Diffuse Optical Imaging (DOI) allows us access to the hemodynamic response in tissue. It has been shown that we can, by detecting the effects of neuro-vascular coupling, relate this to functional events in the brain. Existing technologies in DOI are limited by a number of factors, but most strongly by the absence of viable clinical applications where they may be applied. In this project we are targeting veterans (at the upper end of the pediatric population) with penetrating Traumatic Brain Injury (TBI) and Autistic Spectrum Disorder (ASD) patients. These patients are low-functioning and typically pediatric populations. We have secured a Bench to Bedside grant to fund the latter study and extended the funding for the former study under CNRM at USUS. We have developed novel techniques to assess functional and structural damages in TBI patients, using near infrared imaging methods. On the functional side, we have devised methodologies to study activation in the prefrontal cortex during different cognitive tasks, and develop novel technologies to provide a rapid, handheld field deployable device to detect and image sub and epi dural hematomas. For the structural Imaging a novel device was designed based on new imaging approaches stemming from work conducted in our functional studies. During our functional modeling we were able to identify new methods to handle motion artifact by converting it to signal. By using a novel moving head device we were able to detect the presence of blood-like inclusions in a tissue like phantom. The results of these studies have led to further investigation and we are currently preparing a manuscript on full volumetric imaging of hematoma simulating inclusions in tissue like phantoms. The design of this instrument is based on changing the Near Infra Red imaging paradigm compared to most state-of-the-art diffuse optical imaging, which emphasizes creating stable (or static) sources and detectors. These approaches aim to image small changes in the hemodynamics present in a medium or, in the case of structural imaging, to create an image of the absolute or steady state structure of an object. Given the difficulties of absolute imaging, such as uncertainties in whether non-scattering or anisotropic regions will be detectable or effect images, these approaches are far from being ready to use for the development of a hematoma imaging device. Similarly, a hematoma does not represent a changing medium in the sense of hemodynamic changes over time, as there is no metabolic event causing oxygenation or volume change on a physiological level. It has been shown that some hematomas can be detected by using a contra-lateral difference image. However, in the case of a symmetric bilateral hematoma this method can result in a false negative diagnosis, i.e., missing the trauma. Further, as this approach uses sub-sampling, it can miss potentially localized events, again causing a false negative indication. In this work we present a model, which is based on using a moving optical head imaging system to create the difference signal and detect the hematoma at its boundaries. Additionally, since the device can move over the whole patient head (see the final envisaged design in figure 1);there is no risk of missing hematomas.To test our hypothesis we have developed a specialized holder for a functional brain imaging instrument. An array of fibers from the instrument, mounted on a phantom, enables tracking of the holder. The instrument has also been modified to accept additional input from a motion tracker mounted on the holder to determine the location of the instrument simultaneously with the data collection. The holder has many detector separations to select the correct separation distances and will allow us to characterize, at a later date, the depth sensitivity and specificity of the device with further phantom studies. The functional imaging device being used has been developed at NIH and is designed for the expansion of the functional studies to areas of the brain other than the prefrontal cortex as it has a more adaptable interface. For the functional study 20 Subjects were recruited. Each participant had previous MRI scan and their scan was register with the MNI atlas. Acquired fNIRS data from each channel were compared between the font and complexity. We also looked for the association between stimulus complexity and the magnitude of blood flow increase in the frontopolar cortex. For each experiment, all the channels were co-registered with the MRI anatomical patient image with a stereotactic camera. The group level analysis was made with a random effect model. Each measurement point was projected on the MNI atlas and the oxyhemoglobin and deoxyhemoglobin concentration were reconstructed on this atlas. The results have shown a significant decrease of deoxyhemoglobin and increase of oxyhemoglobin in the frontal polar region. This correlate very well with previous fMRI studies of the same task. Individual responses are investigating in order to create a cognitive response for a healthy population in order to design a metric for further comparison with mild TBI individual response. For this study, 20 healthy participants were recruited. The recruitment has been done under the IRB 07-N-0063, which was amended and approved in 2010. In parallel, two severe TBI patients were tested. Our goal was to revalidate the norm of the Judgment of event task with fNIRS. During the experiment, the participant is seated in front of a computer which displays the stimulus. The optical sensor of the fNIRS is applied on the forehead of the participant. Stimulus display time and optical signals are recorded together. A band pass filter with cutoff frequencies 0.01 and 0.8Hz was applied to the raw fNIRS data before any further processing to remove high frequency instrument level and low frequency drift in HbO and HbR signal. fNIRS time course for each stimulus, in each channel, were temporally marked. Finally, the data, for each channel, were averaged over the 33 presented stimuli for each instruction (font, low complex and high complex). The measurement points were register with the MRI of the patient. And each patient MRI was register on the MNI atlas. Thus, the measurement points were register on the MNI atlas. The registration was done with a stereotactic camera. For each channel, the HRF was integrated over 10s (each stimulus was presented with ten to twelve seconds delay and no deconvolution was need). The integrated data of each patient was normalized with the maximum of the absolute value of the data point. Then, for each patient, we have sixteen measurement point (number channel) register in MNI atlas and the value of each point was normalized between 0 and 1. For group study, we reconstruct the pseudo image of the group data by registering all measurement point location in the MNI atlas and reconstruct our activation in the atlas. In parallel, we also investigate the response of each individual and compare with two severe TBI patients. For each individual, we calculated the angular distance between the target measured in our healthy group and the activation of each individual.

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Anderson, Afrouz A; Smith, Elizabeth; Chowdhry, Fatima A et al. (2017) Prefrontal Hemodynamics in Toddlers at Rest: A Pilot Study of Developmental Variability. Front Neurosci 11:300
Smith, Elizabeth; Anderson, Afrouz; Thurm, Audrey et al. (2017) Prefrontal Activation During Executive Tasks Emerges Over Early Childhood: Evidence From Functional Near Infrared Spectroscopy. Dev Neuropsychol 42:253-264
Karamzadeh, Nader; Amyot, Franck; Kenney, Kimbra et al. (2016) A machine learning approach to identify functional biomarkers in human prefrontal cortex for individuals with traumatic brain injury using functional near-infrared spectroscopy. Brain Behav 6:e00541
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