Abstract. Vasoactive drugs are normally utilized to elevate mean artery pressure and maintain adequate organ perfusion in clinical treatment. During the injection, morphological changes and the subsequent oxygen supply alteration in the brain, e.g., possible hypoxia, are prone to introduce serious damage and even dysfunction to the brain. Therefore, multiparameter monitoring of cerebral microvasculature is necessary during drug injection. An optical-resolution photoacoustic microscopy was used to assess the effects of norepinephrine on microvasculature in the brain cortex of mice. In our experiments, the diameter, total hemoglobin (HbT) and oxygen saturation (SO 2 ) of single cerebral microvessels during tail vein injection of norepinephrine were analyzed. Following the injection, vasoconstriction was observed, and HbT and SO 2 were decreased in turn. The vessel diameter and HbT recovered back to the base value without further injection, while the SO 2 remained low throughout the observation period. Arterioles showed more acute constriction but a smaller decline in HbT during the injection compared with venules, while SO 2 in arterioles increased slightly without further drug injection but not in venules. Our results suggested that photoacoustic microscopy may become a new method for early and comprehensive evaluation of the effect of drugs on microvasculature in brain.

We developed a new reflection-mode optical-resolution photoacoustic microscopy (OR-PAM) based on the cooperation of a reflective objective and an ultrasonic transducer. The reflective objective is used to produce nearly diffraction-limited optical focusing, and the excited ultrasound waves are then directly detected by an ultrasonic transducer that was placed in the central cone of the objective. This new design avoids the coupling between optical focusing and ultrasound transmission in the reflection mode. Moreover, the proposed system is able to provide lateral resolution of 1.2 μm at 580 nm, penetration depth of 0.9 mm in biological tissues, and a work distance of 6.0 mm. We present in vivo imaging of the microvasculature in mouse ears and in vitro imaging of red blood cells (RBCs), which demonstrate the capability of the system to study microcirculation.

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The on-board flat-panel cone-beam computed tomography (CBCT) lacks molecular/functional information for current online image-guided radiation therapy (IGRT). It might not be adequate for adaptive radiation therapy (ART), particularly for biologically guided tumor delineation and targeting which might be shifted and/or distorted during the course of RT. A linear accelerator (Linac) gantry-mounted on-board imager (OBI) was proposed using a single photon counting detector (PCD) panel to achieve single photon emission computed tomography (SPECT), energy-resolved spectral CT, and conventional CBCT triple on-board imaging, which might facilitate online ART with an addition of volumetric molecular/functional imaging information. Methods: The system was designed and evaluated in the GATE Monte Carlo platform. The OBI system including a kV-beam source and a pixelated cadmium zinc telluride (CZT) detector panel mounted on a medical Linac orthogonally to the MV beam direction was designed to obtain online CBCT, spectral CT, and SPECT tri-modal imaging of patients in the treatment room. The spatial resolutions of the OBI system were determined by imaging simulated phantoms. The CBCT imaging was evaluated by a simulated contrast phantom. A PMMA phantom containing gadolinium was imaged to demonstrate quantitative imaging of spectral-CT/CBCT of the system. The capability of tri-modal imaging of the OBI was demonstrated using three different spectral CT imaging methods to differentiate gadolinium, gold, calcium within simulated PMMA and the SPECT to image radioactive 99m Tc distribution. The dual-isotope SPECT imaging of the system was also evaluated by imaging a phantom containing 99m Tc and 123 I. The radiotherapy-related parameters of iodine contrast fraction and virtual non-contrast (VNC) tissue electron density in the Kidney1 inserts of a simulated phantom were decomposed using the Bayesian eigentissue decomposition method for contrastenhanced CBCT/spectral-CT of the OBI in a single scan. Results: The spatial resolutions of CBCT and SPECT of the OBI were determined to be 15.1 lp/cm at 10% MTF and 4.8-12 mm for radii of rotation of 10-40 cm, respectively. In CBCT image of the contrast phantom, most of the soft-tissue inserts were visible with sufficient spatial structure details. As compared to the CBCT image of gadolinium, the spectral CT image provided higher image contrasts. Calcium, gadolinium, and gold were separated well by using the spectral CT material imaging methods. The reconstructed distribution of 99m Tc agreed with the spatial position within the phantom. The two isotopes were separated from each other in dual-isotope SPECT imaging of the OBI. The iodine fractions and the VNC electron densities were estimated in the iodine-enhanced Kidney1 tissue inserts with reasonable RMS errors. The main procedures of the tri-modal imaging guided online ART workflow were presented with new functional features included. Conclusions: Using a single photon counting CZT detector panel, an on-board SPECT, spectral CT, and CBCT tr...

Scanning photoacoustic tomography with a piezoelectric double-ring sensor was explored to image biological tissues, and short laser pulses irradiated tissues to generate acoustic waves by thermoelastic expansion. The laser-induced photoacoustic waves were detected by a piezoelectric double-ring sensor. This double-ring sensor has the advantage that it is more sensitive in the forward direction compared with other conventional sensors. An optical fiber for illumination of the sample was integrated with the sensor, which enabled reflection-mode detection of ultrasonic waves. Consequently, two-dimension photoacoustic tomography of biological tissues could be obtained in a manner analogous to the ultrasound B-scan mode by a linear scan over the tissue surfaces. To reach a large depth, 1064nm laser light was used in our experiments. The experimental results showed that the reconstructed photoacoustic images agree well with the structures of the samples. It demonstrated that this sensor has potential to monitoring tumor angiogenesis, and antiangiogenic therapy in vivo.