In vivo photoacoustic tumor tomography using a quinoline-annulated porphyrin as NIR molecular contrast agent.

The synthesis and photophysical properties of a tetra-PEG-modified and freely water-soluble quinoline-annulated porphyrin are described. We previously demonstrated the ability of quinoline-annulated porphyrins to act as an in vitro NIR photoacoustic imaging (PAI) contrast agent. The solubility of the quinoline-annulated porphyrin derivative in serum now allowed the assessment of the efficacy of the PEGylated derivative as an in vivo NIR contrast agent for the PAI of an implanted tumor in a mouse model. A multi-fold contrast enhancement when compared to the benchmark dye ICG could be shown, a finding that could be traced to its photophysical properties (short triplet lifetimes, low fluorescence and singlet oxygen sensitization quantum yields). A NIR excitation wavelength of 790 nm could be used, fully taking advantage of the optical window of tissue. Rapid renal clearance of the dye was observed. Its straight-forward synthesis, optical properties with the possibility for further optical fine-tuning, nontoxicity, favorable elimination rates, and contrast enhancement make this a promising PAI contrast agent. The ability to conjugate the PAI chromophore with a fluorescent tag using a facile and general conjugation strategy was also demonstrated.

Ultrasound-Guided Diffuse Optical Tomography for Predicting and Monitoring Neoadjuvant Chemotherapy of Breast Cancers: Recent Progress.

In this manuscript, we review the current progress of utilizing ultrasound-guided diffuse optical tomography (US-guided DOT) for predicting and monitoring neoadjuvant chemotherapy (NAC) outcomes of breast cancer patients. We also report the recent advance on optical tomography systems toward portable and robust clinical use at multiple clinical sites. The first patient who has been closely monitored before NAC, at day 2, day 8, end of first three cycles of NAC, and before surgery is given as an example to demonstrate the potential of US-guided DOT technique.

Study of the effect of mechanical pressure on determination of position and size of tumor in biological phantoms.

Diffuse optical tomography (DOT) is an emerging oncological imaging modality that is based on a near-infrared optical technique. DOT provides the spatial volume and depth of tumors by determination of optical properties of biological tissues, such as the absorption and scattering coefficients. During a DOT, the optical fibers are kept in contact with biological tissues that introduce a certain amount of pressure on the local biological tissue. Due to this pressure, the shape of the organ, for instance a breast, deforms. Moreover, this pressure could influence the intrinsic characteristics of the biological tissue. Therefore, pressure can be an important parameter in DOT. In this paper, the effects of pressure on the determination of the size and position of a tumor in biological phantoms are studied. To do so, tissue-like phantoms that are made of intralipid, Indian ink, and agar are constructed. Defects with optical properties similar to those of tumors are placed inside the phantoms. Then various values of pressure are applied to the phantoms. Subsequently, the optical properties of phantoms as well as the position and size of the tumor are reconstructed by inverse models based on the boundary integral method. The variations of reconstructed data induced by pressure are studied. The results demonstrate that pressure causes an increase in the scattering coefficient.

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model.

Significance: Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions. Aim: We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation. Approach: A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model k -values in experimental groups: sham control (SC, n = 5 , 0.0 mA / 0 Hz ), stimulation level 1 (SL1, n = 5 , 3.4 mA / 50 Hz , and k = 2.57 ), and stimulation level 2 (SL2, n = 5 , 6.8 mA / 100 Hz , and k = 3.17 ). Results: The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of + 4 % / - 309 % (SL1/SL2) in phase retardation and - 79 % / - 148 % in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a + 1 % / - 36 % difference in myelin pixel counts and - 13 % / + 29 % difference in axon pixel counts, and an overall increase in cell nuclei pixel count of + 20 % / + 35 % . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis. Conclusions: The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

Treasure hunt for peptides with undefined chemical modifications: Proteomics identification of differential albumin adducts of 2-nitroimidazole-indocyanine green in hypoxic tumor.

2-Nitroimidazole is a well-known chemical probe targeting hypoxic environments of solid tumors, and its derivatives are widely used as imaging agents to investigate tissue and tumor hypoxia. However, the underlying chemistry for the hypoxia-detection capability of 2-nitroimidazole is still unclear. In this study, we deployed a biotin conjugate of 2-nitroimidazole-indocyanine green (2-nitro-ICG) for the investigation of in vivo hypoxia-probing mechanism of 2-nitro-ICG compounds. By implementing mass spectrometry-based proteomics and exhaustive data mining, we report that 2-nitro-ICG and its fragments modify mouse serum albumin as the primary protein target but at two structurally distinct sites and possibly via two different mechanisms. The identification of probe-modified peptides not only contributes to the understanding of the in vivo metabolism of 2-nitroimidazole compounds but also demonstrates a competent analytical workflow that enables the search for peptides with undefined modifications in complex proteome digests.

Adaptive Boosting (AdaBoost)-based multiwavelength spatial frequency domain imaging and characterization for ex vivo human colorectal tissue assessment.

The current gold standard diagnostic test for colorectal cancer remains histological inspections of endoluminal neoplasia in biopsy specimens. However, biopsy site selection requires visual inspection of the bowel, typically with a white-light endoscope. Therefore, this technique is poorly suited to detect small or innocuous-appearing lesions. We hypothesize that an alternative modality-multiwavelength spatial frequency domain imaging (SFDI)-would be able to differentiate various colorectal neoplasia from normal tissue. In this ex vivo study of human colorectal tissues, we report the optical absorption and scattering signatures of normal, adenomatous polyp and cancer specimens. An abnormal vs. normal adaptive boosting (AdaBoost) classifier is trained to dichotomize tissue based on SFDI imaging characteristics, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 is achieved. We conclude that AdaBoost-based multiwavelength SFDI can differentiate abnormal from normal colorectal tissues, potentially improving endoluminal screening of the distal gastrointestinal tract in the future.

Photoacoustic imaging with low-cost sources; A review.

Benefitting from advantages of optical and ultrasound imaging, photoacoustic imaging (PAI) has demonstrated potentials in a wide range of medical applications. In order to facilitate clinical applications of PAI and encourage its application in low-resource settings, research on low-cost photoacoustic imaging with inexpensive optical sources has gained attention. Here, we review the advances made in photoacoustic imaging with low-cost sources.

Laser scanning laser diode photoacoustic microscopy system.

The development of low-cost and fast photoacoustic microscopy systems enhances the clinical applicability of photoacoustic imaging systems. To this end, we present a laser scanning laser diode-based photoacoustic microscopy system. In this system, a 905 nm, 325 W maximum output peak power pulsed laser diode with 50 ns pulsewidth is utilized as the light source. A combination of aspheric and cylindrical lenses is used for collimation of the laser diode beam. Two galvanometer scanning mirrors steer the beam across a focusing aspheric lens. The lateral resolution of the system was measured to be ∼21 µm using edge spread function estimation. No averaging was performed during data acquisition. The imaging speed is ∼370 A-lines per second. Photoacoustic microscopy images of human hairs, ex vivo mouse ear, and ex vivo porcine ovary are presented to demonstrate the feasibility and potentials of the proposed system.

Low-cost compact multispectral spatial frequency domain imaging prototype for tissue characterization.

We present a low-cost, compact, and multispectral spatial frequency domain imaging prototype. Illumination components, including 9 LEDs (660 nm - 950 nm) placed on a custom-designed printed circuit board, linear and rotational motors, a printed sinusoidal pattern, and collimation and projection optics as well as the detection components are incorporated in a compact custom-designed 3D-printed probe. Reconstruction of absorption and reduced scattering coefficients is evaluated via imaging tissue mimicking phantoms and potentials of the probe for biological tissue imaging are evaluated via imaging human ovarian tissue ex vivo.

Protein corona: Opportunities and challenges.

In contact with biological fluids diverse type of biomolecules (e.g., proteins) adsorb onto nanoparticles forming protein corona. Surface properties of the coated nanoparticles, in terms of type and amount of associated proteins, dictate their interactions with biological systems and thus biological fate, therapeutic efficiency and toxicity. In this perspective, we will focus on the recent advances and pitfalls in the protein corona field.

Diffuse optical tomography: image reconstruction and verification.

INTRODUCTION: In this study, we intend to use diffuse optical Tomography (DOT) as a noninvasive, safe and low cost technique that can be considered as a functional imaging method and mention the importance of image reconstruction in accuracy and procession of image. One of the most important and fastest methods in image reconstruction is the boundary element method (BEM). This method is introduced and employed in our works. METHOD: Generally, to image a biological tissue we must obtain its optical properties. In order to reach this goal we benefit from diffusion equation because tissue is highly scattering medium. Diffusion equation is solved by boundary element equation (BEM) in our research. First, we assume a double layer phantom with different scattering and absorption coefficients to simulate and verify precession and accuracy of image reconstruction by BEM. Light absorption can be affected by volume fraction of blood in skin. For a specific skin species the volume fraction is calculated and then the results are compared with the reconstructed values obtained by BEM. Since the depth of tissue is important in light absorption a two layer phantom with known values is made and the depths of layers are reconstructed by BEM then they are compared with the expected values. A homogenous phantom with known scattering and absorption coefficients was made and then these coefficients were reconstructed by BEM. Finally, an inhomogeneous phantom (phantom with defect) whose defect was in a known position was made and the absorption and scattering coefficients were reconstructed and compared with real values. RESULTS: Comparison between real or simulated values and reconstructed values of scattering and absorption coefficients, volume fraction of blood and thickness of phantom layers by BEM shows maximum errors of 24%, 7% and 35%, respectively. CONCLUSION: Comparison between BEM data and real or simulated values shows an acceptabl eagreement. Consequently, we can rely on BEM as a beneficial method in diffuse optical tomography image reconstruction.

Mechanisms of Laser-Tissue Interaction: II. Tissue Thermal Properties.

Laser-tissue interaction is of great interest due to its significant application in biomedical optics in both diagnostic and treatment purposes. Major aspects of the laser-tissue interaction which has to be considered in biomedical studies are the thermal properties of the tissue and the thermal changes caused by the interaction of light and tissue. In this review paper the effects of light on the tissue at different temperatures are discussed. Then, due to the noticeable importance of studying the heat transfer quantitatively, the equations governing this phenomenon are presented. Finally a method of medical diagnosis called thermography and some of its applications are explained.