Blood vessel detection in medical procedures using laser Doppler flowmetry

The needle procedures such as coronary angioplasty and coronary artery bypass graft installation are the most common surgical interventions performed in medical practice, and the accuracy of the catheter needle placement defines the success of the whole operation. Due to anatomical variations in patients, finding and puncturing the correct blood vessel is a challenging step, and the needle guidance might significantly simplify the process. Therefore, the primary aim of this work was to develop a novel blood vessel detection system based on laser Doppler flowmetry (LDF) technology that will improve the quality of medical needle procedures. In this work, LDF measurement setup was designed, assembled and evaluated. The setup includes custom laser-detector system, two invasive measurements probes, two experimental phantoms and data acquisition software. The optical properties of human tissue and blood were examined in order to define the required laser characteristics and relevant tissue-mimicking materials. The data processing was based on the power spectrum analysis, from which the perfusion parameter was extracted. The measurement range of the system was assessed in respect to the various criteria such as penetration angle, depth and site. The applicability of LDF in the needle procedures was evaluated. The experimental results demonstrated that the blood vessel can be successfully detected in the wide angles range and at different penetration sites. The differentiation between low and high blood flow speeds is also possible. Moreover, the potential of the measurements in tissue was demonstrated. However, certain limitations need to be addressed. It was discovered, that the distinction between the arteria and the vein is challenging, and the penetration depth inside the tissue is restricted. Nevertheless, the proposed technology can be implemented in the needle procedures and a number of other medical applications, such as laparoscopic surgeries and biopsies

Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues

Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation by tissue optical properties, an effect that causes spectral corruption. Predictions of the spectral variations of light fluence in tissue are challenging since the spatial distribution of optical properties in tissue cannot be resolved in high resolution or with high accuracy by current methods. Spectral corruption has fundamentally limited the quantification accuracy of optical and optoacoustic methods and impeded the long sought-after goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical but still unattainable target for the assessment of oxygenation in physiological processes and disease. We discover a new principle underlying light fluence in tissues, which describes the wavelength dependence of light fluence as an affine function of a few reference base spectra, independently of the specific distribution of tissue optical properties. This finding enables the introduction of a previously undocumented concept termed eigenspectra Multispectral Optoacoustic Tomography (eMSOT) that can effectively account for wavelength dependent light attenuation without explicit knowledge of the tissue optical properties. We validate eMSOT in more than 2000 simulations and with phantom and animal measurements. We find that eMSOT can quantitatively image tissue sO2 reaching in many occasions a better than 10-fold improved accuracy over conventional spectral optoacoustic methods. Then, we show that eMSOT can spatially resolve sO2 in muscle and tumor; revealing so far unattainable tissue physiology patterns. Last, we related eMSOT readings to cancer hypoxia and found congruence between eMSOT tumor sO2 images and tissue perfusion and hypoxia maps obtained by correlative histological analysis

Frequency-domain diffuse optical spectroscopy for cardiovascular and respiratory applications

Frequency Domain Diffuse Optical Spectroscopy (FD-DOS) is an emerging optical technique that uses near infrared light to probe the hemodynamics of biological tissue. Compared to more common Continuous Wave (CW) methods, FD-DOS uses light that is temporally modulated on the order of MHz to quantify the absorption and scattering of tissue. FD-DOS can also be used to obtain absolute concentration of tissue chromophores such as oxy- and deoxy-hemoglobin, which allow for quantitative measurements of tissue hemodynamics. This dissertation focuses on the evolution of our lab’s custom digital FD-DOS as a platform for taking optical measurement of biological tissue for respiratory and cardiovascular applications. Several important instrumentation improvements will be reviewed that have enhanced the performance of the system while making it more portable and clinic ready. Two translational applications will be described in detail: 1) the use of high-speed FD-DOS for the non-invasive extraction of venous oxygen saturation (SvO2) and 2) the use of FD-DOS to monitor the hemodynamics of the sternocleidomastoid (SCM) muscle towards the non-invasive monitoring of patients on mechanical ventilation. The custom FD-DOS system parameters were adjusted for each application, with a focus on high speed to extract the cardiac signal for the SvO2 project, and a focus on high SNR to measure the highly absorbing SCM. Measurements on healthy volunteers and rabbits were used to assess the feasibility of using FD-DOS for these applications. Finally, preliminary work was conducted to characterize a miniature FD-DOS source and detector with the goal of moving towards a wearable version of FD-DOS.2022-05-15T00:00:00

Haemoglobin sensing with optical spectroscopy during minimally invasive procedures

Many clinical procedures involve the use of minimally invasive devices such as needles and catheters. Providing increased information about tissues that are adjacent to the device tips could reduce the probability of complications in these procedures. Optical fibres are well suited for integration into medical devices and they can be used to provide information relevant to tissue characterisation. This dissertation is centred on the integration of optical fibres into needles and catheters to obtain information about haemoglobin. In two studies, reflectance spectroscopy was performed. Two optical fibre geometries were tested, and for each, Monte Carlo simulations were used to estimate the reflectance values and the pho- ton penetration depths. In the first study, reflectance spectroscopy was performed with a double clad fibre. Experiments using expired human red blood cells were performed to determine the sensitivity of the measurements to oxygen saturation variation at physiological levels. Distinction between normal oxygen saturation values in veins and arteries was possible, making this fibre potentially useful to verify needle placement during a venous catheterisation or during a transseptal puncture. In the second study, two polymer optical light fibres were directly integrated into an epidural catheter. This optical catheter was tested during an ex-vivo swine laminectomy in the lumbar region. Another ex-vivo experiment was performed on chicken wings to discern blood vessels from other tissues. This information could be used during anaesthesic procedures to reduce the risk of toxicity from an intravascular injection. With reflectance spectroscopy, the depth in tissue from which signal is obtained is limited by the inter-fibre distance. This limitation motivated a third study, in which photoacoustic imaging was used to obtain image contrast for haemoglobin. The results of the three studies suggest that the integration of optical fibres into medical devices during minimally invasive procedures can allow for clinically relevant measurements of tissue properties in real-time

Quantification and influence of skin chromophores for remote detection of anemic conditions

Current standards for diagnosing and monitoring anemia are relatively invasive. The superficial symptoms of this condition are due to an underlying deficiency of red blood cells (RBC) or erythrocytes, and hemoglobin in the blood. This results in an inadequate supply of oxygen to the body’s tissues. For point-of-care diagnostic systems, remote determination of blood conditions will depend on an understanding of the interaction of light with hemoglobin. However, the skin acts as the first barrier for this detection. In this study, we pursue the possibility of detecting anemic conditions from the perfused blood in the dermis using optical models and Monte Carlo (MC) methods. The skin is composed of two primary layers, the epidermis and the dermis. The avascular epidermis absorbs light due to its primary chromophore, melanin. Subsequently, the absorption in the dermis layer is quantified by hematocrit and hemoglobin concentrations. Two-layer models of the human skin are set up and optical properties are assigned to these models. The optical variability across these models are defined by six melanin (epidermis) and two erythrocytes (dermis) concentrations. The twelve combinations of optical properties are assessed at six wavelengths of interest in the Virtual Tissue Simulator (VTS) environment. The chosen wavelengths range across the visible and near-infrared spectrum, which is a known and important diagnostic window for biological tissues. In this study, we explore the variability of light interactions for healthy and anemic blood conditions quantified in the dermis while accounting for variable melanin concentrations in the epidermis

Characterization and modeling of the human left atrium using optical coherence tomography

With current needs to better understand the interaction between atrial tissue microstructure and atrial fibrillation dynamics, micrometer scale imaging with optical coherence tomography has significant potential to provide further insight on arrhythmia mechanisms and improve treatment guidance. However, optical coherence tomography imaging of cardiac tissue in humans is largely unexplored, and the ability of optical coherence tomography to identify the structural substrate of atrial fibrillation has not yet been investigated. Therefore, the objective of this thesis was to develop an optical coherence tomography imaging atlas of the human heart, study the utility of optical coherence tomography in providing useful features of human left atrial tissues, and develop a framework for optical coherence tomography-informed cardiac modeling that could be used to probe dynamics between electrophysiology and tissue structure. Human left atrial tissues were comprehensively imaged by optical coherence tomography for the first time, providing an imaging atlas that can guide identification of left atrial tissue features from optical coherence tomography imaging. Optical coherence tomography image features corresponding to myofiber and collagen fiber orientation, adipose tissue, endocardial thickness and composition, and venous media were established. Varying collagen fiber distributions in the myocardial sleeves were identified within the pulmonary veins. A scheme for mapping optical coherence tomography data of dissected left atrial tissues to a three-dimensional, anatomical model of the human left atrium was also developed, enabling the mapping of distributions of imaged adipose tissue and fiber orientation to the whole left atrial geometry. These results inform future applications of structural substrate mapping in the human left atrium using optical coherence tomography-integrated catheters, as well as potential directions of ex vivo optical coherence tomography atrial imaging studies. Additionally, we developed a workflow for creating optical mapping models of atrial tissue as informed by optical coherence tomography. Tissue geometry, fiber orientation, ablation lesion geometry, and heterogeneous tissue types were extracted from optical coherence tomography images and incorporated into tissue-specific meshes. Electrophysiological propagation was simulated and combined with photon scattering simulations to evaluate the influence of tissue-specific structure on electrical and optical mapping signals. Through tissue-specific modeling of myofiber orientation, ablation lesions, and heterogeneous tissue types, the influence of myofiber orientation on transmural activation, the relationship between fluorescent signals and lesion geometry, and the blurring of optical mapping signals in the presence of heterogeneous tissue types were investigated. By providing a comprehensive optical coherence tomography image database of the human left atrium and a workflow for developing optical coherence tomography-informed cardiac tissue models, this work establishes the foundation for utilizing optical coherence tomography to improve the structural substrate characterization of atrial fibrillation. Future developments include analysis of optical coherence tomography imaged tissue structure with respect to clinical presentation, development of automated processing to better leverage the large amount of imaging data, enhancements and validation of the modeling scheme, and in vivo evaluation of the left atrial structural substrate through optical coherence tomography-integrated catheter

An Introduction to Light Interaction with Human Skin

Despite the notable progress in physically-based rendering, there is still a long way to go before one can automatically generate predictable images of organic materials such as human skin. In this tutorial, the main physical and biological aspects involved in the processes of propagation and absorption of light by skin tissues are examined. These processes affect not only skin appearance, but also its health. For this reason, they have also been the object of study in biomedical research. The models of light interaction with human skin developed by the biomedical community are mainly aimed at the simulation of skin spectral properties which are used to determine the concentration and distribution of various substances. In computer graphics, the focus has been on the simulation of light scattering properties that affect skin appearance. Computer models used to simulate these spectral and scattering properties are described in this tutorial, and their strengths and limitations discussed. Keywords: natural phenomena, biologically and physically-based rendering

Widefield functional and metabolic imaging from 600 – 1300 nm in the spatial frequency domain

New methods to measure and quantify tissue molecular composition and metabolism are a major driver of discovery in basic and clinical research. Optical methods are well suited for this task based on the non-invasive nature of many imaging and spectroscopy techniques, the variety of exogenous fluorescent probes available, and the ability to utilize label-free endogenous absorption signatures of tissue chromophores including oxy- and deoxy-hemoglobin, water, lipid, collagen, and glucose. Despite significant advances in biomedical imaging, there remain challenges in probing tissue information in a fast, wide-field, and non-invasive manner. Moreover, quantitative in vivo mapping of endogenous biomarkers such as water and lipids remain relatively less explored by the biomedical optics community due to their characteristic extinction spectra, which have distinct spectral features in the shortwave infrared, a wavelength band that has been traditionally more challenging to measure. The work presented in this dissertation was focused on developing instrumentation and algorithms for non-invasive quantification of tissue optical properties, fluorophore concentrations, and chromophore concentrations in a wide-field imaging format. All of the imaging methods and algorithms developed in this thesis extend the capability of the emerging technique called Spatial Frequency Domain Imaging (SFDI). First, a new imaging technique based on SFDI is presented that can quantify the quantum yield of exogenous fluorophores in tissue. This technique can potentially provide a new non-invasive means for in vivo mapping of local tissue environment such as temperature and pH. Next, an angle correction algorithm was developed for SFDI for more accurate estimation of tissue optical properties as well as chromophore concentrations in highly curved tissue, including small animal tumor models. Next, a wide-field label-free optical imaging system was developed to simultaneously measure water and lipids using the shortwave infrared (SWIR) wavelength region. Last, to break the bottleneck of processing speed in optical property inversion, new deep learning based models were developed to provide over 300× processing speed improvement. Together, these projects substantially extend the available contrasts and throughput of SFDI, providing opportunities for new preclinical and clinical applications.2020-10-22T00:00:00

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

Noninvasive Optical Imaging Techniques as a Quantitative Analysis of Kaposi's Sarcoma Skin Lesions

The visible inspection and palpation of skin lesions have long been used to assess the course of cutaneous disease in individuals with Kaposi's sarcoma (KS). Assessing the KS lesions requires a highly trained evaluator and evaluations made by different observers or by the same observer at different times can be inconsistent. Since lesions can grow from slow to explosively fast, and be associated with mortality and morbidity, reliable assessment of the lesions is important. Optical imaging techniques are quantitative methods that potentially offer a more objective means of assessing skin health that can supplement visual clinical observations. In this dissertation, the first paper describes using thermography and laser Doppler imaging (LDI) to monitor the temperature and vasculature, respectively, of KS lesions undergoing experimental therapy. Results showed that the median temperature elevation of lesions compared to the surrounding tissue was 1.1 ºC (range -0.68 to 3.43 ºC). In addition, 12 of the 16 lesions studied had increased blood perfusion as assessed by LDI (median 66 arbitrary units (AU), range -44 to 451 AU). The second paper describes the use of near-infrared (NIR) multi-spectral imaging to provide functional information about the lesions and surrounding tissue. Multi-spectral images were input to a mathematical optical skin model based on the absorption and scattering properties of skin, including the effects of melanin, blood, and oxygenated and deoxygenated hemoglobin. Functional information about the lesions before and after treatment with experimental therapies was determined. The third paper describes Monte-Carlo simulations of tissue conducted to determine the detection limits of a typical multi-spectral imaging system. The results showed that biological information contained in a typical spectral image reflected a small volume of tissue situated vertically under each pixel from a depth less than 2-3 mm. The objects appearing on a spectral image reasonably reproduce the correct geometrical shape and size of underlying inclusions of pathological tissue. Based on the three papers included in this dissertation, these three imaging techniques were found to be objective, easy to perform, and appear to be very sensitive in quantitatively assessing KS lesion progress upon administration of therapy