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A cohort of N=42 breast lesions has been imaged in-situ with a structured light imaging system through an ongoing clinical study. Multispectral, high spatial frequency scatter images provide additional modes contrast across the tumor-normal boundary.

For the first time in history it is possible to image radiation dose delivered to patients in radiation therapy for cancer, by capturing the Cherenkov light emissions coming from their tissue. These light signals can also be used to excite molecular probes to assay tissue function and potentially response to therapy.

Analysis of MRI parameters together with NIRS values (n=28 subjects) shows that the combinations of Ktrans with either HbT or TOI have high diagnostic accuracy, increasing AUC values to 93-94% and specificity up to 100%.

Multi-parameter functional image guidance is demonstrated to regularize NIRS tomography with MRI dynamic contrast and water diffusion. The approach shows increased contrast in the tumors from 1.76 to 2.23, relative to a regular MRI guidance approach.

Analysis of breast DCE-MR and NIR tomography imaging of 17 NAC patients showed combined pre-TX contrast intensity and HbT were statistically significant in differentiating the patients with versus without complete pathological response (AUC=0.94).

A portable hybrid frequency domain (FD) - continuous wave (CW) Near-Infrared spectroscopy system has been developed for breast imaging. Physiologically reasonable values of chromophore concentrations were recovered for normal subject measurements.

Sub-diffusive structured light imaging can quantitate the density of scatterers versus their size scale distribution in a wide-field geometry. Phantoms with unique fractal distributions and n=22 fresh human breast specimens are imaged and analyzed.

Results of simulation and patient image reconstructions showed that a distance-constrained direct regularization can improve MRI guided near-infrared breast image quality in terms of less artifacts and higher HbT contrast of the tumor to normal tissue.

Cherenkov light emission occurs when high energy radiation (E>220keV) travels through tissue. This optical signal is used for molecular tracer imaging, radiation dose imaging, or molecular sensing in vivo. Human and animal studies are demonstrated.

Cerenkov light emission from MeV gamma-ray and electron beam delivery has recently been shown to be detectable and could be used in some applications for 3D dosimetry in radiation therapy in water tanks[1-3] or 2D surface dosimetry in humans[4, 5]. The major potential benefit of Cerenkov imaging is that it is a way to image beams in real time with several frames per second. As such, it is feasible to image treatment beams dynamically, and create composite visualizations of the treatment plans. This imaging can be used to verify new treatment plans prior to application to patients, or to quickly verify new machines, or testing in situations where access is limited. The strength of this optical imaging is that it is simple to implement, and provides immediate feedback. The drawbacks are related to minor differences between Cerenkov emission and dose, which make it not an exact measurement of dose.

This study describes the use of high spatial frequency imaging to quantitatively map the anisotropic scattering phase function distribution in tissue.

Molecular guided surgery is just now reaching substantial clinical trials stage, with multiple imaging systems, and a groundswell of GMP fluorescent molecular probes. Quantifying receptor expression is one potential way to guide cancer surgery.

This study develops a correction for absorption-based distortions in ratiometric assessments of fluorescent markers that are sampled at different wavelengths.

This study uses simulations to characterize the light path travelled by reflectance and fluorescence photons for multiple sampling geometries and describes the unique sensitivities of each to background optical properties.

The contrast in wide field imaging is dominated by molecular absorbers. By illuminating with high spatial frequency structured light and imaging its perturbation, we demonstrate insensitivity to absorbance and enhance ultrastructure sensitivity.

A cohort of 15 normal women were imaged using a combined CW NIR tomography and breast tomosynthesis unit, as well as a handheld frequency domain NIR probe and three different methods for scattering estimation were compared.

Recently, a validated tissue optics plug-in based on the GEANT4 Monte Carlo framework was developed for radiation-induced light transport. Here we extend the work and highlight its applicability to more general biophotonics simulations.

Fluorescence tomography of tracers enhances accuracy when MRI Gadolinium-contrast difference is used as implicit prior data. This approach improves over using simpler post-contrast images, yet preserves the elegance of non-segmentation based priors.

A breast imaging clinical trial involving 60 patients using a MRI-guided frequency domain-continuous wave near infrared spectroscopic tomography system was completed. Optical images were reconstructed with and without frequency domain phase data.

A fluorescence-guided surgery method is presented using tracer kinetics to exploit contrast in differential molecular expression of EGFR in glioblastoma multiform. Results suggest kinetic analysis can improve resection over traditional intensity FGS.

A method of using temporal analysis of background room lights to drive the timing of image acquisition and enable real time fluorescence imaging in a brightly lit operating room with significant periodic variation in brightness has been developed.

We explore the use of the Cherenkov effect for real-time video-rate optical dosimetry of ionizing radiation beams for quality assurance and verification of dynamic intensity modulated radiation therapy and volumetric modulated arc therapy plans.

Cherenkov photons generated during radiation therapy excite a phosphorescent agent, Platinum(II)G4, whose triplet lifetime is sensitive to pO2. Phosphorescence emission is measured at the boundary of rodent glioma subjects and beam-guided recovery is outlined for local pO2 estimation.

Fluorescence guided surgery is hampered by absorption and scatter, which confound interpretation of fluorescence. High-frequency fluorescence structured light imaging enables real-time model-independent absorption and scatter correction.

In vivo Cherenkov video imaging visualizes the process of external beam radiotherapy. Patient positioning, treatment verification, quality control, superficial dose and skin reaction estimation were explored for this technique, termed Cherenkoscopy.

A cohort of 34 normal, benign and malignant breasts were imaged using a combined NIR tomography and breast tomosynthesis unit with two views and compression levels, recovering region based estimates of hemoglobin, oxygen saturation, water and lipids.

Analysis of NIR tomography imaging of 19 patients undergoing neoadjuvant chemotherapy shows pre-TX tumor HbT was statistically significant in differentiating the patients with and without complete pathological response (P-value=0.01, AUC=0.92).

Structured light scatteroscopy resolves subtle morphological changes in tissue using high-spatial frequency illumination. Lumpectomy specimens were imaged immediately after resection demonstrating feasibility for intraoperative margin assessment.

A non-invasive fluorescence imaging approach is presented to quantify metastatic tumor burden in lymph nodes. The approach employs dual-tracer kinetic modeling to estimate concentrations of cancer-specific molecular markers

This study presents the validation of a tissue-optics software package capable of accurately performing Monte Carlo simulations of Cerenkov-based emission and induced fluorescence by interfacing with the open source radiation-optics transport package Gamos/Geant4.

This study shows the influence that the scattering phase function of Intralipid has on reflectance spectra. Significant spectral remission changes result from simply changing the reflectance probe geometries utilized in tissue spectroscopy research.

Combining nine discrete wavelengths for NIR Spectroscopy with MRI allows quantitative estimation of breast cancers in contrast scans. Combinations of PMT and spectrometers are used with validation in phantoms, normal subjects and pilot human cancers.

The design of a new hybrid breast optical imaging signal detection system is described using photodiodes together with PMTs. The goal of this design is to better quantify chromophores in tissue with a wider wavelength band.

Employing multiple time-bins in the image reconstruction of a time-domain fluorescence tomography dataset provides improved spatial resolution and contrast. Furthermore, these gains can be used to minimize tissue sampling and reduce imaging duration

A comparison of the Diffusion approximation and a Monte Carlo approach in the context of small animal fluorescence tomography is presented, forming a foundation for hybrid approaches to improve accuracy of fluorescence tomography.

Integration of localized molecular spectroscopy into standard medical imaging instrumentation has been slow in developing, yet today there have been major developments which make it achievable on a routine basis. Perhaps the most striking thing about optical imaging is the incredibly wide range of technologies available, and the correspondingly large range of resolutions in which they target, from microscopic imaging at 1 micron resolution, upto macroscopic imaging with 1–5mm resolution. The choice of technology must be done for the application desired. In cancer diagnosis and therapy monitoring, MR spectroscopy of tumors is done routinely in some centers, and the potential for near-infrared spectroscopy (NIRS) is also available. The American College of Radiology Imaging Network (ACRIN) has sponsored the first multicenter trial in NIRS to track response to neoadjuvant chemotherapy for breast cancer. NIRS can also be combined with image-guided recovery of the tissue components, using standard MR images, to quantify the spectroscopic features of breast cancer. A prototype system integrating NIRS into a 3T MR breast coil is outlined, and the ongoing study using the MR image as the template upon with spectroscopy is completed will be presented, with results from neoadjuvant chemotherapy monitoring. In radiology research, two prototype systems broadband spectral imaging of tissue are discussed, and it is shown that the spectral tomography system is ideal for fluorescence or emission tomography in vivo. This type of hybrid imaging is still in its infancy, yet using it to guide therapy or to properly individualize therapy choice is the next logical step. Use of MRI or CT as the backbone technology to exploit NIRS is a logical step for integration of this modality into clinical use. Imaging of molecular features is provided by this approach, such as Raman vibrational fingerprint of bone tissue, and uptake of multiple exogenous fluorescent agents in the same subject. Additional examples of how emission tomography could guide radiation therapy are demonstrated. In imaging for surgical guidance, molecular tracers such as Epidermal Growth Factor and Protoporphyrin IX are shown to be increased in glioma tumors, and are providing actually superior detection of the tumor tissue using standard white light surgical guidance. The state of the art in fluorescence guidance of surgery will be discussed, as well as future directions looking for peptide markers which could be translated to other tumor organ sites.

‘1click’ toolbox for tetrahedral mesh generation is presented that uses stack of 2D images with multiple regions. GUI-based approach to quality inspection and optimization of mesh bridges the gap from volume imaging to mesh generation.

Raman signal is measured through a tomography set-up with 8 distinct spectrometers allowing for increased spectral resolution. Reconstructed images show good localization and contrast of Raman signal to background for Teflon inclusions within gelatin-based phantoms.

A scanning full-spectrum imaging system was used to image and analyze the spectral morphology of resected breast cancer specimens, to evaluate the optimum parameters from which to diagnose involvement of cancer in the margins. Article not available.

This work studies an approach to combine tomosynthesis breast imaging with near infrared spectroscopy to determine tissue chromphore concentrations using spatial prior tomosythesis data and correlated scatter information.

It is shown that an analytic expression of fluorescence ratio detection can provide a direct estimate of depth in multi-spectral sub-surface imaging. This is supported by preliminary fluorescence data acquired with a broad-beam multi-spectral system.

A broadband scanning scatter spectroscopy imaging system has been developed to allow intra-operative assessment of lumpectomy tumor margins based on localized tissue scatter measures. Results from preliminary phantom measurements are discussed.

A surface-shrinking algorithm is demonstrated for automated source position localization one scattering depth into discretized simulation domains, in near-infrared imaging. The algorithm allows users to accurately place source fiber locations with minimal guidance.

A novel hybrid method combining 3-D FE and BE techniques has been implemented for modeling light diffusion combining homogeneous and heterogeneous regions. Results show less than 1% difference in boundary data between the different models.

Accuracy and resolution of image guided near-infrared spectroscopy for breast imaging is characterized through simulations of varying contrasts and sizes. Results show errors of %4 for sizes greater than 20mm, but higher for smaller sizes.

The dynamic vascular change in the breast due to the pressure-displacement kinetics and inspired gas dynamics are imaged by a frequency domain tomographic system with 20 second temporal resolution.

Optimized bands of wavelengths in spectral optical imaging is presented showing improvement in cross talk between parameters. A normalization technique is presented which creates a more uniform update within a spectral image reconstruction model.

A NIR diffuse optical tomography system with spectrally-encoded sources at two wavelength bands allows simultaneous detection at high speed. It works with MR to provide images of high-contrast, fast changes in tissue oxygen saturation.

An automated ultrasound-guided fluorescence tomography system was created to image the Protoporphyrin IX production of subcutaneous tumors in vivo. Negative production and positive production tumors were compared to validate the system capability.