Breast conserving surgery allows complete tumor resection while maintaining acceptable cosmesis for patients. Safe and rapid intraoperative margin assessment during the procedure is important to establish the completeness of tumor excision and minimizes the need for reoperation. Confocal laser endomicroscopy has demonstrated promise for real-time intraoperative margin assessment using acriflavine staining, but it is not approved for routine in-human use. We describe a custom high-speed line-scan confocal laser endomicroscopy (LS-CLE) system at 660 nm that enables high-resolution histomorphological imaging of breast tissue stained with methylene-blue, an alternative fluorescent stain for localizing sentinel nodes during breast surgery. Preliminary imaging results on freshly excised human breast tissue specimens are presented, demonstrating the potential of methylene-blue aided rapid LS-CLE to determine the oncological status of surgical margins in-vivo.

Current clinical tools provide critical information about ocular health such as intraocular pressure (IOP). However, they lack the ability to quantify tissue material properties, which are potent markers for ocular tissue health and integrity. We describe a single instrument to measure the eye-globe IOP, quantify corneal biomechanical properties, and measure corneal geometry with a technique termed applanation optical coherence elastography (Appl-OCE). An ultrafast OCT system enabled visualization of corneal dynamics during noncontact applanation tonometry and direct measurement of micro air-pulse induced elastic wave propagation. Our preliminary results show that the proposed Appl-OCE system can be used to quantify IOP, corneal biomechanical properties, and corneal geometry, which builds a solid foundation for a unique device that can provide a more complete picture of ocular health.

Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ∼5  min. An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p=0.038; 166  μmol/L versus 17  μmol/L, p=0.039, respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling.

Confocal mosaicking microscopy (CMM) enables rapid imaging of large areas of fresh tissue ex vivo without the processing that is necessary for conventional histology. When performed in fluorescence mode using acridine orange (nuclear specific dye), it enhances nuclei-to-dermis contrast that enables detection of all types of basal cell carcinomas (BCCs), including micronodular and thin strands of infiltrative types. So far, this technique has been mostly validated in research settings for the detection of residual BCC tumor margins with high sensitivity of 89% to 96% and specificity of 99% to 89%. Recently, CMM has advanced to implementation and testing in clinical settings by “early adopter” Mohs surgeons, as an adjunct to frozen section during Mohs surgery. We summarize the development of CMM guided imaging of ex vivo skin tissues from bench to bedside. We also present its current state of application in routine clinical workflow not only for the assessment of residual BCC margins in the Mohs surgical setting but also for some melanocytic lesions and other skin conditions in clinical dermatology settings. Last, we also discuss the potential limitations of this technology as well as future developments. As this technology advances further, it may serve as an adjunct to standard histology and enable rapid surgical pathology of skin cancers at the bedside.

Tissue oxygenation estimated by near-infrared spectroscopy (NIRS) is a volume-weighted mean of the arterial and venous hemoglobin oxygenation. <italic>In vivo</italic> validation assumes a fixed arterial-to-venous volume-ratio (AV-ratio). Regulatory cerebro-vascular mechanisms may change the AV-ratio. We used hypotension to investigate the influence of blood volume distribution on cerebral NIRS in a newborn piglet model. Hypotension was induced gradually by inflating a balloon-catheter in the inferior vena cava and the regional tissue oxygenation from NIRS (<inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>rStO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mi>NIRS</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula>) was then compared to a reference (<inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>rStO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mi>COX</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula>) calculated from superior sagittal sinus and aortic blood sample co-oximetry with a fixed AV-ratio. Apparent changes in the AV-ratio and cerebral blood volume (CBV) were also calculated. The mean arterial blood pressure (MABP) range was 14 to 82 mmHg. <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>PaCO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula> and <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>SaO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula> were stable during measurements. <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>rStO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mi>NIRS</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula> mirrored only 25% (95% Cl: 21% to 28%, <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo><</mml:mo> <mml:mn>0.001</mml:mn> </mml:mrow> </mml:math> </inline-formula>) of changes in <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>rStO</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mi>COX</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> </inline-formula>. Calculated AV-ratio increased with decreasing MABP (slope: <inline-formula> <mml:math display="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mo form="prefix">−</mml:mo> <mml:mn>0.007</mml:mn> <mml:mo>·</mml:mo> <mml:msup> <mml:mrow> <mml:mi>mmHg</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> </mml:mrow>

Oxygen saturation (sO2) of red blood cells (RBCs) in capillaries can indirectly assess local tissue oxygenation and metabolic function. For example, the altered retinal oxygenation in diabetic retinopathy and local hypoxia during tumor development in cancer are reflected by abnormal sO2 of local capillary networks. However, it is far from clear whether accurate label-free optical oximetry (i.e., measuring hemoglobin sO2) is feasible from dispersed RBCs at the single capillary level. The sO2-dependent hemoglobin absorption contrast present in optical scattering signal is complicated by geometry-dependent scattering from RBCs. We present a numerical study of backscattering spectra from single RBCs based on the first-order Born approximation, considering practical factors: RBC orientations, size variation, and deformations. We show that the oscillatory spectral behavior of RBC geometries is smoothed by variations in cell size and orientation, resulting in clear sO2-dependent spectral contrast. In addition, this spectral contrast persists with different mean cellular hemoglobin content and different deformations of RBCs. This study shows for the first time the feasibility of, and provides a theoretical model for, label-free optical oximetry at the single capillary level using backscattering-based imaging modalities, challenging the popular view that such measurements are impossible at the single capillary level.

Pressure injuries (PIs) originate beneath the surface of the skin at the interface between bone and soft tissue. We used diffuse correlation spectroscopy (DCS) and diffuse near-infrared spectroscopy (DNIRS) to predict the development of PIs by measuring dermal and subcutaneous red cell motion and optical absorption and scattering properties in 11 spinal cord injury subjects with only nonbleachable redness in the sacrococcygeal area in a rehabilitation hospital and 20 healthy volunteers. A custom optical probe was developed to obtain continuous DCS and DNIRS data from sacrococcygeal tissue while the subjects were placed in supine and lateral positions to apply pressure from body weight and to release pressure, respectively. Rehabilitation patients were measured up to four times over a two-week period. Three rehabilitation patients developed open PIs (POs) within four weeks and eight patients did not (PNOs). Temporal correlation functions in the area of redness were significantly different (p<0.01) during both baseline and applied pressure stages for POs and PNOs. The results show that our optical method may be used for the early prediction of ulcer progression.

A novel method for the automated detection of the outer choroid boundary within spectral-domain optical coherence tomography image data, based on an image model within the space of functions of bounded variation and the application of quadratic measure filters, is presented. The same method is used for the segmentation of retinal layer boundaries and proves to be suitable even for data generated without special imaging modes and moderate line averaging. Based on the segmentations, an automated determination of the central fovea region and choroidal thickness measurements for this and two adjacent 1-mm regions are provided. The quality of the method is assessed by comparison with manual delineations performed by five trained graders. The study is based on data from 50 children of the ages 8 to 13 that were obtained in the framework of the LIFE Child study at Leipzig University.

We propose a three-dimensional (3-D) registration method to correct motion artifacts and construct the volume structure for angiographic and structural optical coherence tomography (OCT). This algorithm is particularly suitable for the nonorthogonal wide-field OCT scan acquired by a ultrahigh-speed swept-source system (>200  kHz A-scan rate). First, the transverse motion artifacts are corrected by the between-frame registration based on en face OCT angiography (OCTA). After A-scan transverse translation between B-frames, the axial motions are corrected based on the rebuilt boundary of inner limiting membrane. Finally, a within-frame registration is performed for local optimization based on cross-sectional OCTA. We evaluated this algorithm on retinal volumes of six normal subjects. The results showed significantly improved retinal smoothness in 3-D-registered structural OCT and image contrast on en face OCTA.

Ultrasound-guided diffuse optical tomography (DOT) is a promising imaging technique that maps hemoglobin concentrations of breast lesions to assist ultrasound (US) for cancer diagnosis and treatment monitoring. The accurate recovery of breast lesion optical properties requires an effective image reconstruction method. We introduce a reconstruction approach in which US images are encoded as prior information for regularization of the inversion matrix. The framework of this approach is based on image reconstruction package “NIRFAST.” We compare this approach to the US-guided dual-zone mesh reconstruction method, which is based on Born approximation and conjugate gradient optimization developed in our laboratory. Results were evaluated using phantoms and clinical data. This method improves classification of malignant and benign lesions by increasing malignant to benign lesion absorption contrast. The results also show improvements in reconstructed lesion shapes and the spatial distribution of absorption maps.

The present study describes utilization of two photon excitation fluorescence (2PE) microscopy for visualization of the hemoglobin in human and porcine erythrocytes and their empty membranes (i.e., ghosts). High-quality, label- and fixation-free visualization of hemoglobin was achieved at excitation wavelength 730 nm by detecting visible autofluorescence. Localization in the suspension and spatial distribution (i.e., mapping) of residual hemoglobin in erythrocyte ghosts has been resolved by 2PE. Prior to the 2PE mapping, the presence of residual hemoglobin in the bulk suspension of erythrocyte ghosts was confirmed by cyanmethemoglobin assay. 2PE analysis revealed that the distribution of hemoglobin in intact erythrocytes follows the cells’ shape. Two types of erythrocytes, human and porcine, characterized with discocyte and echinocyte morphology, respectively, showed significant differences in hemoglobin distribution. The 2PE images have revealed that despite an extensive washing out procedure after gradual hypotonic hemolysis, a certain amount of hemoglobin localized on the intracellular side always remains bound to the membrane and cannot be eliminated. The obtained results open the possibility to use 2PE microscopy to examine hemoglobin distribution in erythrocytes and estimate the purity level of erythrocyte ghosts in biotechnological processes.

We report on the development of a configuration of a multimodal full-field optical coherence tomography (FF-OCT) and fluorescence microscope. Our system can simultaneously acquire FF-OCT and structured illumination microscopy images. Dynamic parallel evolution of tissue microstructures and biochemical environments can be visualized. We use high numerical aperture objectives to optimize the combination of the two modalities. We imaged the propagation of mechanical waves initiated by calcium waves in a heart wall to illustrate the interest of simultaneous recording of mechanical and biochemical information.

An optical coherence tomography (OCT) system with a 2.8-mm beam diameter is presented. Sensorless defocus correction can be performed with a Badal optometer and astigmatism correction with a liquid crystal device. OCT B-scans were used in an image-based optimization algorithm for aberration correction. Defocus can be corrected from −4.3  D to +4.3  D and vertical and oblique astigmatism from −2.5  D to +2.5  D. A contrast gain of 6.9 times was measured after aberration correction. In comparison with a 1.3-mm beam diameter OCT system, this concept achieved a 3.7-dB gain in dynamic range on a model retina. Both systems were used to image the retina of a human subject. As the correction of the liquid crystal device can take more than 60 s, the subject’s spectacle prescription was adopted instead. This resulted in a 2.5 times smaller speckle size compared with the standard OCT system. The liquid crystal device for astigmatism correction does not need a high-voltage amplifier and can be operated at 5 V. The correction device is small (9  mm×30  mm×38  mm) and can easily be implemented in existing designs for OCT.

To measure regional saturation of oxygen (rSO2) of hemoglobin and total hemoglobin index (HbI) in the brain (through the molera of the head) and skeletal muscle (musculus gracilis) of conscious Chihuahua dogs using an examiner’s finger-mounted near-infrared spectroscopy (NIRS) device, Toccare, we investigated brain and skeletal muscle NIRS in 48 Chihuahuas without severe disease. To measure rSO2 and total HbI, a Toccare probe was placed on the molera of the head and musculus gracilis of each dog for real-time recording. Stable NIRS values were obtained within 10 s. We also examined the effect of anesthesia on rSO2 and total HbI of a Chihuahua. Cerebral rSO2 values (59%±7%) were significantly lower than those obtained at femoral regions (67%±6%), whereas total HbI values in the brain (0.38±0.09) were significantly higher than those of the musculus gracilis (0.20±0.05). Sedation with a combination of medetomidine and ketamine decreased cerebral rSO2 along with a corresponding reduction in heart rate. Sevoflurane anesthesia with 100% O2 maintained rSO2 in the brain with a

We have developed a portable, breast margin assessment probe leveraging diffuse optical spectroscopy to quantify the morphological landscape of breast tumor margins during breast conserving surgery. The approach presented here leverages a custom-made 16-channel annular photodiode imaging array (arranged in a 4×4 grid), a raster-scanning imaging platform with precision pressure control, and compressive sensing with an optimized set of eight wavelengths in the visible spectral range. A scalable Monte-Carlo-based inverse model is used to generate optical property [μs′(λ) and μa(λ)] measures for each of the 16 simultaneously captured diffuse reflectance spectra. Subpixel sampling (0.75 mm) is achieved through incremental x, y raster scanning of the imaging probe, providing detailed optical parameter maps of breast margins over a 2×2  cm2 area in ∼9  min. The morphological landscape of a tumor margin is characterized using optical surrogates for the fat to fibroglandular content ratio, which has demonstrated diagnostic utility in delineating tissue subtypes in the breast.

Wavelength tunable temporal focusing multiphoton excitation microscopy (TFMPEM) is conducted to visualize optical sectioning images of multiple fluorophore–labeled specimens through the optimal two-photon excitation (TPE) of each type of fluorophore. The tunable range of excitation wavelength was determined by the groove density of the grating, the diffraction angle, the focal length of lenses, and the shifting distance of the first lens in the beam expander. Based on a consideration of the trade-off between the tunable-wavelength range and axial resolution of temporal focusing multiphoton excitation imaging, the presented system demonstrated a tunable-wavelength range from 770 to 920 nm using a diffraction grating with groove density of 830  lines/mm. TPE fluorescence imaging examination of a fluorescent thin film indicated that the width of the axial confined excitation was 3.0±0.7  μm and the shifting distance of the temporal focal plane was less than 0.95  μm within the presented wavelength tunable range. Fast different wavelength excitation and three-dimensionally rendered imaging of Hela cell mitochondria and cytoskeletons and mouse muscle fibers were demonstrated. Significantly, the proposed system can improve the quality of two-color TFMPEM images through different excitation wavelengths to obtain higher-quality fluorescent signals in multiple-fluorophore measurements.

A typical photoacoustic tomography (PAT) system uses a Q-switched Nd:YAG laser for irradiating the sample and a single-element ultrasound transducer (UST) for acquiring the photoacoustic data. Conventionally, in PAT systems, the UST is held in a horizontal position and moved in a circular motion around the sample in full 2π radians. Horizontal positioning of the UST requires a large water tank to house, and load on the motor is also high. To overcome this limitation, we used the UST in the vertical plane instead of the horizontal plane. The photoacoustic (PA) waves generated from the sample are directed to the detector surface using an acoustic reflector placed at 45 deg to the transducer body. Hence, we can reduce the scanning radius, which, in turn, will reduce the size of the water tank and load on the motor, and the overall conventional PAT system size can be minimized. In this work, we demonstrate that with this system configuration, we acquire nearly similar images for phantom and in vivo data as that of the conventional PAT system using both flat and focused USTs.

The area of in vivo sensing using optical fibers commonly uses materials such as silica and polymethyl methacrylate, both of which possess much higher modulus than human tissue. The mechanical mismatch between materials and living tissue has been seen to cause higher levels of glial encapsulation, scarring, and inflammation, leading to failure of the implanted medical device. We present the use of a fiber made from polyvinyl alcohol (PVA) for use as an implantable sensor as it is an easy to work with functionalized polymer that undergoes a transition from rigid to soft when introduced to water. This ability to switch from stiff to soft reduces the severity of the immune response. The fabricated PVA fibers labeled with fluorescein for sensing applications showed excellent response to various stimuli while exhibiting mechanical switchability. For the dry fibers, a tensile storage modulus of 4700 MPa was measured, which fell sharply to 145 MPa upon wetting. The fibers showed excellent response to changing pH levels, producing values that were detectable in a range consistent with those seen in the literature and in proposed applications. The results show that these mechanically switchable fibers are a viable option for future sensing applications.

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.

Enzyme-functionalized dual-peak long-period fiber grating (LPFG) inscribed in 80-μm-cladding B/Ge codoped single-mode fiber is presented for sugar-level and specific glucose detection. Before enzyme functionalization, the dual-peak LPFG was employed for refractive index sensing and sugar-level detection and high sensitivities of ∼4298.20  nm/RIU and 4.6696  nm/% were obtained, respectively. Glucose detection probe was attained by surface functionalization of the dual-peak LPFG via covalent binding with aminopropyl triethoxysilane used as a binding site. Optical micrographs confirmed the presence of enzyme. The surface-functionalized dual-peak LPFG was tested with D-(+)-glucose solution of different concentrations. While the peak 2 at the longer wavelength was suitable only to measure lower glucose concentration (0.1 to 1.6  mg/ml) recording a high sensitivity of 12.21±0.19  nm/(mg/ml), the peak 1 at the shorter wavelength was able to measure a wider range of glucose concentrations (0.1 to 3.2  mg/ml) exhibiting a maximum resonance wavelength shift of 7.12±0.12  nm/mg/ml. The enzyme-functionalized dual-peak LPFG has the advantage of direct inscription of highly sensitive grating structures in thin-cladding fibre without etching, and most significantly, its sensitivity improvement of approximately one order of magnitude higher than previously reported LPFG and excessively tilted fibre grating (Ex-TFG) for glucose detection.

Two-person neuroscience, a perspective in understanding human social cognition and interaction, involves designing immersive social interaction experiments as well as simultaneously recording brain activity of two or more subjects, a process termed “hyperscanning.” Using newly developed imaging techniques, the interbrain connectivity or hyperlink of various types of social interaction has been revealed. Functional near-infrared spectroscopy (fNIRS)-hyperscanning provides a more naturalistic environment for experimental paradigms of social interaction and has recently drawn much attention. However, most fNIRS-hyperscanning studies have computed hyperlinks using sensor data directly while ignoring the fact that the sensor-level signals contain confounding noises, which may lead to a loss of sensitivity and specificity in hyperlink analysis. In this study, on the basis of independent component analysis (ICA), a source-level analysis framework is proposed to investigate the hyperlinks in a fNIRS two-person neuroscience study. The performance of five widely used ICA algorithms in extracting sources of interaction was compared in simulative datasets, and increased sensitivity and specificity of hyperlink analysis by our proposed method were demonstrated in both simulative and real two-person experiments.

The differentiation of skin melanomas and basal cell carcinomas (BCCs) was demonstrated based on combined analysis of Raman and autofluorescence spectra stimulated by visible and NIR lasers. It was ex vivo tested on 39 melanomas and 40 BCCs. Six spectroscopic criteria utilizing information about alteration of melanin, porphyrins, flavins, lipids, and collagen content in tumor with a comparison to healthy skin were proposed. The measured correlation between the proposed criteria makes it possible to define weakly correlated criteria groups for discriminant analysis and principal components analysis application. It was shown that the accuracy of cancerous tissues classification reaches 97.3% for a combined 6-criteria multimodal algorithm, while the accuracy determined separately for each modality does not exceed 79%. The combined 6-D method is a rapid and reliable tool for malignant skin detection and classification.

Diffuse correlation spectroscopy (DCS) is a noninvasive method to quantify tissue perfusion from measurements of the intensity temporal autocorrelation function of diffusely scattered light. However, DCS autocorrelation function measurements in tissue better match theoretical predictions based on the diffusive motion of the scatterers than those based on a model where the advective nature of blood flow dominates the stochastic properties of the scattered light. We have recently shown using Monte Carlo (MC) simulations and assuming a simplistic vascular geometry and laminar flow profile that the diffusive nature of the DCS autocorrelation function decay is likely a result of the shear-induced diffusion of the red blood cells. Here, we provide theoretical derivations supporting and generalizing the previous MC results. Based on the theory of diffusing-wave spectroscopy, we derive an expression for the autocorrelation function along the photon path through a vessel that takes into account both diffusive and advective scatterer motion, and we provide the solution for the DCS autocorrelation function in a semi-infinite geometry. We also derive the correlation diffusion and correlation transfer equation, which can be applied for an arbitrary sample geometry. Further, we propose a method to take into account realistic vascular morphology and flow profile.

Below the threshold for laser ablation, the mineral phase of enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Studies suggest the possibility of achieving the conversion without visible surface alteration. In this study, changes in the surface morphology, reflectivity, and acid resistance were monitored with varying irradiation intensity. Bovine enamel specimens were irradiated using a CO2 laser operating at 9.4  μm with a Gaussian spatial beam profile—1.6 to 3.1 mm in diameter. After laser treatment, samples were subjected to demineralization to simulate the acidic intraoral conditions of dental decay. The resulting demineralization and erosion were assessed using polarization-sensitive optical coherence tomography, three-dimensional digital microscopy, and polarized light microscopy. Distinct changes in the surface morphology and the degree of inhibition were found within the laser-treated area in accordance with the laser intensity profile. Subtle visual changes were noted below the melting point for enamel that appear to correspond to thresholds for denaturation of the organic phase and thermal decomposition of the mineral phase. There was significant protection from laser irradiation in areas in which the reflectivity was not increased significantly, suggesting that aesthetically sensitive areas of the tooth can be treated for caries prevention.

Existing dosimetric quantities do not fully account for the dynamic interactions between the key components of photodynamic therapy (PDT) or the varying PDT oxygen consumption rates for different fluence rates. Using a macroscopic model, reacted singlet oxygen ( [ O 2 1 ] rx ) was calculated and evaluated for its effectiveness as a dosimetric metric for PDT outcome. Mice bearing radiation-induced fibrosarcoma tumors were treated with benzoporphyrin derivative monoacid ring A (BPD) at a drug-light interval of 3 h with various in-air fluences (30 to 350    J / cm 2 ) and in-air fluence rates (50 to 150    mW / cm 2 ). Explicit measurements of BPD concentration and tissue optical properties were performed and used to calculate [ O 2 1 ] rx , photobleaching ratio, and PDT dose. For four mice, in situ measurements of O 2