Unraveling the major role of vascular (R2') contributions to R2* signal relaxation at ultra-high-field MRI: A comprehensive analysis with quantitative gradient recalled echo in mouse brain

Purpose: Ultra-high-field (UHF) R2* relaxometry is often used for in vivo analysis of biological tissue microstructure without accounting for vascular contributions to R2* signal, that is, the BOLD signal component, and magnetic field inhomogeneities. These effects are especially important at UHF as their contribution to R2* scales linearly with magnetic field. Our study aims to report on the results of separate contributions of R2t* (tissue-specific sub-component) and R2' (vascular BOLD sub-component), corrected for the adverse effects of magnetic field inhomogeneities, to the total R2* signal at in vivo UHF MRI of mouse brain. Methods: Four healthy, 8-week-old C57BL/6J mice were imaged in vivo with multi-gradient echo MRI at 9.4 T and analyzed using the quantitative gradient recalled echo (qGRE) approach. A segmentation protocol was established using the Dorr Mouse Brain Atlas and ANTs Syn registration to warp template brain region labels to subject qGRE maps. Results: By separating R2' contribution from R2* signal, we have established normative R2t* data in mouse brain. Our findings revealed significant contributions of R2' to R2*, with approximately 42% of the R2* signal arising from vascular contributions, thus suggesting the R2t* as a more accurate metric for quantifying tissue microstructural information and its changes in neurodegenerative diseases. Conclusion: qGRE approach allows efficient separation of tissue microstructure-specific (R2t*), vascular BOLD (R2'), and background gradients contributions to the total R2* relaxation at UHF MRI. Due to low concentration of non-heme iron in mouse brain, major contribution to R2t* results from tissue cellular components.