Myelin Quantification Using Ultrashort Echo Time Magnetization Transfer Ratio In A Mouse Model Of Traumatic Brain Injury
National Institutes of Health, Grant RF1 AG075717
Abstract
Background and Purpose: This study aims to assess the potential of ultrashort echo time imaging-based magnetization transfer ratio (UTE-MTR) in detecting demyelination in mice with mild traumatic brain injury (mTBI) caused by an open-field low-intensity blast (LIB) injury model. Methods: This study included 30 male C57BL/6 mice, approximately 8 weeks old, sourced from Jackson Laboratories in Bar Harbor, ME, and conducted under institutional guidelines. The mice were divided into the mTBI group (n = 15) and the sham control group (n = 15). All animal experiments followed the approved protocols for the Care and Use of Laboratory Animals and Animal Research. The mTBI group underwent the open-field LIB injury. Behavioral tests were conducted to assess motor activity and anxiety-like responses. UTE-MT imaging was performed using a 3 Tesla Bruker system to measure UTE-MTR from two UTE-MT datasets with saturation powers of 1500° and 500°, and two frequency offsets of 2 and 50 kHz, respectively. Luxol fast blue (LFB) staining was performed to evaluate myelin content. The mean UTE-MTR values for regions of interest centered at the medial section of the corpus callosum were computed. The behavioral tests, LFB myelin staining, and UTE-MTR values were compared between the two groups using the independent t-test. p values <0.05 were considered significant. Results: The mTBI mice demonstrated decreased motor activity and increased anxiety-like response over sham controls. The mTBI mice also showed significantly lower UTE-MTR values (0.399±0.007 vs. 0.393±0.005; p<0.05) and reduced LFB myelin staining (0.848±0.324 vs. 1.145±0.260; p = 0.048) over sham controls. Conclusion: The significantly lower UTE-MTR values in the corpus callosum of mTBI mice are consistent with reduced LFB myelin staining, indicating that UTE-MTR can detect myelin loss and associated alterations in motor and anxiety domains post-LIB exposure.
