Project

Abstract

DIAGNOPTICS deals with novel tools for the diagnosis and prognosis of skin cancer. Biophotonics-based tools for in-vivo and ex-vivo analysis of lesions will be combined in a pilot diagnostic workflow, which pursues using them as consecutive filters discarding benign lesions, and confirming the malignancy of others in order to guide them to surgery only when required. The in-vivo techniques will better suggest the diagnostic of malignant lesions beyond classical dermoscopy. A combination of non-invasive mature techniques (which will deliver 3D shape, multispectral, and blood flow images) will be combined in an imaging platform for scanning lesions. Then, lesions suspicious to be malignant will be analyzed using in-vivo reflectance confocal microscopy (RCM). When malignity is confirmed and surgery required according to clinical practice, an ex-vivo analysis in the surgical room using multimodal confocal microscopy (MMC) will minimize the excision of healthy tissue around the lesion.

The consortium involves all actors required. UPC is an experienced Centre in photonics engineering, and INPT is expert in blood flow analysis using laser imaging. Hospital Clínic from Barcelona (with IDIBAPS, its associated research institute), and Azienda Ospedaliero Universitaria Policlinico di Modena provide the clinical environment required for implementing the pilot. Both clinical teams are world-class experts in in-vivo and ex-vivo skin cancer diagnosis and prognosis. Finally, two SMEs pursue the commercialization of the results of the project. Carril is a medical device company interested in the exploitation of the in-vivo imaging platform, while MAVIG is a manufacturer of RCMs and MCMs with products already in the market for in-vivo and ex-vivo analysis of skin cancer lesions. All partners have had research collaborations with some other in the consortium in the recent past, including the participation of four of them in COST Action BM1205 “Skin Cancer Detection for Laser Imaging”.

project-1

Skin cancer prevalence is rising due to unsafe exposure practices and larger UV incidence due to ozone layer depletion (red stands for 8 cases per 10000 inhabitants).
Image: Lokal Profil

 


Project objectives

DIAGNOPTICS project aims to launch a hospital service where innovative optical solutions are applied for an enhanced early diagnosis and monitoring of prognosis of skin cancer in real-life conditions. Non-invasive optical technologies with already proven technical feasibility like 3D imaging based on fringe projection, hyperspectral imaging, laser imaging for blood flow measurements, and reflectance confocal microscopy will be applied for the in-vivo diagnosis and analysis of the skin cancer disease. Simpler diagnostics will be evaluated using the simplest techniques, while more advanced analysis will be applied to the patients with complex clinical diagnostics, starting in the simplest in-vivo dermoscopy and ending in ex-vivo multimodal confocal microscopy analysis of excised tissues in the surgical room. These technologies and its associated procedures are envisaged to improve the detection ratio and the evaluation of the prognosis of skin cancer at earlier stages, compared with the conventional approach based on simple naked-eye inspection of lesions or digital dermoscopy. In case of malignancy, surgical excision aided by an ex-vivo multimodal confocal microscopy platform will be carried out. This optical technology is envisaged to better guide the doctor during the surgical procedure and to increase the diagnostic quality compared with conventional ex-vivo histology or frozen section examination. Both the in-vivo and ex-vivo abovementioned technologies will be demonstrated in DIAGNOPTICS pilot project, in accordance with standard clinical workflows, protocols and procedures, involving professional healthcare end-users (basically dermatologists, Mohs surgeons and plastic surgeons) and covering a sufficient range of skin cancer profiles in two healthcare specific institutions: Hospital Clinic i Provincial de Barcelona (and its associated research center, IDIBAPS) and Azienda Ospedaliero Universitaria Policlinico di Modena.

project-2

Early detection is the better guarantee.
Foto: Cristiana Care.

 

The main objectives of the DIAGNOPTICS project are:
  • Demonstrate a novel multi-diagnostic and multi-dimensional biophotonics in-vivo platform with the integration of currently available 3D imaging, hyperspectral imaging, confocal imaging and blood flow imaging technologies that allow for more accurate diagnosis with earlier, faster and more objective skin cancer screening procedures when compared to conventional inspection approaches.
  • Demonstrate a novel ex-vivo multimodal confocal imaging approach that enables fast and reliable detection of malignant and benign tissue during surgery without destruction of the organic material in the samples. This is key for genetic tests which open the way to personalized medicine procedures rather than conventional histological examinations.
  • Implementation of the in-vivo and ex-vivo biophotonic solutions under valid clinical protocols, procedures and medical equipment regulations and standards, within real clinical settings in Hospital Clinic i Provincial de Barcelona and Azienda Ospedaliero Universitaria Policlinico di Modena, while also managing safety, ethical and private issues of patients appropriately.
  • Providing to the professional end-users better instrumentation for the diagnosis, prognosis evaluation and monitoring of skin cancer with a clear added value for the European healthcare sector.

 

In regard to the usage of the pilot solutions proposed, different kinds of professional healthcare end-users are expected, most of them being clinicians dedicated to skin healthcare, in particular focusing onto:
  • Dermatologists, which are healthcare professionals dealing with the diagnosis, prognosis determination and medical treatment of patients affected by skin melanomas.
  • Dermatologic Mohs surgeons and also plastic surgeons, which perform malignant skin tissue surgeries with functional and cosmetic outcomes, respectively, in routine care.
  • Operators of the optical devices that could support the doctor when examining patients affected by melanomas and performing a surgical intervention of the skin tumour within the surgery room.
  • Managing users in reference skin cancer hospitals looking for optimized and more reliable clinical flow.

Pilot implementation

project-3

Dermatoscopes are the leading tool for skin cancer detection. Photonics provides several other technology tools to push forward novel pilot services for skin cancer diagnostics in hospitals.

The pilot deployment in both hospitals (Barcelona and Modena) will be organized both for in-vivo and ex-vivo pilots. The pilot will be implemented with the ultimate goal of enhancing the reliability and precision of the diagnosis processes in skin cancer lesions in the form of a sequential clinical workflow. The in-vivo system will be used for skin lesion evaluation and for examination of apparently normal skin. Patients referred for moles in order to rule out a diagnosis of malignancy will be examined. The workflow will start with classical clinical and dermoscopy inspection, so benign lesions may be discarded fast. Lesions suspicious of malignancy will be analysed further using the novel tools implemented in the imaging platform. 3D topography will provide information on roughness and potential ulceration of the lesions, multispectral imaging will deliver information on the subsurfacing skin tissue at different illumination wavelengths, and blood flow analysis will give clues on the existence of increased cellular activity yielding a potential malign lesion. Lesions not discarded using the imaging platform (which is expected to remove a large number of lesions out of the traditional workflow) will then be analysed in depth using in-vivo reflectance confocal microscopy. Thus, a step-by-step easy and reproducible procedure will be executed in order to grant a systematic and complete collection of the needed information. The process can be interrupted at any step when a high confidence for the diagnosis is obtained. Collected information will be used to refine diagnosis and grade of confidence with use. We expect a diagnostic accuracy of 99% for all lesions examined.

Finally, lesions which are still suspicious of malignancy will be brought to the surgery room. In case of malignancy, when requested according with good clinical practice guidelines, surgical excision with ex-vivo multimodal confocal microscopy driven micro-staging will be performed in order to minimize the surgery with guarantee of safe margin excision. Ex-vivo multimodal confocal microscopy micro-staging excision is performed during the surgical session at the bedside directly in excised fresh tissue, through a simple and short procedure for nuclear staining with a fluorescent dye (accridine orange) in order to make easier the diagnostic reading. In the surgery room, surgeons will be able to instantly evaluate the excised tissue independent from tissue size. The surgeon is thus able to distinguish between benign and malignant tissue in a faster way and avoids currently necessary waiting times due to the transfer of the excised tissue to the histological laboratory and the preparation of frozen histologic and paraffin sections that are required for a histological examination.The complete imaging and reading of a 12×12 mm area is expected to be performed in less than 7 minutes, compared with the 30 to 60 minute procedure needed for each stage in traditional micro-staging, once the pilot is deployed after the technological adaptations performed in the initial part of the project, which required for optimizing the performance of the ex-vivo imaging procedure.

The in-vivo DIAGNOPTICS pilots will be implemented in both Hospitals (Hospital Clínic i Provincial de Barcelona and at Azienda Ospedaliero Universitaria Policlinico di Modena), being integrated in its existent Melanoma and Skin Cancer units. Both Hospitals are equipped with state of the art Dermatological Diagnostic Units where patients are attended and lesions documented before management decisions are taken. The ex-vivo DIAGNOPTICS pilots will be located in the corresponding surgical rooms of both Hospitals, in order to be used during surgical procedures, for the evaluation of skin cancer margins. The implementation of the ex-vivo pilot will not alter the standard procedure but will enormously facilitate the double evaluation and comparison between DIAGNOPTICS pilot performance and standard procedures.

Doctors, nurses and managers will be implicated in the integration of the pilot in the clinical management of skin cancer patients, which has been considered in the WP load of all institutions. The integration of the pilots will preserve the gold standard management of skin cancer patients without impairment and their diagnosis or treatment. Patients will be informed about the possibility to be evaluated with the pilot and their decision will not implicate a change in the final treatment that the patient will receive but in the diagnosis/prognosis procedures used in during treatment. Only after the signed consent, patients will be included in the protocol, and the pilots used.

The proposed solutions are expected to provide to healthcare professionals better tools for an earlier, faster and more accurate diagnosis and prognosis evaluation of patients affected by skin cancer disease, compared to conventional techniques currently applied in daily clinical practice. In particular, from the clinical point of view, 3D high-resolution imaging based on fringe projection will benefit in a better identification of ulceration, which a very important prognostic factor in melanoma. Hyperspectral imaging will provide a precise quantification of the different colors present in the skin lesion, as far as the presence of eumelanin is associated with a worst prognosis. Analysis of blood flow in the tumour by means of laser imaging technique will supply neo-angiogenesis information, which is also important for a better prognosis of the lesion. And reflectance confocal microscopy technology will provide skin data in-vivo characterisation at cellular-level resolution offering improved diagnostic accuracy for skin tumours. Those abovementioned technologies will complement traditional approaches based on digital dermoscopy, which is a well-demonstrated technique with a good accuracy that may be improved and defecting information about the prognosis of tumours, thus offering four in-vivo optical solutions for improving the detection ratio and complementing the information about the biological behavior of the tumour to better adapt the specific treatment allowing personalized medicine possible. When the in-vivo measurements indicate a positive detection, the skin tissue will be excised for conducting a deeper analysis with the aid of an ex-vivo multimodal confocal microscope, which enables a rapid real-time imaging of the lesion during dermatologic surgery. The unique combination of fast fluorescent and multimodal techniques in the ex-vivo confocal system together with the possibility to highlight acquired images with two colours similar to H&E sections integrates the examination of excised tissue into the surgical workflow and thus allows for smooth continuation of the surgery without sometimes repeatedly long waiting times for the histological examination, which can take 30-60 minutes per excision or stage.

The proposed solutions that will be piloted in two hospitals that belongs to the project consortium Hospital Clinic i Provincial de Barcelona and Azienda Ospedaliero Universitaria Policlinico di Modena, are envisaged to provide a more complete diagnosis and prognosis of skin cancer lesions than approaches currently available in routine care. This is expected to make more efficient the selection of patients entering surgical procedures, and consequently a decrease in hospital cost and occupation for skin cancer treatment is expected. The two hospitals and their involved teams selected have a large expertise in in-vivo and ex-vivo practices described in the area of skin cancer. Both clinical teams combine normal patient flow with excellent research contributions in renowned journal in the area of skin cancer.