Near-infrared Spectral Tomography Research Articles

Direct regularization from co-registered anatomical images for MRI-guided near-infrared spectral tomographic image reconstruction.

Combining anatomical information from high resolution imaging modalities to guide near-infrared spectral tomography (NIRST) is an efficient strategy for improving the quality of the reconstructed spectral images. A new approach for incorporating image information directly into the inversion matrix regularization was examined using Direct Regularization from Images (DRI), which encodes the gray-scale data into the NIRST image reconstruction problem. This process has the benefit of eliminating user intervention such as image segmentation of distinct regions. Specifically, the Dynamic Contrast Enhanced Magnetic Resonance (DCE-MR) image intensity value differences within the anatomical image were used to implement an exponentially-weighted regularization function between the image pixels. The algorithm was validated using simulated reconstructions with noise, and the results showed that spatial resolution and robustness of the reconstructed images were significantly improved by appropriate choice of the regularization weight parameters. The proposed approach was also tested on in vivo breast data acquired in a recent clinical trial combining NIRST / MRI for cancer tumor characterization. Relative to the standard "no priors" diffuse recovery, the contrast of the tumor to the normal surrounding tissue increased from 2.4 to 3.6, and the difference between the tumor size segmented from DCE-MR images and reconstructed optical images decreased from 18% to 6%, while there was an overall decrease in surface artifacts.

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 p values = 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 (p value = 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).

Pre-treatment Near-Infrared Spectral Tomography (NIRST) to predict pathologic complete response to neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (LABC).

1047 Background: NIRST has a potential role for easily integrated monitoring and prediction of therapeutic response in women with LABC undergoing NAC. It captures biophysical changes in tissue occu...

Geographic atrophy in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

To examine factors associated with the apparent growth of geographic atrophy (GA) in a consecutive series of eyes with treatment-naive neovascular age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor therapy on a treat-and-extend regimen. This was a retrospective cohort study. Two independent graders identified areas of GA using near-infrared reflectance imaging and spectral domain optical coherence tomography (SD-OCT). Neovascular lesion subtypes were classified based on fluorescein angiography (FA) as occult choroidal neovascularization, classic choroidal neovascularization, retinal angiomatous proliferation, or mixed choroidal neovascularization, and by the anatomical classification system which utilizes FA and SD-OCT as Types 1 (sub-retinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed neovascularization. Ninety-one patients (94 eyes) fit the inclusion criteria, of which 52 eyes (55.3%) experienced apparent GA growth. The odds of developing apparent GA were significantly lower in Type 1 neovascularization compared to the other lesion types (P < 0.001). Using both FA and SD-OCT to classify neovascular age-related macular degeneration significantly improves the goodness of fit in the correlation between apparent GA growth and baseline neovascular lesion type (P < 0.001). Treatment-naive neovascular age-related macular degeneration eyes with Type 1 neovascularization at baseline were less likely to develop GA than eyes with other types. The correlation between apparent GA growth and subtype of neovascularization is stronger when lesions are classified with an anatomic grading that utilizes both FA and SD-OCT.

Anthropomorphic breast phantoms with physiological water, lipid, and hemoglobin content for near-infrared spectral tomography

Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging from 30% for the adipose simulant to 80% for the tumor. Mean measured water content ranged from 30% in simulated adipose to 73% in simulated tumor with the higher water localized to the tumor-like material. This novel heterogeneous phantom design is composed of physiologically relevant concentrations of the major optical absorbers in the breast in the near-infrared wavelengths that should significantly improve imaging system characterization and optimization because the materials have stand-alone structural integrity and can be readily molded into the sizes and shapes of tissues commensurate with clinical breast imaging.

Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide

The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant chemotherapy (NAC) was analyzed. Dynamic NIRS imaging was performed at different time points during treatment. The maximum tumor dynamic changes in deoxy-hemoglobin increased from less than 7% at cycle 1, day 5 (C1, D5) to 17% at (C1, D28), which indicated a complete response to NAC early during treatment and was subsequently confirmed pathologically at the time of surgery.

Characterization of materials for optimal near-infrared and x-ray imaging of the breast

Development of a detector case for complete co-registration of images in a non-fiber-based combined near-infrared spectral tomography and digital breast tomosynthesis, required analysis to find materials that could support a breast under full mammographic compression without affecting the x-ray images or the quality of the near infrared measurements. Several possible solutions were considered, and many types of plastics were tested in the development of the detector case. Light channeling within the detector case changed the data obtained in resin and agarose phantoms, lowering recovered absorption values. Additional developments focusing on blocking stray light were successful and permitted a normal subject imaging exam.

A digital x-ray tomosynthesis coupled near infrared spectral tomography system for dual-modality breast imaging

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as anatomical priors in optical image reconstruction. Currently, the total scan time for a combined NIRST-DBT exam is ~50s with data collection from 8 wavelengths in the optical scan requiring ~42s to complete. The system was tested in breast simulating phantoms constructed using intralipid and blood in an agarose matrix with a 3 cm x 2 cm cylindrical inclusion at 1 cm depth from the surface. Diffuse image reconstruction of total hemoglobin (HbT) concentration resulted in accurate recovery of the lateral size and position of the inclusion to within 6% and 8%, respectively. Use of DBT structural priors in the NIRST reconstruction process improved the quantitative accuracy of the HbT recovery, and led to linear changes in imaged versus actual contrast, underscoring the advantages of dual-modality optical imaging approaches. The quantitative accuracy of the system can be further improved with independent measurements of scattering properties through integration of frequency or time domain data.

Near-infrared spectral tomography integrated with digital breast tomosynthesis: effects of tissue scattering on optical data acquisition design.

Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT∕NIRST system for comparison with simulation results. Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking gelatin phantoms. Accurate characterization of scattering is necessary for quantification of hemoglobin. Based on this study, a system design is described to optimally combine breast tomosynthesis with NIRST.

Broadband frequency-domain near-infrared spectral tomography using a mode-locked Ti:sapphire laser

Frequency-domain near-infrared (NIR) diffuse spectral tomography with a mode-locked Ti:sapphire laser is presented, providing tunable multiwavelength quantitative spectroscopy with maximal power for thick tissue imaging. The system was developed to show that intrinsically high stability can be achieved with many wavelengths in the NIR range, using a mode-locked signal of 80 MHz with heterodyned lock-in detection. The effect of cumulative noise from multiple wavelengths of data on the reconstruction process was studied, and it was shown that inclusion of more wavelengths can reduce skew in the noise distribution. This normalization of the data variance then minimizes errors in estimation of chromophore concentrations. Simulations and tissue phantom experiments were used to quantify this improvement in image accuracy for recovery of tissue hemoglobin and oxygen saturation.

Measurement of pressure-displacement kinetics of hemoglobin in normal breast tissue with near-infrared spectral imaging

Applying localized external displacement to the breast surface can change the interstitial fluid pressure such that regional transient microvascular changes occur in oxygenation and vascular volume. Imaging these dynamic responses over time, while different pressures are applied, could provide selective temporal contrast for cancer relative to the surrounding normal breast. In order to investigate this possibility in normal breast tissue, a near-infrared spectral tomography system was developed that can simultaneously acquire data at three wavelengths with a 15 s time resolution per scan. The system was tested first with heterogeneous blood phantoms. Changes in regional blood concentrations were found to be linearly related to recovered mean hemoglobin concentration (Hb(T)) values (R(2)=0.9). In a series of volunteer breast imaging exams, data from 17 asymptomatic subjects were acquired under increasing and decreasing breast compression. Calculations show that a 10 mm displacement applied to the breast results in surface pressures in the range of 0-55 kPa depending on breast density. The recovered human data indicate that Hb(T) was reduced under compression and the normalized change was significantly correlated to the applied pressure with a p value of 0.005. The maximum Hb(T) decreases in breast tissue were associated with body mass index (BMI), which is a surrogate indicator of breast density. No statistically valid correlations were found between the applied pressure and the changes in tissue oxygen saturation (S(t)O(2)) or water percentage (H(2)O) across the range of BMI values studied.

Electromagnetic Breast Imaging: Results of a Pilot Study in Women with Abnormal Mammograms

To prospectively assess quantitatively the inherent contrast of electromagnetic (EM) properties that can be imaged by using available technology in women with abnormal findings at conventional breast imaging who underwent subsequent biopsy. The protocol was HIPAA compliant and approved by the institutional review board. All participants provided informed consent. Fifty-three women with normal (Breast Imaging Reporting and Data System [BI-RADS] category 1) and ninety-seven women with abnormal (BI-RADS category 4 or 5) screening mammograms were imaged with three EM imaging methods: electrical impedance spectroscopy (EIS), microwave imaging spectroscopy (MIS), and near-infrared spectral tomography (NIR). A region-of-interest (ROI) analysis was used to assess the EM image properties for comparison of findings with conventional image findings and correlation with specific pathologic parameters for women with abnormal findings. Statistical analyses were conducted. One hundred fifty participants (age range, 35-81 years) were included. EM image property contrast ratios of 150%-200% were found in breast abnormality ROIs relative to the ipsilateral breast background. Analysis of variance demonstrated significant differences in ROI image summaries of mammographically normal versus abnormal breasts for EIS, across diagnostic groups for NIR, and for MIS (analysis restricted to lesions larger than 1 cm(3)). Receiver operating curve (ROC) analysis of the EM properties for cancers among subjects with BI-RADS category 4 or 5, compared with the EM properties for the subjects with normal breasts (BI-RADS category 1), yielded areas under the ROC curve ranging from 0.67 to 0.81. Pathologic correlations with mean vessel density, mean vessel area, and epithelium-to-stroma ratio suggest a biological origin of the EM image properties associated with disease. Results from EM breast examinations provide statistical evidence of a mean increase in image contrast of 150%-200% between abnormal (benign and malignant) and normal breast tissue.

Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography.

Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images.

Three-dimensional simulation of near-infrared diffusion in tissue: boundary condition and geometry analysis for finite-element image reconstruction

Imaging of tissue with near-infrared spectral tomography is emerging as a practicable method to map hemoglobin concentrations within tissue. However, the accurate recovery of images by using modeling methods requires a good match between experiments and the model prediction of light transport in tissue. We illustrate the potential for a match between (i) three-dimensional (3-D) frequency-domain diffusion theory, (ii) two-dimensional diffusion theory, (iii) Monte Carlo simulations, and (iv) experimental data from tissue-simulating phantoms. Robin-type boundary conditions are imposed in the 3-D model, which can be implemented with a scalar coupling coefficient relating the flux through the surface to the diffuse fluence rate at the same location. A comparison of 3-D mesh geometries for breast imaging indicates that relative measurements are sufficiently similar when calculated on either cylindrical or female breast shapes, suggesting that accurate reconstruction may be achieved with the simpler cylindrical mesh. Simulation studies directly assess the effects from objects extending out of the image plane, with results suggesting that spherically shaped objects reconstruct at lower contrast when their diameters are less than 15-20 mm. The algorithm presented here illustrates that a 3-D forward diffusion model can be used with circular tomographic measurements to reconstruct two-dimensional images of the interior absorption coefficient.