ASCHOPLEX: A generalizable approach for the automatic segmentation of choroid plexus.

BACKGROUND: The Choroid Plexus (ChP) plays a vital role in brain homeostasis, serving as part of the Blood-Cerebrospinal Fluid Barrier, contributing to brain clearance pathways and being the main source of cerebrospinal fluid. Since the involvement of ChP in neurological and psychiatric disorders is not entirely established and currently under investigation, accurate and reproducible segmentation of this brain structure on large cohorts remains challenging. This paper presents ASCHOPLEX, a deep-learning tool for the automated segmentation of human ChP from structural MRI data that integrates existing software architectures like 3D UNet, UNETR, and DynUNet to deliver accurate ChP volume estimates. METHODS: Here we trained ASCHOPLEX on 128 T1-w MRI images comprising both controls and patients with Multiple Sclerosis. ASCHOPLEX's performances were evaluated using traditional segmentation metrics; manual segmentation by experts served as ground truth. To overcome the generalizability problem that affects data-driven approaches, an additional fine-tuning procedure (ASCHOPLEXtune) was implemented on 77 T1-w PET/MRI images of both controls and depressed patients. RESULTS: ASCHOPLEX showed superior performance compared to commonly used methods like FreeSurfer and Gaussian Mixture Model both in terms of Dice Coefficient (ASCHOPLEX 0.80, ASCHOPLEXtune 0.78) and estimated ChP volume error (ASCHOPLEX 9.22%, ASCHOPLEXtune 9.23%). CONCLUSION: These results highlight the high accuracy, reliability, and reproducibility of ASCHOPLEX ChP segmentations.

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression.

BACKGROUND: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. METHODS: 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. RESULTS: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. CONCLUSION: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: implications for inflammation and depression.

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100ß, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.