Accurate Determination of Blood–Brain Barrier Permeability Using Dynamic Contrast-Enhanced T1-Weighted MRI: A Simulation and in vivo Study on Healthy Subjects and Multiple Sclerosis Patients

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to estimate permeability in situations with subtle blood-brain barrier (BBB) leakage. However, the method's ability to differentiate such low values from zero is unknown, and no consensus exists on optimal selection of total measurement duration, temporal resolution, and modeling approach under varying physiologic circumstances. To estimate accuracy and precision of the DCE-MRI method we generated simulated data using a two-compartment model and progressively down-sampled and truncated the data to mimic low temporal resolution and short total measurement duration. Model fit was performed with the Patlak, the extended Tofts, and the Tikhonov two-compartment (Tik-2CM) models. Overall, 17 healthy controls were scanned to obtain in vivo data. Long total measurement duration (15 minutes) and high temporal resolution (1.25 seconds) greatly improved accuracy and precision for all three models, enabling us to differentiate values of permeability as low as 0.1 ml/100 g/min from zero. The Patlak model yielded highest accuracy and precision for permeability values <0.3 ml/100 g/min, but for higher values the Tik-2CM performed best. Our results emphasize the importance of optimal parameter setup and model selection when characterizing low BBB permeability.

Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI

“…The fitted K trans values from the 2CXM are reflective of more accurate values across the entire K trans range; the extended Tofts generally overestimates K trans ; and Patlak does well at low permeability values (≤5 × 10 −3 min −1) but underestimates K trans at larger values. These findings validate previous studies .…”

Blood–brain barrier permeability measured using dynamic contrast‐enhanced magnetic resonance imaging: a validation study

“…), use of individual AIFs for each subject, partial volume correction of the AIF (Hansen et al . ), selecting the optimal time resolution and total scan time (Cramer & Larsson, ), and choosing a suitable pharmacokinetic modelling approach (Sourbron & Buckley, ) appear to be important for accurate estimation of subtle BBB leakage. Another hurdle is the time and skill required for manual ROI placement and the potential for operator bias.…”

Brain imaging of neurovascular dysfunction in Alzheimer’s disease

“…Due to the wide range of analysis techniques used and their strong dependence on underlying assumptions and acquisition parameters, a lack of inter-study comparability represents a major problem. The importance of appropriate model selection has been demonstrated both theoretically [14, 157] and experimentally in low-permeability brain tissues [42, 103, 115]. …”