Development of optical quality bioresorbable fibers is an emerging area of study where researchers are trying to advance the field by assessing the suitability of these fibers for various biomedical applications. These types of fiber implants dissolve in the human body over a clinically relevant time scale eliminating the need for extraction surgeries.
We conducted both ex-vivo and in vivo diffuse correlation spectroscopic studies using our fibers to measure blood flow and a preliminary trial to integrate a biocompatible electrode material on the fiber for electrical signal measurements. The results demonstrated the potential of Calcium Phosphate glass-based fiber-optic devices in future physiological monitoring applications which can be implanted inside the body without the need of an explant procedure.
Acknowledgement: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 860185.
Calcium phosphate glass based single-mode and multi-mode bioresorbable optical fibers were in-house manufactured. Ex-vivo studies were then conducted to test the suitability of these fibers for time gated diffuse optics spectroscopy, photodynamic therapy and diffuse correlation spectroscopy applications which can be respectively employed for the diagnosis, treatment, and monitoring of malignant tissues. The results demonstrated the potential of calcium phosphate glass-based fiber optic devices towards the realization of an implantable multi-functional class of devices with functionalities ranging from cancer detection to monitoring of the healing process all integrated into a single bioresorbable platform.
Acknowledgement: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 860185
KEYWORDS: Near infrared spectroscopy, Continuous wave operation, Measurement devices, Medical devices, In vivo imaging, Tissues, Tissue optics, Spectroscopes, Reliability, Oxygen
During the first peak of the COVID-19 pandemic, we have set up a clinical campaign in ten hospitals worldwide to assess the endothelial health of COVID-19 patients using commercial continuous-wave near-infrared spectroscopy (CW-NIRS) devices (PortaMon, Artinis, NL). In spite of the wide range of clinical applications, the reliability of common CW-NIRS systems for absolute oxygenation measurements was often questioned, opening issues of standardization. In addition, a multi-center trial itself opens issues about how to compare measurements performed by different operators, in different conditions and longitudinally over more than a year. Here, we present how we address these challenges by characterizing and comparing the performance of the devices, with phantom and in vivo experiments.
The HEMOCOVID-19 clinical trial, carried out in 10 hospitals from 5 countries, aims to non-invasively assess, through continuous-wave near-infrared spectroscopy (CW-NIRS), the microvascular and endothelial health in COVID-19 patients admitted to intensive care. We achieve this by performing a vascular occlusion test on the forearm muscle while continuously measuring local tissue oxygen saturation and hemoglobin concentration. We found significant alterations in systemic microcirculation of COVID-19 patients with respect to healthy subjects (i.e. slower deoxygenation during the ischemia and reoxygenation after releasing the cuff, and lower hyperemic response). In addition, we found that, within the group of COVID-19 patients, the systemic microcirculation alterations correlate with severity of pulmonary disease.
Endothelial dysfunction represents a key factor in the worsening of the COVID-19 disease in up to 20% of the cases of infection from acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2). The combination of diffuse optics and vascular occlusion tests makes the assessment of endothelial and microvasculature health possible by accessing information about microvascular metabolism, reactivity and tissue perfusion just by performing a localized ischemia at the forearm of the patient. In this framework, we will present a smart platform integrating time-domain near-infrared spectroscopy and diffuse correlation spectroscopy alongside an automatized tourniquet and a pulse-oximeter for personalizing therapies targeting endothelial function and avoid ventilator-induced lung injuries.
We propose a standardized approach for performance assessment and quality-control of the novel VASCOVID system based on optical phantoms. This approach is tailored to meet the requirements of the Medical Device Regulation, and is extendable to other biophotonics devices.
LUCA platform combines clinical ultrasound with near-infrared time-domain and correlation spectroscopies to improve thyroid cancer screening. We characterized its precision and classified thyroid nodules in a clinical campaign on 45 subjects.
KEYWORDS: Hemodynamics, Near infrared spectroscopy, Tissues, In vivo imaging, Blood circulation, Tissue optics, Spectroscopes, Skin, Dubnium, Time metrology
A multi-distance Diffuse Correlation Spectroscopy system combined with a compact state-of-the-art Time Domain Near-Infrared Spectroscopy device is presented. The device was used to validate the protocol of VASCOVID project on healthy subject.
HEMOCOVID-19 project spans four countries and eight hospitals to evaluate the microvascular and endothelial health of severe COVID-19 patients using near-infrared spectroscopy (NIRS) of the forearm muscle. In order to implement the project, we have developed protocols and
tested ten commercial continuous-wave NIRS devices of the same model (PortaMon, Artinis, NL). They were characterized and compared for intra- and inter-device, inter- and intra-operator and temporal variability in solid phantoms and in vivo.
The VASCOVID project aims to develop an hybrid diffuse optical device with a vascular occlusion protocol for evaluating endothelial and microvascular health in severe COVID-19 patients admitted to the ICU.
We present the HEMOCOVID-19 study spanning four countries and eight hospitals where near-infrared spectroscopy is utilized to evaluate microvascular and endothelial health of severe COVID-19 patients at the intensive care.
As coronavirus disease 2019 (COVID-19) has spread across the world, the surge in patients requiring ICU admission has been overwhelming.The rapid diagnosis and isolation, clinical management, and infection prevention are the main challenges associated with this pandemic. When the disease becomes critical, adequate management of acute respiratory failure and supporting the hemodynamics is key in order to minimize the negative impact on survival. However, many questions on prognosis and efficient clinical management remain unanswered. HEMOCOVID-19 uses near-infrared diffuse optical technologies to non-invasively evaluate endothelial and microvascular dysfunction to aid both the development of targeted therapies and also to personalize rescue therapies. HEMOCOVID-19 has eleven partners in four countries and is open for new members. I will present the project and the preliminary results. I will then briefly explain the vision for the longer-term.
Diffuse correlation spectroscopy (DCS) is an emerging diffuse optical technique that quantifies microvascular blood flow. In spite of the wide range of clinical/research applications, DCS instrumentation is not yet standardized. In this study, we have analyzed the effect of experimental parameters as the measurement duration time and the number of detectors, at different photon count-rates, on the precision of a DCS experiment. This provides a recipe for finding device and experimental settings that optimize the precision while balancing cost and temporal resolution.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
The LUCA device combines clinical ultrasound, time-domain near infrared and diffuse correlation spectroscopies with the aim of improving thyroid cancer screening sensitivity and specificity. The preliminary clinical campaign on patients (n=31) with thyroid nodules and healthy controls (n=11) allowed the characterization of the precision of the instrument and demonstrated that using a couple of biomarkers the muscle-to-nodule contrast allows an area under the curve of 0.92 for single-nodule patients and 0.77 for all patients in differentiating benign and malignant nodules in a receiver operating characteristic curve. We will present the updated results from the ongoing study.
We localized the thyroid nodules in eleven subjects by ultrasound and measured the microvascular blood flow of the nodules by diffuse correlation spectroscopy.
We present the current status of the LUCA project whose aim is to develop an innovative device combining ultrasound and diffuse optics for an improved screening of the thyroid cancer.
The feasibility of in utero measurement of cerebral blood flow diffuse correlation spectroscopy was demonstrated in lamb fetuses and compared with measurements outside the uterus.
Diffuse optical imaging can be used to probe highly scattering media like biological tissue down to a depth of few centimeters, with spatial resolution limited by light scattering. Its combination with ultrasound imaging can potentially lead to medical imaging systems with, for instance, high specificity in the examination of tumors. However, the presence of the ultrasound coupling gel between probe and tissue can have detrimental effects on the accuracy of optical imaging techniques. Here we present an experimental study on the effect of ultrasound coupling fluids on diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). We demonstrate on tissue-mimicking phantoms that the use of standard water-clear gels, providing a direct path for the light from the source to the detection point, can distort optical measurements generating strong underestimation of both the absorption and the reduced scattering coefficients in DOS measurements, as well as underestimation of the Brownian diffusion coefficient in DCS measurements. On the contrary, various turbid fluids demonstrate excellent performance in preventing this issue.
Among the natural white colored photonics structures, a bio-system has become of great interest in the field of disordered optical media: the scale of the white beetle Chyphochilus. Despite its low thickness, on average 7 μm, and low refractive index, this beetle exhibits extreme high brightness and unique whiteness. These properties arise from the interaction of light with a complex network of chitin nano filaments embedded in the interior of the scales. As it’s been recently claimed, this could be a consequence of the peculiar morphology of the filaments network that, by means of high filling fraction (0.61) and structural anisotropy, optimizes the multiple scattering of light. We therefore performed a numerical analysis on the structural properties of the chitin network in order to understand their role in the enhancement of the scale scattering intensity. Modeling the filaments as interconnected rod shaped scattering centers, we numerically generated the spatial coordinates of the network components. Controlling the quantities that are claimed to play a fundamental role in the brightness and whiteness properties of the investigated system (filling fraction and average rods orientation, i.e. the anisotropy of the ensemble of scattering centers), we obtained a set of customized random networks. FDTD simulations of light transport have been performed on these systems, observing high reflectance for all the visible frequencies and proving the implemented algorithm to numerically generate the structures is suitable to investigate the dependence of reflectance by anisotropy.
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