Tissue optimization strategies for high-quality ex vivo diffusion imaging

TY - JOUR

T1 - Tissue optimization strategies for high-quality ex vivo diffusion imaging

AU - Barrett, Rachel L.C.

AU - Cash, Diana

AU - Simmons, Camilla

AU - Kim, Eugene

AU - Wood, Tobias C.

AU - Stones, Richard

AU - Vernon, Anthony C.

AU - Catani, Marco

AU - Dell'Acqua, Flavio

N1 - Funding Information: The authors thank Bernard Siow for contributing to our supply of Magnevist, Karen Randall for assisting with perfusion and tissue preparation, the members of the NatBrainLab for providing constructive feedback and Steve Williams for facilitating our use of the preclinical MRI system. This research was supported by the Wellcome Trust (103759/Z/14/Z) and NIHR Maudsley Biomedical Research Centre (BRC) (IS‐BRC‐1215‐20018). Publisher Copyright: © 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

PY - 2022/12/4

Y1 - 2022/12/4

N2 - Ex vivo diffusion imaging can be used to study healthy and pathological tissue microstructure in the rodent brain with high resolution, providing a link between in vivo MRI and ex vivo microscopy techniques. Major challenges for the successful acquisition of ex vivo diffusion imaging data however are changes in the relaxivity and diffusivity of brain tissue following perfusion fixation. In this study we address this question by examining the combined effects of tissue preparation factors that influence signal-to-noise ratio (SNR) and consequently image quality, including fixative concentration, contrast agent concentration and tissue rehydration time. We present an optimization strategy combining these factors to manipulate the (Formula presented.) and (Formula presented.) of fixed tissue and maximize SNR efficiency. We apply this strategy in the rat brain, for a diffusion-weighted spin echo protocol with TE = 27 ms on a 9.4 T scanner with a 39 mm volume coil and 660 mT/m 114 mm gradient insert. We used a reduced fixative concentration of 2% paraformaldehyde (PFA), rehydration time more than 20 days, 15 mM Gd-DTPA in perfusate and TR 250 ms. This resulted in a doubling of SNR and an increase in SNR per unit time of 135% in cortical grey matter and 88% in white matter compared with 4% PFA and no contrast agent. This improved SNR efficiency enabled the acquisition of excellent-quality high-resolution (78 (Formula presented.) m isotropic voxel size) diffusion data with b = 4000 s/mm (Formula presented.), 30 diffusion directions and a field of view of (Formula presented.) mm3 in less than 4 days. It was also possible to achieve comparable data quality for a standard resolution (150 (Formula presented.) m) diffusion dataset in (Formula presented.) h. In conclusion, the tissue optimization strategy presented here may be used to improve SNR, increase spatial resolution and/or allow faster acquisitions in preclinical ex vivo diffusion MRI experiments.

AB - Ex vivo diffusion imaging can be used to study healthy and pathological tissue microstructure in the rodent brain with high resolution, providing a link between in vivo MRI and ex vivo microscopy techniques. Major challenges for the successful acquisition of ex vivo diffusion imaging data however are changes in the relaxivity and diffusivity of brain tissue following perfusion fixation. In this study we address this question by examining the combined effects of tissue preparation factors that influence signal-to-noise ratio (SNR) and consequently image quality, including fixative concentration, contrast agent concentration and tissue rehydration time. We present an optimization strategy combining these factors to manipulate the (Formula presented.) and (Formula presented.) of fixed tissue and maximize SNR efficiency. We apply this strategy in the rat brain, for a diffusion-weighted spin echo protocol with TE = 27 ms on a 9.4 T scanner with a 39 mm volume coil and 660 mT/m 114 mm gradient insert. We used a reduced fixative concentration of 2% paraformaldehyde (PFA), rehydration time more than 20 days, 15 mM Gd-DTPA in perfusate and TR 250 ms. This resulted in a doubling of SNR and an increase in SNR per unit time of 135% in cortical grey matter and 88% in white matter compared with 4% PFA and no contrast agent. This improved SNR efficiency enabled the acquisition of excellent-quality high-resolution (78 (Formula presented.) m isotropic voxel size) diffusion data with b = 4000 s/mm (Formula presented.), 30 diffusion directions and a field of view of (Formula presented.) mm3 in less than 4 days. It was also possible to achieve comparable data quality for a standard resolution (150 (Formula presented.) m) diffusion dataset in (Formula presented.) h. In conclusion, the tissue optimization strategy presented here may be used to improve SNR, increase spatial resolution and/or allow faster acquisitions in preclinical ex vivo diffusion MRI experiments.

KW - diffusion MRI

KW - ex vivo

KW - fixed tissue preparation

KW - high resolution

KW - SNR efficiency

KW - tractography

UR - http://www.scopus.com/inward/record.url?scp=85143914013&partnerID=8YFLogxK

U2 - 10.1002/nbm.4866

DO - 10.1002/nbm.4866

M3 - Article

C2 - 36321360

AN - SCOPUS:85143914013

SN - 0952-3480

JO - NMR in Biomedicine

JF - NMR in Biomedicine

ER -