Simulation study of magnetic resonance imaging-guided cortically constrained diffuse optical tomography of human brain function

Diffuse optical imaging can measure brain activity noninvasively in humans through the scalp and skull by measuring the light intensity modulation arising from localized-activity-induced absorption changes within the cortex. Spatial resolution and localization accuracy are currently limited by measurement geometry to approximately 3 cm in the plane parallel to the scalp. Depth resolution is a more significant challenge owing to the limited angle tomography permitted by reflectance-only measurements. We combine previously established concepts for improving image quality and demonstrate, through simulation studies, their application for improving the image quality of adult human brain function. We show in a three-dimensional human head model that localization accuracy is significantly improved by the addition of measurements that provide overlapping samples of brain tissue. However, the reconstructed absorption contrast is significantly underestimated because its depth is underestimated. We show that the absorption contrast amplitude accuracy can be significantly improved by providing a cortical spatial constraint in the image reconstruction to obtain a better depth localization. The cortical constraint makes physiological sense since the brain-activity-induced absorption changes are occurring in the cortex and not in the scalp, skull, and cerebral spinal fluid. This spatial constraint is provided by segmentation of coregistered structural magnetic resonance imaging (MRI). However, the absorption contrast deep within the cortex is reconstructed superficially, resulting in an underestimation of the absorption contrast. The synthesis of techniques described here indicates that multimodality imaging of brain function with diffuse optical imaging and MRI has the potential to provide more quantitative estimates of the total and deoxyhemoglobin response to brain activation, which is currently not provided by either method independently. However, issues of depth resolution within the cortex remain to be resolved.     

Image correction scheme applied to functional diffuse optical tomography scattering images

We have extended our investigation on the use of a linear algorithm for enhancing the accuracy of diffuse optical tomography (DOT) images, to include spatial maps of the diffusion coefficient. The results show that the corrected images are markedly improved in terms of estimated size, spatial resolution, two-object resolving power, and quantitative accuracy. These image-enhancing effects are significant at expected levels of diffusion-coefficient contrast in tissue and noise levels typical of experimental DOT data. Overall, the types and magnitudes of image-enhancing effects obtained here are qualitatively similar to those seen in previous studies on mu(a) perturbations. The implications for practical implementations of DOT time-series imaging are discussed.     

Liquid-crystal tunable filter spectral imaging for brain tumor demarcation

Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient, real-time surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. We describe the design and characterization of a combined fluorescence and diffuse reflectance imaging system that uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine the linearity, field of view, spatial and spectral resolution, and wavelength sensitivity of the imaging system. Spectral images were acquired from tissue phantoms, mouse brain in vitro, and human cortex in vivo for functional testing of the system. The spectral imaging system produces measured intensities that are linear with sample emission intensity and integration time and possesses a 1 in. (2.54 cm) field of view for a 7 in. (18 cm) object distance. The spectral resolution is linear with wavelength, and the spatial resolution is pixel-limited. The sensitivity spectra for the imaging system provide a guide for the distribution of total image integration time between wavelengths. Functional tests in vitro demonstrate the capability to spectrally discriminate between brain tissues based on exogenous fluorescence contrast or endogenous tissue composition. In vivo imaging captures adequate fluorescence and diffuse reflectance intensities within a clinically viable 2 min imaging time frame and demonstrates the importance of hemostasis to acquired signal strengths and imaging speed.     

Optimal linear inverse solution with multiple priors in diffuse optical tomography

A general framework for incorporating single and multiple priors in diffuse optical tomography is described. We explore the use of this framework for simultaneously utilizing spatial and spectral priors in the context of imaging breast cancer. The utilization of magnetic resonance images of water and lipid content as a statistical spatial prior for the diffuse optical image reconstructions is also discussed. Simulations are performed to demonstrate the significant improvement in image quality afforded by combining spatial and spectral priors.     

Image correction algorithm for functional three-dimensional diffuse optical tomography brain imaging

We outline a computationally efficient image correction algorithm, which we have applied to diffuse optical tomography (DOT) image time series derived from a magnetic resonance imaging (MRI)-based brain model. Results show that the algorithm increases spatial resolution, decreases spatial bias, and only modestly reduces temporal accuracy for noise levels typically seen in experiment, and produces results comparable to image reconstructions that incorporate information from MRI priors. We demonstrate that this algorithm has robust performance in the presence of noise, background heterogeneity, irregular external and internal boundaries, and error in the initial guess. However, the algorithm introduces artifacts when the absorption and scattering coefficients of the reference medium are overestimated--a situation that is easily avoided in practice. The considered algorithm offers a practical approach to improving the quality of images from time-series DOT, even without the use of MRI priors.     

Optical properties of microfabricated fully-metal-coated near-field probes in collection mode

A study of the optical properties of microfabricated, fully-metal-coated quartz probes collecting longitudinal and transverse optical fields is presented. The measurements are performed by raster scanning the focal plane of an objective, focusing azimuthally and radially polarized beams by use of two metal-coated quartz probes with different metal coatings. A quantitative estimation of the collection efficiencies and spatial resolutions in imaging both longitudinal and transverse fields is made. Longitudinally polarized fields are collected with a resolution approximately 1.5 times higher as compared with transversely polarized fields, and this behavior is almost independent of the roughness of the probe's metal coating. Moreover, the coating roughness is a critical parameter in the relative collection efficiency of the two field orientations.     

Study on the Spatial Resolution of Imaging Technique for Absorption Loss Measurement of Optical Coatings

The uniformity of optical coatings becomes more and more important as large diameter optical devices are widely used. Absorption loss in optical components, particularly in optical coatings, is a limiting factor in high-power laser applications. This article analyzes the main factors, which affect the spatial resolution of three techniques for surface absorption loss measurement, including the photothermal deflection technique, the surface thermal lens technique, and the photothermal detuning technique. The influence of the size of the heating and probe beam on the photothermal detuning technique is studied in detail. Experiments are conducted to study the photothermal signal of the photothermal detuning technique for absorption measurement of the optical coating point by point. The results show that the main factors, which affect the spatial resolution of imaging measurements for absorption loss of coatings, are the heating beam size and the step accuracy of the sample translation stage. The heating and probe beam sizes has a significant impact on the application of the photothermal detuning technique. Experimental result shows that the photothermal detuning technique can be used for imaging of absorption loss measurements of optical coatings. The results provide theoretical and experimental supports for further application of the photothermal detuning technique.     

Optical slicing of human retinal tissue in vivo with the adaptive optics scanning laser ophthalmoscope

We present imaging results in human retinal tissue in vivo that allowed us to determine the axial resolution of the adaptive optics scanning laser ophthalmoscope (AOSLO). The instrument is briefly described, and the imaging results from human subjects are compared with (a) the estimated axial resolution values for a diffraction-limited, double-pass instrument and (b) the measured one for a calibrated diffuse retinal model. The comparison showed that the measured axial resolution, as obtained from optical sectioning of human retinas in vivo, can be as low as 71 microm for a 50 microm confocal pinhole after focusing a 3.5 mm beam with a 100 mm focal-length lens. The axial resolution values typically fall between the predictions from numerical models for diffuse and specular reflectors. This suggests that the reflection from the retinal blood vessel combines diffuse and specular components. This conclusion is supported by the almost universal interpretation that the image of a cylindrical blood vessel exhibits a bright reflection along its apex that is considered specular. The enhanced axial resolution achieved through use of adaptive optics leads to an improvement in the volume resolution of almost 2 orders of magnitude when compared with a conventional scanning laser ophthalmoscope and almost a factor of 3 better than commercially available optical coherence tomographic instruments.     

Direct measurement of tissue blood flow and metabolism with diffuse optics

Diffuse optics has proven useful for quantitative assessment of tissue oxy- and deoxyhaemoglobin concentrations and, more recently, for measurement of microvascular blood flow. In this paper, we focus on the flow monitoring technique: diffuse correlation spectroscopy (DCS). Representative clinical and pre-clinical studies from our laboratory illustrate the potential of DCS. Validation of DCS blood flow indices in human brain and muscle is presented. Comparison of DCS with arterial spin-labelled MRI, xenon-CT and Doppler ultrasound shows good agreement (0.50相似文献   

Information loss and reconstruction in diffuse fluorescence tomography

This paper is a theoretical exploration of spatial resolution in diffuse fluorescence tomography. It is demonstrated that, given a fixed imaging geometry, one cannot-relative to standard techniques such as Tikhonov regularization and truncated singular value decomposition-improve the spatial resolution of the optical reconstructions via increasing the node density of the mesh considered for modeling light transport. Using techniques from linear algebra, it is shown that, as one increases the number of nodes beyond the number of measurements, information is lost by the forward model. It is demonstrated that this information cannot be recovered using various common reconstruction techniques. Evidence is provided showing that this phenomenon is related to the smoothing properties of the elliptic forward model that is used in the diffusion approximation to light transport in tissue. This argues for reconstruction techniques that are sensitive to boundaries, such as L1-reconstruction and the use of priors, as well as the natural approach of building a measurement geometry that reflects the desired image resolution.     

Noncontact optical imaging in mice with full angular coverage and automatic surface extraction

During the past decade, optical imaging combined with tomographic approaches has proved its potential in offering quantitative three-dimensional spatial maps of chromophore or fluorophore concentration in vivo. Due to its direct application in biology and biomedicine, diffuse optical tomography (DOT) and its fluorescence counterpart, fluorescence molecular tomography (FMT), have benefited from an increase in devoted research and new experimental and theoretical developments, giving rise to a new imaging modality. The most recent advances in FMT and DOT are based on the capability of collecting large data sets by using CCDs as detectors, and on the ability to include multiple projections through recently developed noncontact approaches. For these to be implemented, we have developed an imaging setup that enables three-dimensional imaging of arbitrary shapes in fluorescence or absorption mode that is appropriate for small animal imaging. This is achieved by implementing a noncontact approach both for sources and detectors and coregistering surface geometry measurements using the same CCD camera. A thresholded shadowgrammetry approach is applied to the geometry measurements to retrieve the surface mesh. We present the evaluation of the system and method in recovering three-dimensional surfaces from phantom data and live mice. The approach is used to map the measured in vivo fluorescence data onto the tissue surface by making use of the free-space propagation equations, as well as to reconstruct fluorescence concentrations inside highly scattering tissuelike phantom samples. Finally, the potential use of this setup for in vivo small animal imaging and its impact on biomedical research is discussed.     

Single cell matrix-assisted laser desorption/ionization mass spectrometry imaging

Application of mass spectrometry imaging (MS imaging) analysis to single cells was so far restricted either by spatial resolution in the case of matrix-assisted laser desorption/ionization (MALDI) or by mass resolution/mass range in the case of secondary ion mass spectrometry (SIMS). In this study we demonstrate for the first time the combination of high spatial resolution (7 μm pixel), high mass accuracy (<3 ppm rms), and high mass resolution (R = 100?000 at m/z = 200) in the same MS imaging measurement of single cells. HeLa cells were grown directly on indium tin oxide (ITO) coated glass slides. A dedicated sample preparation protocol was developed including fixation with glutaraldehyde and matrix coating with a pneumatic spraying device. Mass spectrometry imaging measurements with 7 μm pixel size were performed with a high resolution atmospheric-pressure matrix-assisted laser desorption/ionization (AP-MALDI) imaging source attached to an Exactive Orbitrap mass spectrometer. Selected ion images were generated with a bin width of Δm/z = ±0.005. Selected ion images and optical fluorescence images of HeLa cells showed excellent correlation. Examples demonstrate that a lower mass resolution and a lower spatial resolution would result in a significant loss of information. High mass accuracy measurements of better than 3 ppm (root-mean-square) under imaging conditions provide confident identification of imaged compounds. Numerous compounds including small metabolites such as adenine, guanine, and cholesterol as well as different lipid classes such as phosphatidylcholine, sphingomyelin, diglycerides, and triglycerides were detected and identified based on a mass spectrum acquired from an individual spot of 7 μm in diameter. These measurements provide molecularly specific images of larger metabolites (phospholipids) in native single cells. The developed method can be used for a wide range of detailed investigations of metabolic changes in single cells.     

Fundamental imaging properties of transillumination laser CT using optical fiber applicable to bio-medical sensing

We proposed and developed a novel transillumination laser CT imaging system, using optical fibers, based on the optical heterodyne detection method for biomedical use. The use of optical fibers enables portability and robustness against environmental changes such as varying temperature, air-flow shifts, and unexpected vibrations. In addition, motion-artifact-free images can be obtained with the present system as measurements can be performed with the object fixed. We experimentally investigate in detail the fundamental imaging properties of the system, that has a spatial resolution of 500 /spl mu/m, a dynamic range of approximately 110 dB, and a minimum-detectable-optical power of 10/sup -14/ W as a result of the excellent properties of the heterodyne detection. Based on experimental observations, the proposed system can reconstruct tomographic images of highly scattering objects in the transillumination mode, similar to X-ray CT, at sub-millimeter spatial resolution and can derive quantitative information from the images. Finally, we experimentally demonstrate the first in-situ tomographic images of plants using the fiber-optic-based laser CT system.     

Tomographic optical breast imaging guided by three-dimensional mammography

We introduce a modified Tikhonov regularization method to include three-dimensional x-ray mammography as a prior in the diffuse optical tomography reconstruction. With simulations we show that the optical image reconstruction resolution and contrast are improved by implementing this x-ray-guided spatial constraint. We suggest an approach to find the optimal regularization parameters. The presented preliminary clinical result indicates the utility of the method.     

Quantitative 3D mapping of fluidic temperatures within microchannel networks using fluorescence lifetime imaging

We describe a novel method for quantitatively mapping fluidic temperature with high spatial resolution within microchannels using fluorescence lifetime imaging in an optically sectioning microscope. Unlike intensity-based measurements, this approach is independent of experimental parameters, such as dye concentration and excitation/detection efficiency, thereby facilitating quantitative temperature mapping. Micrometer spatial resolution of 3D temperature distributions is readily achieved with an optical sectioning approach based on two-photon excitation. We demonstrate this technique for mapping of temperature variations across a microfluidic chip under different heating profiles and for mapping of the 3D temperature distribution across a single microchannel under applied flow conditions. This technique allows optimization of the chip design for miniaturized processes, such as on-chip PCR, for which precise temperature control is important.     

Wavefront reconstruction by spatial-phase-shift imaging interferometry

Common-path imaging interferometers offer some advantages over other interferometers, such as insensitivity to vibrations and the ability to be attached to any optical system to analyze an imaged wavefront. We introduce the spatial-phase-shift imaging interferometry technique for surface measurements and wavefront analysis in which different parts of the wavefront undergo certain manipulations in a certain plane along the optical axis. These manipulations replace the reference-beam phase shifting of existing interferometry methods. We present the mathematical algorithm for reconstructing the wavefront from the interference patterns and detail the optical considerations for implementing the optical system. We implemented the spatial phase shift into a working system and used it to measure a variety of objects. Measurement results and comparison with other measurement methods indicate that this approach improves measurement accuracy with respect to existing quantitative phase-measurement methods.     

Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys

Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation.     

Experimental determination of photon propagation in highly absorbing and scattering media

Optical imaging and tomography in tissues can facilitate the quantitative study of several important chromophores and fluorophores. Several theoretical models have been validated for diffuse photon propagation in highly scattering and low-absorbing media that describe the optical appearance of tissues in the near-infrared (NIR) region. However, these models are not generally applicable to quantitative optical investigations in the visible because of the significantly higher tissue absorption in this spectral region compared with that in the NIR. We performed photon measurements through highly scattering and absorbing media for ratios of the absorption coefficient to the reduced scattering coefficient ranging approximately from zero to one. We examined experimentally the performance of the absorption-dependent diffusion coefficient defined by Aronson and Corngold [J. Opt. Soc. Am. A 16, 1066 (1999)] for quantitative estimations of photon propagation in the low- and high-absorption regimes. Through steady-state measurements we verified that the transmitted intensity is well described by the diffusion equation by considering a modified diffusion coefficient with a nonlinear dependence on the absorption. This study confirms that simple analytical solutions based on the diffusion approximation are suitable even for high-absorption regimes and shows that diffusion-approximation-based models are valid for quantitative measurements and tomographic imaging of tissues in the visible.     

Limited-angle spatial compound imaging of skin with high-frequency ultrasound (20 MHz)

In dermatology, high-frequency ultrasound (HFUS) is used for high-resolution skin imaging. The conventional B-scan type approach is to perform lateral scans perpendicular to the direction of sound propagation. Ultrasound spatial compounding enables improvement of the image contrast, suppression of speckle and noise, and reduction of imaging artifacts in comparison with conventional B-mode imaging, but it has not yet found its way into HFUS skin imaging applications. In this paper, the potential of HFUS spatial compounding for skin imaging is systematically evaluated. A new HFUS system with a sophisticated scanner for limited-angle (up to +/-40 degrees) spatial compound imaging was developed and implemented. Echo signals are acquired using a 20 MHz spherically focused single-element transducer with an axial and lateral resolution of 69 mum and 165 mum, respectively, in the focus. A calibration scheme for the estimation of unknown system parameters and precise image reconstruction has been developed. The implemented system has been evaluated using measurements of geometrically well-defined structures, speckle phantoms, and in vivo measurements. The results show the advantage of the proposed spatial compound skin imaging concept compared with conventional B-mode imaging in terms of image contrast, isotropy, and independence from the orientation of surfaces.     

Improvement of image quality in diffuse optical tomography by use of full time-resolved data

In the field of diffuse optical tomography (DOT), it is widely accepted that time-resolved (TR) measurement can provide the richest information on photon migration in a turbid medium, such as biological tissue. However, the currently available image reconstruction algorithms for TR DOT are based mostly on the cw component or some featured data types of original temporal profiles, which are related to the solution of a time-independent diffusion equation. Although this methodology can greatly simplify the reconstruction process, it suffers from low spatial resolution and poor quantitativeness owing to the limitation of effectively applicable data types. To improve image quality, it has been argued that exploiting the full TR data is essential. We propose implementation of a DOT algorithm by using full TR data and furthermore a variant algorithm with time slices of TR data to alleviate the computational complexity and enhance noise robustness. Compared with those algorithms where the featured data types are used, our evaluations on the spatial resolution and quantitativeness show that a significant improvement in imaging quality can be achieved when full TR data are used, which convinces the DOT community of the potential advantage of the TR domain over cw and frequency domains.