We propose using noninvasive longitudinal optical-resolution photoacoustic microscopy (L-ORPAM) to quantify blood flow flux, oxygen saturation (sO2), and thereby the metabolic rate of oxygen (MRO2), for a renal tumor model in the same mouse over weeks to months. Experiments showed that the sO2 difference between the artery and vein decreased greatly due to the arteriovenous shunting effect during tumor growth. Moreover, hypermetabolism was exhibited by an increase in MRO2.
Accurate quantification of microvasculature remains of interest in fundamental pathophysiological studies and clinical trials. Current photoacoustic microscopy can noninvasively quantify properties of the microvasculature, including vessel density and diameter, with a high spatial resolution. However, the depth range of focus (i.e., focal zone) of optical-resolution photoacoustic microscopy (OR-PAM) is often insufficient to encompass the depth variations of features of interest—such as blood vessels—due to uneven tissue surfaces. Thus, time-consuming image acquisitions at multiple different focal planes are required to maintain the region of interest in the focal zone. We have developed continuous three-dimensional motorized contour-scanning OR-PAM, which enables real-time adjustment of the focal plane to track the vessels’ profile. We have experimentally demonstrated that contour scanning improves the signal-to-noise ratio of conventional OR-PAM by as much as 41% and shortens the image acquisition time by 3.2 times. Moreover, contour-scanning OR-PAM more accurately quantifies vessel density and diameter, and has been applied to studying tumors with uneven surfaces.
We have developed three-dimensional arbitrary trajectory (3-DAT) scanning, which can rapidly image vessels of interest over a large field of view (FOV) and maintain a high signal-to-noise ratio (SNR) along the depth direction. The concept of 3-DAT scanning was demonstrated by imaging a human hair within a FOV of 3.5 × 2.0 mm2. Further, we showed that hemoglobin oxygen saturation (sO2) and blood flow can be measured simultaneously. The frame rate was 67 times faster than a traditional two-dimensional raster scan. We also observed sO2 dynamics in response to a switch between systemic hyperoxia and hypoxia.
Combined optical and mechanical scanning (COMS) in optical-resolution photoacoustic microscopy (OR-PAM) has provided five scanning modes with fast imaging speed and wide field of view (FOV). With two-dimensional (2D) galvanometer-based optical scanning, we have achieved a 2 KHz B-scan rate and 50 Hz volumetric-scan rate, which enables real-time tracking of cell activities in vivo. With optical-mechanical hybrid 2D scanning, we are able to image a wide FOV (10×8 mm2) within 150 seconds, which is 20 times faster than the conventional mechanical scan in our second-generation OR-PAM. With three-dimensional mechanical-based contour scanning, we can maintain the optimal signal-to-noise ratio and spatial resolution of OR-PAM while imaging objects with uneven surfaces, which is ideal for fast and quantitative studies of tumors and the brain.
We developed multi-contrast photoacoustic microscopy (PAM) for in vivo anatomical, functional, metabolic, and
molecular imaging. This technical innovation enables comprehensive understanding of the tumor microenvironment.
With multi-contrast PAM, we longitudinally determined tumor vascular anatomy, blood flow, oxygen saturation of
hemoglobin, and oxygen extraction fraction.
We have applied optical-resolution photoacoustic microscopy (OR-PAM) for longitudinal monitoring of cerebral
metabolism through the intact skull of mice before, during, and up to 72 hours after a 1-hour transient middle cerebral
artery occlusion (tMCAO). The high spatial resolution of OR-PAM enabled us to develop vessel segmentation
techniques for segment-wise analysis of cerebrovascular responses.
A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally
invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy
(OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral
artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2)
values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After
reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by
~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.