Pankaj pankaj¹, S Senthil Kumaran¹, and Achal Kumar Srivastava^2
1NMR, All India Institute of Medical Sciences, New Delhi, India, ²Neurology, All India Institute of Medical Sciences, New Delhi, India

Spinocerebellar Ataxia (SCA), also known as spinocerebellar degeneration, is a degenerative, progressive and genetic disorder that leads to severe disability. On structural morphometrics of isolated cerebellum, we observed significant white matter atrophy in the anterior lobe of the SCA type 2 and 12 patients. Cerebellum atrophy of gray matter in both bilateral anterior and posterior cerebellar lobes, Cerebellar Tonsil, Uvula, Inferior Semi-Lunar Lobule, Declive, Red Nucleus and Substania Nigra was observed in SCA2, with respect to healthy controls. SCA2 patients exhibited more atrophy in comparison to SCA12. Atrophy in the cerebellum suggest deficits in motor and cognition in SCA patients.

Silvia Maria Marchese¹, Fulvia Palesi^2,3, Mariagrazia Bruzzone⁴, Anna Nigri⁴, Stefano D'Arrigo⁵, Chiara Pantaleoni⁵, Claudia AM Gandini Wheeler-Kingshott^2,3,6, Egidio D'Angelo^2,3, and Paolo Cavallari^1
1Human Physiology Section of the DePT, Università degli Studi di Milano, Milano, Italy, ²Department of Brain and Behavioral Science, Università degli Studi di Pavia, Pavia, Italy, ³Brain Connectivity Center Research Department, IRCCS Mondino Foundation, Pavia, Italy, ⁴Neuroradiology Department, Fondazione IRCCS Istituto Neurologico "C. Besta", Milano, Italy, ⁵Developmental Neurology Department, Fondazione IRCCS Istituto Neurologico "C. Besta", Milano, Italy, ⁶Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, NMR Research Unit, Queen Square MS Centre, London, United Kingdom

The simulation of whole-brain dynamics in a single-subject affected by Joubert syndrome (non-progressive pediatric cerebellar ataxia), allowed us to investigate the impact of cerebro-cerebellar connectivity in a brain network with cerebellar dysfunction. The prediction power resulted strongly disturbed with the exclusion of the cerebro-cerebellar network from the generation of cerebral activity. These preliminary results suggest that compensatory mechanisms and plasticity must have taken place in the damaged cerebellum itself to support whole brain functional dynamics.

Jing jing Wu¹, Xiao jun Guan², Tao Guo², Cheng Zhou², Ting Gao³, Xue qin Bai², Xiao cao Liu³, Lu yan Gu³, Pei yu Huang³, Xiao jun Xu³, and Min ming Zhang^2
1Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, HangZhou, China, ²Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, ³The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

The dysfunction of iron metabolism, especially in substantia nigra (SN), in Parkinson’s disease (PD) has been widely acknowledged, but the genetic influence on iron deposition remains largely unknown. Thus, this study aimed to explore the potential genetic impacts on iron deposition in PD patients. Using imaging genetics association analysis, this study discovers two variants, rs602201 and rs198440, have a positive impact on nigral iron deposition in PD. Specifically, patients with rs602201 polymorphism are particularly vulnerable to iron deposition in SN.

Haishan Qiu¹, Jing Zhao¹, Manshi Hu¹, Mengzhu Wang², and Jianping Chu^1
1Sun Yat-sen University, Guangzhou, China, ²Simens Healthcare, Guangzhou, China

There is an evolving history of structural images with SCA3 patients in different disease stages. The WM damage starts with the impairment of ICP and goes through SCP extends to the midbrain, then widespread to the whole brain. The alteration of GMV does not occur until the arise of ataxia symptom, then began to involve the medulla, cerebellum, and pons, and developed to involve basal ganglion, finally affect the cortical cortex. The impairment of WM tracts precedes the GM atrophy and, irrespective of the patients with or without clinical manifestation, the identified WM damage was significantly correlated with SARA.

Uma Sharma¹, Vishwa Rawat¹, Prasenjit Das ², Achal Kumar Srivastava³, and Govind Makharia^4
1Nuclear Magnetic Resonance and MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Pathology, All India Institute of Medical Sciences, New Delhi, India, ³Neurology, All India Institute of Medical Sciences, New Delhi, India, ⁴Gasteroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India

Present study investigated volumetric volume changes in the brain  of patients suffering from Gluten Ataxia (GA) using MRI. GA patients were seen to have significantly low brain and cerebellar volumes along the lobules which form the part of vermis suggesting cell degeneration and role of vermis in GA. GA patients also had significantly high levels of CSF. No significant changes were observed in whole brain grey matter, cerebrum, caudate, hippocampus and amygdala. Our results suggest that cerebrum volume is not linked to GA but lobes of cerebellum, whole brain white matter and CSF is significantly associated with GA.

Umang Pandey¹, Jitender Saini², Manoj Kumar², Rakesh Gupta³, and Madhura Ingalhalika^1
1Symbiosis Centre for Medical Image Analysis, Symbiosis International University, Pune, India, ²Department of Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India, ³Department of Radiology,Fortis Memorial Research Institute, Gurgaon, India

Radiomics in neuroimaging has gained momentum as a noninvasive prediction tool not only to differentiate between types of brain tumors, but also to create phenotypic signatures in neurological/neuropsychiatric disorders. However, there is currently little understating about the robustness and reproducibility of radiomic features in a baseline normative population. Moreover, the radiomics across cerebellum which has a more complex anatomy has not been evaluated This study investigates and demonstrates the intra- and inter-scanner reproducibility and the spatial variations within the regions of the cerebrum and cerebellum. Our findings suggest that care must be taken while interpreting these features for pathological inferences.

Zenghui Cheng¹, Bin Xiao², Naying He³, Dinggang Shen⁴, Qian Wang⁵, Feng Shi⁴, Youmin Zhang³, Pei Huang³, Yan Li³, Sean K Sethi⁶, Kiarash Ghassaban⁷, Shengdi Chen³, Fuhua Yan³, and Ewart Mark Haacke^7
1Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²Medical Imaging Technology, 、School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ³Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁴Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China, ⁵Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ⁶Magnetic Resonance Innovations, Inc, Bingham Farms, MI, United States, ⁷Wayne State University, Detroit, MI, United States

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of neuromelanin-containing dopaminergic neurons and iron deposition mainly in the substantia nigra (SN). Previous studies mainly focused on global changes in both neuromelanin (NM) and iron content. In this study, we used a voxel-wise analysis to investigate the spatial changes of iron and NM content in PD and found that the ventral and medial part of the SN pars compacta had more iron deposition and less neuromelanin, especially, in early-stage PD.

Mojtaba Jokar¹, Ying Wang^1,2, Zhijia Jin³, Yan Li³, Zenghui Cheng³, Yu Liu³, Naying He³, Fuhua Yan³, and E. Mark Haacke^1,2,3,4,5
1Magnetic Resonance Innovations, Inc., Bingham Farms, MI, United States, ²Department of Radiology, Wayne State University, Detroit, MI, United States, ³Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁴Department of Biomedical Engineering, Wayne State University, Detroit, MI, United States, ⁵Department of Neurology, Wayne State University, Detroit, MI, United States

A total of 37 healthy controls (HC) were used to create a template which was then used to automatically detect neuromelanin, substantia nigra, red nucleus and subthalamic nucleus in the midbrain. In order to evaluate the performance of the template, regions of interest (ROIs) were drawn manually on the MTC and QSM images. DICE similarity coefficients and volume ratios of the template to manual data were calculated for different thresholds for each structure. These showed promising results, validating the performance of the template.

Septian Hartono^1,2, An Sen Tan³, Weiling Lee⁴, Joey Oh⁴, Kuan Jin Lee⁵, Jongho Lee⁶, Eng King Tan^1,2, and Ling Ling Chan^2,4
1National Neuroscience Institute, Singapore, Singapore, ²Duke-NUS Medical School, Singapore, Singapore, ³Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore, ⁴Singapore General Hospital, Singapore, Singapore, ⁵Singapore BioImaging Consortium, Singapore, Singapore, ⁶Seoul National University, Seoul, Korea, Republic of

Asian-specific leucine-rich repeat kinase 2 (LRRK2) gene risk variants are associated with increased risk of idiopathic Parkinson’s disease (PD) and accelerated motor progression in disease. We examined the role of quantitative susceptibility mapping (QSM) and neuromelanin-sensitive MRI (NMS) in quantifying dopaminergic denervation in the substantia nigra (SN) in LRRK2 risk-carriers and non-carriers in PD. QSM susceptibility and high-iron area in the SN were significantly increased in PD risk-carriers compared to non-carriers; NMS showed no difference between these two groups. Combined quantitative QSM models displayed good classification performance discriminating risk-carrier from non-carrier groups (68.4% sensitivity, 92.3% specificity, AUC 0.804) in PD.

A Ankeeta¹, S Senthil Kumaran¹, and Rohit Saxena^2
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, Delhi, India, ²Dr RP Centre of Ophthalmology, All India Institute of Medical Sciences, Delhi, India

This study investigated structural alteration, cerebellar BOLD activation and functional connectivity during Braille reading by congenital blind (CB) children. Functional magnetic resonance imaging (fMRI) during Braille reading and T1 data were acquired on a 3T MR scanner in CB and sighted control (SC) children. CB children showed bilateral activation in posterior lateral cerebellum Crus I, II. BOLD cerebellar, visual signals and functional connectivity measures exhibited positive correlation with duration of Braille reading. Involvement of cerebellum, visual cortex during Braille reading in congenital blind children suggest its role in haptic language processing.

Rahul Gaurav^1,2,3, Emina Arsovic^1,4, Lydia Chougar^1,4, Nadya Pyatigorskaya^1,2,3,4, Marie Vidailhet^2,3,5, and Stephane Lehericy^1,2,3,4
1CENIR, ICM Paris, Paris, France, ²Paris Brain Institute (ICM), Sorbonne University, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France, ³ICM Team “Movement Investigations and Therapeutics” (MOV’IT), Paris, France, ⁴Department of Neuroradiology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France, ⁵Department of Neurology, APHP, Pitié-Salpêtrière Hospital, Paris, France

Atypical Parkinsonian disorders are progressive neurodegenerative diseases characterized clinically by parkinsonism, associated with degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Histological studies suggested that dopaminergic cell neurodegeneration pattern may differ between atypical Parkinsonian disorders and with Parkinson’s disease.

In this study, we aimed to quantify and compare SNc volume and signal intensity using neuromelanin-sensitive T1-weighted MRI between progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, dementia with Lewy body and sporadic Parkinson’s disease.

Po-Yuan Chen¹, Chih-Chien Tsai¹, Chin-Song Lu², Yi-Hsin Weng², Yi-Ming Wu³, and Jiun-Jie Wang^1
1Chang Gung University, Taoyuan, Taiwan, ²Chang Gung Memorial Hospital, Taoyuan, Taoyuan, Taiwan, ³Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

Precise differentiation between MSA subtype is critical in medical intervention and prognosis. The results of previous studies using DTI to differentiate subtypes of MSA is controversial. We use fixel based analysis to examine the tract-specific differences in white matter between individuals with MSA and healthy controls. The results demonstrate the white matter degeneration in specific fibre bundle, including middle cerebellar peduncle, pontine crossing tract and cerebellar white matter tracts in the early MSA-C patients; in contrast, this pattern was not observed in MSA-P patients. This suggests that FBA may be a sensitive marker for early differential diagnosis of MSA subtype.

Naying He¹, Yu Liu¹, Bin Xiao², Junchen Li³, Chencheng Zhang⁴, Yijie Lai⁴, Feng Shi⁵, Dinggang Shen⁵, Yan Li¹, Hongjiang Wei⁶, Ewart Mark Haacke^1,7, Weibo Chen⁸, Qian Wang², Dianyou Li⁴, and Fuhua Yan^1
1Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, Shanghai, China, ³Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, No. 6 Huanghe Road, Changshu, China, Changshu, China, ⁴Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China, ⁵Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China, Shanghai, China, ⁶Institute for Medical Imaging Technology, Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, Shanghai, China, ⁷Department of Radiology, Wayne State University, Detroit, Michigan, USA, Detroit, MI, United States, ⁸Philips Healthcare，Shanghai，China, Shanghai, China

Currently, there are neither individual objective nor quantitative indicators for predicting DBS motor outcome. We hypothesized that the distribution of SN iron changes in PD patients may reflect a specific disease trait and could potentially account for some variability in the motor outcomes after sub-thalamic nucleus (STN) deep brain stimulation (DBS). We developed a radiomics model with machine learning (RA-ML) based on preoperative individual QSM of the SN to predict motor outcome for STN-DBS in PD and it performed best with an AUC of 0.897. In addition, the threshold probability of the RA-ML model can differentiate surgical responders and non-responders.

Cheng Zhou¹ and Minming Zhang^1
1Zhejiang University, Hangzhou, China

We conducted a neuromelanin sensitive magnetic resonance imaging, which is a good indicator for LC integrity, in 57 PD patients. We depicted a significant positive association between LC integrity and motor improvement after levodopa administration. We further confirmed this relationship in the level of objective brain alteration: LC integrity associated with the improvement of somatomotor network synchronization calculated from functional magnetic resonance imaging. We concluded that LC degeneration was an indicator for less levodopa responsiveness. LC integrity evaluation might be an alternative tool in predicting disease prognosis and stratifying patients into clinical trials for improving the efficacy of levodopa.

Junghwa Kang¹, Na Young Shin², and Yoonho Nam^1,2
1Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, South Korea, yongin, Korea, Republic of, ²Seoul St.Mary’s Hospital, Department of Radiology, The Catholic University of Korea, Seoul, South Korea, Seoul, Korea, Republic of

We proposed an automatic evaluation model for estimating the degree of motion artifacts in high-resolution multi-echo gradient echo images for nigrosome-1 visualization in the substantia nigra. A combination of a convolutional neural network and a long short-term memory was used to develop the automatic motion evaluation model. The results demonstrated that the proposed model could be useful tools for N1 visualization for diagnosing Parkinson’s disease.

Jiahao Li^1,2, Kelly Gillen¹, Ilhami Kovanlikaya¹, Thanh Nguyen¹, Alexey Dimov¹, Kailyn Li¹, Weiyuan Huang¹, Xianfu Luo¹, Carly Skudin¹, Eileen Chang¹, Alexander Shtilbans^1,3, and Yi Wang^1,2
1Weill Cornell Medicine, New York, NY, United States, ²Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States, ³Hospital for Special Surgery, New York, NY, United States

Parkinson’s disease (PD) is a neurodegenerative disorder characterized pathologically by loss of dopaminergic neurons and accumulation of iron in the substantia nigra. Our MR imaging study uses quantitative susceptibility mapping (QSM) and magnetization transfer contrast (MTC) to quantify iron and neuromelanin, respectively in healthy controls, patients with REM sleep behavior disorder (RBD), and PD. We demonstrate that patients with PD have an increase in iron but reduction in neuromelanin in the substantia nigra as compared to healthy controls. Loss of dopaminergic neurons can cause release of neuromelanin, thus furthering a neuroinflammatory and neurodegenerative cycle¹.

Rushi Chen¹, Yan Bai¹, Qin Feng¹, Menghuan Zhang¹, Xianchang Zhang², and Meiyun Wang^1
1Henan provincial people's hospital, Zhengzhou, China, ²MR Collaboration, Siemens Healthcare Ltd, Beijing, China, Beijing, China

Conventional magnetic resonance imaging has limitations in differentiating Parkinson’s disease (PD) from essential tremors (ET). Magnetic resonance spectroscopy (MRS) can non-invasively detect neurochemical alterations in biological tissues. In this study, we used MRS to obtain N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in the substantia nigra (SN) of patients with tremor-dominant PD and ET. The NAA/Cr ratio in the contralateral SN was significantly higher in patients with tremor-dominant PD than those with ET, whereas the Cho/Cr ratios showed no significant differences between groups. The findings suggest that MRS in the SN may be helpful in differentiating tremor-dominant PD from ET.    

Koene R.A. Van Dijk¹, Courtney A. Bishop², James O’Callaghan², James A. Goodman¹, Laigao Chen¹, Peter T. Loudon³, Lawrence Charnas⁴, Eugenii A. Rabiner², and Richard Festenstein^5
1Digital Medicine and Translational Imaging, Early Clinical Development, Pfizer, Cambridge, MA, United States, ²Invicro, London, United Kingdom, ³Clinical Sciences, Early Clinical Development, Pfizer, Cambridge, United Kingdom, ⁴Rare Disease Research Unit, Pfizer, Cambridge, MA, United States, ⁵Department of Brain Sciences, Imperial Clinical Research Facility and BRC (NIHR), Imperial College London, London, United Kingdom

We report on feasibility of a short but comprehensive 3T brain MRI protocol in Friedreich ataxia. The multi-parametric protocol includes measures of anatomy, iron content, several indices of white matter, and brain metabolites. The scan session, lasting less than 60 minutes, was tolerated well by all 8 patients who had varying degrees of ataxia symptomatology, and provided good quality imaging data for the majority of sequences and patients. This protocol allows non-invasive quantitative characterization of progressive neurodegeneration in cerebral and cerebellar structures in patients with Friedreich ataxia suggesting the potential for rich, longitudinal phenotyping in this population.

Malte Brammerloh^1,2, Evgeniya Kirilina^1,3, Anneke Alkemade⁴, Pierre-Louis Bazin^1,4, Caroline Jantzen¹, Carsten Jäger^1,5, Andreas Herrler⁶, Kerrin J. Pine¹, Penny Gowland⁷, Markus Morawski⁵, Birte Forstmann⁴, and Nikolaus Weiskopf^1,2
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Faculty of Physics and Earth Sciences, Leipzig University, Leipzig, Germany, ³Center for Cognitive Neuroscience Berlin, Freie Universität Berlin, Berlin, Germany, ⁴Integrative Model-based Cognitive Neuroscience Research Unit, University of Amsterdam, Amsterdam, Netherlands, ⁵Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany, ⁶Department of Anatomy and Embryology, Maastricht University, Maastricht, Netherlands, ⁷Sir Peter Mansfield Imaging Center, University of Nottingham, Nottingham, United Kingdom

MRI holds great promise for diagnosing Parkinson's disease, based on the disappearance of the swallow tail sign in T2*-weighted images, which past research assumed to be nigrosome 1. We studied the sign's anatomical underpinning, combining ultra-high field MRI in vivo and postmortem, 3D-reconstructed microscopy, and immunohistochemistry. Based on block-face images and calbindin-D28K immunohistochemistry, we constructed a 3D nigrosome atlas. We show that nigrosome 1 extends beyond the swallow tail sign by co-registering this atlas to in vivo MRI. As the swallow tail sign only partially overlaps with but is not identical to nigrosome 1, its interpretation needs to be revised.