The early detection and diagnosis of malignant colorectal tumors enables the initiation of early-stage therapy and can significantly increase the survival rate and post-treatment quality of life among cancer patients. Hyperspectral imaging (HSI) is recognized as a powerful tool for noninvasive cancer detection. In the gastrointestinal field, most of the studies on HSI have involved ex vivo biopsies or resected tissues. In the present study, we aimed to assess the difference in the in vivo spectral reflectance of malignant colorectal tumors and normal mucosa. A total of 21 colorectal tumors or adenomatous polyps from 12 patients at Shanghai Zhongshan Hospital were examined using a flexible hyperspectral (HS) colonoscopy system that can obtain in vivo HS images of the colorectal mucosa. We determined the optimal wavelengths for differentiating tumors from normal tissue based on these recorded images. The application of the determined wavelengths in spectral imaging in clinical trials indicated that such a clinical support system comprising a flexible HS colonoscopy unit and band selection unit is useful for outlining the tumor region and enhancing the display of the mucosa microvascular pattern in vivo.

In optoacoustic tomography, detectors with relatively large areas are often employed to achieve high detection sensitivity. However, spatial-averaging effects over large detector areas may lead to attenuation of high acoustic frequencies and, subsequently, loss of fine features in the reconstructed image. Model-based reconstruction algorithms improve image resolution in such cases by correcting for the effect of the detector’s aperture on the detected signals. However, the incorporation of the detector’s geometry in the optoacoustic model leads to a significant increase of the model matrix memory cost, which hinders the application of inversion and analysis tools such as singular value decomposition (SVD). We demonstrate the use of the wavelet-packet framework for optoacoustic systems with finite-aperture detectors. The decomposition of the model matrix in the wavelet-packet domain leads to sufficiently smaller model matrices on which SVD may be applied. Using this methodology over an order of magnitude reduction in inversion time is demonstrated for numerically generated and experimental data. Additionally, our framework is demonstrated for the analysis of inversion stability and reveals a new, nonmonotonic dependency of the system condition number on the detector size. Thus, the proposed framework may assist in choosing the optimal detector size in future optoacoustic systems.

We report a method for edge enhancement in the images of transparent samples using analog image processing in coherent light. The experimental technique is based on adaptive spatial filtering with an acousto-optic tunable filter in a telecentric optical system. We demonstrate processing of microscopic images of unstained and stained histological sections of human thyroid tumor with improved contrast.

Fluorescence molecular tomography (FMT) is a significant preclinical imaging modality that has been actively studied in the past two decades. It remains a challenging task to obtain fast and accurate reconstruction of fluorescent probe distribution in small animals due to the large computational burden and the ill-posed nature of the inverse problem. We have recently studied a nonuniform multiplicative updating algorithm that combines with the ordered subsets (OS) method for fast convergence. However, increasing the number of OS leads to greater approximation errors and the speed gain from larger number of OS is limited. We propose to further enhance the convergence speed by incorporating a first-order momentum method that uses previous iterations to achieve optimal convergence rate. Using numerical simulations and a cubic phantom experiment, we have systematically compared the effects of the momentum technique, the OS method, and the nonuniform updating scheme in accelerating the FMT reconstruction. We found that the proposed combined method can produce a high-quality image using an order of magnitude less time.

Boston keratoprosthesis (KPro) type I is a technique to treat patients with corneal diseases that are not amenable to conventional keratoplasty. Correct assembly and central implantation of the prosthesis are crucial for postoperative visual recovery. This study investigates the potential benefit of intraoperative optical coherence tomography (OCT) to monitor KPro surgery. Retrospective case series are presented for two patients who underwent Boston KPro type I implantation. The surgery in both patients was monitored intraoperatively using a commercially available intraoperative OCT (iOCT) device mounted on a surgical microscope. Microscope-integrated intraoperative OCT was able to evaluate the correct assembly and implantation of the KPro. All parts of the prosthesis were visible, and interfaces between the corneal graft and titanium backplate or anterior optics were clearly depictable. Moreover, iOCT visualized a gap between the backplate and graft in one case, and in the other case, a gap between the anterior optic and graft. Neither gap was visible with a conventional surgical microscope. The gap between the anterior optic and the graft could easily be corrected. Microscope-integrated iOCT delivers enhanced information, adding to the normal surgical microscope view during KPro surgery. Correct assembly can be controlled as well as the correct placement of the Boston KPro into the anterior chamber.

We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ∼1  μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ∼7  μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ∼600  μm, and agreement with histology was within about ±50  μm.

Optical coherence tomography (OCT) has been previously identified as a promising tool for exploring laryngeal pathologies in adults. Here, we present an OCT handheld probe dedicated to imaging the unique geometry involved in pediatric laryngoscopy. A vertical cavity surface emitting laser-based wavelength-swept OCT system operating at 60 frames per second was coupled to the probe to acquire three-dimensional (3-D) volumes in vivo. In order to evaluate the performance of the proposed probe and system, we imaged pediatric vocal fold lesions of patients going under direct laryngoscopy. Through this in vivo study, we extracted OCT features characterizing each pediatric vocal fold lesion, which shows a great potential for noninvasive laryngeal lesion discrimination. We believe OCT vocal fold examination in 3-D will result in improved knowledge of the pediatric anatomy and could aid in managing pediatric laryngeal diseases.

Nondestructive imaging of physiological changes in plants has been intensively used as an invaluable tool for visualizing heterogeneous responses to various types of abiotic and biotic stress. However, conventional approaches often have intrinsic limitations for quantitative analyses, requiring bulky and expensive optical instruments for capturing full spectral information. We report a spectrometerless (or spectrometer-free) reflectance imaging method that allows for nondestructive and quantitative chlorophyll imaging in individual leaves in situ in a handheld device format. The combination of a handheld-type imaging system and a hyperspectral reconstruction algorithm from an RGB camera offers simple instrumentation and operation while avoiding the use of an imaging spectrograph or tunable color filter. This platform could potentially be integrated into a compact, inexpensive, and portable system, while being of great value in high-throughput phenotyping facilities and laboratory settings.

We present experimental results that validate our imaging technique termed photomagnetic imaging (PMI). PMI illuminates the medium under investigation with a near-infrared light and measures the induced temperature increase using magnetic resonance imaging. A multiphysics solver combining light and heat propagation is used to model spatiotemporal distribution of temperature increase. Furthermore, a dedicated PMI reconstruction algorithm has been developed to reveal high-resolution optical absorption maps from temperature measurements. Being able to perform measurements at any point within the medium, PMI overcomes the limitations of conventional diffuse optical imaging. We present experimental results obtained on agarose phantoms mimicking biological tissue with inclusions having either different sizes or absorption contrasts, located at various depths. The reconstructed images show that PMI can successfully resolve these inclusions with high resolution and recover their absorption coefficient with high-quantitative accuracy. Even a 1-mm inclusion located 6-mm deep is recovered successfully and its absorption coefficient is underestimated by only 32%. The improved PMI system presented here successfully operates under the maximum skin exposure limits defined by the American National Standards Institute, which opens up the exciting possibility of its future clinical use for diagnostic purposes.

Frequency domain near-infrared spectroscopy (FD-NIRS) has proven to be a reliable method for quantification of tissue absolute optical properties. We present a full-sampling direct analog-to-digital conversion FD-NIR imager. While we developed this instrument with a focus on high-speed optical breast tomographic imaging, the proposed design is suitable for a wide-range of biophotonic applications where fast, accurate quantification of absolute optical properties is needed. Simultaneous dual wavelength operation at 685 and 830 nm is achieved by concurrent 67.5 and 75 MHz frequency modulation of each laser source, respectively, followed by digitization using a high-speed (180  MS/s) 16-bit A/D converter and hybrid FPGA-assisted demodulation. The instrument supports 25 source locations and features 20 concurrently operating detectors. The noise floor of the instrument was measured at <1.4  pW/√Hz, and a dynamic range of 115+ dB, corresponding to nearly six orders of magnitude, has been demonstrated. Titration experiments consisting of 200 different absorption and scattering values were conducted to demonstrate accurate optical property quantification over the entire range of physiologically expected values.

We present the first experimental demonstration of two-photon Mueller matrix second-harmonic generation (SHG) microscopy for the extraction of representative Mueller matrices. Individual SHG images of porcine sample sets are divided into subimages, and the local nonlinear two-photon Mueller matrices (M⁽²⁾) and degree of polarization (p) are determined. Results of the two-photon Mueller matrices from different sample types and the effects of thickness on the mean p distribution per polarization basis are investigated. We find that the p distribution shape changes and an associated bimodal mean difference (μ_d) increases with thickness. Our approach has potential as a quantitative imaging technique and can be applied to other multiphoton coherent imaging modalities.

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. We introduced and tested a multiview hyperspectral imaging technique for noninvasive topographic imaging of cutaneous wound oxygenation. The technique integrated a multiview module and a hyperspectral module in a single portable unit. Four plane mirrors were cohered to form a multiview reflective mirror set with a rectangular cross section. The mirror set was placed between a hyperspectral camera and the target biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional (3-D) topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. 3-D mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique was validated in a wound model, a tissue-simulating blood phantom, and in vivo biological tissue. The experimental results demonstrated the technical feasibility of using multiview hyperspectral imaging for 3-D topography of tissue functional properties.

Fluorescence lifetime imaging microscopy (FLIM) plays a significant role in biological sciences, chemistry, and medical research. We propose a graphic processing unit (GPU) based FLIM analysis tool suitable for high-speed, flexible time-domain FLIM applications. With a large number of parallel processors, GPUs can significantly speed up lifetime calculations compared to CPU-OpenMP (parallel computing with multiple CPU cores) based analysis. We demonstrate how to implement and optimize FLIM algorithms on GPUs for both iterative and noniterative FLIM analysis algorithms. The implemented algorithms have been tested on both synthesized and experimental FLIM data. The results show that at the same precision, the GPU analysis can be up to 24-fold faster than its CPU-OpenMP counterpart. This means that even for high-precision but time-consuming iterative FLIM algorithms, GPUs enable fast or even real-time analysis.

The study of flowing Brownian particles finds numerous biomedical applications, ranging from blood flow analysis to diffusion research. A mathematical model for the correlation function of laser radiation scattered by flowing Brownian particles measured with fiber-based optical coherence tomography (OCT), which accounts for the effects of sample arm optics, is presented. It is shown that the parameters of an OCT optical system of any complexity can be taken into account by using the ABCD ray tracing matrix approach. Specifically, the impact of any optical system can be characterized by the changes in the effective beam radius, which replaces the Gaussian beam radius in the existing mathematical models of scattered radiation. It is shown that the validity of the developed ABCD matrix formalism is governed by the condition that the source coherence length is much smaller than the Rayleigh range in the sample. The predictions of the developed model are compared with previously published theories and with experimental data and agree well with the latter.

Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)₅). Compared with its anionic ZnPc counterpart, ZnPc-(Lys)₅ showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-(Lys)₅ was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO₂), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO₂) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

Optical fibers, consisting of 240-μm-core trunk fibers with rounded, 450-μm-diameter ball tips, are currently used during Holmium:YAG laser lithotripsy to reduce mechanical damage to the inner lining of the ureteroscope working channel during fiber insertion and prolong ureteroscope lifetime. Similarly, this study tests a smaller, 100-μm-core fiber with 300-μm-diameter ball tip during thulium fiber laser (TFL) lithotripsy. TFL was operated at a wavelength of 1908 nm, with 35-mJ pulse energy, 500-μs pulse duration, and 300-Hz pulse rate. Calcium oxalate/phosphate stone samples were weighed, laser procedure times were measured, and ablation rates were calculated for ball tip fibers, with comparison to bare tip fibers. Photographs of ball tips were taken before and after each procedure to track ball tip degradation and determine number of procedures completed before need for replacement. A high speed camera also recorded the cavitation bubble dynamics during TFL lithotripsy. Additionally, saline irrigation rates and ureteroscope deflection were measured with and without the presence of TFL fiber. There was no statistical difference (P>0.05) between stone ablation rates for single-use ball tip fiber (1.3±0.4  mg/s) (n=10), multiple-use ball tip fiber (1.3±0.5  mg/s) (n=44), and conventional single-use bare tip fibers (1.3±0.2  mg/s) (n=10). Ball tip durability varied widely, but fibers averaged greater than four stone procedures before failure, defined by rapid decline in stone ablation rates. Mechanical damage at the front surface of the ball tip was the limiting factor in fiber lifetime. The small fiber diameter did not significantly impact ureteroscope deflection or saline flow rates. The miniature ball tip fiber may provide a cost-effective design for safe fiber insertion through the ureteroscope working channel and into the ureter without risk of instrument damage or tissue perforation, and without compromising stone ablation efficiency during TFL lithotripsy.

Moderate hyperthermia (MHT) has been shown to enhance the effects of chemotherapeutic agents in a wide variety of cancers. The purpose of this study was to investigate the combined effects of commonly used chemotherapeutic agents with MHT induced by near-infrared (NIR) activation of gold nanoshell (AuNS)-loaded macrophages (Ma). AuNS-loaded murine Ma combined with human FaDu squamous cells, in hybrid monolayers, were subjected to three cytotoxic drugs (doxorubicin, bleomycin, cisplatin) with or without NIR laser irradiation. For all three drugs, efficacy was increased by NIR activation of AuNS-loaded Ma. The results of this in vitro study provide proof-of-concept for the use of AuNS-loaded Ma for photothermal enhancement of the effects of chemotherapy on squamous cell carcinoma.

This PDF file contains the errata for “JBO Vol. 21 Issue 01 Paper JBO-2015-1228-ERR” for JBO Vol. 21 Issue 01