Three-dimensional Diffuse Optical Tomography Research Articles

Osteoarthritis and psoriatic arthritis: findings in three-dimensional biophotonics imaging.

The goal of this study is to capture the quantitative optical features of degenerative finger joints based on x-ray aided three-dimensional (3D) diffuse optical tomography (DOT). It is anticipated that the fused imaging technique can be applied to identifying the significant differences between osteoarthritis (OA) and psoriatic arthritis (PA). For a case study, total 6 subjects were selected to study the distal interphalangeal (DIP) finger joints. 2 OA patients, 2 PA patients and 2 healthy subjects were examined clinically first. Their DIP finger joints were then scanned by the multimodality imaging method. Our findings suggested that the developed multimodality imaging approach may aid to contradistinguish OA patients from PA patients with the healthy control, which is essential for a better diagnosis and treatment of inflammatory arthritis in humans.

Volumetric Diffuse Optical Tomography for Small Animals Using a CCD-Camera-Based Imaging System

We report the feasibility of three-dimensional (3D) volumetric diffuse optical tomography for small animal imaging by using a CCD-camera-based imaging system with a newly developed depth compensation algorithm (DCA). Our computer simulations and laboratory phantom studies have demonstrated that the combination of a CCD camera and DCA can significantly improve the accuracy in depth localization and lead to reconstruction of 3D volumetric images. This approach may present great interests for noninvasive 3D localization of an anomaly hidden in tissue, such as a tumor or a stroke lesion, for preclinical small animal models.

Near-Infrared Imaging of the Breast Using Omocianine as a Fluorescent Dye

To evaluate the efficacy of the near-infrared (NIR) dye Omocianine in a placebo-controlled, dose-escalating multicenter trial for the detection of malignant breast lesions by using a NIR imaging system. The study was approved by the ethical review board of Berlin and Münster,, and all participants provided written informed consent. Fifty-two consecutive patients were examined with NIR imaging before, during, and after intravenous injection of Omocianine. Three-dimensional absorption and fluorescence diffuse optical tomography scans were recorded simultaneously on a prototype NIR imaging unit (Computed Tomography Laser Mammography, Imaging Diagnostic Systems, Inc., Ft. Lauderdale, FL). Two readers assessed the images in consensus and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence diffuse optical tomography mammograms. Imaging results were compared with histopathologic findings. To analyze whether lesion detection rate for malignant lesions depended on the size of the lesion, lesions were dichotomized into those measuring less than 20 mm and those measuring 20 mm or more. Moreover, the shortest diameter between the center of the target lesions and the skin was measured on axial optical mammography data. There were a total of 53 target lesions. Histopathologically, 22 target lesions were diagnosed as benign and 31 target lesions as malignant. In the absorption mode, a detection rate of 11.8% for benign and 44.4% for malignant lesions across all dose groups was found. In the fluorescence mode, a detection rate of 17.6% was revealed for benign and 55.6% for malignant lesions across all dose groups. For dose group 0.1 mg/kg, a detection rate of 100% was found for malignant lesions in the fluorescence mode and 71.4% in the absorption mode. Across all dose groups in the fluorescence mode, detection rate for malignant target lesions in breasts smaller than the median axial breast diameter of 12.8 cm was higher with 69.2% than in median diameters ≥ 12.8 cm with 46.2%. Omocianine-enhanced fluorescence optical mammography allowed a better detection of more superficially located lesions, with detection rates for a lesion-skin distance <20 mm of 63.6%, for <30 mm of 47.4% and for ≥ 30 mm of 25%. Malignant target lesions with a diameter ≥ 20 mm were slightly better detected with 61.5% in contrast to suspicious lesions <20 mm with 53.8%. Optimal imaging time points varied strongly among the different target lesions and Omocianine dose groups, with a mean optimal time point for malignant lesions at 188 ± 385 minutes. Preliminary data suggest that fluorescence imaging after Omocianine administration has the potential to detect malignant breast lesions. As our study showed considerable variations in the detection of breast cancer at different fluorophore concentrations ranging from 20% to 100%, future work needs to be done to assess the suitable dose for NIR imaging.

Comprehensive investigation of three-dimensional diffuse optical tomography with depth compensation algorithm

A depth compensation algorithm (DCA) can effectively improve the depth localization of diffuse optical tomography (DOT) by compensating the exponentially decreased sensitivity in the deep tissue. In this study, DCA is investigated based on computer simulations, tissue phantom experiments, and human brain imaging. The simulations show that DCA can largely improve the spatial resolution of DOT in addition to the depth localization, and DCA is also effective for multispectral DOT with a wide range of optical properties in the background tissue. The laboratory phantom experiment demonstrates that DCA can effectively differentiate two embedded objects at different depths in the medium. DCA is further validated by human brain imaging using a finger-tapping task. To our knowledge, this is the first demonstration to show that DCA is capable of accurately localizing cortical activations in the human brain in three dimensions.

Approximation errors and model reduction in three-dimensional diffuse optical tomography

Model reduction is often required in diffuse optical tomography (DOT), typically because of limited available computation time or computer memory. In practice, this means that one is bound to use coarse mesh and truncated computation domain in the model for the forward problem. We apply the (Bayesian) approximation error model for the compensation of modeling errors caused by domain truncation and a coarse computation mesh in DOT. The approach is tested with a three-dimensional example using experimental data. The results show that when the approximation error model is employed, it is possible to use mesh densities and computation domains that would be unacceptable with a conventional measurement error model.

Differentiation of benign and malignant breast lesions by in-vivo three-dimensional diffuse optical tomography.

Abstract Abstract #805 Background: Diffuse optical tomography (DOT) uses near-infrared light to non-invasively image total hemoglobin concentration and blood oxygen saturation in the human breast. Given its low cost, ease of use, and possibility of repeated measured over time, DOT is a promising adjunctive imaging modality for screening, diagnosis and monitoring of neoadjuvant therapy. In this study we explored the performance of DOT to differentiate benign and malignant breast lesions.&amp;#x2028; Method and Materials: Forty-seven women with clinical or mammographic abnormalities were prospectively recruited for DOT. Most patients underwent gadolinium-enhanced MRI examination. Three-dimensional oxy-, deoxy-hemoglobin, total hemoglobin concentration, blood oxygen saturation and scattering coefficient images of each breast were reconstructed. Tumor-to-normal (T/N) ratios of these parameters were computed by defining tumor regions with guidance from MRI and radiology reports. In addition, optical index was constructed based on these parameters to maximize the T/N contrast. Only the biopsy-proven lesions were selected (51 breast lesions) and classified into three groups: benign lesions (N=10), malignant lesions where DOT preceded core biopsy (N=20) and malignant lesions where DOT was performed after core-biopsy (N=21). We fit a mixed effects model that estimated the mean optical T/N ratios and optical index for each group, and using the resulting standard errors developed 95% confidence intervals and tested the hypothesis that each optical contrast parameter was unity.&amp;#x2028; Results: Malignant cancers showed statistically significant higher total hemoglobin concentration, scattering, oxy-hemoglobin concentration and optical index (P=0.01-0.04) compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in an optical index derived from the endogenous optical parameters (95% CI: 1.4 - 2.4). To test whether bleeding due to core biopsy influence DOT results, we compared if there was statistically significant differences between two groups measured before or after core-biopsy. There were no statistically significant differences in these groups, suggesting that post biopsy hemorrhage did not alter the DOT results. Benign tumors did not show statistical significance in all of the T/N ratios. AUC of total hemoglobin concentration, scattering, oxy-hemoglobin and optical index suggested good discriminatory power with values between 0.90 and 0.99.&amp;#x2028; Discussion: The data demonstrates the feasibility of differentiating benign and malignant lesions by quantitative three-dimensional DOT when the tumor location information is provided by other imaging modality. The main drawback of this study is the small number of benign lesions, which warrants further study. DOT technology is still at its developing stage and needs more investigation to find its niche in breast imaging. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 805.

Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography

We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as well as blood oxygen saturation and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and magnetic resonance imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a twofold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than 1 week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT.

Implementation of a computationally efficient least‐squares algorithm for highly under‐determined three‐dimensional diffuse optical tomography problems

Three-dimensional (3D) diffuse optical tomography is known to be a nonlinear, ill-posed and sometimes under-determined problem, where regularization is added to the minimization to allow convergence to a unique solution. In this work, a generalized least-squares (GLS) minimization method was implemented, which employs weight matrices for both data-model misfit and optical properties to include their variances and covariances, using a computationally efficient scheme. This allows inversion of a matrix that is of a dimension dictated by the number of measurements, instead of by the number of imaging parameters. This increases the computation speed up to four times per iteration in most of the under-determined 3D imaging problems. An analytic derivation, using the Sherman-Morrison-Woodbury identity, is shown for this efficient alternative form and it is proven to be equivalent, not only analytically, but also numerically. Equivalent alternative forms for other minimization methods, like Levenberg-Marquardt (LM) and Tikhonov, are also derived. Three-dimensional reconstruction results indicate that the poor recovery of quantitatively accurate values in 3D optical images can also be a characteristic of the reconstruction algorithm, along with the target size. Interestingly, usage of GLS reconstruction methods reduces error in the periphery of the image, as expected, and improves by 20% the ability to quantify local interior regions in terms of the recovered optical contrast, as compared to LM methods. Characterization of detector photo-multiplier tubes noise has enabled the use of the GLS method for reconstructing experimental data and showed a promise for better quantification of target in 3D optical imaging. Use of these new alternative forms becomes effective when the ratio of the number of imaging property parameters exceeds the number of measurements by a factor greater than 2.

Tomographic x-ray–guided three-dimensional diffuse optical tomography of osteoarthritis in the finger joints

We describe a multimodality imaging approach that combines x-ray tomosynthesis with near-infrared diffuse optical tomography (DOT) for high-resolution imaging of osteoarthritis in the finger joints. In this approach, we take advantage of high resolution x-ray imaging particularly of the bones and incorporate the fine structural maps obtained from x ray as a priori information into DOT reconstructions. To realize this multi-modality approach, we constructed a hybrid imaging platform that integrated a C-arm-based x-ray tomosynthetic system with a multichannel optic-fiber-based DOT system. We also implemented improved hybrid regularization-based reconstruction algorithms that have shown to be especially effective for high-resolution modality-guided DOT. Initial evaluation of our x-ray-guided DOT reconstruction approach in the finger joints shows that spatial resolution of DOT can be enhanced dramatically when the three-dimensional geometry of bones is known a priori. In particular, the improved quantitative capability of imaging absorption and scattering coefficients of the joint tissues allows for more accurate diagnosis of osteoarthritis over x-ray radiography or DOT alone.

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.

Three-dimensional diffuse optical tomography of osteoarthritis: initial results in the finger joints

This work presents a pilot study to show the potential of an emerging imaging modality, near-infrared diffuse optical tomography (DOT), for the diagnosis of osteoarthritis (OA). We report quantitative absorption and scattering images of joint tissue that allow for differentiation between diseased and healthy joints. An automatic, multichannel optical imaging system is used to image finger joints from two OA patients and three healthy volunteers. 3-D optical images of the joint tissue are recovered using a finite-element-based reconstruction algorithm. The reconstructed images demonstrate differences in optical properties at the joint region (cartilage/synovial fluid) between the OA and healthy joints. Quantitative analysis from the patients and healthy volunteers also indicate that the recovered joint sizes are consistent with those from x-ray findings. The results of this pilot study show potential for quantitative imaging and diagnosis of early OA by DOT.

Three-dimensional diffuse optical tomography of simulated hand joints with a 64 × 64-channel photodiodes-based optical system

A continuous-wave (CW) diffuse optical tomography (DOT) system that is specifically designed for three-dimensional (3D) imaging of hand joints is described in this paper. This DOT system consists of eight diode lasers coupled with 64 source optic fibre bundles for light excitations and 64 receiving optic fibre bundles in conjunction with 64 silicon photodiodes for light detection. It has a large dynamic range, high stability and low detective noise equivalent power. In this system, the excitation and detection fibre bundles are arranged in four layers each with 16 excitation and 16 detection fibre bundles, forming a cylindrical imaging volume where an inserted finger is supported by a solid coupling medium. A series of tissue-mimicking experiments have been conducted to evaluate the system using a simple joint model consisting of two 'bones' and one layer of 'cartilage'. These experiments also serve to identify optimal experimental and computational configurations for hand joint imaging. Coupled with our 3D finite-element based reconstruction algorithm, the phantom results suggest that the supporting/coupling medium with proper absorption and scattering coefficients is one of the key factors for high quality image reconstruction. In addition, these phantom investigations show that an off-centre positioned object can be significantly better imaged than a centre placed object. Studies have also been performed to determine an optimal mesh size for 3D hand joint imaging.

Spatial deconvolution technique to improve the accuracy of reconstructed three-dimensional diffuse optical tomographic images

A straightforward spatial deconvolution operation is presented that seeks to invert the information-blurring property of first-order perturbation algorithms for diffuse optical tomography (DOT) image reconstruction. The method that was developed to generate these deconvolving operators, or filters, was conceptually based on the frequency-encoding process used in magnetic resonance imaging. The computation of an image-correcting filter involves the solution of a large system of linear equations, in which known true distributions and the corresponding recovered distributions are compared. Conversely, application of a filter involves only a simple matrix multiplication. Simulation results show that application of this deconvolution operation to three-dimensional DOT images reconstructed by the solution of a first-order perturbation equation (Born approximation) can yield marked enhancement of image quality. In the examples considered, use of image-correcting filters produces obvious improvements in image quality, in terms of both location and mirco(a) of the inclusions. The displacements between the true and recovered locations of an inclusion's centroid location are as small as 1 mm, in an 8-cm-diameter medium with 1.5-cm-diameter inclusions, and the peak value of the recovered micro(a) for the inclusions deviates from the true value by as little as 5%.

Volumetric diffuse optical tomography of brain activity.

We present three-dimensional diffuse optical tomography of the hemodynamic response to somatosensory stimulation in a rat. These images show the feasibility of volumetrically imaging the functional response to brain activity with diffuse light. A combination of positional optode calibration and contrast-to-noise ratio weighting was found to improve imaging performance.

Three-dimensional diffuse optical tomography of bones and joints.

We present for the first time full three-dimensional (3D) volumetric reconstruction of absorption images of in vitro and in vivo bones and joints from near-infrared tomographic measurements. Imaging experiments were conducted on human finger and chicken bones embedded in cylindrical scattering media using a Clemson multichannel diffuse optical imager. The volumetric optical images were recovered with our 3D finite element based reconstruction algorithm. Our results show that 3D imaging methods can provide details of the joint structure/composition that would be impossible from two-dimensional imaging methods.