Periodic Reporting for period 4 - AMPLITUDE (Advanced Multimodal Photonics Laser Imaging Tool for Urothelial Diagnosis in Endoscopy)
Periodo di rendicontazione: 2023-10-01 al 2024-12-31
Bladder cancer is among the most prevalent cancers in the world and is accompanied by similarly high morbidity and mortality. Combined with significant under-investment in bladder cancer research, and the huge impact it can have on quality of life, improvements to managing bladder cancer are a high priority to healthcare service worldwide.
The primary concern with many cancers, particularly bladder cancer, is how invasive the tumour is when diagnosed. The depth of penetration into tissue dictates treatment choice, and so it is essential that this be determined as quickly and accurately as possible. Currently, bladder cancer diagnostics requires a combination of endoscopy using white light, and analysis of cells from patients urine. This takes time and includes non-trivial misdiagnosis risks, which can lead to increased patient mortality, and reduced quality of life following treatment. Furthermore, bladder cancer suffers extremely high (70-80%) 5-year recurrence rates even after treatment, making effective surveillance during and after treatment especially important.
The Amplitude project set out to develop new, advanced multi-modal imaging systems to diagnose bladder cancer faster and more accurately. The stand-out feature of the Amplitude technology is it's ability to view far deeper into tissue than traditional white light spectroscopy. Current imaging systems use light wavelengths less than 1350nm to target two distinct ‘biological windows’, which penetrate only a short distance through tissue. Enabled by a novel new laser technology, Amplitude targeted the third biological window, covering wavelengths between 1550-1870nm. In this window, light can penetrate deeper into tissue at high resolution. By viewing this deep into tissue, cancer detection and staging is made easier, improving the speed and accuracy of diagnosis.
In developing the multi-modal imaging technology Amplitude worked towards achievement of the following objectives:
1. Develop of tuneable ultrafast lasers operating in the 3rd biological window
2. Develop nonlinear mixing to allow this laser to also operate in the 1st biological window
3. Characterise the performance of this laser for deep (≥1mm) fluorescence and metabolic imaging
4. Integrate Raman spectroscopy to this laser for molecular imaging
5. Develop a multi-modal microscope for more specific and sensitive bladder cancer histopathology
6. Develop a multi-modal endoscope for improved in-vivo diagnosis and therapy monitoring
7. Generate pre-clinical data to demonstrate the sensitivity, specificity and accuracy of tissue characterisation and tumour staging in urothelial carcinoma
8. Validate the diagnostic and staging enhancement capabilities of the imaging system on clinical samples.
The primary concern with many cancers, particularly bladder cancer, is how invasive the tumour is when diagnosed. The depth of penetration into tissue dictates treatment choice, and so it is essential that this be determined as quickly and accurately as possible. Currently, bladder cancer diagnostics requires a combination of endoscopy using white light, and analysis of cells from patients urine. This takes time and includes non-trivial misdiagnosis risks, which can lead to increased patient mortality, and reduced quality of life following treatment. Furthermore, bladder cancer suffers extremely high (70-80%) 5-year recurrence rates even after treatment, making effective surveillance during and after treatment especially important.
The Amplitude project set out to develop new, advanced multi-modal imaging systems to diagnose bladder cancer faster and more accurately. The stand-out feature of the Amplitude technology is it's ability to view far deeper into tissue than traditional white light spectroscopy. Current imaging systems use light wavelengths less than 1350nm to target two distinct ‘biological windows’, which penetrate only a short distance through tissue. Enabled by a novel new laser technology, Amplitude targeted the third biological window, covering wavelengths between 1550-1870nm. In this window, light can penetrate deeper into tissue at high resolution. By viewing this deep into tissue, cancer detection and staging is made easier, improving the speed and accuracy of diagnosis.
In developing the multi-modal imaging technology Amplitude worked towards achievement of the following objectives:
1. Develop of tuneable ultrafast lasers operating in the 3rd biological window
2. Develop nonlinear mixing to allow this laser to also operate in the 1st biological window
3. Characterise the performance of this laser for deep (≥1mm) fluorescence and metabolic imaging
4. Integrate Raman spectroscopy to this laser for molecular imaging
5. Develop a multi-modal microscope for more specific and sensitive bladder cancer histopathology
6. Develop a multi-modal endoscope for improved in-vivo diagnosis and therapy monitoring
7. Generate pre-clinical data to demonstrate the sensitivity, specificity and accuracy of tissue characterisation and tumour staging in urothelial carcinoma
8. Validate the diagnostic and staging enhancement capabilities of the imaging system on clinical samples.
The Amplitude Project has led groundbreaking research in next-generation imaging technologies to improve bladder cancer detection. Despite challenges, including the COVID-19 pandemic, the project made significant progress in developing advanced imaging systems.
In its early stages, the team focused on defining technical requirements, designing high-performance lasers for deep-tissue imaging, and creating bladder cancer cell models to identify biomarkers. They also developed designs for a state-of-the-art microscope and endoscopic probe while engaging with specialists, patients, and the public.
During the pandemic, laboratory closures caused delays, but the team successfully designed and tested two bench-top 1700nm lasers, characterized imaging objectives, and developed bladder cancer cell models to evaluate the system’s capabilities. They also designed the Amplitude microscope and endoscope and began prototyping key components.
As the project progressed, technical hurdles caused some delays, but the team delivered a packaged 1675nm laser prototype and a research version of a Tm-doped laser covering 1700-1900nm. They also developed a multi-modal microscope prototype and finalized the endoscopic probe design and conducted Raman and SHG experiments to assess whether different imaging techniques could distinguish between various bladder cancer stages.
In the final phase, the 1675nm laser was successfully integrated with the multi-modal microscope, which was used to demonstrate SHG, Third Harmonic Generation (THG), and elastic scattered light imaging in tissue up to 800 µm thick, and SHG-2PFE and THG-3PFE imaging in unlabelled biological samples.
Further research is needed to validate these findings and advance the laser, microscope, and endoscopic probe toward commercialization. This pioneering work brings us closer to a new era of non-invasive, highly accurate bladder cancer diagnostics, improving early detection and patient outcomes.
In its early stages, the team focused on defining technical requirements, designing high-performance lasers for deep-tissue imaging, and creating bladder cancer cell models to identify biomarkers. They also developed designs for a state-of-the-art microscope and endoscopic probe while engaging with specialists, patients, and the public.
During the pandemic, laboratory closures caused delays, but the team successfully designed and tested two bench-top 1700nm lasers, characterized imaging objectives, and developed bladder cancer cell models to evaluate the system’s capabilities. They also designed the Amplitude microscope and endoscope and began prototyping key components.
As the project progressed, technical hurdles caused some delays, but the team delivered a packaged 1675nm laser prototype and a research version of a Tm-doped laser covering 1700-1900nm. They also developed a multi-modal microscope prototype and finalized the endoscopic probe design and conducted Raman and SHG experiments to assess whether different imaging techniques could distinguish between various bladder cancer stages.
In the final phase, the 1675nm laser was successfully integrated with the multi-modal microscope, which was used to demonstrate SHG, Third Harmonic Generation (THG), and elastic scattered light imaging in tissue up to 800 µm thick, and SHG-2PFE and THG-3PFE imaging in unlabelled biological samples.
Further research is needed to validate these findings and advance the laser, microscope, and endoscopic probe toward commercialization. This pioneering work brings us closer to a new era of non-invasive, highly accurate bladder cancer diagnostics, improving early detection and patient outcomes.
Amplitude has pioneered the development and prototyping of cutting-edge multimodal imaging systems, harnessing the unique properties of its advanced laser sources alongside state-of-the-art imaging and spectroscopic technologies. Designed to address critical gaps in the specificity and accuracy of cancer diagnosis and therapy monitoring, these innovations mark a significant step forward in medical imaging.
By engineering lasers capable of exploring imaging in the 3rd biological window, the project demonstrated that deep multi-photon imaging is achievable within this promising spectral region, an area that holds great potential for more effective and precise medical diagnostics. Meanwhile, efforts to enhance Raman spectroscopy by correlating spectroscopic and metabolomic data have laid a strong foundation for improving the accuracy of bladder cancer detection, grading, and staging, all through the power of a non-invasive optical approach.
Through these breakthroughs, Amplitude has not only expanded the possibilities for cancer imaging but has also set the stage for future research that could revolutionise the diagnosis and treatment of cancer. The work done in this project paves the way for continued advancements, bringing us closer to more accurate, less invasive, and highly effective cancer detection and monitoring technologies.
By engineering lasers capable of exploring imaging in the 3rd biological window, the project demonstrated that deep multi-photon imaging is achievable within this promising spectral region, an area that holds great potential for more effective and precise medical diagnostics. Meanwhile, efforts to enhance Raman spectroscopy by correlating spectroscopic and metabolomic data have laid a strong foundation for improving the accuracy of bladder cancer detection, grading, and staging, all through the power of a non-invasive optical approach.
Through these breakthroughs, Amplitude has not only expanded the possibilities for cancer imaging but has also set the stage for future research that could revolutionise the diagnosis and treatment of cancer. The work done in this project paves the way for continued advancements, bringing us closer to more accurate, less invasive, and highly effective cancer detection and monitoring technologies.