With the use of longer near-infrared (NIR) wavelengths, image quality can be increased due to less scattering (described by the inverse wavelength power dependence 1/λⁿ where n≥1) and minimal absorption from water molecules. Longer NIR windows, known as the second (1100 nm to 1350 nm) and third (1600 to 1870 nm) NIR windows are utilized to penetrate more deeply into tissue media and produce high-quality images. An NIR supercontinuum (SC) laser light source, with wavelengths in the second and third NIR optical windows to image tissue provides ballistic imaging of tissue. The SC ballistic beam can penetrate depths of up to 10 mm through tissue.

Cilia-driven fluid flow is a critical yet poorly understood aspect of pulmonary physiology. Here, we demonstrate that optical coherence tomography-based particle tracking velocimetry can be used to quantify subtle variability in cilia-driven flow performance in Xenopus, an important animal model of ciliary biology. Changes in flow performance were quantified in the setting of normal development, as well as in response to three types of perturbations: mechanical (increased fluid viscosity), pharmacological (disrupted serotonin signaling), and genetic (diminished ciliary motor protein expression). Of note, we demonstrate decreased flow secondary to gene knockdown of kif3a a protein involved in ciliogenesis, as well as a dose-response decrease in flow secondary to knockdown of dnah9, an important ciliary motor protein.

We present an ultrahigh-speed optical coherence tomography (OCT) based on an all-optical swept-source with an A-scan rate of 40 MHz. The inertia-free swept-source, which has its output power of 41.2 mW and tuning range of 40 nm and high scan linearity in wavenumber with Pearson’s correlation coefficients r of 0.9996, consists of a supercontinuum laser, an optical band-pass filter, a linearly chirped fiber Bragg grating, an erbium-doped fiber amplifier, and two buffer stages. With sensitivity of 87 dB, high-speed OCT imaging of biological tissue in vivo is also demonstrated.

We present a review of short-wave infrared (SWIR, defined here as ∼1000 to 2000 nm) spectroscopy and imaging techniques for biological tissue optical property characterization. Studies indicate notable SWIR absorption features of tissue constituents including water (near 1150, 1450, and 1900 nm), lipids (near 1040, 1200, 1400, and 1700 nm), and collagen (near 1200 and 1500 nm) that are much more prominent than corresponding features observed in the visible and near-infrared (VIS-NIR, defined here as ∼400 to 1000 nm). Furthermore, the wavelength dependence of the scattering coefficient has been observed to follow a power-law decay from the VIS-NIR to the SWIR region. Thus, the magnitude of tissue scattering is lower at SWIR wavelengths than that observed at VIS or NIR wavelengths, potentially enabling increased penetration depth of incident light at SWIR wavelengths that are not highly absorbed by the aforementioned chromophores. These aspects of SWIR suggest that the tissue spectroscopy and imaging in this range of wavelengths have the potential to provide enhanced sensitivity (relative to VIS-NIR measurements) to chromophores such as water and lipids, thereby helping to characterize changes in the concentrations of these chromophores due to conditions such as atherosclerotic plaque, breast cancer, and burns.

Photoplethysmography (PPG) is an optical technique with high diagnostic potential, yet clinical applications remain underdeveloped. Standardization of signal recording and quantification of waveform are essential prerequisites for broader clinical use. The aim of this study was to utilize a two-stage multi-Gaussian fitting technique in order to examine the parameters of conduit artery PPG waveform recorded during increasing the unilateral regional vascular resistance (RVR). This study was conducted on 14 young and healthy volunteers; various external compressions (ECs) were performed by inflating a tight cuff at 0, 40, 80, and 200 mmHg, while registering femoral PPG (wavelength 880 nm), diameter, blood flow linear velocity (vascular ultrasound), and the arterial pressure (Finapres) during the states of the baseline, partial, and total arterial occlusion, and resultant reactive hyperemia. An increase of the EC elevated the arterial stiffness (AS) and the unilateral distal RVR, and caused a shift of the fitted multi-Gaussian parameters: a decreased delay between reflected and traverse wave components and an increased ratio of their amplitudes. It was concluded that two-stage multi-Gaussian waveform quantification demonstrates an approach potentially extending the use of arterial site PPG in the assessment of diagnostically useful markers e.g., the RVR and the AS.

The ability to monitor changes in the concentration of hemoglobin in the blood of the skin in real time is a key component to personalized patient care. Since hemoglobin has a unique absorption spectrum in the visible light range, diffuse reflectance spectroscopy is the most common approach. Although the collection of the diffuse reflectance spectrum with an integrating sphere (IS) has several calibration challenges, this collection method is sufficiently user-friendly that it may be worth overcoming the initial difficulty. Once the spectrum is obtained, it is commonly interpreted with a log-inverse-reflectance (LIR) or “absorbance” analysis that can only accurately monitor changes in the hemoglobin concentration when there are no changes to the nonhemoglobin chromophore concentrations which is not always the case. We address the difficulties associated with collection of the diffuse reflectance spectrum with an IS and propose a model capable of retrieving relative changes in hemoglobin concentration from the visible light spectrum. The model is capable of accounting for concentration changes in the nonhemoglobin chromophores and is first characterized with theoretical spectra and liquid phantoms. The model is then used in comparison with a common LIR analysis on temporal measurements from blanched and reddened human skin.

A micro-Raman spectroscopy investigation has been performed in vitro on single human mammary epithelial cells after irradiation by graded x-ray doses. The analysis by principal component analysis (PCA) and interval-PCA (i-PCA) methods has allowed us to point out the small differences in the Raman spectra induced by irradiation. This experimental approach has enabled us to delineate radiation-induced changes in protein, nucleic acid, lipid, and carbohydrate content. In particular, the dose dependence of PCA and i-PCA components has been analyzed. Our results have confirmed that micro-Raman spectroscopy coupled to properly chosen data analysis methods is a very sensitive technique to detect early molecular changes at the single-cell level following exposure to ionizing radiation. This would help in developing innovative approaches to monitor radiation cancer radiotherapy outcome so as to reduce the overall radiation dose and minimize damage to the surrounding healthy cells, both aspects being of great importance in the field of radiation therapy.

Sinus blockages are a common reason for physician visits, affecting one out of seven people in the United States, and often require medical treatment. Diagnosis in the primary care setting is challenging because symptom criteria (via detailed clinical history) plus objective imaging [computed tomography (CT) or endoscopy] are recommended. Unfortunately, neither option is routinely available in primary care. We previously demonstrated that low-cost near-infrared (NIR) transillumination correlates with the bulk findings of sinus opacity measured by CT. We have upgraded the technology, but questions of source optimization, anatomical influence, and detection limits remain. In order to begin addressing these questions, we have modeled NIR light propagation inside a three-dimensional adult human head constructed via CT images using a mesh-based Monte Carlo algorithm (MMCLAB). In this application, the sinus itself, which when healthy is a void region (e.g., nonscattering), is the region of interest. We characterize the changes in detected intensity due to clear (i.e., healthy) versus blocked sinuses and the effect of illumination patterns. We ran simulations for two clinical cases and compared simulations with measurements. The simulations presented herein serve as a proof of concept that this approach could be used to understand contrast mechanisms and limitations of NIR sinus imaging.

Detection and enumeration of circulating cells in the bloodstream of small animals are important in many areas of preclinical biomedical research, including cancer metastasis, immunology, and reproductive medicine. Optical in vivo flow cytometry (IVFC) represents a class of technologies that allow noninvasive and continuous enumeration of circulating cells without drawing blood samples. We recently developed a technique termed computer vision in vivo flow cytometry (CV-IVFC) that uses a high-sensitivity fluorescence camera and an automated computer vision algorithm to interrogate relatively large circulating blood volumes in the ear of a mouse. We detected circulating cells at concentrations as low as 20  cells/mL. In the present work, we characterized the performance of CV-IVFC with low-contrast imaging conditions with (1) weak cell fluorescent labeling using cell-simulating fluorescent microspheres with varying brightness and (2) high background tissue autofluorescence by varying autofluorescence properties of optical phantoms. Our analysis indicates that CV-IVFC can robustly track and enumerate circulating cells with at least 50% sensitivity even in conditions with two orders of magnitude degraded contrast than our previous in vivo work. These results support the significant potential utility of CV-IVFC in a wide range of in vivo biological models.

We report a second derivative multispectral algorithm for quantitative assessment of cutaneous tissue oxygen saturation (StO₂). The algorithm is based on a forward model of light transport in multilayered skin tissue and an inverse algorithm for StO₂ reconstruction. Based on the forward simulation results, a parameter of a second derivative ratio (SDR) is derived as a function of cutaneous tissue StO₂. The SDR function is optimized at a wavelength set of 544, 552, 568, 576, 592, and 600 nm so that cutaneous tissue StO₂ can be derived with minimal artifacts by blood concentration, tissue scattering, and melanin concentration. The proposed multispectral StO₂ imaging algorithm is verified in both benchtop and in vivo experiments. The experimental results show that the proposed multispectral imaging algorithm is able to map cutaneous tissue StO₂ in high temporal resolution with reduced measurement artifacts induced by different skin conditions in comparison with other three commercial tissue oxygen measurement systems. These results indicate that the multispectral StO₂ imaging technique has the potential for noninvasive and quantitative assessment of skin tissue oxygenation with a high temporal resolution.

Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

Quantitative investigations of fiber orientation and structural connectivity at microscopic resolution have led to great challenges for current neuroimaging techniques. Here, we present a structure tensor (ST) analysis of ex vivo rat brain images acquired by a multicontrast (MC) serial optical coherence scanner. The ST considers the gradients of images in local neighbors to generate a matrix whose eigen-decomposition can estimate the local features such as the edges, anisotropy, and orientation of tissue constituents. This computational analysis is applied on the conventional- and polarization-based contrasts of optical coherence tomography. The three-dimensional (3-D) fiber orientation maps are computed from the image stacks of sequential scans both at mesoresolution for a global view and at high-resolution for the details. The computational orientation maps demonstrate a good agreement with the optic axis orientation contrast which measures the in-plane fiber orientation. Moreover, tractography is implemented using the directional information extracted from the 3-D ST. The study provides a unique opportunity to leverage MC high-resolution information to map structural connectivity of the whole brain.

Measuring the partial pressure of oxygen (pO₂) in tissue may provide physicians with essential information about the physiological state of tissue. However, currently available methods for measuring or imaging tissue pO₂ have significant limitations, preventing them from being widely used in clinics. Recently, we have reported a direct and noninvasive in vivo imaging modality based on the photoacoustic lifetime which overcomes certain drawbacks of the existing methods. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflecting the spatial and temporal distributions of tissue oxygen. Here, we present two studies which apply photoacoustic lifetime imaging (PALI) to monitor changes of tissue oxygen induced by external modulations. The first study modulates tissue oxygen by controlling the percentage of oxygen a normal mouse inhales. We demonstrate that PALI is able to reflect the change in oxygen level with respect to normal, oxygen-rich, and oxygen-poor breathing conditions. The second study involves an acute ischemia model using a thin thread tied around the hindlimb of a normal mouse to reduce the blood flow. PALI images were acquired before, during, and after the restriction. The drop of tissue pO₂ and recovery from hypoxia due to reperfusion were tracked and observed by PALI.

Increase in abnormal microvessels in the superficial mucosa is often relevant to diagnostic findings of neoplasia in digestive endoscopy; hence, observation of superficial vasculature is crucial for cancer diagnosis. To enhance the appearance of such vessels, several spectral endoscopic imaging techniques have been developed, such as narrow-band imaging and blue laser imaging. Both techniques exploit narrow-band blue light for the enhancement. The emergence of such spectral imaging techniques has increased the importance of understanding the relation of the light wavelength to the appearance of superficial vasculature, and thus a new method is desired for quantitative analysis of vessel visibility in relation to the actual structure in the tissue. Here, we developed microvessel-simulating phantoms that allowed quantitative evaluation of the appearance of 15-μm-thick vessels. We investigated the relation between the vascular contrast and light wavelength by the phantom measurements and also verified it in experiments with swine, where the endoscopically observed vascular contrast was investigated together with its real vascular depth and diameter obtained by microscopic observation of fluorescence-labeled vessels. Our study indicates that changing the spectral property even in the wavelength range of blue light may allow selective enhancement of the vascular depth for clinical use.

Optical coherence tomography (OCT) is an important interferometric diagnostic technique, which provides cross-sectional views of biological tissues’ subsurface microstructures. However, the imaging quality of high-speed OCT is limited by the large speckle noise. To address this problem, we propose a multiframe algorithmic method to denoise OCT volume. Mathematically, we build an optimization model which forces the temporally registered frames to be low-rank and the gradient in each frame to be sparse, under the constraints from logarithmic image formation and nonuniform noise variance. In addition, a convex optimization algorithm based on the augmented Lagrangian method is derived to solve the above model. The results reveal that our approach outperforms the other methods in terms of both speckle noise suppression and crucial detail preservation.

Due to the various causes of methemoglobinemia and its potential to be confused with other diseases, in vivo measurements of methemoglobin have significant applications in the clinic. Using photoacoustic microscopy (PAM), we quantified the average and the distributed percentage of methemoglobin both in vitro and in vivo. Based on the absorption spectra of methemoglobin, oxyhemoglobin, and deoxyhemoglobin, three wavelengths were chosen to differentiate methemoglobin from the others. The methemoglobin concentrations calculated from the photoacoustic signals agreed well with the preset concentrations. Then we imaged the methemoglobin percentage in microtubes that mimicked blood vessels. Average percentages calculated for five samples with different methemoglobin concentrations also agreed well with the preset values. Finally, we demonstrated the ability of PAM to detect methemoglobin in vivo in a mouse ear. Our results show that PAM can quantitatively image methemoglobin distribution in vivo.

We first investigated the similarity in optical quality of a batch of diffractive intraocular lenses (DIOLs), providing experimental evidence for one DIOL as representative of a batch. Using adaptive optics, we then evaluated one DIOL under different levels of Zernike spherical aberration (SA) by applying both a point spread function test and a psychophysical visual acuity test. We found that for small aperture size SA has the effect of shifting the through-focus curve of DIOL. Also, for a relatively large aperture size, it has different effects on the distant and near foci.

Optical coherence tomography (OCT) has advanced significantly over the past two decades and is currently used extensively to monitor the internal structures of organs, particularly in ophthalmology and dermatology. We used ethylenediamine tetra-acetic acid (EDTA) to decalcify the bony walls of the cochlea and investigated the inner structures by deep penetration of light into the cochlear tissue using OCT on a guinea pig model of endolymphatic hydrops (EH), induced by surgical obliteration of the endolymphatic duct. The structural and functional changes associated with EH were identified using OCT and auditory brainstem response tests, respectively. We also evaluated structural alterations in the cochlea using three-dimensional reconstruction of the OCT images, which clearly showed physical changes in the cochlear structures. Furthermore, we found significant anatomical variations in the EH model and conducted graphical analysis by strial atrophy for comparison. The physical changes included damage to and flattening of the organ of Corti—evidence of Reissner’s membrane distention—and thinning of the lateral wall. These results indicate that observation of EDTA-decalcified cochlea using OCT is significant in examination of gradual changes in the cochlear structures that are otherwise not depicted by hematoxylin and eosin staining.

Early detection and treatment of high-grade dysplasia (HGD) in Barrett’s esophagus may reduce the risk of developing esophageal adenocarcinoma. Confocal endomicroscopy (CLE) has shown advantages over routine white-light endoscopic surveillance with biopsy for histological examination; however, CLE is compromised by insufficient contrast and by intra- and interobserver variation. An FDA-approved PDT photosensitizer was used here to reveal morphological and textural features similar to those found in histological analysis. Support vector machines were trained using the aforementioned features to obtain an automatic and robust detection of HGD. Our results showed 95% sensitivity and 87% specificity using the optimal feature combination and demonstrated the potential for extension to a three-dimensional cell model.

In this work, we demonstrated the possibility of high spatial resolution Cherenkov luminescence imaging (CLI) for objects in transparent media. We also demonstrated the possibility of the CLI of thin opaque objects using optical transducers. Results demonstrate that submillimeter resolution CLI is achievable for beta-emitting radionuclides, including ⁷⁶Br that emits positrons of very high energy. The imaging of beta-emitters through scintillation detectors exhibits lower resolution when compared to CLI of the same sources. The application of optical transducers for the CLI was demonstrated using plants labeled with ¹¹CO₂ and phantoms containing beta-emitters.

A fluorescence resonance energy transfer (FRET)-based microbubble contrast agent system was designed to experimentally demonstrate the concept of ultrasound-modulated fluorescence (UMF). Microbubbles were simultaneously labeled with donor and acceptor fluorophores on the surface to minimize self-quenching and maximize FRET. In response to ultrasound, the quenching efficiency was greatly modulated by changing the distance between the donor and acceptor molecules through microbubble size oscillations. Both donors and acceptors exhibited UMF on individual microbubbles. The UMF strength of the donor was more significant compared to that of the acceptor. Furthermore, the UMF of the donor was observed from a microbubble solution in a turbid media. This study exploits the feasibility of donor–acceptor labeled microbubbles as UMF contrast agents.

The image quality of optical coherence tomography can be severely influenced by speckle noise (i.e., signal-degrading speckle). Averaging multiple B-scans can effectively suppress speckle noise. Because of sample motion, images subject to averaging must be aligned exactly. We propose a two-step image registration scheme that combines global and local registrations for speckle reduction by the averaging of multiple B-scans. The method begins with a global registration to compensate for overall motion, which is estimated based on the rigid transformation model involving translation and rotation. Then each A-scan is aligned by cross-correlation using a graph-based algorithm, followed by a pixel subdivision method to improve smoothness in local registration. The method does not rely on any information about the retinal layer boundaries. We have applied this method to the registration of macular optical coherence tomography images. The results show the reduction of speckle noise and the enhanced visualization of layer structures. A signal-to-noise ratio improvement of nearly the square root of the number of averaged B-scans and a contrast-to-noise ratio improvement of around 11 are achieved through our method.

Obtaining accurate quantitative information on the concentration and distribution of fluorescent markers lying at a depth below the surface of optically turbid media, such as tissue, is a significant challenge. Here, we introduce a fluorescence reconstruction technique based on a diffusion light transport model that can be used during surgery, including guiding resection of brain tumors, for depth-resolved quantitative imaging of near-infrared fluorescent markers. Hyperspectral fluorescence images are used to compute a topographic map of the fluorophore distribution, which yields structural and optical constraints for a three-dimensional subsequent hyperspectral diffuse fluorescence reconstruction algorithm. Using the model fluorophore Alexa Fluor 647 and brain-like tissue phantoms, the technique yielded estimates of fluorophore concentration within ±25% of the true value to depths of 5 to 9 mm, depending on the concentration. The approach is practical for integration into a neurosurgical fluorescence microscope and has potential to further extend fluorescence-guided resection using objective and quantified metrics of the presence of residual tumor tissue.

Quantitative photoacoustic tomography is an emerging imaging technique aimed at estimating optical parameters inside tissues from photoacoustic images, which are formed by combining optical information and ultrasonic propagation. This optical parameter estimation problem is ill-posed and needs to be approached within the framework of inverse problems. It has been shown that, in general, estimating the spatial distribution of more than one optical parameter is a nonunique problem unless more than one illumination pattern is used. Generally, this is overcome by illuminating the target from various directions. However, in some cases, for example when thick samples are investigated, illuminating the target from different directions may not be possible. In this work, the use of spatially modulated illumination patterns at one side of the target is investigated with simulations. The results show that the spatially modulated illumination patterns from a single direction could be used to provide multiple illuminations for quantitative photoacoustic tomography. Furthermore, the results show that the approach can be used to distinguish absorption and scattering inclusions located near the surface of the target. However, when compared to a full multidirection illumination setup, the approach cannot be used to image as deep inside tissues.

We present an implementation of spectrally encoded slit confocal microscopy. The method employs a rapid wavelength-swept laser as the light source and illuminates a specimen with a line focus that scans through the specimen as the wavelength sweeps. The reflected light from the specimen is imaged with a stationary line scan camera, in which the finite pixel height serves as a slit aperture. This scanner-free operation enables a simple and cost-effective implementation in a small form factor, while allowing for the three-dimensional imaging of biological samples.

Based on a terahertz (THz) pipe-based near-field imaging system, we demonstrate the capability of THz imaging to diagnose freshly surgically excised human colonic tissues. Through THz near-field scanning the absorbance of the colonic tissues, the acquired images can clearly distinguish cancerous tissues from healthy tissues fast and automatically without pathological hematoxylin and eosin stain diagnosis. A statistical study on 58 specimens (20 healthy tissues and 38 tissues with tumor) from 31 patients (mean age: 59 years; range: 46 to 79 years) shows that the corresponding diagnostic sensitivity and specificity on colonic tissues are both 100%. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations.

Cell transplantation and stem cell therapy are promising approaches for regenerative medicine and are of interest to researchers and clinicians worldwide. However, currently, no imaging technique that allows three-dimensional in vivo inspection of therapeutically administered cells in host tissues is available. Therefore, we investigate magnetomotive optical coherence tomography (MM-OCT) of cells labeled with magnetic particles as a potential noninvasive cell tracking method. We develop magnetomotive imaging of mesenchymal stem cells for future cell therapy monitoring. Cells were labeled with fluorescent iron oxide nanoparticles, embedded in tissue-mimicking agar scaffolds, and imaged using a microscope setup with an integrated MM-OCT probe. Magnetic particle-induced motion in response to a pulsed magnetic field of 0.2 T was successfully detected by OCT speckle variance analysis, and cross-sectional and volumetric OCT scans with highlighted labeled cells were obtained. In parallel, fluorescence microscopy and laser speckle reflectometry were applied as two-dimensional reference modalities to image particle distribution and magnetically induced motion inside the sample, respectively. All three optical imaging modalities were in good agreement with each other. Thus, magnetomotive imaging using iron oxide nanoparticles as cellular contrast agents is a potential technique for enhanced visualization of selected cells in OCT.

A robust biomedical sensor for ultrasensitive detection of biomarkers in breath based on a tunable external cavity laser (ECL) and an off-axis cavity-enhanced absorption spectroscopy (OA-CEAS) using an amplitude stabilizer is developed. A single-mode, narrow-linewidth, tunable ECL is demonstrated. A broadly coarse wavelength tuning range of 720  cm⁻¹ for the spectral range between 6890 and 6170  cm⁻¹ is achieved by rotating the diffraction grating forming a Littrow-type external-cavity configuration. A mode-hop-free tuning range of 1.85  cm⁻¹ is obtained. The linewidths below 140 kHz are recorded. The ECL is combined with an OA-CEAS to perform laser chemical sensing. Our system is able to detect any molecule in breath at concentrations to the ppbv range that have absorption lines in the spectral range between 1450 and 1620 nm. Ammonia is selected as target molecule to evaluate the performance of the sensor. Using the absorption line of ammonia at 6528.76  cm⁻¹, a minimum detectable absorption coefficient of approximately 1×10⁻⁸  cm⁻¹ is demonstrated for 256 averages. This is achieved for a 1.4-km absorption path length and a 2-s data-acquisition time. These results yield a detection sensitivity of approximately 8.6×10⁻¹⁰  cm⁻¹ Hz^−1/2. Ammonia in exhaled breath is analyzed and found in a concentration of 870 ppb for our example.

Cancer is the main cause of canine morbidity and mortality. The existing evaluation of tumors requires an experienced veterinarian and usually includes invasive procedures (e.g., fine-needle aspiration) that can be unpleasant for the dog and the owner. We investigate visible and near-infrared diffuse reflectance spectroscopy (DRS) as a noninvasive optical technique for evaluation and detection of canine skin and subcutaneous tumors ex vivo and in vivo. The optical properties of tumors and skin were calculated in a spectrally constrained manner, using a lookup table-based inverse model. The obtained optical properties were analyzed and compared among different tumor groups. The calculated parameters of the absorption and reduced scattering coefficients were subsequently used for detection of malignant skin and subcutaneous tumors. The detection sensitivity and specificity of malignant tumors ex vivo were 90.0% and 73.5%, respectively, while corresponding detection sensitivity and specificity of malignant tumors in vivo were 88.4% and 54.6%, respectively. The obtained results show that the DRS is a promising noninvasive optical technique for detection and classification of malignant and benign canine skin and subcutaneous tumors. The method should be further investigated on tumors with common origin.

We have recently applied the technique of drop coating deposition Raman (DCDR) spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of this study was to develop a more convenient and stable method based on blood plasma for noninvasive CRC detection. Significant differences are observed in DCDR spectra between healthy (n=105) and cancer (n=75) plasma from 15 CRC patients and 21 volunteers, particularly in the spectra that are related to proteins, nucleic acids, and β-carotene. The multivariate analysis principal components analysis and the linear discriminate analysis, together with leave-one-out, cross validation were used on DCDR spectra and yielded a sensitivity of 100% (75/75) and specificity of 98.1% (103/105) for detection of CRC. This study demonstrates that DCDR spectroscopy of blood plasma associated with multivariate statistical algorithms has the potential for the noninvasive detection of CRC.

Urodynamic analysis is the predominant method for evaluating dysfunctions in the lower urinary tract. The exam measures the pressure during the filling and voiding process of the bladder and is mainly interested in the contraction of the bladder muscles. The data arising out of these pressure measurements enables the urologist to arrive at a precise diagnosis and prescribe an adequate treatment. A technique based on two optical fiber pressure and temperature sensors with a resolution of better than 0.1  cm H₂O (∼10  Pa), a stability better than 1  cm H₂O/hour, and a diameter of 0.2 mm in a miniature catheter with a diameter of only 5 Fr (1.67 mm), was used. This technique was tested in vivo on four patients with a real-time urodynamic measurement system. The optical system presented showed a very good correlation to two commercially available medical reference sensors. Furthermore, the optical urodynamic system demonstrated a higher dynamic and better sensitivity to detect small obstructions than both pre-existing medical systems currently in use in the urodynamic field.

Hemagglutinin (HA) is the main surface glycoprotein of the influenza A virus. The H9N2 subtype influenza A virus is recognized as the most possible pandemic strain as it has crossed the species barrier, infecting swine and humans. We use terahertz spectroscopy to study the hydration shell formation around H9 subtype influenza A virus’s HA protein (H9 HA) as well as the detection of antigen binding of H9 HA with the broadly neutralizing monoclonal antibody. We observe a remarkable concentration dependent nonlinear response of the H9 HA, which reveals the formation process of the hydration shell around H9 HA molecules. Furthermore, we show that terahertz dielectric properties of the H9 HA are strongly affected by the presence of the monoclonal antibody F10 and that the terahertz dielectric loss tangent can be used to detect the antibody binding at lower concentrations than the standard ELISA test.

Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized optical techniques that can track low-frequency perfusion changes in microcirculation. The aim of this study was to determine, in healthy subjects, the correlation between the techniques for specific low-frequency bands previously defined for microcirculation. Twelve healthy male subjects (age range 18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from their right and left index (PPG) and middle (LDF) fingers. Wavelet analysis comprised dividing the low-frequency integral wavelet spectrum (IWS) into five established physiological bands relating to cardiac, respiratory, myogenic, neurogenic, and endothelial activities. The correlation between PPG and LDF was quantified using wavelet correlation analysis and Spearman correlation analysis of the median IWS amplitude. The median wavelet correlation between signals (right-left side average) was 0.45 (cardiac), 0.49 (respiratory), 0.86 (myogenic), 0.91 (neurogenic), and 0.91 (endothelial). The correlation of IWS amplitude values (right-left side average) was statistically significant for the cardiac (ρ=0.64, p<0.05) and endothelial (ρ=0.62, p<0.05) bands. This pilot study has shown good correlation between PPG and LDF for specific physiological frequency bands. In particular, the results suggest that PPG has the potential to be a low-cost replacement for LDF for endothelial activity assessments.

Spectral measurement of fluorescence resonance energy transfer (FRET), spFRET, is a widely used FRET quantification method in living cells today. We set up a spectrometer-microscope platform that consists of a miniature fiber optic spectrometer and a widefield fluorescence microscope for the spectral measurement of absolute FRET efficiency (E) and acceptor-to-donor concentration ratio (R_C) in single living cells. The microscope was used for guiding cells and the spectra were simultaneously detected by the miniature fiber optic spectrometer. Moreover, our platform has independent excitation and emission controllers, so different excitations can share the same emission channel. In addition, we developed a modified spectral FRET quantification method (mlux-FRET) for the multiple donors and multiple acceptors FRET construct (mD∼nA) sample, and we also developed a spectra-based 2-channel acceptor-sensitized FRET quantification method (spE-FRET). We implemented these modified FRET quantification methods on our platform to measure the absolute E and R_C values of tandem constructs with different acceptor/donor stoichiometries in single living Huh-7 cells.

The aim was to compare two conventional methods used to describe cerebral autoregulation (CA): frequency-domain analysis and time-domain analysis. We measured cerebral oxygenation (as a surrogate for cerebral blood flow) and mean arterial blood pressure (MAP) in 60 preterm infants. In the frequency domain, outcome variables were coherence and gain, whereas the cerebral oximetry index (COx) and the regression coefficient were the outcome variables in the time domain. Correlation between coherence and COx was poor. The disagreement between the two methods was due to the MAP and cerebral oxygenation signals being in counterphase in three cases. High gain and high coherence may arise spuriously when cerebral oxygenation decreases as MAP increases; hence, time-domain analysis appears to be a more robust—and simpler—method to describe CA.

An appropriate expression for the oxygen supply rate (Γ_s) is required for the macroscopic modeling of the complex mechanisms of photodynamic therapy (PDT). It is unrealistic to model the actual heterogeneous tumor microvascular networks coupled with the PDT processes because of the large computational requirement. In this study, a theoretical microscopic model based on uniformly distributed Krogh cylinders is used to calculate Γs=g(1−[³O₂]/[³O₂]₀) that can replace the complex modeling of blood vasculature while maintaining a reasonable resemblance to reality; g is the maximum oxygen supply rate and [³O₂]/[³O₂]₀ is the volume-average tissue oxygen concentration normalized to its value prior to PDT. The model incorporates kinetic equations of oxygen diffusion and convection within capillaries and oxygen saturation from oxyhemoglobin. Oxygen supply to the tissue is via diffusion from the uniformly distributed blood vessels. Oxygen can also diffuse along the radius and the longitudinal axis of the cylinder within tissue. The relations of Γs to [³O₂]/[³O₂]₀ are examined for a biologically reasonable range of the physiological parameters for the microvasculature and several light fluence rates (ϕ). The results show a linear relationship between Γs and [³O₂]/[³O₂]₀, independent of ϕ and photochemical parameters; the obtained g ranges from 0.4 to 1390  μM/s.

This research analyzed the quality of resin-based sealer adaptation after intracanal laser irradiation. Extracted teeth (n=168) were root canal treated and divided into four groups, according to dentin surface treatment: no laser; Nd:YAG laser (1.5 W, 100 mJ, 15 Hz); diode laser (2.5 W in CW), and Er:YAG laser (1 W, 100 mJ, 10 Hz). The teeth were divided into four subgroups according to the sealer used: AH Plus, EndoREZ, Epiphany, and EpiphanySE. For testing the sealing after root canal obturation, the penetration of silver nitrate solution was measured, whereas to evaluate the adaptation and penetration of the sealer into the dentin, environmental scanning electron microscopy (ESEM) was used. The ESEM images were analyzed using a four-grade criteria score by three evaluators. The inter-examiner agreement was confirmed by Kappa test and the scores statistically compared by the Kruskal-Wallis’ test (p<0.05). Both adaptation and sealer penetration in root canals were not affected by the laser irradiation. Nd:YAG and diode laser decreased the tracer penetration for AH Plus, whereas EndoREZ and EpiphanySE performances were affected by Nd:YAG irradiation (p<0.05). It can be concluded that intracanal laser irradiation can be used as an adjunct in endodontic treatment; however, the use of hydrophilic resin sealers should be avoided when root canals were irradiated with Nd:YAG laser.38002

In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20  mg/kg calcein was administered to all of the rats, and on the 80th day, 20  mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey’s post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

This PDF file contains the errata for “JBO Vol. 20 Issue 03 Paper JBO-2015-0320-ERR” for JBO Vol. 20 Issue 03