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Background: The corpus callosum (CC) is the most prominent white matter connection for interhemispheric information transfer. It is implicated in a variety of cognitive functions, which tend to decline with age. The region-specific projections of the fiber bundles with microstructural heterogeneity of the CC are associated with cognitive functions and diseases. However, how the CC is associated with the information transfer within functional networks and the connectivity changes during aging remain unclear. Studying the CC topography helps to understand the functional specialization and age-related changes of CC subregions.Methods: Diffusion tractography was used to subdivide the CC into seven subregions from 1,086 healthy volunteers within a wide age range (21–90 years), based on the connections to the cortical parcellations of the functional networks. Quantitative diffusion indices and connection probability were calculated to study the microstructure differences and age-related changes in the CC subregions.Results: According to the population-based probabilistic topography of the CC, part of the default mode network (DMN) and limbic network (LN) projected fibers through the genu and rostrum; the frontoparietal network (FPN), ventral attention network (VA) and somatomotor networks (SM) were interconnected by the CC body; callosal fibers arising from the part of the default mode network (DMN), dorsal attention network (DA) and visual network (VIS) passed through the splenium. Anterior CC subregions interconnecting DMN, LN, FPN, VA, and SM showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) than posterior CC subregions interconnecting DA and VIS. All the CC subregions showed slightly increasing FA and decreasing MD, RD, and axial diffusivity (AD) at younger ages and opposite trends at older ages. Besides, the anterior CC subregions exhibited larger microstructural and connectivity changes compared with the posterior CC subregions during aging.Conclusion: This study revealed the callosal subregions related to functional networks and uncovered an overall “anterior-to-posterior” region-specific changing trend during aging, which provides a baseline to identify the presence and timing of callosal connection states.

Meningitis retention syndrome (MRS), comprising aseptic meningitis and urinary retention, is a self-limiting disease that resolves within a few weeks. Refractory urinary retention and encephalitic syndromes are rare. A 32-year-old man presented with acute fever and headache followed by acute urinary retention (UT). Neurological examination revealed meningeal irritation, UT, constipation and ataxic gait. The cerebrospinal fluid showed mononuclear leukocytosis, and the etiological examination was negative. We suspected MRS. However, magnetic resonance imaging demonstrated an abnormally intense lesion in the splenium of the corpus callosum (SCC). He also developed delirium on day 4 of hospitalization. We diagnosed the patient with MRS associated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). While his delirium and constipation improved, and the SCC lesion disappeared, UT was refractory and required 6 months to complete recovery. Our case suggests that severe MRS can exhibit refractory UT and may associate with MERS.

Background: Violent acts in patients with schizophrenia are often associated with their hostility and aggression levels. Poor visuospatial processing has been suggested as a possible risk factor of violence in schizophrenia. However, studies investigating the relationship between hostility, aggression, and the visuospatial function have been lacking. Here, we aimed to investigate brain dysconnectivity associated with hostility and aggression in schizophrenia, particularly focusing on the visuospatial function network.Methods: Eighty-eight participants with schizophrenia and 42 healthy controls were enrolled. The visuospatial function network regions of interest were analyzed using Tract-Based Spatial Statistics. The hostility item from the Positive and Negative Syndrome Scale (PANSS), aggressive, and agitated behavior item from the Scale for the Assessment of Positive Symptoms (SAPS), and the Rey Complex Figure Test (R-CFT) were measured.Results: Among the participants with schizophrenia, the SAPS aggressive and agitated behavior scores were significantly correlated with fractional anisotropies (FAs) of the white matter regions in the splenium of the corpus callosum (CC), left posterior thalamic radiations (PTR), and left posterior corona radiata (PCR). Exploratory correlational analysis revealed significant negative correlations between FAs of the splenium of the CC and R-CFT copy and immediate recall scores. In addition, three regions including CC, PTR, and PCR that significantly correlated with the aggression scores showed significant correlations with the total PANSS scores.Conclusion: Our main finding suggests that aggression of patients with schizophrenia may be associated with poor visuospatial ability and underlying white matter dysconnectivity. These may help enhance understanding aggression in patients with schizophrenia.

Highlights • Gait and balance impairments correlated to various imaging abnormalities. • Stride length, cadence and balance varied independently in PSP. • PSP phenotype affects the associations between gait and imaging., Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear palsy has been assessed using MRI. Degeneration of white matter tracts is evident with diffusion tensor imaging and PET methods have been used to assess brain metabolism or presence of tau protein deposits. Patients with progressive supranuclear palsy present with a variety of clinical syndromes; however early onset of gait impairments and postural instability are common features. In this study we assessed the relationship between multimodal imaging biomarkers (i.e., MRI atrophy, white matter tracts degeneration, flortaucipir-PET uptake) and laboratory-based measures of gait and balance abnormalities in a cohort of nineteen patients with progressive supranuclear palsy, using univariate and multivariate statistical analyses. The PSP rating scale and its gait midline sub-score were strongly correlated to gait abnormalities but not to postural imbalance. Principal component analysis on gait variables identified velocity, stride length, gait stability ratio, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with diffusion tensor imaging measures in the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, body and splenium of the corpus callosum and sagittal stratum, with MRI volumes in frontal and precentral regions and with flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was higher in patients presenting more abnormalities on mean diffusivity: this unexpected finding might be related to compensatory gait strategies adopted in progressive supranuclear palsy. Postural imbalance was the main contributor to the third principal component, which was related to flortaucipir-PET uptake in the left paracentral lobule and supplementary motor area and white matter disruption in the superior cerebellar peduncle, putamen, pontine crossing tract and corticospinal tract. A partial least square model identified flortaucipir-PET uptake in midbrain, basal ganglia and thalamus as the main correlate of speed and dynamic component of gait in progressive supranuclear palsy. Although causality cannot be established in this analysis, our study sheds light on neurodegeneration of brain regions and white matter tracts that underlies gait and balance impairment in progressive supranuclear palsy.

Introduction Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiologic syndrome presenting with a reversible lesion in the splenium of the corpus callosum. MERS is associated with many potential etiologies, including cytomegalovirus (CMV) infection in children. We report an adult patient with CMV-associated MERS. Case report A previously healthy 25-year-old man was admitted with a 4-day history of fever, headache, and vomiting. Brain magnetic resonance imaging demonstrated an isolated lesion of the splenium of the corpus callosum with hyperintensity on T2 and diffusion-weighted sequences and reduced values on apparent diffusion coefficient maps. High throughput gene detection for pathogens in cerebrospinal fluid revealed infection with CMV. The splenial lesion resolved 4 weeks after onset. Conclusion This is the first report an adult patient with CMV-associated MERS. Recognition of this clinical-radiologic syndrome can guide diagnosis and management.

INTRODUCTIONLittle is known about longitudinal decline in white matter (WM) microstructure and its associations with cognition in preclinical Alzheimer’s disease (AD).METHODSLongitudinal diffusion tensor imaging and neuropsychological testing from 50 older adults who subsequently developed mild cognitive impairment or dementia (subsequently impaired, SI) and 200 cognitively normal controls. Rates of WM decline were compared between groups using voxel-wise linear mixed-effects models. Associations between change in WM and cognition were examined.RESULTSSI had faster decline in fractional anisotropy (FA) in the right inferior fronto-occipital fasciculus (R.IFOF) and bilateral splenium of the corpus callosum. Decline in R.IFOF FA was related to decline in verbal memory, visuospatial ability, processing speed, and MMSE (p≤ 0.05). Decline in bilateral splenium FA was related to decline in verbal fluency, processing speed, and MMSE (p≤ 0.05).DISCUSSIONAccelerated regional WM decline is characteristic of preclinical AD and related to domain specific cognitive decline.

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.

Recent advancements in radiological techniques have enabled the observation of the topographic distribution of the human corpus callosum. However, its functional connectivity remains to be elucidated. The symptoms of callosal disconnection syndrome (CDS) can potentially reveal the functional connections between the cerebral hemispheres. Herein, we report a patient with CDS, whose callosal lesion was restricted to the posterior midbody, isthmus, and an anterior part of the dorsal splenium. A 53-year-old right-handed woman demonstrated CDS following cerebral infarction associated with subarachnoid hemorrhage. She exhibited CDS including ideomotor apraxia, and tactile anomia with the left hand, cross-replication of hand postures, cross-localization of the fingers, and constructional impairment with the right hand. Six months after onset, the left-handed ideomotor apraxia on imitation improved, but that to command did not, which indicated the difference in the nature of the transcallosal connections between ideomotor apraxia on imitation and ideomotor apraxia to command. Longitudinal CDS observation and corpus callosum tractography will prove useful in expanding our understanding of the nature of the organization of interhemispheric information transference.

Rationale: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). Patient concerns: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. Diagnosis: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. Intervention: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). Outcomes: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. Lessons: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.

A 21-year-old male with history of refractory epilepsy presented for long-term video EEG monitoring. His home antiepileptic medications were weaned off over a seven-day period. On hospital day 4, he had a right temporal electro clinical seizure with secondary generalization and a second right temporal electrographic seizure. On hospital day 8, MRI brain identified an ovoid circumscribed lesion in the splenium of the corpus callosum which had not been present on prior scans (Figure 1).

Objective The aims of the present study were to investigate white matter alterations and their associations with the clinical variables in cervical spondylotic (CS) patients with pain. Design Cross-sectional study. Setting Chinese community. Subjects Forty-two CS patients with pain and 42 matched healthy participants were ultimately recruited from August 2018 to September 2019. Methods Tract-based spatial statistics (TBSS) analysis was performed to investigate the differences of DTI-derived indices (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD)) between the patients and healthy controls throughout brain white matter. The relationship of the severity of cervical pain and affective disturbance to aberrant DTI indices in the patients was also examined using spearman correlation analyses. Results The CS patients with pain showed decreased FA in the genu, body, and splenium portions of corpus callosum (CC), and increased MD and RD along with decreased FA in anterior corona radiata (ACR) compared with healthy controls, whereas no significant difference of AD was observed between groups. Additionally, lower FA of the genu part of CC together with higher MD of the left ACR were statistically correlated with the pain severity in the patient group. Conclusions Decreased FA coupled with increased MD and RD was detected in multiple white matter regions, and several DTI metrics in certain white matter tracts had moderate relationships with the pain severity in the CS patients with pain. These observations may provide alternative imaging clues for the evaluation of the pathophysiological characteristics of CS pain.

Background Neurodevelopmental disorders (NDDs) usually present overlapping symptoms. Abnormal white matter (WM) microstructure has been found in these disorders. Identification of common and unique neural abnormalities across NDDs could provide further insight into the underlying pathophysiological mechanisms. Methods We performed a voxel-based meta-analysis of whole-brain diffusion tensor imaging (DTI) studies in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and other NDDs. A systematic literature search was conducted through March 2020 to identify studies that compared measures of WM microstructure between patients with NDDs and neurotypical controls. Peak voxel coordinates were meta-analyzed via anisotropic effect size-signed differential mapping (AES-SDM) as well as activation likelihood estimation (ALE). Results Our final sample included a total of 4137 subjects from 66 studies across five NDDs. Fractional anisotropy (FA) reductions were found in the splenium of the CC in ADHD, and the genu and splenium of CC in ASD. And mean diffusivity (MD) increases were shown in posterior thalamic radiation in ASD. No consistent abnormalities were detected in specific learning disorder, motor disorder or communication disorder. Significant differences between child/adolescent and adult patients were found within the CC across NDDs, reflective of aberrant neurodevelopmental processes in NDDs. Conclusions The current study demonstrated atypical WM patterns in ASD, ADHD and other NDDs. Microstructural abnormalities in the splenium of the CC were possibly shared among ASD and ADHD.

Objectives Recent case-reports have described an atypical cerebral microbleed (CMB) topography after extracorporeal membrane oxygenation (ECMO). The objective of this study was to examine the prevalence, radiographic patterns, and clinical correlates of possibly-ECMO-related (PER) CMB. Materials and methods We performed a retrospective study of 307 consecutive patients receiving ECMO support at our tertiary-care University Hospital (2013–2018). PER CMB were defined as CMB present in corpus-callosum and/or middle cerebellar peduncle with/without involvement of other lobar/deep structures. Leukoaraiosis was quantified using the Wahlund age-related white matter changes scale. Patient characteristics were compared between cohorts with and without PER CMB. Results Forty patients (median age 60 years; 33% vv-ECMO and 67% va-ECMO) received at-least one MRI-brain within 3 months of ECMO support. CMB were present in 77.5% (n = 31) patients with 39% (n = 12), 17% (n = 5), and 44% (n = 14) having low ( 30 CMB) burden respectively. Among CMB-positive patients, 71% (n = 22) had PER CMB, with 91% of such cases demonstrating involvement of splenium. Leukoaraiosis did not corelate to PER CMB presence (p = 0.267) or burden (ρ = 0.09). Patients with PER CMB had higher rates of ischemic stroke (50 vs. 33%), intracranial hemorrhage (41 vs. 17%), and all-cause mortality (27 vs. 17%); with survivors demonstrating no differences in their discharge disposition or modified Rankin Score. Conclusions Post-ECMO cerebral microbleeds have a distinct distribution pattern that commonly involves the splenium of corpus-callosum. Their etiopathogenesis may be independent of microvascular lipohyalinosis. This requires further study in a larger sample-size.

Introduction: The source of Tissue Sodium Concentration (TSC) increase in Multiple Sclerosis (MS) remains unclear, and could be attributed to altered intracellular sodium concentration or tissue microstructure. This paper investigates sodium in MS using three new MRI sequences.Methods: Three sodium scans were acquired at 4.7 T from 30 patients (11 relapsing-remitting, 10 secondary-progressive, 9 primary-progressive) and 9 healthy controls including: Density-Weighted (NaDW), with very short 30° excitation for more accurate TSC measurement; Projection Acquisition with Coherent MAgNetization (NaPACMAN), designed for enhanced relaxation-based contrast; and Soft Inversion Recovery FLuid Attenuation (NaSIRFLA), developed to reduce fluid space contribution. Signal was measured in both lesions (n = 397) and normal appearing white matter (NAWM) relative to controls in the splenium of corpus callosum and the anterior and posterior limbs of internal capsule. Correlations with clinical and cognitive evaluations were tested over all MS patients.Results: Sodium intensity in MS lesions was elevated over control WM by a greater amount for NaPACMAN (75%) than NaDW (35%), the latter representing TSC. In contrast, NaSIRFLA exhibited lower intensity, but only for region specific analysis in the SCC (−7%). Sodium intensity in average MS NAWM was not significantly different than control WM for either of the three scans. NaSIRFLA in the average NAWM and specifically the posterior limb of internal capsules positively correlated with the Paced Auditory Serial Addition Test (PASAT).Discussion: Lower NaSIRFLA signal in lesions and ~2× greater NaPACMAN signal elevation over control WM than NaDW can be explained with a demyelination model that also includes edema. A NAWM demyelination model that includes tissue atrophy suggests no signal change for NaSIRFLA, and only slightly greater NAWM signal than control WM for both NaDW and NaPACMAN, reflecting experimental results. Models were derived from previous total and myelin water fraction study in MS with T2-relaxometry, and for the first time include sodium within the myelin water space. Reduced auditory processing association with lower signal on NaSIRFLA cannot be explained by greater demyelination and its modeled impact on the three sodium MRI sequences. Alternative explanations include intra- or extracellular sodium concentration change. Relaxation-weighted sodium MRI in combination with sodium-density MRI may help elucidate microstructural and metabolic changes in MS.

A 45-year-old otherwise healthy active duty male was admitted to the medical intensive care unit for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) encephalopathy associated with hyperpyrexia. Magnetic resonance imaging findings demonstrated cytotoxic lesions primarily at the midline of the splenium of corpus callosum (CLOCC). Similar cases involving hyperpyrexia in the setting of SARS-CoV2 infection have demonstrated exceedingly high-mortality outcomes. Three mechanisms exist as to the likely underlying pathophysiology of SARS-CoV2-induced hyperpyrexia: direct brain injury, persistent immune dysregulation of cytokines, and vascular thrombosis. To date, no cases have reported imaging findings consistent with SARS-CoV2-induced brain injury leading to hyperpyrexia. Magnetic resonance imaging findings in this case, however, may finally elucidate the underlying mechanism for hyperpyrexia in this population. Magnetic resonance imaging findings in this case show diffusion restriction of the corpus callosum without evidence of any Central Nervous System (CNS) vessel abnormality. Given that hyperpyrexia has a clear association with increased mortality and morbidity in the SARS-CoV2 infected population, the decision to initiate steroids and remdesivir regardless of respiratory status was made for the concern for severe SARS-CoV2 infection as demonstrated by the CLOCC. Additional cases will be needed to assess their potential use as a radiological marker of disease burden.

A 47-year-old man with a history of aphasic seizures presented to the emergency room with a 12-hour global aphasia. Upon admission, brain MRI did not reveal acute lesions, and EEG showed sharp waves in the left frontal-temporal region. An Aphasic Status Epilepticus was diagnosed and antiepileptic treatment was initiated with adequate response. A week after the episode, a new brain MRI showed a high-signal ovoid lesion on T2-weighted and FLAIR sequences in the central part of the splenium of the corpus callosum. On diffusion-weighted images (DWI) the lesion was hyperintense with decreased apparent diffusion coefficient (ADC) values, indicating restricted diffusion consistent with a cytotoxic lesion of the corpus callosum (CLOCC). Follow-up MRI one month later showed complete image resolution. CLOCCs are secondary lesions associated with various entities in which high levels of cytokines and extracellular glutamate cause intracellular edema and reduced diffusion, a condition called cytotoxic edema, which affects vulnerable brain regions such as the splenium of the corpus callosum. In epileptic patients, CLOCCs may be due to the effect of seizures, especially prolonged ones, as well as antiepileptic treatment itself. CLOCCs are rare radiological findings and must be recognized to avoid misdiagnosis.

Highlights • Mild encephalopathy with reversible splenium lesion (MERS) is a condition characterized by fever, encephalopathy, and a reversible splenium lesion on brain MRI. • MERS has been previously associated with viral infections, such as the influenza virus, and may result from an immune-mediated response to infection. • MERS has not previously been described in conjunction with COVID-19. • We present a case of a patient with MERS and positive SARS-CoV-2 antibodies, the first reported instance of this neurological complication to the virus. • MERS should be considered in a patient with the characteristic clinico-radiological syndrome and COVID-19 infection., Neurological complications of coronavirus 2019 (COVID-19) are common, and novel manifestations are increasingly being recognized. Mild encephalopathy with reversible splenium lesion (MERS) is a syndrome that has been associated with viral infections, but not previously with COVID-19. In this report, we describe the case of a 69 year-old man who presented with fever and encephalopathy in the setting of a diffusion-restricting splenium lesion, initially mimicking an ischemic stroke. A comprehensive infectious workup revealed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, and a pro-inflammatory laboratory profile characteristic of COVID-19 infection. His symptoms resolved and the brain MRI findings completely normalized on repeat imaging, consistent with MERS. This case suggests that MERS may manifest as an autoimmune response to SARS-CoV-2 infection and should be considered in a patient with evidence of recent COVID-19 infection and the characteristic MERS clinico-radiological syndrome.

Primary central nervous system lymphoma (PCNSL) is a rare malignant tumor of the central nervous system. It is associated with poor prognosis. Early diagnosis and subsequent planning of adequate treatment strategy are relevant to improve survival and reduce neurological deficit. Specifically, there are no reports of successful endoscopic biopsy for PCNSL of the corpus callosum in the splenium with bilateral visuomotor ataxia. An 74-year-old woman presented to our hospital with anorexia, depression and ataxia beginning six months earlier. Head computed tomography and magnetic resonance imaging showed malignant tumor suspected in the corpus callosum. Endoscopic biopsy was performed via the low parieatal approach, suspecting GBM or PCNSL. She had no new postoperative neurological deficits and was pathologically diagnosed with diffuse large B-cell lymphoma (DLBCL). She is currently undergoing radiation chemotherapy with a modified Rankin Scale score of 2. Regarding preoperative symptoms, ataxia was considered to be bilateral visuomotor ataxia caused by damage to the corpus callosum in the splenium, and anorexia and depression were considered symptoms of the surrounding limbic system. Delay in the diagnosis of PCNSL can lead to a poor prognosis. Visuomotor ataxia should also consider the potential for the corpus callosum in the splenium lesion, including PCNSL, and appropriate imaging and pathological diagnosis with endoscopic biopsy can contribute to a good clinical outcome.

Marchiafava‐Bignami disease (MBD) is often diagnosed in chronic alcoholics. The disease processes typically involve the corpus callosum and clinically presents with various manifestations on the basis of clinical condition, extent of the splenium of the corpus callosum involvement at brain magnetic resonance imaging (MRI), and prognosis. We report a patient affected by MBD, who presented an isolated reversible splenial lesion at brain MRI and achieved a favorable recovery.

Hemodialysis (HD), especially when first initiated, can cause neurological deterioration. Presumably this is due to transient cerebral edema, which has been observed using diffusion weighted magnetic resonance imaging (MRI) in experimental and human studies; however, this has not been investigated under maintenance hemodialysis (mHD). Moreover, there are no studies to date investigating regional effects of mHD on grey and white matter volumes. In this study eight patients with end stage renal disease (ESRD) were examined immediately before and after mHD sessions with multimodal MRI, including diffusion tensor imaging (DTI) and high-resolution structural imaging. Additionally, eight healthy, age-matched and sex-matched controls were examined for comparison. Data were analyzed using tract-based spatial statistics and voxel-based morphometry. At baseline, ESRD patients had significantly reduced values of fractional anisotropy (FA) and axial diffusivity as well as bilaterally reduced grey matter volume in the insula, compared with controls. After the mHD session, FA further decreased while axial, radial, and mean diffusivity significantly increased ubiquitously throughout the white matter. Voxel-based morphometry revealed a corresponding significant increase in white matter volume in the central right hemisphere and splenium, as well as in cortical grey matter in the anterior medial frontal and cingulate cortex. None of the patients showed neurological deterioration. In this study ESRD patients showed white matter changes indicative of chronic microstructural damage when compared with healthy controls, as previously reported. In addition, patients showed signs of a transient extracellular cerebral edema, which has not yet been observed in the absence of neurological symptoms.

BACKGROUND AND PURPOSE: The effect of white matter hyperintensities as measured by FLAIR MR imaging on functional impairment and recovery after ischemic stroke has been investigated thoroughly. However, there has been growing interest in investigating normal-appearing white matter microstructural integrity following ischemic stroke onset with techniques such as DTI. MATERIALS AND METHODS: Fifty-two patients with acute ischemic stroke and 36 without stroke were evaluated with a DTI and FLAIR imaging protocol and clinically assessed for the severity of motor impairment using the Motricity Index within 72 hours of suspected symptom onset. RESULTS: There were widespread decreases in fractional anisotropy and increases in mean diffusivity and radial diffusivity for the acute stroke group compared with the nonstroke group. There was a significant positive association between fractional anisotropy and motor function and a significant negative association between mean diffusivity/radial diffusivity and motor function. The normal-appearing white matter ROIs that were most sensitive to the Motricity Index were the anterior/posterior limb of the internal capsule in the infarcted hemisphere and the splenium of the corpus callosum, external capsule, posterior limb/retrolenticular part of the internal capsule, superior longitudinal fasciculus, and cingulum (hippocampus) of the intrahemisphere/contralateral hemisphere. CONCLUSIONS: The microstructural integrity of normal-appearing white matter is a significant parameter to identify neural differences not only between those individuals with and without acute ischemic stroke but also correlated with the severity of acute motor impairment.

Background When the epileptogenic foci skip the motor area, the epilepsy can be cured by surgery while preserving the motor function. This surgery has been reported as subtotal hemispherectomy. The disconnective variant of this surgery, subtotal hemispherotomy, is described. Objective To demonstrate each step clearly, a cadaveric brain, 3-dimensional reconstruction and simulation model, and intraoperative photographs were used. Methods A formalin-fixed cadaveric brain was dissected to show each step of this surgery. For the 3-dimensional model, several brain structures were reconstructed from preoperative images, and the surgery was simulated. Intraoperative photographs and postoperative magnetic resonance images were taken from the representative cases. Results Temporo-parieto-occipital disconnection is performed to disconnect these lobes and the insula, limbic system, and splenium of the corpus callosum. The postcentral sulcus is the anterior border of the disconnection. Next, prefrontal disconnection is performed to disconnect the frontal lobe and the insula, frontal lobe and basal ganglia, and the anterior part of the corpus callosum. The precentral sulcus is the posterior border of the disconnection. Finally, corpus callosotomy of the central part is performed. After these steps, subtotal hemispherotomy, with preservation of the pre- and postcentral gyrus, is achieved. The 3-dimensional model clearly shows the anatomic relationships between deep brain structures. In the representative cases, postoperative motor deterioration was transient or none, and seizure-free status was achieved after surgery. Conclusion Subtotal hemispherotomy is generally difficult because of the complicated anatomy and narrow and deep surgical corridors. Combined use of these methods facilitates a clearer understanding of this surgery.

Fractional anisotropy (FA) estimated using diffusion tensor magnetic resonance imaging (dMRI) is considered as a promising biomarker in ischemic stroke (IS). The basis of this study is the assumption that the assessment of FA indices for different white matter tracts will be able to predict the main aspects of the rehabilitation potential even without determining the structural and functional bases of these influences.Objective: to study the diagnostic significance of changes in FA indices to assess various aspects of the rehabilitation potential in acute IS.Patients and methods. Examinations were made in 100 patients with IS and in 10 individuals without stroke and cognitive impairment. All the patients underwent dMRI and assessments of rehabilitation potential indicators on days 3 and 10 of the disease and at discharge.Results and discussion. The indices of FA of the ipsilateral upper longitudinal and cingulum bundles, FA and the size of an infarct focus, asymmetry of FA of the cingulum bundle (rFA), corticospinal tract (at the level of the knee of the internal capsule and bridge) and the anterior limb of the internal capsule, as well as the FA of the splenium and knee of the internal capsule of the intact hemisphere are of the most value for the functional outcome of acute IS. The microstructure of these zones determines the state of most rehabilitation domains. With respect to global outcome, the integrity of the associative tracts of the affected hemisphere is more valuable than the microstructure of the intact hemisphere and rFA. The tracts of the intact hemisphere are of particular importance for the restoration of complex rehabilitation spheres, such as cognitive status and daily living and social skills, which is necessary to ensure patient independence.Conclusion. The FA indices of the tracts under study seem to be a clinically acceptable biomarker of various aspects of the rehabilitation potential in acute IS.

To evaluate the growth trajectories and cluster features of the human fetal brain tissues using signal intensity in utero magnetic resonance imaging. In 136 fetal brain in utero, the signal intensity was measured in 20 region of interests (ROIs) including the bilateral thalamus, pons, genu, body and splenium of corpus callosum, the bilateral frontal, occipital, temporal pole, precentral and postcentral region, cerebellum and the bilateral posterior part of lateral ventricles as a reference. Calculating the signal intensity ratio (SIR) of these ROIs, and then, clustering analysis is used to explore the cluster features of SIR. Furthermore, five representative linear and nonlinear fitting models are used to estimate the relationship between SIR in each region and each cluster and gestational weeks. Over 22–38 gestational weeks, the SIR showed linear decrease in the most of (13 of 18) investigated brain regions, including the pons, bilateral occipital, precentral, postcentral, temporal, cerebellum, and thalamus. By using clustering analysis, the above brain regions could be classified into 6 clusters, and in 4 of 6 clusters, there was similar significant linear growth strategy with that in each of 13 of 18 regions. The applications of a clinical available superfast sequence with sensitivity encoding with balanced turbo field echo sequence and signal intensity-based analysis may to some extent reflect the myelination process and growth strategies of fetal brain following heterogeneous and heterochronicity trajectories. It may be helpful for us to understand the normal fetal brain development pattern through in vivo imaging method prior to birth.

[Abstract] Objective The pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT‐related white matter changes and their correlations with scores from a neuropsychological testing battery. Methods Diffusion tensor imaging measures were compared between 14 OT patients and 14 age‐ and education‐matched healthy controls, using whole‐brain tract‐based spatial statistics analysis. Correlations between altered diffusion metrics and cognitive performance in OT group were assessed. Results In all cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language), OT patients’ cognitive performance was significantly worse than that of healthy controls. OT patients demonstrated altered diffusivity metrics not only in the posterior lobe of the cerebellum (left cerebellar lobule VI) and in its efferent cerebellar fibers (left superior cerebellar peduncle), but also in medial lemniscus bilaterally (pontine tegmentum), anterior limb of the internal capsule bilaterally, right posterior limb of the internal capsule, left anterior corona radiata, right insula, and the splenium of corpus callosum. No relationship was found between diffusion measures and disease duration in OT patients. Diffusion white matter changes, mainly those located in right anterior limb of the internal capsule, were correlated with poor performance on tests of executive function, visuospatial ability, verbal memory, and visual memory in OT patients. Interpretation White matter changes were preferentially located in the cerebellum, its efferent pathways, as well as in the pontine tegmentum and key components of the frontal–thalamic–cerebellar circuit. Further work needs to be done to understand the evolution of these white matter changes and their functional consequences. National Institutes of Health; R01 NS39422 National Institutes of Health; R01 NS094607 National Institutes of Health; R01 NS085136 National Institutes of Health; R01 NS073872 National Institutes of Health; R01 NS088257 European Commission. Grant Number: ICT‐2011‐287739 Ministerio de Ecnomía y Competitividad; RTC‐2015‐3967‐1 Spanish Health Research Agency; FIS PI12/01602 Spanish Health Research Agency; FIS PI16/00451 Ministerio de Ecnomía y Competitividad; DPI‐2015‐68664‐C4‐1‐R

Background: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS.Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis.Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.

Sexual dimorphism exists at all levels of the nervous system, from genetic, anatomical and system levels. The sexual dimorphism in the axonal content of the corpus callosum (CC) has always been controversial; hence, the aim of this study was to analyse the differences in total, myelinated and unmyelinated axons density of various regions of the CC between male and female rats. To assess that, six pairs of adult male and female rats were perfused and the CC was removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium, were stained, and electron microscopic images were captured using stereological guidelines. Later, the axons density for each subregion was calculated and compared between males and females. The findings of the present study indicated region-specific differences in the myelinated, unmyelinated or the ratio of myelinated/total axons in the CC between male and female rats.

Further explorations are needed to determine how behavioral-lifestyle changes of various types influence neural plasticity in the white matter (WM); in particular, little is known about the influence of one’s self-discipline on changes in WM. A retreat program called Templestay follows the self-discipline practices used by Buddhist monks for 3 nights and 4 days; this program mainly involves meditation and other forms of behavioral-lifestyle modifications. In this study, we explored how neural plasticity occurs in WM structures in response to a relatively short retreat program. We designed a longitudinal study that investigates WM neural plasticity over the course of Templestay. The Templestay group experienced the daily life of Buddhist practitioners, whereas the control group only participated in a retreat program at the same temple. Diffusion tensor imaging data were acquired before and after the Templestay program to investigate neural plasticity in the WM. We examined changes in the fractional anisotropy maps. We observed significant changes in the fractional anisotropy maps at the left superior longitudinal fasciculus, left posterior corona radiata, and splenium of the corpus callosum after 4 days of Templestay. Based on the results of our study, a 4-day meditation period in combination with behavioral-lifestyle modifications facilitates WM myelination in regions important for cognitive functions. These results provide evidence of very rapid structural remodeling of the WM, suggesting that activity-dependent changes in myelination are induced by Templestay, a relatively understudied self-discipline program that includes behavioral-lifestyle modifications.

Conduction of action potentials along myelinated axons is affected by their structural features, such as the axonal g-ratio, the ratio between the inner and outer diameters of the myelin sheath surrounding the axon. The effect of g-ratio variance on conduction properties has been quantitatively evaluated using single-axon models. It has recently become possible to estimate a g-ratio weighted measurement in vivo using quantitative MRI. Nevertheless, it is still unclear whether the variance in the g-ratio in the healthy human brain leads to significant differences in conduction velocity. In this work we tested whether the g-ratio MRI measurement can be used to predict conduction delays in the corpus callosum. We present a comprehensive framework in which the structural properties of fibers (i.e. length and g-ratio, measured using MRI), are incorporated in a biophysical model of axon conduction, to model conduction delays of long-range white matter fibers. We applied this framework to the corpus callosum, and found conduction delay estimates that are compatible with previously estimated values of conduction delays. We account for the variance in the velocity given the axon diameter distribution in the splenium, mid-body and genu, to further compare the fibers within the corpus callosum. Conduction delays have been suggested to increase with age. Therefore, we investigated whether there are differences in the g-ratio and the fiber length between young and old adults, and whether this leads to a difference in conduction speed and delays. We found very small differences between the predicted delays of the two groups in the motor fibers of the corpus callosum. We also found that the motor fibers of the corpus callosum have the fastest conduction estimates. Using the axon diameter distributions, we found that the occipital fibers have the slowest estimations, while the frontal and motor fiber tracts have similar estimates. Our study provides a framework for predicting conduction latencies in vivo. The framework could have major implications for future studies of white matter diseases and large range network computations. Our results highlight the need for improving additional in vivo measurements of white matter microstructure.

Subjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer’s disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort. 271 participants with SCD, mild cognitive impairment (MCI) or Alzheimer’s dementia (AD) and healthy controls (CON) were included, recruited prospectively at nine centers of the observational DELCODE study. DTI was acquired using identical protocols. Using voxel-based analyses, we investigated fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) in the white matter (WM). Discrimination accuracy was determined by cross-validated elastic-net penalized regression. Center effects were explored using variance analyses. MO and FA were lower in SCD compared to CON in several anterior and posterior WM regions, including the anterior corona radiata, superior and inferior longitudinal fasciculus, cingulum and splenium of the corpus callosum (p

Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3 T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000 s/mm2). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social–emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

To investigate microstructural alterations in white matter in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using neurite orientation dispersion and density imaging (NODDI) and to assess the potential diagnostic performance of NODDI-derived parameters. In this study 14 MCI patients, 14 AD patients, and 14 healthy controls (HC) were recruited. The diffusion tensor imaging(DTI)-derived fractional anisotropy (FA) and NODDI-derived neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso) were calculated from the diffusion data. The tract-based spatial statistics (TBSS) method was used for statistical analysis with one-way ANOVA. The correlations between the parameter values and mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores were examined. A receiver operating characteristic (ROC) curve was conducted to assess the diagnostic performance of different parameters. Compared with the HC group, the NDI and ODI values decreased significantly and the Viso values were significantly increased in the MCI and AD groups (p

OBJECTIVE Focal edema of the splenium of the corpus callosum (FESCC) is infrequently seen in patients with epilepsy who are undergoing video-electroencephalography (EEG) monitoring. It is diagnosed by qualitative visual inspection of the magnetic resonance imaging (MRI) and is usually assumed to be a dichotomous phenomenon. Rapid reduction of anticonvulsants has been proposed as a cause. In this study we investigate the relationship between dose reduction of anticonvulsants and the occurrence of FESCC, based on absolute drug doses. METHODS We examined in detail the anticonvulsive therapy of all patients during video-EEG monitoring between 2014 and 2018. We compared patients with a radiologically diagnosed FESCC to controls in a 1:2 case-control analysis matched by age, epilepsy syndrome, and adjacent time of admission. In a separate correlation analysis, we examined quantitative effects of reduction of antiseizure drugs on diffusion restriction in the corpus callosum. RESULTS Of 326 patients who had an MRI following video-EEG monitoring, 12 (3.7%) had FESCC. Antiseizure drugs were reduced to a significantly greater extent in FESCC patients than in the 24 controls (P

Background: Lexical tone identification has a unique role in the perceptual processes of Chinese readers. Reduced lexical tone awareness, along with poor word-decoding abilities, is frequently observed in Chinese-speaking children with developmental dyslexia. However, whether this deficit is linked to reduced auditory processing and interrupted structural connectivity in the brain requires further investigation. This study therefore explores the white matter pathways associated with Chinese character recognition and auditory processing of pitch variations, with the objective of to identify the most representative neural correlates for Chinese developmental dyslexia. Methods: Diffusion magnetic resonance imaging and several behavior measures related to reading attainment and phonological awareness were acquired in twenty-four Chinese-speaking children with developmental dyslexia and twenty-two age-matched controls. We used diffusion magnetic resonance imaging connectometry to explore the relationships between behavior performance and specific white matter tracts. Results: The results revealed significant correlations of the left inferior fronto-occipital fasciculus, cerebellar pathways, and thalamopontine tracts with Chinese character recognition (FDR = 0.03235). In addition, the posterior isthmus and anterior splenium of the corpus callosum correlated with auditory processing (FDR = 0.03980). Conclusion: The study provides evidence that the dysconnectivity on white matter pathways correlated with developmental dyslexia in Chinese-speaking children. Furthermore, the impairments of auditory temporal timing processing presented in poor readers with significant phonological deficits are likely to be a result of impoverished myelinization in sub-cortical tracts. Such findings may assist in the clinical identification of Chinese developmental dyslexia. Keywords: auditory frequency-modulation processing, Chinese developmental dyslexia, connectometry, diffusion MRI, lexical tone awareness

The aim of our study is to determine the pathological changes of white matter microstructure in patients with early post-stroke depression (PSD), and to investigate the association between white matter integrity examined by diffusion kurtosis imaging (DKI) and early PSD. Thirty-eight patients with acute cerebral infarction were selected, including 17 patients with depression (PSD group), and 21 patients without depression (N-PSD group). In addition, 20 normal healthy controls (NORM group) were selected. All were taken DKI scans. The white matter of the frontal lobe, temporal lobe, parietal lobe, occipital lobe, anterior limb of internal capsule, and posterior limb of internal capsule, in addition to the genu of corpus callosum and splenium of corpus callosum was selected as a region of interest (ROI). Selected parameters include fractional anisotropy (FA) and mean kurtosis (MK). Compared with N-PSD group and NORM group, FA value of the left frontal lobe and MK value of the bilateral frontal lobe, bilateral temporal lobe, and genu of corpus callosum in PSD group were decreased (P

Background Wilson’s disease (WD) is an autosomal recessive disease of impaired copper metabolism. Previous study demonstrated that WD with corpus callosum abnormalities (WD-CCA) was limited to the posterior part (splenium). This study aimed to compare clinical features between WD-CCA and WD without corpus callosum abnormalities (WD-no-CCA). Methods Forty-one WD patients who had markedly neurological dysfunctions were included in this study. We retrospectively reviewed clinical, biochemical characteristics and MRI findings in the 41 WD patients. All patients were assessed using the Unified Wilson’s Disease Rating Scale. Results Nine patients had corpus callosum abnormalities, 4 of 9 patients had abnormal signal in the genu and splenium, 5 of 9 patients had abnormal signal only in the splenium. WD-CCA had longer course (9.9 ± 4.0 years vs. 3.4 ± 3.6 years, p

Background Prenatal alcohol exposure (PAE) is linked to alterations of cerebral white matter, including volume and nonspecific diffusion magnetic resonance imaging (MRI) indices of microstructure in humans. Some animal models of PAE have demonstrated myelination deficiencies, but myelin levels have not yet been evaluated in individuals with PAE. Multiecho T2 MRI offers a quantitative method to estimate myelin water fraction (MWF; related to myelin content) noninvasively, which was used here to evaluate brain myelination in children with PAE. Methods Participants with PAE (n = 10, 6 females, mean age 13.9 years, range 7 to 18 years) and controls (n = 14, 11 females, mean age 13.2 years, range 9 to 16 years) underwent 3T MRI of the brain. T2 images (15 minutes acquisition for 32 echoes) were used to create MWF maps from which mean MWF was measured in 12 regions of interest (ROIs) including 8 in white matter and 4 in deep gray matter. Results As expected, across the combined sample, MWF was highest for major white matter tracts such as the internal capsule and genu/splenium of the corpus callosum (10 to 18%) while the caudate and putamen had MWF less than 5%. Mean MWF was similar across 11/12 brain white and gray matter regions for the PAE and control groups (L/R internal capsule, major forceps, putamen, caudate nucleus, L minor forceps, genu and splenium of corpus callosum). In the PAE group, MWF was positively correlated with age in the genu of corpus callosum and right minor forceps, notably 2 frontal tracts. Conclusions Given comparable MRI-derived myelination fraction measures in PAE relative to controls, white matter alterations shown in other imaging studies, such as diffusion tensor imaging, may reflect microstructural anomalies related to axon caliber and density.

Impaired illness awareness (Imp-IA) in schizophrenia is associated with interhemispheric imbalance, resulting in left hemisphere dominance, primarily within the posterior parietal area (PPA). This may represent an interhemispheric “disconnection syndrome” between PPAs. To test this hypothesis, we aimed to determine if diffusion-based measures of white matter integrity were disrupted in the corpus callosal tracts linking PPAs (i.e., splenium) in patients with Imp-IA in schizophrenia. T1-weighted and diffusion-weighted scans were acquired on a 1.5T GE scanner for 100 participants with a DSM-IV-TR diagnosis of schizophrenia and 134 healthy controls aged 18 to 79 years. The corpus callosal white matter tracts were compared among patients with Imp-IA (n = 40), intact illness awareness (n = 60), and healthy controls. White matter disruption was measured with fractional anisotropy (FA) and mean diffusivity (MD). Group differences in FA were found in the splenium, with patients with Imp-IA having the lowest FA, which remained significant after controlling for sex, age, global cognition, and premorbid intelligence. No group differences in MD were observed. Splenial white matter tracts of the corpus callosum appear compromised in patients with Imp-IA. Transcallosal interhemispheric PPA white matter disruption may represent a “disconnection syndrome”, manifesting as Imp-IA in schizophrenia. Future studies are required to investigate the effects of noninvasive brain stimulation interventions, such as transcranial direct current or magnetic stimulation, on Imp-IA in association with white matter changes in patients with schizophrenia.

Two patients who showed transient lesions in the splenium of the corpus callosum (SCC) secondary to acute ischemic stroke are reported. Both patients had embolic strokes and showed an isolated lesion in the SCC on magnetic resonance imaging (MRI) 1-2 weeks after the onset of stroke, with a hyperintense lesion on diffusion-weighted imaging and decreased apparent diffusion coefficient values, with no symptoms related to the lesion. In both cases, the lesion disappeared on MRI approximately 1 week later. Clinicians should note that transient SCC lesions can occur following acute ischemic stroke and avoid misdiagnosing them and performing unnecessary examinations or treatment.

Purpose: To investigate whether the genu of the corpus callosum is involved in patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type I. Methods: Twenty-three cases of clinically confirmed MERS I were analyzed retrospectively, and MRI features of the lesion were observed. The apparent diffusion coefficient (ADC) values of the same region of interests in lesions at the splenium and genu of the corpus callosum were measured before and after treatment (i.e., four groups), and the average ADC values were calculated. Paired t-tests were used to compare the ADC values of lesions in the splenium and genu before and after treatment. Independent sample t-tests were used to compare the values in the splenium and genu after treatment. Results: The mean ADC values of the splenium before and after treatment were 0.448 ± 0.124 and 0.790 ± 0.070 × 10−3 mm2/s, respectively, showing significant difference (P < 0.01). The mean ADC values in the genu before and after treatment were 0.783 ± 0.067 and 0.829 ± 0.070 × 10−3 mm2/s, respectively, also showing significant difference (P < 0.01). There was no significant difference in the ADC values between the splenium and genu after treatment (P > 0.05). Conclusion: The genu showed a slight restriction in diffusion in the acute stage of type I MERS. After treatment, this diffusion restriction diminished as it typically does in the splenium. Our results indicate that the pathology in MERS extends well beyond the visible lesions.

Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1-positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. Glial fibrillary acidic protein (GFAP)-positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mTBIs do not necessarily result in worsening pathology. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14508.

BACKGROUND 3D brain proton MR spectroscopic imaging (1 H MRSI) facilitates simultaneous metabolic profiling of multiple loci, at higher, sub-1 cm3 , spatial resolution than single-voxel 1 H MRS with the ability to separate tissue-type partial volume contribution(s). PURPOSE To determine if: 1) white matter (WM) damage in mild traumatic brain injury (mTBI) is homogeneously diffuse, or if specific regions are more affected; 2) partial-volume-corrected, structure-specific 1 H MRSI voxel averaging is sensitive to regional WM metabolic abnormalities. STUDY TYPE Retrospective cross-sectional cohort study. POPULATION Twenty-seven subjects: 15 symptomatic mTBI patients, 12 matched controls. FIELD STRENGTH/SEQUENCE 3T using 3D 1 H MRSI over a 360-cm3 volume of interest (VOI) centered over the corpus callosum, partitioned into 480 voxels, each 0.75 cm3 . ASSESSMENT N-acetyl-aspartate (NAA), creatine, choline, and myo-inositol concentrations estimated in predominantly WM regions: body, genu, and splenium of the corpus callosum, corona radiata, frontal, and occipital WM. STATISTICAL TESTS Analysis of covariance (ANCOVA) to compare patients with controls in terms of regional concentrations. The effect sizes (Cohen's d) of the mean differences were compared across regions and with previously published global data obtained with linear regression of the WM over the entire VOI in the same dataset. RESULTS Despite patients' global VOI WM NAA being significantly lower than the controls', no regional differences were observed for any metabolite. Regional NAA comparisons, however, were all unidirectional (patients' NAA concentrations < controls') within a narrow range: 0.3 ≤ Cohen's d ≤ 0.6. DATA CONCLUSION Since the patient group was symptomatic and exhibiting global WM NAA deficits, these findings suggest: 1) diffuse axonal mTBI damage; that is 2) below the 1 H MRSI detection threshold in small regions. Therefore, larger, ie, more sensitive, single-voxel 1 H MRS, placed anywhere in WM regions, may be well suited for mTBI 1 H MRS studies, given that these results are confirmed in other cohorts. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1424-1432.

Objective Fetal brain diffusion tensor imaging (DTI) offers quantitative analysis of the developing brain. The objective was to 1) quantify DTI measures across gestation in a cohort of fetuses without brain abnormalities using full retrospective correction for fetal head motion 2) compare results obtained in utero to those in preterm infants. Materials and methods Motion-corrected DTI analysis was performed on data sets obtained at 1.5T from 32 fetuses scanned between 21.29 and 37.57 (median 31.86) weeks. Results were compared to 32 preterm infants scanned at 3T between 27.43 and 37.14 (median 33.07) weeks. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were quantified by region of interest measurements and tractography was performed. Results Fetal DTI was successful in 84% of fetuses for whom there was sufficient data for DTI estimation, and at least one tract could be obtained in 25 cases. Fetal FA values increased and ADC values decreased with age at scan (PLIC FA: p = 0.001; R2 = 0.469; slope = 0.011; splenium FA: p

White matter microstructure can be measured with diffusion tensor imaging (DTI). While increasing age is a predictor of white matter (WM) microstructure changes, roles of other possible modifiers, such as cardiovascular risk factors, APOE e4 allele status and biological sex have not been clarified. We investigated 665 cognitively normal participants from the Baltimore Longitudinal Study of Aging (age 50–95, 56.7% female) with a total of 1384 DTI scans. WM microstructure was assessed by fractional anisotropy (FA) and mean diffusivity (MD). A vascular burden score was defined as the sum of five risk factors (hypertension, obesity, elevated cholesterol, diabetes and smoking status). Linear mixed effects models assessed the association of baseline vascular burden on baseline and on rates of change of FA and MD over a mean follow-up of 3.6 years, while controlling for age, race, and scanner type. We also compared DTI trajectories in APOE e4 carriers vs. non-carriers and men vs. women. At baseline, higher vascular burden was associated with lower FA and higher MD in many WM structures including association, commissural, and projection fibers. Higher baseline vascular burden was also associated with greater longitudinal decline in FA in the hippocampal part of the cingulum and the fornix (crus)/stria terminalis and splenium of the corpus callosum, and with greater increases in MD in the splenium of the corpus callosum. APOE e4 carriers did not differ from non-carriers in baseline DTI metrics but had greater decline in FA in the genu and splenium of the corpus callosum. Men had higher FA and lower MD in multiple WM regions at baseline but showed greater increase in MD in the genu of the corpus callosum. Women showed greater decreases over time in FA in the gyrus part of the cingulum, compared to men. Our findings show that modifiable vascular risk factors (1) have a negative impact on white matter microstructure and (2) are associated with faster microstructural deterioration of temporal WM regions and the splenium of the corpus callosum in cognitively normal adults. Reducing vascular burden in aging could modify the rate of WM deterioration and could decrease age-related cognitive decline and impairment.

Prior neuroimaging studies have reported white matter network underconnectivity as a potential mechanism for autism spectrum disorder (ASD). In this study, we examined the structural connectome of children with ASD using edge density imaging (EDI), and then applied machine-learning algorithms to identify children with ASD based on tract-based connectivity metrics. Boys aged 8–12 years were included: 14 with ASD and 33 typically developing children. The edge density (ED) maps were computed from probabilistic streamline tractography applied to high angular resolution diffusion imaging. Tract-based spatial statistics was used for voxel-wise comparison and coregistration of ED maps in addition to conventional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Tract-based average DTI/connectome metrics were calculated and used as input for different machine-learning models: naïve Bayes, random forest, support vector machines (SVMs), and neural networks. For these models, cross-validation was performed with stratified random sampling ( × 1,000 permutations). The average accuracy among validation samples was calculated. In voxel-wise analysis, the body and splenium of corpus callosum, bilateral superior and posterior corona radiata, and left superior longitudinal fasciculus showed significantly lower ED in children with ASD; whereas, we could not find significant difference in FA, MD, and RD maps between the two study groups. Overall, machine-learning models using tract-based ED metrics had better performance in identification of children with ASD compared with those using FA, MD, and RD. The EDI-based random forest models had greater average accuracy (75.3%), specificity (97.0%), and positive predictive value (81.5%), whereas EDI-based polynomial SVM had greater sensitivity (51.4%) and negative predictive values (77.7%). In conclusion, we found reduced density of connectome edges in the posterior white matter tracts of children with ASD, and demonstrated the feasibility of connectome-based machine-learning algorithms in identification of children with ASD.

Background Previous studies have documented a spectrum of brain magnetic resonance imaging (MRI) abnormalities in patients with cerebral malaria, but little is known about the prevalence of such abnormalities in patients with non-cerebral malaria. The aim of this study was to assess the frequency of brain MRI findings in returning travellers with non-cerebral malaria. Methods A total of 17 inpatients with microscopically confirmed Plasmodium falciparum non-cerebral malaria underwent structural brain MRI at 3.0 Tesla, including susceptibility-weighted imaging (SWI). Presence of imaging findings was recorded and correlated with clinical findings and parasitaemia. Results Structural brain abnormalities included a hyperintense lesion of the splenium on T2-weighted imaging (n = 3) accompanied by visible diffusion restriction (n = 2). Isolated brain microhaemorrhage was detected in 3 patients. T2-hyperintense signal abnormalities of the white matter ranged from absent to diffuse (n = 10 had 0–5 lesions, n = 5 had 5–20 lesions and 2 patients had more than 50 lesions). Imaging findings were not associated with parasitaemia or HRP2 levels. Conclusion Brain MRI reveals a considerable frequency of T2-hyperintense splenial lesions in returning travellers with non-cerebral malaria, which appears to be independent of parasitaemia.

Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice. Keywords: Adversity, Child abuse, Psychopathology, Attachment, Brain imaging