Diffuse Correlation Tomography Research Articles

Alignment of sources and detectors on breast surface for noncontact diffuse correlation tomography of breast tumors.

Noncontact diffuse correlation tomography (ncDCT) is an emerging technology for 3D imaging of deep tissue blood flow distribution without distorting hemodynamic properties. To adapt the ncDCT for imaging in vivo breast tumors, we designed a motorized ncDCT probe to scan over the breast surface. A computer-aided design (CAD)-based approach was proposed to create solid volume mesh from arbitrary breast surface obtained by a commercial 3D camera. The sources and detectors of ncDCT were aligned on the breast surface through ray tracing to mimic the ncDCT scanning with CAD software. The generated breast volume mesh along with the boundary data of ncDCT at the aligned source and detector pairs were used for finite-element-method-based flow image reconstruction. We evaluated the accuracy of source alignments on mannequin and human breasts; largest alignment errors were less than 10% in both tangential and radial directions of scanning. The impact of alignment errors (assigned 10%) on the tumor reconstruction was estimated using computer simulations. The deviations of simulated tumor location and blood flow contrast resulted from the alignment errors were 0.77mm (less than the node distance of 1mm) and 1%, respectively, which result in minor impact on flow image reconstruction. Finally, a case study on a human breast tumor was conducted and a tumor-to-normal flow contrast was reconstructed, demonstrating the feasibility of ncDCT in clinical application.

Effect of head model on Monte Carlo modeling of spatial sensitivity distribution for functional near-infrared spectroscopy

Modeling Light propagation within human head to deduce spatial sensitivity distribution (SSD) is important for Near-infrared spectroscopy (NIRS)/imaging (NIRI) and diffuse correlation tomography. Lots of head models have been used on this issue, including layered head model, artificial simplified head model, MRI slices described head model, and visible human head model. Hereinto, visible Chinese human (VCH) head model is considered to be a most faithful presentation of anatomical structure, and has been highlighted to be employed in modeling light propagation. However, it is not practical for all researchers to use VCH head models and actually increasing number of people are using magnet resonance imaging (MRI) head models. Here, all the above head models were simulated and compared, and we focused on the effect of using different head models on predictions of SSD. Our results were in line with the previous reports on the effect of cerebral cortex folding geometry. Moreover, the influence on SSD increases with the fidelity of head models. And surprisingly, the SSD percentages in scalp and gray matter (region of interest) in MRI head model were found to be 80% and 125% higher than in VCH head model. MRI head models induced nonignorable discrepancy in SSD estimation when compared with VCH head model. This study, as we believe, is the first to focus on comparison among full serials of head model on estimating SSD, and provided quantitative evidence for MRI head model users to calibrate their SSD estimation.

Noncontact diffuse correlation tomography of human breast tumor.

Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor is within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor blood flow contrasts. In vivo imaging results from two breast carcinomas show higher average blood flow contrasts (5.9- and 10.9-fold) in the tumor regions compared to the surrounding tissues, which are comparable with previous findings using diffuse correlation spectroscopy. The ncDCT system has the potential to image blood flow distributions in soft and vulnerable tissues without distorting tissue hemodynamics

Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model.

A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.

Speckle contrast diffuse correlation tomography of complex turbid medium flow.

Developed herein is a three-dimensional (3D) flow contrast imaging system leveraging advancements in the extension of laser speckle contrast imaging theories to deep tissues along with our recently developed finite-element diffuse correlation tomography (DCT) reconstruction scheme. This technique, termed speckle contrast diffuse correlation tomography (scDCT), enables incorporation of complex optical property heterogeneities and sample boundaries. When combined with a reflectance-based design, this system facilitates a rapid segue into flow contrast imaging of larger, in vivo applications such as humans. A highly sensitive CCD camera was integrated into a reflectance-based optical system. Four long-coherence laser source positions were coupled to an optical switch for sequencing of tomographic data acquisition providing multiple projections through the sample. This system was investigated through incorporation of liquid and solid tissue-like phantoms exhibiting optical properties and flow characteristics typical of human tissues. Computer simulations were also performed for comparisons. A uniquely encountered smear correction algorithm was employed to correct point-source illumination contributions during image capture with the frame-transfer CCD and reflectance setup. Measurements with scDCT on a homogeneous liquid phantom showed that speckle contrast-based deep flow indices were within 12% of those from standard DCT. Inclusion of a solid phantom submerged below the liquid phantom surface allowed for heterogeneity detection and validation. The heterogeneity was identified successfully by reconstructed 3D flow contrast tomography with scDCT. The heterogeneity center and dimensions and averaged relative flow (within 3%) and localization were in agreement with actuality and computer simulations, respectively. A custom cost-effective CCD-based reflectance 3D flow imaging system demonstrated rapid acquisition of dense boundary data and, with further studies, a high potential for translatability to real tissues with arbitrary boundaries. A requisite correction was also found for measurements in the fashion of scDCT to recover accurate speckle contrast of deep tissues.

Three-dimensional flow contrast imaging of deep tissue using noncontact diffuse correlation tomography.

This study extended our recently developed noncontact diffuse correlation spectroscopy flowmetry system into noncontact diffuse correlation tomography (ncDCT) for three-dimensional (3-D) flow imaging of deep tissue. A linear array of 15 photodetectors and two laser sources connected to a mobile lens-focusing system enabled automatic and noncontact scanning of flow in a region of interest. These boundary measurements were combined with a finite element framework for DCT image reconstruction implemented into an existing software package. This technique was tested in computer simulations and using a tissue-like phantom with anomaly flow contrast design. The cylindrical tube-shaped anomaly was clearly reconstructed in both simulation and phantom. Recovered and assigned flow contrast changes in anomaly were found to be highly correlated: regression slope = 1.00, R2 = 1.00, and p < 10-5 in simulation and regression slope ≥ 0.97, R2 ≥ 0.96, and p < 10-3 in phantom. These results exhibit promise of our ncDCT technique for 3-D imaging of deep tissue blood flow heterogeneities.

Generalized eigenvalue decomposition of the field autocorrelation in correlation diffusion of photons in turbid media

We propose a novel numerical method based on a generalized eigenvalue decomposition for solving the diffusion equation governing the correlation diffusion of photons in turbid media. Medical imaging modalities such as diffuse correlation tomography and ultrasound‐modulated optical tomography have the (elliptic) diffusion equation parameterized by a time variable as the forward model. Hitherto, for the computation of the correlation function, the diffusion equation is solved repeatedly over the time parameter. We show that the use of a certain time‐independent generalized eigenfunction basis results in the decoupling of the spatial and time dependence of the correlation function, thus allowing greater computational efficiency in arriving at the forward solution. Besides presenting the mathematical analysis of the generalized eigenvalue problem on the basis of spectral theory, we put forth the numerical results that compare the proposed numerical method with the standard technique for solving the diffusion equation. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Convergence analysis of the Newton algorithm and a pseudo-time marching scheme for diffuse correlation tomography

We propose a self-regularized pseudo-time marching scheme to solve the ill-posed, nonlinear inverse problem associated with diffuse propagation of coherent light in a tissuelike object. In particular, in the context of diffuse correlation tomography (DCT), we consider the recovery of mechanical property distributions from partial and noisy boundary measurements of light intensity autocorrelation. We prove the existence of a minimizer for the Newton algorithm after establishing the existence of weak solutions for the forward equation of light amplitude autocorrelation and its Fréchet derivative and adjoint. The asymptotic stability of the solution of the ordinary differential equation obtained through the introduction of the pseudo-time is also analyzed. We show that the asymptotic solution obtained through the pseudo-time marching converges to that optimal solution provided the Hessian of the forward equation is positive definite in the neighborhood of optimal solution. The superior noise tolerance and regularization-insensitive nature of pseudo-dynamic strategy are proved through numerical simulations in the context of both DCT and diffuse optical tomography.

Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain

Diffuse optical correlation methods were adapted for three-dimensional (3D) tomography of cerebral blood flow (CBF) in small animal models. The image reconstruction was optimized using a noise model for diffuse correlation tomography which enabled better data selection and regularization. The tomographic approach was demonstrated with simulated data and during in-vivo cortical spreading depression (CSD) in rat brain. Three-dimensional images of CBF were obtained through intact skull in tissues(~4mm) deep below the cortex.

Development of diffuse correlation techniques for non-invasive measurement of cerebral blood flow and oxygen metabolism in rats

Our group has pioneered the development of diffuse correlation tomography (DCT) for measurement of cerebral blood flow (CBF) through the intact skull in animal models and finally in adult human brain. By combining DCT with simultaneous diffuse optical tomography(DOT) which images changes in oxyhemoglobin (rHbO2), deoxyhemoglobin (rHb) and total hemoglobin (rTHC) concentrations, and blood oxygen saturation (dYt), we can derive an image of the relative cerebral metabolic rate of oxygen (rCMRO2). Previously, we have obtained images in rat brain during hypercapnia 1 and focal transient ischemia 2, and now present data in cortical spreading depression (CSD). The development of this technique enables us to carry out longitudinal studies in small animals relatively noninvasively. After validating the combined DOT/DCT technique using a well characterized system (hypercapnia) 1, we then obtained data in a middle cerebral artery occlusion model in the rat 2. In the penumbra, rCBF decreased to 424%, dYt decreased by 114% and rCMRO2 decreased to 594%. These data are in reasonable agreement with values reported in the literature and were the first images of rCMRO2 obtained by diffuse optical methods. Recently, we have induced cortical spreading depression (CSD) in twenty-six rats by applying KCl through a burr hole over the parietal cortex under hypocapnia, normocapnia, and hypercapnia. Figure 1a shows images of rCBF at selected time points and at different depths. A region of increased CBF progressed from the point where the KCl was applied, spreading throughout the cortex. The observed response was mainly constrained to the upper cortex, illustrating the depth selectivity of the imaging technique (Figure 1b). We observed significant correlations of the peak amplitude of rCBF and frequency of the CSD waves with alterations in pCO2 (Figure 1c). Similar results were obtained in the oxygenation and CMRO2 images. By imaging multiple parameters simultaneously we are able to characterize the CSD physiology more thoroughly than usual DOT. Overall these results have validated and demonstrated the utility of DCT methods in obtaining 3D dimensional, dynamic images of blood flow and hence enabling measurement of CMRO2. We discuss the extension of this technique to measurements in the adult human in an accompanying abstract.

Noninvasive measurements of tissue hemodynamics with hybrid diffuse optical methods

Diffuse optical techniques were used to measure hemodynamics of tissues noninvasively. Spectroscopy and tomography of the brain, muscle, and implanted tumors were carried out in animal models and humans. Two qualitatively different methods, diffuse optical tomography and diffuse correlation tomography, were hybridized permitting simultaneous measurement of total hemoglobin concentration, blood oxygen saturation, and blood flow. This combination of information was processed further to derive estimates of oxygen metabolism (e.g., in tissue. The diffuse correlation measurements of blood flow were demonstrated in human tissues, for the first time, demonstrating continous noninvasive imaging of oxygen metabolism in large tissue volumes several centimeters below the tissue surface. The bulk of these investigations focussed on cerebral hemodynamics. Extensive validation of this methodology was carried out in in vivo rat brain models. Three‐dimensional images of deep tissue hemodynamics in middle cerebral artery occlusion and cortical spreading depression (CSD) were obtained. CSD hemodynamics were found to depend strongly on partial pressure of carbon dioxide. The technique was then adapted for measurement of human brain. All optical spectroscopic measurements of during functional activation were obtained through intact human skull noninvasively. Finally, a high spatiotemporal resolution measurement of cerebral blood flow due to somatosensory cortex activation following electrical forepaw stimulation in rats was carried out with laser speckle flowmetry. New analysis methods were introduced for laser speckle flowmetry. In other organs, deep tissue hemodynamics were measured on human calf muscle during exercise and cuff‐ischemia and were shown to have some clinical utility for peripheral vascular disease. In mice tumor models, the measured hemodynamics were shown to be predictive of photodynamic therapy efficacy, again suggesting the promise of clinical utility. In total, the research has pioneered the development of diffuse optical measurements of blood flow, oxygenation, and oxygen metabolism in a large range of research and clinical applications.