Utility of susceptibility-weighted imaging in Parkinson’s disease and atypical Parkinsonian disorders

SWI in the diagnosis of Parkinson’s disease

The majority of research approved that SWI was feasible to indirectly quantify the iron content of different regions of brain through comparing the phase values in SWI which was highly correlated with the iron content [17, 19, 22, 24]. Thus, the comparison of iron content in SWI is conducted by comparing the phase value indirectly rather than by comparing the iron content directly like QSM. There are various forms of iron deposition patterns of PD imaged by SWI among the researches. Some researches supported that iron deposition patterns in SWI can distinguish PD from HC. Jiuquan Zhang et al. reported that the iron concentration was elevated significantly only in the SN of PD compared with HC in SWI [17]. The iron contents of the SNc, CN and RN in PD were significantly higher than those in HC in a SWI study by Wei Zhang et al. [33]. Also, Wu et al. demonstrated the iron accumulation in the SN, RN, CN, PUT, and GP of PD was more remarkable than that of HC [69]. An elevated iron level of the SN was common in PD among SWI research, because the SN is the most pathologically relevant site of PD and become atrophy and brownish discoloration in autopsy [48, 67, 70]. Notably, Dashtipour et al. did not find remarkably increased iron content of SN in PD, and it may be explained by the small sample size [31]. However, the discrepancy of iron accumulation in other nuclei, such as RN, CN, PUT, and GP, in SWI is unclear. One possible reason is that deep brain nuclei are pathologically involved simultaneously with different degrees of iron accumulation [70]. In addition, different iron deposition patterns may relate to disease progression [31]. Furthermore, research has demonstrated that the iron content of the SN is inversely correlated with the severity of PD as measured by UPDRS-motor score and H-Y stage [17, 30, 48], while no correlations were found between the iron content of the SN and the duration, progression, prognosis and levodopa response of PD [17, 31, 33, 69, 71, 72]. Even though with the heterogeneity of iron deposition speed and distribution in the whole disease process, SWI still fails to characterize specific clinical features of PD. For instance, SWI cannot detect the difference between earlier-onset and later-onset PD patients [17]. Neither could SWI show difference between the early and intermediate/advanced stages of PD [69]. Mechanisms, such as gene mutation, alteration of the BBB, and inflammation, may underlie the speed, onset and spatial distribution of iron deposition [12, 29, 50]. Further studies are needed to figure out whether there are correlations between iron content of SN and specific clinical features.

In recent years, a novel imaging biomarker called nigrosome 1, which is the sub-region of the SN, has been extensively studied by researchers. According to the immuno-staining of calbindin that can bind to calcium, the SNc is subdivided into nigrosome (caldbindin-poor) and nigral matrix (caldbindin-rich). Nigrosome 1 is the largest nigrosome containing the biggest group of dopaminergic cells and is affected in almost every PD patient [73]. It was reported that 7T MRI could visualize the three-layered structure of SN and could distinguish patients with PD from HC with both high sensitivity and specificity [14, 74, 75]. In 3T SWI, nigrosome 1 also shows dorsolateral hyperintensity of SN in HC, and disappears in PD with 100% sensitivity and high specificity (shown in Fig. 2) [47, 73]. These evidences suggested that 3T SWI is a reliable tool for the visualization of nigrosome 1 and the diagnosis of PD. However, in some studies nigrosome 1 hyperintensity also disappears in MSA-P and PSP in SWI [14, 53]. Therefore, nigrosome 1 is a safe biomarker for neurodegenerative parkinsonism rather than PD.

Nigrosome 1 of three-layered structure disappears in PD patients, while it exists in health controls (which are pointed out by black arrows)