Quantitative susceptibility mapping of the midbrain in Parkinson's disease

Abstract

Background Parkinson’s disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD. Methods Quantitative susceptibility mapping and R2* maps were obtained from 47 PD patients and 47 healthy controls. Midbrain susceptibility and R2* values were analyzed by using both voxel-based and region-of-interest approaches in normalized space, and analyzed along with clinical data, including disease duration, Unified Parkinson’s Disease Rating Scale (UPDRS) I, II, and III sub-scores, and levodopa-equivalent daily dosage. All studies were done while PD patients were “on drug.” Results Compared with controls, PD patients showed significantly increased susceptibility values in both right (cluster size = 106 mm3) and left (164 mm3) midbrain, located ventrolateral to the red nucleus that corresponded to the substantia nigra pars compacta. Susceptibility values in this region were correlated significantly with disease duration, UPDRS II, and levodopa-equivalent daily dosage. Conversely, R2* was increased significantly only in a much smaller region (62 mm3) of the left lateral substantia nigra pars compacta and was not significantly correlated with clinical parameters. Conclusion The use of quantitative susceptibility mapping demonstrated marked nigral changes that correlated with clinical PD status more sensitively than R2*. These data suggest that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD.

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

“…The voxel-based morphology analysis by Du et al (132) elegantly demonstrates selective SNc iron increase in perfect concordance with post mortem histology, underscoring the potential of QSM as a biophysical marker for therapeutic effects in clinical trials. While these studies may provide little direct value for current symptomatic levodopa medication of PD patients, QSM could be an essential imaging tool for DBS and iron-chelating therapy.…”

“…Devos, et al have recently reported very encouraging results showing that DFP improves PD motor performance and reduces nigral R2* values on GRE MRI, suggesting that DFP can be the first disease-modifying therapy for PD (127). Because QSM is superior to R2* for evaluating nigral iron (131,132,134,135,145), an important potential application of QSM in PD is to measure DFP's effectiveness of target-engagement in clinical trials.…”

How to choose the right MR sequence for your research question at 7 T and above?

“…These can be better observed in susceptibility maps than in simultaneously acquired R 2 * maps (Du et al, 2015;Murakami et al, 2015). This points towards either using multi-echo protocols covering a range of echo times up to 30ms, which will be sufficiently robust to compute R 2 * and susceptibility maps of deep gray matter regions, or single echo acquisitions with a TE~15-20ms and low BW to maximize SNR, and be able to compute susceptibility maps.…”

Quantification of liver iron concentration using the apparent susceptibility of hepatic vessels

“…Conventionally, LIC is measured using either R2 or R2* mapping based methods. It has been shown that R2* has superior sensitivity to changes in cerebral iron content than R2 (36), and QSM has even better sensitivity than R2* (10,37,38). The great potential of QSM has already been demonstrated in a recent study, in which the conventional QSM algorithms were adapted for liver iron quantification.…”