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Hongwei Li¹, Jian Wang^2,3, Jia Jia⁴, Xiali Shao², He Wang^1,5,6, and Lirong Jin^4
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, ²Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China, ³Department of Radiology, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen, China, ⁴Department of Neurology, Zhongshan Hospital, Fudan Universit, Shanghai, China, ⁵Human Phenome Institute, Fudan University, Shanghai, China, ⁶Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China

Keywords: Parkinson's Disease, fMRI (resting state), cerebrovascular reactivity

Increasing evidence showed subtle cerebrovascular reactivity (CVR) impairment in neurodegenerative disease. In the longitudinal study herein, we aimed to investigate regional CVR changes in the patients with Parkinson’s disease (PD) at baseline and 2 years follow up, and CVR was derived from resting state fmri scans. PD patients showed significantly reduced CVR in the left inferior occipital gyrus and right superior temporal cortex. In addition, the reduction of CVR may associate with executive function deficits. Our results also showed that there was a tendency for functional connectivity to be weakened from posterior to anterior with the progression of the disease.

Ting-Chieh Chen¹, Ssu-Ju Li¹, Kai-Yun Chen², Yu-Chun Lo², Yi-Chen Lin¹, Ching-Wen Chang¹, Yao-Wen Liang¹, Tsai-Yu Cho¹, Mu-Hua Wang¹, Sheng-Huang Lin^3,4, and You-Yin Chen^1,2
1Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²PhD Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ³Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ⁴Department of Neurology, School of Medicine, Tzu Chi University, Hualien, Taiwan

Keywords: Parkinson's Disease, Parkinson's Disease

The progression of Parkinson′s disease (PD) is associated with mitochondrial dysfunction, and deep brain stimulation (DBS) of the nucleus accumbens (NAc) was found to enhance mitochondrial function. Therefore, the presented study aimed to explore the therapeutic effects of NAc-DBS on PD. In this study, the NAc-DBS treatment, behavioral tests, brain magnetic resonance imaging analysis, and mitochondrial respiratory assay were conducted on the MitoPark PD mouse model. After NAc-DBS, the PD mouse model showed improvements in motor and cognitive functions with increased functional connectivity and promoted aerobic metabolism in the dopaminergic (DA) pathways.

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Su Yan¹, Jun Lu¹, Weiyin Vivian Liu², and Wenzhen Zhu^1
1Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²MR Research, GE Healthcare, Beijing, China

Keywords: Parkinson's Disease, Quantitative Susceptibility mapping

The purpose of this study was to employ QSM and OEF maps to quantitatively measure iron content and oxygen metabolism levels in deep gray matter of the Parkinson’ s disease brains in different stages and explore their relationship with clinical features. Iron accumulation in SN, RN and GP significantly increased with the progression of PD severity. In contrast, OEF in CAU, PT, and DN elevated in early PD and then gradually decreased with worsening symptoms, indicating a different spatiotemporal pattern. These findings may facilitate to understand the neurobiological mechanisms in PD progression and offered complementary indicators for diagnosis and prediction.

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Gehua Tong¹, John Thomas Vaughan, Jr.^1,2, and Sairam Geethanath^2,3
1Biomedical Engineering, Columbia University, New York, NY, United States, ²Columbia Magnetic Resonance Research Center, Columbia University, New York, NY, United States, ³Accessible MR Laboratory, BioMedical Engineering and Imaging Institute, Dept. of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mt. Sinai, New York, NY, United States

Keywords: Parkinson's Disease, Pulse Sequence Design

2D MSI was tested for recovering the closest layer of off-resonant signals near a DBS lead. The effects of slice thickness and RF profile were measured in an ASTM gel phantom with an in-plane DBS lead. Increasing the slice thickness from 1.5x to 2.5x the lead diameter reduced the apparent lead width by 8.35% and increasing the time-bandwidth product of the RF pulse by four times improved SSIM with a reference TSE image by 88.5%. A trade off between bin definition and echo times limited signal recovery at a given bin bandwidth (800 Hz / 9 bins). 

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Keywords: Parkinson's Disease, Focused Ultrasound

The phase I clinical trial demonstrated the successful application of microbubble-assisted MR-guided Focused Ultrasound for blood-brain barrier (BBB) opening in the putamen to facilitate biweekly therapeutic drug delivery in patients with Parkinson's disease. BBB permeability within the targeted putamen was elevated successfully in all treatments, as revealed by Gd-enhanced T1-weighted MRI immediately post treatment. No contrast enhancement was observed in the treated putamen on MR imaging scans acquired one day following each treatment session, indicating closure of the BBB. FDG-PET revealed a reduction of glucose metabolism of the treated putamen relative to the contralateral putamen in all patients.

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Miguel López-Aguirre^1,2,3, Noelia Esteban-García^1,4, Tiziano Balzano¹, María Ciorraga¹, Javier Blesa^1,3, José A. Obeso^1,3,5, and José A. Pineda-Pardo^1,3,5
1HM CINAC, Hospital Universitario HM Puerta del Sur, Móstoles, Spain, ²Universidad Complutense de Madrid, Madrid, Spain, ³Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain, ⁴Universidad Autónoma de Madrid, Madrid, Spain, ⁵Universidad San Pablo-CEU, Madrid, Spain

Keywords: Parkinson's Disease, Relaxometry, Iron

Iron has an important role in Parkinson’s disease (PD) pathophysiology. However, it is still uncertain how iron accumulates within the nigrostriatal circuit along with PD progression. Here we assessed iron content from early to moderate PD stages using R2* relaxometry, and histologically using a macaque MPTP (1-metil-4-fenil6-tetrahidropiridina) model. Our analyses revealed that in both human PD and MPTP model, iron accumulates progressively within SNpc during early stages , reaching a plateau before moderate PD. Meanwhile,  iron followed a V-shaped progression in the striatum. These results will contribute to improve our understanding of nigrostriatal vulnerability and the course of neurodegeneration in PD.

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Pohchoo Seow¹, Yao-Chia Shih², Septian Hartono³, Pik Hsien Chai⁴, Weiling Lee⁴, Celeste Yan Teng Chen ³, Eng King Tan³, and Ling Ling Chan^1
1Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore, ²Graduate Institute of Medicine, Yuan-Ze University, Taoyuan City, Taiwan, ³Department of Neurology, National Neuroscience Institute, Singapore, Singapore, ⁴Radiography, Singapore General Hospital, Singapore, Singapore

Keywords: Parkinson's Disease, Diffusion/other diffusion imaging techniques

The mechanism by which involvement of the cholinergic pathways underlies the non-motor manifestations of Parkinsonian disorders remains unclear. We mapped and investigated the pedunculopontine nucleus (PPN) projections that exhibit significant correlations with sleep disturbances in 80 Parkinson’s disease (PD) patients and 110 healthy controls (HC) using correlational tractography. Intracellular and extracellular diffusivity (RDI and NRDI metrics respectively) demonstrated significant correlations (r=0.06-0.14, FDR<0.05) with sleep abnormalities in the PPN projections of PD compared to HC. Our findings established non-motor markers of PPN system denervation with sleep disturbances to further understand the pathophysiology of non-motor symptoms in PD.

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Malte Brammerloh¹, Evgeniya Kirilina^1,2, Anneke Alkemade³, Pierre-Louis Bazin^1,3, Caroline Jantzen¹, Sara Schaumberg¹, Carsten Jäger^1,4, Andreas Herrler⁵, Kerrin J. Pine¹, Markus Morawski^1,4, Birte Forstmann³, and Nikolaus Weiskopf^1,6
1Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Center for Cognitive Neuroscience Berlin, Freie Universität Berlin, Berlin, Germany, ³Integrative Model-based Cognitive Neuroscience Research Unit, University of Amsterdam, Amsterdam, Netherlands, ⁴Paul Flechsig Institute - Center of Neuropathology and Brain Research, Leipzig University, Leipzig, Germany, ⁵Department of Anatomy and Embryology, Maastricht University, Maastricht, Netherlands, ⁶Felix Bloch Institute for Solid State Physics, Leipzig University, Leipzig, Germany

Keywords: Parkinson's Disease, Multimodal, Atlas, Subcortex

MRI holds great promise to unravel the selective vulnerability and functional differentiation of the nigrosomes in the human substantia nigra pars compacta. Based on block-face imaging and calbindin-D28K immunohistochemistry, we constructed a 3D nigrosome atlas. Using this atlas, we demonstrate several nigrosomes to show increased R2* values in post mortem tissue. Our results further challenge the common identification of the nigrosomes with hyperintense structures in in vivo MRI, particularly nigrosome 1 and the swallow tail sign.

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Alexandra Grace Roberts^1,2, Ilhami Kovanlikaya², Brian Koppel³, Pascal Spincemaille², Thanh Nguyen², and Yi Wang^1,2
1Electrical Engineering, Cornell University, Ithaca, NY, United States, ²Radiology, Weill Cornell Medicine, New York, NY, United States, ³Radiology, Mount Sinai Hospital, New York, NY, United States

Keywords: Parkinson's Disease, Brain

Morphology Enabled Dipole Inversion (MEDI) is an iterative reconstruction algorithm for Quantitative Susceptibility Mapping (QSM) that is effective in suppressing artifacts by exploiting the magnitude image as a morphological prior. Use of a phase prior such as the local field to determine the $$$L_1$$$ regularization term results in improved visualization of the medial medullary lamina as measured by the contrast-to-noise ratio and was preferred by a radiologist over the magnitude prior in each case.

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Elior Drori¹, Lee Cohen¹, Einat Kohn², David Arkadir³, Gilad Yahalom², and Aviv A Mezer^1
1The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel, ²The Department of Neurology, Shaare Zedek Medical Center, Jerusalem, Israel, ³The Department of Neurology, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel

Keywords: Parkinson's Disease, Quantitative Imaging, striatum

Parkinson’s disease (PD) is associated with degeneration in the striatum, a deep brain structure. It was recently shown with clinical MRI that in vivo gradients in the striatum of PD patients are related to the early-stage symptoms and pathology. However, the spatial variation in quantitative biophysical properties in PD is still unknown. Here, we collected multiparametric quantitative MRI of PD patients. We reveal distinct spatial profiles in the striatum that corroborate previous findings and show a relationship between putamen water fraction and motor behavior. Thus, our study provides new insights for the biological mechanisms associated with PD behavior.

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Samy Abo Seada¹, Anke W. van der Eerden¹, Agnita J.W. Boon², and Juan Antonio Hernandez-Tamames^1,3
1Radiology and nuclear medicine, Erasmus MC, Rotterdam, Netherlands, ²Department of Neurology, Erasmus MC, Rotterdam, Netherlands, ³Department of Imaging Physics, TU Delft, Delft, Netherlands

Keywords: Parkinson's Disease, Normal development

An optimized clinically feasible neuromelanin MRI imaging protocol for visualising the SN and LC simultaneously using deep learning reconstruction is presented. For a 2D sequence we set out to optimize the flip-angle for optimal combined SN and LC depiction. We also experimented with combinations of anisotropic and isotropic in-plane resolution, partial vs full echoes and the number of averages. Phantom and in-vivo experiments on three healthy volunteers illustrate that high-resolution imaging combined with deep-learning denoising shows good depiction of the SN and LC with a clinically feasible sequence of 7 minutes.

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Keywords: Parkinson's Disease, Motion Correction

Neuromelanin-MRI can detect reductions in volume and intensity of the substantia nigra in Parkinson’s disease (PD). High-resolution magnetization transfer (MT) contrast T1-weighted sequences are used, and the MT pulse is time-consuming. We evaluated the degree of motion during a long (~ 12 min) scan in a PD patient and a healthy volunteer, and the effect of motion correction using a wireless RF-triggered acquisition device (WRAD) developed in our group. Despite only minor motion, for both participants, motion correction improved image quality.

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Afis Ajala¹, Jianwei Qiu¹, John Karigiannis¹, Brendan Santyr², Jurgen Germann², Alexandre Boutet², Luca Marinelli¹, Chitresh Bhushan¹, Radhika Madhavan¹, Desmond Yeo¹, and Andres Lozano^2
1GE Global Research, Niskayuna, NY, United States, ²University Health Network and University of Toronto, Toronto, ON, Canada

Keywords: Parkinson's Disease, fMRI

Successful treatment of Parkinson’s disease using deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) requires an optimal set of DBS parameters that involves time-consuming programming sessions (~1 year) by the current standard-of-care optimization protocol. Functional magnetic resonance imaging (fMRI) and deep learning with autoencoder-based feature extraction from DBS-fMRI responses have provided a way to rapidly optimize the DBS parameters.  In this work, we examine the robustness of the unsupervised autoencoder-based feature extraction method to changes in the activation patterns of the DBS-fMRI responses, which may be caused by patient motion, difference in stimulation side and disease condition.

Song'an Shang¹, Weiqiang Dou², and Ye Jing^1
1Clinical Medical College, Yangzhou University, Yangzhou, China, ²GE Healthcare, MR Research China, Beijing, China

Keywords: Parkinson's Disease, Neurodegeneration

Parkinson’s disease (PD) is manifested with disrupted topology of structural connection network (SCN) and functional connection network (FCN). However, SCN and its interactions with FCN remain to be further investigated. This multimodality study attempted to precisely characterize the SCN using diffusion kurtosis imaging (DKI) and further identify the neuropathological pattern of SCN-FCN decoupling. Our study verified the optimization of SCN by applying DKI metrics and its implications for the clinical diagnosis of PD. Moreover, SCN-FCN decoupling is consequent from mismatched disruptions of the SCN and FCN, identifying pathophysiological neuroimaging features for disturbed neural circuits in PD.

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Haoting Wu¹ and Minming Zhang^1
1Radiology, Medical school of Zhejiang university, Hangzhou, China

Keywords: Parkinson's Disease, fMRI (resting state)

The predictive connectome of PD gait overlapped with the dopaminergic and cholinergic systems.