Due to intravascular multiple sequential scattering, Diffuse Correlation Spectroscopy of tissue primarily measures relative red blood cell motion within vessels.

We suggest that Diffuse Correlation Spectroscopy (DCS) measurements of tissue blood flow primarily probe relative red blood cell (RBC) motion, due to the occurrence of multiple sequential scattering events within blood vessels. The magnitude of RBC shear-induced diffusion is known to correlate with flow velocity, explaining previous reports of linear scaling of the DCS "blood flow index" with tissue perfusion despite the observed diffusion-like auto-correlation decay. Further, by modeling RBC mean square displacement using a formulation that captures the transition from ballistic to diffusive motion, we improve the fit to experimental data and recover effective diffusion coefficients and velocity de-correlation time scales in the range expected from previous blood rheology studies.

Laser speckle imaging in the spatial frequency domain.

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects.

Multiphysics neuron model for cellular volume dynamics.

Even though cellular volume dynamics has been linked to cell apoptosis and intrinsic optical signals, there is no quantitative model for describing neuronal volume dynamics on the millisecond time scale. This study introduces a multiphysics neuron model, where the cell volume is a time-varying variable and multiple physical principles are combined to build governing equations. Using this model, we analyzed neuronal volume responses during excitation, which elucidated the variety of optical signals observed experimentally across the literature.

Cerebral blood oxygenation measurement based on oxygen-dependent quenching of phosphorescence.

Monitoring of the spatiotemporal characteristics of cerebral blood and tissue oxygenation is crucial for better understanding of the neuro-metabolic-vascular relationship. Development of new pO2 measurement modalities with simultaneous monitoring of pO2 in larger fields of view with higher spatial and/or temporal resolution will enable greater insight into the functioning of the normal brain and will also have significant impact on diagnosis and treatment of neurovascular diseases such as stroke, Alzheimer's disease, and head injury. Optical imaging modalities have shown a great potential to provide high spatiotemporal resolution and quantitative imaging of pO2 based on hemoglobin absorption in visible and near infrared range of optical spectrum.

Assessment of the frequency-domain multi-distance method to evaluate the brain optical properties: Monte Carlo simulations from neonate to adult.

The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult.

Improved recovery of the hemodynamic response in diffuse optical imaging using short optode separations and state-space modeling.

Diffuse optical imaging (DOI) allows the recovery of the hemodynamic response associated with evoked brain activity. The signal is contaminated with systemic physiological interference which occurs in the superficial layers of the head as well as in the brain tissue. The back-reflection geometry of the measurement makes the DOI signal strongly contaminated by systemic interference occurring in the superficial layers.

Optical coherence tomography for the quantitative study of cerebrovascular physiology.

Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously.

Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain.

Absorption or fluorescence-based two-dimensional (2-D) optical imaging is widely employed in functional brain imaging. The image is a weighted sum of the real signal from the tissue at different depths. This weighting function is defined as "depth sensitivity.

Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring.

Cerebral blood flow (CBF) during stepped hypercapnia was measured simultaneously in the rat brain using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeling MRI (ASL). DCS and ASL CBF values agree very well, with high correlation (R=0.86, p< 10(-9)), even when physiological instability perturbed the vascular response.

Resting state functional connectivity of the whole head with near-infrared spectroscopy.

Resting state connectivity aims to identify spontaneous cerebral hemodynamic fluctuations that reflect neuronal activity at rest. In this study, we investigated the spatial-temporal correlation of hemoglobin concentration signals over the whole head during the resting state. By choosing a source-detector pair as a seed, we calculated the correlation value between its time course and the time course of all other source-detector combinations, and projected them onto a topographic map.

Compositional-prior-guided image reconstruction algorithm for multi-modality imaging.

The development of effective multi-modality imaging methods typically requires an efficient information fusion model, particularly when combining structural images with a complementary imaging modality that provides functional information. We propose a composition-based image segmentation method for X-ray digital breast tomosynthesis (DBT) and a structural-prior-guided image reconstruction for a combined DBT and diffuse optical tomography (DOT) breast imaging system. Using the 3D DBT images from 31 clinically measured healthy breasts, we create an empirical relationship between the X-ray intensities for adipose and fibroglandular tissue.

Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation.

Measuring cerebral oxygen delivery and metabolism microscopically is important for interpreting macroscopic functional magnetic resonance imaging (fMRI) data and identifying pathological changes associated with stroke, Alzheimer's disease, and brain injury. Here, we present simultaneous, microscopic measurements of cerebral blood flow (CBF) and oxygen partial pressure (pO(2)) in cortical microvessels of anesthetized rats under baseline conditions and during somatosensory stimulation. Using a custom-built imaging system, we measured CBF with Fourier-domain optical coherence tomography (OCT), and vascular pO(2) with confocal phosphorescence lifetime microscopy.

Study of neurovascular coupling by modulating neuronal activity with GABA.

Fundamental to the interpretation of neurovascular coupling is determining the neuronal activity that accounts for functional hyperemia. Recently, synaptic and not spiking activity has been found to be responsible for the hemodynamic response. Using pharmacological manipulation in rats, we want to further determine whether the cortical synaptic activity generated by the thalamic input or the subsequent synaptic activity related to secondary cortical processing is driving the hemodynamic response.

Combined optical and X-ray tomosynthesis breast imaging.

Purpose: To explore the optical and physiologic properties of normal and lesion-bearing breasts by using a combined optical and digital breast tomosynthesis (DBT) imaging system.

Materials And Methods: Institutional review board approval and patient informed consent were obtained for this HIPAA-compliant study. Combined optical and tomosynthesis imaging analysis was performed in 189 breasts from 125 subjects (mean age, 56 years ± 13 [standard deviation]), including 138 breasts with negative findings and 51 breasts with lesions.

Spontaneous low-frequency oscillations in cerebral vessels: applications in carotid artery disease and ischemic stroke.

The etiology behind and physiological significance of spontaneous oscillations in the low-frequency spectrum in both systemic and cerebral vessels remain unknown. Experimental studies have proposed that spontaneous oscillations in cerebral blood flow reflect impaired cerebral autoregulation (CA). Analysis of CA by measurement of spontaneous oscillations in the low-frequency spectrum in cerebral vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease (CAD) and stroke.

Lifetime-based tomographic multiplexing.

Near-infrared (NIR) fluorescence tomography of multiple fluorophores has previously been limited by the bandwidth of the NIR spectral regime and the broad emission spectra of most NIR fluorophores. We describe in vivo tomography of three spectrally overlapping fluorophores using fluorescence lifetime-based separation. Time-domain images are acquired using a voltage-gated, intensified charge-coupled device (CCD) in free-space transmission geometry with 750 nm Ti:sapphire laser excitation.

Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal.

Changes in neuronal activity are accompanied by the release of vasoactive mediators that cause microscopic dilation and constriction of the cerebral microvasculature and are manifested in macroscopic blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals. We used two-photon microscopy to measure the diameters of single arterioles and capillaries at different depths within the rat primary somatosensory cortex. These measurements were compared with cortical depth-resolved fMRI signal changes.

Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.

Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes.

Examining the phonological neighborhood density effect using near infrared spectroscopy.

Phonological density refers to the number of words that can be generated by replacing a phoneme in a target word with another phoneme in the same position. Although the precise nature of the phonological neighborhood density effect is not firmly established, many behavioral psycholinguistic studies have shown that visual recognition of individual words is influenced by the number and type of neighbors the words have. This study explored neurobehavioral correlates of phonological neighborhood density in skilled readers of English using near infrared spectroscopy.

Rapid volumetric angiography of cortical microvasculature with optical coherence tomography.

We describe methods and algorithms for rapid volumetric imaging of cortical vasculature with optical coherence tomography (OCT). By optimizing system design, scanning protocols, and algorithms for visualization of capillary flow, comprehensive imaging of the surface pial vasculature and capillary bed is performed in approximately 12 s. By imaging during hypercapnia and comparing with simultaneous CCD imaging, the sources of contrast of OCT angiography are investigated.

Dissociation of processing of featural and spatiotemporal information in the infant cortex.

A great deal is known about the development of visual object processing capacities and the neural structures that mediate these capacities in the mature observer. In contrast, little is known about the neural structures that mediate these capacities in the infant or how these structures eventually give rise to mature processing. The present research used near-infrared spectroscopy to investigate neural activation in visual, temporal, and parietal cortex during object processing tasks.

Near-infrared spectroscopy shows right parietal specialization for number in pre-verbal infants.

Bilateral regions of the intraparietal sulcus (IPS) appear to be functionally selective for both rudimentary non-symbolic number tasks and higher-level symbolic number tasks in adults and older children. Furthermore, the ability to mentally represent and manipulate approximate non-symbolic numerical quantities is present from birth. These factors leave open whether the specialization of the IPS develops through the experience of learning a symbolic number system or if it is already specialized before symbolic number acquisition.

Immunohistochemical detection of Ki-67 is not associated with tumor-infiltrating macrophages and cyclooxygenase-2 in oral squamous cell carcinoma.

Background: An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki-67, tumor-associated macrophages (TAMs), and COX-2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors.

The effect of different anesthetics on neurovascular coupling.

To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol.

Laser speckle contrast imaging in biomedical optics.

First introduced in the 1980s, laser speckle contrast imaging is a powerful tool for full-field imaging of blood flow. Recently laser speckle contrast imaging has gained increased attention, in part due to its rapid adoption for blood flow studies in the brain. We review the underlying physics of speckle contrast imaging and discuss recent developments to improve the quantitative accuracy of blood flow measures.