Abstract

Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications.

Highlights

  • Investigation of myelin damage, repair, and development in the central nervous system (CNS) for the understanding of pathological mechanisms and treatment monitoring in various neurological and psychiatric conditions using non-invasive imaging methods attracted substantial attention over past two decades (Heath et al, 2018; Piredda et al, 2021)

  • While there is no evidence of a superiority of any single myelin imaging method to date, the above studies consistently identified the macromolecular proton fraction (MPF) among the parameters enabling the strongest correlations with myelin histology

  • While most studies to date utilized custom-written software tools, we identified two open-source freely available software packages enabling MPF map reconstruction

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Summary

INTRODUCTION

Investigation of myelin damage, repair, and development in the central nervous system (CNS) for the understanding of pathological mechanisms and treatment monitoring in various neurological and psychiatric conditions using non-invasive imaging methods attracted substantial attention over past two decades (Heath et al, 2018; Piredda et al, 2021). Recent progress in quantitative MRI methods resulted in the development of several specialized techniques with improved specificity to myelin, which potentially can be used as sources of myelin biomarkers. The underlying biophysical tissue properties affected by myelin include single- or multi-component relaxation, magnetization transfer, anisotropic diffusion, and magnetic susceptibility (Heath et al, 2018; Piredda et al, 2021). While there is no evidence of a superiority of any single myelin imaging method to date, the above studies consistently identified the macromolecular proton fraction (MPF) among the parameters enabling the strongest correlations with myelin histology. A popular myelin biomarker, myelin water fraction measured from multicomponent relaxation analysis (MacKay et al, 1994; Deoni et al, 2008; Hwang et al, 2010) is influenced by the iron content (Birkl et al, 2019).

LITERATURE REVIEW
DISCUSSION
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