Kambiz Pourrezaei

Functional near-infrared spectroscopy

The purpose of the this article is to describe an emerging neuroimaging technology, functional near-infrared spectroscopy (fNIRs), which has several attributes that make it possible to conduct neuroimaging studies of the cortex in clinical offices and under more realistic, ecologically valid parameters. fNIRs use near-infrared light to measure changes in the concentration of oxygenated and deoxygenated hemoglobin in the cortex. Although fNIR imaging is limited to the outer cortex, it provides neuroimaging that is safe, portable, and very affordable relative to other neuroimaging technologies. It is also relatively robust to movement artifacts and can readily be integrated with other technologies such as EEG

Functional Optical Brain Imaging Using Near-Infrared During Cognitive Tasks

A symbiotic relation between the operator and the operational environment can be realized by an advanced computing platform designed to understand and adapt to the cognitive and the physiological state of the user, especially during sensitive and cognitively demanding operations. The success of such a complex system depends not only on the efficacy of the individual components, but also on the efficient and appropriate integration of its parts. Because near infrared technology allows the design of portable, safe, affordable, and negligibly intrusive monitoring systems, the functional near infrared (fNIR) monitoring of brain hemodynamics can be of value in this type of complex system, particularly in helping to understand the cognitive and emotional state of the user during mentally demanding operations. This article presents the deployment and statistical analysis of fNIR spectroscopy for the purpose of cognitive state assessment while the user performs a complex task. This article is based on data collected during the Augmented Cognition-Technical Integration Experiment session. The experimental protocol for this session used a complex task, resembling a video game, called the Warship Commander Task (WCT). The WCT was designed to approximate naval air warfare management. Task difficulty and task load were manipulated by changing the following: (a) the number of airplanes that had to be managed at a given time, (b) the number of unknown (vs. known) airplane identities, and (c) the presence or absence of an auditory memory task. The fNIR data analysis explored the following: (a) the relations among cognitive workload, the participants performance, and changes in blood oxygenation levels of the dorsolateral prefrontal cortex; and (b) the effect of divided attention as manipulated by the secondary component of the WCT (the auditory task). The primary hypothesis was that blood oxygenation in the prefrontal cortex, as assessed by fNIR, would rise with increasing task load and would demonstrate a positive correlation with performance measures. The results indicated that the rate of change in blood oxygenation was significantly sensitive to task load changes and correlated fairly well with performance variables.

Functional brain imaging using near-infrared technology

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Registering fNIR Data to Brain Surface Image using MRI templates

25.00©2007IEEE I n the last decade, functional near-infrared spectroscopy (fNIR) has been introduced as a new neuroimaging modality with which to conduct functional brain imaging studies [1]–[24]. fNIR technology uses specific wavelengths of light, irradiated through the scalp, to enable the noninvasive measurement of changes in the relative ratios of deoxygenated hemoglobin (deoxy-Hb) and oxygenated hemoglobin (oxy-Hb) during brain activity. This technology allows the design of portable, safe, affordable, noninvasive, and minimally intrusive monitoring systems. These qualities make fNIR suitable for the study of hemodynamic changes due to cognitive and emotional brain activity under many working and educational conditions, as well as in the field. Functional imaging is typically conducted in an effort to understand the activity in a given brain region in terms of its relationship to a particular behavioral state or its interactions with inputs from another region’s activity. The program of research in cognitive neuroscience conducted by our optical brain imaging group has utilized the current-generation fNIR system to investigate brain activity, primarily in the dorsolateral and inferior frontal cortex [20]–[24]. To date, the fNIR studies of cognition and emotion have focused on functions associated with Brodman’s areas BA9, BA10, BA46, BA45, BA47, and BA44. Recent positron emission tomography (PET) and functional magnetic resonance (fMRI) studies have shown that these areas play a critical role in sustained attention, both the short-term storage and the executive process components of working memory, episodic memory, problem solving, response inhibition, and the perception of smell (for a recent review, see [25] and [26]). In addition, word recognition and the storage of verbal materials activate Broca’s area and left hemisphere supplementary and premotor areas [25], [27], [28]. To date, studies utilizing fNIR have shown results consistent with fMRI and PET findings for working memory and sustained attention [21]–[23]. In this article, we will describe the working principles of fNIR and how the hemodynamic signals are extracted from the raw fNIR measurements using the modified Beer-Lambert Law. We will also introduce the fNIR system that we have developed and used in our studies. Current results from the augmented cognition research conducted in our laboratory are also presented, and the merits of optical imaging in augmented cognition are summarized. Working Principles Typically, an optical apparatus consists of a light source by which the tissue is radiated and a light detector that receives light after it has interacted with the tissue. Photons that enter tissue undergo two different types of interaction, namely absorption (loss of energy to the medium) and scattering [4], [5], [19]. Most biological tissues are relatively transparent to light in the near-infrared range between 700 to 900 nm, which is usually called the “optical window.” This is mainly due to the fact that within this optical window, the absorbance of the main constituents in the human tissue (i.e., water, oxy-Hb, and deoxy-Hb) is small, allowing the light to penetrate the tissue (see Figure 1). Among the main absorbers (chromophores) in the tissue, oxyand deoxy-Hb are strongly linked to tissue oxygenation and metabolism. Fortunately, in the optical window, the absorption spectra of oxyand deoxy-Hb remain significantly different than each other, allowing spectroscopic separation of these compounds to be possible using only a few sample wavelengths. fNIR technology employs specified wavelengths of light within the optical window. Once the photons are introduced into the human head, they are either scattered by extraand intracellular boundaries of different layers of the head (skin, skull, cerebrospinal fluid, brain, etc.) or absorbed mainly by oxyand deoxy-Hb. A photodetector placed a certain distance away from the light source can collect the photons that are not absorbed and those that traveled along the “banana shaped path” between the source and detector due to scattering [9], [29] as shown Figure 2. In functional optical brain imaging studies, the attenuation (reduction in the amount of photons detected by the photodetectors) due to scattering is assumed to be constant since the amount of scatterers within different layers of the head does not change due to cognitive activity. The change in the attenuation measured as a result of cognitive activity is hence due to the changes in absorption resulting from the variation in the concentrations of oxyand deoxy-Hb in the brain tissue. This relationship is not surprising, since cerebral hemodynamic changes are related to functional brain activity through a mechanism that is called neurovascular coupling [8], [30]. In fact, this physiological relationship and the ability of fNIR Functional Brain Imaging Using Near-Infrared Technology

Highly Sensitive Detection of HER2 Extracellular Domain in the Serum of Breast Cancer Patients by Piezoelectric Microcantilevers

Functional near-infrared spectroscopy (fNIR) measures changes in the relative levels of oxygenated and deoxygenated hemoglobin and has increasingly been used to assess neural functioning in the brain. In addition to the ongoing technological developments, investigators have also been conducting studies on functional mapping and refinement of data analytic strategies in order to better understand the relationship between the fNIR signal and brain activity. However, since fNIR is a relatively new functional brain imaging modality as compared to positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), it still lacks brain-mapping tools designed to allow researchers and clinicians to easily interact with their data. The aim of this study is to develop a registration technique for the fNIR measurements using anatomical landmarks and structural magnetic resonance imaging (MRI) templates in order to visualize the brain activation when and where it happens. The proposed registration technique utilizes chain-code algorithm and depicts activations over respective locations based on sensor geometry. Furthermore, registered data locations have been used to create spatiotemporal visualization of fNIR measurements

THE EVOLUTION OF FIELD DEPLOYABLE fNIR SPECTROSCOPY FROM BENCH TO CLINICAL SETTINGS

Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection; however, their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/mL). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection.

Correlation of near infrared absorption and diffuse reflectance spectroscopy scattering with tissue neovascularization and collagen concentration in a diabetic rat wound healing model

In the late 1980s and early 1990s, Dr. Britton Chance and his colleagues, using picosecond-long laser pulses, spearheaded the development of time-resolved spectroscopy techniques in an effort to obtain quantitative information about the optical characteristics of the tissue. These efforts by Chance and colleagues expedited the translation of near-infrared spectroscopy (NIRS)-based techniques into a neuroimaging modality for various cognitive studies. Beginning in the early 2000s, Dr. Britton Chance guided and steered the collaboration with the Optical Brain Imaging team at Drexel University toward the development and application of a field deployable continuous wave functional near-infrared spectroscopy (fNIR) system as a means to monitor cognitive functions, particularly during attention and working memory tasks as well as for complex tasks such as war games and air traffic control scenarios performed by healthy volunteers under operational conditions. Further, these collaborative efforts led to various clinical applications, including traumatic brain injury, depth of anesthesia monitoring, pediatric pain assessment, and brain–computer interface in neurology. In this paper, we introduce how these collaborative studies have made fNIR an excellent candidate for specified clinical and research applications, including repeated cortical neuroimaging, bedside or home monitoring, the elicitation of a positive effect, and protocols requiring ecological validity. This paper represents a token of our gratitude to Dr. Britton Chance for his influence and leadership. Through this manuscript we show our appreciation by contributing to his commemoration and through our work we will strive to advance the field of optical brain imaging and promote his legacy.

Optical properties of wounds: diabetic versus healthy tissue

The objective of this paper was to correlate optical changes of tissue during wound healing measured by near infrared (NIR) and diffuse reflectance spectroscopy (DRS) with histologic changes in an animal model. Amplitude and phase of scattered light were obtained in a diabetic rat and control model and biopsies were taken for blood vessel ingrowth and collagen concentration. NIR absorption coefficient correlated with blood vessel ingrowth over time, in both the control and diabetic animals. DRS data correlated with collagen concentration. Previous publications by this group documented only the NIR changes during the wound healing process but this is the first reported correlation with histology data. The ability to correlate DRS scattering with collagen concentration during healing is another important and novel finding. This technology may play an important role clinically in assessing the efficacy of wound healing agents in diabetics.

Noninvasive assessment of diabetic foot ulcers with diffuse photon density wave methodology: pilot human study

Diffuse photon density wave (DPDW) methodology at Near Infrared frequencies has been used to calculate absorption and scattering from wounds of healthy and diabetic rats. The diffusion equation for semi-infinite media is being used for calculating the absorption and scattering coefficients based on measurements of phase and amplitude with a frequency domain device. Differences observed during the course of healing in the two populations can be correlated to the delayed healing observed in diabetics. These results are encouraging and further work will focus on the implementation of this device to the clinical setting as a monitoring tool in chronic diabetic wounds.

Prediction of wound healing in human diabetic foot ulcers by diffuse near‐infrared spectroscopy: A pilot study

A pilot human study is conducted to evaluate the potential of using diffuse photon density wave (DPDW) methodology at near-infrared (NIR) wavelengths (685 to 830 nm) to monitor changes in tissue hemoglobin concentration in diabetic foot ulcers. Hemoglobin concentration is measured by DPDW in 12 human wounds for a period ranging from 10 to 61 weeks. In all wounds that healed completely, gradual decreases in optical absorption coefficient, oxygenated hemoglobin concentration, and total hemoglobin concentration are observed between the first and last measurements. In nonhealing wounds, the rates of change of these properties are nearly zero or slightly positive, and a statistically significant difference (p<0.05) is observed in the rates of change between healing and nonhealing wounds. Differences in the variability of DPDW measurements over time are observed between healing and nonhealing wounds, and this variance may also be a useful indicator of nonhealing wounds. Our results demonstrate that DPDW methodology with a frequency domain NIR device can differentiate healing from nonhealing diabetic foot ulcers, and indicate that it may have clinical utility in the evaluation of wound healing potential.