Analyzing the co-localization of substantia nigra hyper-echogenicities and iron accumulation in Parkinson's disease: A multi-modal atlas study with transcranial ultrasound and MRI

Background: Transcranial B-mode sonography (TCS) can detect hyperechogenic speckles in the area of the substantia nigra (SN) in Parkinson's disease (PD). These speckles correlate with iron accumulation in the SN tissue, but an exact volumetric localization in and around the SN is still unknown. Areas of increased iron content in brain tissue can be detected in vivo with magnetic resonance imaging, using quantitative susceptibility mapping (QSM). Methods: In this work, we i) acquire, co-register and transform TCS and QSM imaging from a cohort of 23 PD patients and 27 healthy control subjects into a normalized atlas template space and ii) analyze and compare the 3D spatial distributions of iron accumulation in the midbrain, as detected by a signal increase (TCS+ and QSM+) in both modalities. Results: We achieved sufficiently accurate intra-modal target registration errors (TRE<1 mm) for all MRI volumes and multi-modal TCS-MRI co-localization (TRE<4 mm) for 66.7% of TCS scans. In the caudal part of the midbrain, enlarged TCS+ and QSM+ areas were located within the SN pars compacta in PD patients in comparison to healthy controls. More cranially, overlapping TCS+ and QSM+ areas in PD subjects were found in the area of the ventral tegmental area (VTA). Conclusion: Our findings are concordant with several QSM-based studies on iron-related alterations in the area SN pars compacta. They substantiate that TCS+ is an indicator of iron accumulation in Parkinson's disease within and in the vicinity of the SN. Furthermore, they are in favor of an involvement of the VTA and thereby the mesolimbic system in Parkinson's disease.