On the quantitative analysis of lamellar collagen arrangement with second-harmonic generation imaging.

Second harmonic generation (SHG) allows for the examination of collagen structure in collagenous tissues. Collagen is a fibrous protein found in abundance in the human body, present in bones, cartilage, the skin, and the cornea, among other areas, providing structure, support, and strength. Its structural arrangement is deeply intertwined with its function. For instance, in the cornea, alterations in collagen organization can result in severe visual impairments. Using SHG imaging, various metrics have demonstrated the potential to study collagen organization. The discrimination between healthy, keratoconus, and crosslinked corneas, assessment of injured tendons, or the characterization of breast and ovarian tumorous tissue have been demonstrated. Nevertheless, these metrics have not yet been objectively evaluated or compared. A total of five metrics were identified and implemented from the literature, and an additional approach adapted from texture analysis was proposed. In this study, we analyzed their effectiveness on a ground-truth set of artificially generated fibrous images. Our investigation provides the first comprehensive assessment of the performance of multiple metrics, identifying both the strengths and weaknesses of each approach and providing valuable insights for future applications of SHG imaging in medical diagnostics and research.

Phase-Resolved Optical Coherence Elastography: An Insight into Tissue Displacement Estimation.

Robust methods to compute tissue displacements in optical coherence elastography (OCE) data are paramount, as they play a significant role in the accuracy of tissue elastic properties estimation. In this study, the accuracy of different phase estimators was evaluated on simulated OCE data, where the displacements can be accurately set, and on real data. Displacement (∆d) estimates were computed from (i) the original interferogram data (Δφori) and two phase-invariant mathematical manipulations of the interferogram: (ii) its first-order derivative (Δφd) and (iii) its integral (Δφint). We observed a dependence of the phase difference estimation accuracy on the initial depth location of the scatterer and the magnitude of the tissue displacement. However, by combining the three phase-difference estimates (Δdav), the error in phase difference estimation could be minimized. By using Δdav, the median root-mean-square error associated with displacement prediction in simulated OCE data was reduced by 85% and 70% in data with and without noise, respectively, in relation to the traditional estimate. Furthermore, a modest improvement in the minimum detectable displacement in real OCE data was also observed, particularly in data with low signal-to-noise ratios. The feasibility of using Δdav to estimate agarose phantoms' Young's modulus is illustrated.

Retinal imaging in animal models: Searching for biomarkers of neurodegeneration.

There is a pressing need for novel diagnostic and progression biomarkers of neurodegeneration. However, the inability to determine disease duration and stage in patients with Alzheimer's disease (AD) hinders their discovery. Because animal models of disease allow us to circumvent some of these limitations, they have proven to be of paramount importance in clinical research. Due to the clear optics of the eye, the retina combined with optical coherence tomography (OCT) offers the perfect opportunity to image neurodegeneration in the retina in vivo, non-invasively, directly, quickly, and inexpensively. Based on these premises, our group has worked towards uncovering neurodegeneration-associated changes in the retina of the triple-transgenic mouse model of familial AD (3×Tg-AD). In this work, we present an overview of our work on this topic. We report on thickness variations of the retina and retinal layers/layer aggregates caused by healthy aging and AD-like conditions and discuss the implications of focusing research efforts solely on retinal thickness. We explore what other information is embedded in the OCT data, extracted based on texture analysis and deep-learning approaches, to further identify biomarkers that could be used for early detection and diagnosis. We were able to detect changes in the retina of the animal model of AD as early as 1 month of age. We also discuss our work to develop an optical coherence elastography system to measure retinal elasticity, which can be used in conjunction with conventional OCT. Finally, we discuss the potential application of these technologies in human patients and the steps needed to make OCT a helpful screening tool for the detection of neurodegeneration.

Feasibility assessment of the Eye Scan Ultrasound System for cataract characterization and optimal phacoemulsification energy estimation: protocol for a pilot, nonblinded and monocentre study.

BACKGROUND: Cataracts are lens opacifications that are responsible for more than half of blindness cases worldwide, and the only treatment is surgical intervention. Phacoemulsification surgery, the most frequently performed cataract surgery in developed countries, has associated risks, some of which are related to excessive phacoemulsification energy levels and times. The protocol proposed in herein will be used to evaluate the feasibility of a new experimental medical device, the Eye Scan Ultrasound System (ESUS), for the automatic classification of cataract type and severity and quantitative estimation of the optimal phacoemulsification energy. METHODS: The pilot study protocol will be used to evaluate the feasibility and safety of the ESUS in clinical practice. The study will be conducted in subjects with age-related cataracts and on healthy subjects as controls. The procedures include data acquisition with the experimental ESUS, classification based on the Lens Opacity Classification System III (LOCS III, comparator) using a slit lamp, contrast sensitivity test, optical coherence tomography, specular microscopy and surgical parameters. ESUS works in A-scan pulse-echo mode, with a central frequency of 20 MHz. From the collected signals, acoustic parameters will be extracted and used for automatic cataract characterization and optimal phacoemulsification energy estimation. The study includes two phases. The data collected in the first phase (40 patients, 2 eyes per patient) will be used to train the ESUS algorithms, while the data collected in the second phase (10 patients, 2 eyes per patient) will be used to assess the classification performance. System safety will be monitored during the study. DISCUSSION: The present pilot study protocol will evaluate the feasibility and safety of the ESUS for use in clinical practice, and the results will support a larger clinical study for the efficacy assessment of the ESUS as a diagnostic tool. Ultimately, the ESUS is expected to represent a valuable tool for surgical planning by reducing complications associated with excessive levels of phacoemulsification energy and surgical times, which will have a positive impact on healthcare systems and society. The study is not yet recruiting. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04461912 , registered on July 8, 2020.

Distinguishing thermally altered bones from debris using imaging and fluorescence spectrometry.

Bushfires and mass disasters from which result fatal fire victims are two types of events in which Forensic Anthropology acts aiding in the recovery of human remains and the identification of the victims. This is a challenging job since bones that have undergone fire-caused alterations can be unrecognizable. Therefore, collecting evidence at the scene is very important and should be thorough. To evaluate the potential of the application of optical techniques for the recovery and analysis of burnt skeletal material in forensic contexts, this exploratory study focused on analysing reflectance and luminescence properties of bone to differentiate between skeletal remains and debris. The sample includes burnt human bones, as well as non-human bones and debris (like metal, fabric, and others). The reflectance experiments revealed to be quite ineffective, not showing a response pattern that allowed for discrimination between skeletal remains and debris. Three techniques were used to detect luminescence, which included imaging (with a camera), fluorescence spectrometry, and laser-induced fluorescence spectroscopy (excitation: 440 nm). Luminescence results were more promising, registering a positive response for several samples, with a general consistency of results between the different methodologies. Nevertheless, burning conditions and individual characteristics (e.g., pathologies) can introduce limitations to the techniques.

Effectiveness of exercise training on cancer-related fatigue in colorectal cancer survivors: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To investigate the effects of exercise training on cancer-related fatigue (CRF) in colorectal cancer survivors. METHODS: Randomized controlled trials published between 1 January 2010 and 19 October 2020, selected through online search conducted in PubMed, Scopus, Web of Science, SPORTDiscus and PEDro databases, were included. Eligible trials compared the effect of exercise training interventions, versus non-exercise controls on CRF, in colorectal cancer survivors, during or after treatment. The methodological quality of individual studies was analysed using the Physiotherapy Evidence Database (PEDro) scale. Standardized mean differences (SMD) that were pooled using random-effects models were included as the effect size. In addition, 95% prediction intervals (PI) were calculated. RESULTS: Six trials involving 330 colorectal cancer patients met the inclusion criteria and presented reasonable to good methodological quality. An overall small-to-moderate effect of exercise training on CRF was found (SMD = - 0.29: 95% CI: [- 0.53; - 0.06]; p = 0.01; PI: [- 0.63; 0.04]; low-quality evidence). Subgroup analysis revealed moderate effects of exercise interventions performed during chemotherapy (SMD = - 0.63; 95% CI: [- 1.06; - 0.21]; p = 0.003) and small, non-significant effects, when exercise training was performed after cancer treatment (SMD = - 0.14; 95% CI: [- 0.43; 0.14]; p = 0.32). Steady improvements were achieved when a combination of aerobic plus resistance exercise was used, in interventions lasting 12 to 24 weeks. CONCLUSION: Exercise training could be regarded as a supportive therapy for the clinical management of CRF in colorectal cancer patients undergoing chemotherapy, but further studies are necessary to clarify the effects of exercise interventions on CRF after cancer treatment.

Safety Assessment of an A-Scan Ultrasonic System for Ophthalmic Use.

OBJECTIVES: This study describes the safety assessment of an A-scan ultrasonic system for ophthalmic use. The system is an investigational medical device for automatic cataract detection and classification. METHODS: The risk management was based on the International Organization for Standardization (ISO) standard DIN EN ISO 14971:2009-10 and International Electrotechnical Commission (IEC) standard IEC 60601-2-37. The calibration of the ultrasonic field was conducted according to the standards IEC 62127-1:2007 and IEC 62359:2010. The uncertainty on measurements was delineated in agreement with the guide JCGM 100:2008. RESULTS: After risk management, all risks were qualitatively classified as acceptable. The mechanical index (0.08 ± 0.05), soft tissue thermal index (0.08 ± 0.08) and spatial-peak temporal-average intensity (0.56 ± 0.59 mW/cm2 ) were under the maximum index values indicated by the US Food and Drug Administration guidance, Marketing Clearance of Diagnostic Ultrasound Systems and Transducers (0.23, 1, and 17 mW/cm2 , respectively). CONCLUSIONS: This study presents a practical approach for the safety assessment of A-scan ultrasonic systems for ophthalmic use. The safety evaluation of a medical device is mandatory before its use in clinical practice. However, the safety monitoring throughout its life cycle should also be considered, since many device components may deteriorate over time and use.

Image quality of compressive single-pixel imaging using different Hadamard orderings.

Single-pixel imaging is an imaging technique that has recently attracted a lot of attention from several areas. This paper presents a study on the influence of the Hadamard basis ordering on the image reconstruction quality, using simulation and experimental methods. During this work, five different orderings, Natural, Walsh, Cake-cutting, High Frequency and Random orders, along with two different reconstruction algorithms, TVAL3 and NESTA, were tested. Also, three different noise levels and compression ratios from 0.1 to 1 were evaluated. A single-pixel camera was developed using a digital micromirror device for the experimental phase. For a compression ratio of 0.1, the Cake-cutting order achieved the best reconstruction quality, while the best contrast was achieved by Walsh order. For compression ratios of 0.5, the Walsh and Cake-cutting orders achieved similar results. Both Walsh and Cake-cutting orders reconstructed the images with good quality using compression ratios from 0.3. Finally, the TVAL3 algorithm showed better image reconstruction quality, in comparison with NESTA, when considering compression ratios from 0.1 to 0.5.

Simulation of cellular changes on Optical Coherence Tomography of human retina.

We present a methodology to assess cell level alterations on the human retina responsible for functional changes observable in the Optical Coherence Tomography data in healthy ageing and in disease conditions, in the absence of structural alterations. The methodology is based in a 3D multilayer Monte Carlo computational model of the human retina. The optical properties of each layer are obtained by solving the Maxwell's equations for 3D domains representative of small regions of those layers, using a Discontinuous Galerkin Finite Element Method (DG-FEM). Here we present the DG-FEM Maxwell 3D model and its validation against Mie's theory for spherical scatterers. We also present an application of our methodology to the assessment of cell level alterations responsible for the OCT data in Diabetic Macular Edema. It was possible to identify which alterations are responsible for the changes observed in the OCT scans of the diseased groups.