Liangzhong Xiang

Functional imaging of cerebrovascular activities in small animals using high-resolution photoacoustic tomography.

Photoacoustic imaging (PAI) is a noninvasive, nonionizing modality based on the differences in light absorption of various biological tissues. PAI utilizes the endogenous contrast characteristics of traditional optical imaging, while benefiting from high spatial resolution of the ultrasound imaging. A PAI system was developed to reconstruct the two-dimensional cross section image and to visualize the cerebrovascular activities of mouse in vivo. The spatial resolution of the PAI system was determined to be 0.110 mm by a two-point-source phantom with the Rayleigh criterion. The potential applications of the system were clearly demonstrated by successfully mapping a traumatic lesion in the mouse brain cerebral cortex, by its ability to monitor physiological changes in the brain due to carotid ligation and drug stimulation, and two-dimensional sliced images of a traumatic mouse brain at different depths were also provided. Our experimental results indicate that PAI has the potential for studying of traumatic brain injury and physiological functions of the brain.

Noninvasive photoacoustic imaging of the developing vasculature during early tumor growth

In this study, we monitor the progress of vasculature in early tumor growth using photoacoustic imaging over a 20 day period after subcutaneous inoculation of breast cancer tumor cells in a mouse. With 532 nm laser pulses employed as an irradiation source, the photoacoustic images were obtained through the photoacoustic signals received by a hydrophone in orthogonal mode. The morphological characteristics of vasculature in tumor region are clearly resolved in the photoacoustic images, and the change in structure as well as the increase in density can be identified. Moreover, the average photoacoustic signal strength of vasculature in tumor region, which is highly correlated with the total hemoglobin concentration of blood, is enhanced during early tumor growth. These results indicate the feasibility of detecting early stage tumor and monitoring the progress of anti-angiogenic therapy by photoacoustic imaging.

Fast full-view photoacoustic imaging by combined scanning with a linear transducer array

We present a fast full-view photoacoustic imaging system for visualizing tissue structures using a linear transducer array with combined scan. In this system, a 128-element linear transducer array was used to detect photoacoustic signals by combined scanning of electronic scan and mechanical scan. An improved limited-field filtered back projection algorithm with directivity factors was applied to reconstruct the optical absorption distribution. The experiments of phantoms and in vivo blood vessels in a rat brain were performed with this system. And a clear view of the curve boundaries of objects and the network of blood vessels of rats brain were acquired. The experimental results demonstrate the multi-element photoacoustic imaging system has the ability of imaging complicated structures of objects.

4-D Photoacoustic Tomography

Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy.

Photoacoustic molecular imaging with antibody-functionalized single-walled carbon nanotubes for early diagnosis of tumor

Single-walled carbon nanotubes (SWNT) in a poly(ethylene)ghycol solution are a biocompatible transporters with strong optical absorption in the near-infrared region, in which the biological tissue is almost transparent with very low absorbance. Here, antibody-functionalized SWNTs for tumor early detection with photoacoustic molecular imaging in vivo are reported. To lay the groundwork for this goal and insure system stability, images were collected in tissue simulating phantoms to determine appropriate detectable concentrations of SWNTs. Preliminary in vitro and in vivo results showed that a high contrast and a high efficient targeting of integrin alpha(v)beta(3) positive U87 human glioblastoma tumours in mice could be achieved. The nontoxicity of functionalized SWNTs has also been demonstrated in our experiment; this feature ensures that SWNTs can be used for clinical applications. This study suggests that photoacoustic molecular imaging with antibody-functionalized SWNTs has the potential to be an effective early tumor diagnosis method.

Real-time optoacoustic monitoring of vascular damage during photodynamic therapy treatment of tumor

The optoacoustic technique is a noninvasive imaging method with high spatial resolution. It potentially can be used to monitor anatomical and physiological changes. Photodynamic therapy (PDT)-induced vascular damage is one of the important mechanisms of tumor destruction, and real-time monitoring of vascular changes can have therapeutic significance. A unique optoacoustic system is developed for neovascular imaging during tumor phototherapy. In this system, a single-pulse laser beam is used as the light source for both PDT and for concurrently generating ultrasound signals for optoacoustic imaging. To demonstrate its feasibility, this system is used to observe vascular changes during PDT treatment of chicken chorioallantoic membrane (CAM) tumors. The photosensitizer used in this study is protoporphyrin IX (PpIX) and the laser wavelength is 532 nm. Neovascularization in tumor angiogenesis is visualized by a series of optoacoustic images at different stages of tumor growth. Damage of the vascular structures by PDT is imaged before, during, and after treatment. Rapid, real-time determination of the size of targeted tumor blood vessels is achieved, using the time difference of positive and negative ultrasound peaks during the PDT treatment. The vascular effects of different PDT doses are also studied. The experimental results show that a pulsed laser can be conveniently used to hybridize PDT treatment and optoacoustic imaging and that this integrated system is capable of quantitatively monitoring the structural change of blood vessels during PDT. This method could be potentially used to guide PDT and other phototherapies using vascular changes during treatment to optimize treatment protocols, by choosing appropriate types and doses of photosensitizers and doses of light.

Noninvasive monitoring of traumatic brain injury and post-traumatic rehabilitation with laser-induced photoacoustic imaging

A photoacoustic imaging system was used for noninvasive monitoring of traumatic mouse brain in vivo with high-quality reconstructed images. Traumatic lesions accompanying with hemorrhage in the mouse cortical surface were accurately mapped, and foreign bodies of two small copper wires inserted in the mouse brain were also detected. Furthermore, the time course of morphological changes of cerebral blood during rehabilitation process of a mouse brain with traumatic brain injury was obtained using a series of photoacoustic images. Experimental results demonstrate that photoacoustic technique holds the potential for clinical applications in brain trauma and cerebrovascular disease detection.

High antinoise photoacoustic tomography based on a modified filtered backprojection algorithm with combination wavelet

How to extract the weak photoacoustic signals from the collected signals with high noise is the key to photoacoustic signal processing. We have developed a modified filtered backprojection algorithm based on combination wavelet for high antinoise photoacoustic tomography. A Q-switched-Nd: yttrium-aluminum-garnet laser operating at 532 nm is used as light source. The laser has a pulse width of 7 ns and a repetition frequency of 20 Hz. A needle polyvinylidene fluoride hydrophone with diameter of 1 mm is used to capture photoacoustic signals. The modified algorithm is successfully applied to imaging vascular network of a chick embryo chorioallantoic membrane in situ and brain structure of a rat brain in vivo, respectively. In the reconstructed images, almost all of the capillary vessels and the vascular ramifications of the chick embryo chorioallantoic membrane are accurately resolved, and the detailed brain structures of the rat brain organization are clearly identified with the skull and scalp intact. The experimental results demonstrate that the modified algorithm has much higher antinoise capacity, and can greatly improve the reconstruction image quality. The spatial resolution of the reconstructed images can reach 204 microm. The modified filtered back-projection algorithm based on the combination wavelet has the potential in the practical high-noise signal processing for deeply penetrating photoacoustic tomography.

Imaging-guided high-efficient photoacoustic tumor therapy with targeting gold nanorods

UNLABELLED Photoacoustic therapy using the large photoacoustic effect of agents for selectively killing cancer cells is demonstrated. Herein, a highly efficient photoacoustic treatment using gold nanorods (AuNRs) and its antitumor effect are reported. Folic acid conjugated AuNRs are designed to specifically target folate receptor-expressing cancer cells. Following photoacoustic treatment, most of the cancer cells with intracellular AuNRs die within 20s. Compared with single-walled carbon nanotubes and indocyanine green containing nanoparticles, AuNRs can produce much stronger shock waves by absorbing the optical energy and thus induced the more efficient cell death at equal molar concentrations. In addition, the laser-induced shock waves can be detected for photoacoustic imaging. Our in vivo experiments demonstrated that the AuNR-mediated photoacoustic treatment resulted in efficient tumor suppression in mice. Thus, both efficient cancer cell diagnostics and selective photoacoustic treatment can be realized with a single-particle formulation. FROM THE CLINICAL EDITOR Nanotechnology has enabled the development of many novel methods for the treatment of cancer. One of these is photoacoustic therapy. In this article, the authors demonstrated the efficacy of Folic acid conjugated gold nanorods in killing cancer cells after photoacoustic treatment. The findings should provide impetus for future clinical studies.

X-ray acoustic computed tomography with pulsed x-ray beam from a medical linear accelerator

PURPOSE The feasibility of medical imaging using a medical linear accelerator to generate acoustic waves is investigated. This modality, x-ray acoustic computed tomography (XACT), has the potential to enable deeper tissue penetration in tissue than photoacoustic tomography via laser excitation. METHODS Short pulsed (μs-range) 10 MV x-ray beams with dose-rate of approximately 30 Gy∕min were generated from a medical linear accelerator. The acoustic signals were collected with an ultrasound transducer (500 KHz central frequency) positioned around an object. The transducer, driven by a computer-controlled step motor to scan around the object, detected the resulting acoustic signals in the imaging plane at each scanning position. A pulse preamplifier, with a bandwidth of 20 KHz-2 MHz at -3 dB, and switchable gains of 40 and 60 dB, received the signals from the transducer and delivered the amplified signals to a secondary amplifier. The secondary amplifier had bandwidth of 20 KHz-30 MHz at -3 dB, and a gain range of 10-60 dB. Signals were recorded and averaged 128 times by an oscilloscope. A sampling rate of 100 MHz was used to record 2500 data points at each view angle. One set of data incorporated 200 positions as the receiver moved 360°. The x-ray generated acoustic image was then reconstructed with the filtered back projection algorithm. RESULTS The x-ray generated acoustic signals were detected from a lead rod embedded in a chicken breast tissue. The authors found that the acoustic signal was proportional to the x-ray dose deposition, with a correlation of 0.998. The two-dimensional XACT images of the lead rod embedded in chicken breast tissue were found to be in good agreement with the shape of the object. CONCLUSIONS The first x-ray acoustic computed tomography image is presented. The new modality may be useful for a number of applications, such as providing the location of a fiducial, or monitoring x-ray dose distribution during radiation therapy. Although much work is needed to improve the image quality of XACT and to explore its performance in other irradiation energies, the benefits of this modality, as highlighted in this work, encourage further study.