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

TY - JOUR

T1 - Accurate determination of blood–brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI

T2 - a simulation and in vivo study on healthy subjects and multiple sclerosis patients

AU - Cramer, Stig P

AU - Larsson, Henrik B W

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

KW - Adult

KW - Algorithms

KW - Blood-Brain Barrier

KW - Computer Simulation

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Models, Biological

KW - Multiple Sclerosis

KW - Permeability

KW - Sensitivity and Specificity

KW - Young Adult

U2 - 10.1038/jcbfm.2014.126

DO - 10.1038/jcbfm.2014.126

M3 - Journal article

C2 - 25074746

SN - 0271-678X

VL - 34

SP - 1655

EP - 1665

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 10

ER -