Periodic Reporting for period 5 - HYPMED (Digital Hybrid Breast PET/MRI for Enhanced Diagnosis of Breast Cancer)
Berichtszeitraum: 2021-03-01 bis 2022-06-30
HYPMED aimed at developing a novel medical device that will fundamentally improve the early diagnosis and biological characterisation of breast cancer. The consortium has successfully designed and built the “HYPMED device,” a positron emission tomography–radio frequency (PET–RF) insert for focused, i.e. localised, breast-directed PET/MR hybrid imaging. Whereas currently available hybrid PET/MR systems copy the whole-body approach traditionally pursued by conventional PET–CT, HYPMED introduces a new way of “thinking hybrid imaging.” This was sparked by the observation that conventional PET/MR systems proved to be of limited use for the depiction and characterization of the primary breast cancer inside the breast. HYPMED abandons the whole-body approach in favour of targeted imaging designed for high-end precision diagnostics of the breast. The consortium designed an innovative, fully digital and MRI-transparent PET detector that was integrated into a novel, fully PET-transparent, multi-channel breast MRI surface coil. HYPMED will help identify imaging correlates of molecular processes specific for carcinogenesis, i.e. tissue mechanisms that stimulate growth of cancers, maintain their metabolic homeostasis, and promote their metastatic potential.
The project achieved the following objectives:
• Development of a dedicated ultra-low-dose, ultra-high-sensitivity, PET–RF insert for double-breast hybrid PET-MR imaging and with integrated vacuum biopsy capability
• Development of quantitative PET-MRI acquisition, image reconstruction, post-processing and visualization methods for the targeted application of breast cancer
• “Head-to-head” comparison of the technical performance of the HYPMED device with a commercially available whole-body PET-MR system
• Collection of whole-body PET-MRI datasets of 367 patients with well-described breast cancer
• Identification of candidate immune-histochemical and genomic/epigenetic biomarkers that are representative of functional tumour features, for validation of current whole-body PET-MRI and future HYPMED-imaging findings
The project achieved the following objectives:
• Development of a dedicated ultra-low-dose, ultra-high-sensitivity, PET–RF insert for double-breast hybrid PET-MR imaging and with integrated vacuum biopsy capability
• Development of quantitative PET-MRI acquisition, image reconstruction, post-processing and visualization methods for the targeted application of breast cancer
• “Head-to-head” comparison of the technical performance of the HYPMED device with a commercially available whole-body PET-MR system
• Collection of whole-body PET-MRI datasets of 367 patients with well-described breast cancer
• Identification of candidate immune-histochemical and genomic/epigenetic biomarkers that are representative of functional tumour features, for validation of current whole-body PET-MRI and future HYPMED-imaging findings
Following finalisation of the mechanical design of structural parts of the PET–RF insert and the PET detector mounting system, the RF coil prototype was developed and tested, and safety measurements were performed. Electronics prototypes of the PET component were developed and tested (coincidence testing), and performance testing of prototype PET detector electronics inside the MRI environment was performed. The auxiliary systems were assembled, including the detector stacks, cooling system, power supply and associated cables and tubes. With the operational and control software prepared, the insert was introduced into the clinic for testing of its PET and MRI capabilities. In parallel, novel functional MR acquisition methods (MRI fingerprinting) were established and published. Using the PET component of the device, image reconstruction was gauged with a point source and phantoms. Successful data acquisition and image quality demonstrate the success of the integration of the scanner hardware and placement of the detector blocks. The head-to-head comparison of phantom measurements with HYPMED confirmed superior PET sensitivity compared to conventional whole-body PET-MR systems. The HYPMED device achieved a resolution of <1.5 mm – unattainable with conventional whole-body PET-MRI systems. Refinement will further improve PET resolution down to ~1 mm.
To test the diagnostic performance of conventional whole-body PET-MRI, 376 patients have been included, who received [18F]FGD, [18F]FMISO or [18F]choline as tracers. Histopathological specimen were shipped to enable pathological analyses. Whole-body PET-MRI data were analysed to assess diagnostic accuracy in terms of discrimination of benign and malignant lesions as well as characterization of tumour biology. All data (imaging and respective stage & histopathology information on cancers) have been stored in an anonymized database accessible to the HYPMED consortium for future comparison with the clinical performance of the HYPMED device.
The documentation and tests necessary for regulatory approval of the HYMPED device were investigated, concluding requirements for a feasibility study are very similar to those for approval for fundamental research with human subjects. Although the path for regulatory approval of the HYPMED device under the new MDR is uncertain, guidance was produced to outline the relevant norms and regulatory standards in risk management, electrical and biological safety, software and other areas, as well as design specifications and documentation of design processes. A design failure mode and effect analysis was done to identify and mitigate risks from operation, and to ensure radiation safety for patients, a specific absorption rate study conducted by NORAS, PHI and UKA was also described. The identified list of verification tests would effect a comprehensively verified system.
A tissue biobank consisting of 281 pre-invasive and invasive breast cancers and 30 normal samples was set up. For tissue biomarker development, cases were examined by conventional immunohistochemistry and by the Opal system to study relations between different cellular components and their interplay with tumour cells for correlation with whole-body PET-MR and HYPMED imaging findings.
Dissemination activities continued, and an online presence was maintained through the project website and social media. HYPMED was promoted at major congress events mostly via online formats due to COVID-19, but also onsite at ECR 2022. A dedicated HYPMED workshop held in March 2022 drew an audience of more than 270 attendees.
To test the diagnostic performance of conventional whole-body PET-MRI, 376 patients have been included, who received [18F]FGD, [18F]FMISO or [18F]choline as tracers. Histopathological specimen were shipped to enable pathological analyses. Whole-body PET-MRI data were analysed to assess diagnostic accuracy in terms of discrimination of benign and malignant lesions as well as characterization of tumour biology. All data (imaging and respective stage & histopathology information on cancers) have been stored in an anonymized database accessible to the HYPMED consortium for future comparison with the clinical performance of the HYPMED device.
The documentation and tests necessary for regulatory approval of the HYMPED device were investigated, concluding requirements for a feasibility study are very similar to those for approval for fundamental research with human subjects. Although the path for regulatory approval of the HYPMED device under the new MDR is uncertain, guidance was produced to outline the relevant norms and regulatory standards in risk management, electrical and biological safety, software and other areas, as well as design specifications and documentation of design processes. A design failure mode and effect analysis was done to identify and mitigate risks from operation, and to ensure radiation safety for patients, a specific absorption rate study conducted by NORAS, PHI and UKA was also described. The identified list of verification tests would effect a comprehensively verified system.
A tissue biobank consisting of 281 pre-invasive and invasive breast cancers and 30 normal samples was set up. For tissue biomarker development, cases were examined by conventional immunohistochemistry and by the Opal system to study relations between different cellular components and their interplay with tumour cells for correlation with whole-body PET-MR and HYPMED imaging findings.
Dissemination activities continued, and an online presence was maintained through the project website and social media. HYPMED was promoted at major congress events mostly via online formats due to COVID-19, but also onsite at ECR 2022. A dedicated HYPMED workshop held in March 2022 drew an audience of more than 270 attendees.
The HYPMED device offers a more than twofold increase in sensitivity and resolution compared with current whole-body PET-MR hybrid systems and offers the capability to perform PET- and MRI-guided biopsy – an important prerequisite for accurate histologic validation of findings of novel imaging methods. Due to the high sensitivity and thus low tracer dose involved, HYPMED will greatly expand the number of clinical applications, as well as the cost-effectiveness compared with current whole-body PET/MR systems. HYPMED will significantly improve the accuracy and reliability with which we will be able to detect and characterize invasive as well as non-invasive breast cancer, to delineate its extent, and to reliably predict and determine its response to systemic treatment. So HYPMED will improve the non-invasive biological classification of breast cancers, referred to as “imaging phenotyping,” to enable tailored treatment.
Moreover, the HYPMED device can be plugged into any given regular MR scanner, transferring it into a high-performance focused PET-MR hybrid system. This will substantially promote the availability of and demand for PET/MR hybrid imaging and, thus, patients’ access to high-level molecular and functional breast imaging.
Once a clinical study has established the diagnostic advantage of the HYPMED device, healthcare costs associated with breast cancer will be reduced. Moreover, the concept can be translated to other fields and could enable functional hybrid imaging of prostate cancer and cardiac, cerebral, and hepatobiliary disease, bolstering the sustainability of the European healthcare system. The successful completion of HYPMED will unlock a new market estimated to amount to €100 million/year.
Moreover, the HYPMED device can be plugged into any given regular MR scanner, transferring it into a high-performance focused PET-MR hybrid system. This will substantially promote the availability of and demand for PET/MR hybrid imaging and, thus, patients’ access to high-level molecular and functional breast imaging.
Once a clinical study has established the diagnostic advantage of the HYPMED device, healthcare costs associated with breast cancer will be reduced. Moreover, the concept can be translated to other fields and could enable functional hybrid imaging of prostate cancer and cardiac, cerebral, and hepatobiliary disease, bolstering the sustainability of the European healthcare system. The successful completion of HYPMED will unlock a new market estimated to amount to €100 million/year.