The long-term goal of this project is to develop and optimize NIR breast tomography with the objective of identifying the most promising technical approaches which should progress into human studies designed to generate statistically-valid evidence of clinical potential. The scientific hypothesis is that optical signals in the NIR offer unparalleled opportunity to assess the molecular signatures in breast tissue available through both endogenous and exogenous contrast provided the technical challenges associated with tomographic imaging can be overcome. Clinical results obtained to date indicate that (1) NIR optical tomography when unaided by other imaging information is not likely to achieve the performance required to improve clinical decision-making in either a screening or diagnostic setting for small breast abnormalities (<1 cm), and (2) NIR optical tomography when guided by MR has significantly improved quantitative accuracy and spatial resolution which appear to make it amendable to optical characterization of breast lesions of less than 1 cm in size. These findings have motivated our proposal to continue to pursue MR-guided (MRg) NIR optical breast tomography because of the convincing evidence we have generated to date that MR guidance provides for the most accurate, spatially-resolved images of the tissue molecular characteristics that can be probed with NIR optical signals. The opportunity exists to explore potential imaging enhancements made available through exogenous agents in the MRg context as representing the most accurate data that can be obtained with either absorption or emission tomography. To realize the envisioned developments we have proposed (1) to customize a 3T breast imaging coil for simultaneous MR/NIR imaging in collaboration with Philips Medical that will incorporate a contact-insensitive fiber optic breast interface, (2) to advance the processing and reconstruction algorithms associated with concurrent use of MR images in the formation and display of volumetric NIR images of endogenous and exogenous chromophores, exogenous fluorophores and scattering parameters, (3) to optimize, evaluate and compare exogenous contrast MRg NIR imaging based on absorbing versus fluorescing agents through simulation and phantom studies, and (4) to extend the Aim 3 findings to human studies in the breast using GdTex in women with metastatic breast cancer and ICG in women with screen-detected breast abnormalities recommended for biopsy as proofs-of-principles in order to compare MRg NIR tomography of endogenous and exogenous chromophores with exogenous fluorophores when evaluated in combination with conventional contrast-enhanced breast MR. The contributions expected from the proposed research would lead to the imaging platforms required to compare directly exogenous and endogenous absorption contrast with exogenous fluorescence contrast under the optimal conditions of MRg in order to determine their respective sensitivity and specificity to breast pathology in future evaluative trials that would serve to define their relative merits and ultimately their potential clinical roles. PROJECT NARRATIVE The scientific hypothesis that underpins this project is that optical signals in the near infrared (NIR) offer unparalleled opportunity to assess the molecular signatures in breast tissue available through both endogenous and exogenous contrast provided the technical challenges associated with tomographic imaging can be overcome. Current clinical findings have motivated our proposal to pursue MR-guided (MRg) NIR optical breast tomography because of the convincing evidence we have generated to date that MR guidance provides for the most accurate, spatially-resolved images of the tissue molecular characteristics that can be probed with NIR optical signals. The contributions expected from the proposed research would lead to the imaging platforms required to compare directly exogenous and endogenous absorption contrast with exogenous fluorescence contrast under the optimal conditions of MRg in order to determine their respective sensitivity and specificity to breast pathology in future evaluative trials that would serve to define their relative merits and ultimately their potential clinical roles.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA069544-14
Application #
8305763
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Farahani, Keyvan
Project Start
1996-07-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
14
Fiscal Year
2012
Total Cost
$238,690
Indirect Cost
$81,332
Name
Dartmouth College
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
El-Ghussein, Fadi; Mastanduno, Michael A; Jiang, Shudong et al. (2014) Hybrid photomultiplier tube and photodiode parallel detection array for wideband optical spectroscopy of the breast guided by magnetic resonance imaging. J Biomed Opt 19:011010
El-Ghussein, Fadi; Jiang, Shudong; Pogue, Brian W et al. (2014) Comparison of magnetic resonance imaging-compatible optical detectors for in-magnet tissue spectroscopy: photodiodes versus silicon photomultipliers. J Biomed Opt 19:070502
Pogue, Brian W; Davis, Scott C; Leblond, Frederic et al. (2011) Implicit and explicit prior information in near-infrared spectral imaging: accuracy, quantification and diagnostic value. Philos Trans A Math Phys Eng Sci 369:4531-57
Mastanduno, Michael A; Jiang, Shudong; DiFlorio-Alexander, Roberta et al. (2011) Remote positioning optical breast magnetic resonance coil for slice-selection during image-guided near-infrared spectroscopy of breast cancer. J Biomed Opt 16:066001
Carpenter, Colin M; Pogue, Brian W; Jiang, Shudong et al. (2011) MR water quantitative priors improves the accuracy of optical breast imaging. IEEE Trans Med Imaging 30:159-68
Carpenter, C M; Rakow-Penner, R; Jiang, S et al. (2010) Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging. Med Phys 37:1638-46
Davis, Scott C; Samkoe, Kimberley S; O'Hara, Julia A et al. (2010) Comparing implementations of magnetic-resonance-guided fluorescence molecular tomography for diagnostic classification of brain tumors. J Biomed Opt 15:051602
Davis, Scott C; Samkoe, Kimberley S; O'Hara, Julia A et al. (2010) MRI-coupled fluorescence tomography quantifies EGFR activity in brain tumors. Acad Radiol 17:271-6
Li, Zhiqiu; Krishnaswamy, Venkataramanan; Jiang, Shudong et al. (2010) Rapid magnetic resonance-guided near-infrared mapping to image pulsatile hemoglobin in the breast. Opt Lett 35:3964-6
Carpenter, Colin M; Rakow-Penner, Rebecca; Jiang, Shudong et al. (2010) Inspired gas-induced vascular change in tumors with magnetic-resonance-guided near-infrared imaging: human breast pilot study. J Biomed Opt 15:036026

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