Guan Xu

Photoacoustic spectrum analysis for microstructure characterization in biological tissue: A feasibility study

This study investigates the feasibility of characterizing the microstructures within a biological tissue by analyzing the frequency spectrum of the photoacoustic signal from the tissue. Hypotheses are derived from theoretical analyses on the relationships between the dimensions/concentrations of the photoacoustic sources within the region-of-interest and the linear model fitted to the power spectra of photoacoustic signals. The hypotheses are validated, following the procedures of ultrasound spectrum analysis, by simulations and experiments with phantoms fabricated by embedding the polyethylene microspheres in porcine gelatin, indicating that photoacoustic spectrum analysis could be a potential tool for characterizing microstructures in biological samples.

The Functional Pitch of an Organ: Quantification of Tissue Texture with Photoacoustic Spectrum Analysis

PURPOSE To investigate the use of photoacoustic (PA) spectrum analysis (PASA) to identify microstructural changes corresponding to fat accumulation in mouse livers ex vivo and in situ. MATERIALS AND METHODS The laboratory animal protocol for this work was approved by the university committee on use and care of animals. Six mice with normal livers and six mice with fatty livers were examined ex vivo with a PA system at 1200 nm, and nine similar pairs of mice were examined at 532 nm. To explore the feasibility of this technique for future study in an in vivo mouse model, an additional pair of normal and fatty mouse livers was scanned in situ with an ultrasonographic (US) and PA dual-modality imaging system. The PA signals acquired were analyzed by using the proposed PASA method. Results of the groups were compared by using the Student t test. RESULTS Prominent differences between the PASA parameters from the fatty and normal mouse livers were observed. The analysis of the PASA parameters from six normal and six fatty mouse livers indicates that there are differences of up to 5 standard deviations between the PASA parameters of the normal livers and those of the fatty livers at 1200 nm; for parameters from nine normal and nine fatty mouse livers at 532 nm, the differences were approximately 2 standard deviations (P < .05) for each PASA parameter. CONCLUSION The results supported our hypothesis that the PASA allows quantitative identification of the microstructural changes that differentiate normal from fatty livers. Compared with that at 532 nm, PASA at 1200 nm is more reliable for fatty liver diagnosis. Online supplemental material is available for this article.

Photoacoustic and ultrasound dual-modality imaging of human peripheral joints

Abstract. A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.

Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization

Abstract. Photoacoustic tomography (PAT) offers structural and functional imaging of living biological tissue with highly sensitive optical absorption contrast and excellent spatial resolution comparable to medical ultrasound (US) imaging. We report the development of a fully integrated PAT and US dual-modality imaging system, which performs signal scanning, image reconstruction, and display for both photoacoustic (PA) and US imaging all in a truly real-time manner. The back-projection (BP) algorithm for PA image reconstruction is optimized to reduce the computational cost and facilitate parallel computation on a state of the art graphics processing unit (GPU) card. For the first time, PAT and US imaging of the same object can be conducted simultaneously and continuously, at a real-time frame rate, presently limited by the laser repetition rate of 10 Hz. Noninvasive PAT and US imaging of human peripheral joints in vivo were achieved, demonstrating the satisfactory image quality realized with this system. Another experiment, simultaneous PAT and US imaging of contrast agent flowing through an artificial vessel, was conducted to verify the performance of this system for imaging fast biological events. The GPU-based image reconstruction software code for this dual-modality system is open source and available for download from http://sourceforge.net/projects/patrealtime.

Nonlinear optical properties of neodymium-doped bismuth titanate thin films using Z-scan technique

Bi3.75Nd0.25Ti3O12 (BNT0.25) thin film with good surface morphology and layered perovskite structure was fabricated by a metalorganic solution deposition process. Their fundamental optical constants (the band gap, linear refractive index, and absorption coefficient) were obtained through optical transmittance measurements. The nonlinear optical properties of the film were investigated by using a top-hat Z-scan method. Large positive nonlinear refractive index n2 and two-photon absorption coefficient β were determined to be 4.52×10−7 esu and 5.24×10−7 m/W, respectively. All of the results show that the BNT0.25 thin film is promising for applications in nonlinear optical devices.

Photoacoustic spectrum analysis for microstructure characterization in biological tissue: Analytical model

Photoacoustic spectrum (PA) analysis (PASA) has been found to have the ability to identify the microstructures in phantoms and biological tissues. PASA adopts the procedures in ultrasound spectrum analysis, although the signal generation mechanisms related to ultrasound backscatter and PA wave generation differ. The purpose of this study was to theoretically validate PASA. The analytical solution to the power spectrum of PA signals generated by identical microspheres following discrete uniform random distribution in space was derived. The simulation and experiment validation of the analytical solution include: (i) the power spectrum profile of a single microsphere with a diameter of 300 μm, and (ii) the PASA parameters of the PA signals generated by randomly distributed microspheres 100, 200, 300, 400 and 500 μm in diameter, at concentrations of 30, 60, 120, 240, 480 per 1.5(3) cm(3) in the observation range 0.5-13 MHz.

High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy

Conventional gold standard histopathologic diagnosis requires information of both high resolution structural and chemical changes in tissue. Providing optical information at ultrasonic resolution, photoacoustic (PA) technique could provide highly sensitive and highly accurate tissue characterization noninvasively in the authentic in vivo environment, offering a replacement for histopathology. A two-dimensional (2D) physio-chemical spectrogram (PCS) combining micrometer to centimeter morphology and chemical composition simultaneously can be generated for each biological sample with PA measurements at multiple optical wavelengths. This spectrogram presents a unique 2D “physio-chemical signature” for any specific type of tissue. Comprehensive analysis of PCS, termed PA physio-chemical analysis (PAPCA), can lead to very rich diagnostic information, including the contents of all relevant molecular and chemical components along with their corresponding histological microfeatures, comparable to those accessible by conventional histology. PAPCA could contribute to the diagnosis of many diseases involving diffusive patterns such as fatty liver.

Characterization of bone microstructure using photoacoustic spectrum analysis

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and the deterioration in bone microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic (PA) signal from the bone. Modeling and numerical simulation of PA signal were performed on trabecular bone simulations and CT scans with different trabecular thicknesses. The resulting quasi-linear photoacoustic spectra were fittted by linear regression, from which the spectral parameter slope was quantified. The simulation based on two different models both demonstrate that bone specimens with thinner trabecular thicknesses have higher slope. Experiment on osteoporotic rat femoral heads with different mineral content was conducted. The finding from the experiment was in good agreement with the simulation, demonstrating that the frequency-domain analysis of PA signals can provide an objective assessment of bone microstructure and deterioration. Considering that PA measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and non-calcified tissues, this new bone evaluation method based on photoacoustic spectral analysis holds potential for clinical management of osteoporosis and other bone diseases.

Quantifying Gleason scores with photoacoustic spectral analysis: feasibility study with human tissues

Gleason score is a highly prognostic factor for prostate cancer describing the microscopic architecture of the tumor tissue. The standard procedure for evaluating Gleason scores, namely biopsy, is to remove prostate tissue for observation under microscope. Currently, biopsies are guided by transrectal ultrasound (TRUS). Due to the low sensitivity of TRUS to prostate cancer (PCa), non-guided and saturated biopsies are frequently employed, unavoidably causing pain, damage to the normal prostate tissues and other complications. More importantly, due to the limited number of biopsy cores, current procedure could either miss early stage small tumors or undersample aggressive cancers. Photoacoustic (PA) measurement has the unique capability of evaluating tissue microscopic architecture information at ultrasonic resolution. By frequency domain analysis of the broadband PA signal, namely PA spectral analysis (PASA), the microscopic architecture within the assessed tissue can be quantified. This study investigates the feasibility of evaluating Gleason scores by PASA. Simulations with the classic Gleason patterns and experiment measurements from human PCa tissues have demonstrated strong correlation between the PASA parameters and the Gleason scores.

Non-Contact Photoacoustic Imaging Using a Commercial Heterodyne Interferometer

Most current photoacoustic imaging (PAI) systems employ piezoelectric transducers to receive photoacoustic signals, which requires coupling medium to facilitate photoacoustic wave propagation and are not favored in many applications. Here, we report an all-optical non-contact PAI system based on a commercial heterodyne interferometer working at 1550 nm. The interferometer remotely detects ultrasound-induced surface vibration and does not involve any physical contact with the sample. The theoretically predicated and experimentally measured noise equivalent detection limits of the optical sensor are about 4.5 and 810 Pa over 1.2 MHz bandwidth. Using a raster-scan PAI system equipped with the non-contact design, stereotactic boundaries of an artificial tumor in a pig brain were accurately delineated. The non-contact design also enables the tomographic PAI of biological tissue samples in a non-invasive manner. The preliminary results and analyses reveal that the heterodyne interferometer-based non-contact PAI system holds good potential in biomedical imaging.