Receiver Operating Characteristic and Location Analysis of Simulated Near-Infrared Tomography Images

Receiver operating characteristic (ROC) analysis was performed on simulated near-infrared tomography images, using both human observer and contrast-to-noise ratio (CNR) computational assessment, for application in breast cancer imaging. In the analysis, a nonparametric approach was applied for estimating the ROC curves. Human observer detection of objects had superior capability to localize the presence of heterogeneities when the objects were small with high contrast, with a minimum detectable threshold of CNR near 3.0 to 3.3 in the images. Human observers were able to detect heterogeneities in the images below a size limit of 4 mm, yet could not accurately find the location of these objects when they were below 10 mm diameter. For large objects, the lower limit of a detectable contrast limit was near 10% increase relative to the background. The results also indicate that iterations of the nonlinear reconstruction algorithm beyond 4 did not significantly improve the human detection ability, and degraded the overall localization ability for the objects in the image, predominantly by increasing the noise in the background. Interobserver variance performance in detecting objects in these images was low, suggesting that because of the low spatial resolution, detection tasks with NIR tomography is likely consistent between human observers

Multiobjective Guided Priors Improve the Accuracy of Near-Infrared Spectral Tomography for Breast Imaging

An image reconstruction regularization approach for magnetic resonance imaging-guided near-infrared spectral tomography has been developed to improve quantification of total hemoglobin (HbT) and water. By combining prior information from dynamic contrast enhanced (DCE) and diffusion weighted (DW) MR images, the absolute bias errors of HbT and water in the tumor were reduced by 22% and 18%, 21% and 6%, and 10% and 11%, compared to that in the no-prior, DCE- or DW-guided reconstructed images in three-dimensional simulations, respectively. In addition, the apparent contrast values of HbT and water were increased in patient image reconstruction from 1.4 and 1.4 (DCE) or 1.8 and 1.4 (DW) to 4.6 and 1.6

Remote Positioning Optical Breast Magnetic Resonance Coil for Slice-Selection During Image-Guided Near-Infrared Spectroscopy of Breast Cancer

The design and testing of a pneumatic optical positioning interface produced with the goal of improving fiber positioning in magnetic resonance (MR)-guided diffuse spectral imaging of breast cancer is presented. The system was created for vertical positioning of optical fibers inside the MR bore during a patient exam to target suspicious lesions with MR scans for reference and collect multiple planes of optical data. The interface includes new fiber plates for mechanical and optical coupling to the breast, and was tested in phantoms and human imaging. Reconstructions with data taken in the new interface show acceptable linearity over different absorber concentrations (residual norm = 0.067), and exhibit good contrast recovery at different imaging planes, which is consistent with previous work. An example of human breast imaging through the new interface is shown and a discussion of how it compares to other patient interfaces for breast imaging is presented. Design goals of increasing the available degrees of freedom for fiber positioning while maintaining good patient-fiber contact and comfort were accomplished. This interface allows improved volumetric imaging with interactive and accurate slice selection to quantify targeted suspicious lesions

Hybrid Photomultiplier Tube and Photodiode Parallel Detection Array for Wideband Optical Spectroscopy of the Breast Guided by Magnetic Resonance Imaging

A new optical parallel detection system of hybrid frequency and continuous-wave domains was developed to improve the data quality and accuracy in recovery of all breast optical properties. This new system was deployed in a previously existing system for magnetic resonance imaging (MRI)-guided spectroscopy, and allows incorporation of additional near-infrared wavelengths beyond 850 nm, with interlaced channels of photomultiplier tubes (PMTs) and silicon photodiodes (PDs). The acquisition time for obtaining frequency-domain data at six wavelengths (660, 735, 785, 808, 826, and 849 nm) and continuous-wave data at three wavelengths (903, 912, and 948 nm) is 12 min. The dynamic ranges of the detected signal are 105 and 106 for PMT and PD detectors, respectively. Compared to the previous detection system, the SNR ratio of frequency-domain detection was improved by nearly 103 through the addition of an RF amplifier and the utilization of programmable gain. The current system is being utilized in a clinical trial imaging suspected breast cancer tumors as detected by contrast MRI scans

Improved Quantification of Small Objects in Near-Infrared Diffuse Optical Tomography

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final third step, which uses the estimated size and position information from step 2 to yield quantitatively accurate average values for the optical parameters. The algorithm is tested on simulated and experimental data and is found to be insensitive to object contrast and position. The percentage error between the true and the average recovered value for the absorption coefficient in test images is reduced from 47 to 27% for a 10-mm inclusion, from 38 to 13% for a 15-mm anomaly, and from 28 to 5.5% for a 20-mm heterogeneity. Simulated data with absorbing and scattering heterogeneities of 15 mm diam located in different positions show recovery with less than 15% error in absorption and 6% error in reduced scattering coefficients. The algorithm is successfully applied to clinical data from a subject with a breast abnormality to yield quantitatively increased absorption coefficients, which enhances the contrast to 3.8 compared to 1.23 previously

Comparison of Magnetic Resonance Imaging-Compatible Optical Detectors for In-Magnet Tissue Spectroscopy: Photodiodes Versus Silicon Photomultipliers

Tissue spectroscopy inside the magnetic resonance imaging (MRI) system adds a significant value by measuring fast vascular hemoglobin responses or completing spectroscopic identification of diagnostically relevant molecules. Advances in this type of spectroscopy instrumentation have largely focused on fiber coupling into and out of the MRI; however, nonmagnetic detectors can now be placed inside the scanner with signal amplification performed remotely to the high field environment for optimized light detection. In this study, the two possible detector options, such as silicon photodiodes (PD) and silicon photomultipliers (SiPM), were systematically examined for dynamic range and wavelength performance. Results show that PDs offer 108 (160 dB) dynamic range with sensitivity down to 1 pW, whereas SiPMs have 107 (140 dB) dynamic range and sensitivity down to 10 pW. A second major difference is the spectral sensitivity of the two detectors. Here, wavelengths in the 940 nm range are efficiently captured by PDs (but not SiPMs), likely making them the superior choice for broadband spectroscopy guided by MRI

Image-Guided Diffuse Optical Fluorescence Tomography Implemented with Laplacian-Type Regularization

A promising method to incorporate tissue structural information into the reconstruction of diffusion-based fluorescence imaging is introduced. The method regularizes the inversion problem with a Laplacian-type matrix, which inherently smoothes pre-defined tissue, but allows discontinuities between adjacent regions. The technique is most appropriately used when fluorescence tomography is combined with structural imaging systems. Phantom and simulation studies were used to illustrate significant improvements in quantitative imaging and linearity of response with the new algorithm. Images of an inclusion containing the fluorophore Lutetium Texaphyrin (Lutex) embedded in a cylindrical phantom are more accurate than in situations where no structural information is available, and edge artifacts which are normally prevalent were almost entirely suppressed. Most importantly, spatial priors provided a higher degree of sensitivity and accuracy to fluorophore concentration, though both techniques suffer from image bias caused by excitation signal leakage. The use of spatial priors becomes essential for accurate recovery of fluorophore distributions in complex tissue volumes. Simulation studies revealed an inability of the “no-priors” imaging algorithm to recover Lutex fluorescence yield in domains derived from T1 weighted images of a human breast. The same domains were reconstructed accurately to within 75% of the true values using prior knowledge of the internal tissue structure. This algorithmic approach will be implemented in an MR-coupled fluorescence spectroscopic tomography system, using the MR images for the structural template and the fluorescence data for region quantification

Optimization of Image Reconstruction for Magnetic Resonance Imaging–Guided Near-Infrared Diffuse Optical Spectroscopy in Breast

An optimized approach to nonlinear iterative reconstruction of magnetic resonance imaging (MRI)–guided near-infrared spectral tomography (NIRST) images was developed using an L-curve-based algorithm for the choice of regularization parameter. This approach was applied to clinical exam data to maximize the reconstructed values differentiating malignant and benign lesions. MRI/NIRST data from 25 patients with abnormal breast readings (BI-RADS category 4-5) were analyzed using this optimal regularization methodology, and the results showed enhanced p values and area under the curve (AUC) for the task of differentiating malignant from benign lesions. Of the four absorption parameters and two scatter parameters, the most significant differences for benign versus malignant were total hemoglobin (HbT) and tissue optical index (TOI) with pvalues=0.01 and 0.001, and AUC values=0.79 and 0.94, respectively, in terms of HbT and TOI. This dramatically improved the values relative to fixed regularization (pvalue=0.02 and 0.003; AUC=0.75 and 0.83) showing that more differentiation was possible with the optimal method. Through a combination of both biomarkers, HbT and TOI, the AUC increased from 82.9% (fixed regulation=0.1) to 94.3% (optimal method)