Development and Application of Prototype System Based on Light-Emitting Diode Arrays (660 nm) with a Top Hat Beam Profile in Order to Optimize Photobiomodulation Protocols for Treatment of Radiation-Induced Oral Mucositis in Rats.

Background: Oral mucositis (OM) is a common adverse effect of radiation to the head and neck. Recent research has shown that extra oral photobiomodulation (EO-PBM) reduces the severity of OM. However, appropriate EO-PBM therapy parameters for OM severity reduction have not been documented. Objective: This work aims to optimize EO-PBM radiation parameters for lowering the severity of radiation-induced OM in rats by establishing a photobiomodulation (PBM) treatment system based on light-emitting diode arrays with top-hat beam profile. Methods: The 36 rats are separated into 2 control groups and 4 groups receiving PBM treatment. The PBM groups are exposed to irradiance between 4 and 24 J/cm2 at 660 nm. The cheek pouch mucosa is removed after scarification for biochemical and histological examination. Student's t-test, and one-way analysis of variance (ANOVA) followed by Tukey's Multiple were applied to compare the statistical significance of differences between control groups and PBM treatment groups. Results: Statistical analysis reveals that PBM irradiation at 12 J/cm2 (200 sec) with a flatness of 0.8 and a diameter of 3 cm substantially decreased the level of inflammatory cytokines compared with the positive control group. Conclusions: Our results indicate that the designed treatment PBM system is capable of delivering the optical parameters necessary for therapeutic treatment.

Correction of Retinal Nerve Fiber Layer Thickness Measurement on Spectral-Domain Optical Coherence Tomographic Images Using U-net Architecture.

Purpose: In this study, an algorithm based on deep learning was presented to reduce the retinal nerve fiber layer (RNFL) segmentation errors in spectral domain optical coherence tomography (SD-OCT) scans using ophthalmologists' manual segmentation as a reference standard. Methods: In this study, we developed an image segmentation network based on deep learning to automatically identify the RNFL thickness from B-scans obtained with SD-OCT. The scans were collected from Farabi Eye Hospital (500 B-scans were used for training, while 50 were used for testing). To remove the speckle noise from the images, preprocessing was applied before training, and postprocessing was performed to fill any discontinuities that might exist. Afterward, output masks were analyzed for their average thickness. Finally, the calculation of mean absolute error between predicted and ground truth RNFL thickness was performed. Results: Based on the testing database, SD-OCT segmentation had an average dice similarity coefficient of 0.91, and thickness estimation had a mean absolute error of 2.23 ± 2.1 µm. As compared to conventional OCT software algorithms, deep learning predictions were better correlated with the best available estimate during the test period (r2 = 0.99 vs r2 = 0.88, respectively; P < 0.001). Conclusion: Our experimental results demonstrate effective and precise segmentation of the RNFL layer with the coefficient of 0.91 and reliable thickness prediction with MAE 2.23 ± 2.1 µm in SD-OCT B-scans. Performance is comparable with human annotation of the RNFL layer and other algorithms according to the correlation coefficient of 0.99 and 0.88, respectively, while artifacts and errors are evident.

Measurement of retinal nerve fiber layer thickness with a deep learning algorithm in ischemic optic neuropathy and optic neuritis.

This work aims at determining the ability of a deep learning (DL) algorithm to measure retinal nerve fiber layer (RNFL) thickness from optical coherence tomography (OCT) scans in anterior ischemic optic neuropathy (NAION) and demyelinating optic neuritis (ON). The training/validation dataset included 750 RNFL OCT B-scans. Performance of our algorithm was evaluated on 194 OCT B-scans from 70 healthy eyes, 82 scans from 28 NAION eyes, and 84 scans of 29 ON eyes. Results were compared to manual segmentation as a ground-truth and to RNFL calculations from the built-in instrument software. The Dice coefficient for the test images was 0.87. The mean average RNFL thickness using our U-Net was not different from the manually segmented best estimate and OCT machine data in control and ON eyes. In NAION eyes, while the mean average RNFL thickness using our U-Net algorithm was not different from the manual segmented value, the OCT machine data were different from the manual segmented values. In NAION eyes, the MAE of the average RNFL thickness was 1.18 ± 0.69 µm and 6.65 ± 5.37 µm in the U-Net algorithm segmentation and the conventional OCT machine data, respectively (P = 0.0001).

A novel fluorescent cardiac imaging system for preclinical intraoperative angiography.

BACKGROUND: Intraoperative coronary angiography can tremendously reduce early coronary bypass graft failures. Fluorescent cardiac imaging provides an advanced method for intraoperative observation and real-time quantitation of blood flow with high resolution. METHODS: We devised a system comprised of an LED light source, special filters, lenses and a detector for preclinical coronary artery angiography. The optical setup was implemented by using two achromatic doublet lenses, two positive meniscus lenses, a band-pass filter, a pinhole and a CCD sensor. The setup was optimized by Zemax software. Optical design was further challenged to obtain more parallel light beams, less diffusion and higher resolutions to levels as small as arterioles. Ex vivo rat hearts were prepared and coronary arteries were retrogradely perfused by indocyanine green (ICG). Video angiography was employed to assess blood flow and plot time-dependent fluorescence intensity curve (TIC). Quantitation of blood flow was performed by calculating either the gradient of TIC or area under curve. The correlation between blood flow and each calculated parameters was assessed and used to evaluate the quality of flow. RESULTS: High-resolution images of flow in coronary arteries were obtained as precise as 62 µm vessel diameter, by our custom-made ICG angiography system. The gradient of TIC was 3.4-6.3 s-1, while the area under curve indicated 712-1282 s values which ultimately gained correlation coefficients of 0.9938 and 0.9951 with relative blood flow, respectively. CONCLUSION: The present ICG angiography system may facilitate evaluation of blood flow in animal studies of myocardial infarction and coronary artery grafts intraoperatively.

Data on biodistribution and dose calculation of 99mTechnetium -Dimercaptosuccinic acid in pediatric patients using a hybrid planar/single emission computed tomography method.

The Biodistribution and absorbed dose data from the administration of radiopharmaceuticals are necessary to analyze the risk-benefit of the procedure. It has particular significance in children, as their metabolism is very different from adults. 99mTc-DMSA scintigraphy is the golden standard imaging technique for the assessment of renal involvement in febrile urinary tract infection and renal sequels. However, 99mTc-DMSA biodistribution data for children are scarce and usually outdated which have been obtained by older methods. In this data article, we analysed the biodistribution of 99mTc-DMSA in 12 pediatric patients using planar/SPECT method. In addition, the radiation absorbed doses were calculated by MIRDOSE software.

Sensitivity Laplacian Ratio-Based Optimization of the Projection Selection for Diffuse Optical Tomography.

BACKGROUND: In diffuse optical tomography, determining the optimal angle between the source and detector is an effective method to reduce the number of projections while maintaining the quality of the reconstructed images. In this study, a new parameter is introduced to evaluate the source-detector geometries. METHODS: A two-dimensional mesh with the radius of 20 mm and 7987 nodes were built. In each reconstruction, 0.5 mm heterogeneity with the absorption coefficient of 0.06 mm-1 and the dispersion coefficient of 0.6 mm-1 was added in different parts of the sample randomly. The relationship between the mean square error (MSE), sensitivity Laplacian ratio (SLR), and sensitivity standard deviation ratio (SSR) was evaluated based on their correlation coefficients. The quality of the images achieved using the optimized projections were compared with that of the full projections for the same depths. RESULTS: MSE decreases by increasing the SLR magnitudes which indicate that the parameter could be used to evaluate the scanning geometries. There was a negative correlation coefficient (R = -0.76) with the inverse relationship between the SLR and MSE indices. SSR does not have a significant relationship with the quality of the reconstructed images. For each scanning depth, the comparison of the images obtained using the full and optimized-selective projections did not show any considerable difference despite the decrease of the projection numbers in scanning geometry with the optimized-selective projections. CONCLUSION: The unnecessary projections could be eliminated by placing the detectors at the specific angles, which were determined using the SLR. Thus, a proper compromise between the quality of the reconstructed images and reconstruction time might establish.

Sensitivity Uniformity Ratio as a New Index to Optimize the Scanning Geometry for Fluorescent Molecular Tomography.

BACKGROUND: Molecular fluorescence imaging is widely used as a noninvasive method to study the cellular and molecular mechanisms. In the optical imaging system, the sensitivity is the change of the intensity received by the detector for the changed optical characteristics (fluorescence) in each sample point. Sensitivity could be considered as a function of imaging geometry. A favor imaging system has a uniform and high-sensitivity coefficient for each point of the sample. In this study, a new parameter was proposed which the optimal angle between the source and detector could be determined based on this parameter. METHODS: For evaluation of the new method, a two-dimensional mesh with a radius of 20 mm and 5133 nodes was built. In each reconstruction, 0.5-mm fluorescence heterogeneity with a contrast-to-purpose ratio of fluorescence yield of 10 was randomly added at different points of the sample. The source and the detector were simulated in different geometric conditions. The calculations were performed using the NIRFAST and MATLAB software. The relationship between mean squared error (MSE) and sensitivity uniformity ratio (SUR) was evaluated using the correlation coefficient. Finally, based on the new index, an optimal geometrical strategy was introduced. RESULTS: There was a negative correlation coefficient (R = -0.78) with the inverse relationship between the SUR and MSE indices. The reconstructed images showed that the better image quality achieved using the optimal geometry for all scanning depths. For the conventional geometry, there is an artifact in the opposite side of the inhomogeneity at the shallow depths, which has been eliminated in the reconstructed images achieved using the optimal geometry. CONCLUSION: The SUR is a powerful computational tool which could be used to determine the optimal angles between the source and detector for each scanning depth.

Simulation of heat distribution and thermal damage patterns of diode hair-removal lasers: an applicable method for optimizing treatment parameters.

OBJECTIVE: We simulated the heat distribution and thermal damage patterns of diode hair-removal lasers for different spot sizes, pulse durations, and fluences as a guide for optimization. BACKGROUND: Recently, the concept of thermal damage time as a reference for pulse duration has become a subject of debate. METHODS: Laser-Induced-Temperature-Calculation-In-Tissue (LITCIT) was used for the simulations. Skin was modeled as two homogenous layers of epidermis/dermis and two coaxial cylinders as the hair shaft/ follicle. Opto-thermal coefficients of the components and the radiant parameters of the laser (diode, 810 nm) were defined. RESULTS: At constant fluences and pulse durations, the damage occurred deeper when larger spot sizes were used. At constant pulse duration, high fluences caused significant damage to the hair follicle and epidermis. By using longer pulse durations (≤ 400 ms) at constant fluences, there was more effective damage to the hair follicle while sparing the adjacent epidermis and dermis. Because of the time-dependent temperature profiles, an increased pulse duration creates a moderate, gradual rise in the target's temperature. Pulse durations > 400 ms are accompanied by unwanted dermis damage. CONCLUSIONS: Our results show that using very long pulse durations near the tissue damage time (≤ 400 ms) creates better efficacy in treating unwanted hairs while avoiding unwanted damage.

Improving the accuracy of a solid spherical source radius and depth estimation using the diffusion equation in fluorescence reflectance mode.

BACKGROUND: Non-invasive planar fluorescence reflectance imaging (FRI) is used for accessing physiological and molecular processes in biological tissue. This method is efficiently used to detect superficial fluorescent inclusions. FRI is based on recording the spatial radiance distribution (SRD) at the surface of a sample. SRD provides information for measuring structural parameters of a fluorescent source (such as radius and depth). The aim of this article is to estimate the depth and radius of the source distribution from SRD, measured at the sample surface. For this reason, a theoretical expression for the SRD at the surface of a turbid sample arising from a spherical light source embedded in the sample, was derived using a steady-state solution of the diffusion equation with an appropriate boundary condition. METHODS: The SRD was approximated by solving the diffusion equation in an infinite homogeneous medium with solid spherical sources in cylindrical geometry. Theoretical predications were verified by experiments with fluorescent sources of radius 2-6 mm embedded at depths of 2-4 mm in a tissue-like phantom. RESULTS: The experimental data were compared with the theoretical values which shows that the root mean square (RMS) error in depth measurement for nominal depth values d = 2, 2.5, 3, 3.5, 4 mm amounted to 17%, 5%, 2%, 1% and 5% respectively. Therefore, the average error in depth estimation was < or = 4% for depths larger than the photon mean free path. CONCLUSIONS: An algorithm is proposed that allows estimation of the location and radius of a spherical source in a homogeneous tissue-like phantom by accounting for anisotropic light scattering effect using FRI modality. Surface SRD measurement enabled accurate estimates of fluorescent depth and radius in FRI modality, and can be used as an element of a more general tomography reconstruction algorithm.

A comparison of laser-ultrasound detection system sensitivity with a broad-band ultrasonic source for biomedical applications.

BACKGROUND: Laser ultrasound detection systems are used for noninvasive imaging of internal structures and function of soft tissues. The detection systems with a high sensitivity can be used for detecting small tumors located deeply in human tissues, such as the breast. In this study, the sensitivity of existing ultrasonic detection systems has been compared experimentally by using thermoelastic waves as a broadband ultrasonic source. METHODS: For the comparison, an optical stress transducer, a polyvinylidene difluoride (PVDF) sheet and a calibrated PVDF needle hydrophone were used. To ensure that all detection systems were interrogated by the same ultrasonic field, a small optical instrument was constructed to fix the generating laser head. The sensitivity was evaluated by measuring signal-to-noise ratios (SNRs) and noise equivalent pressures (NEPs). RESULTS: The PVDF system, with a 4 kPa NEP, has a 22-dB better performance than the optical stress transducer. The optical stress transducer showed nearly the same sensitivity as the hydrophone for detecting ultrasound waves at a 1-cm distance. CONCLUSIONS: PVDF detection system provides a useful tool for imaging of soft tissues because of its high sensitivity and broadband detection range.

Diffraction-free acoustic detection for optoacoustic depth profiling of tissue using an optically transparent polyvinylidene fluoride pressure transducer operated in backward and forward mode.

An optoacoustic detection method suitable for depth profiling of optical absorption of layered or continuously varying tissue structures is presented. Detection of thermoelastically induced pressure transients allows reconstruction of optical properties of the sample to a depth of several millimeters with a spatial resolution of 24 mum. Acoustic detection is performed using a specially designed piezoelectric transducer, which is transparent for optical radiation. Thus, ultrasonic signals can be recorded at the same position the tissue is illuminated. Because the optoacoustical sound source is placed in the pulsed-acoustic near field of the pressure sensor, signal distortions commonly associated with acoustical diffraction are eliminated. Therefore, the acoustic signals mimic exactly the depth profile of the absorbed energy. This is illustrated by imaging the absorption profile of a two-layered sample with different absorption coefficients, and of a dye distribution while diffusing into a gelatin phantom.