Functional and Structural Optical Brain Imaging

脑结构和功能成像可以帮助阐明创伤性脑损伤（TBI）和自闭症谱系障碍（ASD）的不同生物学/临床表现，其想法是定位脑区域，用于结构和功能障碍的分类，并最终用于治疗干预。虽然功能性磁共振成像（fMRI）和正电子发射断层扫描（PET）是最适合大多数功能性脑研究的成像方式，但它们有一些固有的局限性，特别是在低功能TBI或ASD受试者的情况下。fMRI数据采集的困难主要是由于测量系统对ASD和ADHD儿童的环境不友好，因为他们对运动限制非常敏感。在这方面，对患者友好的近红外光谱可以成为首选的成像方式。近红外光谱（NIRS），特别是功能性近红外光谱（fNIRS）是一种新兴的无创测量技术，用于测量与大脑活动相关的脑血流动力学水平的局部变化。由于生物组织在近红外波长（=700-1000纳米）的低光吸收，近红外光可以穿透足够深的地方，探测到2-3厘米深的大脑外层（即皮层）。组织的近红外吸收光谱对主要组织发色团（如血红蛋白）浓度的变化很敏感。因此，测量背向散射光的时间变化可以捕捉到最外层皮层的功能诱发变化，因此，可以用来评估大脑功能。与其他成熟的脑成像方式（如fMRI和PET）相比，该技术具有独特的功能，包括几毫秒的更高时间分辨率，以及血红蛋白氧- hbo和脱氧-Hb组分的时间变化的光谱信息，而fMRI只能评估脱氧血红蛋白（Hb）的变化。对于儿科应用最重要的是，与fMRI或PET相比，NIRS仪器更小，限制更少，并且可以在更大程度上容忍受试者运动。这些特点使得这项技术适用于研究有ASD和TBI等问题的儿童，因为让受试者长时间保持静止是极具挑战性的。

Imaging of the brain structure and function can help to elucidate different biological/clinical manifestations of Traumatic Brain Injury (TBI) and Autistic Spectrum Disorder (ASD) The idea is to localize brain areas for classification of structural and functional disorders and, ultimately, for therapeutic intervention. While functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are the best suited imaging modalities for the most of the functional brain studies, they have some inherent limitations, particularly in the case of low-functioning TBI or ASD subjects. Difficulties in fMRI data acquisition are mainly due to the non-friendly environment of the measurement system for the children with ASD and ADHD, because they are very sensitive to restrictions on movement. In this regard, patient-friendly NIRS can become an imaging modality of choice. NIRS and, in particular, functional near infrared spectroscopy (fNIRS) is an emerging technology for noninvasive measurements of the local changes in cerebral hemodynamic levels associated with brain activity. Due to the low optical absorption of biological tissues at NIR wavelengths (=700-1000 nm), NIR light can penetrate deep enough to probe the outer layers of brain (i.e., cortex) up to 2-3 cm deep. The NIR absorption spectrum of the tissue is sensitive to changes in the concentration of major tissue chromophores, such as hemoglobin species. Therefore, measurements of temporal variations of backscattered light can capture functionally evoked changes in the outermost cortex, and, thus, can be used to assess the brain functioning. Compared to other well-established brain imaging modalities, such as fMRI and PET, this technique offers unique features, including higher temporal resolution of several milliseconds, and spectroscopic information about temporal variations of both components of hemoglobin Oxy-HbO and deOxy-Hb, while fMRI can assess only deoxy-hemoglobin (Hb) changes. Most importantly for pediatric applications, NIRS instruments are much smaller, less restraining compared to fMRI or PET and can tolerate subject motion to a larger extent that fMRI. These features make the technique appropriate to study children with such problems as ASD as well as TBI patients, when keeping the subjects still for long periods of time is extremely challenging. Due to neuro-vascular coupling local changes in oxyhemoglobin and deoxyhemoglobin levels can serve as an indirect measure of brain activity. At first approximation, these levels are proportional to the intensity of the brain activity. We have used an action complexity judgment task with a varying degree of cognitive load to produce brain activation. Twenty healthy participants were asked to evaluate the complexity of previously normed daily life action (number of steps to achieve the task) and classify the number of steps as few or many. We used the linear relationship between changes in the oxy/deoxyhemoglobin change and activity complexity to map the activation on the cortex. The mapping was possible with a special registration between MRI anatomical image and the optical sensor. The parametric effect of complexity showed activation in the frontopolar cortex. In our experiments we have found that on average the activation area corresponded to an angle of =95 and =10. Though the localization of the activation may be less precise with fNIRS than fMRI (according to fMRI data, this activation area was located at an angle =93 and =11), the parametric analysis, linking cognitive load to cerebrovascular reactivity may reveal physiological data of greater clinical importance than just the location of the activated area. Our preliminary results, obtained for 2 TBI patients, show that such parametric studies, based on fNIRS, have the potential to become a discriminator of cognitive function in TBI patients. To probe changes in Oxy- and Deoxy-hemoglobin concentrations in the cortex that are caused by brain activity, related to chosen basic tasks, the data are collected at two wavelengths. To assess the brain activation in children of 4-8 years, we have used such tests as standard GO/NO-Go, developed to examine the effects of response inhibition and error processing. The NIRS signal is acquired, while children are performing the GO/NO-GO task. The NIRS sensor, placed on the childs forehead, covered Brodmann areas 9, 10 of the prefrontal cortex (PFC). Initial results of fNIRS assessment of the hemodynamic changes in the cortex indicate that mean activation levels (based on changes in oxy-hemoglobin) obtained from left and right prefrontal cortex during both GO and NO-GO trials are much higher in the case of typical child, compared to that of ASD. This fact indicates the hypo-activation of prefrontal cortex in the ASD group. Studies of resting state and task-based functional connectivity aiming to identify brain regions similar in functional behavior have received increased attention over the past few years. Aside from healthy populations, different patient groups, including patients with ASD, TBI have been the subject of functional connectivity (FC) studies. These studies have identified different connectivity networks in patient groups compared to healthy population. Different imaging modalities have been employed to investigate the brains functional connectivity. We attempt to elucidate features of FC by studying both hemodynamic and neural responses of the brain using different modalities. We recorded hemodynamic activity during the Go/No-Go task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Using the data, we presented a reliable detection of fast optical signal (FOS) concurrently with electroencephalogram (EEG) during a Go/No-Go task. According to NIRS the hemodynamic responses showed higher task-related activation (an increase/decrease in oxygenated/deoxygenated hemoglobin, respectively) in the right versus left hemisphere. We have conducted two studies of FC to identify brain regions that are similar in functional behavior. Our more precise and comprehensive presentation of brain FC was achieved by investigating Electroencephalography (EEG) data. We employed a new approach to trace the dynamic patterns of human brain task-based functional connectivity.The EEG signals of 5 healthy subjects were recorded while they performed an auditory oddball and a visual modified oddball tasks. To capture the dynamic patterns of functional connectivity during the execution of each task, EEG signals are segmented into duration that correspond to the temporal windows of previously well-studied event-related potentials (ERPs). For each task, the proposed approach was able to establish a unique sequence of dynamic pattern (observed in all 5 subjects) for brain functional connectivity. The early diagnostics of brain hematomas is known to be crucial for proper therapy and good prognosis. However, in many cases brain traumas occur in places, where imaging modalities, MRI and CT, are not easily accessible. For this reason, there is an urgent need for some portable tool to provide fast initial assessment of the brain injury. Some simplified NIR devices, based on comparison between region of interest (ROI) and contra-lateral side, may not detect the presence of symmetrical bilateral hematomas. Hematoma detector would be clinically viable, if it can provide proper diagnostics for all types of head hematoma. Motion artifacts present a major challenge for conventional NIR imaging, where random errors in the relative positions of the detectors and ROI contribute to measurement noise. We are in the process of patenting this methodology, and a company has already licensed it. We are in negotiation of a collaborative research agreement to bring the technology from bench to bedside.