Brainstem Volume Research Articles

Multimodal, Longitudinal Profiling of SCA1 Identifies Predictors of Disease Severity and Progression.

Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant neurodegenerative disease. Objective surrogate markers sensitive to detect changes in disease severity are needed to reduce sample sizes in interventional trials and identification of predictors of faster disease progression would facilitate patient selection, enrichment, or stratification in such trials. We performed a prospective 1-year longitudinal, multimodal study in 34 ataxic SCA1 individuals and 21 healthy controls. We collected clinical, patient-reported outcomes, biochemical and magnetic resonance (MR) biomarkers at baseline and after 1 year. We determined 1-year progression and evaluated the potential predictive value of several baseline markers on 1-year disease progression. At baseline, multiple structural and spectroscopic MR markers in pons and cerebellum differentiated SCA1 from healthy controls and correlated with disease severity. Plasma and cerebrospinal fluid (CSF) neurofilament light (NfL) chain and CSF glial fibrillary acidic protein (GFAP) were elevated in SCA1. In longitudinal analysis, total brainstem and pontine volume change, inventory of non-ataxia signs (INAS) count, and SCA functional index (SCAFI) showed larger responsiveness compared to the Scale for Assessment and Rating of Ataxia (SARA). Longer disease duration, longer non-expanded CAG repeat length, and higher disease burden were associated with faster SARA increase after 1-year in the SCA1 group. Similarly, lower baseline brainstem, pontine, and cerebellar volumes, as well as lower levels of N-acetylaspartate and glutamate in the cerebellar white matter, were also associated with faster SARA increase. Our results guide the selection of the most sensitive measures of disease progression in SCA1 and have identified features associated with accelerated progression that could inform the design of clinical trials. ANN NEUROL 2024.

Multi-Dimensional Morphometric and Volumetric Analysis of the Posterior Cranial Fossa to Study Type I Chiari Malformation

Chiari malformation type I (CM-1) is a complex disorder in which tonsillar herniation through the foramen magnum manifests with a spectrum of clinical symptoms. This work analyzes morphometric and volumetric characteristics of CM-1 patients. With Institutional Review Board (IRB) approval, we retrospectively reviewed a total of 72 adult CM-1 patients and 26 healthy adult volunteers who underwent volumetric magnetic resonance brain imaging. Clinical data was retrospectively extracted from the electronic medical record. We analyzed multi-dimensional morphometric and volumetric features within the posterior cranial fossa and correlated these features with syrinx formation and the decision to undergo surgical decompression. In our study, CM-1 patients had decreased cerebellar, brainstem and 4th ventricular volumes but larger tonsillar volume with increased total tonsillar length. CM-1 patients who underwent surgery had significantly more neural tissue within the cross-sectional area of cisterna magna. Logistic regression demonstrated that combining neural tissue at foramen magnum with cerebellar & 4th ventricular volumes led to great degree of correlation with syrinx formation (AUC 0.911). Our findings suggest that the amount of tissue at the foramen magnum correlates with CM-1 patients who underwent decompressive surgery, more so than tonsillar length. Additionally, the combination of neural tissue at foramen magnum, cerebellar & 4th ventricular volumes led to great degree of correlation with syrinx formation. Together, these findings suggest that a global compressive phenomenon within the posterior fossa leads to CM-1 symptomatology and syrinx formation.

Association Between Cannabis Use and Brain Structures: A Mendelian Randomization Study.

Background Observational studies suggested that cannabis use was associated with alternation of brain structures; however, as subjected to confounding factors, they were difficult to make causal inferences and direction determinations. In this study, a two-sample Mendelian randomization (MR) analysis was employed to examine the potential causal association between cannabis use and brain structures. Methods The genome-wide association studies (GWAS) data forlifetime cannabis use (LCU), cannabis use disorder (CUD), and brain cortical and subcortical structureswere utilized in this study. Cortical structures were divided into 34 distinct gyral-defined regionswith surface area (SA) and thickness (TH)measured.Subcortical structures encompassed volumes from seven specified regions. The primary estimator used in our analysis was inverse-variance weighted (IVW), complemented by MR-Egger and weighted median methods to enhance the robustness of theresults. The Cochran's Q test, funnel plots, and MR-Egger intercept tests were used to detect heterogeneity and pleiotropy. Results No causal relationship was detected between LCU and global cortical SA or TH. However, at the regional cortex level, LCU was associated with decreased TH in the fusiform (β = -0.0168 mm, SE = 0.00581, P = 0.0039) and lateral occipital (β = -0.0141 mm, SE = 0.00531, P = 0.0079) regions, while increasing TH in the postcentral region (β = 0.0093 mm, SE = 0.00445, P =0.0374). At the subcortical level, LCU was found to increase the brainstem volume (β = 0.224 mm3, SE = 0.09, P = 0.0128). CUD did not show any causal association with brain structure at either cortical or subcortical levels. Nonetheless, after applying multiple comparison corrections, the P values for the MR analysis of causal relationships between cannabis use and these brain structures did not meet the significance threshold. Conclusion The evidence for cannabis use causally influencing brain structures is insufficient.

Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome.

The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics. Standardized 3T MRIs including 3D isotropicT1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired datawere analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord. The study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of -4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event,a greater reduction in medulla-upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443). The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures.

Gait Analysis and Magnetic Resonance Imaging Characteristics in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparison of detailed brain volume measurements in schizophrenia with healthy individuals

Aims: This study aims to provide insights into the preliminary and definitive diagnosis, treatment modalities, and elucidation of the underlying pathophysiological mechanisms of schizophrenia, alongside ongoing research efforts. Methods: This retrospective study examined a cohort of 31 patients (17 male, 14 female) diagnosed with schizophrenia according to the criteria specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM V) at the Psychiatry Clinic of the University Hospital. The healthy control group, comprising 31 individuals (17 male, 14 female), was selected from archived records at the same hospital, with sociodemographic characteristics matching those of the patient group. High-resolution T1-weighted MRI images of the individuals were analyzed using the VolBrain AssemblyNet program. Results: It has been observed that the volumes of various brain structures, including white matter (WM), gray matter (GM), subcortical GM, cortical GM, WM+GM, IC, total cerebrum, right cerebrum, left cerebrum, cerebrum WM, cerebrum GM, are significantly reduced (p<0.05) in patients diagnosed with schizophrenia compared to healthy controls. Additionally, volumes of cerebellar WM, GM, vermis, brainstem, accumbens, hippocampus, thalamus, ventral diencephalon (DC), amygdala, and basal forebrain were found to be decreased in schizophrenia patients compared to healthy controls. Conversely, volumes of the pallidum, caudate, putamen, inferior lateral ventricle, lateral ventricle, third ventricle, fourth ventricle, and CSF were observed to be increased. Conclusion: These findings underscore the widespread nature of neuroanatomical alterations in schizophrenia and highlight the importance of understanding these changes for elucidating the disorder's pathophysiology and developing targeted therapeutic interventions. Further research is warranted to explore the interplay of genetic, developmental, and environmental factors in schizophrenia.

Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials.

Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed. Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials. Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data. Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems. This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predicting the risk of neurocognitive decline after brain irradiation in adult patients with a primary brain tumor.

Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study aimed to develop and evaluate normal-tissue complication probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year, and 2-year Neurocognitive Decline (ND) postradiotherapy. A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included. Controlled oral word association test, Hopkins verbal learning test-revised, and trail making test were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modeling. Clinical, dose-volume and combined models were constructed and internally tested in terms of discrimination (area under the curve, AUC), calibration (mean absolute error, MAE), and net benefit. Fifty percent, 44.5%, and 42.7% of the patients developed ND at 6-month, 1-year, and 2-year time points, respectively. The following predictors were included in the combined model for 6-month ND: age at radiotherapy > 56 years (OR = 5.71), overweight (OR = 0.49), obesity (OR = 0.35), chemotherapy (OR = 2.23), brain V20 Gy ≥ 20% (OR = 3.53), brainstem volume ≥ 26 cc (OR = 0.39), and hypothalamus volume ≥ 0.5 cc (OR = 0.4). Decision curve analysis showed that the combined models had the highest net benefits at 6-month (AUC = 0.79, MAE = 0.021), 1-year (AUC = 0.72, MAE = 0.027), and 2-year (AUC = 0.69, MAE = 0.038) time points. The proposed NTCP models use easy-to-obtain predictors to identify patients at high risk of ND after brain RT. These models can potentially provide a base for RT-related decisions and post-therapy neurocognitive rehabilitation interventions.

Seasonal Affective Disorder: A Narrative Review

This narrative review of research includes summaries of 46 papers on seasonal affective disorder that were published during the period 2019-2023. The publications are primarily cross-sectional studies of risk factors, randomized controlled trials for light therapy and cognitive behavioral therapy and systematic reviews. A few of the papers are focused on the prevalence of seasonal affective disorder which has varied by latitudes and climates from 3% in Saudi Arabia to 21% in Norway, suggesting length of day and sunlight effects. Only a few studies focused on the negative effects of seasonal affective disorder including sleep problems, depression and poor performance on memory tasks. Most of the research has addressed risk factors for developing seasonal affective disorder including younger age, female gender, dependent personality, seasonal beliefs, chronotype (eveningness), inactivity, insomnia and depression. Very few potential underlying mechanism studies appeared in this literature with the exception of MRI studies suggesting reduced brainstem volume. In contrast, many intervention studies were published recently including light therapy and cognitive behavioral therapy. Methodological problems relate to the variability in the assessments of seasonal affective disorder, the reliance on self-report measures and the cross-sectional data that are not definitive about directionality of predictors and effects of seasonal affective disorder.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

The role of the brainstem in sleep disturbances and chronic pain of Gulf War and Iraq/Afghanistan veterans.

Gulf War Illness is a type of chronic multisymptom illness, that affects about 30% of veterans deployed to the 1990-91 Persian Gulf War. Veterans deployed to Iraq/Afghanistan after 2000 are reported to have a similar prevalence of chronic multisymptom illness. More than 30 years after the Persian Gulf War, Gulf War Illness still has an unexplained symptom complex, unknown etiology and lacks definitive diagnostic criteria and effective treatments. Our recent studies have found that substantially smaller brainstem volumes and lower fiber integrity are associated with increased sleep difficulty and pain intensity in 1990-91 Persian Gulf War veterans. This study was conducted to investigate whether veterans deployed to Iraq/Afghanistan present similar brainstem damage, and whether such brainstem structural differences are associated with major symptoms as in Gulf War Illness. Here, we used structural magnetic resonance imaging and diffusion tensor imaging to measure the volumes of subcortices, brainstem subregions and white matter integrity of brainstem fiber tracts in 188 veterans including 98 Persian Gulf War veterans and 90 Iraq/Afghanistan veterans. We found that compared to healthy controls, veterans of both campaigns presented with substantially smaller volumes in brainstem subregions, accompanied by greater periaqueductal gray matter volumes. We also found that all veterans had reduced integrity in the brainstem-spinal cord tracts and the brainstem-subcortical tracts. In veterans deployed during the 1990-91 Persian Gulf War, we found that brainstem structural deficits significantly correlated with increased sleep difficulties and pain intensities, but in veterans deployed to Iraq/Afghanistan, no such effect was observed. These structural differences in the brainstem neurons and tracts may reflect autonomic dysregulation corresponding to the symptom constellation, which is characteristic of Gulf War Illness. Understanding these neuroimaging and neuropathological relationships in Gulf War and Iraq/Afghanistan veterans may improve clinical management and treatment strategies for modern war related chronic multisymptom illness.

Neuroquantification enhances the radiological evaluation of term neonatal hypoxic-ischaemic cerebral injuries.

Injury patterns in hypoxic-ischaemic brain injury (HIBI) are well recognised but there are few studies evaluating cerebral injury using neuroquantification models. Quantification of brain volumes in a group of patients with clinically determined cerebral palsy. In this retrospective study, 297 children with cerebral palsy were imaged for suspected HIBI with analysis of various cerebral substrates. Of these, 96 children over the age of 3 years with a clinical diagnosis of cerebral palsy and abnormal MRI findings underwent volumetric analyses using the NeuroQuant® software solution. The spectrum of volumetric changes and the differences between the various subtypes (and individual subgroups) of HIBI were compared. Compared with the available normative NeuroQuant® database, the average intracranial volume was reduced to the 1st percentile in all patient groups (p < 0.001). Statistically significant differences were observed among the types and subgroups of HIBI. Further substrate volume reductions were identified and described involving the thalami, brainstem, hippocampi, putamina and amygdala. The combined volumes of five regions of interest (frontal pole, putamen, hippocampus, brainstem and paracentral lobule) were consistently reduced in the Rolandic basal ganglia-thalamus (RBGT) subtype. This study determined a quantifiable reduction of intracranial volume in all subtypes of HIBI and predictable selective cerebral substrate volume reduction in subtypes and subgroups. In the RBGT subtype, a key combination of five substrate injuries was consistently noted, and thalamic, occipital lobe and brainstem volume reduction was also significant when compared to the watershed subtype. This study demonstrates the value of integrating an artificial intelligence programme into the radiologists' armamentarium serving to quantify brain injuries more accurately in HIBI. Going forward this will be an inevitable evolution of daily radiology practice in many fields of medicine, and it would be beneficial for radiologists to embrace these technological innovations.

Volumetric alteration of brainstem in female migraineurs with and without aura

Background and AimBrainstem descending modulatory circuits have been postulated to be involved in migraine. Differences in brainstem volume between migraineurs and healthy controls have been demonstrated in previous research, nevertheless, the effect of migraine aura on brainstem volume is still uncertain. The aim of this study was to investigate the brainstem volume in migraineurs and examine the effect of migraine aura on brainstem volume. MethodsOur study included 90 female migraine patients without white matter lesions. (29 migraine patients with aura (MwA) and 61 migraine patients without aura (MwoA) and 32 age-matched female healthy controls (HC). Using the FreeSurfer image analysis suite, the volumes of the entire brainstem and its subfields (medulla, pons, and midbrain) were measured and compared between migraine subgroups (MwA vs. MwoA) and the healthy control group. The possible effects of migraine characteristics (i.e., disease duration and migraine attack frequency) on brainstem volume were also investigated. ResultsMigraineurs had greater medulla volume (MwoA 3552 ± 459 mm3, MwA 3424 ± 448 mm3) than healthy controls (3236 ± 411 mm3). Statistically, MwA vs. HC p = 0.040, MwoA vs. HC p = 0.002, MwA vs. MwoA p = 0.555. A significant positive correlation was found between disease duration and the volume of medulla in the whole migraine group (r = 0.334, p = 0.001). Neither the whole brainstem nor its subfields were significantly different in volume between migraine subgroups. ConclusionBrainstem volume changes in migraine are mainly localized to the medulla and not specific to the presence of aura.

Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia

BackgroundHypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication that can result in 40–60 % of long-term morbidity. Magnetic Resonance Imaging (MRI) is a noninvasive method which is usually performed before discharge to visually assess acquired cerebral lesions associated with HIE and severity of lesions possibly providing a guide for detecting adverse outcomes. This study aims to evaluate the impact of HIE on brain volume changes observed in MRI scans performed at a mean 10 days of life, which can serve as a prognostic indicator for abnormal neurodevelopmental (ND) outcomes at 18–24 months among HIE infants. MethodsWe retrospectively identified a cohort of HIE patients between June 2013 and March 2017. The inclusion criteria for therapeutic hypothermia (TH) were a gestational age ≥35 weeks, a birth weight ≥1800 g, and the presence of ≥ moderate HIE. Brain MRI was performed at a mean 10 days of life and brain volumes (total brain volume, cerebral volume, cerebellar volume, brain stem volume, and ventricle volume) were measured for quantitative assessment. At 18–24 months, the infants returned for follow-up evaluations, during which their cognitive, language, and motor skills were assessed using the Bayley Scales of Infant and Toddler Development III. ResultsThe study recruited a total of 240 infants between 2013 and 2017 for volumetric brain MRI evaluation. Among these, 83 were normal control infants, 107 were TH-treated HIE infants and 37 were HIE infants who did not receive TH due to contraindications. Clinical evaluation was further proceeded. We compared the brain volumes between the normal control infants (n = 83) with normal ND but TH-treated HIE infants (n = 76), abnormal ND TH-treated HIE infants (n = 31), and the severe HIE MRI group with no TH (n = 37). The abnormal ND TH-treated HIE infants demonstrated a significant decrease in brainstem volume and an increase in ventricle size (p < 0.001) (Table 4). Lastly, the severe brain MRI group who did not receive TH showed significantly smaller brain stem (p = 0.006), cerebellar (p = 0.006) and cerebrum volumes (p = 0.027), accompanied by larger ventricular size (p = 0.013) compared to the normal control group (Table 5). ConclusionIn addition to assessing the location of brain injuries in MRI scans, the reduction in brain stem volume coupled with an increase in ventricular volume in HIE infants may serve as a biomarker indicating severe HIE and adverse long-term ND outcomes among HIE infants who either received therapeutic hypothermia (TH) treatment or not.

Mean Intracranial Volume of Brain among Patients with Normal Magnetic Resonance Imaging Referred to the Department of Radiology and Imaging of a Tertiary Care Centre.

The measurement of brain volume is an important aspect of the assessment of brain structure and function. However, limited data is available on brain volumetry in the Nepalese population. The study aimed to find the mean intracranial volume of the brain among patients with normal magnetic resonance imaging referred to the Department of Radiology and Imaging of a tertiary care centre. A descriptive cross-sectional study was conducted among patients with normal magnetic resonance imaging referred to the Department of Radiology and Imaging in a tertiary care centre. All magnetic resonance imaging of the brain during the study period was reviewed by a radiologist. Magnetic resonance imaging with abnormal findings, clinical signs of neurological deficit, dementia and psychiatric symptoms were excluded from the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among 285 Magnetic Resonance Imaging datasets, the mean intracranial volume was 1286.30±129.88 cc (1271.22-1301.38, 95% of Confidence Interval). The mean cerebral volume was 985.06±106.4 cc, cerebellar volume was 126.99±13.05 cc and brain stem volume was 19.97±2.54 cc. The mean intracranial volume of the brain among patients with normal magnetic resonance imaging was found to be lower than other studies done in similar settings. brainstem; cerebellum; cerebrum; magnetic resonance imaging.

Atrophy in brainstem nuclei with early Alzheimer’s Disease pathology, a biomarker for identification of at risk individuals?

AbstractBackgroundAutopsy studies suggest that AD‐related tau pathology may affect the brainstem already in adolescence/young adulthood suggesting that it could be a biomarker for the identification of at risk individuals in the preclinical stage. The overall goal was to investigate a. if a newly developed method for the segmentation of internal brainstem structures from T1 and T2 weighted MRIs can be used to identify subjects with volume losses in brainstem nuclei known to be affected by tau pathology, and b. if these brainstem volume losses affect cognition.MethodThe age‐adjusted Total Cognition Composite Score (CCS) and T1 and T2 weighted images were obtained from 675 participants in the Human Connectome Project of typical Aging. The T1 and T2 image intensities were recalibrated and a T1/T2 image calculated. The brainstem was extracted from these 3 images, and k‐means clustering used to identify five brainstem tissue types (Figure 1). The five tissue maps were warped onto a brainstem tissue template on which 48 structures were labeled. Jacobian determinant (JD) maps were calculated and the mean JD from these rois extracted. Linear regression with the mean roi JD as dependent and age as independent variable were used to generate a 675×48 matrix where residuals &gt;2 SD above the fit line were set to 1 (larger than age‐average), those &gt;2 SD below to ‐1 (smaller than age‐average) and all others to 0. Hierarchical clustering analysis with the 675×48 matrix as input was used to identify different brainstem atrophy patterns.ResultThe cluster analysis identified 11 clusters. 31 individuals (mean(SD) age: 56.2(16.2), range:36‐100) were assigned to Cluster 8. This cluster had the most rois (n = 17) with significant volume loss (Figure 2 for detailed results) and the 31 individuals the lowest CCS score compared to those assigned to other clusters (98.2(19.5) vs.109.6(15.2), p = 0.003).ConclusionThe new brainstem segmentation identified a subgroup with lower cognitive performance and widespread volume loss exceeding that in their age cohort in brainstem nuclei known to be affected by AD. Additional studies will be necessary to determine if individuals showing this specific brainstem atrophy pattern are indeed at risk to develop AD in their later life.

Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer's disease.

Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demoimagedatas, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD. Chictr.org.cn, ChiCTR2100049131.

Artificial intelligence based auto-contouring solutions for use in radiotherapy treatment planning of head and neck cancer

BackgroundManual contouring is time-consuming and subjective. Thus, auto-segmentation methods, which can be deployed in the existing workflow, are needed. The objective of this study was to assess the feasibility of Limbus AI and AI Rad Companion auto-contours for head and neck treatment planning. MethodsHead and neck patients treated with RapidArc were selected retrospectively. The manual contours on the planning CT were used as reference. Geometric analysis of the auto-contours was performed using several evaluation metrics such as the Dice Similarity Coefficient (DSC) and the Mean Distance to Conformity (MDC). Dosimetric analysis was performed by recalculating the original plan on the auto-contours and comparing Dose Volume Histogram (DVH) metrics to the original plan. Results and discussionBoth AI tools tend to underestimate the volumes of brainstem and cord. For brainstem and parotids, median DSC values were ≥ 0.8. For all auto-contours, median MDC values were ∼ 3–6 mm. Median differences were found of up to ±7 % in DVH points on the auto-contours relative to the planning CT contours, but these were not statistically-significant. ConclusionThe auto-contours could be used as a starting point to assist the clinician with the manual contouring of structures on the planning and re-scanning planning CT.

Abstract 13302: Associations of Allostatic Load With Brain Macro-Morphology, Subclinical Cerebrovascular Disease, and Microstructural Integrity of White Matter Pathways: The Boston Puerto Rican Health Study

Introduction: Allostatic load (AL), a measure of overall body wear and tear, has been associated with structural and functional alterations of the brain, but the evidence remains scarce. We aimed to evaluate the prospective associations of AL with brain MRI measures in the Boston Puerto Rican Health Study (BPRHS). Research Questions: Whether AL is associated with 1) brain macro-morphology: brain age and volumes, 2) subclinical cerebrovascular disease: white matter hyperintensity (WMH) and brain infarcts, and 3) microstructural integrity of white matter (WM) pathways in Puerto Rican adults. Methods: Adults from the BPRHS cohort who provided blood and urine samples at baseline, 2-y, and 6-y visits and underwent MRI scans at 13-y visit were included in analyses (n=226). AL was evaluated as a composite score (0-11) of 11 physiological parameters in five body systems. An overall AL score was calculated by averaging the scores of the baseline, 2-y, and 6-y visits, with higher scores indicating greater dysregulation. We evaluated brain age and volumes using T1-weighted MRI, WMH and brain infarcts using T2-weighted MRI, and microstructural integrity of WM pathways using diffusion tensor imaging. Multivariable logistic regression models were used to examine the associations between AL and brain infarcts, and linear regression models were used for other MRI outcomes. Results: Mean age at baseline was 54.6 ± 6.6 y, with 79.2% female. Higher AL was associated with higher brain age z scores (β = 0.129, P = 0.031) and lower volumes of total WM, cerebral WM (especially parietal and temporal lobes), cerebellum, and brain stem. Higher AL was also associated with higher grades of WMH (β = 0.207, P = 0.024) and higher odds of small vessel infarcts [OR (95% CI) = 3.50 (1.56-7.87), P = 0.002], but not large vessel infarcts [OR (95% CI) = 1.33 (0.73-2.40), P = 0.348]. Diffusion tensor imaging parameters showed that participants with higher AL had more microstructural deterioration patterns in major WM pathways. Conclusions: Higher AL score was associated with brain macro- and microstructural disruptions and a higher risk of subclinical cerebrovascular disease, suggesting that AL may be a potential indicator of the need for early intervention in preventing neuronal damage in older adults.

Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.