Blood‐brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects

Abstract

Purpose To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood‐brain barrier (BBB) water exchange measurements using FEXI (BBB‐FEXI), and to quantify the accuracy, precision, and repeatability of BBB‐FEXI exchange rate estimates at 3 T$$ \mathrm{T} $$. Methods Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two‐compartment model (2CM$$ 2\mathrm{CM} $$) explicitly representing intra‐ and extravascular signal components, and (iii) a two‐compartment model additionally accounting for finite compartmental normalT1$$ {\mathrm{T}}_1 $$ and normalT2$$ {\mathrm{T}}_2 $$ relaxation times (2CMr$$ 2{\mathrm{CM}}_r $$). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and 2CM$$ 2\mathrm{CM} $$ models, as well as the accuracy and precision of all three models. The scan–rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23–52 years; five female). Results The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/2CM$$ 2\mathrm{CM} $$ models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan–rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of RCAXR=0.43$$ {\mathrm{RC}}_{\mathrm{AXR}}=0.43 $$ s0.3emprefix−1$$ {\mathrm{s}}^{-1} $$, RC2CM=0.51$$ {\mathrm{RC}}_{2\mathrm{CM}}=0.51 $$ s0.3emprefix−1$$ {\mathrm{s}}^{-1} $$, and RC2CMr=0.61$$ {\mathrm{RC}}_{2{\mathrm{CM}}_r}=0.61 $$ s0.3emprefix−1$$ {\mathrm{s}}^{-1} $$. Conclusion Compartmental modelling of BBB‐FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model‐dependent biases.

Quantification of water exchange across the blood‐brain barrier using noncontrast MR fingerprinting

“…6,7 An alternative approach, which may offer greater sensitivity than dynamic control enhanced-MRI, while also avoiding the use of gadolinium-based contrast agents, is to measure exchange of the smaller, and endogenously abundant, water molecules across the BBB. However, existing water exchange techniques, such as those based on arterial spin labeling [8][9][10] or diffusion MRI methods such as filter exchange imaging, 11,12 also suffer from low SNR.…”

Assessment of Microvascular Disease in Heart and Brain by MRI: Application in Heart Failure with Preserved Ejection Fraction and Cerebral Small Vessel Disease

“…The main limitations of the technique are the requirement for GBCA, prolonged delay required between GBCA administration and acquisition (>15 min), and the low signal-to-noise ratio of the leakage effect [ 38 ]. Newer techniques [ 114 , 115 ] have been developed targeting the water exchange across the endothelium that do not require contrast material.…”

Blood–brain barrier water exchange measurements using contrast‐enhanced ASL

“… 13 Several methods have been developed for measuring trans‐BBB water exchange. While some methods have utilized differences in the relaxation time 3 , 4 , 14 or intrinsic diffusion properties 15 , 16 , 17 of the blood water directly, many adopt an arterial spin labelling (ASL) approach. Proposed ASL techniques have aimed to separate the intra‐ and extravascular signals using diffusion 18 , 19 , 20 or magnetization transfer 21 effects, properties 11 , 22 , 23 , 24 , 25 or velocity encoding.…”