Periodic Reporting for period 1 - CoDaFlight (Colouring the Dark in Fluorescence Light)
Okres sprawozdawczy: 2022-10-01 do 2023-09-30
Our main aim in CoDaFlight is to advance the capabilities of time-domain fluorescence lifetime imaging (tdFLI) for real-time and non-invasive assessment of novel (patho-)physiological and molecular processes. Compared to traditional fluorescent imaging, tdFLI offers enhanced contrast, enabling better differentiation between real fluorescence and background signals. It also facilitates objective in situ planning of resection lines with potential reductions in surgical margins, improved detection of small malignancies at greater depths, sensitive identification of invaded lymph nodes, and accurate colocalization with vital organs (multiplexing). tdFLI can be used for endoscopic or intravascular procedures, whether with or without exogenously administered contrast agents (label-free), to improve the diagnosis, staging, and in situ characterization of cancerous tissue or suspicious lesions like tumors or atherosclerotic lesions.
One particularly promising aspect of tdFLI is its ability to monitor real-time parameters such as pH, tissue oxygenation, and other metabolites. This novel approach holds great potential for assessing tissue viability during surgical interventions. Prompt recognition of decreased tissue oxygenation can facilitate immediate reestablishment of blood flow and help predict tissue desaturation-related injuries. Moreover, tdFLI can assist in the precise excision of devitalized tissues. Furthermore, by enabling accurate and reliable real-time measurements, tdFLI allows for monitoring dynamic changes deep within wound environments, such as those resulting from conditions like diabetes or burns.
We have developed the following research objectives:
RO1. Develop the technological foundations that are needed to enable real-time in vivo tdFLI in the near-infrared region (NIR): time-domain NIR image sensors, biocompatible fluorescent contrast agents with programmable FLTs and time-domain models, methods and algorithms that can extract and objectify the hidden biomedical information.
RO2. Integrate these foundations into an imaging system and provide the seeds for a technical ecosystem in which such a system can exist, software, validation techniques and characterization tools such as phantoms.
RO3. Demonstrate and disseminate the capabilities and potentials of this novel technology through in vivo proof-of-concepts with the goal to facilitate technology acceptance by end-users in the biomedical field and uptake in new markets and applications.
Our project involves two development cycles to achieve the final proof-of-concepts (PoCs) for medical applications. It is divided into three major phases: assessment, adjustment, and breakthrough.
Figure 1.
During the assessment phase, we will initiate the development of core technologies based on our assumptions. We will explore the possibilities and limitations of our initial system using various in vitro and in vivo models. This phase will provide valuable insights into the possibilities and limitations of our initial system.
In the adjustment phase, we will compile the results from the assessment phase and use them to guide the refinement of our technology development. By aligning our efforts with the right targets, we can ensure that our project progresses in the most effective direction.
In the breakthrough phase, all developments come together, are finetuned and demonstrated in proof-of-concepts.
One particularly promising aspect of tdFLI is its ability to monitor real-time parameters such as pH, tissue oxygenation, and other metabolites. This novel approach holds great potential for assessing tissue viability during surgical interventions. Prompt recognition of decreased tissue oxygenation can facilitate immediate reestablishment of blood flow and help predict tissue desaturation-related injuries. Moreover, tdFLI can assist in the precise excision of devitalized tissues. Furthermore, by enabling accurate and reliable real-time measurements, tdFLI allows for monitoring dynamic changes deep within wound environments, such as those resulting from conditions like diabetes or burns.
We have developed the following research objectives:
RO1. Develop the technological foundations that are needed to enable real-time in vivo tdFLI in the near-infrared region (NIR): time-domain NIR image sensors, biocompatible fluorescent contrast agents with programmable FLTs and time-domain models, methods and algorithms that can extract and objectify the hidden biomedical information.
RO2. Integrate these foundations into an imaging system and provide the seeds for a technical ecosystem in which such a system can exist, software, validation techniques and characterization tools such as phantoms.
RO3. Demonstrate and disseminate the capabilities and potentials of this novel technology through in vivo proof-of-concepts with the goal to facilitate technology acceptance by end-users in the biomedical field and uptake in new markets and applications.
Our project involves two development cycles to achieve the final proof-of-concepts (PoCs) for medical applications. It is divided into three major phases: assessment, adjustment, and breakthrough.
Figure 1.
During the assessment phase, we will initiate the development of core technologies based on our assumptions. We will explore the possibilities and limitations of our initial system using various in vitro and in vivo models. This phase will provide valuable insights into the possibilities and limitations of our initial system.
In the adjustment phase, we will compile the results from the assessment phase and use them to guide the refinement of our technology development. By aligning our efforts with the right targets, we can ensure that our project progresses in the most effective direction.
In the breakthrough phase, all developments come together, are finetuned and demonstrated in proof-of-concepts.
We have engineered a Preclinical Time-Domain Fluorescence Imaging Instrument, to enable and pioneer fluorescence lifetime imaging in mesoscopic preclinical research.
This preclinical instrument serves as a precursor to a future medical device intended for application in human and patient scenarios. In the realm of clinical research, it is imperative to initially demonstrate problem-solving capabilities in non-human models.
Our developed instrument boasts a state-of-the-art Near-Infrared (NIR) sensitive fast-gated sensor, a camera for image capture, firmware, and user-friendly software for seamless data processing into tangible results. Additionally, research has been conducted to identify illumination sources capable of delivering normal and structured pulsed excitation light to the specimen.
Simultaneously, the project's chemists have synthesized novel static dyes with unique characteristics, poised to enhance fluorescence lifetime imaging parameters when applied to preclinical models.
Equipped with the inaugural system and contrast agents we will reach Project milestone one, end of March 2024. Then we can start showcasing the potential of fluorescence lifetime imaging to revolutionize optical imaging.
Another noteworthy outcome is the design and development of a second novel sensor, which holds the potential to match the capabilities of the current time-gated sensor within the camera. This development is particularly significant as the time-gated sensor in the camera is experimental, and we are aware of the necessity for high-resolution, video-rate imaging in the final medical applications. We now find ourselves with two promising avenues to achieve this goal.
This preclinical instrument serves as a precursor to a future medical device intended for application in human and patient scenarios. In the realm of clinical research, it is imperative to initially demonstrate problem-solving capabilities in non-human models.
Our developed instrument boasts a state-of-the-art Near-Infrared (NIR) sensitive fast-gated sensor, a camera for image capture, firmware, and user-friendly software for seamless data processing into tangible results. Additionally, research has been conducted to identify illumination sources capable of delivering normal and structured pulsed excitation light to the specimen.
Simultaneously, the project's chemists have synthesized novel static dyes with unique characteristics, poised to enhance fluorescence lifetime imaging parameters when applied to preclinical models.
Equipped with the inaugural system and contrast agents we will reach Project milestone one, end of March 2024. Then we can start showcasing the potential of fluorescence lifetime imaging to revolutionize optical imaging.
Another noteworthy outcome is the design and development of a second novel sensor, which holds the potential to match the capabilities of the current time-gated sensor within the camera. This development is particularly significant as the time-gated sensor in the camera is experimental, and we are aware of the necessity for high-resolution, video-rate imaging in the final medical applications. We now find ourselves with two promising avenues to achieve this goal.
The project is poised to propel fluorescence intensity imaging to new heights in sensitivity and specificity. As is customary with pioneering advancements, our initial focus lies in demonstrating the concept and tangible results, laying the foundation before committing substantial investments, and then accelerating the team, business idea, and technology within the challenges of a highly regulated landscape. This step is crucial in establishing the credibility and potential of our innovation. We then will need to find investments and team acceleration.
In this project, we are committed to showcasing the viability and efficacy of our technology through a comprehensive proof-of-concept demonstration.
Our commitment extends beyond the initial breakthrough, but in this project, we aim for the following
1.) Design, develop, and deliver the tdFLI instrument for the PoC with the right illumination from the developed models, translated into the right algorithms and user software.
2.) Show in a PoC a better, real-time contrast in fluorescence-guided surgery that can in time increase surgical precision and patient safety.
3.) Show in a PoC, that measuring the sub-nanosecond decay of the lifetime of responsive fluorescence tracers can sense differences in tissue pH and oxygenation, and that can kickstart the utilization of these parameters for diagnostic use.
4.) Provide a PoC for the tissue analysis (fingerprinting) capability of tdFLI, by utilizing the natural auto-fluorescence of different types of tissues, e.g. detecting cancer or wound healing, possibly in combination with artificial intelligence (ai) and deep learning capabilities.
In this project, we are committed to showcasing the viability and efficacy of our technology through a comprehensive proof-of-concept demonstration.
Our commitment extends beyond the initial breakthrough, but in this project, we aim for the following
1.) Design, develop, and deliver the tdFLI instrument for the PoC with the right illumination from the developed models, translated into the right algorithms and user software.
2.) Show in a PoC a better, real-time contrast in fluorescence-guided surgery that can in time increase surgical precision and patient safety.
3.) Show in a PoC, that measuring the sub-nanosecond decay of the lifetime of responsive fluorescence tracers can sense differences in tissue pH and oxygenation, and that can kickstart the utilization of these parameters for diagnostic use.
4.) Provide a PoC for the tissue analysis (fingerprinting) capability of tdFLI, by utilizing the natural auto-fluorescence of different types of tissues, e.g. detecting cancer or wound healing, possibly in combination with artificial intelligence (ai) and deep learning capabilities.