The overall goal of this proposal is to develop a dual-modality single photon emission computed tomography (SPECT) and x-ray computed mammotomography (CmT) scanner for dedicated breast and axillary imaging, and to incorporate this system into routine diagnostic breast healthcare. We are the first group to conceive, implement, and begin to clinically evaluate such a dual-modality molecular breast imaging device. In the first 5- year period of this project, three dedicated human breast imaging devices were developed and fully characterized: SPECT, CmT and a hybrid device integrating the two. The imaging performances exceeded the expectations and goals of the original Specific Aims. For the SPECT subsystem, we integrated a high- performance semiconductor detector on a novel gantry capable of arbitrary, fully 3-dimensional (3D) trajectories. We imaged smaller lesions with lower simulated biological uptake than has been imaged by others. For the CmT subsystem, we developed an innovative and robust quasi-monochromatic x-ray cone beam that can provide 3D anatomical images with isotropic resolution throughout a uniformly sampled breast volume. We have shown statistically significantly improved observer detectability of small, low contrast lesions in breast phantoms compared with 2D digital x-ray mammography. Importantly, this CmT system helped yield these results with total absorbed dose below that of dual-view screening mammography. The integrated hybrid system has been thoroughly characterized with phantom imaging studies, successfully used in imaging women with breast cancer, and yielded high quality 3D registered and fused images. This 4-year continuation proposal includes incorporation of our existing hybrid imaging device into an ongoing NIH funded hyperthermia breast therapeutics clinical trial. This trial will evaluate the semiquantitative 3D radiopharmaceutical-loaded liposome biodistributions in 40 human subjects. Using a narrow edge digital flat-panel detector developed specifically for this proposal, along with a compact x-ray source-filtration combination allowing real-time scatter correction measurements, a totally new CmT subsystem will be developed, providing enhanced anterior chest wall imaging. This new geometrically optimal and patient friendly system will be the first hybrid imaging technology to allow isotropically uniform imaging of the full breast and axillary nodes. Both subsystems will provide fully-3D high resolution data for our generalized iterative reconstruction code that will incorporate motion, scatter and attenuation corrections. The new system will be characterized and calibrated to provide absolute signal quantification to within 5% of known values. This new hybrid mammotomography system will be evaluated in 20 locally advanced breast cancer patients, so that the variance of image parameters can be determined with a modified BIRADS lexicon, and statistical power can be determined for a Phase 2 clinical trial. Given our positive developments and results thus far, we think it is likely that our new hybrid SPECT-CmT system will prove to be a valuable clinical tool.

Public Health Relevance

The overall goal of this research proposal is to develop and evaluate dedicated three-dimensional (3D) breast imaging, termed """"""""mammotomography,"""""""" simultaneously capable of functional-emission imaging with SPECT and anatomical-transmission imaging with CT of a pendant, uncompressed breast and associated axillary regions. Significant strides were made in the first 5-year period, and this revised proposal presents a paradigm changing approach to dedicated breast imaging that is expected to result in better clinical interpretation and quantification of information from the combined imaging modalities, and ultimately lead to better diagnosis for and monitoring of breast cancer, which is of great importance in the public and personal health problem of breast cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Zhang, Yantian
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Duke University
Schools of Medicine
United States
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Mann, Steve D; Tornai, Martin P (2015) Characterization of simulated incident scatter and the impact on quantification in dedicated breast single-photon emission computed tomography. J Med Imaging (Bellingham) 2:033504
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Mann, Steve D; Perez, Kristy L; McCracken, Emily K E et al. (2012) Initial In Vivo Quantification of Tc-99m Sestamibi Uptake as a Function of Tissue Type in Healthy Breasts Using Dedicated Breast SPECT-CT. J Oncol 2012:146943
Shinnar, Shlomo; Bello, Jacqueline A; Chan, Stephen et al. (2012) MRI abnormalities following febrile status epilepticus in children: the FEBSTAT study. Neurology 79:871-7
Pachon, Jan H; Shah, Jainil; Tornai, Martin P (2011) Characterization of Image Quality for 3D Scatter Corrected Breast CT Images. Proc SPIE Int Soc Opt Eng 7961:
Shah, Jainil; Pachon, Jan H; Madhav, Priti et al. (2011) Detailed Characterization of 2D and 3D Scatter-to-Primary Ratios of Various Breast Geometries Using a Dedicated CT Mammotomography System. Proc SPIE Int Soc Opt Eng 7961:
Perez, Kristy L; Cutler, Spencer J; Madhav, Priti et al. (2011) Towards Quantification of Functional Breast Images Using Dedicated SPECT With Non-Traditional Acquisition Trajectories. IEEE Trans Nucl Sci 58:2219-2225
Crotty, Dominic J; Brady, Samuel L; Jackson, D'Vone C et al. (2011) Evaluation of the absorbed dose to the breast using radiochromic film in a dedicated CT mammotomography system employing a quasi-monochromatic x-ray beam. Med Phys 38:3232-45
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Perez, K L; Cutler, S J; Madhav, P et al. (2010) Characterizing the contribution of cardiac and hepatic uptake in dedicated breast SPECT using tilted trajectories. Phys Med Biol 55:4721-34

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