Periodic Reporting for period 2 - PIUR tUS (Tomographic 3D Ultrasound for Safe and More Cost Effective Vascular Diagnostics andTreatment Planning) Reporting period: 2018-05-01 to 2019-10-31 Summary of the context and overall objectives of the project "Ultrasound is a widely used imaging technology due to its differentiated properties from other imaging modalities – affordable price, availability, safety, and real-time capabilities. Ultrasound is therefore the imaging technology of choice for many clinical fields, including vascular, thyroid, and nerve diagnostics. Its role in the diagnostic and interventional markets is further growing due to increasing price pressure and safety concerns of healthcare providers. But ultrasound is mainly limited to two-dimensional imaging capabilities. With the exception of certain cardiac and pre-natal imaging scenarios for which three-dimensional ultrasound technologies had already existed, patients have to be sent to Computed Tomography (CT) or Magnetic Resonance (MR) scanning to acquire three-dimensional images for comprehensive diagnostics and treatment decisions.The idea of PIUR tomographic ultrasound (""PIUR tUS"") is to bridge the gap between two-dimensional ultrasound and alternative three-dimensional imaging modalities, while combining the benefits of each technology and eliminating most of their drawbacks. PIUR tUS extends any third-party ultrasound scanner with 3D capabilities, no matter if it is built by GE, Siemens, or any other vendor on the market. All that is needed is a digital video output to assure high-resolution imaging. A huge advantage over standard 3D-ultrasound technologies that are sometimes built into high-end ultrasound machines is the independence of the ultrasound transducer. While built-in 3D solutions are usually based on special matrix transducers with a limited frequency range, PIUR tUS produces tomographic images with the best-suited ultrasound transducer for the currently relevant clinical scenario. Tomographic images can be produced with a curved array transducer, if depth is required, or with a high-frequency linear transducer, if high resolution is required. The images are fully quantifiable and can be analyzed as multi-planar reconstructions or as volume renderings. Examples for its use are follow-ups of Endovascular Aneurysm Repairs or the diagnostics of peripheral arterial disease in the lower limb. In both cases, PIUR tUS is a safe alternative for CT or catheter angiography that expose patients to risks due to radiation and nephrotoxic contrast agents. Its 3D vascular mapping capabilities allow better planning of interventions, improve communication among doctors, and enable complete documentation of ultrasound examinations.The overall objectives of this project are the development and certification of a mobile, affordable, and extremely user-friendly 2nd Generation of PIUR´s current system, that will support additional clinical applications and an innovative sensor-tracking technology to produce the tomographic data. The project also includes several studies to produce clinical evidence to market the product to a wide range of clinical users after its release." Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Sensor-Tracking:Based on User and System Requirements, we have defined the overall system architecture of the Sensor Tracking system, and also provided a detailed description of the concept and architecture of the two main system components: 1) the Control Unit which contains the reconstruction software based on a deep learning module, namely a convolutional neural network (CNN); and 2) the Sensor Unit which is hardware attached to an ultrasound transducer that provides sensor data from an IMU to the Tracking Unit as additional input for its CNN.During the project, a sensor with sufficient accuracy of the reconstruction for the planned clinical applications could be developed. For accurate and efficient trajectory reconstruction, different algorithms have been prototyped and investigated. Final decision was for an image-based reconstruction method where probe-orientation measured by the Sensor Unit is being fed in for improved accuracy. A product-ready Sensor Unit has been developed, including both a dedicated PCB and the relevant firmware for operation of the tracking sensor. This final version of the Sensor Unit was subject to a series of certification-relevant tests, e.g. electric safety test and EMC test. Finally, we trained the CNN network for trajectory estimation with more than 5,000 datasets in order to produce a stable product version of the Sensor Tracking.Clinical Studies:All preparation work for the execution of the clinical studies of this project have been completed. This includes the preparation of a clinical studies planning document, as well as the necessary clinical studies documents to apply for ethics approval and run the studies at several clinical centers.Ethics approval for all four clinical studies of this projects has been completed. Total patient recruitment for each of the four clinical studies until the end of the reporting period is as follows:Study 1: Peripheral Arterial Disease (PAD) 181 of 200 scans completed Study 2: Conduit Mapping – 200 of 200 scans completedStudy 3: AV Fistula Evaluation – 127 of 200 scans completedStudy 4: Carotid Plaque Volume (CPV) – 149 of 200 scans completedAll studies have been submitted for publication to a peer-reviewed journal.Regulatory Strategy:We have established a quality management (QM) system at PIUR imaging according to ISO13485. This QM system has been certified by the notified body SIQ at the beginning of 2018. We have also prepared and submitted to the Notified Body the technical documentation for CE-certification of the PIUR tUS Infinity as a Class 1m medical device. In addition, we have CE-certified the system as a Class 1 medical device.Commercialisation Planning:We have put significant work in strengthening our brand image in the European and international market. To do so, we have redesigned our website and hired professional photographers and a video team to shoot promotional pictures and a video. The brand-building is part of a three-staged marketing and sales strategy and will increase the recognition of our brand in the market.We have also joined several European and non-European conferences as exhibitors to promote our brand and product to target customers and third-party medical device companies directly. We have generated a significant amount of clinical leads, contracted several distributors, and generated pre-orders for our new technology. 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 sensor-based solution that was developed during this project is a considerably more user- friendly and more flexible advancement of the current PIUR tUS system and can also be directly integrated into third-party ultrasound scanners. Complete arms and legs can be imaged and analyzed with the PIUR technology in seconds and for a price that is significantly less than that of a CT or MR. Our vision is to create a solution that enables doctors to navigate needles for biopsies or ablation of tumors faster and more accurately, and place stents without the need for C-arm suites. This will have a huge impact, especially in low-cost markets where access to expensive healthcare equipment might be limited outside the urban areas. Our technology is mobile, inexpensive and can provide rural areas with access to advanced diagnostic imaging possibilities. Final product: PIUR tUS Infinity - Video Box with Sensor Unit Tomographic ultrasound image of a long saphenous vein
