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

Abstract

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.

Keywords: R2*; biophysical modeling; qGRE; ultra‐high‐field MRI.

FIGURE 1

Example of mouse registration: T2‐like image (left), overlayed transformed Template labels (center), and Dorr Template Brain (right). Note that dark regions in lower part of T2‐like image are caused by strong field inhomogeneities.

FIGURE 2

Example of T1‐weighted, R2*, R2t*, and R2' qGRE images. Figure depicts (left to right): Image of the first gradient echo (T1‐weighted) image of mouse head; The corresponding R2*, R2t*, and R2' maps. The scale bar shows relaxation parameters (R2*, R2t*, and R2') values in 1/s.

FIGURE 3

qGRE metrics in GM: R2* (blue), R2t* (orange), R2' (green). Bars represent mean values across all subjects and error bars represent corresponding SDs. Regions correspond to organization levels within the Allen Brain Atlas as specified in Supplementary Table 1S.

FIGURE 4

R2* values in WM labels. Bars represent mean values across all subjects and error bars represent corresponding SDs. Regions correspond to organization levels within the Allen Brain Atlas as specified in Supplementary Table 2S.