Periodic Reporting for period 3 - InSiDe (Integrated silicon photonics for Cardiovascular Disease monitoring)
Reporting period: 2023-01-01 to 2024-12-31
The unmet need to accelerate the access for the medical community to a new prototype of a diagnostic device, based on a silicon photonics integrated circuit, able to identify and characterize different stages of cardiovascular diseases while proving its efficacy to drive the proper therapy adoption and to monitor its evolution, in order to reduce the healthcare costs and improve patient outcome, will be the rationale and driver of the InSiDe project.
Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, valvular disease and other conditions. CVDs take the lives of 17.9 million people every year, 31% of all global deaths. Of these deaths, 85% are due to myocardial infarction (heart attack) secondary to coronary heart disease (7.3 million) and stroke (6.2 million). Individuals at risk of CVD may demonstrate raised blood pressure, glucose, and lipid levels as well as overweight and obesity. These can all be easily measured in primary care facilities. Identifying those at highest risk of CVDs and ensuring they receive appropriate treatment can prevent premature deaths.
There is a huge interest in deploying the optimal diagnosis to institute a timely preventative therapy among those individuals considered to be at low or moderate risk according to current guidelines.
Assessment of arterial stiffness by measurement of aortic pulse wave velocity (aPWV) is included in the latest guidelines for cardiovascular risk prediction – arterial stiffness is an early marker for hypertension. Early identification of arterial stenosis and heart dyssynchrony can be used to improve CVD risk classification. However, no tools are available today to screen a large population under primary care for these indicators, and individuals that are considered to be at low or moderate risk are too often undiagnosed.
The InSiDe project is a follow-up of the successful CARDIS project on ‘Early-stage cardiovascular disease detection with integrated silicon photonics’. All efforts in InSiDe are geared towards providing a solution for monitoring/diagnosing presymptomatic cardiovascular diseases (CVD) as well as to assist monitoring of CVD disease progression in order to keep patients in their home environment and still intervene in due time to prevent unnecessary progression of their CVD condition.
The objective of InSiDe is to provide access for the medical community to a new diagnostic device, based on a silicon photonics integrated homodyne laser interferometer, able to identify and characterize different stages of cardiovascular diseases proving its efficacy to drive an indicated therapy institution and to monitor its follow-up, in order to reduce the healthcare costs and improve patients outcome.
The objective of the InSiDe project is to take the CARDIS device a major step further towards commercialization by means of the following steps:
• Development and release of a true handheld, battery operated, wireless clinical investigational split device, which can be operated as one unit for arterial stenosis and dyssynchrony measurements as well as two separate units for PWV measurements.
• To demonstrate in clinical feasibility studies with the developed clinical investigational device that it is useful for GPs and cardiologists.
Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, valvular disease and other conditions. CVDs take the lives of 17.9 million people every year, 31% of all global deaths. Of these deaths, 85% are due to myocardial infarction (heart attack) secondary to coronary heart disease (7.3 million) and stroke (6.2 million). Individuals at risk of CVD may demonstrate raised blood pressure, glucose, and lipid levels as well as overweight and obesity. These can all be easily measured in primary care facilities. Identifying those at highest risk of CVDs and ensuring they receive appropriate treatment can prevent premature deaths.
There is a huge interest in deploying the optimal diagnosis to institute a timely preventative therapy among those individuals considered to be at low or moderate risk according to current guidelines.
Assessment of arterial stiffness by measurement of aortic pulse wave velocity (aPWV) is included in the latest guidelines for cardiovascular risk prediction – arterial stiffness is an early marker for hypertension. Early identification of arterial stenosis and heart dyssynchrony can be used to improve CVD risk classification. However, no tools are available today to screen a large population under primary care for these indicators, and individuals that are considered to be at low or moderate risk are too often undiagnosed.
The InSiDe project is a follow-up of the successful CARDIS project on ‘Early-stage cardiovascular disease detection with integrated silicon photonics’. All efforts in InSiDe are geared towards providing a solution for monitoring/diagnosing presymptomatic cardiovascular diseases (CVD) as well as to assist monitoring of CVD disease progression in order to keep patients in their home environment and still intervene in due time to prevent unnecessary progression of their CVD condition.
The objective of InSiDe is to provide access for the medical community to a new diagnostic device, based on a silicon photonics integrated homodyne laser interferometer, able to identify and characterize different stages of cardiovascular diseases proving its efficacy to drive an indicated therapy institution and to monitor its follow-up, in order to reduce the healthcare costs and improve patients outcome.
The objective of the InSiDe project is to take the CARDIS device a major step further towards commercialization by means of the following steps:
• Development and release of a true handheld, battery operated, wireless clinical investigational split device, which can be operated as one unit for arterial stenosis and dyssynchrony measurements as well as two separate units for PWV measurements.
• To demonstrate in clinical feasibility studies with the developed clinical investigational device that it is useful for GPs and cardiologists.
Based on the completed system design, subsystems for the clinical investigational device were manufactured in sufficient quantities to deliver a number of systems.
A custom designed program for device control and wireless connection to the devices was made. The software has a graphic user interface and algorithms that calculate PWV based on synchronized time series data received from 2 devices measuring skin vibrations over 2 superficial arteries.
Engineering prototypes were made and used to show the feasibility to conduct direct skin measurements as opposed to using a retroreflective patch attached as was the case for CARDIS.
Development, manufacturing and assembly activities were conducted in accordance with Medtronic’s quality procedure with the aim to release a clinical investigational device. However, due to technical problems concerning the wireless connection between the devices and the computer, InSide did not succeed in releasing a clinical investigational device. The effect of this has in a way been mitigated by using CARDIS devices, made in Period 2, for a series of clinical studies.
An algorithm for automated LDV measurement of carotid-femoral PWV was calibrated and tested using CARDIS data, and implemented in the InSiDe software. Similarly, we tested and implemented an algorithm for the LDV-based assessment of heart-carotid PWV, a new biomarker which specifically samples the most elastic part of the aorta. For this study, we used newly acquired LDV data in 100 subjects, including cardiac magnetic resonance imaging data. Furthermore, we developed and tested algorithms for the assessment of heart sound features from LDV which may provide a novel diagnostic tool to assess cardiac dyssynchrony and heart valve defects. Finally, algorithms for the detection of carotid artery stenosis from LDV data features have been tested and implemented in the InSiDe software. Data for the 2 latter studies were newly acquired using CARDIS hardware coupled to InSiDe software.
A custom designed program for device control and wireless connection to the devices was made. The software has a graphic user interface and algorithms that calculate PWV based on synchronized time series data received from 2 devices measuring skin vibrations over 2 superficial arteries.
Engineering prototypes were made and used to show the feasibility to conduct direct skin measurements as opposed to using a retroreflective patch attached as was the case for CARDIS.
Development, manufacturing and assembly activities were conducted in accordance with Medtronic’s quality procedure with the aim to release a clinical investigational device. However, due to technical problems concerning the wireless connection between the devices and the computer, InSide did not succeed in releasing a clinical investigational device. The effect of this has in a way been mitigated by using CARDIS devices, made in Period 2, for a series of clinical studies.
An algorithm for automated LDV measurement of carotid-femoral PWV was calibrated and tested using CARDIS data, and implemented in the InSiDe software. Similarly, we tested and implemented an algorithm for the LDV-based assessment of heart-carotid PWV, a new biomarker which specifically samples the most elastic part of the aorta. For this study, we used newly acquired LDV data in 100 subjects, including cardiac magnetic resonance imaging data. Furthermore, we developed and tested algorithms for the assessment of heart sound features from LDV which may provide a novel diagnostic tool to assess cardiac dyssynchrony and heart valve defects. Finally, algorithms for the detection of carotid artery stenosis from LDV data features have been tested and implemented in the InSiDe software. Data for the 2 latter studies were newly acquired using CARDIS hardware coupled to InSiDe software.
With Medtronic, Microchip, imec, Tyndall, Argotech, the Universiteit Gent, Politecnico di Torino, INSERM and the Universiteit Maastricht, InSiDe is partnering European leaders in respectively medical devices, micro-electronics, silicon photonics and arterial biomechanics. InSiDe will help to secure their leadership by developing a new application that advances the existing background. In this collaboration, the partners will be sharing their experience and background for the purpose of creating a state-of-the-art CVD screening device that they would not be able to develop alone and in the same timeframe.
The possibility for earlier detection of risk for CVD makes it possible to start earlier treatment. In these early stages of the disease this could be achieved simply by a change in lifestyle and/or relatively cheap cholesterol lowering drugs such as statins. Thus, more complicated treatments, like stenting and ultimately cerebral and myocardial infarction may be prevented.
InSiDe will enable Medtronic to access a new market segment, Hypertension Management and extend its Diagnostics business, currently focused on Insertable Cardiac Monitors. Microchip has a well-established customer base in medical electronics, particularly in cardiac management, electro-stimulation and robotics as well as high speed communication modules. The Diagnostics market is however an area that Microchip is not currently strongly involved in and therefore offers a new revenue and product stream.
The new knowledge and expertise developed by imec, UGent and Tyndall in InSiDe will be made available to EU companies in the medical diagnostics market and other markets. It will be used to bring integrated photonics to the next level, for use in all kind of applications. It is the mission of these institutions to transfer technology to industrial partners so as to create an economical and societal impact with the developed technology.
Further information can be found on the InSiDe public website (www.inside-h2020.eu).
The possibility for earlier detection of risk for CVD makes it possible to start earlier treatment. In these early stages of the disease this could be achieved simply by a change in lifestyle and/or relatively cheap cholesterol lowering drugs such as statins. Thus, more complicated treatments, like stenting and ultimately cerebral and myocardial infarction may be prevented.
InSiDe will enable Medtronic to access a new market segment, Hypertension Management and extend its Diagnostics business, currently focused on Insertable Cardiac Monitors. Microchip has a well-established customer base in medical electronics, particularly in cardiac management, electro-stimulation and robotics as well as high speed communication modules. The Diagnostics market is however an area that Microchip is not currently strongly involved in and therefore offers a new revenue and product stream.
The new knowledge and expertise developed by imec, UGent and Tyndall in InSiDe will be made available to EU companies in the medical diagnostics market and other markets. It will be used to bring integrated photonics to the next level, for use in all kind of applications. It is the mission of these institutions to transfer technology to industrial partners so as to create an economical and societal impact with the developed technology.
Further information can be found on the InSiDe public website (www.inside-h2020.eu).