Time domain functional NIRS imaging for human brain mapping

AbstractThis review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community

In-vivo multilaboratory investigation of the optical properties of the human head

The in-vivo optical properties of the human head are investigated in the 600–1100 nm range on different subjects using continuous wave and time domain diffuse optical spectroscopy. The work was performed in collaboration with different research groups and the different techniques were applied to the same subject. Data analysis was carried out using homogeneous and layered models and final results were also confirmed by Monte Carlo simulations. The depth sensitivity of each technique was investigated and related to the probed region of the cerebral tissue. This work, based on different validated instruments, is a contribution to fill the existing gap between the present knowledge and the actual in-vivo values of the head optical properties

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

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. For each age, we determined the optimal set of source-detector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8–24% in neonates and infants, while the error increased to 19–44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions. Keywords: DCS; NIRS; diffuse optics; functional neuroscience; optical imaging; optical spectroscop

Optical dosimetry tools and Monte Carlo based methods for applications in image guided optical therapy in the brain

Purpose: The long-term goal of this research is to determine the feasibility of using near infra-red light to stimulate drug release in metastatic lesions within the brain. In this work, we focused on developing the tools needed to quantify and verify photon fluence distribution in biological tissue. To accomplish this task, an optical dosimetry probe and Monte Carlo based simulation code were fabricated, calibrated and developed to predict light transport in heterogeneous tissue phantoms of the skull and brain. Empirical model (EM) of photon transport using CT images as input were devised to provide real-time calculations capable of being translated to preclinical and clinical applications. Methods and Materials: A GPU based 3D Monte Carlo code was customized to simulate the photon transport within head phantoms consisting of skull bone, white and gray matter with differing laser beam properties, including flat, Gaussian, and super-Gaussian profiles that are converging, parallel, or diverging. From these simulations, the local photon fluence and tissue dosimetric distribution was simulated and validated through the implementation of a novel titanium-based optical dosimetry probe with an isotropic acceptance and 1.5mm diameter. Empirical models (EM) of photon transport were devised and calibrated to MC simulated data to provide 3D fluence and optical dosimetric maps in real-time developed around on a voxel-based convolution technique. Optical transmission studies were performed using human skull bone samples to determine the optical transmission characteristics of heterogeneous bone structures and the effectiveness of the Monte Carlo in simulating this heterogeneity. These tools provide the capability to develop and optimize treatment plans for optimal release of pharmaceuticals to metastatic breast cancer in the brain. Results: At the time of these experiments, the voxel-based CUDA MC code implemented and further developed in this study had not been validated by measurement. A novel optical dosimetry probe was fabricated and calibrated to measure the absolute photon fluence (mW/mm2) in phantoms resembling white matter, gray matter and skull bone and compared to 3D Monte Carlo simulated data. The TiO2-based dosimetry probe was shown to have superior linearity and isotropicity of response to previous Nylon based probes, and was better suited to validate the Monte Carlo using localized 3D measurement (\u3c 25% systematic error for white matter, gray matter and skull bone phantoms along illumination beam axis up to a depth of 2cm in homogeneous tissue and 3.8cm in heterogeneous head phantom). Next, the transport parameters of the empirical algorithm was calibrated using the 3D Monte Carlo and EMs and validated by optical dosimetry probe measurements (with error of 10.1% for White Matter, 45.1% for Gray Matter and 22.1% for Skull Bone phantoms) along illumination beam axis. Conclusions: The design and validation of the Monte Carlo, the optical dosimetry probe and the Empirical algorithm increases the clinical feasibility of optical therapeutic planning to narrow down the complex possibilities of illumination conditions, further compounded by the heterogeneous structure of the brain, such as varying skull thicknesses and densities. Our ultimate goal is to design a fast Monte Carlo based optical therapeutic protocol to treat brain metastasis. The voxelated nature of the MC and EM provides the necessary 3D photon distribution to within 25% error to guide future clinical studies involving optically triggered drug release

Functional Near Infrared Spectroscopy and Diffuse Optical Tomography in Neuroscience

Diseases & disorder

Wavelength Tuneable Frequency Domain Photon Migration Spectrometer for Tissue-like Media

Frequency domain spectrometers use intensity modulated light to quantitatively interrogate turbid media. The modulation frequencies employed are in the radiofrequency range. Intensity modulated light launched into a turbid medium generates photon density fluctuations with wave like character that oscillates at the modulation frequency. These density fluctuations are named diffuse photon density waves, and it has been shown that the amplitude and phase of the photon density wave inside the medium depends on its optical properties. Hence by measuring the amplitude and phase of the photon density wave the optical properties of the medium can be estimated. This is the basic working principle of a frequency domain photon migration spectrometer. Frequency domain spectrometers fabricated with laser diodes are limited to discrete wavelengths thereby making compromises on the information about the media under test. In this research a wavelength tuneable frequency domain spectrometer was constructed by modulating the output intensity of a titanium: sapphire laser using an acousto-optic modulator. A low noise avalanche photodiode module in conjunction with a lock-in amplifier was used to measure the amplitude attenuation and phase lag inside a turbid sample. The frequency domain spectrometer was tested for accuracy and precision by estimating the optical properties of an important tissue simulation phantom, Intralipid , at a representative wavelength 790 nm. The results indicated that the spectrometer estimates absorption with an accuracy of 10%. The instrument estimates the absorption and reduced scattering coefficients with a precision of 3% and 6%, respectively. Optical properties of Intralipid were measured from 710-850 nm in the therapeutic window. The results were compared with published data measured by other methods and similar frequency domain techniques. The absorption coefficient agrees within 10% with results from a time domain measurement. The reduced scattering coefficient was within the error limits of other reported measurements. At 750 nm the reduced scattering agrees within 5% with the results from a continuous wave, time domain and within 1% from another frequency domain measurement, and at 811 and 849 nm this agreement is within 9%. A Mie theory prediction of the reduced scattering coefficient based on a measurement of the particle size distribution by a Mastersizer 2000 is larger than the frequency domain results by 6%. The spectrometer was used to determine the optical temperature coefficient of Intralipid , exploring its potential as a non invasive temperature monitoring device. The measured minute change in the absorption coefficient suggests a minimum observable temperature change of 4'C, which for most practical applications means that the precision needs to improve. The effect of glucose on the optical properties of Intralipid indicates that the absorption coefficient decreases steadily at 730 nm up to 1000mg/dL. The reduced scattering coefficient decreases with increasing glucose concentration at most of the wavelengths. This work quantified the absorption and reduced scattering of Intralipid over a larger wavelength range (in the therapeutic window) than before. This is the first time the effects of temperature on the optical properties of a turbid medium monitored with a frequency domain spectrometer. Specific information about the precision and accuracy which can be achieved with the current technology is documented. Current precision is not sufficient for many applications that would benefit from separation of absorption and scattering