Mona ElSheikh¹, Arvin Arani¹, Avital Perry², Nealey Cray², Fredric Meyer², David Lake¹, Armando Manduca³, Kevin Glaser¹, Richard L Ehman¹, and John Huston^1
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.

Andreas Fehlner¹, Lea M Gerischer², Agnes Flöel^2,3, Jürgen Braun⁴, and Ingolf Sack^1
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.

Kamal Saba¹, Niharika Rajnala¹, and Anant Bahadur Patel^1
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.

Anne Rijpma^1,2, Marinette van der Graaf^3,4, Olga Meulenbroek^1,2, Marcel Olde Rikkert^1,2, and Arend Heerschap^3
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. 

Leonardo A Rivera-Rivera¹, Tilman Schubert², Kevin M Johnson¹, Sterling C Johnson³, Oliver Wieben^1,2, and Patrick Turski^2
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.

Yuanxin Chen¹, Yong Wang^1,2, Kem A Rogers¹, John A Ronald¹, and Brian K Rutt^3
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.  

Xiuming Zhang¹, Elizabeth C. Mormino², Reisa A. Sperling², Mert R. Sabuncu^3,4, and B.T. Thomas Yeo^1,3,5
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.

fan su^1
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.

Jing Guo¹, Tonia Munder², Charlotte Klein², Anna Pfeffer², Jürgen Braun³, Barbara Steiner², and Ingolf Sack^1
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.

Rui Wang¹, Chunmei Li¹, Yongming Dai², Dantao Peng³, Xuna Zhao⁴, and Min Chen^1
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.