Neurodegenerative Disease (Not Alzheimer's Disease or Dementia)

Wednesday 14 May 2014

Owen Thomas¹, Ammar Issa², Thomas P Hansen², John Cain², Nitin Purandare³, and Alan Jackson^2
1Department of Neuroradiology, Salford Royal NHS Hospitals Foundation Trust, Manchester, Lancashire, United Kingdom, ²Wolfson Molecular Imaging Centre, University of Manchester, Manchester, Lancashire, United Kingdom, ³Greater Manchester Old Age Psychiatry Service, University of Manchester, Manchester, Lancashire, United Kingdom

We examine the discriminative power of brainstem hyperintensities in an elderly population of patients with vascular dementia (VaD), Alzheimer’s dementia (AD) and age-matched normal controls. Hyperintensities in the pons were scored using a novel system and combined with scores of hyperintensity in the hemispheric white-matter, dilated perivascular spaces, lacunar and hemispheric infarcts. The presence of pontine and medial lemniscus hyperintensities provided the greatest independent discriminative power for the separation of VaD and AD accounting for 40% and 12% of the variance in the linear regression model respectively. The area under the receiver operator curve was 0.833.

Gulin Oz¹, Emily Colonna¹, Doene Demirgoez¹, Orion Rainwater¹, Lynn E. Eberly¹, Harry T. Orr¹, and H. Brent Clark^1
1University of Minnesota, Minneapolis, MN, United States

A conditional transgenic mouse model of spinocerebellar ataxia type 1 (SCA1) was used to determine if ¹H MRS reflects the extent of neurodegeneration reversal. Transgene expression was suppressed from 12-24 weeks and cerebellar neurochemical profiles of treated and untreated conditional mice and controls were measured at 9.4T using short echo LASER. The data demonstrate that ultra-high field MRS accurately reflects the extent of recovery from neurodegeneration (based on significant correlations with histology and residual transgene expression by qPCR) and is more sensitive than the standard motor behavioral testing (Rotarod) in detecting treatment effects.

Štefan Holiga¹, Karsten Mueller¹, Filip Ruzicka², Dušan Urgošík³, Harald E. Möller¹, Evzen Ruzicka², Matthias L. Schroeter^1,4, and Robert Jech^2
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Czech Republic, ³Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague, Czech Republic, ⁴Clinic for Cognitive Neurology, University of Leipzig, Germany

Microlesion-effect (MLE) is a phenomenon appearing during implantation of deep-brain stimulation electrodes in subthalamic nucleus (STN) of patients suffering from Parkinson’s disease (PD). It is associated with transient, but marked improved of patients’ motor symptoms. We took advantage of this invasive intervention and combined it with hypothesis-free resting-state fMRI analytical method of eigenvector centrality, which gave us a unique opportunity to study the impact of disrupted STN on the motor-circuitry in human PD in-vivo. We linked several central brain structures with the MLE. Further, brainstem, cerebellum and putamen/globus-pallidus were found to account for improvements in particular PD symptoms.

Kenji Ito¹, Makoto Sasaki¹, Chigumi Ohtuka², Ikuko Uwano¹, Fumio Yamashita¹, Satomi Higuchi¹, Jonathan Goodwin^1,3, Taisuke Harada^1,3, and Yasuo Terayama^2
1Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Japan, ²Department of Neurology and Gerontology, Iwate Medical University, Morioka, Japan, ³Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan

The differential diagnosis of early-stage parkinsonisms such as PD, MSA-P, MSA-C, and PSP is often difficult. Hence, we investigated whether diffusion kurtosis imaging (DKI), which enables detecting subtle pathological changes, can differentiate these disorders by using an automated ROI-based quantitative analysis. Mean kurtosis (MK) values of the gray matter structures were significantly different between patients with PD and PSP, while fractional anisotropy and/or mean diffusivity in the white matter structures were different between patients with PD and patients with MSA-C/PSP. A combined usage of DKI and other classical diffusion metrics can therefore contribute to the differential diagnosis of early-stage parkinsonisms.

Pierre-Gilles Henry¹, Dinesh Deelchand¹, Isabelle Iltis¹, Diane Hutter¹, Khalaf O Bushara¹, Gulin Oz¹, and Christophe Lenglet^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

We measured ¹H MR spectra and acquired diffusion MRI data of the spinal cord in patients with Friedreich’s Ataxia and control subjects at 3T. With ¹H MRS, we observed a 40% decrease in NAA and 46% increase in myo-inositol concentrations in the spinal cord of patients compared to controls, reflecting neuronal degeneration and gliosis, respectively. With diffusion, we observed a decrease in fractional anisotropy of the spinal cord, as well as alteration of the nerve roots. These findings may be useful to monitor disease progression and assess therapeutic efficacy in prospective clinical trials.

Govind Nair¹, Katherine C Gao¹, Irene C. M. Cortese¹, Alan Koretsky¹, and Daniel S Reich^1
1NINDS, National Institutes of Health, Bethesda, MD, United States

Cerebral atrophy is a common feature in neurological diseases that contributes to disability. CSF volume increases to occupy the space left by the atrophying brain. CSF volume can be quantified by intensity thresholding a heavily T2-weighted scan. This brain-free water (BFW) volume, and BFW-volume normalized to the intracranial space, exhibited significant correlation with various clinical measures of disability in 83 multiple sclerosis cases. These measures outperformed brain volume measurements using Lesion-TOADS by 8-19%. The better performance of this new algorithm was attributed to higher resolution enabling improved visualization of sulcal spaces, and the simpler segmentation algorithm in this new BFW-method.

Jason Langley¹, Daniel Huddleston^2,3, Xiangchuan Chen¹, Jan Sedlacik⁴, Shiyang Chen¹, and Xiaoping Hu^1
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States,²Department of Neurology, Emory University, Atlanta, GA, United States, ³Center for Health Research, Southeast, Kaiser Permanente, Atlanta, GA, United States, ⁴Department of Neuroradiology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

Degeneration of the substantia niagra(SN) is a hallmark of many neurodegenerative disorders including Parkinson’s disease and Alzheimer’s disease. Visualization and volumetric quantification of the SN would be beneficial to early detection of both diseases. Magnetization transfer contrast (MTC) imaging is sensitive to neuromelanin-containing structures in the brain and susceptibility weighted imaging (SWI) is sensitive to iron. This abstract compares the segmentation results of the SN from MTC and SWI images. Both methods give volumetric estimates that are approximately similar but the spatial overlap between the two regimes is ~11%. Indicating a multimodal approach will yield more accurate segmentation results.

Frank C.G. van Bussel¹, Walter H. Backes¹, Paul A.M. Hofman¹, Alfons G.H. Kessels², Tamar M. van Veenendaal¹, Harm J. van de Haar¹, Martin P.J. van Boxtel³, Miranda T. Schram⁴, Coen D.A. Stehouwer⁴, Joachim E. Wildberger¹, and Jacobus F.A. Jansen^1
1Radiology, Maastricht University Medical Center, Maastricht, Netherlands, ²Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, Netherlands, ³Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, Netherlands,⁴Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands

Type 2 Diabetes Mellitus (T2DM) is associated with cognitive decline. A prominently affected cognitive domain is memory, for which the hippocampus is essential. Blood glucose levels can affect hippocampal microstructure and memory performance. IVIM metrics (diffusion coefficient (D) and perfusion fraction (f)) might be a good candidate as MRI biomarkers for memory decline in T2DM. This study showed that in the left hippocampus, a high D was associated with lower memory performance, and an association of f with increased blood glucose levels. This suggests that hippocampal microstructure is injured and a vascular component is involved which might underlie memory problems.

Nadya Pyatigorskaya^1,2, Michael Sharman², Jean-Christophe Corvol^2,3, Romain Valabregue^2,3, Fabrice Poupon⁴, Florence Cornier², Marie Vidailhet³, Alexis Brice², and Stephane Lehéricy^1,2
1Centre de NeuroImagerie de Recherche – CENIR, ICM; Service de Neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, ²Institut du Cerveau et de la Moelle épinière – ICM, Paris, France, ³CRICM, INSERM, UPMC Univ Paris 06, CNRS, CRICM, UMR_S975 and UMR 7225, Paris, France,⁴NeuroSpin, Commissariat à l’Energie Atomique (CEA), Gif-Sur-Yvette, France

Our goal was investigating iron deposition in the basal ganglia of patients with Leucine-rich repeat kinase 2 and Parkin-mutation associated Parkinson’s disease (PD). 19 affected and presymptomatic mutation-carrying subjects were compared with 20 idiopathic PD (IPD) and 20 healthy subjects. R2 and R2* values were calculated in the substantia nigra (SN), the basal ganglia and the thalamus. R2* values in SN were increased in IPD and mutation-carrying subjects as compared to controls and in mutation-carrying as compared to IPD patients. These results suggest that iron load, analyzed with R2* can be a biomarker of the nigrostriatal damage in mutation-carrying subjects.

Junseok Kim^1,2, Jackie Leung², Jason Lerch³, Suzan Williams⁴, and Andrea Kassner^1,2
1Medical Imaging, University of Toronto, Toronto, Ontario, Canada, ²Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada, ³MICe, Toronto Center for Phenogenomics, Toronto, Ontario, Canada, ⁴Haematology, The Hospital for Sick Children, Toronto, Ontario, Canada

Sickle cell disease (SCD) is a genetic disorder associated with severe cerebrovascular risks and may also disrupt neurological development. Cerebrovascular reactivity (CVR) can assess cerebrovascular health in SCD children. Studies have shown grey matter thinning in SCD children suggesting a connection to neurocogntive decline. We investigated whether CVR is associated with cortical thinning in children with SCD. CVR and grey matter thickness (from T1 anatomical) data were acquired in 42 SCD patients and 15 controls on a 3T MRI. We found a linear relation between the degree of cortical thinning and reduced CVR in multiple regions in the brain.