Brainstem Volume Research Articles

Differentiation of early mild cognitive impairment in brainstem MR images using multifractal detrended moving average singularity spectral features

Brainstem texture analysis can provide valuable information in the diagnosis of Early Mild Cognitive Impairment (EMCI) condition. In this work, 3D brainstem structure is segmented and analysed for texture alterations using multifractal features to differentiate EMCI from other Alzheimer’s disease stages. The images obtained from public domain database are preprocessed for spatial registration, skull stripping and contrast enhancement. White matter volume is segmented from the preprocessed images using fuzzy ‘C’ means clustering algorithm. Midsagittal white matter tissue is used as the initial seed to segment the brainstem volume using sparse field level set method. Multifractal detrended moving average algorithm is used to compute the fluctuation function, generalized Hurst exponent and mass exponent to study the multifractal characteristics of brainstem structure. Features extracted from the multifractal spectrum are analysed to differentiate the images pertaining to EMCI subject group. Results indicate that the proposed technique is able to segment the brainstem structure from all the considered images. The fluctuation function is observed to have linear relationship with scale. The generalized Hurst exponent decreases with order and mass exponent follows a non-linear trend demonstrating the multifractal nature of brainstem. Singularity spectral features namely strength of multifractality, Holder exponent at f(2.8), tangent slope and maximum Holder exponent are found to be most significant in differentiating EMCI from subject groups. As this complex EMCI distinction is clinically important, the proposed approach is useful for early diagnosis of Alzheimer’s condition.

A Risk-Adjusted Control Chart to Evaluate Intensity Modulated Radiation Therapy Plan Quality

PurposeThis study aimed to develop a quality control framework for intensity modulated radiation therapy plan evaluations that can account for variations in patient- and treatment-specific risk factors. Methods and MaterialsPatient-specific risk factors, such as a patient’s anatomy and tumor dose requirements, affect organs-at-risk (OARs) dose-volume histograms (DVHs), which in turn affects plan quality and can potentially cause adverse effects. Treatment-specific risk factors, such as the use of chemotherapy and surgery, are clinically relevant when evaluating radiation therapy planning criteria. A risk-adjusted control chart was developed to identify unusual plan quality after accounting for patient- and treatment-specific risk factors. In this proof of concept, 6 OAR DVH points and average monitor units serve as proxies for plan quality. Eighteen risk factors are considered for modeling quality: planning target volume (PTV) and OAR cross-sectional areas; volumes, spreads, and surface areas; minimum and centroid distances between OARs and the PTV; 6 PTV DVH points; use of chemotherapy; and surgery. A total of 69 head and neck cases were used to demonstrate the application of risk-adjusted control charts, and the results were compared with the application of conventional control charts. ResultsThe risk-adjusted control chart remains robust to interpatient variations in the studied risk factors, unlike the conventional control chart. For the brainstem, the conventional chart signaled 4 patients with unusual (out-of-control) doses to 2% brainstem volume. However, the adjusted chart did not signal any plans after accounting for their risk factors. For the spinal cord doses to 2% brainstem volume, the conventional chart signaled 2 patients, and the adjusted chart signaled a separate patient after accounting for their risk factors. Similar adjustments were observed for the other DVH points when evaluating brainstem, spinal cord, ipsilateral parotid, and average monitor units. The adjustments can be directly attributed to the patient- and treatment-specific risk factors. ConclusionsA risk-adjusted control chart was developed to evaluate plan quality, which is robust to variations in patient- and treatment-specific parameters.

Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3.MethodsSeventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements.ResultsSerum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = − 0.4217, p = 0.0003) and brainstem volumes (r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat.ConclusionsLevels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.

Cortical and Subcortical Structural Segmentation in Alzheimer’s Disease

Purpose: Alzheimer’s disease is a neurodegenerative disease that begins before clinical symptoms emerge. Amyloid-beta plaques and tau neurofibrillary tangles are the hallmark lesions of Alzheimer’s Disease (AD). Amyloid-beta plaques deposition is associated with increased hippocampal volume loss. The tissue volume measures reflect multiple underlying pathologies contributing to neurodegeneration, of which are the most characteristics of AD. Anatomical atrophy, as evidenced using Magnetic Resonance Imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of AD. Measurements of whole brain and hippocampal atrophy rates from serial structural MRI are potential markers of the underlying neuroaxonal damage and disease progression in AD. In this study, we extract automatically subcortical brain structures in AD and control subjects. Materials and Methods: In this study we used 20 images (10 AD patients and 10 controls) taken from the Minimal Interval Resonance Imaging in Alzheimer's Disease (MIRIAD) dataset. We obtained volumes of Cerebrospinal Fluid (CSF), White Matter (WM), Grey Matter (GM), brain hemispheres, cerebellum and brainstem using volBrain pipeline. Subcortical brain structure segments and related volumes and label maps information were extracted. We compared left and right sides of some of the important brain area in AD for obtaining a biomarker with brain atrophy. Amygdala, caudate and hippocampus have shown to be undergone atrophy in AD. Results: We provided volume information of some intracranial areas such as brain hemispheres, cerebellum and brainstem. Conclusion: The results showed smaller hippocampal volume in AD patients compared to the controls. In addition to hippocampus, similar atrophy is also observable in amygdala and caudate.

Comparative Volumetric Analysis of the Brain and Cerebrospinal Fluid in Chiari Type I Malformation Patients: A Morphological Study.

Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients.

Quantitative MRI study of infant regional brain size following surgery for long-gap esophageal atresia requiring prolonged critical care

IntroductionLittle is known regarding the impact of concurrent critical illness and thoracic noncardiac perioperative critical care on postnatal brain development. Previously, we reported smaller total brain volumes in both critically ill full-term and premature patients following complex perioperative critical care for long-gap esophageal atresia (LGEA). Our current report assessed trends in regional brain sizes during infancy, and probed for any group differences. MethodsFull-term (n = 13) and preterm (n = 13) patients without any previously known neurological concerns, and control infants (n = 16), underwent non-sedated 3 T MRI in infancy (<1 year old). T2-weighted images underwent semi-automated brain segmentation using Morphologically Adaptive Neonatal Tissue Segmentation (MANTiS). Regional tissue volumes of the forebrain, deep gray matter (DGM), cerebellum, and brainstem are presented as absolute (cm3) and normalized (% total brain volume (%TBV)) values. Group differences were assessed using a general linear model univariate analysis with corrected age at scan as a covariate. ResultsAbsolute volumes of regions analyzed increased with advancing age, paralleling total brain size, but were significantly smaller in both full-term and premature patients compared to controls. Normalized volumes (%TBV) of forebrain, DGM, and cerebellum were not different between subject groups analyzed. Normalized brainstem volumes showed group differences that warrant future studies to confirm the same finding. DiscussionBoth full-term and premature critically ill infants undergoing life-saving surgery for LGEA are at risk of smaller total and regional brain sizes. Normalized volumes support globally delayed or diminished brain growth in patients. Future research should look into neurodevelopmental outcomes of infants born with LGEA.

Human gestational N-methyl-d-aspartate receptor autoantibodies impair neonatal murine brain function.

Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N-methyl-d-aspartate receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface ABs, yet little is known about effects on fetal development during pregnancy. We established a murine model of in utero exposure to human recombinant NR1 and isotype-matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected on embryonic days 13 and 17 each with 240μg of human monoclonal ABs. Offspring were investigated for acute and chronic effects on NMDAR function, brain development, and behavior. Transferred NR1 ABs enriched in the fetus and bound to synaptic structures in the fetal brain. Density of NMDAR was considerably reduced (up to -49.2%) and electrophysiological properties were altered, reflected by decreased amplitudes of spontaneous excitatory postsynaptic currents in young neonates (-34.4%). NR1 AB-treated animals displayed increased early postnatal mortality (+27.2%), impaired neurodevelopmental reflexes, altered blood pH, and reduced bodyweight. During adolescence and adulthood, animals showed hyperactivity (+27.8% median activity over 14 days), lower anxiety, and impaired sensorimotor gating. NR1 ABs caused long-lasting neuropathological effects also in aged mice (10 months), such as reduced volumes of cerebellum, midbrain, and brainstem. The data collectively support a model in which asymptomatic mothers can harbor low-level pathogenic human NR1 ABs that are diaplacentally transferred, causing neurotoxic effects on neonatal development. Thus, AB-mediated network changes may represent a potentially treatable neurodevelopmental congenital brain disorder contributing to lifelong neuropsychiatric morbidity in affected children. ANN NEUROL 2019;86:656-670.

Effect of MRI/CT Image Fusion on Radiotherapy Planning for Central Nervous System Lymphoma

We investigate the impact of MRI/CT images fusion on radiotherapy planning for patients with central nervous system lymphoma(CNSL). This was a single center study in patients with CNSL who received radiotherapy simulated with CT and MR from January 2015 to December 2017.10 patients were proven by pathology, 9 patients with diffuse large B-cell lymphoma and 1 patient with follicular lymphoma; including 5 males and 5 females; median age 55 years old （rang 23-72 years old）. There were 5 cases of primary central nervous system lymphoma and 5 cases of secondary central nervous system lymphoma. All patients received conventional fractionated radiotherapy(2 Gy per fraction,5 days per week) after chemotherapy: The whole brain irradiation dose ranged from 30Gy to 36 Gy, followed by a limited field to gross tumor volume (GTV) to 45 Gy. MR images were registered with the CT acquired for treatment planning system. The MR (including DWI, T1- and T2-weighted image) and CT images were subsequently fused by means of a dedicated RT planning system image fusion tool based on a mutual information algorithm. Statistical analysis was performed using a statistical analysis software, with P < 0.05 as the statistical significance. The mean volume of GTVMRI/CT was significantly smaller than that of GTVCT (29.22±9.96 cm3 vs 33.41±11.11 cm3, P=0.042).The average volume of brainstem was no significant difference between brainstemMRI/CT and brainstemCT (26.14±1.54 cm3 vs 26.64±1.84cm3, P=0.256). After target volume reduction, The objective response rate (ORR) was 100% and the l-year overall survival (OS) was 50% ,1 patient failed out of GTV radiation field, 2 cases failed in distant. MRI/CT image fusion is a useful tool in radiotherapy treatment planning for central nervous system lymphoma, which improves the definition of tumor volume, reduces organs at risk dose, and does not increase the local recurrence rate.

Repeat variations in polyglutamine disease–associated genes and cognitive function in old age

Although the heritability of cognitive function in old age is substantial, genome-wide association studies have had limited success in elucidating its genetic basis, leaving a considerable amount of “missing heritability.” Aside from single nucleotide polymorphisms, genome-wide association studies are unable to assess other large sources of genetic variation, such as tandem repeat polymorphisms. Therefore, here, we studied the association of cytosine-adenine-guanine (CAG) repeat variations in polyglutamine disease–associated genes (PDAGs) with cognitive function in older adults. In a large cohort consisting of 5786 participants, we found that the CAG repeat number in 3 PDAGs (TBP, HTT, and AR) were significantly associated with the decline in cognitive function, which together accounted for 0.49% of the variation. Furthermore, in an magnetic resonance imaging substudy, we found that CAG repeat polymorphisms in 4 PDAGs (ATXN2, CACNA1A, ATXN7, and AR) were associated with different imaging characteristics, including brain stem, putamen, globus pallidus, thalamus, and amygdala volumes. Our findings indicate that tandem repeat polymorphisms are associated with cognitive function in older adults and highlight the importance of PDAGs in elucidating its missing heritability.

Sleep disturbances in Wolfram syndrome

BackgroundWolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.MethodsGenetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements.ResultsTwenty-one patients were evaluated ranging from age 8.9–29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI’s ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients’ scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders.ConclusionsWolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.

Altered neuropsychological performance and reduced brain volumetrics in people living with HIV on integrase strand transfer inhibitors.

Neuropsychiatric symptoms have been reported in people living with HIV (PLWH) on integrase strand transfer inhibitors (INSTIs) in postmarketing analysis. Limited data exist regarding brain integrity (function and structure) in PLWH prescribed INSTIs compared with other HIV treatment regimens. A cross-sectional analysis of PLWH on combined antiretroviral therapy aged more than 18 years at a single institution. Neuropsychological tests were administered to calculate domain deficit scores in learning/memory, executive function and motor/psychomotor domains. Cortical and subcortical volumes from MRI were obtained using the FreeSurfer software suite (v5.3). Of 202 participants, median age 55 (48, 60) years old, 49% were on INSTI-based combined antiretroviral therapy. PLWH on INSTIs were similar to individuals on non-INSTIs in terms of age, sex, race, education years, smoking history, depression scores, psychiatric medication use, presence of hepatitis C infection, history of substance use, HIV infection duration and recent or nadir CD4 T-cell count. Participants in the INSTI group performed worse than non-INSTI users in the verbal learning and memory domain [1.5 (interquartile range 0, 2.5) versus 1 (0, 2); P = 0.016]. The INSTI and non-INSTI groups were similar for other cognitive domains. Frontal, brain stem and cerebellar volumes were reduced in INSTI compared with non-INSTI users (all P = <0.05). We demonstrated modest differences in learning/memory performance and smaller brain volumes in PLWH on INSTI-based regimens compared with non-INSTI users. Prospective studies are needed to define mechanisms and the clinical significance of reduced brain integrity in PLWH on INSTIs.

Is 1H-MR spectroscopy useful as a diagnostic aid in MSA-C?

BackgroundMultiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease with a cerebellar subtype where ataxic symptoms predominate (MSA-C) associated with autonomic dysfunction and a grave prognosis. The purpose of this analysis was to identify if cerebellar volumetry and MR spectroscopy obtained as part of routine clinical work up of patients with sporadic ataxia differentiates patients with multiple system atrophy- cerebellar type (MSA-C) from those with sporadic adult-onset ataxia of unknown etiology (SAOA) who’s condition follows a more benign course.MethodsRetrospective comparison was undertaken of 20 clinically probable or possible MSA-C patients, 20 age and sex matched patients with SAOA and 20 healthy control subjects. Single voxel 1H-MR spectroscopy of the cerebellar hemisphere and vermis and volumetric analysis of the cerebellum and brainstem were undertaken on baseline scans, comparing all groups.ResultsThere was significant reduction in NAA/Cr levels in patients with MSA-C when compared to those with ISA (p = 0.005) and healthy controls (p < 0.001) in both the hemisphere and vermis. Brainstem volume was significantly reduced in MSA-C patients compared to SAOA patients (p < 0.001) and healthy controls (p < 0.001). There was no difference in cerebellar volume between MSA-C patients and SAOA patients.ConclusionThis paper demonstrates that at presentation, MSA-C patients have a significant reduction of NAA/Cr in the cerebellum and significant decrease in brainstem volume when compared to SAOA and healthy controls. This is the first study to sucessfully show clinical utility of MR spectroscopy of the cerebellum for differentiating MSA-C from patients with SAOA.

Accurate, rapid and reliable, fully automated MRI brainstem segmentation for application in multiple sclerosis and neurodegenerative diseases.

Neurodegenerative disorders, such as Alzheimer's disease (AD) and progressive forms of multiple sclerosis (MS), can affect the brainstem and are associated with atrophy that can be visualized by MRI. Anatomically accurate, large-scale assessments of brainstem atrophy are challenging due to lack of automated, accurate segmentation methods. We present a novel method for brainstem volumetry using a fully-automated segmentation approach based on multi-dimensional gated recurrent units (MD-GRU), a deep learning based semantic segmentation approach employing a convolutional adaptation of gated recurrent units. The neural network was trained on 67 3D-high resolution T1-weighted MRI scans from MS patients and healthy controls (HC) and refined using segmentations of 20 independent MS patients' scans. Reproducibility was assessed in MR test-retest experiments in 33 HC. Accuracy and robustness were examined by Dice scores comparing MD-GRU to FreeSurfer and manual brainstem segmentations in independent MS and AD datasets. The mean %-change/SD between test-retest brainstem volumes were 0.45%/0.005 (MD-GRU), 0.95%/0.009 (FreeSurfer), 0.86%/0.007 (manually edited segmentations). Comparing MD-GRU to manually edited segmentations the mean Dice scores/SD were: 0.97/0.005 (brainstem), 0.95/0.013 (mesencephalon), 0.98/0.006 (pons), 0.95/0.015 (medulla oblongata). Compared to the manual gold standard, MD-GRU brainstem segmentations were more accurate than FreeSurfer segmentations (p < .001). In the multi-centric acquired AD data, the mean Dice score/SD for the MD-GRU-manual segmentation comparison was 0.97/0.006. The fully automated brainstem segmentation method MD-GRU provides accurate, highly reproducible, and robust segmentations in HC and patients with MS and AD in 200 s/scan on an Nvidia GeForce GTX 1080 GPU and shows potential for application in large and longitudinal datasets.

Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years

To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition. We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10years of age (73 males; 93 females). Top quartile levels on ≥2days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions. Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r=-0.18; P=.021), and cerebellum and brainstem was highly correlated with grey matter (r=0.55; P<.001) and white matter (r=0.29; P<.001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P=.016), but the association with white matter was marginally significant (P=.051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ. Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.

0936 Sleep Disturbances in Wolfram Syndrome

Abstract Introduction Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients. Methods Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements. Results Twenty-one patients were evaluated ranging from age 8.9 - 29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI’s ≥1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients’ scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders. Conclusion Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life. Support (If Any) This work was supported by the NICHD (HD070855; Hershey, PI) and supported by CTSA (UL1 RR024992) and Diabetes Research Center (DK 020579).

Structural Magnetic Resonance Imaging-Based Brain Morphology Study in Infants and Toddlers With Down Syndrome: The Effect of Comorbidities

BackgroundDown syndrome (DS) is the most prevalent chromosomal disorder characterized by intellectual disability, multiple organ anomalies, generalized muscular hypotonia, and characteristic physical features. The presence of DS-associated medical comorbidities has contributed to brain morphologic changes. The aim of this study was to evaluate brain morphologic characteristics during infant and toddler ages in patients with DS using structural brain magnetic resonance imaging. MethodsStructural brain T1-weighted magnetic resonance images from participants with DS with complete chromosome 21 trisomy (n = 20; 1.6 ± 0.6 [mean ± standard deviation] years old) were analyzed using FreeSurfer. The measurements were compared with those of 60 gender- and age-matched neurotypical controls by Cohen’s d statistic and unpaired t test with false discovery rate correction for multiple comparisons and analyzed using a univariate general linear model with the following DS-associated medical comorbidities: congenital cardiac disease, infantile spasms, and hypothyroidism. ResultsWe identified 27 candidate measurements with large effect sizes (absolute d > 0.8) and statistically significant differences (P < 6.9 × 10−3). Among them were decreased volumes in bilateral cerebellar gray matter and right cerebellar white matter and brainstem and cortical abnormalities in the right superior temporal, right rostral anterior cingulate, and left rostral middle frontal gyrus, independent of comorbid effects. Only bilateral cerebellar gray matter volumes and brainstem volume showed differences between DS and healthy groups during infancy. ConclusionThese results suggest that cerebellar gray matter and brainstem may represent the primary regions affected by the presence of an additional copy of chromosome 21.

Brain atrophy in Parkinson's disease with polysomnography-confirmed REM sleep behavior disorder.

We aimed to investigate cortical and subcortical brain alterations in people with Parkinson's disease with polysomnography-confirmed rapid eye movement (REM) sleep behavior disorder (RBD). Thirty people with Parkinson's disease, including 15 people with RBD, were recruited and compared with 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. People with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared with people without RBD. Compared with controls, people with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, people without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson's disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson's disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in people with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in people with Parkinson's disease with RBD.

Characterization of Alzheimer conditions in MR images using volumetric and sagittal brainstem texture features

Background and ObjectiveBrainstem analysis in Magnetic Resonance Images is essential to detect Alzheimer's condition in the preclinical stages. In this work, an attempt has been made to segment the brainstem in sagittal (2D) and volumetric (3D) images and evaluate texture changes to differentiate Alzheimer's disease (AD) stages. MethodThe images obtained from a public access database are spatial normalized, skull stripped and contrast enhanced. Morphological Reconstruction based Fast and Robust Fuzzy ‘C’ Means technique is used to cluster the brain tissue in preprocessed images into three groups namely cerebrospinal fluid, grey matter and white matter. Brainstem is segmented from the white matter tissue using connected component labelling. Texture features from volumetric and sagittal brainstem slices are extracted and its statistical significance is evaluated. ResultsResults show that the proposed approach is able to segment the brainstem from all the considered images. Variation in texture is observed to be less than 2% among sagittal brainstem slices. Additionally, midsagittal and volumetric features are correlated, suggesting that midsagittal brainstem structure gives an estimate of brainstem volume. Texture features extracted from midsagittal slice shows significant variation (p < 0.05) and is able to differentiate AD classes. ConclusionMidsagittal brainstem texture features are able to capture the changes occurring in the early stages of disease condition. As the distinction of AD in preclinical stage is complex and clinically significant, this approach could be useful for early diagnosis of the disease.

Chronic Alcohol Drinking Slows Brain Development in Adolescent and Young Adult Nonhuman Primates.

The transition from adolescence to adulthood is associated with brain remodeling in the final stages of developmental growth. It is also a period when a large proportion of this age group engages in binge alcohol drinking (occasional consumption of four to five drinks leading to intoxication) and heavy alcohol drinking (binge drinking on ≥5 d in a month). Here we report on magnetic resonance imaging of developmental changes in the brain occurring during late adolescence and early adulthood (3.5–7.5 years of age) in a rhesus macaque model of alcohol self-administration. Monkeys were imaged prior to alcohol exposure, and following ∼6 and ∼12 months of daily (22 h/d) access to ethanol and water. The results revealed that the brain volume increases by 1 ml/1.87 years throughout the late adolescence and early adulthood in controls. Heavy alcohol drinking reduced the rate of brain growth by 0.25 ml/year per 1 g/kg daily ethanol. Cortical volume increased throughout this period with no significant effect of alcohol drinking on the cortical growth rate. In subcortical regions, age-dependent increases in the volumes of globus pallidus, thalamus, brainstem, and cerebellum were observed. Heavy drinking attenuated the growth rate of the thalamus. Thus, developmental brain volume changes in the span of late adolescence to young adulthood in macaques is altered by excessive alcohol, an insult that may be linked to the continuation of heavy drinking throughout later adult life.

Updated Imaging Findings in Congenital Zika Syndrome: A Disease Story That is Still Being Written.

In congenital Zika virus syndrome (CZS), the most frequent radiological findings are calcifications in the cortical-white matter junction and malformations of cortical development (pachygyria or polymicrogyria, which occur predominantly in the frontal lobes, or a simplified gyral pattern), ventriculomegaly, enlargement of the cisterna magna and the extra-axial subarachnoid space, corpus callosum abnormalities, and reduced brain volume. This syndrome can also result in a decrease in the brainstem and cerebellum volumes and delayed myelination. Infants with CZS may show venous thrombosis and lenticulostriate vasculopathies. Over a 3-year follow-up period, many infants with CZS showed hydrocephalus, reduction in brain calcifications, and greater reduction in brain thickness.