Photoacoustic (PA) imaging is hybrid imaging modality with good optical contrast and spatial resolution. Portable, cost-effective, smaller footprint LEDs are rapidly becoming important PA optical sources. However, the key challenge faced by the LED-based systems is the low fluence that is generally compensated by high frame averaging; consequently reducing acquisition frame-rate. In this study, we present a simple deep learning U-Net framework that enhances the signal-to-noise ratio (SNR) and contrast of the low number of frame-averaged PA images. The SNR increased by approximately 4-fold for both in-class in vitro phantoms (4.39 ± 2.55) and out-of-class in vivo models (4.27 ± 0.87). We also demonstrate the noise invariancy of the network and discuss the downsides (blurry outcome and fails to reduce the salt & pepper noise). Overall, the developed U-Net framework can provide a real-time image enhancement platform for clinically translatable low-cost and low-energy light source-based PA imaging systems.

We report on the spectroscopic investigation of common bacteria encountered in biopharmaceutical industries with spectroscopic definition and specificity using mid-infrared laser spectroscopy. This study describes the detection of three different bacteria species using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Stainless steel substrates were used as support for the bacterial samples. QCL-GAP spectroscopy was assisted by multivariate analysis (MVA) to assemble a powerful spectroscopic technique with classification, identification, and quantification resources. The bacterial species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique’s capability to discriminate microorganisms from the same family. Principal component analysis and partial least squares-discriminant analysis differentiated between the bacterial species using QCL-GAP. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity values.

Purpose: To assess the role of femtosecond laser-assisted capsulotomy centration in the long-term intraocular positioning of a multifocal intraocular lens. Design: Prospective comparative study. Methods: A total of 60 eyes of 30 patients underwent femtosecond laser–assisted Refractive Lens Exchange (RLE). For every patient, capsulotomy centration was randomly performed according to pupil centre (PC) in one eye and first Purkinje reflex (FPR) in the other. The intraocular lens (IOL) positioning, visual acuities, spherical equivalent, internal aberrometry and quality of vision were assessed and compared at 3 years’ follow-up between groups (PC and FPR). Results: Intraocular lens positioning showed a statistically significant difference between groups, with a closer centration to the visual axis in the FPR patients (p=<0.001). Internal aberrometry showed higher values in the PC capsulotomy centration group (p<0.01). Conclusions: First Purkinje reflex (FPR) centered capsulotomy is associated to a closer centration of the IOL to the visual axis.

Photoacoustic imaging (PAI) has been applied to many biomedical applications over the past decades. However, the received PA signal usually suffers from poor signal-to-noise ratio (SNR). Conventional solution of employing higher-power laser, or doing long-time signal averaging, may raise the system cost, time consumption, and tissue damage. Another strategy is de-noising algorithm design. In this paper, we propose a new de-noising method, termed gradient-based adaptive wavelet de-noising, which sets the energy gradient mutation point of low-frequency wavelet components as the threshold. We conducted simulation, ex vivo and in vivo experiments to validate the performance of the algorithm. The quality of de-noised PA image/signal by our proposed algorithm has improved by 20%-40%, in comparison to the traditional signal denoising algorithms, which produces better contrast and clearer details. The proposed de-noising method provides potential to improve the SNR of PA signal under single-shot low-power laser illumination for biomedical applications in vivo.

The cochlea forms a key element of the human auditory system in the temporal bone. Damage to the cochlea continues to produce significant impairment for sensory reception of environmental stimuli. To improve this impairment, the optical cochlear implant forms a new research approach. A prerequisite for this method is to understand how light propagation, as well as scattering, reflection and absorption, takes place within the cochlea. We offer a method to study the light distribution in the human cochlea through phantom materials and Monte-Carlo simulations. The calculation of an angular distribution after scattering requires a phase function. Often approximate functions like Henyey-Greenstein, two-term Henyey-Greenstein or Legendre polynomial decompositions are used as phase function. An alternative is to exactly calculate a Mie distribution for each scattering event. This method provides a better fit to the data measured in this work.

The objective of this study is to evaluate the effect of photobiomodulation (PBM) on pain control during pterygomandibular puncture. A patient received anesthesia on both sides of the mouth in a randomized manner. On the right side, an 808nm infrared low-level laser was applied before local anesthesia. On the left side, a sham laser was applied using the same technique. There was a 50% reduction in pain levels on the PBM-treated side compared to the sham PBM side, as measured by the visual analog scale. Sensitivity tests revealed that anesthesia was more effective on the PBM side. There was no significant difference in blood pressure before and after anesthesia on either side. While these findings are based on a single case report, they suggest that photobiomodulation before anesthesia may alleviate puncture pain associated with anesthesia. Nevertheless, further well-designed clinical trials are necessary to confirm the effectiveness of this complementary therapy.

Metformin hydrochloride, an antihyperglycemic agent, and sulindac, a nonsteroidal anti-inflammatory drug, are FDA-approved drugs known to exert anticancer effects. Previous studies demonstrated sulindac and metformin’s anticancer properties through mitochondrial dysfunction and inhibition of mitochondrial electron transport chain (ETC) complex I, as well as key signaling pathways. In this study, various drugs were adminsitered to A549 lung cancer cells, and results revealed that a combination of sulindac and metformin enhanced cell death compared to administration of the drugs separately. To measure superoxide production over time, we employed a time-lapse fluorescence imaging technique using mitochondrial-targeted hydroethidine. Fluorescence microscopy data showed largest increases in superoxide production in the combination treatment of metformin and sulindac. Results showed significant differences between the combined drug treatment and control groups, as well as between the positive control and control groups. This approach can be utilized to quantify anticancer efficacy of drugs, creating possibilities for additional therapeutic options.

A document by Alexander E. Moskalensky. Click on the document to view its contents.

During thyroid surgery fast and reliable intra-operative pathological feedback has the potential to avoid a two-stage procedure and significantly reduce health care costs in patients undergoing a diagnostic hemithyroidectomy (HT). We explored higher harmonic generation (HHG) microscopy, which combines second harmonic generation (SHG), third harmonic generation (THG), and multiphoton excited autofluorescence (MPEF) for this purpose. With a compact, portable HHG microscope, images of freshly excised healthy tissue, benign nodules (follicular adenoma) and malignant tissue (papillary carcinoma, follicular carcinoma and spindle cell carcinoma) were recorded. The images were generated on unprocessed tissue within minutes and show relevant morphological thyroid structures in good accordance with the histology images. The thyroid follicle architecture, cells, cell nuclei (THG), collagen organization (SHG) and the distribution of thyroglobulin and/or thyroid hormones T3 or T4 (MPEF) could be visualized. We conclude that SHG/THG/MPEF imaging is a promising tool for clinical intraoperative assessment of thyroid tissue.

A single-mode-fiber (SMF)-multimode-fiber (MMF)-tri-core-fiber (TCF) Michelson probe structure is proposed for trace detection of canine distemper virus (CDV). One end of the TCF is cut flat and fused with the multimode fiber, and the other end is coated with a silver film to enhance the reflection, and an optic-fiber sensing probe with SMF-MMF-TCF structure is obtained. The (PDDA/PSS) 3 multilayer film is modified on the surface of the fiber by layer-by-layer self-assembly method as a polyelectrolyte binder to immobilize CDV antibodies to form a (PDDA/PSS) 3/CDV antibody composite membrane for specific detection of CDV antigens. The response-recovery test of the sensor is performed to verify its repeatability. The detection limit, the sensitivity, and the linear fitting degree for CDV antigen are 0.1236 pg/ml, 1.1776 dB/(pg/ml), and 0.9899, respectively. At the same time, the stability, selectivity, and clinical samples of the sensors were also verified.

Histopathology for tumor margin assessment is time-consuming and expensive. High-resolution full-field optical coherence tomography (FF-OCT) images fresh tissues rapidly at cellular resolution, facilitating evaluation. We imaged fresh ex vivo skin tissues (normal and neoplastic) from Mohs surgery. FF-OCT features were defined and diagnostic accuracy for malignancies was performed by the two experts OCT readers via a blinded analysis. A convolutional neural network was built to distinguish and outline normal structures and tumors. Of the 113 tissues imaged, 95 (84%) had a tumor (75 BCCs and 17 SCCs). The average reader diagnostic accuracy was 88.1%, a sensitivity of 93.7%, and a specificity of 58.3%. The AI model achieved a diagnostic accuracy of 87.6%±5.9%, sensitivity of 93.2%±2.1%, and specificity of 81.2%±9.2%. A mean intersection-over-union of 60.3%±10.1% was achieved delineating nodular BCC from normal. We envision FF-OCT for rapid evaluation of surgical margins and AI tumor detection leading to widespread technique integration.

Considering difficulties of achieving vertical incidence of beam in different positions of skin, it’s significant to study potential effects of incidence angles of laser on incisions. Surgical platform with a 1064nm continuous fiber laser was established. Incident angle was adopted and real-time temperature fluctuations in laser operating area could be monitored. The rats were treated with laser at day 0 and day 3 after incision modeling, and H&E, Masson, Sirius Red and Immuno-histochemical staining and enzyme-linked immunosorbent assay were adopted at day 3,7,14 to analyze the performance of healing. Laser with energy density of 67.54J/mm 2 can effectively accelerate wound healing in vivo, in which laser with incident angle around 60° can effectively avoid scar hyperplasia. Therefore, the use of low energy laser with small deflection angle has a good clinical application prospect in promoting wound healing.

The present study presents an alternative analytical workflow that combines mid-infrared (MIR) microscopic imaging and deep learning to diagnose human lymphoma and differentiate between small and large cell lymphoma. We could show that using a deep learning approach to analyze MIR hyperspectral data obtained from benign and malignant lymph node pathology results in high accuracy for correct classification, learning the distinct region of 3900 cm-1 to 850 cm-1. The accuracy is above 95% for every pair of malignant lymphoid tissue and still above 90% for the distinction between benign and malignant lymphoid tissue for binary classification. These results demonstrate that a preliminary diagnosis and subtyping of human lymphoma could be streamlined by applying a deep learning approach to analyze MIR spectroscopic data.

Colorectal cancer is one of the most prevalent malignancies worldwide, and long-term chronic colitis is considered to be an important factor in the etiological study of colorectal cancer. As an emerging detection technology, the non-invasive, non-ionizing, and fingerprint spectroscopic features of terahertz technology have tremendous application prospects in disease diagnosis. Therefore, this study aims to explore the value of terahertz technology in colitis-related cancers by constructing an inflammation-associated mouse colorectal cancer model. In this paper, we found that the terahertz spectroscopy technique can effectively distinguish colitis-associated cancer from normal tissue, and for the first time, we searched that 1.8 THz may be the best terahertz frequency for diagnosing colorectal cancer in mice, suggesting that we can use the terahertz technique for rapid diagnosis of colorectal cancer histopathology.

The Optical Kerr Effect was investigated for the first time in biological tissues. This nonlinear optical effect was explored in both human brain and avian breast tissues using a time-resolved femtosecond pump-probe Optical Kerr Gate. The Optical Kerr Effect describes the nonlinear change in a material’s refractive index in response to an electric field. It is fundamental to spectral effects that are commonly used in biological science. The tested tissues produced a unique ultrafast (700-800 fs) doubled peaked Kerr signal, which is indicative of temporal interplay between the different components (electronic plasma, and molecular) that make up the Kerr index. Temporal properties varied between samples suggesting that this method could be used as a new diagnostic. Understanding this Kerr behavior can help improve current spectral diagnostic techniques, such as SRS, and potentially create a new Kerr based biopsy method for the detection of diseased tissues, such as cancer and Alzheimer’s.

Capillary Refill Time (CRT) assesses peripheral perfusion in resource-limited settings. However, the repeatability and reproducibility of CRT measurements are limited for individuals with darker skin. This paper presents quantitative CRT measurements demonstrating good performance and repeatability across all Fitzpatrick skin phototypes. The study involved 22 volunteers and utilized controlled compression at 7 kPa, an RGB video camera, and cocircular polarized white LED light. CRT was determined by calculating the time constant of an exponential regression applied to the mean pixel intensity of the green (G) channel. An adaptive algorithm identifies the optimal regression region for noise reduction, and flags inappropriate readings. The results indicate that 80% of the CRT readings fell within a 20% range of the expected CRT value. The repetition standard deviation was 17%. These findings suggest the potential for developing reliable and reproducible quantitative CRT methods for robust measurements in patient triage, monitoring, and telehealth applications.

A document by Caio Calarga C. Click on the document to view its contents.

The aim of this study was to develop a clinical SWIR reflectance handpiece to assess the activity of lesions on the occlusal surfaces. The time-resolved reflectivity of ten active and ten arrested occlusal caries lesions on extracted teeth was monitored at 1470 nm using a benchtop system and a modified clinical prototype during forced air drying. The presence of a highly mineralized surface zone measured with microcomputed tomography (microCT) was used to indicate lesion activity. Multiple kinetic parameters were extracted from the acquired SWIR time versus intensity dehydration curves and used to assess lesion activity. Three parameters: delay, %I fin, and rate calculated from the SWIR dehydration curves were significantly different (P < 0.05) between active and arrested lesions. The modified clinical probe was able to completely dehydrate all the active lesion areas in the occlusal pits and fissures in less than 30 seconds.