Alper Corlu

Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans.

We present three-dimensional (3D) in vivo images of human breast cancer based on fluorescence diffuse optical tomography (FDOT). To our knowledge, this work represents the first reported 3D fluorescence tomography of human breast cancer in vivo. In our protocol, the fluorophore Indocyanine Green (ICG) is injected intravenously. Fluorescence excitation and detection are accomplished in the soft-compression, parallel-plane, transmission geometry using laser sources at 786 nm and spectrally filtered CCD detection. Phantom and in vivo studies confirm the signals are due to ICG fluorescence, rather than tissue autofluorescence and excitation light leakage. Fluorescence images of breast tumors were in good agreement with those of MRI, and with DOT based on endogenous contrast. Tumorto- normal tissue contrast based on ICG fluorescence was two-to-four-fold higher than contrast based on hemoglobin and scattering parameters. In total the measurements demonstrate that FDOT of breast cancer is feasible and promising.

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI.

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.

Diffuse optical tomography with spectral constraints and wavelength optimization

We present an algorithm that explicitly utilizes the wavelength dependence of tissue optical properties for diffuse optical tomography. We have previously shown that the method gives superior separation of absorption and scattering. Here the technique is described and tested in detail, and optimum wavelength sets for a broad range of chromophore combinations are discovered and analyzed.

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.

Uniqueness and wavelength optimization in continuous-wave multispectral diffuse optical tomography.

We derive conditions for the unique and simultaneous recovery of chromophore concentrations and scattering coefficients in multispectral continuous-wave diffuse optical tomography. These conditions depend strongly on measurement wavelengths. We introduce and demonstrate a general methodology for choosing those wavelengths, which yields superior separation of scattering from absorption and superior separation of one chromophore from another. Application of these concepts should significantly improve the fidelity of continuous-wave diffuse near-infrared optical tomography in tissues.

Comparison of diffuse optical tomography of human breast with whole‐body and breast‐only positron emission tomography

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Standardized platform for coregistration of nonconcurrent diffuse optical and magnetic resonance breast images obtained in different geometries

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques. The resulting superposed 3-D tomographs facilitate tissue analyses based on structural and functional data derived from both modalities, and readily permit enhancement of DOT data reconstruction using MRI-derived a-priori structural information. We demonstrate the multimodal registration method using a simulated phantom, and we present initial patient studies that confirm that tumorous regions in a patient breast found by both imaging modalities exhibit significantly higher total hemoglobin concentration (THC) than surrounding normal tissues. The average THC in the tumorous regions is one to three standard deviations larger than the overall breast average THC for all patients.

Transmission RF diffuse optical tomography instrument for human breast imaging

In this paper, we describe a novel clinical breast diffuse optical tomography (DOT) instrument for CW and RF data acquisition in transmission geometry. It is designed to be able to acquire a massive amount of data in a short amount of time available for patient measurement by using a 209-channel galvo-based fast optical switch and a fast electron-multiplying CCD. In addition to CW measurements, RF measurements were made by using an electro-optic modulator for source modulation and a gain-modulated image intensifier for detection. The patient bed has many clinically-oriented features as well as improved data acquisition rate and transmission RF measurement capability. A series of preliminary results will be shown, including a heterodyne RF experiment for bulk property measurement and a CW experiment for 3D imaging. In order to deal with large data size, a linear reconstruction algorithm that exploits separability of the inverse problem in Fourier domain is used for fast and memory-load-free reconstruction.

Multimodal information integration and visualization: optical imaging and MRI

We have developed a software platform for multimodal integration and visualization of diffuse optical tomography (DOT) and magnetic resonance imaging (MRI) of breast cancer. The image visualization platform allows multimodality 3D image visualization and manipulation of datasets, such as a variety of 3D rendering technique, and the ability to simultaneously control multiple fields of view. This platform enables quantitative and qualitative analysis of structural and functional diagnostic data, using both conventional & molecular imaging. The functional parameters, together with morphological parameters from MR can be suitably combined and correlated to the absolute diagnosis from histopathology. Fusion of the multimodal datasets will eventually lead to a significant improvement in the sensitivity and specificity of breast cancer detection. Fusion may also allow a priori structural information derived from MRI to be incorporated into the reconstruction of diffuse optical tomography images. We will present the early results of image visualization and registration on multimodal breast cancer data, DOT and MRI.

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

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts 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. 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. 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. 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.