Diffuse reflectance spectroscopy for colorectal cancer surgical guidance: towards real-time tissue characterization and new biomarkers.

Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide, representing 11.3% of the diagnosed cancer cases and resulting in 10.2% (0.88 million) of the cancer related deaths in 2020. CRCs are typically detected at the late stage, which leads to high mortality and morbidity. Mortality and poor prognosis are partially caused by cancer recurrence and postoperative complications. Patient survival could be increased by improving precision in surgical resection using accurate surgical guidance tools based on diffuse reflectance spectroscopy (DRS). DRS enables real-time tissue identification for potential cancer margin delineation through determination of the circumferential resection margin (CRM), while also supporting non-invasive and label-free approaches for laparoscopic surgery to avoid short-term complications of open surgery as suitable. In this study, we have estimated the scattering properties and chromophore concentrations based on 2949 DRS measurements of freshly excised ex vivo specimens of 47 patients, and used this estimation to classify normal colorectal wall (CW), fat and tumor tissues. DRS measurements were performed with fiber-optic probes of 630 µm source-detector distance (SDD; probe 1) and 2500 µm SDD (probe 2) to measure tissue layers ∼0.5-1 mm and ∼0.5-2 mm deep, respectively. By using the 5-fold cross-validation of machine learning models generated with the classification and regression tree (CART) algorithm, we achieved 95.9 ± 0.7% sensitivity, 98.9 ± 0.3% specificity, 90.2 ± 0.4% accuracy, and 95.5 ± 0.3% AUC for probe 1. Similarly, we achieved 96.9 ± 0.8% sensitivity, 98.9 ± 0.2% specificity, 94.0 ± 0.4% accuracy, and 96.7 ± 0.4% AUC for probe 2.

Effects of Red and Infrared Laser Therapy in Patients with Tinnitus: A Double-Blind, Clinical, Randomized Controlled Study Combining Light with Ultrasound, Drugs and Vacuum Therapy.

BACKGROUND: tinnitus is a symptom with no specific cause known to date, and there are no associated pharmacogenomics of hearing disorders and no FDA-approved drugs for tinnitus treatment. The effectiveness of drug treatments is not reproducible on idiopathic patients and inexistent in refractory patients. Personalized treatments for these patients are a great clinical need. Our study investigated the outcome of potential alternative and complementary treatment modalities for idiopathic and refractory tinnitus patients. METHODS: we were the first to evaluate the tinnitus handicap inventory (THI) score changes over the course of treatment up to 15 days after complete cessation of treatment for novel transmeatal low-level laser therapy (LLLT) modalities using light alone, as well as LLLT combined with vacuum therapy (VT), ultrasound (US), Ginkgo biloba (GB) and flunarizine dihydrochloride (FD), while also comparing all treatment outcomes with laser puncture (LP), FD alone and GB alone. RESULTS: a positive treatment outcome (superior to a placebo effect) was achieved by using either LP or transmeatal LLLT, whereas short-term antagonistic effects of VT, US, GB and FD when combined with LLLT. For transmeatal LLLT, an improvement in the treatment outcome was observed by increasing the irradiation time from 6 min to 15 min (with 100-mW of applied laser power at 660 nm). Finally, a lasting therapeutic effect higher than the placebo was observed at 15 days after treatment upon combining LLLT with VT, GB or by using FD alone, by using the transmeatal LLLT alone or by using LP. CONCLUSIONS: LP and Transmeatal LLLT can be promising alternative treatments for idiopathic and refractory tinnitus patients. Future studies should investigate the long-term effects of LLLT in tinnitus patients, as well as the dosimetry and wavelength of transmeatal LLLT.

Insights into Biochemical Sources and Diffuse Reflectance Spectral Features for Colorectal Cancer Detection and Localization.

Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide. Early detection not only reduces mortality but also improves patient prognosis by allowing the use of minimally invasive techniques to remove cancer while avoiding major surgery. Expanding the use of microsurgical techniques requires accurate diagnosis and delineation of the tumor margins in order to allow complete excision of cancer. We have used diffuse reflectance spectroscopy (DRS) to identify the main optical CRC biomarkers and to optimize parameters for the integration of such technologies into medical devices. A total number of 2889 diffuse reflectance spectra were collected in ex vivo specimens from 47 patients. Short source-detector distance (SDD) and long-SDD fiber-optic probes were employed to measure tissue layers from 0.5 to 1 mm and from 0.5 to 1.9 mm deep, respectively. The most important biomolecules contributing to differentiating DRS between tissue types were oxy- and deoxy-hemoglobin (Hb and HbO2), followed by water and lipid. Accurate tissue classification and potential DRS device miniaturization using Hb, HbO2, lipid and water data were achieved particularly well within the wavelength ranges 350-590 nm and 600-1230 nm for the short-SDD probe, and 380-400 nm, 420-610 nm, and 650-950 nm for the long-SDD probe.

Photodynamic therapy dosimetry using multiexcitation multiemission wavelength: toward real-time prediction of treatment outcome.

Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient (>0.99) in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and 40 J cm - 2 were delivered at two fluence rates (100 and 40 mW cm - 2). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.

New insights of Raman spectroscopy for oral clinical applications.

Oral injuries are currently diagnosed by histopathological analysis of biopsy, which is an invasive procedure and does not give immediate results. On the other hand, the Raman spectroscopy technique is a real-time and minimally invasive analytical tool with a notable diagnostic capability. At the current stage, researchers are widely aware of the diagnostic potential of the technique and how it is considered promising for providing biochemical information in real time and without damaging the tissue. The problem originates from a lack of relevant studies and clinical trials that could show the actual use of Raman spectroscopy to help patients. Our goal here is to narrow the relationship between physicists, chemists, engineers, computer scientists, and the medical community, and in fact discuss the potential of Raman spectroscopy as a novel clinical analysis method. In the present study, we focused on the use of Raman spectroscopy as a daily clinical practice. In this context, additional studies and in vivo tests should be performed with the same approach as a real application. We want to show the scientific and industrial community what is really necessary for this, starting from a clinical point of view. Using our previous experience publishing different oral pathologies and types of samples, we also aim to discuss the current state and potential of Raman spectroscopy and what is required to implement Raman spectroscopy for oral clinical applications.

Portable fluorescence lifetime spectroscopy system for in-situ interrogation of biological tissues.

Fluorescence spectroscopy and lifetime techniques are potential methods for optical diagnosis and characterization of biological tissues with an in-situ, fast, and noninvasive interrogation. Several diseases may be diagnosed due to differences in the fluorescence spectra of targeted fluorophores, when, these spectra are similar, considering steady-state fluorescence, others may be detected by monitoring their fluorescence lifetime. Despite this complementarity, most of the current fluorescence lifetime systems are not robust and portable, and not being feasible for clinical applications. We describe the assembly of a fluorescence lifetime spectroscopy system in a suitcase, its characterization, and validation with clinical measurements of skin lesions. The assembled system is all encased and robust, maintaining its mechanical, electrical, and optical stability during transportation, and is feasible for clinical measurements. The instrument response function measured was about 300 ps, and the system is properly calibrated. At the clinical study, the system showed to be reliable, and the achieved spectroscopy results support its potential use as an auxiliary tool for skin diagnostics.