Periodic Reporting for period 1 - HDEFONE (Novel algorithmic frameworks for functional neuroimaging using hybrid high density speckle contrast optical tomography and high density diffuse optical tomography)
Período documentado: 2023-11-01 hasta 2025-10-31
Infants with severe CHD undergo complex surgical procedures in the early days of life; a critical period when the neuro-vascular networks in the brain are developing and maturing. Complications arising out of CHD can delay these developments and affect brain function, and are typically observed as developmental delays and learning deficits. These can have significant impact on the quality of life of the patients and their families. A better understanding of the microvascular origins of impaired brain function is possible by examining cerebral oxygenation and blood flow in the peri-operative period to assess functional status of the neuro-vascular networks via neurovascular coupling (the physiological mechanism that manages the complex of interplay of neuronal activation, blood flow and oxygenation). Established functional neuroimaging methods such as functional magnetic resonance imaging (fMRI), require complex equipment and are non-portable and as such cannot be easily deployed in challenging environments such as the intensive care unit or the surgical room. There is a scientific and clinical need for non-invasive functional neuroimaging techniques that can be deployed in clinical environments and enable probing brain function of challenging populations at the cot-side. Hybrid diffuse optical tomography methods, that provide images of cerebral oxygenation and blood flow, are well-poised to meet this need and are increasingly finding their way in clinical environments. However, infants are not merely small adults. Carefully designed adaptations are essential to allow development of an effective tomographic setup that adapts well to the infant head and provides high resolution images of brain function.
The HDEFONE project has supported the development of hybrid high density diffuse correlation tomography and diffuse optical tomography (HDDCT/DOT), a new tool for non-invasive neuroimaging that can provide concurrent and colocalised estimates of cerebral oxygenation and blood flow, with a focus on neonates with CHD under critical care. The ability to assess brain-function in these infants has the potential to support early detection of impairments and corrective interventions. Going beyond the CHD patients, HDDCT/DOT can be deployed in paediatric research as well as clinical environments to further our understanding of the developing infant brain, and plan supportive or corrective actions in earnest to minimise the impact of impairments.
The HDEFONE project has supported the development of hybrid high density diffuse correlation tomography and diffuse optical tomography (HDDCT/DOT), a new tool for non-invasive neuroimaging that can provide concurrent and colocalised estimates of cerebral oxygenation and blood flow, with a focus on neonates with CHD under critical care. The ability to assess brain-function in these infants has the potential to support early detection of impairments and corrective interventions. Going beyond the CHD patients, HDDCT/DOT can be deployed in paediatric research as well as clinical environments to further our understanding of the developing infant brain, and plan supportive or corrective actions in earnest to minimise the impact of impairments.
The HDEFONE project aimed towards advancing the state of the art in functional optical neuroimaging through new algorithmic frameworks for hybrid high density diffuse optical tomography. After the onset of the project, since there were active in vivo clinical measurements and the possibility to maximize the project impact, it was decided to re-orient the algorithms and software pipelines developed in the HDEFONE project towards the concurrent development of instrumentation for HDDCT/DOT in the TinyBrains project (grant agreement No 101017113).
With inputs from the HDEFONE project, a HDDCT/DOT imaging platform was developed in the TinyBrains project, for bilateral imaging of the auditory cortex, with 44 overlapping channels in a high-density configuration capable of imaging upto a depth of 10 cm inside the neonatal head with field of view of 10 cm2 over each hemisphere. The in vivo validations demonstrated the ability of the developed system to simultaneously capture changes in oxygenation and blood flow, and report on the status of neurovascular coupling. Additionally, the tomographic images provided the ability to visualise distributed brain function, and in future can enable investigations into the developmental status and maturity of the underlying neurovascular networks.
One of the main achievements of this project is that the developed algorithms and allied technological developments were successfully used for assessment of functional status of the brain via in vivo data acquisition in 16 neonates with CHD in the neonatal intensive care unit. This was a significantly complex and involved undertaking than what was originally envisaged while writing the project, and was successfully fulfilled.
In summary, the work performed in this project encompassed the complete pipeline of translational research from the bench to bedside and can be summarised as (i) development of model-backed methods for optimisation and testing of the acquisition setup for HDDCT/DOT in neonates, (ii) development of reconstruction algorithms to maximise the use of available information in DCT and HDDCT/DOT using data fusion methods, and (iii) in vivo validation and testing of the developed methods on infants with CHD.
With inputs from the HDEFONE project, a HDDCT/DOT imaging platform was developed in the TinyBrains project, for bilateral imaging of the auditory cortex, with 44 overlapping channels in a high-density configuration capable of imaging upto a depth of 10 cm inside the neonatal head with field of view of 10 cm2 over each hemisphere. The in vivo validations demonstrated the ability of the developed system to simultaneously capture changes in oxygenation and blood flow, and report on the status of neurovascular coupling. Additionally, the tomographic images provided the ability to visualise distributed brain function, and in future can enable investigations into the developmental status and maturity of the underlying neurovascular networks.
One of the main achievements of this project is that the developed algorithms and allied technological developments were successfully used for assessment of functional status of the brain via in vivo data acquisition in 16 neonates with CHD in the neonatal intensive care unit. This was a significantly complex and involved undertaking than what was originally envisaged while writing the project, and was successfully fulfilled.
In summary, the work performed in this project encompassed the complete pipeline of translational research from the bench to bedside and can be summarised as (i) development of model-backed methods for optimisation and testing of the acquisition setup for HDDCT/DOT in neonates, (ii) development of reconstruction algorithms to maximise the use of available information in DCT and HDDCT/DOT using data fusion methods, and (iii) in vivo validation and testing of the developed methods on infants with CHD.
The HDEFONE project has developed two key methodologies that can propel further advances in neuroscience research, optical neuroimaging and the instrumentation required therefore.
First, methods have been developed that provide new perspectives for quantitative assessment of the data generated by an acquisition setup and prescribe protocols for further tuning the system design. These strategic methodologies can potentially serve as templates for the design and development of neuroimaging devices using quantitative model-backed methods to minimise the ethical impacts of in vivo tests for tuning and optimisation of the setup. In future, these methodologies could be further extended to develop individualised tuning targets to maximise data-fidelity.
Second, the new algorithms can provide improved assessments of neurovascular function. In tandem with the technological developments in hybrid diffuse optics instrumentation, these advances will benefit neuroscience research and neuro-critical care by providing large field of view imaging of brain function, to generate new scientific insights into the development, maturity and status of functional brain networks and guide individualised care decisions. Further research and investment in these technologies will open the possibility to image new demographics such as individuals under critical care, or infants in naturalistic environments.
In the short term, further refinement of the methodologies developed and thorough validations over a larger data set is essential to promote adoption of these methods. Continued research and demonstrations across different use-cases will pave the way to create a global appeal for these methods.
Furthermore, the activities of this project were aligned with another Horizon 2020 project, the TinyBrains (No. 101017113), which advanced the state of the art in instrumentation, probe design and scientific knowledge bringing new insights into assessment of brain function and injury in the peri-operative period. The project had significant potential for social impact, through indirect means via the scientific knowledge generated and direct means via the development of non-invasive cot-side neuromonitoring devices that can drive individualisation of critical care in CHD patients, paving the way for improvements in patient outcomes and hence their quality of life. The technologies developed therein, are on the path for further exploitation for scientific research as well as commercialisation.
First, methods have been developed that provide new perspectives for quantitative assessment of the data generated by an acquisition setup and prescribe protocols for further tuning the system design. These strategic methodologies can potentially serve as templates for the design and development of neuroimaging devices using quantitative model-backed methods to minimise the ethical impacts of in vivo tests for tuning and optimisation of the setup. In future, these methodologies could be further extended to develop individualised tuning targets to maximise data-fidelity.
Second, the new algorithms can provide improved assessments of neurovascular function. In tandem with the technological developments in hybrid diffuse optics instrumentation, these advances will benefit neuroscience research and neuro-critical care by providing large field of view imaging of brain function, to generate new scientific insights into the development, maturity and status of functional brain networks and guide individualised care decisions. Further research and investment in these technologies will open the possibility to image new demographics such as individuals under critical care, or infants in naturalistic environments.
In the short term, further refinement of the methodologies developed and thorough validations over a larger data set is essential to promote adoption of these methods. Continued research and demonstrations across different use-cases will pave the way to create a global appeal for these methods.
Furthermore, the activities of this project were aligned with another Horizon 2020 project, the TinyBrains (No. 101017113), which advanced the state of the art in instrumentation, probe design and scientific knowledge bringing new insights into assessment of brain function and injury in the peri-operative period. The project had significant potential for social impact, through indirect means via the scientific knowledge generated and direct means via the development of non-invasive cot-side neuromonitoring devices that can drive individualisation of critical care in CHD patients, paving the way for improvements in patient outcomes and hence their quality of life. The technologies developed therein, are on the path for further exploitation for scientific research as well as commercialisation.