Developing an SNR-efficient tensor-valued diffusion encoding protocol for studying brain microstructural changes in neurodegeneration
- 1Stanford University; Brigham and Womens Hospital, Harvard Medical School
Abstract
Tensor-valued diffusion encoding (TDE) is an emerging diffusion MRI technique that uses advanced diffusion-encoding waveforms and modeling to provide enhanced specificity to brain microstructure compared with conventional Stejskal-Tanner pulsed-gradient encoding. However, the diffusion encoding duration to achieve the same b-value is substantially increased in TDE, resulting in relatively low SNR and spatial resolution (>2 mm isotropic). In this study, we developed an SNR-efficient, high-resolution TDE protocol with 1.8-mm isotropic resolution and clinically feasible scan time and evaluated its reproducibility and sensitivity to age-related microstructural differences. Eleven cognitively normal older adults (5F/6M, 62-71 years) and seven younger adults (3F/4M, 22-31 years) were scanned at 3T using an in-house TDE sequence incorporating an SNR-efficient multi-band multi-shot EPI readout and reconstruction. Quantitative diffusion metrics, including mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (FA), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), and total mean kurtosis (MKT), were evaluated in the bilateral temporal parts of the cingulum bundles (CBT), bilateral fornix (FX), and global white matter (WM). Older participants underwent two scans to assess reproducibility using intraclass correlation coefficients (ICCs) and Bland-Altman analysis, and diffusion metrics were compared between younger and older groups using Wilcoxon signed-rank tests with false discovery rate (FDR) correction. All metrics except MKI demonstrate moderate-to-excellent reproducibility across all WM regions (ICCs[≥]0.64). Exploratory comparisons show age-related differences in FA, FA, and MKA with p<0.05 before FDR correction, particularly in the fornix, although none remains significant after correction. These findings demonstrate the feasibility of SNR-efficient TDE at 1.8-mm isotropic resolution with approximately 70-mm brain coverage in approximately 12 minutes and establish its reproducibility for high-resolution brain microstructural imaging.
Key PointsO_LIAn SNR-efficient tensor-valued diffusion encoding (TDE) protocol was developed with 1.8-mm isotropic resolution. C_LIO_LIThe high-resolution TDE protocol achieved [~]70-mm brain coverage within a clinically feasible scan time of [~]12 minutes. C_LIO_LIThe developed TDE protocol was evaluated in two white matter bundles closely associated with neurodegeneration and global white matter. C_LIO_LIAll quantitative diffusion metrics except MKI demonstrate moderate-to-excellent scan-rescan reproducibility in across white matter ROIs (ICC[≥]0.64). C_LIO_LIExploratory comparisons show age-related differences in FA, FA, and MKA before FDR correction, particularly in the fornix. C_LI
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BibTeX
@misc{dai2026developing,
title = {{Developing an SNR-efficient tensor-valued diffusion encoding protocol for studying brain microstructural changes in neurodegeneration}},
author = {E. Dai and X. Zhou and S. Shailja and M. K. Schneider and M. A. Millar and M. Zeineh and C.-F. Westin and J. A. McNab},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.26363267},
url = {https://www.medrxiv.org/content/10.64898/2026.09.16.26363267v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Developing an SNR-efficient tensor-valued diffusion encoding protocol for studying brain microstructural changes in neurodegeneration
AU - E. Dai
AU - X. Zhou
AU - S. Shailja
AU - M. K. Schneider
AU - M. A. Millar
AU - M. Zeineh
AU - C.-F. Westin
AU - J. A. McNab
PY - 2026
DA - 2026/09/16
PB - medRxiv
DO - 10.64898/2026.09.16.26363267
UR - https://www.medrxiv.org/content/10.64898/2026.09.16.26363267v1
AB - Tensor-valued diffusion encoding (TDE) is an emerging diffusion MRI technique that uses advanced diffusion-encoding waveforms and modeling to provide enhanced specificity to brain microstructure compared with conventional Stejskal-Tanner pulsed-gradient encoding. However, the diffusion encoding duration to achieve the same b-value is substantially increased in TDE, resulting in relatively low SNR and spatial resolution (>2 mm isotropic). In this study, we developed an SNR-efficient, high-resolution TDE protocol with 1.8-mm isotropic resolution and clinically feasible scan time and evaluated its reproducibility and sensitivity to age-related microstructural differences. Eleven cognitively normal older adults (5F/6M, 62-71 years) and seven younger adults (3F/4M, 22-31 years) were scanned at 3T using an in-house TDE sequence incorporating an SNR-efficient multi-band multi-shot EPI readout and reconstruction. Quantitative diffusion metrics, including mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (FA), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), and total mean kurtosis (MKT), were evaluated in the bilateral temporal parts of the cingulum bundles (CBT), bilateral fornix (FX), and global white matter (WM). Older participants underwent two scans to assess reproducibility using intraclass correlation coefficients (ICCs) and Bland-Altman analysis, and diffusion metrics were compared between younger and older groups using Wilcoxon signed-rank tests with false discovery rate (FDR) correction. All metrics except MKI demonstrate moderate-to-excellent reproducibility across all WM regions (ICCs[≥]0.64). Exploratory comparisons show age-related differences in FA, FA, and MKA with p<0.05 before FDR correction, particularly in the fornix, although none remains significant after correction. These findings demonstrate the feasibility of SNR-efficient TDE at 1.8-mm isotropic resolution with approximately 70-mm brain coverage in approximately 12 minutes and establish its reproducibility for high-resolution brain microstructural imaging. Key PointsO_LIAn SNR-efficient tensor-valued diffusion encoding (TDE) protocol was developed with 1.8-mm isotropic resolution. C_LIO_LIThe high-resolution TDE protocol achieved [~]70-mm brain coverage within a clinically feasible scan time of [~]12 minutes. C_LIO_LIThe developed TDE protocol was evaluated in two white matter bundles closely associated with neurodegeneration and global white matter. C_LIO_LIAll quantitative diffusion metrics except MKI demonstrate moderate-to-excellent scan-rescan reproducibility in across white matter ROIs (ICC[≥]0.64). C_LIO_LIExploratory comparisons show age-related differences in FA, FA, and MKA before FDR correction, particularly in the fornix. C_LI
ER -