Unconstrained quantitative magnetization transfer imaging: disentangling T1 of the free and semi-solid spin pools

TL;DR

This study develops an optimized imaging method to separately measure the relaxation times of free and semi-solid spin pools in the brain, revealing distinct T1 values and differences in MS patients versus controls.

Contribution

It introduces an unconstrained MT model with a hybrid-state pulse sequence enabling voxel-wise quantification of T1 in both spin pools in a clinical setting.

Findings

T1 of semi-solid pool is much shorter than free pool T1.

Semi-solid spin pool size is larger than previously thought.

MS patients show significant differences in free pool T1 compared to controls.

Abstract

Since the inception of magnetization transfer (MT) imaging, it has been widely assumed that Henkelman's two spin pools have similar longitudinal relaxation times, which motivated many researchers to constrain them to each other. However, several recent publications reported a $T_1^s$ of the semi-solid spin pool that is much shorter than $T_1^f$ of the free pool. While these studies tailored experiments for robust proofs-of-concept, we here aim to quantify the disentangled relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, i.e., with an effective resolution of 1.24mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned four people with relapsing-remitting multiple sclerosis (MS) and four healthy controls with this pulse sequence and estimated $T_1^f \approx 1.84$s and $T_1^s \approx 0.34$s in healthy white matter. Our results confirm the reports that $T_1^s \ll T_1^f$ and we argue that this finding identifies MT as an inherent driver of longitudinal relaxation in brain tissue. Moreover, we estimated a fractional size of the semi-solid spin pool of $m_0^s \approx 0.212$, which is larger than previously assumed. An analysis of $T_1^f$ in normal-appearing white matter revealed statistically significant differences between individuals with MS and controls.