Perivascular spaces as a marker of psychological trauma in depression: A 7‐Tesla MRI study

Abstract

Introduction:Emerging evidence in depression suggests that blood-brain barrier (BBB) breakdown and elevated inflammatory cytokines in states of persistent stress or trauma may contribute to the development of symptoms. Signal-to-noise ratio afforded by ultra-high field MRI may aid in the detection of maladaptations of the glymphatic system related to BBB integrity that may not be visualized at lower field strengths. Methods:We investigated the link between glymphatic neuroanatomy via perivascular spaces (PVS) and trauma experience in patients with major depressive disorder (MDD) and in healthy controls using 7-Tesla MRI and a semi-automated segmentation algorithm.Results: After controlling for age and gender, the number of traumatic events was correlated with total PVS volume in MDD patients (r = 0.50, p = .028) and the overall population (r = 0.34, p = .024). The number of traumatic events eliciting horror was positively correlated with total PVS volume in MDD patients (r = 0.50, p = .030) and the overall population (r = 0.32, p = .023). Age correlated positively with PVS count, PVS total volume, and PVS density in all participants (r > 0.35, p < .01). Conclusions:These results suggest a relationship between glymphatic dysfunction related to BBB integrity and psychological trauma, and that glymphatic impairment may play a role in trauma-related symptomatology.

A critical guide to the automated quantification of perivascular spaces in magnetic resonance imaging

“…In disease, abnormal PVS measures have been observed in patients with depression, COVID-19, traumatic brain injury, Multiple Sclerosis (MS), Parkinson's disease (PD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) (Table 2; Cai et al, 2015;Ramirez et al, 2015Ramirez et al, , 2016Ramirez et al, , 2022Niazi et al, 2018;Donahue et al, 2021Donahue et al, , 2022George et al, 2021;Piantino et al, 2021;Sepehrband et al, 2021;Shen et al, 2021;Kamagata et al, 2022;Langan et al, 2022;Ranti et al, 2022). Significant higher PVS counts, but not volumes, have been found in COVID-19 patients, compared to controls (Langan et al, 2022).…”

“…Several studies have employed semi-automated methods, e.g., with the Frangi filter, to efficiently generate PVS maps ( Park et al, 2016 ; Sepehrband et al, 2021 ; Langan et al, 2022 ; Ranti et al, 2022 ). Subsequently, these masks can be compared to the raw predictions to derive Dice similarity coefficients, and thus measure model performance.…”

“…The gold standard of manual segmentation should be used as a benchmark for judging algorithm performance. Semi-automated methods of model validation may result in inflated and biased Dice scores ( Sepehrband et al, 2021 ; Langan et al, 2022 ; Ranti et al, 2022 ). Another reason for inflated Dice scores may be the under-labeling of PVS, which lowers number of PVS that the algorithm is required to detect.…”

“…Significant higher PVS counts, but not volumes, have been found in COVID-19 patients, compared to controls ( Langan et al, 2022 ). In patients with major depressive disorder, the severity of PVS volume enlargement has been associated with the number of traumatic events experienced in patients diagnosed with major depressive disorder (MDD) ( Ranti et al, 2022 ). Notably, there were no significant differences in PVS measures (counts, density, and volumes) between MDD patients and controls ( Ranti et al, 2022 ).…”

“…Ramirez et al, 2015Berezuk et al, 2015Cai et al, 2015Zong et al, 2016Wang et al, 2016Niazi et al, 2018Piantino et al, 2020Ballerini et al, 2020aBallerini et al, 2020bValdés Hernández et al, 2020Zong et al, 2020Barisano et al, 2021bSepehrband et al, 2021 Ramirez et al, 2021Shen et al, 2021George et al, 2021Piantino et al, 2021Donahue et al, 2021 Langan et al, 2022Ranti et al, 2022Lynch et al, 2022, Preprint Barisano et al, 2022bHupfeld et al, 2022Barnes et al, 2022Kamagata et al, 2022Donahue et al, 2022Ramirez et al, 2022Jokinen et al, 2020Zong et al, 2020Wang et al, 2021Huang et al, 2021 Spijkerman et al, 2022 PVS measures can be broadly categorized as quantitative metrics (volume, count, and volume fractions), and morphological metrics (length, width, solidity, and tortuosity). Listed first are the methods that utlize classical image filtering technique.…”