Darrell Ting Hung Li¹, Edward Sai Kam Hui¹, Queenie Chan², Nailin Yao³, Siew-eng Chua⁴, Grainne M. McAlonan^4,5, Shu Leong Ho⁶, and Henry Ka Fung Mak^1
1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, ²Philips Healthcare, Hong Kong, Hong Kong, ³Department of Psychiatry, Yale University, New Haven, CT, United States,⁴Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong, ⁵Department of Forensic and Neurodevelopmental Science, King’s College London, London, United Kingdom, ⁶Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong

Parkinson’s disease (PD) patients may develop other non-motor comorbidities when the disease progress. While increased nigral iron was considered as a biomarker of the disease, it was also believed that iron deposition is associated with the development of other non-motor symptoms. In this study, magnetic susceptibility as a surrogate of iron concentration was measured in six major subcortical brain regions on the QSM images. Increased magnetic susceptibilities were observed in hippocampus and amygdala of the PD patients with dementia, suggesting a possible association of iron with the development of dementia symptom in late stage of PD.

Dan Wu¹, Laurent Younes^2,3,4, Andreia V Faria¹, Christopher A Ross⁵, Susumu Mori^1,6, and Michael I Miller^3,4,7
1Radiology, Johns Hopkins University School of Medicine, BALTIMORE, MD, United States, ²Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United States, ³Center for Imaging Science, Johns Hopkins University, Baltimore, MD, United States, ⁴Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, United States, ⁵Departments of Psychiatry, Neurology, Neuroscience and Pharmacology, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, BALTIMORE, MD, United States, ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁷Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

In order to understand the temporal and spatial order of brain atrophy in Huntington’s disease (HD), we aim to characterize the whole brain volumetric changes based on T1-weighted whole brain segmentation. We adapted a novel multi-variant linear statistical model to capture the change points of volumetric changing courses from 412 control and HD subjects. The change point analysis revealed that the brain atrophy initiated in the deep gray matter structures and progressed to the peripheral white matter and cortical regions, and it also suggested the posterior brain atrophy proceeded the anterior brain.  

Silvina G Horovitz¹, Nora Vanegas-Arroyave^1,2, Ling Huang², Peter M Lauro², Paul A Taylor^3,4,5, Mark Hallett¹, Kareem A Zaghloul⁶, and Codrin Lungu^2
1Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States, ²Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States, ³Scientific and Statistical Computing Core, National Institutes of Health, Bethesda, MD, United States, ⁴Department of Human Biology, Faculty of Health Sciences, University of Cape Town, MRC/UCT Medical Imaging Research Unit, Cape Town, South Africa, ⁵African Institute for Mathematical Sciences, Muizenberg, South Africa, ⁶Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical treatment for Parkinson’s Disease (PD). However, its mechanism is unclear. We have developed a pipeline for processing diffusion tensor imaging (DTI) data in DBS patients, and applied it to analyze 22 PD patients implanted with bilateral STN-DBS. With this approach, we have identified the motor nuclei of the thalamus and the superior frontal cortex as the most common targets and predictors of clinical benefits.

Stephen Edward Jones¹, Hyun-Joo Park², Pallab Bhattacharyya¹, and Andre Machado^2
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Neurologic Institute, Cleveland Clinic, Cleveland, OH, United States

We present a new intra-operative MRI technique for evaluating placement of DBS electrodes in patients with movement disorders, using simultaneous electrical stimulation and fMRI.  This technique can elicit a strong BOLD effect whose pattern can reflect underlying networks. There is strong spatial sensitivity of these patterns to electrode position, which is important for clinical utility in predicting clinical response and unwanted side-effects.

Xiaojun Guan¹, Min Xuan¹, Quanquan Gu¹, Xiaojun Xu¹, Chunlei Liu^2,3, Peiyu Huang¹, Nian Wang², Yong Zhang⁴, Wei Luo⁵, and Minming Zhang^1
1Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, People's Republic of, ²Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, American Samoa, ³Department of Radiology, Duke University School of Medicine, Durham, American Samoa, ⁴MR Research, GE Healthcare, Shanghai, China, People's Republic of, ⁵Neurology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, People's Republic of

We explored the relationships between cerebral iron and the motor impairments in PD.   Quantitative susceptibility mapping was used to quantify the iron content in vivo.  

Iron content in dentate and red nuclei had close associations with tremor symptom.  

Caudate and nigral iron content significantly correlated with akinetic/rigid symptom.  

These might support the idea that regional iron is related to the motor impairments.

Darrell Ting Hung Li¹, Edward Sai Kam Hui¹, Queenie Chan², Nailin Yao³, Siew-eng Chua⁴, Grainne M. McAlonan^4,5, Shu Leong Ho⁶, and Henry Ka Fung Mak^1
1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, ²Philips Healthcare, Hong Kong, Hong Kong, ³Department of Psychiatry, Yale University, New Haven, CT, United States,⁴Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong, ⁵Department of Forensic and Neurodevelopmental Science, King’s College London, London, United Kingdom, ⁶Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong

Abnormal nigral iron deposition is considered one of the major biomarkers in Parkinson’s disease (PD). Extensive studies had been performed to evaluate iron concentration in substantia nigra using different in vivo imaging methods. Whole structure ROI-based analysis of basal nuclei is a majority approach in similar studies. In this study, we investigated the distribution of iron in substantia nigra with both voxel-wise and split ROI methods. Location of significant higher iron concentration was identified to be around pars compacta of the substantia nigra in PD brain. The two methods adopted in this study agreed with each other.

Stephen J Sawiak¹, Nigel I Wood¹, T Adrian Carpenter¹, and A Jennifer Morton^1
1University of Cambridge, Cambridge, United Kingdom

Huntington’s disease is caused by an unstable gene carrying excessive polyglutamine CAG repeats. Patients with genes carrying more CAG repeats have a less favourable outcome. The R6/2 mouse has a fragment of the human HD gene with 100 CAG repeats. We compared mice carrying longer CAG repeats (250 and 350) with wildtype controls using high-resolution in vivo longitudinal MRI and spectroscopy. Paradoxically, the 350CAG mice live longer, with ultimately similar but much slower atrophy and metabolic changes than 250CAG mice. They may, therefore, be a more useful model of HD with a longer window to evaluate pathology and treatments. 

Matt Gabel¹, Rebecca Broad², Daniel C. Alexander³, Hui Zhang³, Nicholas G. Dowell¹, Peter Nigel Leigh², and Mara Cercignani^1
1Clinical Imaging Sciences Centre, Brighton & Sussex Medical School, Falmer, United Kingdom, ²Trafford Centre for Medical Research, Brighton & Sussex Medical School, Falmer, United Kingdom, ³Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom

NODDI is a multi-compartment model of diffusion MRI that overcomes some of the limitations of DTI. Our aim was to assess whether voxelwise analysis of NODDI parameters could provide a more comprehensive picture than DTI in assessing the microstructural changes associated with ALS. We analysed NODDI and DTI parameters for 17 patients with ALS and 19 healthy controls using Advanced Normalization Tools (ANTs) 2.1.0 and SPM12, with age included as a covariate.  Both NODDI and DTI indices are sensitive to pathological changes in ALS, but NODDI provides more specific tissue microstructure characterisation.

Dikoma C. Shungu¹, Kristin Engelstadt², Xiangling Mao¹, Guoxin Kang¹, Aya Goji¹, Robert H. Fryer², Savalatore DiMauro², and Darryl C. De Vivo^2
1Radiology, Weill Cornell Medical College, New York, NY, United States, ²Neurology, College of Physicians and Surgeons of Columbia University, New York, NY, United States

Although mitochondrial dysfunction has been associated with redox dysregulation, in vivo human brain evidence of such an association is currently lacking. This study aimed to use ¹H MRS to measure brain levels of the primary tissue antioxidant glutathione (GSH) in patients with MELAS – a primary mitochondrial disorder –  as an objective marker of CNS oxidative stress in such disorders. Compared to healthy control subjects, patients with MELAS showed a 31% lower cortical GSH levels, thereby directly implicating CNS oxidative stress as a player in the disorder and pointing to potential therapeutic interventions based on elevating the levels of cerebral antioxidants.

Stefano Zanigni^1,2, Stefania Evangelisti^1,2, Claudia Testa^1,2, David Neil Manners^1,2, Giovanna Calandra-Buonaura^1,3, Maria Guarino⁴, Anna Gabellini^3,5, Luisa Sambati^1,3, Pietro Cortelli^1,3, Raffaele Lodi^1,2, and Caterina Tonon^1,2
1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, ²Policlinico S.Orsola-Malpighi, Functional MR Unit, Bologna, Italy, ³IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ⁴Policlinico S.Orsola-Malpighi, Neurology Unit, Bologna, Italy, ⁵Ospedale Maggiore, Neurology Unit, Bologna, Italy

We applied a probabilistic tractography FSL-based method to evaluate alterations in the cortico-spinal tract (CST), middle and superior cerebellar peduncles (MCP and SCP, respectively) in 90 patients with neurodegenerative parkinsonisms (Progressive Supranuclear Palsy, Multiple System Atrophy, and Parkinson’s disease). Patients and healthy controls were evaluated on a 1.5T GE scanner. DTI metrics were evaluated in the whole CST, MCP and SCP tracts, and in addition, an along tract analysis for CST has been performed. We found that specific patterns of neurodegeneration within these specific tracts are evident and that they reflect the neuropathological and clinical profile of each syndrome.