Meng-n Li

ELASTIC MODULUS MEASUREMENTS OF HUMAN LIVER AND CORRELATION WITH PATHOLOGY

Viral hepatitis causes fibrosis in the liver and may change mechanical properties of the liver. To evaluate the impact of fibrosis on elastic properties of human liver and to investigate potential benefits of ultrasonic elasticity imaging, 19 fresh human liver samples and 1 hepatic tumor (focal nodular hyperplasia) sample obtained during operations were studied. Simple 1-D estimates based on the cyclic compression-relaxation method were performed. Elastic modulus values were derived from the predetermined strain (controlled by a step motor system) and the stress values (measured by an electronic balance). Each specimen subsequently received histologic examination and a grade of liver fibrosis was scored from 0 to 5. Results show that the elastic modulus values were on the order of several hundreds to thousands of Pascals. The elastic modulus generally increased with the fibrosis grade, although some discrepancies existed at the middle grades of fibrosis (scores 1 to 3). The correlation between the fibrosis score and the elastic modulus was significant (p < 0.01) based on the statistical analysis using the Pearson correlation method. In addition, the relation between the elastic modulus and the fibrosis grade generally exhibited a quadratic trend. It was concluded that severity of fibrosis had a good correlation with stiffness of the liver. Results also indicated that the elasticity imaging of the liver may provide significant clinical values if the elastic modulus can be accurately measured.

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.

Adaptive imaging using the generalized coherence factor

Sound-velocity inhomogeneities degrade both spatial and contrast resolutions. This paper proposes a new adaptive imaging technique that uses the generalized coherence factor (GCF) to reduce the focusing errors resulting from the sound-velocity inhomogeneities. The GCF is derived from the spatial spectrum of the received aperture data after proper receive delays have been applied. It is defined as the ratio of the spectral energy within a prespecified low-frequency range to the total energy. It is demonstrated that the low-frequency component of the spectrum corresponds to the coherent portion of the received data, and that the high-frequency component corresponds to the incoherent portion. Hence, the GCF reduces to the coherence factor defined in the literature if the prespecified low-frequency range is restricted to dc only. In addition, the GCF is also an index of the focusing quality and can be used as a weighting factor for the reconstructed image. The efficacy of the GCF technique is demonstrated for focusing errors resulting from the sound-velocity inhomogeneities. Simulations and real ultrasound data are used to evaluate the efficacy of the proposed GCF technique. The characteristics of the GCF, including the effects of the signal-to-noise ratio and the number of channels, are also discussed. The GCF technique also is compared with the correlation-based technique and the parallel adaptive receive compensation algorithm; the improvement in image quality obtained with the proposed technique rivals that of the latter technique. In the presence of a displaced phase screen, this proposed technique also outperforms the correlation-based technique. Computational complexity and implementation issues also are addressed.

Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy

Dual-wavelength reflection-mode photoacoustic microscopy is used to noninvasively obtain three-dimensional (3-D) images of subcutaneous melanomas and their surrounding vasculature in nude mice in vivo. The absorption coefficients of blood and melanin-pigmented melanomas vary greatly relative to each other at these two optical wavelengths (764 and 584 nm). Using high-resolution and high-contrast photoacoustic imaging in vivo with a near-infrared (764-nm) light source, the 3-D melanin distribution inside the skin is imaged, and the maximum thickness of the melanoma (approximately 0.5 mm) is measured. The vascular system surrounding the melanoma is also imaged with visible light (584 nm) and the tumor-feeding vessels found. This technique can potentially be used for melanoma diagnosis, prognosis, and treatment planning.

Improved in vivo photoacoustic microscopy based on a virtual-detector concept.

Recently an in vivo high-resolution backward-mode photoacoustic microscope was developed that shows potential for applications in dermatology and related cancer research. However, the limited depth of focus of the large-numerical-aperture (NA) ultrasonic lens employed in this system causes the image quality to deteriorate significantly in the out-of-focus region. To solve this problem, we devised and explored, for the first time to our knowledge, a virtual-detector-based synthetic-aperture focusing technique, combined with coherence weighting, for photoacoustic microscopy with such a large-NA transducer. Images of phantoms show that the proposed technique improves the -6 dB lateral resolution from 49-379 to 46-53 microm and increases the signal-to-noise ratio by up to 29 dB, depending on the distance from the ultrasonic focal point. In vivo experiments show that the technique also provides a clearer representation of the vascular distribution in the rats scalp.

In vivo volumetric imaging of subcutaneous microvasculature by photoacoustic microscopy

Photoacoustic microscopy was developed to achieve volumetric imaging of the anatomy and functions of the subcutaneous microvasculature in both small animals and humans in vivo with high spatial resolution and high signal-to-background ratio. By following the skin contour in raster scanning, the ultrasonic transducer maintains focusing in the region of interest. Furthermore, off-focus lateral resolution is improved by using a synthetic-aperture focusing technique based on the virtual point detector concept. Structural images are acquired in both rats and humans, whereas functional images representing hemoglobin oxygen saturation are acquired in rats. After multiscale vesselness filtering, arterioles and venules in the image are separated based on the imaged oxygen saturation levels. Detailed structural information, such as vessel depth and spatial orientation, are revealed by volume rendering.

In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature

In this study, high resolution backward-mode photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. PAM takes advantage of the strong near-infrared absorption of nanoshells and their extravasation tendency from leaky tumor vasculatures for imaging. Subcutaneous tumors are grown on immunocompetent BALB/c mice. Polyethylene glycol (PEGylated) nanoshells with a peak optical absorption at approximately 800 nm are intravenously administered. With an 800-nm laser source, a prescan prior to nanoshell injection is taken to determine the background that is free of nanoshell accumulation. After injection, the 3-D nanoshell distribution at the tumor foci is monitored by PAM for 6 h. Experimental results show that accumulated nanoshells delineate the tumor position. Nanoshell accumulation is heterogeneous in tumors: more concentrated within the tumor cortex and largely absent from the tumor core. Because nanoshells have been recently demonstrated to enhance thermal therapy of subcutaneous tumors, we anticipate that PAM will be an important aid before, during, and after nanoshell thermal therapy.

Photoacoustic imaging of the microvasculature with a high-frequency ultrasound array transducer

Visualization of microvascular networks could provide new information about function and disease. We demonstrate the capabilities of a 30-MHz ultrasound array system for photoacoustic microscopy of small (< or = 300 microm) vessels in a rat. 3D images obtained by translating the array in the elevation direction are compared with photographs of excised skin. The system is shown to have 100-microm lateral resolution, 25-microm axial resolution, and 3-mm imaging depth. To our knowledge this is the first report on photoacoustic microscopy of the microvasculature with a high-frequency array transducer. It is anticipated that the system can be used for studying and diagnosing a number of diseases including cancer, atherosclerosis, dermatological disorders, and peripheral microvascular complications in diabetes.

Magnetic gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy

Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.

Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy

The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models.