Rapid, high-resolution quantitative magnetization transfer MRI of the human spinal cord

Abstract

Quantitative magnetization transfer (qMT) imaging can provide indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular proton fraction (MPF), which has been shown to correlate with myelin content in white matter. Because of the long scan times required for high-resolution spinal cord imaging, qMT studies of the human spinal cord have not found wide-spread application. Herein, we investigated whether these limitations could be overcome by utilizing only a single MT-weighted acquisition and a reference measurement, as was recently proposed in the brain. High-resolution, in vivo qMT data were obtained at 3.0 tesla in the spinal cords of healthy volunteers and patients with relapsing remitting multiple sclerosis (MS). Low- and high-resolution acquisitions (low/high resolution = 1×1×5 mm3/0.65×0.65×5 mm3) with clinically acceptable scan times (12 min/7 min) were evaluated. We also evaluated the reliability over time and the sensitivity of the model to the assumptions made in the single-point method, both in disease and healthy tissue. Our findings suggest that the single point qMT technique can provide maps of the MPF in the spinal cord in vivo with excellent grey/white matter contrast, can be reliably obtained within reasonable scan times, and are sensitive to MS pathology. Consistent with previous qMT studies in the brain, the observed MPF values were higher in healthy white matter (0.16±0.01) than in grey matter (0.13±0.01) and in MS lesions (0.09±0.01). The single point qMT technique applied at high resolution provides an improved method for obtaining qMT in the human spinal cord and may offer a reliable outcome measure for evaluating spinal cord disease.

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

“…In vivo mapping of myelin density15 and g‐ratio16; iron deposition17; sodium concentration18; inflammation and axonal injury19 are examples of quantitative MRI techniques being developed to detect early multiple sclerosis pathology. Similar quantitative MRI metrics require extensive validation, in order to confirm their specificity and relevance to clinical outcomes 20, 21, 22…”

Pool size ratio of the substantia nigra in Parkinson’s disease derived from two different quantitative magnetization transfer approaches

“…The lack of significant differences in qMT values other than an increase in PSR between HC and PD groups accompanied by a small but insignificant increase in MTR on the other hand, is at odds with prior reports of reduced MTR in the SNc of PD patients [27, 29, 47, 48]. Reductions in MTR and PSR have been attributed to inflammation and neuronal death through an increase in the absolute volume of the free pool, as well as myelin damage and elimination from the site of injury, and have been well-reported in multiple sclerosis lesions and demyelination models [34, 35]. Unlike the white matter typically affected by multiple sclerosis however, the dopaminergic neurons that degenerate in PD are highly branched and relatively poorly myelinated [50].…”

“…Moreover, in terms of understanding the mechanisms of NM-MRI contrast, MTR is hampered by the fact that it reflects the collective impacts of several inter-related physico-chemical properties, including the macromolecular content [29], as well as vendor-specific choices regarding MT and excitation RF pulse characteristics. By using quantitative MT (qMT) methods [31–33] we have sought to decouple these factors, a process that has been demonstrated to generate scanner independent indices of tissue physiology that may prove more reproducible [34, 35] and have a physical meaning in quantifying SNc degeneration in PD.…”

“…Although pulsed-saturation qMT offers several indices of tissue physiology, doing so reliably within a clinically feasible scan time is challenging. A number of methods for obtaining some or all of the qMT-derived indices are available in the literature [36–39], but we will focus our attention on the previous work of Yarnykh et al [40], which suggests concentrating on the derivation of a single qMT parameter such that a single MT prepared acquisition and a reference measurement are sufficient for the calculation [34, 35, 40]. Using this approach, PSR maps can be obtained in clinically relevant scan times, making it a valuable approach for the SN.…”

“…While several studies have evaluated the clinical utility of qMT imaging in other neurological disorders, particularly multiple sclerosis [34, 35], the application of qMT in patients with PD, has not yet been reported. Thus, the aim of the present study was to compare the MT properties of the SNc in PD patients and healthy controls (HCs) using a full qMT analysis, and determine whether a rapid single-point measurement yields equivalent results for the PSR.…”