ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Scientific Session • Alzheimer's Disease

Tuesday 2 June 2015

Constitution Hall 107

13:30 - 15:30


Masaaki Hori, M.D., Ph.D., T.B.A.

13:30 0394.   
Comparing in vivo and ex vivo imaging in an Alzheimer’s mouse model using tensor-based morphometry
Holly Elizabeth Holmes1, Nicholas Powell1,2, Jack Wells1, Niall Colgan1, Ozama Ismail1, James O'Callaghan1, Da Ma1,2, Michael J O'Neill3, Emily Catherine Collins4, Manuel Jorge Cardoso2, Marc Modat2, Elizabeth Fisher5, Sebastian Ourselin2, and Mark F Lythgoe6
1Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom, 2Centre for Medical Image Computing, University College London, London, Greater London, United Kingdom, 3Eli Lilly & Co. Ltd, Windlesham, Surrey, United Kingdom, 4Eli Lilly & Company, Indianapolis, United States, 5Department of Neurodegenerative Diseases, University College London, London, Greater London, United Kingdom, 6University College London, London, Greater London, United Kingdom

The tradeoffs when imaging mouse models of neurodegenerative disease using in vivo and ex vivo MRI have been explored using the rTg4510 mouse model of Alzheimer's disease

13:42 0395.   
Probing in vivo T2 relaxation time alterations in the corpus callosum of a mouse model of Alzheimer’s disease
Firat Kara1,2, Steffen Roßner3, Annemie Van der Linden1, Huub J.M. de Groot2, and A. Alia2,4
1Bioimaging Lab, University of Antwerp, Antwerp, Belgium, 2Leiden Institute of Chemistry, Gorlaeus Laboratoria, Leiden University, Leiden, Netherlands, 3Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany, 4Institute of Medical Physics and Biophysics, Leipzig University, Leipzig, Germany

The transverse relaxation time (T2) measurements are sensitive to explore subtle microstructural changes in the corpus callosum. There is an emergent need for new in vivo non-invasive studies to monitor corpus callosum (CC) changes longitudinally in order to clarify how and when the integrity of CC alters in Alzheimer’s disease (AD). In this study we probed in vivo T2 changes longitudinally in the CC of a mouse model of AD with age and investigated potential biological mechanisms, such as demyelination, Aβ deposition and gliosis, contributing alterations in the biophysical environment of the CC.

13:54 0396.   Corpus Callosum Atrophy Rate in Mild Cognitive Impairment and Prodromal Alzheimer’s Disease
Babak Ardekani1,2, Sahar Elahi1, Alvin Bachman1, Sang Han Lee1, and John Sidtis1,2
1The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States, 2Department of Psychiatry, New York University School of Medicine, New York, NY, United States

We examined temporal rates of change in CC morphology in MCI patients to determine the differences between converters to AD and non-converters. The spatial and temporal patterns of CC morphological change in MCI-NC are similar to healthy controls, while those in MCI-C are similar to very mild/mild AD. CC atrophy is quantifiable in a one-year longitudinal observation period, making this a practical imaging biomarker. Amongst the measures considered, circularity proved to be the most sensitive measure separating convertors from non-convertors regardless of their gender.

14:06 0397.   
Increased cortical volume revealed by atlas-based volumetry in a bigenic mouse model of Alzheimer's Disease
Kristof Govaerts1, Janaki Raman Rangarajan2, Tom Struys3, Fred Van Leuven4, Uwe Himmelreich1, and Tom Dresselaers1
1Imaging & Pathology, KU Leuven, Leuven, Vlaams-Brabant, Belgium, 2Electrical Engineering, KU Leuven, Leuven, Vlaams-Brabant, Belgium, 3Morphology, Universiteit Hasselt, Hasselt, Limburg, Belgium, 4Human Genetics, KU Leuven, Leuven, Vlaams-Brabant, Belgium

Although atrophy is a well-established biomarker for Alzheimer’s Disease (AD) in human patients, MRI-based studies on this subject in mice are scarce. Here, we made use of an atlas-based registration protocol, and we show that the bigenic biAT mouse model displays increased rather than decreased cortical volume, both at 3 and at 12 months of age. Differences were small but highly significant. Histological assessment also showed decreased neuronal density in the frontal cortex.

14:18 0398.   Cortical volume and perfusion are influenced by vascular risk factors in addition to cognitive status: new insight made available from the ADNI study
Ekaterina Tchistiakova1,2 and Bradley J. MacIntosh1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, 2Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, ON, Canada

Recent studies demonstrated that vascular risk factors (VRFs) increase the risk of AD. Little, however, is known on the interaction of AD progression and VRF burden and their impact on brain health. In this study we used a multivariate approach to examine the impact of VRFs on the cortical volume in normal controls and MCI groups. Our results indicate that cortical volume variability is predominantly driven by MCI individuals with high VRF burden. Our secondary analysis showed no association between cortical volumes and cerebral blood flow in those groups, but it was apparent in MCI individuals with low VRF burden.

14:30 0399.   Brain Magnetic Susceptibility is Increased with Cognitive Impairment in a Community Population
Armin Eilaghi1,2, D Adam McLean3, Cheryl R. McCreary1,2, David Gobbi3, M Louis Lauzon1,2, Marina Salluzzi3, Eric E Smith1,2, and Richard Frayne1,2
1Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, 2Seaman Family MR Centre, Foothills Medical Centre, Calgary, Alberta, Canada, 3Calgary Image Processing and Analysis Centre, Foothills Medical Centre, Calgary, Alberta, Canada

We demonstrated that susceptibility obtained with QSM was significantly higher in the cognitively impaired group than the normal group, after controlling for age in a cohort of volunteers drawn from the community. This proof-of-concept study underscores the potential value of susceptibility to distinguish cognition decline at the early, pre-symptomatic phase.

14:42 0400.   Regional cerebral iron concentrations as indicated by magnetic susceptibilities measured with Quantitative Susceptibility Mapping (QSM) at 7 Tesla correlate with brain Aβ plaque density as measured by 11-C-Pittsburgh Compound B Positron-Emission-Tomography (PiB-PET) in elderly subjects at risk for Alzheimer’s disease (AD)
Jiri M.G. van Bergen1,2, Xu Li2, Michael Wyss3, Simon J. Schreiner1, Stefanie C. Steininger1, Anton F. Gietl1, Valerie Treyer1,4, Sandra E. Leh1, Fred Buck4, Jun Hua2, Roger Nitsch1, Klaas P. Pruessmann3, Peter C.M. van Zijl2, Christoph Hock1, and Paul G. Unschuld1
1Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Zurich, Switzerland, 2F.M. Kirby center for Functional Brain Imaging, Kennedy Krieger Institute and Johns Hopkins School of Medicine, Baltimore, Maryland, United States, 3Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland, 4Division of Nuclear Medicine, University of Zurich, Zurich, Switzerland

In subjects with Mild Cognitive Impairment it was shown that susceptibility values as measured by Quantitative Susceptibility Mapping (QSM) correlate with Alower case Greek beta plaque density as measured by 11-C-Pittsburgh Compound B Positron-Emission-Tomography (PiB-PET). Susceptibility in gray matter has been shown to relate to tissue iron content. Correlations were observed in the frontal, parietal, temporal and occipital cortices and the caudate nucleus. The correlation was driven by carriers of the Apolipoprotein E gene, an Alzheimer’s Disease (AD) associated risk factor. Our results suggest that cerebral iron accumulation may reflect Alower case Greek beta associated brain dysfunction in subjects at increased risk for late onset AD.

14:54 0401.   Mapping the effect of APOE lower case Greek epsilon4 genotype on intrinsic functional network centrality in patients with amnestic mild cognitive impairment - permission withheld
Zan Wang1, Zhengjia Dai2, Yongmei Shi1, Hao Shu1, Duan Liu1, Yong He2, and Zhijun Zhang1
1Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, Jiangsu, China, 2State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

Mapping the effect of APOE ¦Ĺ4 genotype on intrinsic functional network centrality in patients with amnestic mild cognitive impairment.

15:06 0402.   Combined functional and tractography connectome to investigate Alzheimer brain networks
Fulvia Palesi1,2, Gloria Castellazzi2,3, Elena Sinforiani4, Paolo Vitali5,6, Claudia A. M. Wheeler-Kingshott7, and Egidio D'Angelo2,6
1Department of Physics, University of Pavia, Pavia, PV, Italy, 2Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, PV, Italy,3Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, PV, Italy, 4Neurology Unit, C. Mondino National Neurological Institute, Pavia, PV, Italy, 5Brain MRI 3T Mondino Research Center, C. Mondino National Neurological Institute, Pavia, PV, Italy, 6Department of Brain and Behavioral Sciences, University of Pavia, Pavia, PV, Italy, 7NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre​, UCL Institute of Neurology, London, England, United Kingdom

Several resting-state fMRI studies have revealed a generalized alteration of the resting state networks (RSNs) in patients affected by Alzheimer’s disease but few studies have focused on the interaction between functional and structural global connectivity. We developed a small-world approach combining RSNs (nodes) and probabilistic tractography (edges) to investigate structural alterations inside those networks that were functionally impaired by the pathology. Our findings suggest that mean diffusivity is the best marker for graph-theory calculations and that it is essential to assess both functional and structural connectivity of RSNs to understand different stages of brain pathology and their evolution.

15:18 0403.   Free water elimination DTI in preclinical Alzheimer's: evidence for early axonal degeneration
Andrew R. Hoy1,2, Sterling C. Johnson3,4, Ozioma C. Okonkwo4,5, Cynthia M. Carlsson3,4, Henrik Zetterberg6, Kaj Blennow7, Sanjay Asthana3,4, Mark A. Sager4,5, Andrew L. Alexander1,8, and Barbara B. Bendlin4,5
1Medical Physics, University of Wisconsin, Madison, Wisconsin, United States, 2Medical Service Corp, United States Navy, Falls Church, Virginia, United States,3Geriatric Research, Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, United States, 4Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, United States, 5Wisconsin Alzheimer's Institute, University of Wisconsin, Madison, Wisconsin, United States, 6Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenberg, Gothenberg, Sweden, 7Department of Clinical Neuroscience, University of Gothenberg, Gothenberg, Sweden, 8Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, Wisconsin, United States

This study is the first to investigate the association between CSF markers and white matter microstructure in an asymptomatic population using the FWE-DTI model. A targeted tractography method and voxel based analysis was used to demonstrate a relation between pTau181 and NFL and the FWE isotropic volume fraction. Given that tau and NFL are components of the axonal cytoskeleton our results suggest that f-value may be sensitive to early axonal degeneration. Our results suggest that diffusion imaging with FWE may hold promise for early disease detection, in addition to providing a novel outcome measure for prevention and treatment trials.