Background
The tissue field generated by a magnetic susceptibility source, such as iron, and experienced by the surrounding water protons is linearly related to the MR signal phase, which can be measured with high precision in MRI. Quantitative susceptibility mapping (QSM) provides an effective means to directly map the distribution of susceptibility sources by solving the field-to-source inversion problem. The clinical utility of QSM has been primarily applied to the brain and has shown utility across a vast range of neurodegenerative diseases.
Objectives
This presentation will provide the participants an opportunity to gain insight into the clinical potential of QSM, as it relates to the study of multiple sclerosis (MS).
Methods
QSM provides extensive insight into the early MS lesion, opening a new venue to investigate MS lesion inflammatory activity after blood brain barrier (BBB) closure. Chronic CNS inflammation in the MS lesion is maintained with pro-inflammatory microglia and macrophages (m/M), which have been demonstrated to be present at the rim of chronic active MS lesions and at the site of ongoing demyelination. The majority of the m/M found at the rim of chronic active multiple sclerosis lesions contain iron, and conversely iron-enriched microglia and macrophages are not found at the rim of remyelinated or shadow plaques. MRI with a gradient echo (GRE) sequence is sensitive to iron and has been utilized by many investigators to detect an iron rim in chronic active multiple sclerosis lesions. QSM provides quantification and localization of the magnetic sources, thus yielding benefits over other methods to identify and assess the paramagnetic rim present within this subset of chronic lesions.
Results
Utilizing PK11195-PET, it has been demonstrated that lesions with a rim of hyperintensity on QSM (rim+) have a significantly higher level of inflammation as compared on lesions lacking this rim. QSM rim+ lesions were also found to have more tissue injury, as measured by myelin water imaging. Building on this work, as well as histopathological validation studies, larger clinical studies are being are designed to establish the role of QSM rim+ lesions as a prognostic biomarker for disease activity and identify patients at risk for future disability. Similarly, the quantitative aspect of QSM provides the potential tool to assess treatment effect for drugs that may cross the BBB and target the innate immune response. Lastly, additional clinical applications of QSM for MS will be introduced and future directions will be discussed.
Conclusions
In conclusion, QSM is a validated quantitative imaging tool to explore the impact of chronic lesion pathology on clinical disability and to assess the potential therapeutic benefit of drugs targeting the innate immune response.