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Digital Hybrid Breast PET/MRI for Enhanced Diagnosis of Breast Cancer

Periodic Reporting for period 3 - HYPMED (Digital Hybrid Breast PET/MRI for Enhanced Diagnosis of Breast Cancer)

Reporting period: 2019-01-01 to 2019-12-31

HYPMED will develop and evaluate a novel PET-RF insert for breast PET/MRI hybrid imaging. The project will integrate an innovative, fully digital MRI-transparent PET-detector directly into a novel, fully PET-transparent breast MRI surface coil. The PET-RF insert will allow precision imaging of breast cancer by combining high-resolution and ultra-low dose breast positron emission tomography (PET) with highest level structural and multi-parametric functional MR imaging.
The need for improved methods for cancer diagnosis is ever-increasing in parallel with the increasing demands of personalized medicine. The concept of targeted therapies requires not only knowing about the presence or absence of cancer, but also an analysis of a given cancer for appropriate treatment. PET and MRI provide functional and molecular information that is of pivotal importance for such treatment concepts. However, current approaches to PET/MR imaging lack the sensitivity that is essential for the type of information needed to guide tailored therapies. HYPMED will use a novel PET-RF insert to identify imaging correlates of molecular processes that are specific for carcinogenesis, i.e. tissue mechanisms that stimulate cancer growth, metastatic potential of cancers.
The specific project objectives are:
• Technical development of a dedicated ultra-low-dose, ultra-high-sensitivity, PET-RF insert with biopsy capability as the ultimate tool for breast cancer diagnosis
• Development and evaluation of quantitative PET-MRI acquisition, image reconstruction, post-processing and visualization methods for the targeted application of breast cancer
• Establish the clinical use and diagnostic utility of the novel PET-RF insert
• Correlation of multiparametric functional imaging information with established and novel tissue-based biomarkers
By working towards these objectives we want to introduce a paradigm shift in the field of hybrid PET/MR imaging as a whole. Once the concept of a combined PET-RF insert for breast imaging proves successful, we plan to expand this approach to other clinical applications e.g. cardiac hybrid imaging, and hybrid imaging of the abdomen or soft tissue tumours. With such dedicated integrated PET-RF inserts, any conventional clinical MR-system can be used as a full-range hybrid system that allows one to exploit the full potential of simultaneous highest-level PET and MR imaging in a targeted fashion.
The mechanical designs of structural parts of the PET/RF insert, several subsystems of the PET/RF insert and the PET detector mounting system was finalised. The RF coil prototype was developed and tested, and safety measurements were performed. In terms of the PET detector the electronics prototypes were developed and tested (coincidence testing) and performance testing of prototype PET detector electronics inside the MRI environment was performed.
In terms of required software implementations that are needed to operate the device, MR-fingerprinting for different patients was investigated. Attenuation Maps for MR-DIXON based images showing the operation of the segmentation and the assignment of linear attenuation coefficient values were generated.
In terms of the clinical study ethical approval for several tracers among them 18FGD, 18FMISO and 18FCholin mpPET/MRI were obtained. Based on 150 patients for 18FGD mpPET/MRI and 40 patients for 18FCholin mpPET/MRI were included. In addition, a protocol entitled multiparametric 18F-Fluoroestradiol PET/MRI coupled with radiomics analysis and machine learning for prediction and assessment of response to neoadjuvant endocrine therapy in patients with hormone receptor+/HER2− invasive breast cancer was also approved. First results indicate that due to the complimentary information of different parameters 18FDG mpPET/MRI has the potential to improve diagnostic accuracy by lowering false positives. In addition, it was demonstrated that 18FDG mpPET/MRI allows accurate evaluation of the axillary status in breast cancer patients.
For tissue biomarkers more than 40 cases were examined by conventional immunohistochemistry. In parallel, the Opal-System is now established to allow parallel immunofluorescent stainings on the same slide with up to six fluorescent markers to study relations between the different cellular component between each other and their interplay with the tumour cells. A tissue collection of pre-invasive breast lesions with sufficient pathological and clinical data has been selected from a stock of 146 DCIS cases. Pure tumour cells were captured using laser microdissection from 19 DCIS stages. Extracted DNA quantity ranges between 2.2 ng and 78.8 ng. Reduced Representation Bisulfit Sequencing (RRBS), a large-scale high-resolution DNA methylation analysis, has been established for investigation of epigenetic aberrations.The RRBS technology has been set up on DNA samples from invasive ductal carcinoma.
In terms of dissemination activities, the stakeholder database was amplified, and online presence was maintained through the project website and appearance in social media. HYPMED was promoted on major congress events in the field. During the third project period project management ensured the legal, financial and day to day activities. As project coordinator, EIBIR liaised with the European Commission, facilitated effective information exchange within the consortium and addressed contractual and reporting requirements.
HYPMED develops a breast PET-RF insert with a more than twofold increase in sensitivity and resolution and the capability to perform PET- and MRI-guided biopsy. Due to the high sensitivity and low radiation dose involved, it will be indicated for many more clinical applications than ever before. The concept of HYPMED will greatly increase the availability of this technique, and, thus patients’ access to high-level molecular and functional breast imaging.
The accuracy and reliability of the non-invasive detection of breast cancer and of the delineation of its extent will be significantly improved. Beyond the mere diagnosis of presence or absence of breast cancer, we will improve the non-invasive biological classification of breast cancers, i.e. improve the assessment of its aggressiveness, in order to improve appropriate treatment selection.
The expected improved prediction of response, response assessment and prognostication in patients undergoing therapy will allow an earlier adaption in case of treatment failure. Based on the innovative PET-RF insert, HYPMED will enable a more accurate and early diagnosis of breast cancer and will provide new imaging biomarkers that are needed to guide local and systemic treatment of breast cancer. Moreover, the HYPMED approach can be translated to other areas.
The introduction the breast PET-RF insert will reduce the overall economic costs associated with breast cancer and pave the way for similar developments in prostate cancer, cardiac imaging, brain and abdominal imaging among others, bolstering the sustainability of the European healthcare system. The successful completion of HYPMED will unlock a new market that is estimated to amount to €100 million per year. In the beginning, this market will be exclusively served by the industry partners participating in the project. Extending the concept will to cardiac and prostate imaging will enlarge the market size to estimated €300 million per year.