Our study results showed that both PD and PPS patients had reduced CBF in several brain regions compared with healthy controls. PPS patients had lower CBF in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus than PD patients. Further ROC analysis showed that CBF value in these five brain regions had a desirable AUC for discrimination between PD and PPS, with CBF of the left SMA achieving the highest AUC of 0.831.
Previously, arterial spin labeling imaging combined with diffusion tensor imaging has been shown as useful markers for early Parkinson's disease [25]. The arrival time of cerebral arteries in primary Parkinson's disease was found to be prolonged on ASL imaging, indicating abnormal changes in neurovascular status [26, 27]. In our study, 3D-pCASL was performed to measure the cerebral perfusion. Compared with healthy controls, PD showed reduced CBF in five brain regions, i.e., the right cerebelum_crus2, the left MFG, the left IFG_Tri, the left FG_Med_Orb, and the left CN. These results were consistent with previous imaging studies in PD patients using PET/SPECT and ASL [28–33], where hypoperfusion was found in widespread cortical regions [20, 28], particularly in frontal regions [28, 29–31], as well as CN [28], cerebellar regions [33]. Compared with healthy control, the CBF value of frontal regions in PD patients decreased 11.4–15.9% in our study. This reduction of brain perfusion is similar to previously reported 9.4%-20.8% in PD patients [20, 28]. Frontal lobe dysfunction is a well-known character for PD patients [34]. These areas are often associated with motor function, and cognitive impairments or depression in PD [35, 36] and hypoperfusion in the prefrontal region might lead to emotional and cognitive disorders [37, 38]. In addition, our study also showed hypoperfusion in the left CN and the right cerebelum_crus2 in PD patients. Previously, significant hypoperfusion was detected in the right and left CN in patients with PD by using ASL technique [26, 28]. The hypoperfusion of CN maybe relate to the dopamine loss in the CN, which is associated with the cognitive decline [39] and depressive symptoms [40] in PD. Furthermore, the CBF laterality pattern in the CN was reported to a biomarker for PD diagnosis [41]. The cerebellum is an important component in motor control. Whereas, contradictory results have been reported for the cerebellum CBF change in the PD; thus, the exact role of the cerebellum in PD remains to be further understood [33].
The early-middle stage of PPS is challenging to differentiate from PD in terms of clinical symptoms. Previously, SPECT and PET-CT have been used to discriminate PD from parkinsonian disorders, such as Parkinson variant of MSA and PSP [42, 43]. These patients showed a distinct hypoperfusion pattern in the frontal cortex, thalamus, and cerebellum [42]. In our study, 3D pCASL imaging was used to determine the CBF changes in PPS patients. Our results showed that PPS had reduced CBF in five brain regions similar to those of PD and two additional brain regions, i.e., the left SMA and the right thalamus. Comparatively, the PPS group had altered CBF in more widespread brain regions. The additional involvement of these two brain regions suggests that PPS patients might have more severe impairment of motor function than PD patients. It is known that the extrapyramidal system includes a cortical-ponto-cerebella-thalamocortical circuit [44]. The cerebellum, thalamus and SMA play essential role in the cerebella-thalamocortical circuit and participant in motor control [45]. The association between the hypoperfusion in the cerebellum, thalamus, SMA and the damage in the extrapyramidal system has been described in PPS patients [46]. Thus, more widespread and severe impairment of CBF in PPS might reflect more severity of PPS or later stage of disease.
Our study showed that PPS patients had lower CBF values in the left IFG_Tri, the left MFG, the left CN, the left SMA, and the right thalamus compared with PD patients. This different pattern of reduced brain perfusion between PPS and PD is consistent with the previous study, where the perfusion distribution patterns were found to be different among MSA-P, PSP and PD [47]. More obvious impairment of CBF might reflect a more severe brain damage in the PPS group. Indeed, neuropsychiatric symptoms are common in patients with PPS; and the incidence and prevalence of depressive symptoms were higher in atypical parkinsonian syndromes and also appear to be more severe than in PD [48, 49]. MSA patients have glial cytoplasmic inclusions in the motor region and SMA, which is responsible for bradykinesia [50]. In our study, further ROC analysis showed that CBF value in these five brain regions ha d a desirable AUC for discrimination between PD and PPS, with CBF of the left SMA achieving the highest AUC of 0.831. Previously, a multitude of imaging parameters have been used to differentiate between PD and PPS [9, 52–54]. Tir et al. found that PSP had a lower fractional anisotropy value derived from diffusion tensor imaging in the SMA, indicating an abnormal motor pathway in PSP [51]. Calloni et al. reported that the middle cerebellar peduncle width and putaminal hypointensity on susceptibility-weighted imaging (SWI) can be used in combination to distinguish atypical parkinsonisms from idiopathic PD, with an AUC = 0.98 [52]. In addition, swallow tail (AUC = 0.85) and putaminal hypointensity (AUC = 0.68) also were reported to be able to distinguish MSA from PD [9]. Comparatively, the participants in these studies were older and had longer disease duration. In our study, PPS patients in the earlier stage of the disease were included. Our results showed the CBF of the SMA had the greatest AUC (0.831) and might be used as a surrogate marker for the differential diagnosis between the two diseases in an earlier stage.
There are some limitations to this study. First, we did not investigate CBF in early PD patients. The CBF as detected by ASL has been reported in early PD patients and perfusion reduction did not differ among different stages of PD [25]. Second, the sample size is small. The numbers of clinical scales collected are insufficient. Further large-scale, longitudinal studies and correlation analysis are needed to validate the discriminative CBF in these two diseases.