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. 2014 Oct;34(10):1655-65.
doi: 10.1038/jcbfm.2014.126. Epub 2014 Jul 30.

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

Stig P Cramer  1 , Henrik B W Larsson  2
Affiliations

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

Stig P Cramer et al. J Cereb Blood Flow Metab. 2014 Oct.

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.

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Figures

Figure 1
Figure 1
F=20 ml/100 g/min; Vb=2 ml/100 g/min. Estimated Ki (y-axis) based on 1,000 simulations plotted against true Ki (x-axis). Dotted line represents the identity line. Vertical full lines represent the precision of the measurement (s.d. 2). eTofts, extended Tofts model; F, cerebral blood flow; Ki, permeability; Tik-2C, Tikhonov two-compartment model; Vb, cerebral blood volume.
Figure 2
Figure 2
F=50 ml/100 g/min; Vb=3 ml/100 g/min. Estimated Ki (y-axis) based on 1,000 simulations plotted against true Ki (x-axis). Dotted line represents the identity line. Vertical full lines represent the precision of the measurement (s.d. 2). eTofts, extended Tofts model; F, cerebral blood flow; Ki, permeability; Tik-2C, Tikhonov two-compartment model; Vb, cerebral blood volume.
Figure 3
Figure 3
F=80 ml/100 g/min; Vb=6 ml/100 g/min. Estimated Ki (y-axis) based on 1,000 simulations plotted against true Ki (x-axis). Dotted line represents the identity line. Vertical full lines represent the precision of the measurement (s.d. 2). eTofts, extended Tofts model; F, cerebral blood flow; Ki, permeability; Tik-2C, Tikhonov two-compartment model; Vb, cerebral blood volume.
Figure 4
Figure 4
F=20 ml/100 g/min; Vb=2 ml/100 g/min. Estimated Ki (y-axis) based on 1,000 simulations plotted against true Ki (x-axis). Dotted line represents the identity line. Vertical full lines represent the precision of the measurement (s.d. 2). eTofts, extended Tofts model; F, cerebral blood flow; Ki, permeability; Tik-2C, Tikhonov two-compartment model; Vb, cerebral blood volume.
Figure 5
Figure 5
F=80 ml/100 g/min; Vb=6 ml/100 g/min. Estimated Ki (y-axis) based on 1,000 simulations plotted against true Ki (x-axis). Dotted line represents the identity line. Vertical full lines represent the precision of the measurement (s.d. 2). eTofts, extended Tofts model; F, cerebral blood flow; Ki, permeability; Tik-2C, Tikhonov two-compartment model; Vb, cerebral blood volume.
Figure 6
Figure 6
Permeability in basal gray matter (left column) and frontal white matter (right column) in 17 healthy controls estimated with Patlak, eTofts, and Tik-2C models with decreasing total measurement duration and time resolution. eTofts, extended Tofts model; Ki, permeability; Tik-2C, Tikhonov two-compartment model.
Figure 7
Figure 7
Permeability in eight visibly contrast-enhancing lesions (each line representing one lesion) estimated with Patlak, eTofts, and Tik-2C models with decreasing time resolution and total measurement duration. As true permeability increases, the Patlak model progressively underestimates permeability, hence supporting the findings from our simulations. All enhancing lesions were located in the periventricular region, with a mean area size of 29.3 mm2 (s.d. 21.3 mm2). There was no correlation between area size and permeability values. eTofts, extended Tofts model; Ki, permeability; Tik-2C, Tikhonov two-compartment model.
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