Introduction

Idiopathic REM sleep behavior disorder (iRBD) serves as a prodromal stage for Parkinson's disease (PD) and related neurodegenerative conditions^[1]. A comprehensive understanding of the neurophysiological changes associated with iRBD can aid in the development of effective diagnostic and treatment strategies. The aim of this study is to employ arterial spin labeling (ASL)^[2], a non-invasive MRI technique, to examine cerebral blood flow (CBF) discrepancies and CBF-connectivity^[3] patterns in iRBD, PD, and healthy controls (HC). Furthermore, we aim to identify potential biomarkers that could facilitate the early diagnosis and monitoring of iRBD and PD progression.

Methods

Subjects: Fifty-nine right-handed were enrolled, including 15 subjects with iRBD (M/F: 7/8, age: 60 ± 12), 20 subjects with PD^[4] (M/F: 10/10, age: 60±10), and 24 healthy controls (M/F: 11/13, age: 65±9).
Data acquisition: All subjects underwent cranial magnetic resonance scans on a 3.0T MRI scanner (Prisma, Siemens Healthcare, Erlangen, Germany) equipped with a 64-channel phased array head coil. T1-weighted (T1w) imaging was performed using a three-dimensional Magnetization Prepared Rapid Acquisition Gradient Recalled Echo (3D MP-RAGE), sequence with parameters: TR=2300ms, TE=3ms, TI=900ms, spatial resolution=0.8×0.8×0.8mm³. A pulsed ASL (PASL) sequence was employed to obtain quantitative CBF maps. The acquisition parameters were as follows: TR=3200ms, TE=12ms, flip angle=90°, FOV=256mm, voxel size=4×4×6 mm³, slice thickness=6mm, total scan time = 6min32s.
Data analysis: T1-weighted data processing procedures including resampling and reorientation, brain extraction, and brain label. ASL images were preprocessed using a Matlab-based toolkit^[5] with procedures as follows: motion correction, co-registration to the anatomical image, smoothing, and normalization to MNI standard space. Quantification of CBF and construction of CBF-connectivity network: Initially, the CBF was quantified within each region based on the Automated Anatomical Labeling (AAL)^[6] employing arterial spin labeling (ASL) techniques. Our analysis focused on distinct brain regions associated with significant CBF changes in iRBD, PD, and HC. We estimated CBF connectivity through Pearson correlation coefficients between each pair of brain regions, subsequently constructing a CBF-connectivity network with the identified brain regions as seed points.
Statistical analysis: The normality distribution of CBF and demographic data was tested by Kolmogorov-Smirnov methods. An independent t-test with age and sex as the nuisance variables was performed for CBF (Cerebral Blood Flow) variations in a voxel-size manner among the three groups. Multiple comparisons were corrected using the classical Benjamini-Hochberg procedure of FDR correction with a corrected threshold of 0.05. For each subject, the region with significant group differences was extracted and used as the region of interest (ROI). Then, we used Cohen’s d to describe the effect size (ES) of each ROI-based comparison. Likewise, the group differences in the CBF connectivity were compared using an independent t-test and a family-wise error (FEW) method with a corrected threshold of 0.05. The t-value was used as the indicator of correlation.

Results

Figure 1 shows the brain regions of significant CBF differences between the PD and iRBD, and PD and HC.
Figure 2 shows group differences in CBF. Compared with healthy subjects, the PD patients showed increased CBF in the Frontal_Mid_Orb_L(ES=1.08), Occipital_Mid_R,(ES=1.37), and Angular_L(ES=0.83). In contrast, these patients had significantly decreased CBF in Caudate_L(ES=-1.64). Similarly, compared to iRBD patients, PD showed the same trend. Frontal_Mid_Orb_L(ES=0.95), Occipital_Mid_R,(ES=1.16), and Angular_L(ES=1.46). Caudate_L(ES=-0.94).
Figure 3 denotes the group differences in CBF connectivity. Compared with the iRBD group, the PD group exhibited elevated connectivity between the left orbital part of the middle frontal gyrus and the left caudate nucleus (t =2.536), the right middle occipital gyrus and the left caudate nucleus (t=3.153), left angular gyrus and the left caudate nucleus (t=3.220). Compared with the HC group, the PD group demonstrates a similar trend in the regions where increased connectivity was observed above. Additionally, between the left orbital part of the middle frontal gyrus and the right middle occipital gyrus (t=-2.619), the PD group exhibited decreased CBF connectivity.

Discussion

Significant changes of CBF values and CBF connectivity have been revealed in PD patients as compared to iRBD patients and healthy controls, demonstrating that ASL is valuable in detecting cerebral perfusion and network changes. This provides a direction for us to understand the characteristics of the lesions from the aspect of cerebral perfusion, as well as to interfere with the possible brain atrophy and functional abnormalities. To achieve more robust results, multi-modal studies will be conducted by increasing the sample size.

Conclusion

Arterial spin labeling is able to detect alterations in brain perfusion and network in iRBD and PD and is valuable for individualized diagnosis, which is of potential clinical value in revealing its pathophysiological basis and assisting further treatment.

Acknowledgements

No acknowledgement found.