Periodic Reporting for period 2 - LASER-HISTO (In vivo histology using femtosecond laser multiphoton tomograph for the early diagnosis of skin cancer and corneal diseases while simultaneously reducing Europe’s health care costs)
Reporting period: 2017-09-01 to 2018-08-31
1.3 million – this is the sad number of people dying in Europe each year by cancer. According to the World Health Organisation “cancer is the most important cause of death and morbidity in Europe after cardiovascular diseases.” The dramatic development can be particularly seen in the rise of skin cancer incidents. In the last years, the number of skin cancer incidents grew to 82’100 in 2012. Reasons for this might be the growing depletion of the ozone layer in combination with the increasing beauty trend of being tanned. Because in contrast to other cancer types, causes for skin cancer are pretty clear: in the majority of cases, UV radiation causes skin cancer. Particularly for skin cancer, the statement of the WHO that “Cancer is in many cases avoidable and early detection increases the chance of cure substantially” is true as early diagnosis is crucial for the successful medication of skin cancer to avoid spreading.
To detect skin cancer, dermatologists currently examine suspicious lesions with naked eye, a CCD camera (dermoscopy) or a reflected-light microscope. In case of not being able to rebut the suspicion by this examination, dermatologists have to take a biopsy, i.e. a piece of tissue has to be cut out of the skin to be examined by a pathologist. The reason for the need of taking a biopsy is missing information on possible tumour cells inside the skin because of insufficient resolution and depth information. Between taking the biopsy and getting the result from the pathologist several days up to a week pass, depending on the necessary pre-processing (chemical fixation, slicing into 7µm thick sections, staining).
A second serious disease becoming more and more prevalent among Europe’s population is diabetes, mostly caused by increases in overweight, obesity, unhealthy diets and physical inactivity. Diabetes (diabetes mellitus) comes along with many other health impairments. These health impairments concern particularly devastating effects on ocular health, like corneal diseases, resulting often in loss of sight. Knowing that one European in every 30 will experience sight loss, knowing that the risk of visual loss in people with diabetes is up to 25 times higher than for the population not affected by diabetes and knowing that the large majority of the visually impaired will be unemployed, it becomes clear that blindness constitutes a major burden on the European society.
Against the backdrop of these developments it is not surprising that simultaneously health care costs are tremendously increasing in Europe. From 2006 to 2011, Europe’s health care costs increased by 32% to 1.78 trillion EURO. This is also reflected by increasing health insurance contributions.
JenLab, a high-tech company with university background based in Berlin (Germany), has therefore developed an innovative novel diagnostic medical device based on femtosecond laser radiation for immediate, non-invasive early diagnosis of skin cancer avoiding the many thousands of tissue biopsies and for detecting corneal diseases within seconds and without any labelling. By exciting molecules in cells inside the tissue with near-infrared radiation and measuring the resulting fluorescence and Raman signals, JenLab’s multiphoton tomograph MPTflex-CARS is able to depict the morphology of an intra-tissue cell on a subcellular submicron level and provides even information on metabolic processes. By a special optomechanical adaption, JenLab’s solution is even applicable to ophthalmology for imaging of human cornea. The MPTflex tomographs provide label-free optical biopsies and are able to recognize cell damages already before they become visible giving dermatologists and ophthalmologist a tremendous temporal head start in fighting against diseases. In a first pilot study a sensitivity and a specificity of 95% and 97%, respectively, were obtained for multiphoton tomography of patients with malignant melanoma. Additionally, JenLab’s prototype (TRL 7) can be applied for both effectively preparing surgeries and transplantations and for postoperative evaluation and companionship of therapies.
The overall objective is to make an effective, affordable, compact and portable instrument for life-saving early diagnosis available to dermatologists and ophthalmologists (to fight against skin diseases like cancer or against increasing loss of sight) while simultaneously reducing Europe’s public and private health care costs. Due to the latter and due to more patient-friendliness –reducing consequences of invasive methods like scar formation and risk of inflammation by possibilities and means of modern medical technology– it moreover aims to offer an innovative way of reducing invasive in-vitro methods for diagnosis by a non-invasive in-vivo instrument. Furthermore, it provides rapid information on cell morphology and metabolism within seconds directly on the computer screen and allows diagnosis within minutes. Last but not least, objective of the development is also to enable dermatologists and ophthalmologists preparing effectively surgeries and transplantations as well as to allow enhanced postoperative evaluation and companionship of therapies to improve medication.
To detect skin cancer, dermatologists currently examine suspicious lesions with naked eye, a CCD camera (dermoscopy) or a reflected-light microscope. In case of not being able to rebut the suspicion by this examination, dermatologists have to take a biopsy, i.e. a piece of tissue has to be cut out of the skin to be examined by a pathologist. The reason for the need of taking a biopsy is missing information on possible tumour cells inside the skin because of insufficient resolution and depth information. Between taking the biopsy and getting the result from the pathologist several days up to a week pass, depending on the necessary pre-processing (chemical fixation, slicing into 7µm thick sections, staining).
A second serious disease becoming more and more prevalent among Europe’s population is diabetes, mostly caused by increases in overweight, obesity, unhealthy diets and physical inactivity. Diabetes (diabetes mellitus) comes along with many other health impairments. These health impairments concern particularly devastating effects on ocular health, like corneal diseases, resulting often in loss of sight. Knowing that one European in every 30 will experience sight loss, knowing that the risk of visual loss in people with diabetes is up to 25 times higher than for the population not affected by diabetes and knowing that the large majority of the visually impaired will be unemployed, it becomes clear that blindness constitutes a major burden on the European society.
Against the backdrop of these developments it is not surprising that simultaneously health care costs are tremendously increasing in Europe. From 2006 to 2011, Europe’s health care costs increased by 32% to 1.78 trillion EURO. This is also reflected by increasing health insurance contributions.
JenLab, a high-tech company with university background based in Berlin (Germany), has therefore developed an innovative novel diagnostic medical device based on femtosecond laser radiation for immediate, non-invasive early diagnosis of skin cancer avoiding the many thousands of tissue biopsies and for detecting corneal diseases within seconds and without any labelling. By exciting molecules in cells inside the tissue with near-infrared radiation and measuring the resulting fluorescence and Raman signals, JenLab’s multiphoton tomograph MPTflex-CARS is able to depict the morphology of an intra-tissue cell on a subcellular submicron level and provides even information on metabolic processes. By a special optomechanical adaption, JenLab’s solution is even applicable to ophthalmology for imaging of human cornea. The MPTflex tomographs provide label-free optical biopsies and are able to recognize cell damages already before they become visible giving dermatologists and ophthalmologist a tremendous temporal head start in fighting against diseases. In a first pilot study a sensitivity and a specificity of 95% and 97%, respectively, were obtained for multiphoton tomography of patients with malignant melanoma. Additionally, JenLab’s prototype (TRL 7) can be applied for both effectively preparing surgeries and transplantations and for postoperative evaluation and companionship of therapies.
The overall objective is to make an effective, affordable, compact and portable instrument for life-saving early diagnosis available to dermatologists and ophthalmologists (to fight against skin diseases like cancer or against increasing loss of sight) while simultaneously reducing Europe’s public and private health care costs. Due to the latter and due to more patient-friendliness –reducing consequences of invasive methods like scar formation and risk of inflammation by possibilities and means of modern medical technology– it moreover aims to offer an innovative way of reducing invasive in-vitro methods for diagnosis by a non-invasive in-vivo instrument. Furthermore, it provides rapid information on cell morphology and metabolism within seconds directly on the computer screen and allows diagnosis within minutes. Last but not least, objective of the development is also to enable dermatologists and ophthalmologists preparing effectively surgeries and transplantations as well as to allow enhanced postoperative evaluation and companionship of therapies to improve medication.
JenLab adapted the prototype technology towards two market ready product versions for two applications: (1) research in skin cancer/corneal diseases and (2) diagnosis of skin cancer/corneal diseases. Moreover, the production capacities for the expected market demand have been up-scaled and the production processes of the new systems have been integrated into the JenLab processes and structure. Demonstrations systems have been built up and clinical studies for validating the adapted product version haven been initiated. The MPTflex-CARS system passed the tests and was CE-certified. Finally, strategic sales partners and stakeholders have been acquired and sales network was established. In addition, communication and dissemination measures were implemented to promote and disseminate project results to targeted audiences. The tomographs were also exhibited at different main fairs.
In contrast to conventional ways of tissue examination, JenLab’s cell imaging system is able to generate in-vivo and within seconds high-resolution pictures of intra-tissue cells’ morphology on a subcellular level while simultaneously measuring metabolic processes. Current solutions at market are able to depict cells in-vivo by reflection microscopy with a resolution of about 1-2 µm. On the contrary, the multiphoton tomographs of JenLab are able to depict cells in vivo with a lateral resolution of 300 nm. Furthermore, the tomograph is in contrast to the state of the art able to provide information on metabolic processes of the cells and to measure autofluorescence AF of e.g. intramitochondrial coenzymes, SHG to detect the collagen network, fluorescence lifetimes (FLIM) for optical metabolic imaging (OMI), and Raman signals by CARS for chemical information, simultaneously.