Two-photon phosphorescence lifetime microscopy has been a key tool for studying cerebral oxygenation in mice. However, the accuracy of the partial pressure of oxygen (pO2) measurements is affected by out-of-focus signal. In this work, we applied reconfigurable differential aberration imaging to characterize and correct for out-of-focus signal contamination in intravascular pO2 imaging. Our results show that signal contamination is higher in more oxygenated vessels and that it could be effectively removed using the proposed method.

Functional near-infrared spectroscopy (fNIRS) technology has been steadily advancing since the first measurements of human brain activity over 30 years ago. Initially, efforts were focused on increasing the channel count of fNIRS systems and then to moving from sparse to high density arrays of sources and detectors, enhancing spatial resolution through overlapping measurements. Over the last ten years, there have been rapid developments in wearable fNIRS systems that place the light sources and detectors on the head as opposed to the original approach of using fiber optics to deliver the light between the hardware and the head. The miniaturization of the electronics and increased computational power continues to permit impressive advances in wearable fNIRS systems. Here we detail our design for a wearable fNIRS system that covers the whole head of an adult human with a high-density array of 56 sources and up to 192 detectors. We provide characterization of the system showing that its performance is among the best in published systems. Additionally, we provide demonstrative images of brain activation during a ball squeezing task. We have released the hardware design to the public, with the hope that the community will build upon our foundational work and drive further advancements.

Significance: Functional near-infrared spectroscopy (fNIRS) is a popular neuroimaging technique with proliferating hardware platforms, analysis approaches, and software tools. There has not been a standardized file format for storing fNIRS data, which has hindered the sharing of data as well as the adoption and development of software tools. Aim: We endeavored to design a file format to facilitate the analysis and sharing of fNIRS data that is flexible enough to meet the community's needs and sufficiently defined to be implemented consistently across various hardware and software platforms. Approach: The shared NIRS format (SNIRF) specification was developed in consultation with the academic and commercial fNIRS community and the Society for functional Near Infrared Spectroscopy. Results: The SNIRF specification defines a format for fNIRS data acquired using continuous wave, frequency domain, time domain, and diffuse correlation spectroscopy devices. Conclusions: We present the SNIRF along with validation software and example datasets. Support for reading and writing SNIRF data has been implemented by major hardware and software platforms, and the format has found widespread use in the fNIRS community. (c) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

We report the implementation and demonstration of an imaging system that combines two-photon phosphorescence lifetime microscopy (2PLM) and adaptive optics for improving oxygen partial pressure (pO2) measurement accuracy in deep cortical layers of mice. The technique retrieves the background signal by forming an aberrated torus focus on the sample plane with an optical phase mask imposed on the system wavefront and subtracts it from normal phosphorescence emission signal. The proposed method is validated with intravascular pO2 measurements from six mice imaged at up to ~600 μm depth.

Intracranial pressure (ICP) monitoring has a key role in the management of neurosurgical and neurological injuries. Currently, the standard clinical monitoring of ICP requires an invasive transducer into the parenchymal tissue or the brain ventricle, with possibility of complications such as hemorrhage and infection. A non-invasive method for measuring ICP, would be highly preferable, as it would allow clinicians to promptly monitor ICP during transport and allow for monitoring in a larger number of patients. We have introduced diffuse correlation spectroscopy (DCS) as a non-invasive ICP monitor by fast measurement of pulsatile cerebral blood flow (CBF). The method is similar to Transcranial Doppler ultrasound (TCD), which derives ICP from the amplitude of the pulsatile cerebral blood flow velocity, with respect to the amplitude of the pulsatile arterial blood pressure. We believe DCS measurement is superior indicator of ICP than TCD estimation because DCS directly measures blood flow, not blood flow velocity, and the small cortical vessels measured by DCS are more susceptible to transmural pressure changes than the large vessels. For fast DCS measurements to recover pulsatile CBF we have developed a custom high-power long-coherent laser and a strategy for delivering it to the tissue within ANSI standards. We have also developed a custom FPGA-based correlator board, which facilitates DCS data acquisitions at 50-100 Hz. We have tested the feasibility of measuring pulsatile CBF and deriving ICP in two challenging scenarios: humans and rats. SNR is low in human adults due to large optode distances. It is similarly low in rats because the fast heart rate in this setting requires a high repetition rate.

Polarization sensitive optical coherence tomography (PSOCT) with serial sectioning has enabled the investigation of 3D structures in mouse and human brain tissue samples. By using intrinsic optical properties of back-scattering and birefringence, PSOCT reliably images cytoarchitecture, myeloarchitecture and fiber orientations. In this study, we developed a fully automatic serial sectioning polarization sensitive optical coherence tomography (as-PSOCT) system to enable volumetric reconstruction of human brain samples with unprecedented sample size and resolution. The 3.5 μm in-plane resolution and 50 μm through-plane voxel size allow inspection of cortical layers that are a single-cell in width, as well as small crossing fibers. We show the abilities of as-PSOCT in quantifying layer thicknesses of the cerebellar cortex and creating microscopic tractography of intricate fiber networks in the subcortical nuclei and internal capsule regions, all based on volumetric reconstructions. as-PSOCT provides a viable tool for studying quantitative cytoarchitecture and myeloarchitecture and mapping connectivity with microscopic resolution in the human brain.

Optical coherence tomography (OCT) and optical coherence microscopy (OCM) have demonstrated the ability to investigate cyto- and myelo-architecture in the brain. Polarization-sensitive OCT provides sensitivity to additional contrast mechanisms, specifically the birefringence of myelination and, therefore, is advantageous for investigating white matter fiber tracts. In this Letter, we developed a polarization-sensitive optical coherence microscope (PS-OCM) with a 3.5 mu m axial and 1.3 mu m transverse resolution to investigate fiber organization and orientation at a finer scale than previously demonstrated with PS-OCT. In a reconstructed mouse brain section, we showed that at the focal depths of 20-70 mu m, the PS-OCM reliably identifies the neuronal fibers and quantifies the in-plane orientation. (C) 2016 Optical Society of America

Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies. AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies.

The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy- and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensory cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO2 estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/consumption ratio to values closer to adult values reported in the literature. We are the first to report changes in local rCBF and rCMRO2 during functional activation in preterm infants. The ability to measure these variables in addition to hemoglobin concentration changes is critical for understanding neurovascular coupling in the developing brain, and for using this coupling as a reliable functional imaging marker in neonates.

Frequency domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) use near-infrared light to quantify static and dynamic properties of brain tissue. We present a novel FDNIRS-DCS system and characterize its performance.

Near-infrared spectroscopy (NIRS) estimations of the adult brain baseline optical properties based on a homogeneous model of the head are known to introduce significant contamination from extracerebral layers. More complex models have been proposed and occasionally applied to in vivo data, but their performances have never been characterized on realistic head structures. Here we implement a flexible fitting routine of time-domain NIRS data using graphics processing unit based Monte Carlo simulations. We compare the results for two different geometries: a two-layer slab with variable thickness of the first layer and a template atlas head registered to the subject's head surface. We characterize the performance of the Monte Carlo approaches for fitting the optical properties from simulated time-resolved data of the adult head. We show that both geometries provide better results than the commonly used homogeneous model, and we quantify the improvement in terms of accuracy, linearity, and cross-talk from extracerebral layers.

Time-domain near-infrared spectroscopy (TD-NIRS) offers the ability to measure the absolute baseline optical properties of a tissue. Specifically, for brain imaging, the robust assessment of cerebral blood volume and oxygenation based on measurement of cerebral hemoglobin concentrations is essential for reliable cross-sectional and longitudinal studies. In adult heads, these baseline measurements are complicated by the presence of thick extra-cerebral tissue (scalp, skull, CSF). A simple semi-infinite homogeneous model of the head has proven to have limited use because of the large errors it introduces in the recovered brain absorption. Analytical solutions for layered media have shown improved performance on Monte-Carlo simulated data and layered phantom experiments, but their validity on real adult head data has never been demonstrated. With the advance of fast Monte Carlo approaches based on GPU computation, numerical methods to solve the radiative transfer equation become viable alternatives to analytical solutions of the diffusion equation. Monte Carlo approaches provide the additional advantage to be adaptable to any geometry, in particular more realistic head models. The goals of the present study were twofold: (1) to implement a fast and flexible Monte Carlo-based fitting routine to retrieve the brain optical properties; (2) to characterize the performances of this fitting method on realistic adult head data. We generated time-resolved data at various locations over the head, and fitted them with different models of light propagation: the homogeneous analytical model, and Monte Carlo simulations for three head models: a two-layer slab, the true subject's anatomy, and that of a generic atlas head. We found that the homogeneous model introduced a median 20 to 25% error on the recovered brain absorption, with large variations over the range of true optical properties. The two-layer slab model only improved moderately the results over the homogeneous one. On the other hand, using a generic atlas head registered to the subject's head surface decreased the error by a factor of 2. When the information is available, using the true subject anatomy offers the best performance.

We describe the validation of an anatomical brain atlas approach to the analysis of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare the diffuse optical images of simulated cortical activation reconstructed using a registered atlas with those obtained using a subject's true anatomy. The error in localization of the simulated cortical activations when using a registered atlas is due to a combination of imperfect registration, anatomical differences between atlas and subject anatomies and the localization error associated with diffuse optical image reconstruction. When using a subject-specific MRI, any localization error is due to diffuse optical image reconstruction only. In this study we determine that using a registered anatomical brain atlas results in an average localization error of approximately 18mm in Euclidean space. The corresponding error when the subject's own MRI is employed is 9.1mm. In general, the cost of using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling of the localization error. Our results show that despite this increase in error, reasonable anatomical localization is achievable even in cases where the subject-specific anatomy is unavailable.

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. Caffini, A. Torricelli, R. Cubeddu, A. Custo, J. Dubb, and D. A. Boas, "Validating an anatomical brain atlas for analyzing NIRS measurements of brain activation," in Biomedical Optics and 3-D Imaging, OSA Technical Digest (CD) (Optica Publishing Group, 2010), paper JMA87. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article