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Multi-modal, Endoscopic Biophotonic Imaging of Bladder Cancer for Point-of-Care Diagnosis

Periodic Reporting for period 1 - MIB (Multi-modal, Endoscopic Biophotonic Imaging of Bladder Cancer for Point-of-Care Diagnosis)

Reporting period: 2016-01-01 to 2017-06-30

In the Western World bladder cancer is among the most expensive diseases in oncology in terms of treatment costs – each procedure requires days of hospitalisation and recurrence rates are high. Current unmet clinical needs can be addressed by optical methods due to the combination of non-invasive and real-time capture of unprecedented biomedical information.

The MIB objective is to provide robust, easy-to-use, cost-effective optical methods with high sensitivity and specificity, to enable a step-change in point-of-care diagnostics of bladder cancer. The concept relies on combining optical methods – optical coherence tomography (OCT), multi-spectral opto-acoustic tomography (MSOT), shifted excitation Raman difference spectroscopy (SERDS), and multiphoton microscopy (MPM) – providing structural, biochemical and functional information. The hypothesis is that this combination enables in situ diagnosis of bladder cancer with superior sensitivity and specificity due to unprecedented combined anatomic, biochemical and molecular tissue information, thus enabling earlier onset of treatment. The step-change is that this hybrid concept is provided endoscopically for in vivo clinical use.

Overall, the MIB consortium sees an opportunity to radically improve bladder cancer point-of-care diagnosis through the combination of the above-mentioned modalities into one common, endoscopic-based imaging platform that provides the biomarkers needed for superior diagnosis.
During the first 18 months, MIB has been heavily focusing on the technical development of devices and components. MIB initiated developing customised laser sources for Raman spectroscopy (SERDS) and multiphoton imaging systems, with initial results showing great promise for achieving our ambitious goals. The most important and challenging part of realising the MIB imaging platform is the delivery system, i.e. probes that fit into cystoscopies combined with compact scanning technologies. Following successful first testing, MIB has now finished designing probe heads for multimodal imaging, allowing the desired modalities to be combined. Furthermore, appropriate delivery systems have been designed. Finally, delivery fibres for the various modalities have been selected and tested. The first tests of distal scanning mechanisms for OCT/MSOT and MSOT detection schemes have also been successfully completed. These tests allows finalizing the probe head designs, thus enabling first in-vitro and ex-vivo testing, involving the development of appropriate image co-registration algorithms.

In preparing for first tests with human tissues, ex vivo and in vitro, adequate clinical protocols and ethics approvals has been prepared and filed. Laboratory space, embedded in a clinical ward, for safe laser use/examination of ex vivo human tissue testing has been established.

Finally, in preparation of the MIB exploitation route, a first set of user requirement specifications has been defined, emphasizing the needs from a clinical applications point-of-view. The first steps in business plan development were taken, which will be updated as the project develops.
In clinical and medical diagnostic procedures, excisional biopsy and histopathology remain the golden standard. However, the information needed for diagnosis is not available in real time. Optical imaging and diagnostics have recently offered great promise to address unmet clinical needs due to the combination of non-invasive, real-time capture of biomedical information. Therefore, non-invasive optical imaging approaches enable earlier onset of treatment, reduced therapy costs, reduced recurrence rates, improved clinical outcomes, and a better patient experience.

Optical coherence tomography (OCT), multi-spectral opto-acoustic tomography (MSOT), multiphoton microscopy (MPM), and shifted excitation Raman difference spectroscopy (SERDS) are considered established or emerging optical modalities. Up to now, these optical imaging modalities were applied as standalone techniques, each targeting one biomarker. However, recently it has been shown that diagnosis is significantly improved by combining different contrast mechanisms in a multimodal approach, i.e. utilizing different contrast phenomena simultaneously. Hence, multimodal biomedical imaging allows objective assessment of the status of a disease such as staging and grading of lesions, including cancer, or cellular-level functional imaging being considered the next generation technology within diagnostics.

MIB proposes to combine the above-mentioned optical modalities for diagnosing and staging of bladder cancer facilitating superior diagnosis: suspicious lesions are analysed with OCT, MSOT, MPM or SERDS to provide morphological (tumour borders, penetration depth – invasiveness), label-free microangiography (vascular structure), and intrinsic biochemical and molecular information (classification into aggressive vs nonaggressive cell, or metabolic information), respectively. Each of the combined methods has high sensitivity or specificity for (at least) one biomarker, and the combination would retain these advantages, whilst eliminate the disadvantages of each of the individual methods.

By introducing new multi-modal optical imaging, the overarching vision is that MIB improves the diagnostic performance of bladder cancer allowing earlier onset of treatment and thereby reducing the recurrence rate by at least 10%, which currently is 50% after 12 months follow-up. Due to the currently high recurrence rate, there is a need for a high number of expensive follow-up procedures. By improving diagnosis and, therefore, reducing recurrence rate, the need for follow-up procedures is reduced.

The project relies on the development of new compact light sources, high-speed imaging systems, and novel probes for endoscopes being combined and applied clinically. The consortium comprises world-leading academic organisations in a strong, unique partnership with innovative SMEs and clinical end-users. Through commercialization of a novel generation of minimally invasive, point-of-care imaging system for bladder cancer diagnosis, MIB is expected to reinforce leading market positions in medical devices and healthcare for the SMEs in areas where European industry is already strong. The impact is that improved diagnostic procedures facilitate earlier onset of effective treatment, thus recurrence and follow-up procedures would be reduced by 10%, which in turn drastically reduces public healthcare costs. By using MIB technology, health cost savings in the order of €360 million are expected for the whole EU. Equally important, prognosis and patient quality of life would improve drastically.
MIB is in its early stage of development. However, the above-mentioned objective, thus impact, is still relevant and within reach.
MIB Impact