Synopsis

Water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI was recently proposed for non-contrast assessment of blood-brain barrier (BBB) permeability to water. However, this approach has not been directly compared with contrast-based method. In this study, we used Gd-based MRI method to validate the WEPCAST MRI. Two methods provide consistent results, suggesting that WEPCAST MRI has a potential to become an alternate to clinical contrast-based BBB permeability assessment.

INTRODUCTION

METHODS

MRI experiments

Six healthy subjects (33.5±14.7years, 5F) were studied. WEPCAST MRI¹ (see Figure 1 for sequence diagram and signal model) was performed in mid-sagittal plane with the following parameters: labeling-duration=2000ms, post-labeling delay=3500ms, encoding velocity (V_enc)=15cm/s, followed by a M₀ scan with same V_enc and a TR=10000ms. In addition, a dynamic contrast-agent scan was performed in which 30 T₁-weighted images (multi-echo VASO MRI sequence²) were acquired with contrast agent injection (Prohance, 0.1mmol/kg) taking place at the beginning of the 4^th dynamic (see Figure 2 for scan timing illustration and signal model).

WEPCAST MRI data processing

Details of WEPCAST processing can be found in Lin et al¹. Briefly, phase-contrast velocity-encoded images (which measure vessel signals only) were collected for control and label conditions (like ASL), and their subtraction yielded arterially labeled signals. ROIs were manually drawn in the superior sagittal sinus (SSS) and the resulting signal was used to quantify water extraction fraction (E). Then BBB permeability, denoted by permeability-surface-area product (PS_WEPCAST), is estimated by: $$$PS_{WEPCAST}=-ln(1-E)\times f(mL/100g/min)$$$, where f is global cerebral blood flow (CBF) and is measured by flow-sensitive MRI in the internal carotid and vertebral arteries³.

VASO MRI data processing

The contrast-agent scan used a VASO MRI sequence because the VASO sequence is designed such that the pre-contrast blood signal is 0 while the post-contrast blood signal is at equilibrium when Gd concentration is sufficiently high (e.g.>0.5mM)². The advantage is that the effect of cerebral blood volume (CBV) and PS can be temporally separated.

The quantitative analysis focused on gray matter (GM) ROI. Initial concentration of Gd was estimated from the T₂ difference between pre- and post-contrast images. Gd concentration decay was modeled as bi-exponential function. A two-compartment water exchange model was applied to the VASO signal time course², and a non-linear fitting yielded the estimation of three physiological parameters: PS_VASO,gm, CBV and Gd decay rate. To facilitate the comparison of contrast-agent results with that of WEPCAST MRI which is a global measurement and reflects an average of gray and white matter PS, PS_VASO,gm was converted to PS_VASO,global using: $$$PS_{VASO,global}=PS_{VASO,gm}\times\frac{V_{gm}}{V_{gm}+V_{wm}}+R\times PS_{VASO,gm}\times\frac{V_{wm}}{V_{gm}+V_{wm}}$$$, where V_gm and V_wm are volumes of gray and white matter, R is the ratio of white matter and gray matter PS and was assumed to be 0.27 based on CBV ratio⁴.

RESULTS AND DISCUSSION

Figure 3 shows representative WEPCAST control, label and difference images from one subject. Because of our phase-contrast flow-encoded acquisition scheme, vessel signals are selectively measured and tissue signals (which reflects perfusion) are successfully suppressed. Based on the signal at SSS, the average PS_WEPCAST for six subjects was 135.5±18.1 ml/100g/min.

Figure 4a shows dynamic VASO images (pre- and post-contrast) for the same subject as in Figure 3. The time course of gray-matter signal and the corresponding model fitting are shown in Figure 4b. It can be seen that, following Gd injection, VASO signal revealed an immediate increase due to the presence of the contrast agent. As the concentration of the contrast agent decreases with time, the VASO signal revealed a biphasic decay. The early fast decay is primarily attributed to BBB exchange effect, as the CBV effect is not affected by the Gd concentration during this time period. The late-phase slow decay is more attributed to CBV effect since the water exchange contribution becomes lower at later time period². The model fitting gives an average PS_VASO,global of six subjects of 164.3±21.7 ml/100g/min.

Figure 5 shows a scatter plot between PS_WEPCAST and PS_VASO,global. It can be seen that WEPCAST MRI showed a strong correlation with Gd-based BBB method (R²=0.75 and p=0.025).

CONCLUSION

Acknowledgements

References

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2. Uh J, Lewis-Amezcua K, Varghese R, Lu H. On the measurement of absolute cerebral blood volume (CBV) using vascular-space-occupancy (VASO) MRI. Magn Reson Med 2009;61:659-667.

3. Peng SL, Su P, Wang FN, Cao Y, Zhang R, Lu H, Liu P. Optimization of phase-contrast MRI for the quantification of whole-brain cerebral blood flow. J Magn Reson Imaging 2015;42:1126-1133.

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