LED-based photoacoustic imaging for early detection of joint inflammation in rodents:Towards achieving 3Rs in rheumatoid arthritis research

Synovial angiogenesis and hypoxia in the joints are biomarkers of Rheumatoid Arthritis (RA). The ability to probe blood and accurately estimate the oxygen concentration make multiwavelength Photoacoustic (PA) imaging a potential tool for early detection of RA. In this work, a multiwavelength LED-based PA imaging system was characterized based on its imaging depth, resolution and accuracy of oxygen saturation estimation. A multicenter 3R (Replace, Refine and Reduce) focused small animal study was conducted. The 3R strategy was devised by reusing RA animal models, in vivo imaging of healthy animals and ex vivo studies with human blood. RA animal cadaver models with different levels of synovial angiogenesis (control, positive RA and treated) were imaged and compared against results from a previous study using the same samples. An ex vivo PA oxygen saturation imaging using human blood was validated against oximeter readings and further verified it with in vivo animal studies. An imaging depth of 8 mm with an SNR of 10 dB was achieved for RA samples. A difference in PA intensity was observed for RA models compared to control and treated group. The PA oxygen saturation estimation correlates with oximeter readings, which is confirmed with in vivo studies. The results show the efficacy of the LED-based PA imaging system in RA diagnosis based on synovial angiogenesis and hypoxia. The imaging depth, resolution and oxygen saturation estimate are sufficient to differentiate RA samples from control. Our future work will focus on validating the method using arthritis animal models and demonstrating the 3R potential.</p

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance

SIGNIFICANCE: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed. AIM: Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL). APPROACH: A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions (1.65 at the time of treatment were associated with successful outcomes. CONCLUSION: These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware

Molecular specific photoacoustic imaging using plasmonic gold nanoparticles

textCancer has become one of the leading causes of death today. The early detection of cancer may lead to desired therapeutic management of cancer and to decrease the mortality rate through effective therapeutic strategies. Advances in materials science have enabled the use of nanoparticles for added contrast in various imaging techniques. More recently there has been much interest in the use of gold nanoparticles as optical contrast agents because of their strong absorption and scattering properties at visible and near-infrared wavelengths. Highly proliferative cancer cells overexpress molecular markers such as epidermal growth factor receptor (EGFR). When specifically targeted gold nanoparticles bind to EGFR they tend to cluster thus leading to an optical red-shift of the plasmon resonances and an increase in absorption in the red region. These changes in optical properties provide the foundation for photoacoustic imaging technique to differentiate cancer cells from surrounding benign cells. In photoacoustic imaging, contrast mechanism is based on the optical absorption properties of the tissue constituents. Studies were performed on tissue phantoms, ex-vivo and in-vivo tumor models to evaluate molecular specific photoacoustic imaging technique. The results indicate that highly sensitive and selective detection of cancer cells can be achieved by utilizing the plasmon resonance coupling effect of EGFR targeted gold nanoparticles and photoacoustic imaging. In conclusion, the combined ultrasound and photoacoustic imaging technique has the ability to image molecular signature of cancer using bioconjugated gold nanoparticles.Biomedical Engineerin

Combined ultrasound, photoacoustic and elasticity microscope for tissue engineers

textTissue engineering is an interdisciplinary field that combines various aspects of engineering and life sciences and aims to develop biological substitutes to restore, repair or maintain tissue function. Currently, the ability to have quantitative functional assays of engineered tissues is limited to existing invasive methods like biopsy. Hence, an imaging tool for non-invasive and simultaneous evaluation of the anatomical and functional properties of the engineered tissue is needed. In this thesis, we present an advanced in-vivo imaging technology - ultrasound biomicroscopy combined with complementary photoacoustic and elasticity imaging techniques, capable of accurate visualization of both structural and functional changes in engineered tissues, sequential monitoring of tissue adaptation and/or regeneration, and possible assistance of drug delivery and treatment planning. The combined imaging at microscopic resolution was evaluated on tissue mimicking phantoms imaged with 25 MHz single element focused transducer. The results of our study demonstrate that the ultrasonic, photoacoustic and elasticity images synergistically complement each other in detecting features otherwise imperceptible using the individual techniques. Finally, we illustrate the feasibility of the combined ultrasound, photoacoustic and elasticity imaging techniques in accurately assessing the morphological and functional changes occurring in engineered tissue.Biomedical Engineerin

Photoacoustic technique to measure beam profile of pulsed laser systems

The beam profiles of pulsed lasers are currently measured using either complementary metal oxide semiconductor (CMOS) or charge coupled device (CCD) cameras. Despite providing high-resolution beam profiles, these devices cannot work with high power lasers. If additional optical attenuators are used, beam distortions may occur. In this paper we demonstrate a high-resolution photoacoustic technique capable of measuring the beam profile of pulsed lasers. The beam profiles of a pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser and a pulsed optical parametric oscillator (OPO) laser system were measured using a polydimethylsiloxane film and a single element high-frequency ultrasonic transducer. The advantages and limitations of the developed photoacoustic technique are discussed

Pulsed Magneto-motive Ultrasound Imaging Using Ultrasmall Magnetic Nanoprobes

Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magnetomotive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magnetomotive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures

Pulsed Magneto-motive Ultrasound Imaging Using Ultrasmall Magnetic Nanoprobes

Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magnetomotive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magnetomotive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures

Oxygen saturation imaging using LED-based photoacoustic system

Oxygen saturation imaging has potential in several preclinical and clinical applications. Dual-wavelength LED array-based photoacoustic oxygen saturation imaging can be an affordable solution in this case. For the translation of this technology, there is a need to improve its accuracy and validate it against ground truth methods. We propose a fluence compensated oxygen saturation imaging method, utilizing structural information from the ultrasound image, and prior knowledge of the optical properties of the tissue with a Monte-Carlo based light propagation model for the dual-wavelength LED array configuration. We then validate the proposed method with oximeter measurements in tissue-mimicking phantoms. Further, we demonstrate in vivo imaging on small animal and a human subject. We conclude that the proposed oxygen saturation imaging can be used to image tissue at a depth of 6–8 mm in both preclinical and clinical applications