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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - HYPMED (Digital Hybrid Breast PET/MRI for Enhanced Diagnosis of Breast Cancer)

Teaser

Summary

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:
â€¢ 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
â€¢ Development and evaluation of quantitative PET-MRI acquisition, image reconstruction, post-processing and visualization methods for the targeted application of breast cancer
â€¢ Establish the clinical use and diagnostic utility of the novel PET-RF insert
â€¢ 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.

Work performed

The PET-RF insert mechanical design was defined and the prototype components were tested. The high sensitive RF-coil and low-loss RF screen were designed and MR-compatible PET detector modules were developed. The full design lock/system construction set will start in the first half of 2019 and housing production will begin. The final phase coil and low-loss RF screen prototype are currently tested. Initial tests of the first version of the MR-compatible PET detector module sensors showed a promising performance.
Good progress was also made in terms of image reconstruction that is needed to operate the device. The PET reconstruction framework is ready to be tested with first measured data from the PET device.
It has been extended by a Random correction method based on delayed coincidences. A first test with measured data using a pre-clinical PET insert from a point source has been performed for debugging the algorithm. Also a quantitative MR-Fingerprinting sequence was adapted and extended by a water-fat separation approach. In the following the distinction between normal and cancerous tissue based on the quantitative MR Fingerprinting results will be investigated.
Work regarding the clinical use of the PET-RF insert and its diagnostic utility comprised the further preparation and refinements of ethical approval from the Federal Office for Radiation Protection (Germany). Also the regulatory framework for feasibility studies and product specific legal requirements has been acquired. For the intra-individual comparison of the diagnostic utility of multiparametric breast MRI alone vs. high-resolution PET-MRI 135 patients were included for 18FDG mpPET/MRI. mpPET/MRI of breast tumours and the whole body with various tracers was performed on 25 patients for 18FCholin mpPET/MRI.
For the correlation of multiparametric functional imaging information with established and novel tissue-based biomarkers a control series of different breast lesions has been generated to define different types of immune infiltrate and other components of the tumour microenvironment. Twenty two cases were already examined by conventional immunohistochemistry. An Opal-System was purchased to allow parallel immunofluorescent staining on the same slide 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 was selected. Pure tumour cells were captured using laser microdissection from 19 DCIS stages and DNA was extracted by magnetic beads technology. A large-scale high-resolution DNA methylation analysis was established for investigation of epigenetic aberrations and was set up on DNA samples from invasive ductal carcinoma.
Dissemination activities embraced the promotion of HYPMED through an annual newsletter, the project`s representation at major medical imaging conferences as well as the publication of peer reviewed articles. The project website (www.hypmed.eu) is constantly updated.

Final results

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 patientsâ€™ 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 â‚¬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 â‚¬300 million per year.