Sub-millimeter PET for Improving Outcomes in Breast Cancer

Institution: University of California, Davis
Investigator(s): Abhijit Chaudhari, Ph.D. -
Award Cycle: 2012 (Cycle 18) Grant #: 18IB-0018 Award: $149,332
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis

Initial Award Abstract (2012)

Molecular-level assessment of breast cancer is crucial for developing a detailed understanding of the how the disease originates and spreads. Current clinical and research tools however lack the ability to perform such analyses at a sub-millimeter level. Our overall goal is to develop a unique tool – a sub-millimeter resolution PET molecular imaging system– capable of accurately visualizing the molecular processes underlying breast cancer. The project aims are: (1) design and characterize the PET system with sub-millimeter resolving power; (2) integrate the system with the 1.5 mm resolution PET/CT scanner and validate the performance using test objects; (3) develop efficient image reconstruction techniques for rapid image generation; and (4) perform proof-of-concept studies on five breast cancer patients who are candidates of mastectomy. We will compare the imaging outcomes with pathology findings.

The proposed PET system will consist of a C-shaped partial ring of four detectors with high-density detection elements to allow for improved resolving power. We will develop a mechanical system to optimally integrate this PET system with the current breast PET/CT system, hence enabling high focusing power on regions of interest like the tumor site and ductal carcinoma in situ. We will perform detailed analysis of the detector performance and develop an improved image reconstruction method to best utilize the improved resolving power. Finally, we will perform proof-of-concept studies on five breast cancer patients who are candidates for mastectomy. We will compare the imaging outcomes with pathology results.

If successful, our novel device will be capable of performing detailed measurements of glucose utilization, hypoxia, angiogenesis or other key processes. This will unleash the potential to interrogate the tumor microenvironment in pre- and post-treatment conditions, accurately define disease extent, and produce detailed quantifiable maps of biological processes.

We anticipate that physicians and scientists will use this information to evaluate early response to neoadjuvant chemotherapy (NAC), choose individualized treatment regimens based on the affected areas, and rapidly test new advanced breast cancer therapies.

Final Report (2015)

Conventional PET/CT imaging systems are already having an evolving role in breast cancer management, with evidence that for tumors over 3 mm, such systems are capable of providing an earlier assessment of response to therapy compared to conventional techniques. For smaller lesions, which women now-a-days frequently present with, however, treatment response cannot be accurately quantified with these systems. The main limitation in this regard is the poor resolving power of these systems, which is typically 4-6 mm. We hypothesize that a PET system affording a sub-millimeter resolving power will provide detailed molecular-level assessment of cancer lesions in human patients. This knowledge can be capitalized upon to predict response to therapy earlier than currently used non-invasive techniques. Our scientific goals were to design and fabricate a proof-of-principle prototype for such a system, integrate it with the current breast PET/CT scanning device at our institution, develop software tools for processing the data from the device, and demonstrate the feasibility of the system for breast imaging.

The design and characterization of the PET detectors required for the system was successfully completed. Software tools were built to create computational models of the system to better understand trade-offs of the different candidate designs. Based on this work, the final design of the system with respect to the other components of the existing PET/CT scanner was completed. Regarding integration of this sub-mm system with the existing breast PET/CT system, we implemented changes to the design of the existing system that allowed for flexible trajectories of the sub-mm system. We designed data communication ports and an interface system that allowed us to switch between the existing and the sub-mm system rapidly. The complete integration of the sub-mm system however is ongoing. One barrier we faced was that we had to re-design the mechanical assembly of the existing system for obtaining optimal performance from the sub-mm system. We overcame this barrier, but lost time in the process. A second barrier was that of re-programming the software code for the commercial electronics used by the existing system. While we have made great strides in this regard with a new collaborator, this work is not completed yet and will continue. Recently we scanned our first breast cancer patient on the re-designed system. The resulting data are providing us a means to validate the data processing tools developed for the sub-mm system. We plan on writing grant proposals to the NIH and Department of Defense to continue this work.

Our major accomplishments during the project period were the development of a rapid prototyping technique for the design of new breast PET systems, validation of image processing methods for optimizing scanner performance, and the testing of tools for rapid derivation of imaging biomarkers from breast PET/CT images that would result from the sub-mm system. Our work resulted in one peer-reviewed manuscript, six conference abstracts (2 won trainee awards) and one patent application. The grant was instrumental in providing resources and training support to two post-doctoral fellows and an undergraduate student. The funding also allowed the investigators to engage with patient advocates of “Save Ourselves” and provide lectures regarding radiation dose and breast imaging to the community.

Non-rigid registration of serial dedicated breast CT, longitudinal dedicated breast CT and PET/CT images using the diffeomorphic demons method
Periodical:Physica Medica
Index Medicus: Phys Med
Authors: Santo J, Chaudhari AJ, Joshi AA, Ferrero A Yang K, Boone JM Badawi RD
Yr: 2014 Vol: PMID Nbr: 25022452 Abs: Pg: