The impact of edema and fiber crossing on diffusion MRI metrics assessed in an ex vivo nerve phantom: Multi-tensor model vs. diffusion orientation distribution function

• Authors: Zezhong Ye, Washington University; Sam E Gary, University of Alabama Birmingham; Peng Sun, Washington University School of Medicine; Sourajit Mitra Mustafi, Indiana University; George Russell Glenn, Emory University; Fang-Cheng Yeh, University of Pittsburgh; Harri Merisaari, University of Turku; Chunyu Song, Washington University; Ruimeng Yang, South China University of Technology; Guo-Shu Huang, National Defense Medical Center Taiwan; Hung-Wen Kao, National Defense Medical Center Taiwan; Chien-Yuan Lin, GE Healthcare; Yu-Chien Wu, Indiana Univ Sch Med; Jens H Jensen, Medical University of South Carolina; Sheng-Kwei Song, Washington University
• Journal Title: NMR IN BIOMEDICINE
• Volume: Volume 34, Number 1
• Publisher: WILEY | 2020-10-04, Pages e4414-e4414
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/nbm.4414
• Subjects: Health Sciences, Radiology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Technology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy; angular resolution; diffusion basis spectrum imaging; diffusion MRI; diffusion orientation distribution function; brain tumor; white matter tractography; GAUSSIAN WATER DIFFUSION; SPHERICAL DECONVOLUTION; QUANTIFICATION; DEMYELINATION; TRACTOGRAPHY; INFLAMMATION; CELLULARITY; VALIDATION; TRACTS; INJURY

Abstract

Diffusion tensor imaging (DTI) has been employed for over 2 decades to noninvasively quantify central nervous system diseases/injuries. However, DTI is an inadequate simplification of diffusion modeling in the presence of coexisting inflammation, edema and crossing nerve fibers. We employed a tissue phantom using fixed mouse trigeminal nerves coated with various amounts of agarose gel to mimic crossing fibers in the presence of vasogenic edema. Diffusivity measures derived by DTI and diffusion basis spectrum imaging (DBSI) were compared at increasing levels of simulated edema and degrees of fiber crossing. Furthermore, we assessed the ability of DBSI, diffusion kurtosis imaging (DKI), generalized q-sampling imaging (GQI), q-ball imaging (QBI) and neurite orientation dispersion and density imaging to resolve fiber crossing, in reference to the gold standard angles measured from structural images. DTI-computed diffusivities and fractional anisotropy were significantly confounded by gel-mimicked edema and crossing fibers. Conversely, DBSI calculated accurate diffusivities of individual fibers regardless of the extent of simulated edema and degrees of fiber crossing angles. Additionally, DBSI accurately and consistently estimated crossing angles in various conditions of gel-mimicked edema when compared with the gold standard (r2 = 0.92, P = 1.9 × 10−9, bias = 3.9°). Small crossing angles and edema significantly impact the diffusion orientation distribution function, making DKI, GQI and QBI less accurate in detecting and estimating fiber crossing angles. Lastly, we used diffusion tensor ellipsoids to demonstrate that DBSI resolves the confounds of edema and crossing fibers in the peritumoral edema region from a patient with lung cancer metastasis, while DTI failed. In summary, DBSI is able to separate two crossing fibers and accurately recover their diffusivities in a complex environment characterized by increasing crossing angles and amounts of gel-mimicked edema. DBSI also indicated better angular resolution compared with DKI, QBI and GQI.