Periodic Reporting for period 4 - ENCOMOLE-2i (Endoscopic Comprehensive Optical Multimodal Molecular Intelligent Imaging)
Reporting period: 2020-07-01 to 2020-12-31
The most simple form of optical imaging in medicine is simply looking at the patient for visual diagnosis. However, this also reveals the main problem of optics in medicine, which is the poor penetration of light into the human body, which is a couple of millimetres only. To solve this problem, we saw already 150 years ago the advent of the first endoscopes.
By now endoscopes are standard tools in medicine and find widespread applications throughout all disciplines. Most of these endoscopes are standard reflection imaging type endoscopes, meaning they provide a simple visual impression of the tissue, like if observed with the naked eye. However, modern optics, especially if using lasers, can provide many more imaging modalities and types of contrast. There is multiphoton imaging, hyperspectral imaging, Raman imaging, mid infrared vibrational imaging and many more. Today, hardly any of these advanced imaging devices can be found in endoscopes, even so they might be much more powerful to detect diseases earlier. This problem is addressed in ENCOMOLE-2i, where advanced endoscope based imaging systems are developed, which are capable of rapidly scanning large areas of tissue. To take full advantage of the wealth of information, these systems will provide an artificial intelligence based control unit to adaptively adjust the system.
We hope that these new advanced endoscopic systems will enable to detect the onset of disease earlier and more precisely. This will help to more efficiently treat diseases, because in many cases the earlier a pathologic condition is diagnosed the better are the chances for effective treatment. Maybe patients at risk can even be identified and diagnosed before the onset of disease symptoms. This can relate to early cancer diagnosis but also to other diseases like inflammatory disorders. Such a system can contribute to a more personalized and more individualized therapy for precision medicine.
Considering that optics in form of microscopes or endoscopes is used for all groups of major diseases, i.e. cardiovascular diseases, cancer and infectious diseases, the impact of advanced optical systems for in vivo imaging inside patients cannot be underestimated. Not only with respect to our ageing society the earlier diagnosis of disease and the improved management and treatment can contribute to a substantially decreased cost of health care but more importantly it may contribute to improved health and wellbeing of many millions of citizens.
The second research track focused on the 3 imaging modalities to be used with our advanced endoscopes. These were: (1) MHz-OCT, i.e. optical coherence tomography with line rates of more than 1 million depth scans per second. This is the prerequisite to use OCT as online imaging modality for navigation and for live feedback. (2) The second imaging modality is stimulated Raman sensing using the OCT laser to detect and identify the biomolecules present in a sample. This molecular imaging technique is slower but it is capable of providing label-free endogeneous contrast of the molecular composition of a sample. Stimulated Raman sensing can be extremely sensitive and powerful for the detection of early pathological changes of tissue caused by the onset of disease. However, stimulated Raman sensing, especially if it is performed in the highly desired fingerprint region, can be slow. For this reason we suggested to apply special, smart, sparse spectral sampling in order to find the optimum compromise between speed, resolution and signal strength. We successfully developed and published this technique. (3) The third imaging modality, which will be integrated into our multimodal intelligent endoscope is 2-photon microscopy using sub-nanosecond laser pulses for excitation. The comparably long pulse duration suppresses self-phase modulation and pulse breakup in optical fibres as a prerequisite to make 2-photo fiber endoscopes more feasible. We developed, implemented and demonstrated such a sub-nanosecond 2-photon engine and could also show that the longer duration of the laser pulses is also enabling a new way to detect fluorescence lifetime signals. Enabled by high-speed analogue to digital converters, the direct real time sampling of the fluorescence lifetime signal is possible. This enabled us to demonstrate two-photon fluorescence lifetime imaging at a record speed of more than 1 million lifetime traces per second.
So in summary we were able to develop new appropriate endoscope devices, improve our imaging engines with the three different imaging modalities and even discover a new way to add additional functionally sensitive contrast.