Periodic Reporting for period 2 - Prometeus (Preterm Brain-Oxygenation and Metabolic EU-Sensing: Feed the Brain)
Okres sprawozdawczy: 2024-02-01 do 2025-07-31
Prometeus introduces a new-paradigm for personalized nutrition of prematurely born neonates in neonatal intensive care unit (NICU), by developing a groundbreaking technology for real-time adjustment of glucose and nutrients intakes to target neonatal brain needs. The brain of a baby born prematurely is highly susceptible to early neonatal injuries that, in turn, increase the risk for neurodevelopmental disability. Provision of adequate nutrients and oxygen is essential for proper brain development and growth. However, current nutritional strategies are unfit to target real-time brain necessities, and are driven by pre-specified (non personalised) nutritional charts, in the absence of contemporary cot-side monitoring of both brain “health” and metabolic supplies. As a consequence, sudden changes of brain fuel-requirements cannot be promptly addressed by real-time adjustment of glucose and nutrients provision. Prometeus will develop a metabolic model of the interaction between the three key brain fuels [glucose, lactate and beta-hydroxybutyrate (BHB)] and their effect on regional cerebral blood flow (CBF), oxygen saturation (StO2) and metabolism (CMRO2). The model will serve to individualize brain nutrition targeting “brain health” according to the inputs derived from two novel minimally invasive metabolic sensing systems: a wearable cap measuring regional CBF, StO2 and CMRO2 (neo-opticap) and a subcutaneous miniaturized metabolic sensor for glucose, lactate and BHB (CMM). The system will create a metabolic “womb” to feed the brain of preterm neonates. Prometeus will be paralleled by a parent-dedicated interface, exploiting a purposely developed family adjusted visual language, that will inform parents of preterm babies during their NICU admission and stay. Prometeus groundbreaking technology will be advised by a feed-forward interaction with families of preterms and health care personnel to shape the new device aiming at incorporating the needs of the final users. This approach will create a novel paradigm for the industrial development of neonatal devices along with an archive for the future scientists and historians of infancy. Prometeus will dramatically reduce the risk for prematurity-associated disability in Europe and worldwide, with a consequent incalculable ethical, social and economic impact.
So far, we have developed and tested in the lab neo-opticap. The device has been assembled and all lab tests yielded stable and expected results. The device has been tested also on adult humans undergoing a known physiological challenge, providing the expected results. A fine tuning of neo-opticap before the final deployment in the clinic is still in progress.
The CMM sensor is still under development. Several clinical proof-of-concept evaluations in animals have been performed, yielding promising results for safety and efficacy of the sensor. Multi analyte sensing capabilities using galvanic separated dedicated electronics has also been demonstrated. Experiments for establishing in vitro and in vivo Ketone sensing have also been performed. A CMM sensor prototype with initial clinical data for lactate has been produced, which will undergo an upcoming pilot study in humans soon. The integration of the ketone sensing into the CMM sensor measuring glucose and lactate is still in progress.
The experimental protocols to collect data in rat pups to build the metabolic neonatal model is now established, after several problems due to unforeseen events. Data collection is still ongoing. The metabolic neonatal model has therefore been currently built using other in house data and will be modified and improved as soon as the animal experimental data are analyzed. The algorithm to provide personalized nutrition to target brain health has been developed based on the available neonatal model, and will improved as soon as the final model is delivered. Two controllers have been tested so far, Model Predictive Control (MPC) and Proportional-Integral-Derivative (PID), providing expected and stable results.
The development of the Prometeus Cloud-based environment for handling, in the neonatal intensive care unit, the on-body monitoring system developed during Prometeus has been development and completed, while the integration with the sensors and algorithm for nutritional suggestions is still under development. The system consists of the Prometeus Edge Unit, a field device that interoperates with neo-opticap and CMM and handle the individual nutritional information provided by the above-mentioned algorithm, and the Prometeus Cloud Service (PCS), a cloud platform that manages the Prometeus Edge Unit and collects and back-up the data. The PCS also includes a web application for parents. This application provides information about the health of the baby and care provided. This application is under development and will be released soon.
Finally, the assessment tool used to evaluate the impact of on-body monitoring devices on parents and health care personnel and their experience with preterm neonates is completed and data collection started. Preliminary data have been analyzed and shared with other partners to improve their work (e.g. to improve the interface set up of the Prometeus Edge Unit). The script used in the interviews of parents and health care personnels for the creation of the first Visual and Oral Archive of prematurity has been finalized and the first interviews have been performed.
The CMM sensor is still under development. Several clinical proof-of-concept evaluations in animals have been performed, yielding promising results for safety and efficacy of the sensor. Multi analyte sensing capabilities using galvanic separated dedicated electronics has also been demonstrated. Experiments for establishing in vitro and in vivo Ketone sensing have also been performed. A CMM sensor prototype with initial clinical data for lactate has been produced, which will undergo an upcoming pilot study in humans soon. The integration of the ketone sensing into the CMM sensor measuring glucose and lactate is still in progress.
The experimental protocols to collect data in rat pups to build the metabolic neonatal model is now established, after several problems due to unforeseen events. Data collection is still ongoing. The metabolic neonatal model has therefore been currently built using other in house data and will be modified and improved as soon as the animal experimental data are analyzed. The algorithm to provide personalized nutrition to target brain health has been developed based on the available neonatal model, and will improved as soon as the final model is delivered. Two controllers have been tested so far, Model Predictive Control (MPC) and Proportional-Integral-Derivative (PID), providing expected and stable results.
The development of the Prometeus Cloud-based environment for handling, in the neonatal intensive care unit, the on-body monitoring system developed during Prometeus has been development and completed, while the integration with the sensors and algorithm for nutritional suggestions is still under development. The system consists of the Prometeus Edge Unit, a field device that interoperates with neo-opticap and CMM and handle the individual nutritional information provided by the above-mentioned algorithm, and the Prometeus Cloud Service (PCS), a cloud platform that manages the Prometeus Edge Unit and collects and back-up the data. The PCS also includes a web application for parents. This application provides information about the health of the baby and care provided. This application is under development and will be released soon.
Finally, the assessment tool used to evaluate the impact of on-body monitoring devices on parents and health care personnel and their experience with preterm neonates is completed and data collection started. Preliminary data have been analyzed and shared with other partners to improve their work (e.g. to improve the interface set up of the Prometeus Edge Unit). The script used in the interviews of parents and health care personnels for the creation of the first Visual and Oral Archive of prematurity has been finalized and the first interviews have been performed.
Given the early phase of the project, only few results are currently available that could have high scientific, technologic, business or economic potential. In particular, some improvements in the hardware and modeling obtained during the development of neo-opticap and the results of the preclinical proof of concept studies that demonstrated for the first time the safe and effective skin introduction of silicon microprobes, as well as the possibility to continuously sensing lactate in humans and BHB in pigs during CMM development, might have future potential market distribution.
The several rat pup experiments devised to collect data to build the metabolic neonatal model allowed to develop and improve a preclinical model to study the consequences of early weaning/prematurity and perform hypoglycemic clamps on rat pups. These clinical model might have further future exploitation.
The first version of the neonatal simulator, which, when finalized, will be the first neonatal simulator and could be used to safely develop and test control algorithms to optimally feed this fragile population, might have future potential marker distribution as well.
The Neo-Opticap demonstrator integrated paves the way to future development of this class of hybrid NIRS systems. One of the partners is planning to actively include in its product catalog the TD-NIRS module customizations, which were specifically developed for the integration of the device in the neo-opticap platform. These include: firmware customization for sw-triggered measurements, independent operation of light sources and external software libraries.
The several rat pup experiments devised to collect data to build the metabolic neonatal model allowed to develop and improve a preclinical model to study the consequences of early weaning/prematurity and perform hypoglycemic clamps on rat pups. These clinical model might have further future exploitation.
The first version of the neonatal simulator, which, when finalized, will be the first neonatal simulator and could be used to safely develop and test control algorithms to optimally feed this fragile population, might have future potential marker distribution as well.
The Neo-Opticap demonstrator integrated paves the way to future development of this class of hybrid NIRS systems. One of the partners is planning to actively include in its product catalog the TD-NIRS module customizations, which were specifically developed for the integration of the device in the neo-opticap platform. These include: firmware customization for sw-triggered measurements, independent operation of light sources and external software libraries.