Evidence for the ultra-soft brain provided by uniqueness in intrinsic MR elastography

IntroductionBrain tissue is exceptionally soft. Recent in vivo work, including intrinsic MRE using naturally occurring cardiac pulsations, has shown stiffness values far below those obtained from post-mortem testing or externally actuated MRE. Such extreme softness allows a balance of elastic and inertial forces at even low frequencies, restoring uniqueness in viscoelastic iMRE inversion. Here, we demonstrate that viscoelastic iMRE can provide unique and stable stiffness estimates across frequencies, enabled by the brains ultra-soft nature. MethodiMRE data was obtained for 8 healthy subjects from a previous 7T MRI study, and MRE data was obtained at 50 Hz for 38 healthy subjects from two prior studies. The elastic-to-inertial force ratio was calculated for all subjects and compared between intrinsic and extrinsic datasets. The convergence of the viscoelastic iMRE was evaluated across a range of initial conditions and was examined at approximately 1, 2, and 3 Hz. ResultsAt a brain stiffness of 2600 Pa, the iMRE force ratio exceeded the MRE value by nearly four orders of magnitude, whereas at 4-35 Pa it fell to within approximately 0.5-2.5 orders of magnitude. Convergence was consistent across initial stiffness estimates. The mean storage modulus across all subjects was 5.29{+/-}0.95 Pa at 1 Hz, 34{+/-}17 Pa at 2 Hz, and 160{+/-}98 Pa at 3 Hz, consistent with previously reported frequency dependency. ConclusionBalanced force ratios, consistent convergence, and physiologically plausible results support uniqueness of the viscoelastic inversion. These findings resolve a key limitation in iMRE modeling and provide further evidence for the brains ultra-soft nature at low frequencies.