Holly Elizabeth Holmes¹, Nicholas Powell^1,2, Jack Wells¹, Niall Colgan¹, Ozama Ismail¹, James O'Callaghan¹, Da Ma^1,2, Michael J O'Neill³, Emily Catherine Collins⁴, Manuel Jorge Cardoso², Marc Modat², Elizabeth Fisher⁵, Sebastian Ourselin², and Mark F Lythgoe^6
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

Firat Kara^1,2, Steffen Roßner³, Annemie Van der Linden¹, Huub J.M. de Groot², and A. Alia^2,4
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.

Babak Ardekani^1,2, Sahar Elahi¹, Alvin Bachman¹, Sang Han Lee¹, and John Sidtis^1,2
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.

Kristof Govaerts¹, Janaki Raman Rangarajan², Tom Struys³, Fred Van Leuven⁴, Uwe Himmelreich¹, and Tom Dresselaers^1
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.

Ekaterina Tchistiakova^1,2 and Bradley J. MacIntosh^1,2
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.

Armin Eilaghi^1,2, D Adam McLean³, Cheryl R. McCreary^1,2, David Gobbi³, M Louis Lauzon^1,2, Marina Salluzzi³, Eric E Smith^1,2, and Richard Frayne^1,2
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.

Jiri M.G. van Bergen^1,2, Xu Li², Michael Wyss³, Simon J. Schreiner¹, Stefanie C. Steininger¹, Anton F. Gietl¹, Valerie Treyer^1,4, Sandra E. Leh¹, Fred Buck⁴, Jun Hua², Roger Nitsch¹, Klaas P. Pruessmann³, Peter C.M. van Zijl², Christoph Hock¹, and Paul G. Unschuld^1
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 A 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 A associated brain dysfunction in subjects at increased risk for late onset AD.

Zan Wang¹, Zhengjia Dai², Yongmei Shi¹, Hao Shu¹, Duan Liu¹, Yong He², and Zhijun Zhang^1
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 ¦Å4 genotype on intrinsic functional network centrality in patients with amnestic mild cognitive impairment.

Fulvia Palesi^1,2, Gloria Castellazzi^2,3, Elena Sinforiani⁴, Paolo Vitali^5,6, Claudia A. M. Wheeler-Kingshott⁷, and Egidio D'Angelo^2,6
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.

Andrew R. Hoy^1,2, Sterling C. Johnson^3,4, Ozioma C. Okonkwo^4,5, Cynthia M. Carlsson^3,4, Henrik Zetterberg⁶, Kaj Blennow⁷, Sanjay Asthana^3,4, Mark A. Sager^4,5, Andrew L. Alexander^1,8, and Barbara B. Bendlin^4,5
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.