Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied.

Guest editors introduce contributors to the Special Section Celebrating the Exponential Growth of Optoacoustic/Photoacoustic Imaging.

Blockage of healthy blood vessels by blood clots can lead to serious or even life-threatening complications. The use of a combined ultrasound (US) and photoacoustic (PA) imaging was explored for blood clot monitoring during microbubble-assisted sonothrombolysis. PA imaging is an emerging hybrid imaging modality that has garnered the attention of the biomedical imaging community in recent years. It enables the study of the composition of a blood clot due to its sensitivity toward optical absorption. Here, in vitro imaging of the side of a blood clot facing the microbubbles was done over time. The US and PA signal-to-noise (SNR) ratio value changes during microbubble-assisted sonothrombolysis were studied for two different local environments: blood clot in deionized water and blood clot in blood. In the first case, US and PA SNR values increased by 4.6% and reduced by 20.8%, respectively after 30 min of sonothrombolysis treatment. After 10 min of sonothrombolysis treatment of the blood clot in blood, the US and PA SNR values increased by 7.7% and 38.3%, respectively. The US and PA SNR value changes were recorded in response to its local environment. This technique can be used to determine the final composition of the blood clot which may, in turn, help in the administration of clot-dissolving drugs.

Utility of glycol-chitosan-coated gold nanoparticles (GC-AuNPs) as a photoacoustic contrast agent for cancer cell imaging was demonstrated. Through the synergistic effect of glycol chitosan and gold nanoparticles, GC-AuNPs showed cellular uptake in breast cancer cells and resulted in strong photoacoustic signals in tissue-mimicking cell phantoms. The performance of GC-AuNPs as contrast agents was established with photoacoustic imaging and confirmed with dark-field microscopy. The cell phantoms displayed strong photoacoustic signals if cells were incubated more than 3 h with GC-AuNPs, compared with PEG-AuNPs that showed no photoacoustic signal increase. The enhanced photoacoustic signals originated from the plasmon coupling effect of GC-AuNPs after the cellular uptake in cancer cells. Importantly, photoacoustic imaging of cancer cells was achieved with GC-AuNPs—contrast agents that did not require antibodies or complex surface modification. The endocytosis of GC-AuNPs was also confirmed with dark-field microscopy. The results show that GC-AuNPs have potential as a photoacoustic contrast agent for cellular imaging including tumor tissue imaging.

Photoacoustic imaging (PAI) provides high-resolution and high-optical-contrast imaging beyond optical diffusion limit. Further improvement in imaging depth has been achieved by using near-infrared window-I (NIR-I, 700 to 900 nm) for illumination, due to lower scattering and absorption by tissues in this wavelength range. Recently, near-infrared window-II (NIR-II, 900 to 1700 nm) has been explored for PAI. We studied the imaging depths in biological tissues for different illumination wavelengths in visible, NIR-I, and NIR-II regions using Monte Carlo (MC) simulations and validated with experimental results. MC simulations were done to compute fluence in tissue, absorbance in blood vessel, and in a spherical absorber (mimicking sentinel lymph node) embedded at different depths in breast tissue. Photoacoustic tomography and acoustic resolution photoacoustic microscopy experiments were conducted to validate the MC results. We demonstrate that maximum imaging depth is achieved by wavelengths in NIR-I window (∼800  nm) when the energy density deposited is same for all wavelengths. However, illumination using wavelengths around 1064 nm (NIR-II window) gives the maximum imaging depth when the energy density deposited is proportional to maximum permissible exposure (MPE) at corresponding wavelength. These results show that it is the higher MPE of NIR-II window that helps in increasing the PAI depth for chromophores embedded in breast tissue.

Abdominal surgeries carry considerable risk of gastrointestinal and intra-abdominal hemorrhage, which could possibly cause patient death. Photoacoustic imaging is one solution to overcome this challenge by providing visualization of major blood vessels during surgery. We investigate the feasibility of in vivo blood vessel visualization for photoacoustic-guided liver and pancreas surgeries. In vivo photoacoustic imaging of major blood vessels in these two abdominal organs was successfully achieved after a laparotomy was performed on two swine. Three-dimensional photoacoustic imaging with a robot-controlled ultrasound (US) probe and color Doppler imaging were used to confirm vessel locations. Blood vessels in the in vivo liver were visualized with energies of 20 to 40 mJ, resulting in 10 to 15 dB vessel contrast. Similarly, an energy of 36 mJ was sufficient to visualize vessels in the pancreas with up to 17.3 dB contrast. We observed that photoacoustic signals were more focused when the light source encountered a major vessel in the liver. This observation can be used to distinguish major blood vessels in the image plane from the more diffuse signals associated with smaller blood vessels in the surrounding tissue. A postsurgery histopathological analysis was performed on resected pancreatic and liver tissues to explore possible laser-related damage. Results are generally promising for photoacoustic-guided abdominal surgery when the US probe is fixed and the light source is used to interrogate the surgical workspace. These findings are additionally applicable to other procedures that may benefit from photoacoustic-guided interventional imaging of the liver and pancreas (e.g., biopsy and guidance of radiofrequency ablation lesions in the liver).

To achieve fast imaging and large field of view (FOV), we improved our multimodal imaging system, which integrated optical resolution photoacoustic microscopy, optical coherence tomography (OCT), and confocal fluorescence microscopy in one platform, by combining optical scanning with mechanical scanning. To ensure good focusing of the objective lens over all the imaged area, we employed OCT-guided dynamic focusing. Different from our previous point-by-point dynamic focusing, we employed an area-by-area focusing adjustment strategy, in which each fast optical scanning area has a fixed focusing depth. We have demonstrated the performance of the system by imaging biological samples ex vivo (plant leaf) and in vivo (mouse ear). The system has achieved uniform resolution in an FOV of 10  mm  ×  10  mm with an imaging time of about 5 min.

Since it was first demonstrated more than a decade ago, the single-pixel camera concept has been used in numerous applications in which it is necessary or advantageous to reduce the channel count, cost, or data volume. Here, three-dimensional (3-D), compressed-sensing photoacoustic tomography (PAT) is demonstrated experimentally using a single-pixel camera. A large area collimated laser beam is reflected from a planar Fabry–Pérot ultrasound sensor onto a digital micromirror device, which patterns the light using a scrambled Hadamard basis before it is collected into a single photodetector. In this way, inner products of the Hadamard patterns and the distribution of thickness changes of the FP sensor—induced by the photoacoustic waves—are recorded. The initial distribution of acoustic pressure giving rise to those photoacoustic waves is recovered directly from the measured signals using an accelerated proximal gradient-type algorithm to solve a model-based minimization with total variation regularization. Using this approach, it is shown that 3-D PAT of imaging phantoms can be obtained with compression rates as low as 10%. Compressed sensing approaches to photoacoustic imaging, such as this, have the potential to reduce the data acquisition time as well as the volume of data it is necessary to acquire, both of which are becoming increasingly important in the drive for faster imaging systems giving higher resolution images with larger fields of view.

Photoacoustic tomography (PAT) is intrinsically sensitive to blood oxygen saturation (sO₂) in vivo. However, making accurate sO₂ measurements without knowledge of tissue- and instrumentation-related correction factors is extremely challenging. We have developed a low-cost flow phantom to facilitate validation of PAT systems. The phantom is composed of a flow circuit of tubing partially embedded within a tissue-mimicking material, with independent sensors providing online monitoring of the optical absorption spectrum and partial pressure of oxygen in the tube. We first test the flow phantom using two small molecule dyes that are frequently used for photoacoustic imaging: methylene blue and indocyanine green. We then demonstrate the potential of the phantom for evaluating sO₂ using chemical oxygenation and deoxygenation of blood in the circuit. Using this dynamic assessment of the photoacoustic sO₂ measurement in phantoms in relation to a ground truth, we explore the influence of multispectral processing and spectral coloring on accurate assessment of sO₂. Future studies could exploit this low-cost dynamic flow phantom to validate fluence correction algorithms and explore additional blood parameters such as pH and also absorptive and other properties of different fluids.

We present the Twente Photoacoustic Mammoscope 2, a photoacoustic breast imaging system employing a tomographic configuration. It images one breast pendant inside an imaging tank filled with water while a woman lies prone on a bed. A dual-head laser (755 and 1064 nm) illuminates the breast with one beam directed at the nipple and nine beams directed at the sides. Ultrasound signals are detected using 12 arc-shaped arrays, each curving along the pendant breast. Each array comprises 32 piezocomposite elements each with a center frequency of 1 MHz. The imaging tank and the ultrasound arrays rotate around the breast in steps to obtain additional multiple projections. Three-dimensional images are reconstructed using a filtered backprojection algorithm. The system is described in detail, and measurements on a test object are presented. As part of a preliminary study to assess the system’s in vivo performance, the breasts of two healthy volunteers were imaged. These images show the breast contour, the nipple, and the vascular anatomy within the breast. In the nipple of one case, multiple high-intensity “hot spots” are observed, which we suspect are associated with the lactiferous ducts terminating in the nipple.

As photoacoustic imaging (PAI) technology matures, computational modeling will increasingly represent a critical tool for facilitating clinical translation through predictive simulation of real-world performance under a wide range of device and biological conditions. While modeling currently offers a rapid, inexpensive tool for device development and prediction of fundamental image quality metrics (e.g., spatial resolution and contrast ratio), rigorous verification and validation will be required of models used to provide regulatory-grade data that effectively complements and/or replaces in vivo testing. To address methods for establishing model credibility, we developed an integrated computational model of PAI by coupling a previously developed three-dimensional Monte Carlo model of tissue light transport with a two-dimensional (2D) acoustic wave propagation model implemented in the well-known k-Wave toolbox. We then evaluated ability of the model to predict basic image quality metrics by applying standardized verification and validation principles for computational models. The model was verified against published simulation data and validated against phantom experiments using a custom PAI system. Furthermore, we used the model to conduct a parametric study of optical and acoustic design parameters. Results suggest that computationally economical 2D acoustic models can adequately predict spatial resolution, but metrics such as signal-to-noise ratio and penetration depth were difficult to replicate due to challenges in modeling strong clutter observed in experimental images. Parametric studies provided quantitative insight into complex relationships between transducer characteristics and image quality as well as optimal selection of optical beam geometry to ensure adequate image uniformity. Multidomain PAI simulation tools provide high-quality tools to aid device development and prediction of real-world performance, but further work is needed to improve model fidelity, especially in reproducing image noise and clutter.

Breast cancer is one of the leading causes for cancer related deaths in women, and early detection is extremely important to improve survival rates. Currently, x-ray mammogram is the only modality for mass screening of asymptomatic women. However, it has decreased sensitivity in radiographically dense breasts, which is also associated with a higher risk for breast cancer. Photoacoustic (PA) imaging is an emerging modality that enables deep tissue imaging of optical contrast at ultrasonically defined spatial resolution, which is much higher than that can be achieved in purely optical imaging modalities. Because of high optical absorption from hemoglobin molecules, PA imaging can map out hemo distribution and dynamics in breast tissue and identify malignant lesions based on tumor associated angiogenesis and hypoxia. We review various PA breast imaging systems proposed over the past few years and summarize the PA features of breast cancer identified in these systems.

We have developed a photoacoustic (PA) sensor using a low-power, continuous- wave laser and a kHz-range microphone. The sensor is simple, flexible, cost-effective, and compatible with commercial optical microscopes. The sensor enables noncontact PA measurements through air, whereas most current existing PA techniques require an acoustic coupling liquid for detection. The PA sensor has three main components: one is the chamber that holds the sample, the second is a resonator column used to amplify the weak PA signals generated within the sample chamber, and the third is a microphone at the end of the resonator column to detect the amplified signals. The chamber size was designed to be 8  mm  ×  3  mm as the thermal diffusion length and viscous-thermal damping of air at room pressure and temperature are 2 and 1 mm, respectively. We numerically and experimentally examined the effect of the resonator column size on the frequency response of the PA sensor. The quality factor decreased significantly when the sample chamber size was reduced from 4  mm  ×  3  mm to 2  mm  ×  3  mm due to thermos-viscous damping of the air. The quality factor decreased by 27%, demonstrating the need for optimal design for the sample chamber and resonator column size. The system exhibited noise equivalent molecular sensitivity (NEM) per unit bandwidth (NEM  /    √  Δf) of ∼19,966  Hz^−  1/2 or 33  ×  10^−  21  mol or 33 zeptomol, which is an improvement of 2.2 times compared to the previous system design. This PA sensor has the potential for noncontact high-resolution PA imaging of materials without the need for coupling fluids.

Colorectal cancer is the second most common malignancy diagnosed globally. Critical gaps exist in diagnostic and surveillance imaging modalities for colorectal neoplasia. Although prior studies have demonstrated the capability of photoacoustic imaging techniques to differentiate normal from neoplastic tissue in the gastrointestinal tract, evaluation of deep tissue with a fast speed and a large field of view remains limited. To investigate the ability of photoacoustic technology to image deeper tissue, we conducted a pilot study using a real-time co-registered photoacoustic tomography (PAT) and ultrasound (US) system. A total of 23 ex vivo human colorectal tissue samples were imaged immediately after surgical resection. Co-registered photoacoustic images of malignancies showed significantly increased PAT signal compared to normal regions of the same sample. The quantitative relative total hemoglobin (rHbT) concentration computed from four optical wavelengths, the spectral features, such as the mean spectral slope, and 0.5-MHz intercept extracted from PAT and US spectral data, and image features, such as the first- and second-order statistics along with the standard deviation of the mean radon transform of PAT images, have shown statistical significance between untreated colorectal tumors and the normal tissue. Using either a logistic regression model or a support vector machine, the best set of parameters of rHbT and PAT intercept has achieved area-under-the-curve (AUC) values of 0.97 and 0.95 for both training and testing data sets, respectively, for prediction of histologically confirmed invasive carcinoma.

Linear spectroscopic inversions, in which photoacoustic amplitudes are assumed to be directly proportional to absorption coefficients, are widely used in photoacoustic imaging to estimate blood oxygen saturation because of their simplicity. Unfortunately, they do not account for the spatially varying wavelength-dependence of the light fluence within the tissue, which introduces “spectral coloring,” a potentially significant source of error. However, accurately correcting for spectral coloring is challenging, so we investigated whether there are conditions, e.g., sets of wavelengths, where it is possible to ignore the spectral coloring and still obtain accurate oxygenation measurements using linear inversions. Accurate estimates of oxygenation can be obtained when the wavelengths are chosen to (i) minimize spectral coloring, (ii) avoid ill-conditioning, and (iii) maintain a sufficiently high signal-to-noise ratio (SNR) for the estimates to be meaningful. It is not obvious which wavelengths will satisfy these conditions, and they are very likely to vary for different imaging scenarios, making it difficult to find general rules. Through the use of numerical simulations, we isolated the effect of spectral coloring from sources of experimental error. It was shown that using wavelengths between 500 nm and 1000 nm yields inaccurate estimates of oxygenation and that careful selection of wavelengths in the 620- to 920-nm range can yield more accurate oxygenation values. However, this is only achievable with a good prior estimate of the true oxygenation. Even in this idealized case, it was shown that considerable care must be exercised over the choice of wavelengths when using linear spectroscopic inversions to obtain accurate estimates of blood oxygenation. This suggests that for a particular imaging scenario, obtaining accurate and reliable oxygenation estimates using linear spectroscopic inversions requires careful modeling or experimental studies of that scenario, taking account of the instrumentation, tissue anatomy, likely sO₂ range, and image formation process.

Opto-acoustic imaging involves using light to produce sound waves for visualizing blood in biological tissue. By using multiple optical wavelengths, diagnostic images of blood oxygen saturation and total hemoglobin are generated using endogenous optical contrast, without injection of any external contrast agent and without using any ionizing radiation. The technology has been used in recent clinical studies for diagnosis of breast cancer to help distinguish benign from malignant lesions, potentially reducing the need for biopsy through improved diagnostic imaging accuracy. To enable this application, techniques for mapping oxygen saturation differences within tissue are necessary. Using biologically relevant opto-acoustic phantoms, we analyze the ability of an opto-acoustic imaging system to display colorized parametric maps that are generated using a statistical mapping approach. To mimic breast tissue, a material with closely matching properties for optical absorption, optical scattering, acoustic attenuation, and speed of sound is used. The phantoms include two vessels filled with whole blood at oxygen saturation levels determined using a sensor-based approach. A flow system with gas-mixer and membrane oxygenator adjusts the oxygen saturation of each vessel independently. Datasets are collected with an investigational Imagio^® breast imaging system. We examine the ability to distinguish vessels as the oxygen saturation level and imaging depth are varied. At depth of 15 mm and hematocrit of 42%, a sufficient level of contrast to distinguish between two 1.6-mm diameter vessels was measured for an oxygen saturation difference of ∼4.6  %  . In addition, an oxygenated vessel was visible at a depth of 48 mm using an optical wavelength of 1064 nm, and a deoxygenated vessel was visible to a depth of 42 mm with 757 nm. The results provide insight toward using color mapped opto-acoustic images for diagnosing breast cancer.

The optical properties of human tissues are an important parameter in medical diagnostics and therapy. The knowledge of these parameters can encourage the development of automated, computer-driven optical tissue analysis methods. We determine the absorption coefficient μ_a and scattering coefficient μs′ of different tissue types obtained during parotidectomy in the wavelength range of 250 to 800 nm. These values are determined by high precision integrating sphere measurements in combination with an optimized inverse Monte Carlo simulation. To conserve the optical behavior of living tissues, the optical spectroscopy measurements are performed immediately after tissue removal. Our study includes fresh samples of the ear, nose, and throat (ENT) region, as muscle tissue, nervous tissue, white adipose tissue, stromal tissue, parotid gland, and tumorous tissue of five patients. The measured behavior of adipose corresponds well with the literature, which sustains the applied method. It is shown that muscle is well supplied with blood as it features the same characteristic peaks at 430 and 555 nm in the absorption curve. The parameter μs′ decreases for all tissue types above 570 nm. The accuracy is adequate for the purposes of providing μ_a and μs′ of different human tissue types as muscle, fat, nerve, or gland tissue, which are embedded in large complex structures such as in the ENT area. It becomes possible for the first time to present reasonable results for the optical behavior of human soft tissue located in the ENT area and in the near-UV, visual, and near-infrared areas.

Corneal thickness (CoT) is an important tool in the evaluation process for several disorders and in the assessment of intraocular pressure. We present a method enabling high-precision measurement of CoT based on secondary speckle tracking and processing of the information by machine-learning (ML) algorithms. The proposed configuration includes capturing by fast camera the laser beam speckle patterns backscattered from the corneal–scleral border, followed by ML processing of the image. The technique was tested on a series of phantoms having different thicknesses as well as in clinical trials on human eyes. The results show high accuracy in determination of eye CoT, and implementation is speedy in comparison with other known measurement methods.

Live-subject microscopies, including microendoscopy and other related technologies, offer promise for basic biology research as well as the optical biopsy of disease in the clinic. However, cellular resolution generally comes with the trade-off of a microscopic field-of-view. Microimage mosaicking enables stitching many small scenes together to aid visualization, quantitative interpretation, and mapping of microscale features, for example, to guide surgical intervention. The development of hyperspectral and multispectral systems for biomedical applications provides motivation for adapting mosaicking algorithms to process a number of simultaneous spectral channels. We present an algorithm that mosaics multichannel video by correlating channels of consecutive frames as a basis for efficiently calculating image alignments. We characterize the noise tolerance of the algorithm by using simulated video with known ground-truth alignments to quantify mosaicking accuracy and speed, showing that multiplexed molecular imaging enhances mosaic accuracy by leveraging observations of distinct molecular constituents to inform frame alignment. A simple mathematical model is introduced to characterize the noise suppression provided by a given group of spectral channels, thus predicting the performance of selected subsets of data channels in order to balance mosaic computation accuracy and speed. The characteristic noise tolerance of a given number of channels is shown to improve through selection of an optimal subset of channels that maximizes this model. We also demonstrate that the multichannel algorithm produces higher quality mosaics than the analogous single-channel methods in an empirical test case. To compensate for the increased data rate of hyperspectral video compared to single-channel systems, we employ parallel processing via GPUs to alleviate computational bottlenecks and to achieve real-time mosaicking even for video-rate multichannel systems anticipated in the future. This implementation paves the way for real-time multichannel mosaicking to accompany next-generation hyperspectral and multispectral video microscopy.

We study a problem scenario of super-resolution (SR) algorithms in the context of whole slide imaging (WSI), a popular imaging modality in digital pathology. Instead of just one pair of high- and low-resolution images, which is typically the setup in which SR algorithms are designed, we are given multiple intermediate resolutions of the same image as well. The question remains how to best utilize such data to make the transformation learning problem inherent to SR more tractable and address the unique challenges that arises in this biomedical application. We propose a recurrent convolutional neural network model, to generate SR images from such multi-resolution WSI datasets. Specifically, we show that having such intermediate resolutions is highly effective in making the learning problem easily trainable and address large resolution difference in the low and high-resolution images common in WSI, even without the availability of a large size training data. Experimental results show state-of-the-art performance on three WSI histopathology cancer datasets, across a number of metrics.

Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field en-face images of amplitude, quantitative phase, and resolved polarimetric properties through an MCF. We first demonstrate imaging and quantification of biologically relevant amounts of optical scattering and birefringence in tissue-mimicking phantoms. We present an entropy metric that enables imaging of phase heterogeneity, indicative of disordered tissue microstructure associated with early tumors. Finally, we demonstrate that the spatial distribution of phase and polarization information enables label-free visualization of early tumors in esophageal mouse tissues, which are not identifiable using conventional amplitude-only information.

We demonstrate the possibility of measuring FRET efficiency with a low-cost frequency-domain fluorescence lifetime imaging microscope (FD-FLIM). The system utilizes single-frequency-modulated excitation, which enables the use of cost-effective laser sources and electronics, simplification of data acquisition and analysis, and a dual-channel detection capability. Following calibration with coumarin 6, we measured the apparent donor lifetime in mTFP1-mVenus FRET standards expressed in living cells. We evaluated the system’s sensitivity by differentiating the short and long lifetimes of mTFP1 corresponding to the known standards’ high and low FRET efficiency, respectively. Furthermore, we show that the lifetime of the vinculin tension sensor, VinTS, at focal adhesions (2.30  ±  0.16  ns) is significantly (p  <  ^{10  −  6}) longer than the lifetime of the unloaded TSMod probe (2.02  ±  0.16  ns). The pixel dwell time was 6.8  μs for samples expressing the FRET standards, with signal typically an order of magnitude higher than VinTS. The apparent FRET efficiency (EFRETapp) of the standards, calculated from the measured apparent lifetime, was linearly related to their known FRET efficiency by a factor of 0.92 to 0.99 (R²  =  0.98). This relationship serves as a calibration curve to convert apparent FRET to true FRET and circumvent the need to measure multiexponential lifetime decays. This approach yielded a FRET efficiency of 18% to 19.5%, for VinTS, in agreement with published values. Taken together, our results demonstrate a cost-effective, fast, and sensitive FD-FLIM approach with the potential to facilitate applications of FLIM in mechanobiology and FRET-based biosensing.

When analyzing multidiameter single-fiber reflectance (MDSFR) spectra, the inhomogeneous distribution of melanin pigments in skin tissue is usually not accounted for. Especially in heavily pigmented skins, this can result in bad fits and biased estimation of tissue optical properties. A model is introduced to account for the inhomogeneous distribution of melanin pigments in skin tissue. In vivo visible MDSFR measurements were performed on heavily pigmented skin of type IV to VI. Skin tissue optical properties and related physiological properties were extracted from the measured spectra using the introduced model. The absorption of melanin pigments described by the introduced model demonstrates a good correlation with the co-localized measurement of the well-known melanin index.

Researchers have found that decreased levels of circulating citrulline could be an indicator of intestinal failure. Typically, this amino acid, which is produced by the intestinal mucosa cells, circulates in the blood at a physiological level of ∼40  μM. The current methodology for measuring this level involves the use of bulky equipment, such as mass spectroscopy and analysis at a central laboratory, which can delay diagnosis. Therefore, the current detection method is unsuited for routine monitoring at a doctor’s office. Our research group proposes the development of a point-of-care (POC) device to overcome this issue. The proposed device utilizes surface-enhanced Raman spectroscopy (SERS) coupled with a specifically designed aptamer, capable of binding to citrulline, conjugated to colloidal gold nanoparticles. The assay is then embedded within a vertical flow paper-fluidic platform as a deliverable at the POC, and a handheld Raman spectrometer (638-nm excitation) was used to interrogate the sample. Results showed good dynamic range and specificity with an average 73% decrease in SERS signal intensity with increasing concentrations of citrulline (0 to 50  μM) in phosphate-buffered saline compared to its controls: glycine, glutamine, histidine, and valine, which showed less than 10% average decrease in the presence of 200  μM of each analyte. Further, the limit of detection (LOD) within a chip was determined to be 0.56  μM, whereas the LOD across chips was below 10  μM.

Sapphire capillary needles fabricated by edge-defined film-fed growth (EFG) technique hold strong potential in laser thermotherapy and photodynamic therapy, thanks to the advanced physical properties of sapphire. These needles feature an as-grown optical quality, their length is tens of centimeters, and they contain internal capillary channels, with open or closed ends. They can serve as optically transparent bearing elements with optical fibers introduced into their capillary channels in order to deliver laser radiation to biological tissues for therapeutic and, in some cases, diagnostic purposes. A potential advantage of the EFG-grown sapphire needles is associated with an ability to form the tip of a needle with complex geometry, either as-grown or mechanically treated, aimed at controlling the output radiation pattern. In order to examine a potential of the radiation pattern shaping, we present a set of fabricated sapphire needles with different tips. We studied the radiation patterns formed at the output of these needles using a He–Ne laser as a light source, and used intralipid-based tissue phantoms to proof the concept experimentally and the Monte-Carlo modeling to proof it numerically. The observed results demonstrate a good agreement between the numerical and experimental data and reveal an ability to control within wide limits the direction of tissue exposure to light and the amount of exposed tissue by managing the sapphire needle tip geometry.

Suturing of corneal incisions requires significant skill. We demonstrate a noncontact method that will simplify the bonding process. 5-mm-long penetrating vertical and slanted incisions were made in corneas of eyes, extracted from dead piglets. A fiber-optic laser system was used for laser soldering of the incisions, under close temperature control, using albumin solder. The burst-pressure P_B immediately after the soldering was found to be P_B  ≈  92 and 875 mmHg, for vertical and slanted incisions, respectively. P_B  =  875  mmHg is an exceptionally high figure, ≈10 times the clinically acceptable value for sutured incisions. Laser soldering was then performed on penetrating incisions made in the corneas of live healthy piglets, of weight ≈10  Kg. After a healing period, the eyes were extracted, and the corneas were examined by histopathology and by optical coherence tomography. Our method immediately generated watertight and strong bonding without noticeable corneal shape distortion. These results would be beneficial for cataract surgery and for corneal transplantations. The fiber-optic system makes it much easier to bond corneal incisions. In the future, laser soldering could be automated and efficiently used by less experienced surgeons, thereby reducing the workload on the experienced ones.

The erratum corrects an error in the article “Development of a blood oxygenation phantom for photoacoustic tomography combined with online pO₂ detection and flow spectrometry.”