno-markers changes and the brain WM disruptions in MDD and BDD patients.MethodsBased on PRISMA 2020 guidelines (Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372), we performed a systematic search on original DTI studies exploring the association between WM integrity, neuroimmune alterations and inflammation in patients affected by MDD or BDD.ResultsConcerning MDD, most of the reviewed studies provided evidence of a link between systemic immune dysregulation, detected through the elevation of peripheral markers (IL-1β and TNF-alfa) or an altered ratio between proinflammatory and counterregulatory cytokines (IL-8/IL-10), and DTI alterations in specific WM tracts, such as the genu of corpus callosum and the IFOF. As for the BDD, we detected an increase of pro-inflammatory molecules (such as TNF-alfa, IL-8, IFN-γ etc.) that correlated with DTI changes in different cerebral areas such as cingulum, forceps, corona radiata, corpus callosum, longitudinal fasciculus and internal capsule. Furthermore, other molecules seem to play a specific role in BDD pathogenesis, including counter-regulatory cytokines, kynurenine and specific lymphocyte classes, such as Th1 and Th17.ConclusionsTaken together, these pathogenetic insights could outline an integrated clinical perspective to affective disorders, helping psychiatrists to develop novel biotype-to-phenotype models of depression and opening the way to tailored approaches in treatments.Disclosure of InterestNone Declared

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.