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Stephanie van de Ven,
Andrea Wiethoff, Tim Nielsen,
Bernhard Brendel,
Marjolein van der Voort,
Rami Nachabe,
Martin Van der Mark,
Michiel Van Beek,
Leon Bakker,
Lueder Fels,
Sjoerd Elias,
Peter Luijten,
Willem Mali
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ABSTRACT: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT).
Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison.
Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-to-background signals were obtained after 8 h. No adverse events occurred.
Lowest doses of Omocianine performed best in lesion detection; DOT using a low-dose fluorescent agent is feasible and safe for breast cancer visualization in patients.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 10/2009; 12(3):343-8. · 2.47 Impact Factor
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ABSTRACT: We report on the nonlinear reconstruction of local absorption and fluorescence contrast in tissuelike scattering media from measured time-domain diffuse reflectance and transmittance of laser as well as laser-excited fluorescence radiation. Measurements were taken at selected source-detector offsets using slablike diffusely scattering and fluorescent phantoms containing fluorescent heterogeneities. Such measurements simulate in vivo data that would be obtained employing a scanning, time-domain fluorescence mammograph, where the breast is gently compressed between two parallel glass plates, and source and detector optical fibers scan synchronously at various source-detector offsets, allowing the recording of laser and fluorescence mammograms. The diffusion equations modeling the propagation of the laser and fluorescence radiation were solved in frequency domain by the finite element method simultaneously for several modulation frequencies using Fourier transformation and preprocessed experimental data. To reconstruct the concentration of the fluorescent contrast agent, the Born approximation including higher-order reconstructed photon densities at the excitation wavelength was used. Axial resolution was determined that can be achieved by various detection schemes. We show that remission measurements increase the depth resolution significantly.
Applied Optics 09/2009; 48(24):4651-62. · 1.41 Impact Factor
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ABSTRACT: Diffuse optical tomography (DOT) is a potential new imaging modality to detect or monitor breast lesions. Recently, Philips developed a new DOT system capable of transmission and fluorescence imaging, where the investigated breast is hanging freely into the measurement cup containing scattering fluid. We present a fast and robust image reconstruction algorithm that is used for the transmission measurements. The algorithm is based on the Rytov approximation. We show that this algorithm can be used over a wide range of tissue optical properties if the reconstruction is adapted to each patient. We use estimates of the breast shape and average tissue optical properties to initialize the reconstruction, which improves the image quality significantly. We demonstrate the capability of the measurement system and reconstruction to image breast lesions by clinical examples.
Applied Optics 05/2009; 48(10):D1-13. · 1.41 Impact Factor
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ABSTRACT: Using a statistical (chi-square) test on simulated data and a realistic noise model derived from the system's hardware we study the performance of diffuse optical tomography systems for fluorescence imaging. We compare the predicted smallest size of detectable lesions at various positions in slab and cup geometry and model how detection sensitivity depends on breast compression and lesion fluorescence contrast. Our investigation shows that lesion detection is limited by relative noise in slab geometry and by absolute noise in cup geometry.
Physics in Medicine and Biology 02/2009; 54(2):413-31. · 2.83 Impact Factor
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Stephanie M W Y van de Ven,
Sjoerd G Elias,
Andrea J Wiethoff,
Marjolein van der Voort, Tim Nielsen,
Bernhard Brendel,
Claas Bontus,
Falk Uhlemann,
Rami Nachabe,
Rik Harbers,
Michiel van Beek,
Leon Bakker,
Martin B van der Mark,
Peter Luijten,
Willem P Th M Mali
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ABSTRACT: This paper presents an evaluation of a prototype diffuse optical tomography (DOT) system. Seventeen women with 18 breast lesions (10 invasive carcinomas, 2 fibroadenomas, and 6 benign cysts; diameters 13-54 mm) were evaluated with DOT and magnetic resonance imaging (MRI). A substantial fraction of the original 36 recruited patients could not be examined using this prototype due to technical problems. A region of interest (ROI) was drawn at the lesion position as derived from MRI and at the mirror image site in the contralateral healthy breast. ROIs were assessed quantitatively and qualitatively by two observers independently in two separate readings. Intra- and interobserver agreements were calculated using kappa statistics (k) and intraclass correlation coefficients (ICCs). Discriminatory values for presence of malignancy were determined by receiver operating characteristic (ROC) analyses. Intraobserver agreements were excellent (k 0.88 and 0.88; ICC 0.978 and 0.987), interobserver agreements were good to excellent (k 0.77-0.95; ICC 0.96-0.98). Discriminatory values for presence of malignancy were 0.92-0.93 and 0.97-0.99 for quantitative and qualitative ROC analysis, respectively. This DOT system has the potential to discriminate malignant from benign breast tissue in a reproducible qualitative and quantitative manner. Important technical improvements are required before this technique is ready for clinical application.
European Radiology 02/2009; 19(5):1108-13. · 3.22 Impact Factor
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ABSTRACT: We present a method to enhance tumor detectability in breasts imaged with our optical fluorescence mammography system. During a measurement, transmission data at 4 wavelengths and fluorescence data for excitation at 1 wavelength are collected after injection of an optical contrast agent. The data are reconstructed into 3D images of the absorption and fluorescence distributions. Combining those images enables the identification of various breast tissue compounds. Here, we investigate the relevance of our method in phantom experiments.
Optical Tomography and Spectroscopy of Tissue (SPIE vol. 7174); 02/2009
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ABSTRACT: Reconstruction in diffuse optical tomography (DOT) necessitates solving the diffusion equation, which is nonlinear with respect to the parameters that have to be reconstructed. Currently applied solving methods are based on the linearization of the equation. For spectral three-dimensional reconstruction, the emerging equation system is too large for direct inversion, but the application of iterative methods is feasible. Computational effort and speed of convergence of these iterative methods are crucial since they determine the computation time of the reconstruction. In this paper, the iterative methods algebraic reconstruction technique (ART) and conjugated gradients (CGs) as well as a new modified ART method are investigated for spectral DOT reconstruction. The aim of the modified ART scheme is to speed up the convergence by considering the specific conditions of spectral reconstruction. As a result, it converges much faster to favorable results than conventional ART and CG methods.
Applied Optics 01/2009; 47(34):6392-403. · 1.41 Impact Factor
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Stephanie van de Ven,
Sjoerd Elias,
Andrea Wiethoff,
Marjolein van der Voort,
Anais Leproux, Tim Nielsen,
Bernhard Brendel,
Leon Bakker,
Martin van der Mark,
Willem Mali,
Peter Luijten
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ABSTRACT: The purpose of this study was to validate a newly developed diffuse optical tomography (DOT) system on benign cysts in the breast.
Eight patients with 20 benign cysts were included. Study procedures consisted of optical breast imaging and breast magnetic resonance imaging (MRI) for comparison. A reconstruction algorithm computed three-dimensional images for each of the four near-infrared wavelengths used by our DOT system (Philips Healthcare, Best, The Netherlands). These images were combined using a spectroscopic model to assess tissue composition and lesion size.
Twenty cysts were analyzed in eight patients. By using the spectroscopic information, 13 of 20 cysts (65%) were visualized with DOT, confirming their high water and low total hemoglobin content. Lesion size and location showed good agreement with MRI; Pearson correlation coefficient was 0.7 (p < 0.01).
DOT can visualize benign cysts in the breast and elucidate their high water and low total hemoglobin content by spectroscopic analysis.
Molecular Imaging & Biology 12/2008; 11(2):64-70. · 3.84 Impact Factor
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ABSTRACT: Using lasers with different wavelengths in diffuse optical tomography (spectral DOT) has the advantage that the concentrations of chromophores can be reconstructed quantitatively. In continuous wave spectral DOT, it is furthermore possible to distinguish between scattering and absorption. The choice of the laser wavelengths has a strong impact on how well the scattering parameter and chromophore concentrations can be determined. Current methods to optimize the set of wavelengths disregard the sensitivity of the reconstruction result to uncertainties in the absorption spectra of the chromophores. But since available absorption spectra show significant deviations, it seems to be necessary to take this into account. The wavelength optimization approach presented here is an extension to a method of Corlu et al. The original method optimizes the wavelength sets such that scattering parameters and chromophore concentrations can be separated optimally. We introduce an additional criterion that evaluates the dependence of reconstructed chromophore concentrations on deviations of the extinction coefficients. The wavelength sets found by the new approach are different from those determined with the original method. Reconstructions of simulated data show the effect of using various absorption spectra for reconstruction with different wavelength sets and illustrate the advantages of the new wavelength sets.
Journal of Biomedical Optics 14(3):034041. · 3.16 Impact Factor
