TY - JOUR
T1 - Assessment of the clinical feasibility of detecting subtle blood-brain barrier leakage in cerebral small vessel disease using dynamic susceptibility contrast MRI
AU - Elschot, Elles P.
AU - Backes, Walter H.
AU - de Jong, Joost J.A.
AU - Drenthen, Gerhard S.
AU - Wong, Sau May
AU - Staals, Julie
AU - Postma, Alida A.
AU - Rouhl, Rob P.W.
AU - van Oostenbrugge, Robert J.
AU - Jansen, Jacobus F.A.
N1 - Publisher Copyright:
© 2023
PY - 2023/10
Y1 - 2023/10
N2 - 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 DSC-MRI 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∙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 T2∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects.
AB - 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 DSC-MRI 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∙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 T2∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects.
KW - Blood-brain barrier leakage
KW - Cerebral small vessel disease
KW - DCE-MRI
KW - DSC-MRI
KW - Perfusion
KW - White Matter
KW - Humans
KW - Contrast Media/pharmacology
KW - Cerebral Small Vessel Diseases/diagnostic imaging
KW - Magnetic Resonance Imaging/methods
KW - Feasibility Studies
KW - Aged
KW - Blood-Brain Barrier/diagnostic imaging
UR - http://www.scopus.com/inward/record.url?scp=85156097557&partnerID=8YFLogxK
U2 - 10.1016/j.mri.2023.04.004
DO - 10.1016/j.mri.2023.04.004
M3 - Article
C2 - 37137345
AN - SCOPUS:85156097557
SN - 0730-725X
VL - 102
SP - 55
EP - 61
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
ER -