Silicon photomultiplier based continuous-wave functional near-infrared spectroscopy module with multi-distance measurements

In recent years, there has been growing interest in developing fiberless and wireless functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT) instruments. However, developing such instruments poses multiple challenges, interms of cost, safety, system complexity and achievable signal quality. One crucial factor in developing wireless and fiberless instruments is the appropriate choice of detectors. Currently, the majority of existing wireless and/or fiberless systems use photodiodes due to their low cost and low power requirements. However, under low-light conditions, the SNR of photodiodes diminishes significantly, making them less effective for measurements with long source–detector separations. The silicon photomultiplier (SiPM) is a relatively new type of detector that contains high internal amplification; this makes SiPMs suitable for low-light applications. Although SiPMs can increase signal quality at long source–detector distances, they cost more and have higher power requirements than photodiodes. This thesis presents the design of a multi-distance, multichannel DOT prototype that uses a hybrid detector arrangement. This arrangement uses photodiodes for short-distance measurements (i.e., 1 cm) and silicon photomultipliers for long-distance measurements (i.e., 3 cm and 4.5 cm). The developed system consists of two printed circuit boards (PCBs): a DOT sensor PCB, a data acquisition and control PCB as well as a graphical user interface. The performance of the developed DOT system prototype was validated using a dynamic optical phantom. The results show that the prototype works as intended

Toward a Wireless Open Source Instrument: Functional Near-infrared Spectroscopy in Mobile Neuroergonomics and BCI Applications

Brain-Computer Interfaces (BCIs) and neuroergonomics research have high requirements regarding robustness and mobility. Additionally, fast applicability and customization are desired. Functional Near-Infrared Spectroscopy (fNIRS) is an increasingly established technology with a potential to satisfy these conditions. EEG acquisition technology, currently one of the main modalities used for mobile brain activity assessment, is widely spread and open for access and thus easily customizable. fNIRS technology on the other hand has either to be bought as a predefined commercial solution or developed from scratch using published literature. To help reducing time and effort of future custom designs for research purposes, we present our approach toward an open source multichannel stand-alone fNIRS instrument for mobile NIRS-based neuroimaging, neuroergonomics and BCI/BMI applications. The instrument is low-cost, miniaturized, wireless and modular and openly documented on www.opennirs.org. It provides features such as scalable channel number, configurable regulated light intensities, programmable gain and lock-in amplification. In this paper, the system concept, hardware, software and mechanical implementation of the lightweight stand-alone instrument are presented and the evaluation and verification results of the instrument's hardware and physiological fNIRS functionality are described. Its capability to measure brain activity is demonstrated by qualitative signal assessments and a quantitative mental arithmetic based BCI study with 12 subjects

Development of a low-cost point of care device for near-infrared spectroscopy (NIRS) based online imaging during non-invasive electrical brain stimulation

All of us are exposed to optical (i.e., visible and near-infrared) radiation from the sun and othersources throughout our lives. Assuming our eyes are shielded from excessive intensity, and ourskin is protected from the ultraviolet content of sunlight, we accept this exposure in theknowledge that it is perfectly safe. Unlike x-rays, optical photons are insufficiently energetic toproduce ionisation, and unless light is concentrated to such a high degree that it causes burningto the skin, optical radiation offers no significant hazard. The diagnostic potential of opticalmethods has been widely known since Jöbsis [1] first demonstrated that transmittancemeasurements of near-infrared (NIR) radiation could be used to monitor the degree ofoxygenation of certain metabolites. This led to the development and increasingly widespread useof clinical near-infrared spectroscopy (NIRS), which offers a safe, non-invasive means ofmonitoring cerebral function at the bedside without the use of radioisotopes or other contrastagents [2]

Review of recent advances in frequency-domain near-infrared spectroscopy technologies [Invited]

Over the past several decades, near-infrared spectroscopy (NIRS) has become a popular research and clinical tool for non-invasively measuring the oxygenation of biological tissues, with particular emphasis on applications to the human brain. In most cases, NIRS studies are performed using continuous-wave NIRS (CW-NIRS), which can only provide information on relative changes in chromophore concentrations, such as oxygenated and deoxygenated hemoglobin, as well as estimates of tissue oxygen saturation. Another type of NIRS known as frequency-domain NIRS (FD-NIRS) has significant advantages: it can directly measure optical pathlength and thus quantify the scattering and absorption coefficients of sampled tissues and provide direct measurements of absolute chromophore concentrations. This review describes the current status of FD-NIRS technologies, their performance, their advantages, and their limitations as compared to other NIRS methods. Significant landmarks of technological progress include the development of both benchtop and portable/wearable FD-NIRS technologies, sensitive front-end photonic components, and high-frequency phase measurements. Clinical applications of FD-NIRS technologies are discussed to provide context on current applications and needed areas of improvement. The review concludes by providing a roadmap toward the next generation of fully wearable, low-cost FD-NIRS systems

Clinical Near-infrared Spectroscopy Instrumentation: Postural Orthostatic Tachycardia Syndrome Studies

ABSTRACT CLINICAL NEAR-INFRARED SPECTROSCOPY INSTRUMENTATION: POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME STUDIES by Parvathi Kadamati The University of Wisconsin-Milwaukee, 2017 Under the Supervision of Professor Mahsa Ranji Aims: Postural orthostatic tachycardia syndrome (POTS) is a type of chronic orthostatic intolerance, annually affecting around 500,000 young Americans. Symptoms of POTS include lightheadedness and persistent increase in heart rate with upright body posture [1-3]. It requires a medical diagnosis. Impaired cerebral oxygenation of patients with POTS has been reported [4]. The pathophysiology remains unclear, and research is needed to understand the underlying conditions that lead to POTS. The aim of this research is to design a medical device called Cytoximeter and apply it to conduct a study between POTS patients and healthy controls for objective monitoring and quantitative measurements. Introduction: A custom build near-infrared spectroscopy (NIRS) device called Cytoximeter was constructed to monitor the blood oxygenation and the redox behavior of intact tissue’s Cytochrome C Oxidase (CCO), in clinical and research setting, noninvasively. The presence of hemoglobin absorption leads to complex algorithm implementation to separate the signals of the hemoglobin and CCO. Today we have different kinds of oximetry available, which provide information about the hemoglobin levels. However, the hemoglobin signals can only provide information regarding the changes of oxygen in the tissue. Monitoring CCO may give us information about the metabolic status of the tissue and intracellular levels of oxygen [5]. CCO is the final acceptor in the electron transport chain (ETC) and is an essential part of aerobic or anaerobic metabolism [3, 6]. CCO reduces by taking electrons in ETC cycle. This enzyme accepts electrons and changes to reduced state. The custom build optical device is designed to monitors the optical densities of the tissue by applying Beer-Lamberts law to monitor the change in concentration of these chemicals. This ability can give the NIRS many applications for research and clinical purposes. POTS is a clinical application for this device; a study was conducted to monitor the POTS patients and healthy control subjects to observe the difference in oxygenation levels between these two groups while undergoing the head up tilt table test. Methods: I measured and compared the difference in the changes in oxyhemoglobin and deoxyhemoglobin by applying this Cytoximeter to POTS patients and healthy controls while undergoing the heads-up tilt. The device uses the optimal source to detector separations to acquire the CCO signal and change in oxygenation of hemoglobin signals, which uses the six wavelengths near-infrared spectroscopic design. Validation of the device includes conducting the phantom studies and employing new experimental protocols. In the clinical setting, the device was applied to the muscles and brain tissue of the patients with POTS and Epilepsy under the standard care of neurological examiners. Results: The results showed significant differences in deoxyhemoglobin, oxygenation change and blood volume between the control subjects and POTS patients. We found that the arterial system is less compliant with the inability to receive additional blood volume in POTS patients. Results of the phantom studies that I conducted showed that the device was able to monitor the real-time changes in oxygenation of blood and the redox state of CCO. Conclusion: The custom build Cytoximeter successfully monitored the hemoglobin signal along with the CCO signal. The device provided an objective means of measuring and physiological findings in understanding the underlying reasons of POTS. Further work is required to determine whether the calf muscle activation of POTS patients is comparable to the healthy controls

Towards a wireless open source instrument: functional Near-Infrared Spectroscopy in mobile neuroergonomics and BCI applications

Brain-Computer Interfaces (BCIs) and neuroergonomics research have high requirements regarding robustness and mobility. Additionally, fast applicability and customization are desired. Functional Near-Infrared Spectroscopy (fNIRS) is an increasingly established technology with a potential to satisfy these conditions. EEG acquisition technology, currently one of the main modalities used for mobile brain activity assessment, is widely spread and open for access and thus easily customizable. fNIRS technology on the other hand has either to be bought as a predefined commercial solution or developed from scratch using published literature. To help reducing time and effort of future custom designs for research purposes, we present our approach toward an open source multichannel stand-alone fNIRS instrument for mobile NIRS-based neuroimaging, neuroergonomics and BCI/BMI applications. The instrument is low-cost, miniaturized, wireless and modular and openly documented on www.opennirs.org. It provides features such as scalable channel number, configurable regulated light intensities, programmable gain and lock-in amplification. In this paper, the system concept, hardware, software and mechanical implementation of the lightweight stand-alone instrument are presented and the evaluation and verification results of the instrument\u27s hardware and physiological fNIRS functionality are described. Its capability to measure brain activity is demonstrated by qualitative signal assessments and a quantitative mental arithmetic based BCI study with 12 subjects

Monitoring Cellular Metabolism with Near-infrared Spectroscopy

Aims: Although NIRS oximetry has been widely used in clinical and research settings to monitor oxygen consumption in muscles (1), it is not necessarily able to obtain cellular metabolic levels directly. Oxygen saturation will only change with aerobic metabolism (2); however, anaerobic metabolism cannot be assessed by monitoring oxygen saturation. This work aims to measure cell oxygenation and blood oxygenation, simultaneously, by applying oximetry to hemoglobin/deoxyhemoglobin and to cytochrome c oxidase (CCOX). A custom build NIRS device called the cytoximeter was constructed to achieve this goal. This work could have important impacts on monitoring neurological diseases, Postural Tachycardia Syndrome (POTS), and epilepsy. Introduction: CCOX is the terminal enzyme in the electron transport chain (ETC) and as such will be responsive in changes in either aerobic or anaerobic metabolism (3). CCOX transports a number of electrons over a single cycle of the ETC. As the enzyme accepts electrons, it enters a reduced state. Monitoring the redox state of CCOX in a given tissue will reflect the amount of metabolic activity in that tissue (9). We developed a novel device that monitors the changes in optical densities of a tissue. Using Beer’s law and the difference in absorption spectra of reduced and oxidized CCOX, it is possible to measure the relative changes in concentration of these chemicals (4). Methods: In order to observe and separate the CCOX signals from absorption changes due to whole blood changes, a six wavelength absorption spectroscopy device is constructed. This device uses the optimal source detector separations, obtained by numerical photon migration simulations, for monitoring superficial muscles and cortical brain tissue. In order to validate the device performance, several phantom studies are conducted followed by clinical investigations. In the clinical setting, the device was applied to the gastrocnemius muscles of patients undergoing a tilt table test during a standard of care neurological examination. Results: The phantom studies showed that the device was able to obtain changes in the concentration and the redox state of CCOX in a medium with optical properties similar to the tissues found in the calf and skull. When applied in a clinical setting, the device produced reproducible and predictable results. The clinical results are partially verified by the use of a commercially available oximeter, which validates the changes in hemoglobin and oxy hemoglobin obtained by our custom-made cytoximeter. Conclusion: This work is a novel approach to the non-invasive monitoring of CCOX simultaneously with blood oxygen saturation by use of NIR spectroscopy. While there is currently no gold standard with which to compare these results to, the ability to separate cellular metabolism in the presence of large changes in blood volume during a clinical procedure is a promising first step toward clinically monitoring the energy expenditure of tissues. Further work is underway to correlate changes in CCOX redox state to the level muscular exertion. This will allow the researchers to quantitatively monitor CCOX redox changes during different levels of exercise

Development of a portable multi-channel broadband near infrared spectroscopy instrument to measure brain tissue oxygenation and metabolism during functional activation and seizures

Epilepsy is a common neurological disorder often developed during childhood, characterised by abnormal neuronal discharges. These spontaneous recurrent seizures can be associated with poor long-term neurological development. Near-infrared spectroscopy (NIRS) is a non-invasive tech- nique able to monitor cerebral concentration changes in oxygenated- (∆[HbO2]) and deoxygenated- (∆[HHb]) haemoglobin. However, current commercial NIRS systems use only a few wavelengths, limiting their use to haemodynamic monitoring. Broadband NIRS (bNIRS) systems use a larger number of wavelengths enabling changes in concentration of the oxidation state of cytochrome-c- oxidase (∆[oxCCO]) to be determined, a marker of cellular metabolism. This thesis describes the development and miniaturisation of an existing bNIRS system to monitor haemodynamic and metabolic changes in children with epilepsy. Using the latest technological advancements, the bulk and complexity of the system was reduced while increasing the number of measurement channels. Two miniature tungsten halogen light sources were utilised with time- multiplexing capabilities implemented (0.5Hz). Bifurcated optical fibre bundles (2.8mm diameter) connected to each light source and twelve detector fibre bundles (1mm diameter) arranged linearly into a ferrule (25mm diameter); modification of the interface between the detectors and lens-based spectrograph ensured compatibility with the increased detector number. Light was collimated to a diffraction grating with a wider 308nm bandwidth and the largest CCD image sensor available (1340x1300 array, 26.8x26mm) was integrated into the system. LabVIEW software was updated to enable simultaneous, real-time collection and display of intensity and concentration changes. Extensive testing of the system was performed; in-vivo testing in healthy adults using a Stroop task demonstrated a typical haemodynamic response with regional variation in metabolism. Si- multaneous bNIRS and electroencephalography data were collected from 12 children with epilepsy in the Neurology Unit. One patient case study is presented in detail, with temporal data from 17 seizures collected. A large decrease in metabolism was observed in the left posterior region, corresponding to a region of cortical malformation, suggesting an energetic deficiency in this re- gion. This indicates the potential for ∆[oxCCO] as an investigative marker in monitoring seizures, providing localised information about cellular oxygen utilisation