Interview with Nien-Chu Shih and Farshid Sepehrband

2023 NeuroImage: Clinical Editor’s Choice Award

Author: Yohan Yee
Editor: Elizabeth DuPre

Wrapping up the Editor’s Choice Award interviews in our 2023 OHBM award winner interview series is Nien-Chu Shih, who received the 2023 NeuroImage: Clinical Editor’s Choice Award. Nien-Chu is recognized for her publication titled Microstructural mapping of dentate gyrus pathology in Alzheimer’s disease: A 16.4 Tesla MRI study, which correlates quantitative MRI measurements with histological markers of Alzheimer’s disease pathology across layers of the dentate gyrus. 

Nien-Chi Shih

[ You can read our interviews with the other Editor’s Choice Award winners with Lanxin Ji (Human Brain Mapping); Laura V. Cuaya (NeuroImage); Eduarda Gervini Zampieri Centeno (Brain Structure and Function) on the OHBM Blog. ]

Farshid Sepehrband

Nien-Chu is a researcher at the Laboratory of Neuro Imaging (LONI) within the University of Southern California’s (USC) Stevens Neuroimaging and Informatics Institute. Prior to her work at USC, she worked at Stanford University’s School of Medicine, and National Taiwan University Hospital. Nien-Chu holds Master’s degrees from USC and from National Yang Ming University in Taiwan. long with her work on microstructural mapping of dentate gyrus pathology, she is also studying how sleep and cerebral vascular risk factors influence the perivascular spaces, and has published on the effects of sleep on brain perivascular spaces. Farshid Sepehrband, an adjunct Professor of Research Neurology at USC and the senior author of the publication recognized by this award, joins Nien-Chu in answering our questions below.

Q1: What are the main advantages of using ultra-high field (16.4T) MRI and of performing ex vivo MRI?

Nien-Chu Shih (NCS): Ex vivo studies using 16.4T MRI provide exceptional imaging resolution. A major advantage of this technology is its high level of detail, with voxel resolutions exceeding 50 micrometers. This level of precision is approximately thousands of times higher than what's achieved in clinical MRI settings.

Farshid Sepehrband (FS): Ex vivo imaging allows us to validate quantitative MRI against histological imaging. With reduced partial volume effects due to high resolution, and high tissue microstructure sensitivity due to strong gradient strength, we could bridge the gap between clinical MRI and histological imaging, and we could assess tissue microstructure with MRI but without the physical and time limitations of clinical MRI.

Q2: What are the main challenges of using ultra-high field (16.4T) MRI and of performing ex vivo MRI?

NCS: A significant challenge is the substantial preparation and acquisition time required. For instance, obtaining data at this resolution took a considerable 68 hours of MRI scanning. Research or diagnostic applications that use ex vivo MRI often face this long acquisition period, which impacts both time and resource utilization.

FS: The biggest challenges for us were related to sample preparation, scan protocol design, and histology validation. We prepared brain tissue samples at USC in Los Angeles and then shipped them to the University of Queensland in Australia where we had developed optimized imaging sequences. We then scanned each sample for around 68 hours. You can imagine that maintaining the temperature of samples and consistency in the scanner’s signal (e.g., avoiding signal drift and maintaining/monitoring temperature, to name a few) were extremely challenging. These were among the reasons that it took us years to complete this study. In terms of limitations, the main one would be the difficulty in drawing a direct translational line between ex vivo ultra-high field MRI to in vivo clinical MRI.

Q3: How can these techniques be applied to better understand normative and pathological brain function?

NCS: It might take time to integrate these high field strengths into practical in vivo applications, but they've got a lot of potential to unlock the mysteries of brain function and pathology. Through these techniques, researchers can understand brain structure, aging, and pathophysiology. They offer a window to explore normative brain function and decode pathological processes, potentially aiding in the interpretation of imaging findings like hippocampal volume loss. While ultra-high-field MRI poses challenges, it offers profound insights into health physiology and brain function, allowing us to better understand both normal and abnormal brain function.

FS: It could also be used to understand how brain tissue changes during the course of the disease and the associated quantitative MRI signature. A disease-specific imaging marker that is sensitive to change over time will be of high clinical value for prognosis assessment and to evaluate the efficacy of a given treatment.

Q4: What are the clinical implications of this work?

NCS: This study reveals exciting new possibilities for MRI in mapping Alzheimer’s Disease (AD) pathology in 3D with intact tissue, something traditional histopathology can't do. It's possible to detect subtle neurite changes within the hippocampal formation with DTI and quantitative MRI. In AD, alterations in connectivity are believed to precede cortical atrophy, so they might have crucial diagnostic value. The clinical implications of this work are substantial. In this study, MRI techniques, which can detect early neurite changes and capture 3D details, could make AD diagnoses more precise and earlier, as well as advance our understanding of the disease.

FS: While our ex-vivo ultra-high field MRI has a long way to be translated into clinical imaging, we believe it is an important step towards it.