Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression

Photoacoustic microscopy at super depths

Combining light and ultrasound in a single hybrid technology enables multiscale, high-resolution imaging deep into biological tissue

Video-rate photoacoustic microscopy of micro-vasculatures

We report the development of photoacoustic microscopy capable of video-rate high-resolution in-vivo imaging in deep tissue. A lightweight photoacoustic probe is made of a single-element broadband ultrasound transducer, a compact photoacoustic beam combiner, and a bright-field light delivery system. Focused broadband ultrasound detection provides a 44-μm lateral resolution and a 28-μm axial resolution. A multimode optical fiber is used to deliver laser pulses. The bright-field light delivery system can effectively improve the illumination efficiency. The photoacoustic probe weighs less than 40 grams and is mounted on a voice-coil scanner to acquire 40 cross-sectional images per second over several-mm range. The fast speed can effectively improve imaging throughput, reduce motion artifacts, and enable the visualization of highly dynamic biomedical processes. High-resolution micro-vascular imaging is successfully demonstrated

Ultrasound array photoacoustic microscopy for dynamic in vivo 3D imaging

Using realtime ultrasound array photoacoustic microscopy (UA-PAM), we demonstrated the feasibility of noninvasive in vivo imaging of human pulsatile dynamics, as well as 3-D dynamic imaging of sentinel lymph nodes (SLNs) in a murine model. The system, capable of realtime B-scan imaging at 50 Hz and high-speed 3-D imaging, was validated by imaging the subcutaneous microvasculature in rats and humans. After the validation, a human superficial palmar was imaged, and its pulsatile dynamics monitored, with 20-ms B-scan imaging temporal resolution. In addition, noninvasive photoacoustic sentinel lymph node (SLN) mapping with high spatial resolution has the potential to reduce the false negative rate and eliminate the use of radioactive tracers. Upon intra-dermal injection of Evans blue, the system maps SLNs accurately in mice and rats. Furthermore, the ~6 s 3-D imaging temporal resolution offers the capability to quantitatively and noninvasively monitor the dye dynamics in SLNs in vivo through sequential 3-D imaging. The demonstrated capability suggests that high-speed 3-D photoacoustic imaging should facilitate the understanding of the dynamics of various dyes in SLNs, and potentially help identify SLNs with high accuracy. With the results shown in this study, we believe that UA-PAM can potentially enable many new possibilities for studying functional and physiological dynamics in both preclinical and clinical imaging settings

Carbon nanoparticles as a multimodal thermoacoustic and photoacoustic contrast agent

We demonstrated the potential of carbon nanoparticles (CNPs) as exogenous contrast agents for both thermoacoustic (TA) tomography (TAT) and photoacoustic (PA) tomography (PAT). In comparison to deionized water, the CNPs provided a four times stronger signal in TAT at 3 GHz. In comparison to blood, The CNPs provided a much stronger signal in PAT over a broad wavelength range of 450-850 nm. Specifically, the maximum signal enhancement in PAT was 9.4 times stronger in the near-infrared window of 635-670 nm. In vivo blood-vessel PA imaging was performed non-invasively on a mouse femoral area. The images, captured after the tail vein injection of CNPs, show a gradual enhancement of the optical absorption in the vessels by up to 230%. The results indicate that CNPs can be potentially used as contrast agents for TAT and PAT to monitor the intravascular or extravascular pathways in clinical applications

Mouse brain imaging using photoacoustic computed tomography

Photoacoustic computed tomography (PACT) provides structural and functional information when used in small animal brain imaging. Acoustic distortion caused by bone structures largely limits the deep brain image quality. In our work, we present ex vivo PACT images of freshly excised mouse brain, intending that can serve as a gold standard for future PACT in vivo studies on small animal brain imaging. Our results show that structures such as the striatum, hippocampus, ventricles, and cerebellum can be clearly di erentiated. An artery feature called the Circle of Willis, located at the bottom of the brain, can also be seen. These results indicate that if acoustic distortion can be accurately accounted for, PACT should be able to image the entire mouse brain with rich structural information

Photoacoustic microscopy at super depths

Combining light and ultrasound in a single hybrid technology enables multiscale, high-resolution imaging deep into biological tissue

Molecular photoacoustic imaging using gold nanoparticles as a contrast agent

Gold nanoparticles have received much attention due to their potential diagnostic and therapeutic applications. Gold nanoparticles are attractive in many biomedical applications because of their biocompatibility, easily modifiable surfaces for targeting, lack of heavy metal toxicity, wide range of sizes (35-100 nm), tunable plasmonic resonance peak, encapsulated site-specific drug delivery, and strong optical absorption in the near-infrared regime. Specifically, due to their strong optical absorption, gold nanoparticles have been used as a contrast agent for molecular photoacoustic (PA) imaging of tumor. The plasmonic resonance peak of the gold nanocages (AuNCs) was tuned to the near-infrared region, and the ratio of the absorption cross-section to the extinction cross-section was approximately ~70%, as measured by PA sensing. We used PEGylated gold nanocages (PEG-AuNCs) as a passive targeting contrast agent on melanomas. After 6-h intravenous injection of PEG-AuNCs, PA amplitude was increased by ~14 %. These results strongly suggest PA imaging paired with AuNCs is a promising diagnostic tool for early cancer detection

Compressed sensing in photoacoustic tomography with in vivo experiments

The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition rate and the number of parallel ultrasound detecting channels. Reconstructing PACT image with a less number of measurements can effectively accelerate the data acquisition and reduce the system cost. Recently emerged Compressed Sensing (CS) theory enables us to reconstruct a compressible image with a small number of projections. This paper adopts the CS theory for reconstruction in PACT. The idea is implemented as a non-linear conjugate gradient descent algorithm and tested with phantom and in vivo experiments