Yujian Diao¹, Catarina Tristão Pereira², Carole Poitry-Yamate¹, Ting Yin¹, Analina Raquel da Silva¹, Rolf Gruetter¹, and Ileana Ozana Jelescu^1
1Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal

Impaired brain glucose consumption is a possible trigger of Alzheimer’s disease (AD). Animal models can help characterize each contributor to the cascade independently. Here we report a comprehensive longitudinal study of functional connectivity, white matter microstructure and brain glucose metabolism using resting-state fMRI, diffusion MRI and FDG-PET in the intracerebroventricular-streptozotocin rat model of AD. Our study highlights the dynamics of how brain insulin resistance affects brain structure and function, and identifies potent MRI-derived biomarkers to track neurodegeneration in human AD and diabetic populations. 

Jianpan Huang¹, Xiongqi Han¹, Celia M. Dong², Gerald W. Y. Cheng³, Kai-Hei Tse³, Lin Chen^4,5, Joseph H. C. Lai¹, Ed X. Wu², Peter C. M. van Zijl^4,5, Jiadi Xu^4,5, and Kannie W. Y. Chan^1,4
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China, ³Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China, ⁴Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

On-resonance variable delay multiple pulse (onVDMP) CEST MRI was applied to detect dynamic D-glucose enhanced signal in brain parenchyma and CSF of 6- and 16-month old APP/PS1 AD mice. A significantly slower D-glucose clearance from CSF was observed in young AD mice compared to age-matched wild type (WT) mice. Moreover, a reduced D-glucose uptake was observed both in parenchyma and CSF of old APP/PS1 mice. D-glucose kinetics detected by onVDMP can be used to assess the alterations in D-glucose uptake and clearance in AD and in the course of AD progression at 3T, a clinical relevant MRI field.

Jason F. Moody¹, Douglas C. Dean III^1,2,3, Steven R. Kecskemeti³, Jennifer M. Oh⁴, Nagesh Adluru³, Sterling C. Johnson^4,5, Barbara B. Bendlin⁴, and Andrew L. Alexander^1,2,3,6
1Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States, ³Waisman Center, University of Wisconsin-Madison, Madison, WI, United States, ⁴Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin-Madison, Madison, WI, United States, ⁵Geriatric Research Education and Clinical Center, Middleton Memorial VA Hospital, University of Wisconsin-Madison, Madison, WI, United States, ⁶Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, United States

We implement Laplacian-regularized MAP MRI to investigate distinct white matter (WM) microstructural changes associated with mild cognitive impairment (MCI).

Comparisons of diffusion parameters (via TBSS) between healthy controls and MCI patients revealed significant group differences in a wide variety of WM pathways previously shown to be altered in MCI and Alzheimer’s Dementia (AD). In particular, the MCI group exhibited WM clusters with lower return to origin probability (RTOP) and return to plane probability (RTPP) magnitudes, suggesting structurally affected axons in those tracts.

Our findings provide an early quantitative framework for identifying specific WM microstructural deficiencies characteristic of MCI and AD.

Leonardo A Rivera-Rivera¹, Laura B Eisenmenger², Sterling C Johnson³, and Kevin M Johnson^1,2
1Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, ²Department of Radiology, University of Wisconsin - Madison, Madison, WI, United States, ³Department of Medicine, University of Wisconsin - Madison, Madison, WI, United States

Microvascular oscillations have been speculated to be markers of autoregulation and to be driving forces of glymphatic clearance of interstitial fluid, Aβ, and other soluble metabolites of the brain. To probe spontaneous low frequency oscillations (LFO) in the brain vasculature, measures of blood flow variance during several minutes might hold potential. In this study, we investigated induced LFOs in blood flow with 4D flow using 3D radial sampling and low-rank regularization for real time blood flow variance estimates. Preliminary results showed significant increased blood flow fluctuations in age-matched controls compared to AD subjects. 

Jialin Hu¹, Miao Zhang², Rong Guo^3,4, Yudu Li^3,4, Wanqing Sun¹, Danni Wang¹, Hui Huang¹, Yibo Zhao^3,4, Ziyu Meng^1,3, Biao Li², Jun Liu⁵, Binyin Li⁵, Jie Luo¹, Zhi-Pei Liang^3,4, and Yao Li^1
1Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁵Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

As a progressive neurodegenerative disease, early diagnosis of Alzheimer’s disease (AD) is important but remains difficult. MRSI is a useful tool for detecting neurometabolic alterations in AD, but most studies were limited by using single-slice or single-voxel techniques with low spatial resolution and long data acquisition time. In this study, we performed 3D MRSI of AD patients at a nominal spatial resolution of 2.0 × 3.0 × 3.0 mm³ in a 7-min scan using a new technique called SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation). Our experimental results showed noticeable neurometabolic changes in AD patients.  

Shuyue Wang¹, Kaicheng Li¹, Xiao Luo¹, Qingze Zeng¹, Yeerfan Jiaerken¹, Xiaopei Xu¹, Yong Zhang², Peiyu Huang¹, and Minming Zhang^1
1The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China, ²GE Healthcare, Shanghai, China

Along with Alzheimer’s disease (AD) continuum, AD neuropathologies propagate trans-neuronally, causing the memory circuit disorganization. The ‘misfolded tau protein propagation theory’ indicates that tau pathology spread through synaptic connectivity and cause the structural impairments. Here, we hypothesized that HP is the first to suffer from AD neuropathology, then followed by the connected tract and downstream cortex. We defined the memory circuit as the hippocampus (HP), cingulum-angular bundles (CAB), and precuneus cortex, respectively representing the starting point, core connecting fibre and connected downstream cortex. Our results support the tau propagation theory in the memory circuit in vivo.

Chun Ki Franklin Au¹, Jill Abrigo¹, Jack Lee², Chunlei Liu³, Wing Chi Lisa Au⁴, Queenie Chan⁵, Qianyun Maxine Chen¹, Chung Tong Vincent Mok⁴, and Weitian Chen^1
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, ²Centre For Clinical Research And Biostatistics, Centre for Clinical Research and Biostatistics, The Chinese University of Hong Kong, Hong Kong, Hong Kong, ³Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, USA, CA, United States, ⁴Division of Neurology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, ⁵Philips, Hong Kong, Hong Kong

Iron accumulation has been reported in specific brain regions of Alzheimer disease patients. In this study, we used Quantitative Susceptibility Mapping to show iron deposition in hippocampal fimbria and its strong correlation with hippocampus volume and AD stages. Our result might provide further insight of potential disconnection injury in AD pathophysiology.

Sandeepa Sur¹, Zixuan Lin¹, Yang Li¹, Sevil Yasar², Paul Rosenberg³, Abhay Moghekar⁴, Shruti Agarwal¹, Xirui Hou¹, Rita Kalyani⁵, Kaisha Hazel¹, George Pottanat¹, Cuimei Xu¹, Peter van Zijl⁶, Jay Pillai⁷, Peiying Liu¹, Marilyn Albert⁴, and Hanzhang Lu^1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Department of Gerontology, Johns Hopkins University, Baltimore, MD, United States, ³Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, baltimore, MD, United States, ⁴Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Medicine, Johns Hopkins University, Baltimore, MD, United States, ⁶F.M. Kirby Research Center, Kennedy Krieger Institute, baltimore, MD, United States, ⁷Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, United States

This study addresses the question, whether quantitative cerebrovascular reactivity (CVR) is a potential vascular biomarker in dementia with Alzheimer’s and vascular pathologies. This was tested in a cross-sectional study, where CBF-CVR assessed via Phase-Contrast-MRI during a CO₂ breathing-challenge predicted cognitive and functional performance, disease-severity, and diabetes-risk, in 67 normal and mild-cognitive-impairment subjects. The performance and severity relationships remained robust after adjusting for Alzheimer’s disease and competing vascular markers. These findings suggest that quantitative CBF-CVR has potential as a sensitive biomarker for early changes in cognitive and functional performance, and of disease severity in dementia, independent of Alzheimer’s disease.

 

Feng Vankee Lin^1
1Center for Advanced Imaging and Neurophysiology, University of Rochester, ROCHESTER, NY, United States

The current lack of effective pharmacological treatments for managing clinical symptoms in Alzheimer’s dementia highlights the urgent need for developing non-pharmacological interventions in the field. Here we report a phase II randomized controlled trial that examined the immediate and mid-term effect of a cognitive process based training on multiple cognitive domains in mild cognitive impairment. We found robust intervention effect on processing speed/attention and working memory. These cognitive improvements were associated with both activation changes and network changes involving ACC, a hub for maintaining successful cognitive aging. These results provide new insights about non-pharmacological interventions in preventing dementia.

Zhengshi Yang¹, Karthik Sreenivasan¹, Xiaowei Zhuang¹, Aaron Ritter¹, Jessica Caldwell¹, Sarah J Banks², Virendra Mishra¹, Marwan Sabbagh¹, Dietmar Cordes^1,3, and Jeffrey Cummings^1,4
1Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States, ²Department of Neuroscience, University of California, San Diego, CA, United States, ³Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, United States, ⁴Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, NV, United States

Inflammatory reactions contribute to disease progression and severity of Alzheimer’s disease (AD). While multiple animal studies have suggested that increased neuroinflammation occurs in AD, few studies have investigated neuroinflammation in human subjects. This is the first study using the third-generation TSPO ligand [18F]-GE180 to evaluate the neuroinflammation in AD on human subjects. Our study suggests that neuroinflammation accumulates together with amyloid deposition and reaches a plateau when the regional amyloid SUVR reaches 1.1 threshold. Compared to amyloid pathology, neuroinflammation is more closely related to hyperconnectivity in MCI/AD subjects.