Periodic Reporting for period 2 - InSiDe (Integrated silicon photonics for Cardiovascular Disease monitoring)
Période du rapport: 2021-07-01 au 2022-12-31
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). Today, risk stratification is based on lifestyle indicators such as raised blood pressure, glucose, and lipid levels as well as overweight and obesity. These can all be easily measured in primary care facilities, thus identifying patients at highest risk of CVDs and ensuring they receive appropriate treatment to prevent premature deaths.
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. An early diagnosis will allow for timely preventative therapy, which will delay, stop or even to some extent reverse disease progression.
As such, the unmet need to accelerate the access for the medical community to a new prototype of a diagnostic device 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.
In order to allow for a low-cost high volume CVD screening device, the device will utilize a packaged photonic assembly based on a silicon photonics integrated circuit.
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 pre-symptomatic 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 Pulse Wave Velocity measurements.
• To demonstrate in clinical feasibility studies with the developed clinical investigational device that it is useful for GPs and cardiologists.
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. An early diagnosis will allow for timely preventative therapy, which will delay, stop or even to some extent reverse disease progression.
As such, the unmet need to accelerate the access for the medical community to a new prototype of a diagnostic device 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.
In order to allow for a low-cost high volume CVD screening device, the device will utilize a packaged photonic assembly based on a silicon photonics integrated circuit.
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 pre-symptomatic 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 Pulse Wave Velocity measurements.
• To demonstrate in clinical feasibility studies with the developed clinical investigational device that it is useful for GPs and cardiologists.
Based on user requirements and preliminary product specifications developed during Period 1, development of a clinical investigational device is being conducted per Medtronic product development procedure and is currently in the late stage of this development process.
A four beam Laser Doppler Vibrometer photonic chip has been fabricated using wafer scale processes and found functional. The LDV chip receives input from a 1310 nm laser assembly fabricated using large scale manufacturing processes. The Laser Doppler Vibrometer has been integrated into a hermetically sealed photonic package together with the first stage of the amplifier chain.
The photonic package interfaces to an optical system, which sends the four output beams of the on-chip LDV to four spots on the skin with a spacing of 5 mm.
Electronics for instrument control, data acquisition and wireless transmission of data have been designed and fabricated. The electronics have a powerful onboard processor to translate the raw LDV data into displacement data before they are transmitted to an external computer for further processing and data presentation.
Two methods, template matching and matrix profiling, were assessed using all available carotid-femoral and local carotid CARDIS datasets and found suitable for the automated quantification of signal quality using logistic regression modelling. Template matching is put forward as method of choice for the automated real-time identification of heart beats and grading of signal quality within the InSiDe device. An algorithm for determining carotid-femoral pulse wave velocity is proposed.
Software has been developed to run on an external connected computer receiving LDV time series displacement data from the handheld devices and to conduct real-time signal processing and data presentation.
A four beam Laser Doppler Vibrometer photonic chip has been fabricated using wafer scale processes and found functional. The LDV chip receives input from a 1310 nm laser assembly fabricated using large scale manufacturing processes. The Laser Doppler Vibrometer has been integrated into a hermetically sealed photonic package together with the first stage of the amplifier chain.
The photonic package interfaces to an optical system, which sends the four output beams of the on-chip LDV to four spots on the skin with a spacing of 5 mm.
Electronics for instrument control, data acquisition and wireless transmission of data have been designed and fabricated. The electronics have a powerful onboard processor to translate the raw LDV data into displacement data before they are transmitted to an external computer for further processing and data presentation.
Two methods, template matching and matrix profiling, were assessed using all available carotid-femoral and local carotid CARDIS datasets and found suitable for the automated quantification of signal quality using logistic regression modelling. Template matching is put forward as method of choice for the automated real-time identification of heart beats and grading of signal quality within the InSiDe device. An algorithm for determining carotid-femoral pulse wave velocity is proposed.
Software has been developed to run on an external connected computer receiving LDV time series displacement data from the handheld devices and to conduct real-time signal processing and data presentation.
With Medtronic, Microchip, imec, Tyndall, Argotech, the Universiteit Gent (UGent), Politecnico di Torino, INSERM and the Universiteit Maastricht (UM), 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 a wide range 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 a wide range 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).