Xue Wang1, Weiqiang Dou2, and Jingtao Wu3
1Dalian Medical University, Dalian, China, 2GE Healthcare, Beijing, China, 3Clinical medical college, Yangzhou University, Yangzhou, China
Synopsis
Keywords: Arterial Spin Labelling, Machine Learning/Artificial Intelligence
Motivation: Hemodynamic disturbance is one of the neuropathological characteristics of Parkinson's disease (PD). Multi-delay arterial spin labeling (m-ASL) MRI can optimize the accuracy of cerebral blood flow (CBF) quantification by taking into account arterial transit time (ATT).
Goal(s): We aimed to comprehensively explore the detailed abnormalities of hemodynamics in PD and verify the application of m-ASL in PD diagnosis.
Approach: Voxel-based analysis and machine learning approach were applied to this study.
Results: Our findings identified impaired hemodynamics in PD with regional abnormalities of CBF, ATT and cerebral blood volume, providing complementary depictions of perfusion disruption in PD and highlighting the clinical feasibility of m-ASL.
Impact: Our results provided
complementary depictions of perfusion disruption in PD, and validated the
promise of m-ASL in the investigation of underlying neurodegeneration and the
clinical diagnosis of PD, providing an effective neuroimaging biomarkers for
the diagnosis of neurodegenerative diseases.
Introduction
Parkinson’s
disease (PD) suffers from hemodynamic abnormalities,
which could be effectively mapped via perfusion imaging approaches with
quantification of cerebral blood flow (CBF)1.
However, a major concern with the above mentioned findings in patients with PD was
inaccurate quantification of CBF (uncorrected-CBF) by conventional ASL (c-ASL)
with a single post labeling delay (PLD) due to individual differences in
cerebral hemodynamics2.
Multi-delay arterial spin labeling (m-ASL) strategy has been developed to optimize
the accuracy of CBF quantification and obtain multiple perfusion indices,
including arterial transit time (ATT), CBF
with ATT correction (corrected-CBF) and cerebral blood volume (CBV)3, 4.
The feasibility of m-ASL
technique has been validated in cerebrovascular diseases5,
but few studies have been performed in PD. Hence, we aimed to investigate
whether m-ASL with the derived metrics of corrected-CBF as well as ATT and CBV
can systematically evaluate the hemodynamics of patients with PD by comparing with
healthy control (HC). We hypothesized that m-ASL is a feasible method to
investigate neurodegeneration in PD, complementing other sources of information
on regional perfusion alterations, and that greater diagnostic efficacy could
be improved by taking more perfusion information into account than by using
c-ASL alone.Materials and Methods
Subjects
47 (29 male and 18 female) patients with
PD, and 50 (28 male and 22 female) matched HC subjects
were
recruited. The Mini-Mental State Examination was assessed the global cognitive
function of all subjects. The Unified
Parkinson’s Disease Rating Scale part III and Hoehn-Yahr scale were scored for
disease severity and stage of PD.
MRI experiment
MRI
experiments were performed using a 3.0-tesla MRI scanner (Discovery MR750, GE, USA) with an 8-channel head coil. M-ASL
sequence
was acquired with
scan parameters shown as follows: labeling duration, (220, 260, 300, 370, 480,
680, 1180) ms; PLD, (1000, 1220, 1480, 1780, 2150, 2630, 3320) ms; TR, 6019 ms;
TE, 11.4 ms; FOV, 220×220 mm2; arms, 4; points, 640; 4.5 mm without
gap; scan duration, 4 min 3 s.
Perfusion
data were preprocessed in SPM 12 embedded in the MATLAB
2018a platform. First, motion correction was performed to exclude translation
and rotation greater than 3 mm and 3°, respectively. Co-registration
between ASL imaging and T1-weighted imaging with a resampling voxel size of
3×3×3 mm3. Standardization was conducted by subtracting the global mean and dividing by
the standard deviation. Finally, the standardized perfusion images were
spatially smoothed with a 6 mm× 6 mm× 6 mm full width at half maximum Gaussian
kernel.
Statistical analysis
A paired t test was
utilized to compare the difference between uncorrected-CBF and corrected-CBF within each
group and a two-sample t test to analyze the intergroup differences in
perfusion metrics through a voxel-wise manner using SPM 12 software. Spearman
rank correlation was calculated to explore the potential correlations between regional perfusion parameters and scores of clinical
assessments. Machine learning (ML) analysis was used to identify the
classification performance of perfusion indices in
discriminating patients with PD from HC subjects.Results
Relative
to the uncorrected-CBF map, the corrected-CBF map further refined the
distributed brain regions in PD group versus HC group, manifested as the
extension of motor-related regions (Figure 1 and 2). Compared to HC group, PD patients
had elevated ATT and CBV in the right putamen, a
shortened ATT in the superior frontal gyrus, and
specific CBV variations in the left precuneus and the right supplementary
motor area (Figure 3 and 4). The integration of hemodynamic features from m-ASL
provided improved performance (area under the curve 0.97) in PD diagnosis (Figure 5).Discussion
Convergent perfusion
alterations that accompany neuronal dysfunction have been proposed as imaging
features of PD. In
this preliminary study, hemodynamic impairments in patients with PD were
comprehensively detected with the superiority of m-ASL. Our findings revealed
that m-ASL is capable of visualizing detailed brain regions with abnormal CBF in
patients with PD and provides more information on perfusion injury of ATT and
CBV than c-ASL, especially in motor-related regions. Moreover, the ML analysis
validated that m-ASL could achieve improved diagnostic efficiency using
features of corrected-CBF and even optimal classification performance via integrated
perfusion features.Conclusion
In conclusion, we
comprehensively identified the aberrant pattern of hemodynamics in patients
with PD by implementing a m-ASL approach, demonstrating extensive regional
disturbances of perfusion characteristics that are responsible for movement
disorders. m-ASL is feasible for the investigation of PD with optimized
quantification of CBF, detailed information on cerebral blood and improved classification
performance. These findings in our study provided complementary insights into
the neurodegenerative process and validated the clinical application of m-ASL
for the diagnosis of PD.Acknowledgements
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