Xueding Wang

Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain

Imaging techniques based on optical contrast analysis can be used to visualize dynamic and functional properties of the nervous system via optical signals resulting from changes in blood volume, oxygen consumption and cellular swelling associated with brain physiology and pathology. Here we report in vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT). The advantage of PAT over pure optical imaging is that it retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound. We accurately mapped rat brain structures, with and without lesions, and functional cerebral hemodynamic changes in cortical blood vessels around the whisker-barrel cortex in response to whisker stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic changes. This neuroimaging modality holds promise for applications in neurophysiology, neuropathology and neurotherapy.

Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography

Simultaneous transcranial imaging of two functional parameters, the total concentration of hemoglobin and the hemoglobin oxygen saturation, in the rat brain in vivo is realized noninvasively using laser-based photoacoustic tomography (PAT). As in optical diffusion spectroscopy, PAT can assess the optical absorption of endogenous chromophores, e.g., oxygenated and deoxygenated hemoglobins, at multiple optical wavelengths. However, PAT can provide high spatial resolution because its resolution is diffraction-limited by photoacoustic signals rather than by optical diffusion. Laser pulses at two wavelengths are used sequentially to acquire photoacoustic images of the vasculature in the cerebral cortex of a rat brain through the intact skin and skull. The distributions of blood volume and blood oxygenation in the cerebral cortical venous vessels, altered by systemic physiological modulations including hyperoxia, normoxia, and hypoxia, are visualized successfully with satisfactory spatial resolution. This technique, with its prominent sensitivity to endogenous contrast, can potentially contribute to the understanding of the interrelationship between neural, hemodynamic, and metabolic activities in the brain.

Propagation of polarized light in birefringent turbid media: A Monte Carlo study

A detailed study, based on a Monte Carlo algorithm, of polarized light propagation in birefringent turbid media is presented in this paper. Linear birefringence, which results from the fibrous structures, changes the single scattering matrix and alters the polarization states of photons propagating in biological tissues. Some Mueller matrix elements of light backscattered from birefringent anisotropic turbid media present unusual intensity patterns compared with those for nonbirefringent isotropic turbid media. This result is in good agreement with the analytic results based on the double-scattering model. Degree of polarization, Stokes parameters, and diffuse reflectance as functions of linearly birefringent parameters based on numerical results and theoretical analysis are discussed and compared in an effort to understand the essential physical processes of polarized light propagation in fibrous tissues.

Noninvasive photoacoustic angiography of animal brains in vivo with near-infrared light and an optical contrast agent

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.

Imaging of tumor angiogenesis in rat brains in vivo by photoacoustic tomography

Green laser pulses at a wavelength of 532 nm from a Q-switched Nd:YAG laser were employed as irradiation sources for photoacoustic tomography (PAT). The vascular structure of the brain was imaged clearly, with optimal contrast, because blood has strong absorption near this wavelength. The photoacoustic images of rat brain tumors in this study clearly reveal the angiogenesis that is associated with tumors. Brain tumors can be identified based on the distorted vascular architecture of brain tumorigenesis and related vascular changes, such as hemorrhage. This research demonstrates that PAT can potentially provide a powerful tool for small-animal biological research.

Three-dimensional laser-induced photoacoustic tomography of mouse brain with the skin and skull intact

Three-dimensional laser-induced photoacoustic tomography, also referred to as optoacoustic tomography, is developed to image animal brain structures noninvasively with the skin and skull intact. This imaging modality combines the advantages of optical contrast and ultrasonic resolution. The distribution of optical absorption in a mouse brain is imaged successfully. The intrinsic optical contrast reveals not only blood vessels but also other detailed brain structures, such as the cerebellum, hippocampus, and ventriculi lateralis. The spatial resolution is primarily diffraction limited by the received photoacoustic waves. Imaged structures of the brain at different depths match the corresponding histological pictures well.

Multiple-bandwidth photoacoustic tomography

Photoacoustic tomography, also referred to as optoacoustic tomography, employs short laser pulses to generate ultrasonic waves in biological tissues. The reconstructed images can be characterized by the convolution of the structure of samples, the laser pulse and the impulse response of the ultrasonic transducer used for detection. Although the laser-induced ultrasonic waves cover a wide spectral range, a single transducer can receive only part of the spectrum because of its limited bandwidth. To systematically analyse this problem, we constructed a photoacoustic tomographic system that uses multiple ultrasonic transducers simultaneously, each at a different central frequency. The photoacoustic images associated with the different transducers were compared and analysed. The system was tested by imaging both mouse brains and phantom samples. The vascular vessels in the brain were revealed by all of the transducers, but the image resolutions differed. The higher frequency detectors provided better image resolution while the lower frequency detectors delineated the major structural traits with a higher signal-noise ratio.

Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles

Multimodality imaging based on complementary detection principles has broad clinical applications and promises to improve the accuracy of medical diagnosis. This means that a tracer particle advantageously incorporates multiple functionalities into a single delivery vehicle. In the present work, we explore a unique combination of MRI and photoacoustic tomography (PAT) to detect picomolar concentrations of nanoparticles. The nanoconstruct consists of ferromagnetic (Co) particles coated with gold (Au) for biocompatibility and a unique shape that enables optical absorption over a broad range of frequencies. The end result is a dual-modality probe useful for the detection of trace amounts of nanoparticles in biological tissues, in which MRI provides volume detection, whereas PAT performs edge detection.

Photoacoustic tomography of biological tissues with high cross-section resolution: Reconstruction and experiment

A modified back-projection approach deduced from an exact reconstruction solution was applied to our photoacoustic tomography of the optical absorption in biological tissues. Pulses from a Ti:sapphire laser (4.7 ns FWHM at 789.2 nm) were employed to generate a distribution of photoacoustic sources in a sample. The sources were detected by a wide-band nonfocused ultrasonic transducer at different positions around the imaging cross section perpendicular to the axis of the laser irradiation. Reconstructed images of phantoms made from chicken breast tissue agreed well with the structures of the samples. The resolution in the imaging cross section was experimentally demonstrated to be better than 60 microm when a 10 MHz transducer (140% bandwidth at -60 dB) was employed, which was nearly diffraction limited by the detectable photoacoustic waves of the highest frequency.

Monte Carlo model and single-scattering approximation of the propagation of polarized light in turbid media containing glucose

We present a single-scattering model as well as a Monte Carlo model of the effect of glucose on polarized light in turbid media. Glucose alters the Mueller-matrix patterns of diffusely backscattered and forward-scattered light because glucose molecules rotate the polarization plane of linearly polarized light. For example, the angles of rotation in Mueller-matrix elements S21 and S12 are linearly related to the concentration of glucose and increase with the source-detector distance. In the nondiffusion regime, the two models agree well with each other. In the diffusion regime, the single-scattering model is invalid, but there still exists a linear relationship between the angles of rotation in the Mueller-matrix elements and the concentration of glucose, which is predicted by the Monte Carlo model.