Periodic Reporting for period 4 - IXSI3D (Translating Hybrid Imaging for Interventions: Intra-operative Guidance and Evaluation using 2D and 3D Interventional X-ray Scintigraphy Imaging) Reporting period: 2020-06-01 to 2021-11-30 Summary of the context and overall objectives of the project The problemThe purpose of this IXSI3D project was to research, build and evaluate a hybrid x-ray/nuclear imaging device that enables interventional radiologists and surgeons to exploit the power of molecular imaging and x-ray in the operating theatre. Hybrid imaging systems, like the successful PET/CT and SPECT/CT, have revolutionized diagnostic medical imaging. Interventional hybrid imaging would require the simultaneous acquisition of live x-ray and live nuclear images from an identical viewpoint, not sequentially (as in SPECT/CT) or from different angles. Heretofore, this has been impossible, as the simple alignment of one component (gamma camera) obstructed the field of view of the others (x-ray tube and detector). To solve this I proposed a design using pinholes in the project proposal. However during the project I have invented a better alternative, called a dual-layer detector, which has been patented worldwide. Importance for societyIntra arterial radionuclide therapies including radioembolization are some of the most hopeful innovative treatments in the fight against cancer. One limitation of these therapies is the lack of guidance which causes substantial under treatment to guarantee safety.Therefore, we will construct and evaluate a highly innovative hybrid C-arm that can guide these therapies. This has the promise to make it more targeted and personalized, with shorter procedure times and better outcomes. Also other disease may profit from this technology including cardiology. This work has the strong interest of medical technology, physicians and patients. Overall objectivesSimultaneous hybrid imaging is technically ambitious but provides an exceptional return on investment, as shown by the high anticipations of PET/MRI. A clinically useful combination of X-ray and nuclear imaging must fulfill the following requirements or objectives:- Uncompromised live X-ray Imaging. - Simultaneous Hybrid Imaging. X-ray and nuclear images should be acquired simultaneously, hence without a delay, to guarantee lag-free overlap. - Tomographic 3D Imaging for peri-interventional assessments.- Motion free quantitative images for dosimetry.The final objective of this project is the demonstration of our technology in a clinical setting. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Period 1 dec 2015 – june 2017The project started with the pinhole concept as suggested in the proposal. This system was simulated in constructed in a physical prototype. Using this, image quality was evaluated for different collimators of the set-up. While successful test were conducted they also exposed flaws of the concept in terms of limited sensitivity and image resolution. As alternative a second concept was formulated, that places the gamma camera behind a x-ray flat panel detector and relies on the fact the x-ray is detector is mainly sensitive for the x-ray photons and partial transparent to the gamma photons. The gamma is equipped with a cone beam collimator so guarantees perfect overlap of the x-ray and nuclear images. For this a new prototype was constructed with the help of Philips Medical Systems. This company showed interest in our work and decided to support it with knowledge about x-ray imaging and by making x-ray parts available on loan for the project.Period 2 July 2017 – June 2018During this period the second prototype was further developed to show case its ability to do live x-ray/nuclear imaging in 2D and also in 3D. The live 2D experiments were documented and published. For the 3D part, reconstruction algorithm needed to be developed, implemented and evaluated. We have also shown that dosimetry is even possible at very low levels of radio-activity. As indicated by the work in the previous period, motion of organs is a detrimental factor in (quantitative) imaging. This can be compensated by exploiting the specific x-ray and nuclear capabilities of our concept as we have reported. Since in the interventional setting time is even more of critical factor as in the diagnostic setting we also investigated the possibilities of speeding up the acquisition. Especially when lung shunting is to be evaluated the acquisition can be as short as 1 minute.Besides reconstruction and simulations, we have also worked on the hardware, mainly the performance of the detector. We have researched the detrimental impact of the x-ray flux on the gamma camera and come up with a number of solutions, which were however too costly for our budget. Therefore a simpler design using an off focus collimator was tested and implemented. Period 3 July 2018 – Dec 2021In this period all the scientific work of the earlier stages of the project comes together, and the main objective is to come, at the end of the project, to a new clinical-grade scanner, which can be employed in a clinical setting to demonstrate the performance of our innovations. This required the construction of a C-arm gantry, that is able to hold the relatively heavy dual layer detector (150kg), the preparation of a Medical Device Dossier (constituting almost 1000 documents), approval of the Institutional Review Board for Medical Ethics clearance of applying the new technology in a patient study and finally the clinical study itself. Altogether this was a major achievement of our team, as few academic groups are used to complete the route from bench to bedside. I am very proud that we managed this and can now demonstrate our technology in clinical setting. We get enthusiastic response from both health care professionals and patients, and both value the potential to improve the quality of the intervention and the increased comfort and speed of the procedure. Besides this study we have disseminated the results of our work in a patent and more than 10 journal papers including top journals as Radiology. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The current state of the art in hybrid imaging is found in clinical and conceptual PET/CT, SPECT/CT and PET/MRI. Although they are in constant development, and improves are introduced by all major companies on a regular basis and the impact of these scanners is indisputable, these scanners however are dedicated to the diagnostic setting. No device exists yet that effectively makes the benefits of hybrid imaging available in the interventional setting. The purpose of this project was therefore to accomplish a hybrid C-arm that has the right features for interventional use.We have conceived an innovative dual-layer detector capable of acquiring both x-ray as nuclear images simultaneously and perfectly registered, all required for seamless integration in the intervention or operation theatre. We have simulated the device to evaluate technical aspect and build a working prototype to show case in reality. To support 3D imaging we have developed algorithm to convert data from the hybrid dual layer detector into quantitative 3D images, necessary for personalized dosimetry. In addition we shown that limitation of the dual-layer concept in x-ray flux and image quality can be mitigated using relatively simple adaptions to a standard clinical gamma camera. And finally we have translated our technology from bench to bedside by realizing a clinical grade interventional scanner (hybrid C-arm) and have demonstrated it in a clinical study with enthusiastic response from both health care professionals as patients. final setup of the constructed new medical imagin device (hybrid C-arm)
