Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Mr volumetry of intracranial and brain volume in normal adult population aged 40 years old and above.

Magnetic Resonance Imaging (MRI) has significantly accelerated many studies involving the brain with more researchers looking into not only anatomy and structural aspects of the brain, but also functional aspect due to excellent soft tissue discrimination (Kennedy et al., 2003). MRI also enables researchers to study the changes involving intracranial volume, brain volume and compartmental volumes, giving valuable data regarding the normal human brain morphological changes and in certain degenerative diseases or psychiatric illnesses (Ohnishi et al., 2001; Peters, 2006)

Reliability of brain atrophy measurements in multiple sclerosis using MRI: an assessment of six freely available software packages for cross-sectional analyses

PURPOSE: Volume measurement using MRI is important to assess brain atrophy in multiple sclerosis (MS). However, differences between scanners, acquisition protocols, and analysis software introduce unwanted variability of volumes. To quantify theses effects, we compared within-scanner repeatability and between-scanner reproducibility of three different MR scanners for six brain segmentation methods. METHODS: Twenty-one people with MS underwent scanning and rescanning on three 3 T MR scanners (GE MR750, Philips Ingenuity, Toshiba Vantage Titan) to obtain 3D T1-weighted images. FreeSurfer, FSL, SAMSEG, FastSurfer, CAT-12, and SynthSeg were used to quantify brain, white matter and (deep) gray matter volumes both from lesion-filled and non-lesion-filled 3D T1-weighted images. We used intra-class correlation coefficient (ICC) to quantify agreement; repeated-measures ANOVA to analyze systematic differences; and variance component analysis to quantify the standard error of measurement (SEM) and smallest detectable change (SDC). RESULTS: For all six software, both between-scanner agreement (ICCs ranging 0.4–1) and within-scanner agreement (ICC range: 0.6–1) were typically good, and good to excellent (ICC > 0.7) for large structures. No clear differences were found between filled and non-filled images. However, gray and white matter volumes did differ systematically between scanners for all software (p < 0.05). Variance component analysis yielded within-scanner SDC ranging from 1.02% (SAMSEG, whole-brain) to 14.55% (FreeSurfer, CSF); and between-scanner SDC ranging from 4.83% (SynthSeg, thalamus) to 29.25% (CAT12, thalamus). CONCLUSION: Volume measurements of brain, GM and WM showed high repeatability, and high reproducibility despite substantial differences between scanners. Smallest detectable change was high, especially between different scanners, which hampers the clinical implementation of atrophy measurements

Fetal body MRI and its application to fetal and neonatal treatment: an illustrative review

This Review depicts the evolving role of MRI in the diagnosis and prognostication of anomalies of the fetal body, here including head and neck, thorax, abdomen and spine. A review of the current literature on the latest developments in antenatal imaging for diagnosis and prognostication of congenital anomalies is coupled with illustrative cases in true radiological planes with viewable three-dimensional video models that show the potential of post-acquisition reconstruction protocols. We discuss the benefits and limitations of fetal MRI, from anomaly detection, to classification and prognostication, and defines the role of imaging in the decision to proceed to fetal intervention, across the breadth of included conditions. We also consider the current capabilities of ultrasound and explore how MRI and ultrasound can complement each other in the future of fetal imaging

후윤상피열근 부피측정을 통한 일측성대마비 예후 분석

학위논문 (석사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 권택균.서론 성대마비는 다양한 원인에 의해 한쪽 혹은 양쪽 성대가 움직이지 않는 상태를 말한다. 컴퓨터 단층촬영을 이용하여 성대마비의 방향 및 예후를 예측하려는 연구들이 선행되어 왔다. 최근 연구에 의하면 일측성대마비 환자에서 환측의 후윤상피열근의 부피를 건측과 비교하였을 때 부피가 작을 수록 후두근전도의 소견도 악화되었고, 일측 성대마비는 회복되지 않았다. 하지만, 이는 후윤상피열근의 부피를 정량적으로 측정한 연구가 아니었기에 다음과 같은 목적으로 연구를 시행하였다. 첫째, 후윤상피열근의 부피를 ITK-SNAP 프로그램을 이용하여 정량적으로 측정하고 재현성을 확인한다. 둘째, 측정한 후윤상피열근 부피의 환측 대 건측 비율을 구하여 근전도의 결과와 상관관계를 가지는지 분석한다. 셋째, 후윤상피열근의 환측 대 건측 비율이 영구적 성대마비를 예측할 수 있는 지표로 활용할 수 있을지 탐구해보고자 한다. 방법 2005년부터 2016년까지 서울대병원을 내원하여 일측성대마비로 진단받은 성인 환자를 대상으로 후향적 의무기록 분석을 시행하였다. 일측성대마비 발생 최소 3개월 이후 시행된 컴퓨터 단층 촬영과 후두근전도가 있는 환자를 분석대상으로 하였다. 후윤상피열근이 컴퓨터 단층 촬영에서 주변 구조물과 구분이 되지 않는 경우는 연구대상에서 제외하였다. ITK-SNAP을 통해 후윤상피열근의 윤곽을 후윤상피열근이 존재하는 모든 평면에서 지정을 하였다. 측정자가 지정한 윤곽을 바탕으로 프로그램이 후윤상피열근의 부피를 측정하였고, 환측 대 건측 비율을 구하였다. 후두근전도 결과는 정도에 따라서 5개의 집단으로 구분하였다. 이후 환측 대 건측 비율과 후두근전도, 환측 대 건측 비율과 예후의 상관성을 분석하였다. 결과 총 41명의 환자를 대상으로 분석하였으며 일측성대마비의 방향은 좌측(71%)이 우세하였으며 원인은 특발성인 경우가 가장 흔했다. 2명의 분석자가 후윤상피열근의 부피를 측정하였으며 유의미한 재현성을 보였다. (P<0.001) 후윤상피열근의 환측 대 건측 비율은 0.50이었으며 이는 후두 근전도 결과와 음의 상관관계를 가졌다. (Rho = -0.351, P = 0.024) 하지만, 후윤상피열근의 위축 정도가 증가할수록 즉 환측 대 건측 비율이 감소할 수록 영구적인 일측성대마비의 비율이 유의미하게 증가하였다. 후윤상피열근이 건측과 비교하여 82% 이상 감소한 경우에는 영구적 성대마비 양성예측도는 100%였다. 결론 후윤상피열근의 정량적인 부피측정은 신뢰도가 높았으며, 환측 대 건측 후윤상피열근의 비율은 기존의 예후 예측 방법인 후두근전도 결과와 연관성이 유의미하게 있었다. 이는 선행 연구와 일치하는 경향을 보이며, 향후 예측 지표로 활용 가능하다. 더 많은 환자군을 대상으로 자동화된 방법으로 분석하여 측정값이 참값에 근접할 수 있도록 후속연구가 필요하다.Introduction: Vocal fold paralysis (VFP) refers to a condition in which one or both vocal cords do not move due to various reasons. Studies have been conducted to predict the direction of VFP and prognosis of VFP using computed tomography (CT). According to a recent study, in patients with unilateral VFP (UVFP), the lower the volume of the posterior cricoarytenoid (PCA) muscle on the affected side, the worse the laryngeal electromyography (LEMG) findings, the smaller the volume, and the less chances for UVFP to recover. However, there was no study that has quantitatively measured the volume of the PCA muscle and analyzed it as a continuous variable. Therefore, this study was conducted for the following purposes. First, the volume of the PCA muscle was measured using the ITK-SNAP program, and reproducibility was checked. Second, the PCA muscle volume ratio was calculated and analyzed to find whether there was a correlation with the result of LEMG findings. Third, we explored whether the PCA muscle volume ratio could be used as an index to predict permanent UVFP. Methods: From 2005 to 2016, a retrospective medical record review of adult patients who visited the Seoul National University Hospital diagnosed with UVFP was performed. Patients with CT and LEMG performed at least 3 months after the onset of UVFP were analyzed. Cases in which the PCA muscle was indistinguishable from the surrounding structures by CT were excluded from the study. Through ITK-SNAP, the contours of the PCA muscle were specified in all planes where the PCA muscle was present. Based on the contour specified by the measurer, ITK-SNAP calculated the volume and PCA muscle atrophy ratio. The LEMG results were divided into 5 groups according to the severity. Subsequently, the correlations between the PCA muscle volume ratio and the LEMG as well as PCA muscle volume ratio and prognosis were analyzed. Results: Analysis of 41 patients showed that the left side was more dominant (71%) with idiopathic VFP as the most common etiology. PCA muscle measured by two clinicians had significant reproducibility (P<0.001). The average PCA muscle volume ratio was 0.50, which had a negative correlation with LEMG grades (Rho=-0.351, P=0.024). However, as the PCA volume atrophy increased, the proportion of permanent UVFP significantly increased (P<0.001). When PCA muscle volume decreased by 82% or more compared to the normal side, the positive predictive value for permanent UVFP was 100%. Conclusion: The quantitative volume measurement of the PCA muscle was highly reliable, and the PCA muscle volume ratio was significantly correlated with the LEMG results, which is a conventional tool for anticipating the prognosis. This was consistent with the findings of previous studies and can be used as an index for the prognosis of UVFP. Follow-up studies are required in which a greater number of patients are analyzed by the automated process so that the measured value can reach the true value.Abstract i Contents iv List of Figures v List of Tables vi List of Abbreviations vii Introduction 1 Materials and Methods 4 Study design 4 PCA muscle volume measurements with ITK-SNAP 5 LEMG 7 Statistical analysis 8 Results 10 Demographics and clinical characteristics 10 Diagnostic accuracy of the UVFP side 11 PCA muscle volume and ratio 11 Correlation between PCA muscle volume and LEMG patterns 11 Prediction of permanent UVFP using the PCA muscle volume ratio 12 Discussion 13 Conclusion 17 Figures and Tables 18 Reference 39 Abstract in Korean (국문 초록) 43Maste

Spinal cord volume quantification and clinical application in multiple sclerosis

Magnetic resonance imaging of the spinal cord is a valuable part of the diagnostic work-up in patients with multiple sclerosis and other neurological disorders. Currently, mainly signal intensity changes within the cord in MR-images are considered in the clinical management of disorders of the central nervous system. However, cross-sectional or longitudinal measurements of spinal cord volume may deliver additional valuable information. Hence, the overall goal of this doctoral thesis was twofold: i) to clinically validate methods for quantification of spinal cord volume and spinal cord compartments, which are suitable for longitudinal assessment of large patient cohorts and clinical practice and ii) to evaluate spinal cord volume as a potential valuable biomarker and provide new insights into the role of spinal cord damage in multiple sclerosis. The first part focuses on the validation of quantification methods for spinal cord volume and includes two projects. While several MRI-based approaches of semi- and fully automatic techniques for volumetric spinal cord measurements have been proposed, up to now no gold standard exists and only a few methods have been validated and/or evaluated on patient follow-up scans to demonstrate their applicability in longitudinal settings. One of the latter segmentation methods was recently developed in-house and showed excellent reliability for cervical cord segmentation (Cordial, the cord image analyzer). In a first project, we extended its applicability to the lumbar cord, since no other software has been tested so far within this anatomical region of interest. On a well-selected dataset of 10 healthy controls (scanned in a scan-rescan fashion) we were able to show that - even within this technically challenging region - this segmentation algorithm provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. In a second project, we aimed at obtaining volumetric information on particular compartments of the spinal cord such as the cord grey and white matter, since recent studies in multiple sclerosis provided evidence that measuring spinal cord grey matter volume changes may be a better biomarker for disease progression than quantifying cord white matter pathology or even volumetric brain measures. We therefore implemented a novel imaging approach, the averaged magnetization inversion recovery acquisitions sequence, for better grey and white matter visualization within the cord and scanned 24 healthy controls in a scan-rescan fashion. Further we applied an innovative fully automatic variational segmentation algorithm with a shape prior modified for 3D data with a slice similarity prior to segment the spinal cord grey and white matter. This pipeline allowed for highly accurate and reproducible grey and white matter segmentation within the cord. In view of its features, our automatic segmentation method seems promising for further application in both cross-sectional and longitudinal and in large multi-center studies. The second goal of this thesis was the clinical application of the above-mentioned methods for the evaluation of spinal cord volume changes as a potential biomarker in multiple sclerosis patients. For this purpose, we quantified spinal cord volume change in a large cohort of 243 multiple sclerosis patients, followed over a period of 6 years with annual clinical and MRI examinations. Spinal cord volume proved to be a strong predictor of physical disability and disease progression, indicating that it may be a suitable marker for monitoring disease activity and severity in all disease types but especially in progressive multiple sclerosis. Spinal cord volume also proved to be the only MRI metric to strongly explain the clinical progression over time as opposed to brain atrophy and lesion measures

Quantification of spinal cord atrophy in magnetic resonance images

Quantifying the volume of the spinal cord is of vital interest for studying and understanding diseases of the central nervous system such as multiple sclerosis (MS). In this thesis, which is motivated by MS research, we propose methods for measuring the spinal cord cross-sectional area and volume in magnetic resonance (MR) images. These measurements are used for determining neural atrophy and for performing both longitudinal and cross-sectional comparisons in clinical trials. We present three evolutionary steps of our approach: In the first step, we use graph cut–based image segmentation on the intensities of T1-weighted MR images. In the second step, we combine a continuous max flow segmentation algorithm with a cross-sectional similarity prior and Hessian-based structural features, which we apply to T1- and T2-weighted images. The prior leverages the fact that the spinal cord is an elongated structure by constraining its cross-sectional shape to vary only slowly along one image axis. In conjunction with the additional features, the segmentation robustness is thus increased. In the third step, we combine continuous max flow with anisotropic total variation regularization, which enables us to direct the regularization of the cross-sectional shape of the spinal cord more flexibly. We implement the proposed approach as a semi-automatic software toolchain that automatically segments the spinal cord, reconstructs its surface, and acquires the desired measurements. The software employs a user-provided anatomical landmark as well as hints for the location of the spinal cord and its surroundings. It accounts for the bending of the spine, MR-induced image distortions, and noise. We evaluate the proposed methods in experiments on phantom, healthy subject, and patient data. Our measurement accuracy and precision are on par with the state of the art. At the same time, our measurements on MS patient data are in accordance with the medical literature

Volumetric and symmetry comparison of intracranial matter between preterm and full-term children

BACKGROUND: Pre-term delivery is known to cause developmental problems due to the fragile nature of the premature brain. In particular, ventriculomegaly is a commonly observed phenomenon due to the hemorrhaging of the germinal matrix, and may cause alterations in the volumes of gray matter, white matter and cerebrospinal fluid in growing pre-term children. METHODS: The volume and symmetry of a sample population of ELGAN (Extremely Low Gestational Age Newborns) and normal-term population obtained from the NIH Study of Normal Brain Development was evaluated. The ELGAN group consisted of 88 subjects from age group 9 to 11 and the normal-term group consisted of 68 subjects from age group 7 to 11. Magnetic resonance images were taken from both samples and the intracranial matter was measured and segmented. RESULTS: Histograms of the obtained volumes showed a normal distribution and statistical analysis for each sample group and gender. The ELGAN group had higher intracranial volumes and showed statistically significant asymmetry that was not present in the normal term population with a larger right brain than left brain. Discussion: Results indicate that preterm delivery may alter processes that allow for symmetrical brain development and heavily favor the relative higher expansion of the right side of the brain. CONCLUSION: Further analysis of the concentration and location of the white matter and gray matter in both preterm and normal term children is necessary in order to understand the adaptive mechanisms that may be activated in order to offset the damage done to the premature brain

Towards a standard MRI protocol for multiple sclerosis across the UK.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system. It is the most common non-traumatic cause of chronic disability in young adults. An early and accurate diagnosis, and effective disease modifying treatment (DMT) are key elements of optimum care for people with MS (pwMS). Magnetic resonance imaging (MRI) has become a critical tool to confirm the presence of dissemination in space and time of lesions characteristic of inflammatory demyelination, a cornerstone of MS diagnosis, over and above exclusion of numerous differential diagnoses. In the modern era of early and highly effective DMT, follow-up of pwMS also relies heavily on MRI, to both confirm efficacy and for pharmacovigilance. Since criteria for MS rely heavily on MRI, an agreed standardized acquisition and reporting protocol enabling efficient and equitable application across the UK is desirable. Following a recent meeting of MS experts in London (UK), we make recommendations for a standardized UK MRI protocol that captures the diagnostic phase as well as monitoring for safety and treatment efficacy once the diagnosis is established. Our views take into account issues arising from the (repeated) use of contrast agents as well as the advent of (semi-) automated tools to further optimise disease monitoring in pwMS.Edmond J Safra FoundationLily SafraMRCUK Dementia Research InstituteImperial College Healthcare Trust Biomedical Research Centr

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the ‘‘time of diagnosis’’ phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation