Mohammed Salman Shazeeb¹, Elizabeth Degrush^2,3, Zeynep Vardar¹, Clifford Lindsay¹, Matthew Gounis¹, and Nils Henninger^2,3
1Department of Radiology, University of Massachusetts Medical School, Worcester, MA, United States, ²Department of Neurology, University of Massachusetts Medical School, Worcester, MA, United States, ³Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States

Decreased cerebral metabolism has been implicated in pathogenesis of Alzehimer’s disease. The endothelial nitric oxide synthase (eNOS) pathway plays a major role in cerebral blood flow regulation. This study used DSC-MRI in 10 patients treated with a drug regimen for supporting the eNOS pathway to investigate how perfusion patterns were associated with treatment response based on clinical psychometrics. Regional analysis on rCBF maps showed significant signal changes in the cognitively improved cohort based on ADAS-cog scores while patients that showed cognitive deterioration or no change based on ADAS-cog scores did not show significant rCBF changes.

Ana-Maria Oros-Peusquens*¹, Jonas Kielmann*¹, and N. Jon Shah^1,2,3,4
1INM-4, Research Centre Juelich, Juelich, Germany, ²Faculty of Medicine, JARA, RWTH Aachen University, Aachen, Germany, ³INM-11, JARA, Research Centre Juelich, Juelich, Germany, ⁴Department of Neurology, RWTH Aachen University, Aachen, Germany

Quantitative MRI parameters are determined by the properties of tissue on a microscopic scale and can be expected to reflect microstructural changes created by aging. Here, we investigate a multiparametric qMRI signature of healthy ageing on 26 healthy volunteers, characterised in a high-dimensional parametric space (water content, relaxometry, qMT). Changes with age in the mean values and correlations between parameters are observed and interpreted.

Qian Chen¹, Jiaming Lu², Xin Zhang², Jilei Zhang³, and Bing Zhang^1
1Department of Radiology, Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China, ²Department of Radiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China, ³Philips Healthcare, Shanghai, China

Subjective cognitive decline (SCD) is considered a clinically-based approach for the detection of potential Alzheimer’s disease patients. We observed altered temporal properties of fractional windows, mean dwell time, and the number of transitions by dynamic functional connectivity (DFC) analysis in SCD individuals compared to the control subjects. The altered DFC parameters showed significant associations with cognitive performance. Our findings shed light on the role of DFC in the early detection of subjects with potential Alzheimer’s disease, and the alterations in DFC may suggest the neural basis underlying early cognitive decline in the SCD stage. 

Yu Veronica Sui¹ and Mariana Lazar^1
1Radiology, New York University Grossman School of Medicine, New York, NY, United States

Demyelination is recognized as a major process in both normal aging and neurodegenerative diseases. Using the Human Connectome Project Aging dataset, we investigated intracortical demyelination in normal aging using T₁w/T₂w maps. To capture the fine changes across cortical layers, we employed a surface-based approach in contrast to the commonly used volumetric approach by constructing a cortical myelin profile for each region, which was then quantified using a nonlinearity index. We showed that the nonlinearity of cortical myelin profile exhibits a steeper decline with aging than cortical thickness and therefore presents the potential of a unique marker of age-related microstructural changes.

Mohammad S. E. Sendi¹, Robyn L Miller², Elizabeth Mormino³, David H Salat⁴, and Vince D Calhoun^5
1Georgia Institute of Technology/Emory University, ATLANTA, GA, United States, ²Georgia State University, Atlanta, GA, United States, ³Stanford University, Stanford,, GA, United States, ⁴Harvard University, Cambridge, MA, United States, ⁵Georgia Institute of Technology, Atlanta, GA, United States

Finding a biomarker predicting the Alzheimer’s disease (AD) progression from a healthy stage to mild dementia is an essential step toward early medical intervention. In recent years, dynamic functional network connectivity (dFNC) from resting state-fMRI, which estimates brain states during the scan, uncovered excellent knowledge about AD progression's underlying mechanism. This study explored whether the AD brain produces similar and stable dFNC states across different scanning sessions and introduced dFNC state (or brain) instability as a potential biomarker of AD progression. Our finding suggests a need for multiple sessions scanning in analyzing rs-fMRI data in this group of patients.

Nazanin Makkinejad¹, Ashish A. Tamhane², David A. Bennett², Julie A. Schneider², Boris Gutman¹, and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Age-related neuropathologies have devastating effects on subcortical brain structures. MRI can be used to explore patterns of atrophy associated with various diseases, however, definitive diagnosis of age-related neuropathologies is only possible at autopsy. Therefore, this work combined ex-vivo MRI and detailed pathologic assessment (gold standard) in a large (N=814) community cohort of older adults to investigate the link between age-related neuropathologies and the shape of different subcortical brain structures. The resulting patterns of deformation may contribute towards development or enhancement of in-vivo classifiers of these neuropathologies.

Grant S Roberts¹, Leonardo A Rivera-Rivera², Kevin M Johnson^1,3, Sterling C Johnson², Douglas C Dean III^1,4, Andrew L Alexander^1,5, Oliver Wieben¹, and Laura B Eisenmenger^3
1Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, ²Medicine, University of Wisconsin - Madison, Madison, WI, United States, ³Radiology, University of Wisconsin - Madison, Madison, WI, United States, ⁴Pediatrics, University of Wisconsin - Madison, Madison, WI, United States, ⁵Psychiatry, University of Wisconsin - Madison, Madison, WI, United States

White matter (WM) microstructural alterations have been shown to occur in Alzheimer’s disease (AD) and may be partially mediated by cerebrovascular disease (CVD). The objective of this study is to use neurite orientation dispersion and density imaging (NODDI) to assess differences in neurite density (NDI) and its relationship to measures of CVD from 4D flow MRI in cognitively normal (CN) and AD subjects. Our results showed differences in NDI between groups in various WM tracts and found correlations between NDI and cerebral blood flow in CN subjects in several WM structures.

Matthew Christopher Murphy¹, Petrice M Cogswell¹, Joshua D Trzasko¹, Armando Manduca², Matthew L Senjem¹, Clifford R Jack, Jr.¹, Fredric B Meyer³, Richard L Ehman¹, and John Huston, III^1
1Radiology, Mayo Clinic, Rochester, MN, United States, ²Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States, ³Neurosurgery, Mayo Clinic, Rochester, MN, United States

A non-parametric statistical framework is outlined to display the result of brain MRE exams in terms of an effect size. This approach is built upon a neural network-based MRE inversion that estimates the posterior cumulative distribution function at each voxel, and accounts for age, sex, spatial variation in stiffness, and uncertainty in property estimation. Using these effect size maps but no summary statistics, neuoradiologists were able to diagnose normal pressure hydrocephalus with 70% sensitivity and 100% positive predictive value.

Mahir Tazwar¹, Arnold M Evia Jr.², Ashish A Tamhane², David A Bennett², Julie A Schneider², and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is now recognized as a common age-related neuropathology that has been linked to cognitive decline and dementia. In this work, the spatial pattern of R₂ alterations associated with LATE-NC was investigated in a large (N=797) community cohort of older adults. Voxel-wise analysis revealed a pattern of lower R₂ for greater LATE-NC burden, controlling for all other neuropathologies and demographics. This pattern involved mainly the temporal, frontal, occipital lobes and basal ganglia. To our knowledge this is the first R₂ investigation in LATE-NC.

Jason Langley¹, Daniel E Huddleston², Sumanth Dara³, Ilana Bennett⁴, and Xiaoping P Hu^1,3
1Center for Advanced Neuroimaging, University of California Riverside, Riverside, CA, United States, ²Department of Neurology, Emory University, Atlanta, GA, United States, ³Department of Bioengineering, University of California Riverside, Riverside, CA, United States, ⁴Department of Psychology, University of California Riverside, Riverside, CA, United States

We examine the impact of APOE-ε4 carrier status on cortical iron, gray matter microstructure, and tau-PET signal in mild cognitive impairment. We found significant increases in susceptibility (p=0.01), tau-PET SUVR (p=0.01), and MD (p=0.046) in the temporal lobe of APOE-ε4 positive compared to APOE-ε4 negative participants. Significant correlations were seen between tau-PET SUVR and susceptibility (r=0.717), FA (r=-0.431), and MD (r=0.435) in the temporal lobe of APOE-ε4 positive participants. Taken together, these findings suggest that APOE-ε4 allele increases the risk of developing AD pathology and accumulating iron, which in turn leads to degradation of cortical tissue microstructure.