Investigating Glymphatic Dysfunction in Neuropsychiatric Systemic Lupus Erythematosus by dMRI

516 

Abstract Submission 

Yi Ting Hsieh¹, Chih-Chin Heather Hsu², Ni-Jung Chang³, Jyh-Wen Chai³, Ching-Po Lin^2,4

¹School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan, ³Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan, ⁴Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

Yi Ting Hsieh  
School of Medicine, College of Medicine, National Yang Ming Chiao Tung University
Taipei, Taiwan

Chih-Chin Heather Hsu  
Institute of Neuroscience, National Yang Ming Chiao Tung University
Taipei, Taiwan

Ni-Jung Chang  
Department of Radiology, Taichung Veterans General Hospital
Taichung, Taiwan

Jyh-Wen Chai  
Department of Radiology, Taichung Veterans General Hospital
Taichung, Taiwan

Ching-Po Lin  
Institute of Neuroscience, National Yang Ming Chiao Tung University|Department of Education and Research, Taipei City Hospital
Taipei, Taiwan|Taipei, Taiwan

Neuropsychiatric systemic lupus erythematosus (NPSLE) significantly impacts the nervous system and mortality rates. Despite the typical presentation of white matter hyperintensity (WMH) on routine MRI scans in NPSLE patients, the macrostructure appears normal in 50% of cases, posing challenges in disease assessment and treatment [1]. Previous research has proposed that the NPSLE autoantibodies can traverse the blood-brain barrier and induce glymphatic system abnormalities [2]. Additionally, NPSLE patients commonly experienced hypoperfusion in the area served by the middle cerebral artery (MCA) [3, 4]. In this study, we investigated regional variations in three glymphatic system stages in NPSLE patients without abnormal WMH: 1) perivascular space (PVS) enlargement depicted by PVS mapping; 2) interstitial fluid stagnation assessed by free water (FW) mapping; and 3) decrease in glymphatic clearance efficiency evaluated by diffusion tensor image analysis along the perivascular space (ALPS). Our goal is to identify imaging biomarkers indicative of NPSLE, as well as improve its diagnosis and treatment.

There were 27 female patients (age 22-63 y/o) in the NPSLE group and 34 age-matched females in the normal control group (NC). All participants underwent cognitive assessment, including Montreal Cognitive Assessment (MoCA), Mini Mental Status Examination (MMSE), and Frontal Assessment Battery (FAB). MRI images were acquired on a Siemens MAGNETOM Aera 1.5T MRI scanner, including 1 mm^...3 isotropic T1w image (TR/TE=2800/3.98 ms, TI=930 ms), T2w image (TR/TE=3000/280 ms), FLAIR image (TR/TE=5000/350 ms, TI=1800 ms), and diffusion-weighted image (TR/TE=10000/107 ms, 30 directions with NEX=3). Firstly, the UBO detector [5] was used for WMH mapping. Next, an enhanced contrast method [6] with automatic PVS quantification [7] was utilized for PVS mapping. The PVS volume was normalized by total intracranial volume as PVS volume fraction (PVSVF). Single shell FW algorithm was used via DIPY (https://dipy.org/). The mean FW values calculation excluded the PVS and WMH maps [8]. ALPS evaluated the diffusivity along the medullary perivenous space in the plane of the lateral ventricle body [9]. The 3D brain MRI arterial atlas [10] was applied on WMH, PVS, and FW for evaluation of regional variation. Last, we analyzed group differences by the Mann-Whitney U test with Bonferroni correction for multiple comparisons.

NPSLE and NC groups showed age-related increases in brain WMH volume without significant group differences (Fig. 1A). There were no differences between groups in whole brain PVSVF and FW mean values (Fig. 1B and 1C). In arterial subregions: medial lenticulostriate (MLS) of anterior cerebral artery (ACA) and lateral lenticulostriate (LLS) of MCA, FW mean values were significantly higher in the NPSLE group (Fig. 1E). ALPS reduced significantly in the NPSLE group (Fig.1D). In the cognitive assessment results for the NPSLE group (Fig. 2), whole brain PVSVF and WMH volume negatively correlated with all assessments, while ALPS and FW correlated positively. Only PVSVF had a significant negative correlation with MMSE. In ACA subregion, significant negative correlations were between MMSE and PVSVF and between MoCA and WMH volume, while MoCA positively correlated with FW.

The study unveiled the glymphatic abnormalities in NPSLE patients. While global PVSVF showed no significant differences, localized glymphatic dysfunction in specific arterial subregions, along with reduced waste clearance efficiency, were evident in NPSLE patients. Cognitive assessments suggested glymphatic abnormalities may contribute to NPSLE-related cognitive impairment. Correlation trends with ALPS and PVSVF support glymphatic dysfunction's role in cognitive decline. Intriguingly, a positive FW correlation challenged prior assumptions of the expectations of deteriorating brain function. Our findings provide valuable insights into the pathophysiology of NPSLE.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Diffusion MRI Modeling and Analysis ²

Cerebral Metabolism and Hemodynamics

Cognition

MRI

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - Neuropsychiatric systemic lupus erythematosus (NPSLE), Glymphatic system, perivascular space