Assessment of perivascular space filtering methods using a three-dimensional computational model

Bernal, José; Valdés-Hernández, Maria del C.; Escudero, Javier; Duarte, Roberto; Ballerini, Lucia; Deary, Ian J.; Thrippleton, Michael J.; Touyz, Rhian M.; Wardlaw, Joanna M.

doi:10.1016/j.mri.2022.07.016

Cited by 14 publications

(26 citation statements)

References 45 publications

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“…Standard operating procedures, quality assurance and assessment were provided and supervised by the DZNE imaging network (iNET, Magdeburg) as described in [16]. We computed the mean background intensity as a surrogate measure of image quality and motion artefacts [24,25] and adjusted statistical models for it, as the quality of the scans determine also segmentation performance [26–28].…”

Section: Methodsmentioning

confidence: 99%

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Bernal

Schreiber

Ostendorf

et al. 2022

Preprint

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ImportancePosterior white matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology —not just arterial hypertension— impacts WMH, adversely influencing cognition.ObjectiveTo characterise the effects of AD pathology, namely β-amyloid (Aβ) and hypertension on WMH and cognition.DesignCross-sectional and longitudinalSettingMulticentreParticipantsWe analysed data from subjects with normal cognition (NC), subjective cognitive decline (SCD), and mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study. We focused on participants with available magnetic resonance imaging (MRI), cerebrospinal fluid biomarkers, and cognitive and hypertension information. We conducted analyses between 02.2022 and 06.2022.Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)NAMain Outcomes and MeasuresSpatial distribution and volume of MRI WMH in relation to Aß42/40 levels and arterial hypertension. Mediation of the relationship between Aβ positivity and hypertension on cognition by the regional WMH volume.ResultsWe included 355 participants (median age 70.3 [IQR 66.0-74.4] years; 168 female; 121 NC, 154 SCD, 80 MCI). Hypertension and Aβ positivity were positively associated (pFTR<0.05) with WMH volume, with large spatial overlap in the occipital lobes (regression coefficient ± standard error; hypertension: 0.49±0.14; Aβ: 0.41±0.15), parietal lobes (hypertension: 0.62±0.23; Aβ: 0.61±0.24), corona radiata (hypertension: 0.55±0.19; Aβ: 0.61±0.24), optic radiation (hypertension: 0.64±0.19; Aβ: 0.50±0.20) and splenium (hypertension: 0.38±0.13; Aβ: 0.39±0.13). Global and occipital WMH volumes were strongly associated cognitive changes over a three-year period, estimated with preclinical Alzheimer’s cognitive composite 5 (PACC5) (global: 2.18±0.61, pFDR<0.01; occipital: 3.31±0.75, pFDR<0.01), regardless of Aβ and hypertension status. The association between Aβ positivity and baseline cognitive performance (direct-memory: -0.42±0.08, pFDR<0.01; executive: - 0.28±0.28, pFDR<0.01) was partially mediated by WMH in the corona radiata (indirect-memory: -0.04±0.02, pFDR<0.05; executive: -0.04±0.02, pFDR<0.01) and splenium (indirect-memory: -0.02±0.02, pFDR<0.01; executive: -0.04±0.02, pFDR<0.01). Evidence supporting hypertension affected cognition was insufficient (direct-memory: 0.03±0.07, pFDR=0.683; executive: -0.05±0.07, pFDR=0.499; PACC5 change: 0.01±0.02, pFDR =0.588).Conclusions and RelevancePosterior white matter is susceptible to vascular disease and Aβ accumulation. Its deterioration is involved in the association between Aβ and cognitive dysfunction. Posterior WMH could be a promising target to tackle the downstream damage related to the interacting and potentiating effect of these two pathologies.Trial RegistrationGerman Clinical Trials Register (DRKS00007966, 04/05/2015)Key PointsQuestionIs the spatial distribution and volume of cerebral white matter hyperintensities (WMH) related to arterial hypertension, amyloid pathology, and cognition?FindingsIn this cross-sectional and longitudinal cohort study, WMH increased with hypertension and amyloid, with a spatial overlap in occipital and parietal lobes. Amyloid is involved in the relationship between WMH in corona radiata and splenium on cognitive performance. Global, occipital, and frontal WMH were strongly associated cognitive performance and worsening, regardless of hypertension and amyloid status.MeaningPosterior white matter is susceptible to vascular disease and amyloid pathology; its damage plays a role in the effect of amyloid pathology on cognition.

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Section: Methodsmentioning

confidence: 99%

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Bernal

Schreiber

Ostendorf

et al. 2022

Preprint

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“…In summary, the considered pipeline uses FreeSurfer [115] and FAST [116] for segmenting healthy and pathological white matter regions (T1w for whole brain parcellation and FLAIR for white matter hyperintensity segmentation), the Frangi filter for enhancing tubular structures (e.g. PVS), hard thresholding for segmenting PVS, and connected component analysis for determining counts and volumes [117]. We transformed measurements using the Yeo-Johnson transform to deal with skewness.…”

Section: Mr Markers Of Microvascular Healthmentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber¹,

Bernal²,

Ulbrich³

et al. 2023

Preprint

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Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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“…However, these studies are based on algorithms with certain disadvantages. The conventional methods relying on image processing techniques require further parameter optimization for different datasets ( Ballerini et al, 2016 ; Smith et al, 2020 , Preprint; Boutinaud et al, 2021 ; Bernal et al, 2022 ). Currently, only one fully automatic segmentation pipeline is freely available, making it difficult to replicate previous methods ( Boutinaud et al, 2021 ).…”

Section: Automated Segmentation Of Perivascular Spacesmentioning

confidence: 99%

“…These are convenient assessments of reliability and accuracy of PVS cluster quantification, but not voxel-wise segmentation performance, and therefore voxel-based volumetric assessments of PVS. One critique of the Frangi filter is that its performance deteriorates as the size of a PVS cluster increases ( Bernal et al, 2022 ). The implication for PVS research is that PVS counts, rather than volumes, are more likely to demonstrate statistical differences.…”

Section: Automated Segmentation Of Perivascular Spacesmentioning

confidence: 99%

“…The gray matter can be reliably segmented via established methods e.g., Freesurfer, FSL, and ANTs ( Dale et al, 1999 ; Zhang et al, 2001 ; Avants et al, 2014 ). Another reason is that the PVS intensity appears to most closely resemble GM, as opposed to CSF intensity ( Zong et al, 2020 ; Bernal et al, 2022 ). Thus, CNR measures based on GM intensity should be simple to compute and highly comparable between studies.…”

Section: Automated Segmentation Of Perivascular Spacesmentioning

confidence: 99%

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

Pham

Lynch²,

Spitz³

et al. 2022

Front. Neurosci.

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The glymphatic system is responsible for waste clearance in the brain. It is comprised of perivascular spaces (PVS) that surround penetrating blood vessels. These spaces are filled with cerebrospinal fluid and interstitial fluid, and can be seen with magnetic resonance imaging. Various algorithms have been developed to automatically label these spaces in MRI. This has enabled volumetric and morphological analyses of PVS in healthy and disease cohorts. However, there remain inconsistencies between PVS measures reported by different methods of automated segmentation. The present review emphasizes that importance of voxel-wise evaluation of model performance, mainly with the Sørensen Dice similarity coefficient. Conventional count correlations for model validation are inadequate if the goal is to assess volumetric or morphological measures of PVS. The downside of voxel-wise evaluation is that it requires manual segmentations that require large amounts of time to produce. One possible solution is to derive these semi-automatically. Additionally, recommendations are made to facilitate rigorous development and validation of automated PVS segmentation models. In the application of automated PVS segmentation tools, publication of image quality metrics, such as the contrast-to-noise ratio, alongside descriptive statistics of PVS volumes and counts will facilitate comparability between studies. Lastly, a head-to-head comparison between two algorithms, applied to two cohorts of astronauts reveals how results can differ substantially between techniques.

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Assessment of perivascular space filtering methods using a three-dimensional computational model

Cited by 14 publications

References 45 publications

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

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

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