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Assessment of temporary cerebral effects induced by focused ultrasound with optical coherence tomography angiography

Meng-Tsan Tsai, Jia-Wei Zhang, Kuo-Chen Wei, Chih-Kuang Yeh, and Hao-Li Liu

Open Access Open Access

Abstract

Focused ultrasound (FUS) in combination with microbubbles temporally and locally increases the permeability of the blood-brain barrier (BBB) for facilitating drug delivery. However, the temporary effects of FUS on the brain microstructure and microcirculation need to be addressed. We used label-free optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the morphological and microcirculation changes in mouse brains due to FUS exposure at different power levels. Additionally, the recovery progress of the induced effects was studied. The results show that FUS exposure causes cerebral vessel dilation and can be identified and quantitatively analyzed via OCT/OCTA. Micro-hemorrhages can be detected when an excessive FUS exposure power is applied, causing the degradation of OCTA signal owing to strong scattering by leaked red blood cells (RBCs) and weaker backscattered intensity from RBCs in vessels. The vessel dilation effect due to FUS exposure was found to abate in several hours. This study demonstrates that the FUS-induced cerebral transiently dilated effects can be in-vivo differentiated and monitored with OCTA, and shows the feasibility of using OCT/OCTA as a novel tool for long-time monitoring of cerebral vascular dynamics during FUS-BBB opening process.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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Figures (7)
Fig. 1
Fig. 1 Schematic diagrams of (a) the FUS system and (b) the SS-OCT setup. FC: fiber coupler; DC: dispersion compensator; M: mirror; GV: two-axis galvanometer; SL: scanning lens; BD: balanced detector.

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Fig. 2
Fig. 2 2D OCT images of mouse brains obtained before (a)-(d) and at 30 minutes after the exposure to different FUS power levels of (e) 1 W, (f) 2 W (g) 2.5 W, and (h) 5 W, respectively. DM: dura mater, AM: arachnoid mater, SDS: subdural space, SAS: subarachnoid space, PM: pia mater, BV: blood vessel, and C: cortex. Yellow arrows represent the AM location before the exposure; red arrows represent the AM location after the exposure. The scalar bar in (h) represents 1 mm.

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Fig. 3
Fig. 3 (a)-(d) 2D OCT images of the same brain region as in Fig. 2(d) obtained at 60, 90, 120, and 150 minutes after FUS exposure. (e) The scattering intensity profiles along the transverse direction at the locations indicated by the yellow-dash lines in Figs. 2(d), 2(h), and 3(a)-3(d). BV: blood vessel. The scalar bar represents 1 mm.

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Fig. 4
Fig. 4 Corresponding MIP OCT angiographies of Fig. 2. (a)-(d) OCT angiographies obtained before FUS exposure. (e)-(h) OCT angiographies obtained at 30 minutes after FUS exposure at different power levels of 1, 2, 2.5, and 5 W, respectively. (i), (k) Photos of the entire brain of (g) and (h) by using Evans blue as the contrast agent (power is 2.5 W and 5W, respectively). (j), (l) Stained brain slices (power is 2.5W and 5W, respectively). White line in (i) and (k) indicate the corresponding locations of (j) and (l). The scalar bar in (h) represents 500 μm.

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Fig. 5
Fig. 5 Time series of (a) R and (b) RVD values obtained without FUS exposure (0-W case) and after FUS exposure with different FUS power of 1, 2, and 2.5 W. The regions for the RVD estimation for each power level are marked by the white lines in Figs. 4(a)-4(c).

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Fig. 6
Fig. 6 (a)-(g) MIP angiographies of the mouse brain (the same brain measured in Fig. 4(a)) obtained at 210, 240, 270, 300, 330, 360, and 390 minutes after 1-W FUS exposure. (h)-(n) MIP angiographies of the mouse brain (the same brain measured in Fig. 4(b)) obtained at 210, 240, 270, 300, 330, 360, and 390 minutes after 2-W FUS exposure.

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Fig. 7
Fig. 7 Time series of (a) R and (b) RVD values measured after FUS exposure with different FUS power of 1 and 2 W. The regions for the RVD estimation were marked by the dash lines in Figs. 6(a) and 6(h).

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Equations (3)

Equations on this page are rendered with MathJax. Learn more.

S V i j k = 1 N ∑ k = 1 N ( I i j k − 1 N ∑ k = 1 N I i j k ) 2
R = D FUS D i
R V D = A FUS A i
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