Analytical reconstruction of the bioluminescent source with priors.

Bioluminescence imaging has been a popular tool in small animal imaging. During the last decade, the efforts have focused on the development of tomographic systems. However, due to the difficulties in the nature of inverse source problem, multi-modal systems have been the center of attention for the last couple of years. These systems provide complementary information such that the difficulties of the inverse source problem could be overcome using the a priori information obtained. Motivated by these advances in multi-modal systems, this work presents a novel analytical reconstruction of the bioluminescent source. It is shown that if source strength is known a priori then source position could be calculated or vice versa, if source location is known a priori, source strength could be calculated as well as the photon fluence rate. The determination of the source location can be achieved by another imaging system such as X-ray computed tomography. Therefore, in bioluminescence tomography together with an imaging system can be utilized as a multi-modal system. In this work, conventional finite element based simulations are also performed and the numerical results are compared with the analytical ones. It turns out to be that the analytical results are in a good accordance with the numerical results.

Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals.

Non-invasive glucose monitoring (NIGM) represents an attractive alternative to finger pricking for blood glucose assessment and management of diabetes. Nevertheless, current NIGM techniques do not measure glucose concentrations in blood but rely on indirect bulk measurement of glucose in interstitial fluid, where glucose is diluted and glucose dynamics are different from those in the blood, which impairs NIGM accuracy. Here we introduce a new biosensor, termed depth-gated mid-infrared optoacoustic sensor (DIROS), which allows, for the first time, non-invasive glucose detection in blood-rich volumes in the skin. DIROS minimizes interference caused by the stratum corneum and other superficial skin layers by time-gating mid-infrared optoacoustic signals to enable depth-selective localization of glucose readings in skin. In measurements on the ears of (female) mice, DIROS displays improved accuracy over bulk-tissue glucose measurements. Our work demonstrates how signal localization can improve NIGM accuracy and positions DIROS as a holistic approach, with high translational potential, that addresses a key limitation of current NIGM methods.

Application of scanning acoustic microscopy for evaluation of MMP activation in multiple cancer cell lines with a smart probe.

Background/aim: Matrix metalloproteinases (MMPs) play an important role in the evaluation of many cancer types; however, the detection usually presents a challenge. Further assays for a better understanding of the fundamental roles of MMPs in pathophysiology are still needed. We aimed to use an activatable probe in scanning acoustic microscopy (SAM) to evaluate acoustically if the probe can aid the visualization of the effects of in vitro MMP activity. Materials and methods: We applied scanning acoustic impedance microscopy to obtain acoustic impedance maps of the cell line models of HT1080, THP-1, and SK-MEL-28 with and without MMPSense 680 probe incubation. We visually validated our results using confocal laser scanning microscopy imaging. We further analyzed the effects of MMPSense 680 probe on cell viabilities to eliminate any artifacts. Results: This is the first study presenting the applicability of SAM in the acoustical evaluation of MMPSense 680 probe cleavage in a cellular medium through acoustic impedance measurements. We proposed that SAM measurement with the activatable probe can be used as an effective tool for studying the acoustical variations of MMP activities in cell lines. As a result, we detected MMPSense 680 probe cleavage in HT1080 human fibrosarcoma cell line. Conclusion: We showed that SAM with the smart probe can detect proteolytic activity using MMPSense 680 in in vitro HT1080 cell line by acoustic impedance measurements. SAM could be proposed as an alternative tool leading a novel way for a better understanding of the roles of MMPs in cancer progression before clinical settings.

Comparison of noise reduction methods in photoacoustic microscopy.

Photoacoustic microscopy (PAM) is classified as a hybrid imaging technique based on the photoacoustic effect and has been frequently studied in recent years. Photoacoustic (PA) signals are inherently recorded in a noisy environment and are also exposed to noise by system components. Therefore, it is essential to reduce the noise in PA signals to reconstruct images with less error. In this study, an image reconstruction algorithm for PAM system was implemented and different filtering approaches for denoising were compared. Studies were carried out in three steps: simulation, experimental phantom and blood cell studies. FIR low-pass and band-pass filters and Discrete Wavelet Transform (DWT) based filters (mother wavelets: "bior3.5″, "bior3.7″, "sym7″) with four different thresholding techniques were examined. For the evaluation purposes, Root Mean Square Error (RMSE), Signal to Noise Ratio (SNR) and Contrast to Noise Ratio (CNR) metrics were calculated. In the simulation studies, the most effective methods were obtained as: sym7/heursure/hard thresh. combination (low and medium level noise) and bior3.7/sqtwolog/soft thresh. combination (high-level noise). In experimental phantom studies, noise was classified into five levels. Different filtering approaches perform better depending on the SNR of PA images. For the blood cell study, based on the standard deviation in the background, sym7/sqtwolog/soft thresh. combination provided the best improvement and this result supported the experimental phantom results.

Extended photoacoustic transport model for characterization of red blood cell morphology in microchannel flow.

The dynamic response behavior of red blood cells holds the key to understanding red blood cell related diseases. In this regard, an understanding of the physiological functions of erythrocytes is significant before focusing on red blood cell aggregation in the microcirculatory system. In this work, we present a theoretical model for a photoacoustic signal that occurs when deformed red blood cells pass through a microfluidic channel. Using a Green's function approach, the photoacoustic pressure wave is obtained analytically by solving a combined Navier-Stokes and photoacoustic equation system. The photoacoustic wave expression includes determinant parameters for the cell deformability such as plasma viscosity, density, and red blood cell aggregation, as well as involving laser parameters such as beamwidth, pulse duration, and repetition rate. The effects of aggregation on blood rheology are also investigated. The results presented by this study show good agreements with the experimental ones in the literature. The comprehensive analytical solution of the extended photoacoustic transport model including a modified Morse type potential function sheds light on the dynamics of aggregate formation and demonstrates that the profile of a photoacoustic pressure wave has the potential for detecting and characterizing red blood cell aggregation.

Development of a Fiber Laser with Independently Adjustable Properties for Optical Resolution Photoacoustic Microscopy.

Photoacoustic imaging is based on the detection of generated acoustic waves through thermal expansion of tissue illuminated by short laser pulses. Fiber lasers as an excitation source for photoacoustic imaging have recently been preferred for their high repetition frequencies. Here, we report a unique fiber laser developed specifically for multiwavelength photoacoustic microscopy system. The laser is custom-made for maximum flexibility in adjustment of its parameters; pulse duration (5-10 ns), pulse energy (up to 10 µJ) and repetition frequency (up to 1 MHz) independently from each other and covers a broad spectral region from 450 to 1100 nm and also can emit wavelengths of 532, 355, and 266 nm. The laser system consists of a master oscillator power amplifier, seeding two stages; supercontinuum and harmonic generation units. The laser is outstanding since the oscillator, amplifier and supercontinuum generation parts are all-fiber integrated with custom-developed electronics and software. To demonstrate the feasibility of the system, the images of several elements of standardized resolution test chart are acquired at multiple wavelengths. The lateral resolution of optical resolution photoacoustic microscopy system is determined as 2.68 µm. The developed system may pave the way for spectroscopic photoacoustic microscopy applications via widely tunable fiber laser technologies.