Periodic Reporting for period 2 - TinyBrains (BIO-PHOTONIC IMAGING OF THE INFANT BRAIN, THE MISSING LINK BETWEEN THE CELLULAR BRAIN DAMAGE AND THE NEUROVASCULAR UNIT DURING ACUTE ILLNESS)
Okres sprawozdawczy: 2022-07-01 do 2023-12-31
The overall objective of the TinyBrains project is to build a neuroimaging platform that allows the non-invasive, three-dimensional imaging of cerebral hemodynamics and oxygen metabolism simultaneously with cerebral electrophysiology to understand the biological origins of brain damage that occurs in infants born with congenital heart defects (CHD). The project is organized, around the motto “the quality of life resides in the brain” and we posit that new scientific knowledge will aid in the development of strategies for avoiding brain injury.
We have now reached the stage of the project where patients are being recruited for measurements and preliminary analysis of the animal models are available. We were able to adapt the project timeline to the emerging new knowledge and the global realities (in particular the limitations of the post-pandemic world) and begun data acquisition in certain aspects earlier than originally planned while making compromises on the number of channels of the high-density system to fit better the ergonomics of the neonatal head, and the emerging use of commercial optical devices for routine clinical use. While those devices do not replace our measurements, concurrent measurements are potentially detrimental to the clinically utilized data so we took additional measures. Overall, earlier start of measurements is providing us with more data than originally planned while delays in the full high-density hybrid deployment and these changes are shifting the focus from imaging to monitoring. We expect that the overall scientific goals will be surpassed.
We have now reached the stage of the project where patients are being recruited for measurements and preliminary analysis of the animal models are available. We were able to adapt the project timeline to the emerging new knowledge and the global realities (in particular the limitations of the post-pandemic world) and begun data acquisition in certain aspects earlier than originally planned while making compromises on the number of channels of the high-density system to fit better the ergonomics of the neonatal head, and the emerging use of commercial optical devices for routine clinical use. While those devices do not replace our measurements, concurrent measurements are potentially detrimental to the clinically utilized data so we took additional measures. Overall, earlier start of measurements is providing us with more data than originally planned while delays in the full high-density hybrid deployment and these changes are shifting the focus from imaging to monitoring. We expect that the overall scientific goals will be surpassed.
This second period of the project saw the onset of the studies on animal models six months earlier than originally planned. This happened because the consortium was able to face the need to include a new location for animal studies (about an hour away from the original study site) that required the construction of a previously unplanned instrument on-time. We did this by compromising on imaging and focusing on neuromonitoring which provides sufficient information on the animal model. Our studies have shown that the platform is indeed capable detecting the effects of the different phases of the study, that we are able to assess cerebral-autoregulation, ischemia/hypoxia and that the electrophysiology and hemodynamics provide a way to assess hypothermia effects during circular arrest.
In parallel, we have adopted to the needs of the clinical environment which now utilizes a clinical optical device, and were able to deploy a neuro-monitor with EEG during surgery earlier than planned – was planned for the last twelve months beyond this reporting period. This validated our initial head-gear and the possibility to acquire multi-modal data during this complex, critical heart surgery. During this period, we have also completed the hybrid full TinyBrains platform which will soon be deployed for pre- and post-surgical imaging studies during evoked, auditory stimuli.
Finally, we have re-organized the project and carried out an amendment to the project plan to meet the new needs, especially with the better understanding of the sample sizes needed and the re-definition of the animal study cohorts, we have extended the project by six months. On the other hand, the project is not only about building and testing platform, but also is about optimal exploitation of the results for impact. The originally foreseen technical, social, clinical and economic impacts are still pertinent to the project. Furthermore, the importance of combined fNIRS, fDCS and EEG is continuously better appreciated by the neuroscience and clinical communities.
Since TinyBrains project has been started, the primary hypotheses have been well-supported by the community. In other words, it is well appreciated that the combination of electrophysiology and hemodynamics provide better sensitivity to brain injury which agrees with the claim that the origins of the injury related to the impairment of the neurovascular unit. Furthermore, we and others have identified that combined hemodynamic and electrophysiological data has uses in emerging new areas such as brain computer interfaces, studies of neurodevelopment in healthy and diseases infants and in brain/body cognition experiments. Therefore, the potential impact of the technologies that are being assembled and tested here is increasing. Our groups are on top of these advances and we are deeply involved in scientific, clinical and industrial societies/networks related to these topics and we have presented TinyBrains project to relevant audiences. As our results are arriving, we have been adjusting our approach and exploitation methodologies to meet these needs. We have carried out extensive new studies of markets and needs.
In parallel, we have adopted to the needs of the clinical environment which now utilizes a clinical optical device, and were able to deploy a neuro-monitor with EEG during surgery earlier than planned – was planned for the last twelve months beyond this reporting period. This validated our initial head-gear and the possibility to acquire multi-modal data during this complex, critical heart surgery. During this period, we have also completed the hybrid full TinyBrains platform which will soon be deployed for pre- and post-surgical imaging studies during evoked, auditory stimuli.
Finally, we have re-organized the project and carried out an amendment to the project plan to meet the new needs, especially with the better understanding of the sample sizes needed and the re-definition of the animal study cohorts, we have extended the project by six months. On the other hand, the project is not only about building and testing platform, but also is about optimal exploitation of the results for impact. The originally foreseen technical, social, clinical and economic impacts are still pertinent to the project. Furthermore, the importance of combined fNIRS, fDCS and EEG is continuously better appreciated by the neuroscience and clinical communities.
Since TinyBrains project has been started, the primary hypotheses have been well-supported by the community. In other words, it is well appreciated that the combination of electrophysiology and hemodynamics provide better sensitivity to brain injury which agrees with the claim that the origins of the injury related to the impairment of the neurovascular unit. Furthermore, we and others have identified that combined hemodynamic and electrophysiological data has uses in emerging new areas such as brain computer interfaces, studies of neurodevelopment in healthy and diseases infants and in brain/body cognition experiments. Therefore, the potential impact of the technologies that are being assembled and tested here is increasing. Our groups are on top of these advances and we are deeply involved in scientific, clinical and industrial societies/networks related to these topics and we have presented TinyBrains project to relevant audiences. As our results are arriving, we have been adjusting our approach and exploitation methodologies to meet these needs. We have carried out extensive new studies of markets and needs.
The project is motivated because infants who were born with congenital malformations, in particular, those born with CHD, face significant morbidities. Until recent years, the focus has been on their survival but as the clinical practice has improved and the number of survivors has significantly increased, there is an increased amount of attention to the reduction of morbidity. In TinyBrains project we aim to introduce a new, novel research tool to focus on cutting-edge research and development in the prevention of brain injury in the new born and the infant.
This complex undertaking requires a trans-disciplinary collaboration with inter-linked objectives. If this platform is successful and it provides important knowledge after the project, it also has a strong potential for both indirect (through the knowledge gained) and direct (by using an adapted version as a bed-side imager) social-impact. Paraphrasing the original proposal, the optimization of the early care of CHD and other critically ill infants/neonates with potential cerebral issues with appropriate neuro monitoring to detect and mitigate the profound burden of neurological injury has the potential to provide life-long improvements in academic achievement and quality of life. These conditions have a high prevalence and their long-term effects lead to a significant socio-economic health issue worldwide, so even modest improvements in outcome have a high potential for ground-breaking social impact. Our initial findings demonstrate that the original hypotheses, i.e. that such a platform could be utilized in the clinical setting and that it would have sensitivity to the cerebral well-being of the infant are still valid and we have taken important steps towards their validation. The upcoming final phase of the project will see a period busy with data acquisition, analysis and interpretation alongside industrialization activities.
This complex undertaking requires a trans-disciplinary collaboration with inter-linked objectives. If this platform is successful and it provides important knowledge after the project, it also has a strong potential for both indirect (through the knowledge gained) and direct (by using an adapted version as a bed-side imager) social-impact. Paraphrasing the original proposal, the optimization of the early care of CHD and other critically ill infants/neonates with potential cerebral issues with appropriate neuro monitoring to detect and mitigate the profound burden of neurological injury has the potential to provide life-long improvements in academic achievement and quality of life. These conditions have a high prevalence and their long-term effects lead to a significant socio-economic health issue worldwide, so even modest improvements in outcome have a high potential for ground-breaking social impact. Our initial findings demonstrate that the original hypotheses, i.e. that such a platform could be utilized in the clinical setting and that it would have sensitivity to the cerebral well-being of the infant are still valid and we have taken important steps towards their validation. The upcoming final phase of the project will see a period busy with data acquisition, analysis and interpretation alongside industrialization activities.