Table 1 Summary of main review study samples, MRI methodologies and relationship investigated
Author (Year) | Sample/Group (N)a | Age, M ± SD | MRI Methodb,c | Inter-relationship | |||
|---|---|---|---|---|---|---|---|
ePVS × BBB permeability | ePVS | BBBP | Region | Association | Summary | ||
Chen et al. (2022) | T2DM CSVD (n = 25) | 69 ± 10 | T1 or T2 visual count | Gd-DOTA DCE ktrans | Global ePVS and BBBP in: frontal white matter, parietal white matter, gray matter, caudate head, putamen, thalamus | None (only with presence of cerebral microbleeds; (statistics not reported) | Non-significant |
Chen et al. (2022) | Non-T2DM CSVD (n = 12) | 56 ± 19 | T1 or T2 visual count | Gd-DOTA DCE ktrans | Global ePVS and BBBP in: frontal white matter | When ePVS ≥ 6, ≥ 7 or ≥ 8; p = 0.028 to 0.035 | Positive |
Chen et al. (2022) | Non-T2DM (n = 12) | 56 ± 19 | T1 or T2 visual count | Gd-DOTA DCE ktrans | Global ePVS and BBBP in: parietal white matter, gray matter, caudate head, putamen, thalamus | None (statistics not reported) | Non-significant |
Li et al. (2019) | Healthy (N = 109) | 70 ± 9 | T2 visual count grade | gadolinium DCE ktrans | BG ePVS and global BBBP | When comparing low (0–1) and high (2–4) grade ePVS; p < 0.001 | Positive |
CSO ePVS and global BBBP | When comparing low (0–1) and high (2–4) grade ePVS; p = 0.88 | Non-significant | |||||
Li et al. (2018) | Healthy (N = 99) (same cohort as 2019 study) | 70 ± 9 | T2 visual count grade | gadolinium DCE ktrans | Global ePVS and BBBP in: NAWM, WMH, cortical gray matter and deep gray matter | R2 = 0.082 to 0.214, p ≤ 0.001 to 0.004 | Unspecified |
Wardlaw et al. (2009) | Lacunar stroke (n = 51) & Cortical stroke (n = 46) | 64 ± 12 69 ± 10 | 1.5 T T2 visual count grade | 1.5 T Gd-DTPA DCE signal enhancement | Global ePVS and BBBP in: white matter, gray matter | F = 0.9 to 1.75, p = 0.13 to 0.46 | Non-significant |
ePVS × Cerebral perfusion | ePVS | Perfusion | Region | Association | Summary | ||
Gyanwali et al. (2022) | All memory clinic patients (N = 333) | Median = 73 (IQR = 10) | T2 visual count | pCASL CBF | Global ePVS and CBF in: gray matter, white matter | β < 0.01, p = 0.45 to 0.90 | Non-significant |
BG ePVS and CBF in: gray matter, white matter | β = − 0.02 to − 0.04, p = 0.17 to 0.52 | Non-significant | |||||
CSO ePVS and CBF in: gray matter, white matter | β < 0.01, p = 0.70 to 0.83 | Non-significant | |||||
Gyanwali et al. (2022 | Normal cognition (n = 87) | Not reported | T2 visual count | pCASL CBF | Global ePVS and CBF in: gray matter, white matter | β = − 0.01 to 0.00, p = 0.86 to 0.94 | Non-significant |
BG ePVS and CBF in: gray matter, white matter | β = − 0.05 to 0.01, p = 0.21 to 0.83 | Non-significant | |||||
CSO ePVS and CBF in: gray matter, white matter | β = − 0.01 to 0.00, p = 0.59 to 0.99 | Non-significant | |||||
Gyanwali et al. (2022 | Cognitive impairment no dementia (n = 153) | Not reported | T2 visual count | pCASL CBF | Global ePVS and CBF in: gray matter, white matter | β = − 0.01, p = 0.30 to 0.54 | Non-significant |
BG ePVS and CBF in: gray matter, white matter | β = − 0.04 to − 0.01, p = 0.32 to 0.73 | Non-significant | |||||
CSO ePVS and CBF in: gray matter, white matter | β = − 0.01 to 0.00, p = 0.79 to 0.98 | Non-significant | |||||
Gyanwali et al. (2022) | Dementias (n = 93) | Not reported | T2 visual count | pCASL CBF | Global ePVS and CBF in: gray matter, white matter | β = − 0.01 to 0.01, p = 0.54 to 0.74 | Non-significant |
BG ePVS and CBF in: gray matter, white matter | β = − 0.03 to 0.00, p = 0.58 to 0.92 | Non-significant | |||||
CSO ePVS and CBF in: gray matter, white matter | β = 0.01 to 0.03, p = 0.25 to 0.83 | Non-significant | |||||
Kapoor et al. (2022) | Healthy (n = 37) | 66 ± 7 | T2 visual count grade | pCASL CVR to hypercapnia/ hypocapnia | Global | Hypocapnia: B = − 2.02, p = 0.015 Hypocapnia: B = − 0.33, p = 0.871 | Non-significant Non-significant |
BG ePVS and global CVR | Hypercapnia: B = − 2.7, p = 0.009 Hypocapnia: None (statistics not reported) | Negative Non-significant | |||||
CSO ePVS and global CVR | Hypercapnia: B = − 1.8, p = 0.068 Hypocapnia: None (statistics not reported) | Non-significant Non-significant | |||||
Lee et al. (2021) | Spontaneous ICH (n = 21) | 63 ± 11 | 1.5 T T2 visual count | 1.5 T pulsed ASL CVR to dipyridamole | Global | p > 0.05 | Non-significant |
Liu et al. (2021) | Healthy (N = 406) | 70 ± 8 | T2 visual count grade (BG only) | pCASL CBF | BG ePVS and CBF in: cortical regions and left thalamus | When comparing mild (grade < 3) and severe (grade ≥ 3) ePVS: p < 0.05 | Negative |
Lu et al. (2022) | CSVD (n = 121) Healthy (n = 53) | 64 ± 9 57 ± 9 | T2 visual count grade | pCASL CBF pattern category (discriminative analysis) | Total ePVS and CBF pattern | When comparing between three pattern groups: p > 0.05 | Non-significant |
BG ePVS and CBF pattern | When comparing between three pattern groups: p > 0.05 | Non-significant | |||||
CSO ePVS and CBF pattern | When comparing between three pattern groups: p > 0.05 | Non-significant | |||||
Neumann et al. (2022) | CSVD (n = 10) and Healthy (n = 4) | 70 (IQR = 14) 72 (IQR = 9) | T2 visual count (BG/CSO/Hippocampus) | Pulsed ASL CBF | Total ePVS and CBF in: gray matter, white matter, basal ganglia, hippocampus | r = − 0.80 to − 0.39 significance value not available | Negative |
BG ePVS and CBF in: gray matter, white matter, basal ganglia, hippocampus | r = − 0.82 to − 0.60 significance value not available | Negative | |||||
CSO ePVS and CBF in: gray matter, white matter, basal ganglia, hippocampus | r = − 0.49 to 0.15 significance value not available | Non-significant | |||||
Onkenhout et al. (2020) | Vascular cognitive impairment (N = 132) | 73 ± 10 | T2 visual count grade | phase-contrast CBF | Global | When comparing mild (grade < 3) and severe (grade ≥ 3) ePVS (adjusted difference = 3.3, p = 0.1) | Non-significant |
When ePVS severe (grade ≥ 3) (OR = 0.67, p = 0.03) | Negative | ||||||
Shi et al. (2020) | Minor stroke (N = 56) | 68 ± 8 | 1.5 T T1, T2 visual count grade | 1.5 T phase-contrast CBF | BG ePVS and global CBF | OR = 1.01–1.03, significance not available, ORs overlap null | Non-significant |
CSO ePVS and global CBF | OR = 0.99–1.00, significance not available, ORs overlap null | Non-significant | |||||
ePVS × Free water | ePVS | Free water | Region | Association | Summary | ||
Huang et al. (2022) | CSVD (n = 84) | 61 ± 11 | T2 visual count grade | DTI ISOVF | Global | β = 0.224, p < 0.001 | Positive |
Huang et al. (2022) | Healthy (n = 144) | 61 ± 6 | T2 3D volume | DTI ISOVF | Global | β = 0.290, p < 0.001 | Positive |
Huang et al. (2021) | Healthy (N = 136) | Median = 60 (range 56–65) | T2 3D non-WMH volume | DTI non-PVS ISOVF | Global | β = 0.332, p < 0.001 | Positive |
High-WMH (above median): ePVS × WMH is mediated by free water (β = 0.118, p < 0.006) | Unspecified | ||||||
Low-WMH (below median): ePVS × WMH is not mediated by free water (β = − 0.046, p = 0.074) | Non-significant | ||||||
Jiaerken et al. (2021) | Severe CSVD (n = 15) | 67 (range 57–81) | T2 visual label location | DTI ISOVF | ePVS voxels and local free water | Compared to NAWM, free water is higher in (0–2 mm; p < 0.001) and lower 3–4 mm from ePVS (p < 0.001) | Unspecified |
Jiaerken et al. (2021) | Healthy Elderly (n = 20) | 64 (range 56–83) | T2 3D segmentation | DTI ISOVF | ePVS voxels and local free water | Compared to NAWM, free water is higher in (0–2 mm; p < 0.001) and lower 2–4 mm from ePVS (p < 0.001) | Unspecified |
Jiaerken et al. (2021) | Healthy Adults (n = 28) | 32 (range 20–59) | T2 3D segmentation | DTI ISOVF | ePVS voxels and local free water | Compared to NAWM, free water is higher in (0–2 mm; p < 0.001) and lower 3–6 mm from ePVS (p < 0.001) | Unspecified |
Lan et al. (2022) | CSVD (N = 129) | 60 ± 11 | 1.5 T T1, T2 visual count grade (BG only) | 1.5 T DTI ISOVF | BG ePVS and global free water | r = 0.428, p < 0.001; β = 0.154, p = 0.045 | Positive |
Zotin et al. (2022; gray literature) | Probable CAA (N = 38) | 73 ± 7 | Not reported | DTI ISOVF | CSO ePVS and global free water | β = 0.496, p < 0.001 | Positive |
BBB permeability × Cerebral perfusion | BBBP | Perfusion | Region | Association | Summary | ||
Chen et al. (2022; gray literature) | Asymptomatic carotid artery stenosis (N = 30) | Not reported | DCE ktrans | ASL perfusion (not reported) | Cerebral hemisphere with carotid artery stenosis | Areas with increased BBBP also had reduced perfusion, statistics not available | Negative |
Chi et al. (2019) | SLE (n = 6) | 38 ± 13 | gadabutrol DCE ktrans and volume in extravascular extracellular space (Ve) | gadabutrol DCE CBF | Global | ktrans: r = 0.47, R2 = 0.22, p = < 0.001 | Positive |
Ve: r = 0.47, R2 = 0.23, p = < 0.001 | Positive | ||||||
Chi et al. (2019) | Healthy (n = 5) | 34 ± 11 | gadabutrol DCE ktrans and volume in extravascular extracellular space (Ve) | gadabutrol DCE CBF | Global | ktrans: r = 0.22, p > 0.05 | Non-significant |
Ve: r = 0.25, p > 0.05 | Non-significant | ||||||
Haselhorst et al. (2000) | Multiple sclerosis (N = 25) | 43 (range 22–61) | 1.5 T Gd-DOTA enhancing lesion locations | 1.5 T Gd-DOTA regional CBV | CBV in DCE enhancing lesions and white matter | When comparing enhancing lesions to NAWM, p < .01 | Positive |
van de Haar et al. (2016) | MCI/AD (n = 14) | 75 (range 65–85) | gadobutrol DCE influx (Ki) and fraction of leaking voxels (VL) | pCASL CBF | Gray matter BBBP and gray matter CBF | Ki: r = − 0.73, p = 0.011 | Negative |
VL: r = − 0.57, p = 0.07 | Non-significant | ||||||
van de Haar et al. (2016) | Healthy (n = 16) | 77 (range 65–85) | gadobutrol DCE influx (Ki) and fraction of leaking voxels (VL) | pCASL CBF | Gray matter BBBP and gray matter CBF | Ki: p = 0.60 | Non-significant |
VL: p = 0.60 | Non-significant | ||||||
Varatharaj et al. (2019) | RR-MS (n = 12) Healthy (n = 13) | 43 ± 10 31 ± 10 | Gadovist DCE influx | Gadovist DCE CBF and CBV | Global | CBF: rho = 0.32, p = 0.11 | Non-significant |
CBV: B = 0.036, p < 0.001 | Positive | ||||||
Wengler et al. (2019) | Healthy (N = 15) | 28 ± 9 | pCASL surface area product (PS) and extraction fraction (EF) | pCASL CBF | Global | PS: r = 0.89, p < 0.05 | Positive |
EF: r = − 0.32, p < 0.05 | Negative | ||||||
Wong et al. (2019) | CSVD (N = 27) | 69 ± 12 | gadobutrol DCE influx (Ki) and fraction of leaking voxels (VL) | DSC CBF | Global CBF and BBBP in: white matter | Ki: r = − 0.40, p = 0.045 | Negative |
VL: r = − 0.41, p = 0.033 | Negative | ||||||
Global CBF and BBBP in: gray matter | Ki: r = − 0.36, p = 0.094 | Non-significant | |||||
VL: r = − 0.37, p = 0.077 | Non-significant | ||||||
Wuerfel et al. (2004) | RR-MS (N = 20) | 32 ± 9 | 1.5 T Gd-DPTA enhancing lesion locations | 1.5 T T2a CBF and CBV | CBF/CBV in DCE enhancing lesions | CBF: When comparing baseline to time of initial enhancement (p = 0.015) and baseline to 3-weeks before BBB leakage (17.9% increase, p = 0.008) | Positive |
CBV: When comparing baseline to time of initial enhancement (p = 0.008) and baseline to 3-weeks before BBB leakage (18.0% increase, p = 0.008) | Positive | ||||||
BBB permeability × Free water | BBBP | Free water | Region | Association | Summary | ||
Hillmer et al. (2022) | VCID/AD/Leukoaraiosis (N = 136) | 68 (IQR = 13) | Gd-DTPA DCE ktrans | DTI ISOVF | Global | p < 0.001 | Positive |