Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for
safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood
vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of
chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood
vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with
fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was
applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood
vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized
blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal
characteristics of EB that was transvascularly delivered to the target tissue in the brain.
Acoustic-resolution photoacoustic microscopy (AR-PAM) with dark-field confocal illumination enables unique
high-resolution visualization of chromophores in tissue, such as microvasculatures, within depths of a few millimeters.
However, most current systems are bulky and use complex optical components for illumination, thus requiring highly
sensitive alignment. In this study, we developed a compact alignment-free acoustic-resolution photoacoustic imaging
system with simple fiber illumination. Four optical fibers were placed in four directions around a high-frequency
(30-MHz) ultrasound sensor attached with the high-numerical-aperture acoustic lens. The setting angle of the fibers were
determined to form a dark field on the tissue surface under the acoustic lens and for the four light beams from the fibers
to be combined near the focal point of the acoustic lens, i.e., at a depth of around 1.2 mm in the tissue. The acoustic lens
and output ends of the fibers were capped with an acoustically and optically transparent engineering plastic sheet, whose
surface can be directly placed and scanned on the tissue surface with ultrasound gel. The diameter and height of this
imaging head were as small as 32 mm and 27 mm respectively. The phantom study showed that the lateral signal
spreading was 120 μm, which agreed well with the theoretical value of 112 μm. With the system, we attempted to image
vasculatures in the rat skin, demonstrating high-contrast visualization of the blood vessels of a few hundred micrometers
in diameter in the tissue.
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