ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Dementia: Alzheimer's Disease

Monday, May 9, 2016
Hall 606
14:15 - 16:15
Moderators: Ellen Ackerstaff, Ganesh Adluru

MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias
Mona ElSheikh1, Arvin Arani1, Avital Perry2, Nealey Cray2, Fredric Meyer2, David Lake1, Armando Manduca3, Kevin Glaser1, Richard L Ehman1, and John Huston1
1Radiology, Mayo Clinic, Rochester, MN, United States, 2Neurosurgery, Mayo Clinic, Rochester, MN, United States, 3Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States

The development of advanced MRI techniques has enabled noninvasive evaluation of subtle changes of brain architecture in dementia. We report a specific pattern of regional brain stiffness changes using Magnetic Resonance Elastography (MRE) in three different dementia groups: Alzheimer’s disease, frontotemporal dementia, and normal pressure hydrocephalus. MRE offers a potential biomarker to characterize the viscoelastic properties of the brain in dementia patients, and may have a role in the diagnosis and differentiation between common subtypes of dementia.

High resolution MR elastography of the hippocampus reveals differential tissue elasticity in Alzheimer's disease – a pilot study
Andreas Fehlner1, Lea M Gerischer2, Agnes Flöel2,3, Jürgen Braun4, and Ingolf Sack1
1Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 2Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 3NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany, 4Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany
Multifrequency MR elastography (MMRE) was applied to 14 patients with Alzheimer's disease (AD) and compared to 14 age matched asymptomatic controls. We observed a marked decrease of the white-matter complex shear modulus |G*| in patients with AD. This reduction in |G*| was even more pronounced in the hippocampal region. In this region a diagnostic performance of 78% sensitivity and 92% specificity (AUROC-value 0.918) was obtained based on a viscoelasticity cutoff value of 0.9 kPa. In the future MMRE-measured |G*| could serve as a quantitative imaging marker for early diagnosis and progression monitoring of AD.

1H-[13C]-NMR Investigation of Neuroprotective Action of Ayurvedic Formulation in AßPP-PS1 Mouse Model of Alzheimer’s Disease
Kamal Saba1, Niharika Rajnala1, and Anant Bahadur Patel1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Currently no definite treatment available for AD. We have examined the efficacy of Rasa Sindoor, an Ayurvedic formulation, for the improvement of memory and neuronal activity in AβPP-PS1 mouse model of AD. Neuronal metabolism was followed by 1H-[13C]-NMR spectroscopy together with an infusion of [1,6-13C2]glucose. Our results indicate that the Rasa-Sindoor improved memory, and excitatory and inhibitory neuronal metabolic activity in AD mice.

Brain phospholipid and energy metabolism in mild Alzheimer’s disease and healthy aging: a 31P Magnetic Resonance Spectroscopy study - Permission Withheld
Anne Rijpma1,2, Marinette van der Graaf3,4, Olga Meulenbroek1,2, Marcel Olde Rikkert1,2, and Arend Heerschap3
1Geriatric Medicine, Radboud university medical center, Nijmegen, Netherlands, 2Radboud Alzheimer Centre, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, Netherlands, 3Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, Netherlands, 4Paediatrics, Radboud university medical center, Nijmegen, Netherlands
In this study we assessed phospholipid and energy metabolism in patients with mild Alzheimer’s disease and healthy age-matched control subjects by 3D 31P MRS imaging. Four brain regions were investigated: left and right hippocampus, anterior cingulate cortex, and retrosplenial cortex. Disease specific differences as well as differences between brain regions were found. 

4D Flow MRI for assessing flow pulsatility along the carotid siphon in Alzheimer’s disease
Leonardo A Rivera-Rivera1, Tilman Schubert2, Kevin M Johnson1, Sterling C Johnson3, Oliver Wieben1,2, and Patrick Turski2
1Medical Physics, University of Wisconsin Madison, Madison, WI, United States, 2Radiology, University of Wisconsin Madison, Madison, WI, United States, 3Medicine, University of Wisconsin Madison, Madison, WI, United States
Cerebral arteries are often morphologically altered and dysfunctional in Alzheimer’s disease (AD). In this study, 4D flow MRI was used to assess flow pulsatility along the carotid siphon in patients with AD, mild cognitive impairment (MCI) and in healthy age matched controls. We found the physiologic dampening of pulsatility along the distal ICA is significantly diminished in patients with AD. With the large volume coverage and high temporal and spatial resolution, 4D flow MRI can provide additional biomarkers of vascular health that can contribute to the identifying patients who could benefit from interventions to improve circulatory system functions.

In Vivo Visualization of Iron-Rich Amyloid Plaques In Cholesterol-Fed Rabbits using Clinical Field-Strength Magnetic Resonance Imaging
Yuanxin Chen1, Yong Wang1,2, Kem A Rogers1, John A Ronald1, and Brian K Rutt3
1Western University, London, ON, Canada, 2Lawson Health Research Institute, London, ON, Canada, 3Stanford University, Stanford, CA, United States
Hypercholesterolemia is a risk factor for AD and promotes increased production of beta-amyloid protein. Our lab has developed a rabbit model of AD by enriching the diets of rabbits with low amounts of cholesterol. In this study, we combined this cholesterol-fed rabbit model of AD with iron-sensitive, high-resolution MRI and demonstrated non-invasive in vivo visualization of AD plaques throughout the brains of these animals. The imaging techniques have been developed and optimized using a clinical field strength scanner (3T), which is an important step towards clinical application in human AD patients.  

Latent Atrophy Factors in Alzheimer's Disease
Xiuming Zhang1, Elizabeth C. Mormino2, Reisa A. Sperling2, Mert R. Sabuncu3,4, and B.T. Thomas Yeo1,3,5
1ASTAR-NUS Clinical Imaging Research Centre, Department of Electrical and Computer Engineering, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore, Singapore, 2Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, 3Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, 4Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, United States, 5Centre for Cognitive Neuroscience, Duke-NUS Graduate Medical School, Singapore, Singapore
Alzheimer's disease (AD) is the most common form of dementia and greatly heterogeneous. Here we develop a model of the heterogeneity of AD-related atrophy, demonstrating that most AD dementia patients and at-risk nondemented participants express multiple latent atrophy factors to varying degrees. Our study also demonstrates that these atrophy factors are associated with distinct cognitive decline trajectories across the preclinical and clinical stages. Our results provide a framework by which biomarker readouts could potentially predict disease progression at the individual level. Our analytic strategy is general and might be utilized to discover subtypes within and across other heterogeneous brain disorders.

Association of Alzheimer’s disease GWAS loci with default mode network
fan su1
1southeast university, nanjing, China, People's Republic of
To investigate the altered pattern of DMN in amnestic mild cognitive impairment (aMCI) subjects and the genetic factors that lead to the DMN dysfunctions, 87 individuals with aMCI and 131 matched healthy controls were recruited and an average 3-year follow-up study was performed. We studied the differences of DMN between aMCI subjects and healthy controls at baseline and how the DMN changed over time. Regression analyses were performed to explore whether the GRS influence the DMN dysfunctions. We observed that DMN disengage in the early stage of AD and the combined effect of AD-related loci influence the DMN pattern.

The effect of Alzheimer's disease on the viscoelasticity of the mouse brain under the influence of enriched environment. - Permission Withheld
Jing Guo1, Tonia Munder2, Charlotte Klein2, Anna Pfeffer2, Jürgen Braun3, Barbara Steiner2, and Ingolf Sack1
1Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany, 2Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany, 3Institute of Medical Informatics, Charité - University Medicine Berlin, Berlin, Germany
MRE was used to study environmental influences on viscoelasticity of the murine hippocampus in Alzheimer's disease (AD). In wild type control mice, hippocampal viscosity was significantly increased within 6 months while elasticity remained unchanged. This suggests that environment-stimulated neuronal proliferation adds mobile elements to the mechanical matrix of the brain which increases mechanical attenuation properties. Within 6 months, AD caused a decline of hippocampal viscosity only in the enriched environment while standard mouse remained unaffected suggesting that AD in an early phase primarily affects new neurons in the murine hippocampus.

A preliminary study on MR amide proton imaging in patients with Alzheimer’s disease and mild cognitive impairment - Video Not Available
Rui Wang1, Chunmei Li1, Yongming Dai2, Dantao Peng3, Xuna Zhao4, and Min Chen1
1Radiology, Beijing Hospital, Beijing, China, People's Republic of, 2Philips Heathcare, Shanghai, China, People's Republic of, 3China-Japan Friendship Hospital, Beijing, China, People's Republic of, 4Philips Heathcare, Beijing, China, People's Republic of
The aim of this study is to evaluate the feasibility of MR amide proton transfer (APT) imaging for the detection of cerebral abnormalities in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI), and to explore its clinical utility. Twenty-one AD patients, 11 aMCI patients and 19 normal controls (NC) underwent APT MR imaging. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5ppm of bilateral hippocampi, temporal white matter regions, occipital white matter regions and cerebral peduncles were measured on the oblique APT images. We found that MTRasym(3.5ppm)asym in bilateral hippocampi showed a consistently increasing trend from NC to MCI, to AD. MTRasym(3.5ppm) values of bilateral hippocampi were significantly negatively correlated with MMSE. Our results suggested that APT imaging is a useful tool to diagnose early AD and monitor the disease.

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