Assessment of the clinical feasibility of detecting subtle blood-brain barrier leakage in cerebral small vessel disease using dynamic susceptibility contrast MRI

Purpose: Cerebral small vessel disease (cSVD) involves several pathologies affecting the small vessels, including blood-brain barrier (BBB) impairment. Dynamic susceptibility contrast (DSC) MRI is sensitive to both blood perfusion and BBB leakage, and correction methods may be crucial for obtaining reliable perfusion measures. These methods might also be applicable to detect BBB leakage itself. This study investigated to what extent DSCMRI can measure subtle BBB leakage in a clinical feasibility setting. Methods: In vivo DCE and DSC data were collected from fifteen cSVD patients (71 (+/- 10) years, 6F/9M) and twelve elderly controls (71 (+/- 10) years, 4F/8M). DSC-derived leakage fractions were obtained using the Boxerman-Schmainda-Weisskoff method (K2). K2 was compared with the DCE-derived leakage rate Ki, obtained from Patlak analysis. Subsequently, differences were assessed between white matter hyperintensities (WMH), cortical gray matter (CGM), and normal-appearing white matter (NAWM). Additionally, computer simulations were performed to assess the sensitivity of DSC-MRI to BBB leakage. Results: K2 showed significant differences between tissue regions (P < 0.001 for CGM-NAWM and CGM-WMH, and P = 0.001 for NAWM-WMH). Conversely, according to the computer simulations the DSC sensitivity was insufficient to measure subtle BBB leakage, as the K2 values were below the derived limit of quantification (4 center dot 10 (-3) min (-1)). As expected, Ki was elevated in the WMH compared to CGM and NAWM (P < 0.001). Conclusions: Although clinical DSC-MRI seems capable to detect subtle BBB leakage differences between WMH and normal-appearing brain tissue it is not recommended. K2 as a direct measure for subtle BBB leakage remains ambiguous as its signal effects are due to mixed T1- and T-2*-weighting. Further research is warranted to better disentangle perfusion from leakage effects.

Automated summary

This study investigated the ability of dynamic susceptibility contrast (DSC) MRI to measure subtle blood-brain barrier (BBB) leakage in cerebral small vessel disease (cSVD) in a clinical feasibility setting. The results showed that DSC-MRI is capable of detecting subtle BBB leakage differences between white matter hyperintensities (WMH) and normal-appearing brain tissue. However, further research is needed to better differentiate perfusion from leakage effects due to signal uncertainties.