NONINVASIVE NEAR-INFRARED DIFFUSE OPTICAL MONITORING OF CEREBRAL HEMODYNAMICS AND AUTOREGULATION

Many cerebral diseases are associated with abnormal cerebral hemodynamics and impaired cerebral autoregulation (CA). CA is a mechanism to maintain cerebral blood flow (CBF) stable when mean arterial pressure (MAP) fluctuates. Evaluating these abnormalities requires direct measurements of cerebral hemodynamics and MAP. Several near-infrared diffuse optical instruments have been developed in our laboratory for hemodynamic measurements including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), hybrid NIRS/DCS, and dual-wavelength DCS flow-oximeter. We utilized these noninvasive technologies to quantify CBF and cerebral oxygenation in different populations under different physiological conditions/manipulations. A commercial finger plethysmograph was used to continuously monitor MAP. For investigating the impact of obstructive sleep apnea (OSA) on cerebral hemodynamics and CA, a portable DCS device was used to monitor relative changes of CBF (rCBF) during bilateral thigh cuff occlusion. Compared to healthy controls, smaller reductions in rCBF and MAP following cuff deflation were observed in patients with OSA, which might result from the impaired vasodilation. However, dynamic CAs quantified in time-domain (defined by rCBF drop/MAP drop) were not significantly different between the two groups. We also evaluated dynamic CA in frequency-domain, i.e., to quantify the phase shifts of low frequency oscillations (LFOs) at 0.1 Hz between cerebral hemodynamics and MAP under 3 different physiological conditions (i.e., supine resting, head-up tilt (HUT), paced breathing). To capture dynamic LFOs, a hybrid NIRS/DCS device was upgraded to achieve faster sampling rate and better signal-to-noise. We determined the best hemodynamic parameters (i.e., CBF, oxygenated and total hemoglobin concentrations) among the measured variables and optimal physiological condition (HUT) for detecting LFOs in healthy subjects. Finally, a novel dual-wavelength DCS flow-oximeter was developed to monitor cerebral hemodynamics during HUT-induced vasovagal presyncope (VVS) in healthy subjects. rCBF was found to have the best sensitivity for the assessment of VVS among the measured variables and was likely the final trigger of VVS. A threshold of ~50% rCBF decline was observed which can completely separate subjects with or without presyncope, suggesting its potential role for predicting VVS. With further development and applications, NIRS/DCS techniques are expected to have significant impacts on the evaluation of cerebral hemodynamics and autoregulation

A novel device for non-invasive cerebral perfusion assessment

Currently brain perfusion can be assessed by the means of radio-invasive methods, such as single-photon emission computed tomography and positron emission tomography, or by hightech methods such as magnetic resonance imaging. These methods are known to be very expensive, with long examination time, and finally, cannot be used for assessing brain oxygen distribution in relation to exercise and/or cognition-tests. The near infrared spectroscopy (NIRS) is a non-invasive diagnostic technique. In real time it is capable of measuring tissue oxygenation using portable instrumentation with a relative low cost. We and other groups previously adopted this instrument for investigation of the oxygen consumption in the muscles at rest and during exercise. NIRS can be now used to assess brain perfusion through the intact skull in human subjects by detecting changes in blood hemoglobin concentrations. Changes in perfusion can be related to both arterial and venous problems. This novel equipment features allow for a wide field of innovative applications where portability, wearability, and a small footprint are essential. The present review shows how to use it in relation to exercise protocols of the upper and lower extremities, measured in healthy people and in conditions of arterial and chronic cerebro-spinal venous insufficiency

BEst (Biomarker Estimation): Health Biomarker Estimation Non-invasively and Ubiquitously

This dissertation focuses on the non-invasive assessment of blood-hemoglobin levels. The primary goal of this research is to investigate a reliable, affordable, and user-friendly point-of-care solution for hemoglobin-level determination using fingertip videos captured by a smartphone. I evaluated videos obtained from five patient groups, three from the United States and two from Bangladesh, under two sets of lighting conditions. In the last group, based on human tissue optical transmission modeling data, I used near-infrared light-emitting diode sources of three wavelengths. I developed novel image processing techniques for fingertip video analysis to estimate hemoglobin levels. I studied video images creating image histogram and subdividing each image into multiple blocks. I determined the region of interest in a video and created photoplethysmogram signals. I created features from image histograms and PPG signals. I used the Partial Least Squares Regression and Support Vector Machine Regression tools to analyze input features and to build hemoglobin prediction models. Using data from the last and largest group of patients studied, I was able to develop a model with a strong linear correlation between estimated and clinically-measured hemoglobin levels. With further data and methodological refinements, the approach I have developed may be able to define a clinically accurate public health applicable tool for hemoglobin level and other blood constituent assessment

Remote Assessment of the Cardiovascular Function Using Camera-Based Photoplethysmography

Camera-based photoplethysmography (cbPPG) is a novel measurement technique that allows the continuous monitoring of vital signs by using common video cameras. In the last decade, the technology has attracted a lot of attention as it is easy to set up, operates remotely, and offers new diagnostic opportunities. Despite the growing interest, cbPPG is not completely established yet and is still primarily the object of research. There are a variety of reasons for this lack of development including that reliable and autonomous hardware setups are missing, that robust processing algorithms are needed, that application fields are still limited, and that it is not completely understood which physiological factors impact the captured signal. In this thesis, these issues will be addressed. A new and innovative measuring system for cbPPG was developed. In the course of three large studies conducted in clinical and non-clinical environments, the system’s great flexibility, autonomy, user-friendliness, and integrability could be successfully proven. Furthermore, it was investigated what value optical polarization filtration adds to cbPPG. The results show that a perpendicular filter setting can significantly enhance the signal quality. In addition, the performed analyses were used to draw conclusions about the origin of cbPPG signals: Blood volume changes are most likely the defining element for the signal's modulation. Besides the hardware-related topics, the software topic was addressed. A new method for the selection of regions of interest (ROIs) in cbPPG videos was developed. Choosing valid ROIs is one of the most important steps in the processing chain of cbPPG software. The new method has the advantage of being fully automated, more independent, and universally applicable. Moreover, it suppresses ballistocardiographic artifacts by utilizing a level-set-based approach. The suitability of the ROI selection method was demonstrated on a large and challenging data set. In the last part of the work, a potentially new application field for cbPPG was explored. It was investigated how cbPPG can be used to assess autonomic reactions of the nervous system at the cutaneous vasculature. The results show that changes in the vasomotor tone, i.e. vasodilation and vasoconstriction, reflect in the pulsation strength of cbPPG signals. These characteristics also shed more light on the origin problem. Similar to the polarization analyses, they support the classic blood volume theory. In conclusion, this thesis tackles relevant issues regarding the application of cbPPG. The proposed solutions pave the way for cbPPG to become an established and widely accepted technology

Orally Available Near Infrared Imaging Agents for the Early Detection of Diseases

Early detection and treatment of diseases has the potential to dramatically improve patient outcomes. Diseases like cancer have shown remarkably higher survival rates when the cancer is detected early, before it has had a chance to metastasize and migrate to different regions. One way to increase rates of early detection is to implement annual screenings. Current screening methods often focus on blood tests, which gather molecular information from the circulation, or imaging, which provides anatomical details. Molecular imaging has the ability to provide both types of information, but the high cost and radiation risk often preclude its use in population screening. In this thesis, we hypothesized that near-infrared fluorescent imaging agents could be administered orally and yield sufficient contrast for disease diagnosis. The use of NIR fluorescent targeting ligands provides both spatial and molecular information while making the entire process fast, inexpensive, completely non-invasive, and safe with the use of non-ionizing radiation. For proof-of-concept studies to develop this novel technique, we selected integrin of the form αvβ3 as the target, and a high affinity peptidomimetic as the ligand. The major challenge of developing an orally available imaging agent is that orally available drugs are typically small in size and lipophilic in nature, while imaging agents tend to be larger in size and hydrophilic. In spite of these challenges, an IRDye800CW-labeled agent had an oral absorption of 2.3% and was selected for studies in the detection of two diseases: breast cancer and rheumatoid arthritis. Mammography uses x-rays to detect suspicious lesions when screening for breast cancer but only provides anatomical data, which has lead to high false positive rates and an estimated $4 billion in expenditure due to overdiagnosis. The IRDye800CW agent was dosed at 5 mg/kg in an orthotopic tumor xenograft mouse model. Live animal imaging at 6, 24 and 48 hours post administration showed the highest target to background ratio of ~4 at 48 hours and histology showed high uptake of the agent by macrophages and breast cancer cells. Rheumatoid arthritis (RA) is an autoimmune disease that leads to largely irreversible joint damage over time, but effective treatments are available. Therefore, there is intense interest in early detection of RA to prevent further damage, and some studies have even indicated that the disease could be cured if detected early. However, current methods lack the sensitivity to detect RA at an early stage. Oral delivery of the IRDye800CW agent in a collagen antibody induced arthritis mouse model showed significantly higher uptake in the inflamed joints compared to healthy joints. To scale the expected signal to clinically relevant depths, we developed a 3D COMSOL model for optical simulations of RA detection in the human hand. The simulations showed that for target to background concentration ratios of the imaging agent of 5.5 and 6.5, there was 95% and 98% probability of detection of the inflamed joint. The in vivo mouse model had an estimated target to background concentration ratio of ~20, which makes the detection of RA in humans very promising. This dissertation demonstrates the oral delivery of molecular imaging agents for the detection of breast cancer and RA in relevant mouse models. These studies provide the foundation to develop a range of oral molecular imaging agents for other biomarkers and diseases with the potential for earlier diagnosis to improve patient outcomes.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147662/1/sumitbh_1.pd

Photoplethysmography in noninvasive cardiovascular assessment

The electro-optic technique of measuring the cardiovascular pulse wave known as photoplethysmography (PPG) is clinically utilised for noninvasive characterisation of physiological components by dynamic monitoring of tissue optical absorption. There has been a resurgence of interest in this technique in recent years, driven by the demand for a low cost, compact, simple and portable technology for primary care and community-based clinical settings, and the advancement of computer-based pulse wave analysis techniques. PPG signal provides a means of determining cardiovascular properties during the cardiac cycle and changes with ageing and disease. This thesis focuses on the photoplethysmographic signal for cardiovascular assessment. The contour of the PPG pulse wave is influenced by vascular ageing. Contour analysis of the PPG pulse wave provides a rapid means of assessing vascular tone and arterial stiffness. In this thesis, the parameters extracted from the PPG pulse wave are examined in young adults. The results indicate that the contour parameters of the PPG pulse wave could provide a simple and noninvasive means to study the characteristic change relating to arterial stiffness. The pulsatile component of the PPG signal is due to the pumping action of the heart, and thus could reveal the circulation changes of a specific vascular bed. Heart rate variability (HRV) represents one of the most promising quantitative markers of cardiovascular control. Calculation of HRV from the peripheral pulse wave using PPG, called pulse rate variability (PRV), is investigated. The current work has confirmed that the PPG signal could provide basic information about heart rate (HR) and its variability, and highly suggests a good alternative to understanding dynamics pertaining to the autonomic nervous system (ANS) without the use of an electrocardiogram (ECG) device. Hence, PPG measurement has the potential to be readily accepted in ambulatory cardiac monitoring due to its simplicity and comfort. Noncontact PPG (NPPG) is introduced to overcome the current limitations of contact PPG. As a contactless device, NPPG is especially attractive for physiological monitoring in ambulatory units, NICUs, or trauma centres, where attaching electrodes is either inconvenient or unfeasible. In this research, a prototype for noncontact reflection PPG (NRPPG) with a vertical cavity surface emitting laser (VCSEL) as a light source and a high-speed PiN photodiode as a photodetector is developed. The results from physiological experiments suggest that NRPPG is reliable to extract clinically useful information about cardiac condition and function. In summary, recent evidence demonstrates that PPG as a simple noninvasive measurement offers a fruitful avenue for noninvasive cardiovascular monitoring. Key words: Photoplethysmography (PPG), Cardiovascular assessment, Pulse wave contour analysis, Arterial stiffness, Heart rate (HR), Heart rate variability (HRV), Pulse rate variability (PRV), Autonomic nervous system (ANS), Electrocardiogram (ECG).EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Biomedical Photoacoustic Imaging and Sensing Using Affordable Resources

The overarching goal of this book is to provide a current picture of the latest developments in the capabilities of biomedical photoacoustic imaging and sensing in an affordable setting, such as advances in the technology involving light sources, and delivery, acoustic detection, and image reconstruction and processing algorithms. This book includes 14 chapters from globally prominent researchers , covering a comprehensive spectrum of photoacoustic imaging topics from technology developments and novel imaging methods to preclinical and clinical studies, predominantly in a cost-effective setting. Affordability is undoubtedly an important factor to be considered in the following years to help translate photoacoustic imaging to clinics around the globe. This first-ever book focused on biomedical photoacoustic imaging and sensing using affordable resources is thus timely, especially considering the fact that this technique is facing an exciting transition from benchtop to bedside. Given its scope, the book will appeal to scientists and engineers in academia and industry, as well as medical experts interested in the clinical applications of photoacoustic imaging

Imaging photoplethysmography: towards effective physiological measurements

Since its conception decades ago, Photoplethysmography (PPG) the non-invasive opto-electronic technique that measures arterial pulsations in-vivo has proven its worth by achieving and maintaining its rank as a compulsory standard of patient monitoring. However successful, conventional contact monitoring mode is not suitable in certain clinical and biomedical situations, e.g., in the case of skin damage, or when unconstrained movement is required. With the advance of computer and photonics technologies, there has been a resurgence of interest in PPG and one potential route to overcome the abovementioned issues has been increasingly explored, i.e., imaging photoplethysmography (iPPG). The emerging field of iPPG offers some nascent opportunities in effective and comprehensive interpretation of the physiological phenomena, indicating a promising alternative to conventional PPG. Heart and respiration rate, perfusion mapping, and pulse rate variability have been accessed using iPPG. To effectively and remotely access physiological information through this emerging technique, a number of key issues are still to be addressed. The engineering issues of iPPG, particularly the influence of motion artefacts on signal quality, are addressed in this thesis, where an engineering model based on the revised Beer-Lambert law was developed and used to describe opto-physiological phenomena relevant to iPPG. An iPPG setup consisting of both hardware and software elements was developed to investigate its reliability and reproducibility in the context of effective remote physiological assessment. Specifically, a first study was conducted for the acquisition of vital physiological signs under various exercise conditions, i.e. resting, light and heavy cardiovascular exercise, in ten healthy subjects. The physiological parameters derived from the images captured by the iPPG system exhibited functional characteristics comparable to conventional contact PPG, i.e., maximum heart rate difference was <3 bpm and a significant (p < 0.05) correlation between both measurements were also revealed. Using a method for attenuation of motion artefacts, the heart rate and respiration rate information was successfully assessed from different anatomical locations even in high-intensity physical exercise situations. This study thereby leads to a new avenue for noncontact sensing of vital signs and remote physiological assessment, showing clear and promising applications in clinical triage and sports training. A second study was conducted to remotely assess pulse rate variability (PRV), which has been considered a valuable indicator of autonomic nervous system (ANS) status. The PRV information was obtained using the iPPG setup to appraise the ANS in ten normal subjects. The performance of the iPPG system in accessing PRV was evaluated via comparison with the readings from a contact PPG sensor. Strong correlation and good agreement between these two techniques verify the effectiveness of iPPG in the remote monitoring of PRV, thereby promoting iPPG as a potential alternative to the interpretation of physiological dynamics related to the ANS. The outcomes revealed in the thesis could present the trend of a robust non-contact technique for cardiovascular monitoring and evaluation

Optical Diagnostics in Human Diseases

Optical technologies provide unique opportunities for the diagnosis of various pathological disorders. The range of biophotonics applications in clinical practice is considerably wide given that the optical properties of biological tissues are subject to significant changes during disease progression. Due to the small size of studied objects (from μm to mm) and despite some minimum restrictions (low-intensity light is used), these technologies have great diagnostic potential both as an additional tool and in cases of separate use, for example, to assess conditions affecting microcirculatory bed and tissue viability. This Special Issue presents topical articles by researchers engaged in the development of new methods and devices for optical non-invasive diagnostics in various fields of medicine. Several studies in this Special Issue demonstrate new information relevant to surgical procedures, especially in oncology and gynecology. Two articles are dedicated to the topical problem of breast cancer early detection, including during surgery. One of the articles is devoted to urology, namely to the problem of chronic or recurrent episodic urethral pain. Several works describe the studies in otolaryngology and dentistry. One of the studies is devoted to diagnosing liver diseases. A number of articles contribute to the studying of the alterations caused by diabetes mellitus and cardiovascular diseases. The results of all the presented articles reflect novel innovative research and emerging ideas in optical non-invasive diagnostics aimed at their wider translation into clinical practice

Pulse Oxigraphy: And other new in-depth perspectives through the near infrared window

The aim of this thesis was to investigate the feasability of contactless imaging pulse oximetry (proposed term: pulse oxigraphy). The patent disclosed in chapter 2 claims that such pulse oxigraphy can be achieved with camera-derived photoplethysmographic pulse waves at three wavelengths, preferably being 660, 810 and 940nm. From the absorption curves of hemoglobin and oxyhemoglobin it can be easily derived that two of these wavelengths (660 and 940nm) contain oxygenation-related information, and they have proven to be useful for conventional pulse oximetry (in transmission- mode as well as in reflectance-mode). The additional third wavelength (810nm) lies at a so-called isobestic point where the absorption curves of hemoglobin and oxyhemoglobin intersect. Thus, images and/or plethysmographic pulse waves recorded at 810nm do not contain oxygenation-related information, which is useful for reference purposes when dealing with shadows, reflections, movement artifacts and variations in geometry. With regard to pulse oxigraphy the following results were obtained: In chapter 3 we proved that it is possible to derive photoplethysmographic pulse waves containing the heart rythm of a living person at all three required wavelengths from camera recordings collected at a distance of 72 cm. To investigate and validate the capabilities for pulse oxigraphy with this set up, direct measurements on volunteers were sub optimal, because of: Signal-to-noise issues, sequentially recorded heartbeats for oxygen saturation calculations, and lack of a method to induce prolonged stable and adjustable oxygen saturation levels