Clinical Applications of Near-Infrared Diffuse Correlation Spectroscopy and Tomography for Tissue Blood Flow Monitoring and Imaging

Objective. Blood flow is one such available observable promoting a wealth of physiological insight both individually and in combination with other metrics. Approach. Near-infrared diffuse correlation spectroscopy (DCS) and, to a lesser extent, diffuse correlation tomography (DCT), have increasingly received interest over the past decade as noninvasive methods for tissue blood flow measurements and imaging. DCS/DCT offers several attractive features for tissue blood flow measurements/imaging such as noninvasiveness, portability, high temporal resolution, and relatively large penetration depth (up to several centimeters). Main results. This review first introduces the basic principle and instrumentation of DCS/DCT, followed by presenting clinical application examples of DCS/DCT for the diagnosis and therapeutic monitoring of diseases in a variety of organs/tissues including brain, skeletal muscle, and tumor. Significance. Clinical study results demonstrate technical versatility of DCS/DCT in providing important information for disease diagnosis and intervention monitoring

New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging

Jöbsis was the first to describe the in vivo application of near-infrared spectroscopy (NIRS), also called diffuse optical spectroscopy (DOS). NIRS was originally designed for the clinical monitoring of tissue oxygenation, and today it has also become a useful tool for neuroimaging studies (functional near-infrared spectroscopy, fNIRS). However, difficulties in the selective and quantitative measurements of tissue hemoglobin (Hb), which have been central in the NIRS field for over 40 years, remain to be solved. To overcome these problems, time-domain (TD) and frequency-domain (FD) measurements have been tried. Presently, a wide range of NIRS instruments are available, including commonly available commercial instruments for continuous wave (CW) measurements, based on the modified Beer–Lambert law (steady-state domain measurements). Among these measurements, the TD measurement is the most promising approach, although compared with CW and FD measurements, TD measurements are less common, due to the need for large and expensive instruments with poor temporal resolution and limited dynamic range. However, thanks to technological developments, TD measurements are increasingly being used in research, and also in various clinical settings. This Special Issue highlights issues at the cutting edge of TD DOS and diffuse optical tomography (DOT). It covers all aspects related to TD measurements, including advances in hardware, methodology, the theory of light propagation, and clinical applications

WearLight: Towards a Wearable, Configurable Functional NIR Spectroscopy System for Noninvasive Neuroimaging

Functional near-infrared spectroscopy (fNIRS) has emerged as an effective brain monitoring technique to measure the hemodynamic response of the cortical surface. Its wide popularity and adoption in recent time attribute to its portability, ease of use, and flexibility in multimodal studies involving electroencephalography. While fNIRS is still emerging on various fronts including hardware, software, algorithm, and applications, it still requires overcoming several scientific challenges associated with brain monitoring in naturalistic environments where the human participants are allowed to move and required to perform various tasks stimulating brain behaviors. In response to these challenges and demands, we have developed a wearable fNIRS system, WearLight that was built upon an Internet-of-Things embedded architecture for onboard intelligence, configurability, and data transmission. In addition, we have pursued detailed research and comparative analysis on the design of the optodes encapsulating an near-infrared light source and a detector into 3-D printed material. We performed rigorous experimental studies on human participants to test reliability, signal-to-noise ratio, and configurability. Most importantly, we observed that WearLight has a capacity to measure hemodynamic responses in various setups including arterial occlusion on the forearm and frontal lobe brain activity during breathing exercises in a naturalistic environment. Our promising experimental results provide an evidence of preliminary clinical validation of WearLight. This encourages us to move toward intensive studies involving brain monitoring

Next generation near infrared (NIR) and shortwave infrared (SWIR) wearables for breast cancer imaging

Neoadjuvant chemotherapy (NAC) is a common breast cancer treatment that involves administering chemotherapy for 3-6 months prior to surgery. This treatment enables more breast-conserving surgeries and even allows for the omission of surgery in some cases. However, about 31% of patients receiving NAC do not respond to the treatment. Therefore, there is a need for real-time methods to predict treatment response and improve patient outcomes. Over the last two decades, diffuse optical imaging has been investigated as a potential solution to this problem. This noninvasive and inexpensive technology uses near or shortwave infrared (NIR or SWIR) light to illuminate tissue, and detects multiply-scattered photons. However, bulky instrumentation and complicated imaging procedures have limited the clinical adoption of this technology. Furthermore, measured biomarkers including oxy- and deoxy-hemoglobin (HbO2 and HHb, respectively), water, and lipid, have had mixed results in terms of prognostic capability. To address these limitations, a new wearable optical probe technology was developed and validated in this project, including a high-optode density NIR probe for monitoring hemodynamics and a first-generation SWIR probe for quantifying water and lipid. Measurements on tissue-mimicking channel flow phantoms confirmed the ability of the NIR probe to quantify absorption contrast in vitro, and a cuff occlusion measurement demonstrated sensitivity to HbO2 and HHb in vivo. Hemodynamic oscillations at the respiratory rate were also explored in healthy volunteers and breast cancer patients as a potential new biomarker. It was demonstrated that traditional and novel breathing-related hemodynamic metrics provide tumor contrast and can potentially track treatment response. A deep-learning algorithm was developed to extract water and lipid concentrations from multi-distance SWIR measurements. The SWIR probe was validated by comparing measured water and lipid concentrations against ground truth values in emulsion phantoms. This work represents a significant step toward the development of technologies for frequent breast cancer treatment monitoring in the clinic and potentially at home

Diffusion-tensor MRI methods to study and evaluate muscle architecture

The thesis describes the development of various approaches for measuring muscle architectural parameters using Diffusion Tensor MR Imaging (DTI). It also illustrates how to apply them to study changes in muscle architecture after an injury prevention program.In Chapter 2, because manual segmentation of muscles is cumbersome, we validated a semi-automatic framework for estimating DTI indices in upper leg muscles. This method reduced segmentation time by a factor of three in a cross-sectional study design and can be used fully automatically in a longitudinal assessment of changes in DTI indices.Chapter 3 was a feasibility study measuring fiber orientation changes with DTI in calf muscles and sub-compartments of the Soleus and Tibialis Anterior during plantarflexion and dorsiflexion. Differences in fiber orientations corresponded to the known agonist-antagonist function of the muscles. This shows that DTI can be utilized to assess changes in muscle orientation due to posture or training.In Chapter 4, we compared DTI fiber tractography for Vastus Lateralis fiber architecture assessment with 3D ultrasonography (3D-US). We discovered that both methods have their advantages and disadvantages, with the agreement between the two techniques being moderate.Finally, in Chapter 5, we examined the effects of a hamstring injury prevention exercise on the muscle architectural parameters of basketball players. DTI was employed to quantify changes in fiber orientation and length using tractography and fiber orientation maps. It was observed that the Semitendinosus fascicle length increased after the Nordics exercise, while the Biceps Femoris long head fiber orientation decreased following the Divers intervention

Analysis of forearm muscles activity by means of new protocols of multichannel EMG signal recording and processing

Los movimientos voluntarios del cuerpo son controlados por el sistema nervioso central y periférico a través de la contracción de los músculos esqueléticos. La contracción se inicia al liberarse un neurotransmisor sobre la unión neuromuscular, iniciando la propagación de un biopotencial sobre la membrana de las fibras musculares que se desplaza hacia los tendones: el Potencial de Acción de la Unidad Motora (MUAP). La señal electromiográfica de superficie registra la activación continua de dichos potenciales sobre la superficie de la piel y constituye una valiosa herramienta para la investigación, diagnóstico y seguimiento clínico de trastornos musculares, así como para la identificación de la intención movimiento tanto en términos de dirección como de potencia. En el estudio de las enfermedades del sistema neuromuscular es necesario analizar el nivel de actividad, la capacidad de producción de fuerza, la activación muscular conjunta y la predisposición a la fatiga muscular, todos ellos asociados con factores fisiológicos que determinan la resultante contracción mioeléctrica. Además, el uso de matrices de electrodos facilita la investigación de las propiedades periféricas de las unidades motoras activas, las características anatómicas del músculo y los cambios espaciales en su activación, ocasionados por el tipo de tarea motora o la potencia de la misma. El objetivo principal de esta tesis es el diseño e implementación de protocolos experimentales y algoritmos de procesado para extraer información fiable de señales sEMG multicanal en 1 y 2 dimensiones del espacio. Dicha información ha sido interpretada y relacionada con dos patologías específicas de la extremidad superior: Epicondilitis Lateral y Lesión de Esfuerzo Repetitivo. También fue utilizada para identificar la dirección de movimiento y la fuerza asociada a la contracción muscular, cuyos patrones podrían ser de utilidad en aplicaciones donde la señal electromiográfica se utilice para controlar interfaces hombre-máquina como es el caso de terapia física basada en robots, entornos virtuales de rehabilitación o realimentación de la actividad muscular. En resumen, las aportaciones más relevantes de esta tesis son: * La definición de protocolos experimentales orientados al registro de señales sEMG en una región óptima del músculo. * Definición de índices asociados a la co-activación de diferentes músculos * Identificación de señales artefactuadas en registros multicanal * Selección de los canales mas relevantes para el análisis Extracción de un conjunto de características que permita una alta exactitud en la identificación de tareas motoras Los protocolos experimentales y los índices propuestos permitieron establecer que diversos desequilibrios entre músculos extrínsecos del antebrazo podrían desempeñar un papel clave en la fisiopatología de la epicondilitis lateral. Los resultados fueron consistentes en diferentes ejercicios y pueden definir un marco de evaluación para el seguimiento y evaluación de pacientes en programas de rehabilitación motora. Por otra parte, se encontró que las características asociadas con la distribución espacial de los MUAPs mejoran la exactitud en la identificación de la intención de movimiento. Lo que es más, las características extraídas de registros sEMG de alta densidad son más robustas que las extraídas de señales bipolares simples, no sólo por la redundancia de contacto implicada en HD-EMG, sino también porque permite monitorizar las regiones del músculo donde la amplitud de la señal es máxima y que varían con el tipo de ejercicio, permitiendo así una mejor estimación de la activación muscular mediante el análisis de los canales mas relevantes.Voluntary movements are achieved by the contraction of skeletal muscles controlled by the Central and Peripheral Nervous system. The contraction is initiated by the release of a neurotransmitter that promotes a reaction in the walls of the muscular fiber, producing a biopotential known as Motor Unit Action Potential (MUAP) that travels from the neuromuscular junction to the tendons. The surface electromyographic signal records the continuous activation of such potentials over the surface of the skin and constitutes a valuable tool for the diagnosis, monitoring and clinical research of muscular disorders as well as to infer motion intention not only regarding the direction of the movement but also its power. In the study of diseases of the neuromuscular system it is necessary to analyze the level of activity, the capacity of production of strength, the load-sharing between muscles and the probably predisposition to muscular fatigue, all of them associated with physiological factors determining the resultant muscular contraction. Moreover, the use of electrode arrays facilitate the investigation of the peripheral properties of the active Motor Units, the anatomical characteristics of the muscle and the spatial changes induced in their activation of as product of type of movement or power of the contraction.The main objective of this thesis was the design and implementation of experimental protocols, and algorithms to extract information from multichannel sEMG signals in 1 and 2 dimensions of the space. Such information was interpreted and related to pathological events associated to two upper-limb conditions: Lateral Epicondylitis and Repetitive Strain Injury. It was also used to identify the direction of movement and contraction strength which could be useful in applications concerning the use of biofeedback from EMG like in robotic- aided therapies and computer-based rehabilitation training.In summary, the most relevant contributions are:§The definition of experimental protocols intended to find optimal regions for the recording of sEMG signals. §The definition of indices associated to the co- activation of different muscles. §The detection of low-quality signals in multichannel sEMG recordings.§ The selection of the most relevant EMG channels for the analysis§The extraction of a set of features that led to high classification accuracy in the identification of tasks.The experimental protocols and the proposed indices allowed establishing that imbalances between extrinsic muscles of the forearm could play a key role in the pathophysiology of lateral epicondylalgia. Results were consistent in different types of motor task and may define an assessment framework for the monitoring and evaluation of patients during rehabilitation programs.On the other hand, it was found that features associated with the spatial distribution of the MUAPs improve the accuracy of the identification of motion intention. What is more, features extracted from high density EMG recordings are more robust not only because it implies contact redundancy but also because it allows the tracking of (task changing) skin surface areas where EMG amplitude is maximal and a better estimation of muscle activity by the proper selection of the most significant channels