An ultra-fast digital diffuse optical spectroscopic imaging system for neoadjuvant chemotherapy monitoring

Up to 20% of breast cancer patients who undergo presurgical (neoadjuvant) chemotherapy have no response to treatment. Standard-of-care imaging modalities, including MRI, CT, mammography, and ultrasound, measure anatomical features and tumor size that reveal response only after months of treatment. Recently, non-invasive, near-infrared optical markers have shown promise in indicating the efficacy of treatment at the outset of the chemotherapy treatment. For example, frequency domain Diffuse Optical Spectroscopic Imaging (DOSI) can be used to characterize the optical scattering and absorption properties of thick tissue, including breast tumors. These parameters can then be used to calculate tissue concentrations of chromophores, including oxyhemoglobin, deoxyhemoglobin, water, and lipids. Tumors differ in hemoglobin concentration, as compared with healthy background tissue, and changes in hemoglobin concentration during neoadjuvant chemotherapy have been shown to correlate with efficacy of treatment. Using DOSI early in treatment to measure chromophore concentrations may be a powerful tool for guiding neoadjuvant chemotherapy treatment. Previous frequency-domain DOSI systems have been limited by large device footprints, complex electronics, high costs, and slow acquisition speeds, all of which complicate access to patients in the clinical setting. In this work a new digital DOSI (dDOSI) system has been developed, which is relatively inexpensive and compact, allowing for use at the bedside, while providing unprecedented measurement speeds. The system builds on, and significantly advances, previous dDOSI setups developed by our group and, for the first time, utilizes hardware-integrated custom board-level direct digital synthesizers (DDS) and analog to digital converters (ADC) to generate and directly measure signals utilizing undersampling techniques. The dDOSI system takes high-speed optical measurements by utilizing wavelength multiplexing while sweeping through hundreds of modulation frequencies in tens of milliseconds. The new dDOSI system is fast, inexpensive, and compact without compromising accuracy and precision

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions. Keywords: DCS; NIRS; diffuse optics; functional neuroscience; optical imaging; optical spectroscop

Development of a portable time-domain system for diffuse optical tomography of the newborn infant brain

Conditions such as hypoxic-ischaemic encephalopathy (HIE) and perinatal arterial ischaemic stroke (PAIS) are causes of lifelong neurodisability in a few hundred infants born in the UK each year. Early diagnosis and treatment are key, but no effective bedside detection and monitoring technology is available. Non-invasive, near-infrared techniques have been explored for several decades, but progress has been inhibited by the lack of a portable technology, and intensity measurements, which are strongly sensitive to uncertain and variable coupling of light sources and detector to the scalp. A technique known as time domain diffuse optical tomography (TD-DOT) uses measurements of photon flight times between sources and detectors placed on the scalp. Mean flight time is largely insensitive to the coupling and variation in mean flight time can reveal spatial variation in blood volume and oxygenation in regions of brain sampled by the measurements. While the cost, size and high power consumption of such technology have hitherto prevented development of a portable imaging system, recent advances in silicon technology are enabling portable and low-power TD-DOT devices to be built. A prototype TD-DOT system is proposed and demonstrated, with the long-term aim to design a portable system based on independent modules, each supporting a time-of-flight detector and a pulsed source. The operation is demonstrated of components that can be integrated in a portable system: silicon photodetectors, integrated circuit-based signal conditioning and time detection -- built using a combination of off-the-shelf components and reconfigurable hardware, standard computer interfaces, and data acquisition and calibration software. The only external elements are a PC and a pulsed laser source. This thesis describes the design process, and results are reported on the performance of a 2-channel system with online histogram generation, used for phantom imaging. Possible future development of the hardware is also discussed

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

Development of Portable Diffuse Optical Spectroscopic Systems For Treatment Monitoring

The goal of this dissertation is to demonstrate the utility of portable, small-scale diffuse optical spectroscopic (DOS) systems for the diagnosis and treatment monitoring of various diseases. These systems employ near-infrared light (wavelength range of 650nm to 950nm) to probe human tissue and are sensitive to changes in scattering and absorption properties of tissues. The absorption is mainly influenced by the components of blood, namely oxy- and deoxy-hemoglobin (HbO2 and Hb) and parameters that can be derived from them (e.g. total hemoglobin concentration [THb] and oxygen saturation, StO2). Therefore, I focused on diseases in which these parameters change, which includes vascular diseases such as Peripheral Atrial Disease (PAD) and Infantile Hemangiomas (IH) as well as musculoskeletal autoimmune diseases such as Rheumatoid Arthritis (RA). In each of these specific diseases, current monitoring techniques are limited by their sensitivity to disease progression or simply do not exist as a quantitative metric. As part of this project, I first designed and built a wireless handheld DOS device (WHDD) that can perform DOS measurements at various tissue depths. This device was used in a 15-patient pilot study for infantile hemangiomas (IH) to differentiate diseased skin from normal skin and monitor the vascular changes during intervention. In another study, I compare the ultra-small form- factor WHDD’s ability to monitor synovitis and disease progression during a patient’s treatment of RA against the capabilities of a proven frequency domain optical tomographic (FDOT) system that has shown to differentiate patients with and without RA. Learning from clinical utility of the WHDD from these two studies, I adapted the WHDD technology to develop a compact multi- channel DOS measurement system to monitor perfusion changes in the lower extremities before and after surgical intervention for patients with peripheral artery disease (PAD). Using this multi- channel system, which we called the vascular optical spectroscopic measurement (VOSM) system, our group conducted a 20-subject pilot study to quantify its ability to monitor blood perfusion before and after revascularization of stenotic arteries in the lower extremities. This proof-of- concept study demonstrated how DOS may help vascular surgeons perform revascularization procedures in the operating room and assists in post-operative treatment monitoring of vascular diseases

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

A wearable near-infrared diffuse optical system for monitoring in vivo breast tumor hemodynamics during chemotherapy infusions

Neoadjuvant chemotherapy (NAC) is increasingly being utilized to reduce tumor burden prior to surgery for breast cancer patients with stage II or higher disease. A pathologic complete response (pCR) to NAC has been correlated with longer 5-year survival and is generally considered as an absence of invasive cancer in the breast and axillary nodes at the time of surgery. Unfortunately, only about 10% of patients achieve pCR during NAC, and it may take months after the first infusion to determine response with methods that rely on anatomic information, such as palpation, mammography, ultrasound, and MRI. Functional imaging technologies such as Positron Emission Tomography, Magnetic Resonance Spectroscopy, and more recently, Diffuse Optical Spectroscopy, have shown promise for earlier predictions of therapy response. However, most of these techniques suffer from high expense, lack of portability, and safety issues related to the use of ionizing radiation or exogenous contrast agents. Furthermore, the repeated patient visits required by these techniques may hamper their clinical adoption for this purpose. This project aims to develop a new wearable diffuse optical device that can be used to investigate if very early timepoints during a patient’s first chemotherapy infusion are predictive of overall response (pCR versus non-pCR) to NAC. These timepoints correspond to an already scheduled patient visit and have so far been unexplored for their prognostic value. The development of this continuous-wave diffuse optical imaging device was conducted in three stages. First, a prototype rigid probe was designed and developed to test key optical and electrical components. Second, a high optode-density flexible probe was design and fabricated which can conform to the curved surface of the human breast. Finally, a control box with miniaturized electronics and high-speed electronics was designed and fabricated to complete a clinic-ready system. This system was then tested in both the laboratory setting and as part of a normal-volunteer clinical study in healthy subjects during a breath hold hemodynamic challenge.2019-10-22T00:00:00