Volume and Dynamic Blood Flow of the Choroid Plexus in Neuroinflammatory Disease
Poster No:
1711
Submission Type:
Abstract Submission
Authors:
Mark DiFrancesco1, Hermine Brunner1, Elizabeth Wilson1
Institutions:
1Cincinnati Children's Hospital Medical Center, Cincinnati, OH
First Author:
Co-Author(s):
Introduction:
Systemic lupus erythematosus (SLE) and multiple sclerosis (MS) are autoimmune neuroinflammatory diseases that lead to cerebral vascular alterations. Compromise of cerebral microvasculature is widely considered a plausible route by which immune actors infiltrate the brain parenchyma, resulting in damage. The blood-brain-barrier (BBB), is the most studied regulator of blood-parenchyma exchange and comprised of the brain capillary endothelial cell layer with tight junctions. We and others have demonstrated regionally increased permeability of the BBB in SLE compared to healthy controls (Gulati et al., 2017). A recent murine study of SLE found CSF immune infiltrates in CSF even with the BBB intact, suggesting a currently neglected alternative mechanism of brain tissue infiltration at interfaces between the blood and CSF (Gelb, Stock, Anzi, Putterman, & Ben-Zvi, 2018). The Blood-CSF barriers (BCSFB) are in the choroid plexus (CP) within ventricles and at the meningeal barrier that surrounds the brain. In the CP, fenestrated capillaries exchange with a stromal layer at the basal side of an epithelium that acts to regulate exchange with ventricular CSF. Once an infiltrate enters the ventricular CSF, it can exchange with parenchyma through the ependymal layer at the ventricular surface. Recent imaging studies provide evidence for a BCSFB route to MS pathology by observation of periventricular gradients of tissue abnormalities. Our ongoing study is investigating alteration of the BCSFB in SLE and MS, specifically at the CP, including changes in volume, blood flow, and periventricular gradients in microstructural and microvascular properties of normal-appearing white matter. We report preliminary findings for volume and dynamic blood flow of the CP in SLE and MS patients vs. healthy controls.
Methods:
Preliminary analysis includes 5 SLE (4 F, 15.8(2.9)yrs), 5 MS (5 F, 18.6(3.2)yrs), and 15 healthy controls (HC, 8 F, 21.7(3.1)yrs) who completed MRI to assess CP volume (3D T1-weighted) and perfusion dynamics (pseudocontinuous arterial spin labeling at 15 label+delay times from 900 to 4000 ms). The protocol also included diffusion, relaxometry, and quantitative susceptibility imaging to assess periventricular white matter. ASCHOPLEX (Visani et al., 2024), a deep learning toolbox, was used to segment the CP and determine volume on the T1-weighted images. Dynamic perfusion signal was fitted to a model to determine arrival time and blood flow at the CP. Pairwise group comparisons of volume, arrival time, and blood flow were expressed as effect size (Cohen's d) with statistically significant results reported at p<0.05.
Results:
Total CP volume was found to be significantly lower for MS compared to either HC (p=0.012) or SLE (p=0.032) groups (Figure 1). HC and SLE volumes did not differ with even small effect size (d < 0.2). Among all three groups, arrival time was not found to differ pairwise with remarkable effect size (d < 0.2). Pairwise blood flow differences did not reach statistical significance at p<0.05, but did attain robust effect sizes (Figure 2). CP blood flow was greater in both MS and SLE groups compared to HC with effect sizes of d=0.84 and 1.11, respectively. SLE blood flow exceeded MS with a moderate effect size of d=0.33.
Conclusions:
Preliminary volumetric and blood flow changes in the CP were observed in neuroinflammatory disease compared to controls. Interestingly, reduced CP volume was evident only in MS but not SLE, suggesting differences in pathophysiology between these conditions. Increased blood flow to the CP in both SLE and MS was unexpected assuming vascular compromise but might be explained by increased blood flow associated with some inflammatory processes, possibly indicating a compensatory mechanism. Moving forward, if evidence for a CP route of brain infiltration is found with collection of more data, it could realign ways to phenotype SLE and MS and develop targeted therapies.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 1
Neuroanatomy Other
Novel Imaging Acquisition Methods:
Anatomical MRI
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Cerebral Blood Flow
Cerebrovascular Disease
Degenerative Disease
DISORDERS
MRI
Neurological
Structures
Other - choroid plexus
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Gulati, G., Jones, J. T., Lee, G., Altaye, M., Beebe, D. W., Meyers-Eaton, J., . . . DiFrancesco, M. W. (2017). Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach. Arthritis Care Res (Hoboken), 69(2), 299-305. doi:10.1002/acr.22923
Visani, V., Veronese, M., Pizzini, F. B., Colombi, A., Natale, V., Marjin, C., . . . Castellaro, M. (2024). ASCHOPLEX: A generalizable approach for the automatic segmentation of choroid plexus. Computers in Biology and Medicine, 182, 109164. doi:https://doi.org/10.1016/j.compbiomed.2024.109164