Photoacoustic spectrum analysis (PASA) offers potential advantages in identifying optically absorbing microstructures in biological tissues. Working at high ultrasound frequency, PASA is capable of identifying the morphological features of cells based on their intrinsic optical absorption. Adipocyte size is correlated with metabolic disease risk in the form of diabetes mellitus, thus it can be adopted as a pathology predictor to evaluate the condition of obese patient, and can be helpful for assessing the patient response to bariatric surgery. In order to acquire adipocyte size, usually adipose tissue biopsy is performed and histopathology analysis is conducted. The whole procedure is not well tolerated by patients, and is also labor and cost intensive. An unmet need is to quantify and predict adipocyte size in a mild and more efficient way. This work aims at studying the feasibility to analyze the adipocyte size of human fat tissue using the method of PASA. PA measurements were performed at the optical wavelength of 1210 nm where lipid has strong optical absorption, enabling the study of adipocyte without need of staining. Both simulation and ex vivo experiments have been completed. Good correlation between the quantified photoacoustic spectral parameter slope and the average adipocyte size obtained by the gold-standard histology has been established. This initial study suggests the potential opportunity of applying PASA to future clinical management of obesity.
Gold nanoparticles (AuNPs) have been extensively explored as a model nanostructure in nanomedicine and have been widely used to provide advanced biomedical research tools in diagnostic imaging and therapy. Due to the necessity of targeting AuNPs to individual cells, evaluation and visualization of AuNPs in the cellular level is critical to fully understand their interaction with cellular environment. Currently imaging technologies, such as fluorescence microscopy and transmission electron microscopy all have advantages and disadvantages. In this paper, we synthesized AuNPs by femtosecond pulsed laser ablation, modified their surface chemistry through sequential bioconjugation, and targeted the functionalized AuNPs with individual cancer cells. Based on their high optical absorption contrast, we developed a novel, label-free imaging method to evaluate and visualize intracellular AuNPs using photoacoustic microscopy (PAM). Preliminary study shows that the PAM imaging technique is capable of imaging cellular uptake of AuNPs in vivo at single-cell resolution, which provide an important tool for the study of AuNPs in nanomedicine.
Sound velocity measurement is of great importance to the application of biomedical especially in the research of acoustic detection and acoustic tomography. Using correct sound velocities in each medium other than one unified sound propagation speed, we can effectively enhance sound based imaging resolution. Photoacoustic tomography (PAT), is defined as cross-sectional or three-dimensional (3D) imaging of a material based on the photoacoustic effect and it is a developing, non-invasive imaging method in biomedical research. This contribution proposes a method to concurrently calculate multiple acoustic speeds in different mediums. Firstly, we get the size of infra-structure of the target by B-mode ultrasonic imaging method. Then we build the photoacoustic (PA) image of the same target with different acoustic speed in different medium. By repeatedly evaluate the quality of reconstruct PA image, we dynamically calibrate the acoustic speeds in different medium to build a finest PA image. Thus, we take these speeds of sound as the correct acoustic propagation velocities in according mediums. Experiments show that our non-invasive method can yield correct speed of sound with less than 0.3% error which might benefit future research in biomedical science.
Photoacoustic (PA) technique involving both ultrasound and light has been explored for potential application in the assessment of bone health. The optical and ultrasound penetration in bone have been studied. The feasibility of conducting 3D PA imaging of bone, and performing quantitative evaluation of bone microstructures by using photoacoustic spectrum analysis (PASA) has also been investigated. The findings from the experiments demonstrate that PA measurement could offer information of bone mineral density and bone microstructure, both relevant to bone health.
Photoacoustic (PA) measurements encode the information associated with both physical microstructures and chemical contents in biological tissues. A two-dimensional physio-chemical spectrogram (PCS) can be formulated by combining the power spectra of PA signals acquired at a series of optical wavelengths. The analysis of PCS, or namely PA physio-chemical analysis (PAPCA), enables the quantification of the relative concentrations and the spatial distributions of a variety of chemical components in the tissue. This study validated the feasibility of PAPCA in characterizing liver conditions during the progression of non-alcoholic fatty liver disease. A catheter based setup facilitating measurement in deep tissues was also tested.
Laser-induced thermotherapy (LITT), i.e. tissue destruction induced by a local increase of temperature by means of laser light energy transmission, has been frequently used for minimally invasive treatments of various diseases such as benign thyroid nodules and liver cancer. The emerging photoacoustic (PA) imaging, when integrated with ultrasound (US), could contribute to LITT procedure. PA can enable a good visualization of percutaneous apparatus deep inside tissue and, therefore, can offer accurate guidance of the optical fibers to the target tissue. Our initial experiment demonstrated that, by picking the strong photoacoustic signals generated at the tips of optical fibers as a needle, the trajectory and position of the fibers could be visualized clearly using a commercial available US unit. When working the conventional US Bscan mode, the fibers disappeared when the angle between the fibers and the probe surface was larger than 60 degree; while working on the new PA mode, the fibers could be visualized without any problem even when the angle between the fibers and the probe surface was larger than 75 degree. Moreover, with PA imaging function integrated, the optical fibers positioned into the target tissue, besides delivering optical energy for thermotherapy, can also be used to generate PA signals for on-line evaluation of LITT. Powered by our recently developed PA physio-chemical analysis, PA measurements from the tissue can provide a direct and accurate feedback of the tissue responses to laser ablation, including the changes in not only chemical compositions but also histological microstructures. The initial experiment on the rat liver model has demonstrated the excellent sensitivity of PA imaging to the changes in tissue temperature rise and tissue status (from native to coagulated) when the tissue is treated in vivo with LITT.
Stiffness of arteries, especially small arteries, is an important marker for many diseases and a good parameter to evaluate the risks of cardiovascular problems. In this research, we proposed a new method for measurement of local arterial distensibility by using photoacoustic microscopy (PAM) technology. Taking advantages from its excellent sensitivity and high spatial resolution, PAM can evaluate the morphology and volume change of a small artery accurately without involving any contrast agent. When working in the linear elastic range of a vessel, measuring the initial and the distended diameters of the vessel before and after pressure change facilitates quantitative assessment of vessel distensibility. The preliminary experiment on well-controlled gel phantoms demonstrates the feasibility of this technology.