Optics in Medicine is a highly interdisciplinary topic: Implications come from the technical side concerning set-ups and applications for diagnostics and therapy as well as from a bio-medical side concerning anatomy, physiology and pathology of biological structures from the sub-cellular level to the complete human body. Due to the diversity and heterogeneity of biological tissue in all its facets and the goal of adapting optical technologies to these challenges, Optics in Medicine is a demanding field of research. To cover the whole variety of theoretical knowledge and practical skills for reaching competency and to succeed in this fast developing field, it is a necessity for young researchers to receive a focused and specialized training in all aspects of medical optics.

The SAOT program ”Optics in Medicine” focuses on the comprehensive development of all abilities necessary for the independent realization of bio-optical research projects at the top of the scale. For this process SAOT has built up a unique infrastructure representing an interdisciplinary fusion point for technicians, engineers, physicists and clinicians of all expertise.

The Clinical Photonics Laboratory (CPL) was established as a central area for bio-optical experiments where both needs are satisfied – the purity of high-tech optical equipment and the safety and hygiene necessary for bio-tissue treatment. A special hands-on course concerning safety and hygiene as well as bio-tissue treatment is established for all students choosing the Optics in Medicine topic to allow for a practical and deeper understanding of the characteristics and special needs concerning bio-material treatment.

Supported by the outstanding infrastructure of SAOT, several interdisciplinary projects arose in the topic “Optics in Medicine” which were externally reviewed and receive highly-ranked funding (DFG). Exploration of new concepts for sensor based tissue specific laser surgery, Development of basic methods applied on time-of-flight camera-technology in open and lapraroscopic surgery, Pilot study on the three-dimensional prediction of morphological surface structures of the human face, Fusion of fluorescence based and micro-CT imaging for diagnostic purposes. SAOT-PhD-students with a focus on the topic “Optics in Medicine” are integrated in these projects as integral part of research activities providing a high level training “on the job” from planning and conducting experimental work, followed by analyzing and assessing the data, to presenting the results on international congresses and in high quality journals in the field.

All the mentioned projects inherit a major translational aspect, combining medical and technical aspects at its best to enhance future diagnostics and treatment. The straight forward goal of these projects is to evolve the knowledge in both fields – optics and medicine – and in a further step promote the transfer of the achievements to bring new ideas to daily life clinical applications and improve the patients’ health and quality of life.

Modular Education, Training and Research in Optics in Medicine

According to the goal of SAOT several synergistic tracks of education, training and research sounding the wide field of medicine and optics were combined providing a comprehensive and elite curriculum to qualify high-end professionals in biomedical optics.

These tracks are given in 4 consecutive Modules: “Basics of Optics in Medicine” (Module 1) covers fundamental knowledge of human biology (physiology and biochemistry) and pathology at the beginning of the curriculum. Possibilities and boundaries of the combination of optical technologies and medicine are discussed in detail.

A clear understanding of human anatomy is essential for any further bio-optical training and research. Module 2 “Basics of Anatomy” builds up on the first introductory module and provides an even deeper understanding of the micro and macro structure of the human body. A special focus is laid on the optical system of the eye as it is a unique biological model for the transformation of light into chemical and electrical energy and further on into meaningful information.

Combining the sound understanding of human biology with opto-technical know-how is the essence of bio-optics and one major goal of the interdisciplinary SAOT topic “Optics in Medicine”. Only the artful combination of both domains enables the valuable development of optical applications in medicine.

One broad field of optical application in medicine is diagnostics. Module 3 “Application of Optics in Medical Diagnosis” imparts knowledge about the use of optical diagnostic systems on a cellular level (biophotonics) as well as on a tissue/organ level (endoscopy, spectroscopy, ophthalmology) or on the level of surface structures (optical face/skull scan, 3D-reconstruction). Non-invasive optical diagnostics has to come with an intensified understanding of optical bio-tissue properties and the optical change by pathological alteration of the tissues. Hence, a focus of this module is laid on optical tissue identification for early diagnosis and therapy planning, especially in terms of malignancy.

Therapy is another important application of optical technologies. Module 4 “Optics in Therapy” deepens the knowledge about light-tissue interaction, established in Module 3, and allows for an intensive experience concerning the use of light for therapy. Two widely used clinical applications of optics, laser surgery and photodynamic therapy, are discussed and reviewed in detail concerning the different reactions of various tissues towards the source of light and the applied parameters.

Basics of Optics in Medicine

The multiple activities and main topics, forming the basis of the thematic structure of SAOT, may have important implications for future applications in medicine. The graduate school offers a unique opportunity to explore the frontiers of optical technologies as applied to health and disease by networking science and technology with medical and clinical optical programs. Graduate students will learn about optical technologies in medicine, how new technologies could be forged into prototype diagnostic and therapeutic tools and what must be known about ethical, legal and ergonomic aspects of medical optics. Accompanying the multidisciplinary fundamentals of optics and their application in the technical field the medical institutes (anatomy) and departments (ophthalmology, oral and maxillofacial surgery, internal medicine) present to the graduates the transfer of this knowledge to biological systems. A special focus will be laid on the comprehensive understanding of the interaction between light and living tissue, complementing the knowledge about the interaction between light and technical matter. The deep understanding and technological specification sheet for developing and producing new optical equipment will be achieved by an interdisciplinary approach, an appropriate learning background, including hospital based training and research, by special-topic-academies, inter-professional seminars and the interdisciplinary mentoring program consisting of technicians and specialists from the medical field.

Basics of Anatomy

A sound understanding of the functional morphology of the human body is a basic need for an interdisciplinary approach to bio-optics in medicine. Knowledge of the biological building plan and the functional processes - from the sub-cellular level, over the organ level, to the whole body system – allows for the development of opto-technical solutions for medical problems and vice versa. Hence, providing competence in the field of anatomy and physiology of the human body is an essential and integral part of the education and training curriculum in “Optics in Medicine”.  On base of normal anatomy and function the PhD-students get a deeper understanding of pathological alterations of the different systems in the human body – an understanding which is crucial for any further training and research concerning clinical applications of optics in diagnostics and therapy.

A central focus is laid on the eye being the optical apparatus of humans. From several points of view this “bio-optical system” seems to represent the interdisciplinarity of optics in medicine:  The eye is unique among all other sensory organs because it can transform light into chemical and electrical energy, which then is translated into information. The functional knowledge of this anatomical unit allows for direct detection of the interactions between light and living cells. Following the stream of light the young researchers learn about the biological ocular systems of cornea and lens, followed by the temporal and spatial conversion of the electromagnetic waves into a high number of synchronized streams of data which are conducted via the optic nerve and its more than 1,000,000 fibres to the optic cortex where they are translated into the visible picture. Hence, studying the biological optical system provides a new vision on technical optical systems initiating cross-linking the experiences from both fields of knowledge.

On base of that, research as part of the “Basics in Anatomy” module concentrates on factors and circumstances causing severe vision defects on morphological, physiological and molecular levels: The structures of the eye are closely analyzed, in order to develop eye simulations for therapeutic purposes. Loss of accommodation during human life (presbyopia) as well as the opacification of the human lens in the context of cataract drives the development of intraocular lenses. Multifocal as well as accommodative lenses are currently under investigation to restore far as well as near sight following cataract surgery. Additionally, the eye contains a variety of different tissues in close proximity to each other (retina = brain derived, uvea = vascular tissue, cornea = avascular tissue) which can easily and uniquely in the body be investigated under direct vision through the optical apparatus of the eye enabling to develop optical scanning and early detection methods for a huge variety of diseases. 

Application of Optics in Medical Diagnostics

Laser optical, photonic and biophotonic principles revolutionize diagnostic investigational and clinical medicine. Light-based technologies are often contact-free, have little impact on the integrity of living matter and can therefore easily be applied in situ. Advanced optical technologies in medicine are applied to detect and monitor cellular biochemistry and function, tissue characteristics, structure and function of organs and interchange between functional body units. Several optical specialties are closely related to this issue – building the interdisciplinary background of optical technologies in medical diagnostics: Optical Materials and Systems develop and optimize laser systems for opto-medical diagnostic applications; Optical Metrology is an integral issue for any diagnostic application of diagnostics in medicine including the huge field of Imaging, an ever growing domain in medical science and detection of diseases. Tissue, cells, proteins and DNA can be labelled with optical tags and their fluorescence or incandescence is measured and modifications interpreted according to the physiological or pathological situation. Native, untagged methods have been in the focus of biophotonics and represent an important medical diagnostic technique of the future: Confocal laser microscopy and optical coherent tomography are most often applied, recently combined with endoscopes and indwelling catheters. These modalities can be combined with other imaging modalities (ultrasound, CT, MRT, PET, nuclear medicine) to evolve as molecular imaging tools for functional analysis and navigation. Fluorescence spectroscopy, light absorption and scattering analysis, angle-resolved low coherence interferometry and spontaneous biophotonic activity will also offer opportunities for non-invasive tissue or blood/body fluid analysis. Technological challenges will be miniaturization, integration of optical technologies into chip and sensor development and new biooptic materials including new laser sources like ultrashort laser pulses, organic diodes and ultrasensitive metrological methods.

Recent research projects concerning Optics in Diagnosis were implemented and performed in the interdisciplinary setting of SAOT. Clinicians work together with engineers in a wide range from fundamental research on optical identification and imaging of normal and pathological    conditions of biological matter to precise and innovative prototype-tools for diagnostic applications:

The correct function of all the components of the human optical system is dependent on a sufficient nutrition. Sophisticated laser technology has allowed the visualisation of vasculature and other structures of the retina and the optic nerve head to diagnose ocular diseases precisely. Visualization of changes in ocular capillaries also allows the diagnosis of general vascular disorders. Examples for such diagnostic tools are laser scanning systems, laser polarimetry, optical coherence tomography, all of which allow for optaining precise information about the retinal vessels, the retina, the retinal pigment epithelium and the choroid. Furthermore metabolic products like lipofuscin can be used to judge disease processes in the retina and help to determine the dignity of tumors of the choroid. Further improvement of the resolution of imaging techniques might allow progress into the cellular or molecular level.

The intra-operative application of optical 3D sensors and metrology will dramatically meliorate the control of reconstruction procedures and enhance the outcome of surgical interventions. Starting from the assessment of facial symmetry a model is established which allow for the creation of surface target data of the face in cases of congenital or acquired facial defects caused by trauma or cancer. Based on that, optical scanning of the face deformity enables the surgeon to evaluate the necessary surgical steps and the pre-fabrication of alloplastic implants for a correct and precise construction or reconstruction of the patients face according to the optical established surface model. A focus is put on a high-speed and reliable diagnostic and modelling system for an intra-operative real-time evaluation of the intended surgical outcome.

Differentiation between malignant and physiological tissue is successfully performed by existing fluorescence imaging systems. Several systems for this “optical biopsy” are already used in the clinical setting. However, the histological evaluation after invasive surgical tissue resection is still the “gold standard due to its higher accuracy. Hence, the accuracy of optical diagnostic systems in tumor diagnostic need further technical enhancement, followed by clinical evaluation to enable a highly reliable diagnostic alternative to the invasive standard of surgical and pathological tumor verification. Additionally, any surgical manipulation by a scalpel, electric cutting or coagulation, ultrasound based surgery and laser surgery cause an alteration of the tissue which may be followed by an alteration of the optical properties of tissue. An interdisciplinary research group investigates the fundamentals and possibilities of optical tumor tissue identification after alteration by surgical procedures. Solving this problem would allow for an intraoperative optical tumor detection in terms of a guidance for exact and complete cancer removal with an tremendous impact on the survival rate and the life quality of patients.

Application of Optics in Medical Therapy

Laser tissue processing has many advantages. The possibility to work remotely leads to high precision and little trauma. Furthermore, a high level of sterility can be guaranteed.  Spreading of germs by mechanical procedures is avoided. The same applies to malignant cells, a risk in tumor resection not to be underestimated.  The cutting geometry can be selected unrestrictedly as this procedure does not depend on the dimensions of classical surgical instruments. The laser can thus also be used for endoscopic surgery in areas that are difficult to reach and may be combined with robotic and automated surgery.

Several types of lasers are currently used in surgery. The effects of the laser beam on biological tissue depend on the wavelength of the monochromatic light that can be reflected, scattered or absorbed. Different components of biological tissue absorb light in different wavelength regions, followed by a deposition of energy in the tissue. Factors influencing the interaction of biological tissue and laser light are - from a technical point of view - the mode of application, e.g., contious or pulsed mode, pulse duration, all over application time and diameter of the application field and from a biomedical point of view the type of tissue, the amount of blood circulation, pathological alterations of the tissue, the proportion of tissue types in organs or compound tissues, to name just some of them. Hence, one focus of research is concentrated on the investigation of the interaction of different laser wave length with the variety of different biological tissues. New developments and technical optimizations for laser surgical instruments are an interdisciplinary challenge, approached by a close cooperation of Optics in Medicine with other SAOT topics and Medical Departments: Optical Material Processing, Optical Material and Systems, Department of Oral and Maxillofacial Surgery and Department of Ophthalmology.

However, in spite of all advantages of laser assisted surgery, there is one major drawback which limits the surgical application of lasers: the lack of haptic feedback during the laser surgery. Due to that fact the use of laser surgery is restricted to the treatment of superficial tissue layers in clinical practice so far which allows a direct control of the ablation by the surgeon. Performing laser surgery with a deeper penetration of the tissue, the surgeon gets neither information about the actual ablation depth nor information about the ablated tissue at the bottom of the cut. Therefore, in cases where the anatomy of the operation area is complex, the use of lasers involves the risk of iatrogenic damage or destruction of structures that should be preserved, e.g., blood vessels and nerves. Their damage may affect immensely both function and aesthetics with a huge impact on life quality of the patients. Hence, one major goal is the development of a tissue-specific laser surgery. Different topics of SAOT contribute to this field of research, combining optical diagnostics with therapeutic applications of optics – optical metrology provides the possibility of remote tissue identification and differentiation. Additionally, the interaction of laser and tissue causes itself optical and acoustic emissions such as burn- or pyrolysis lights, thermal radiation, air- and structure-borne sounds which can be detected by photodiodes, pyrometers, microphones and piezoelectric accelerometers to identify the actually processed biological material. On base of that, closed loop control systems are developed for the control of a laser surgery which ablates tissue specific, e.g., removes fat tissue and muscle but does not harm nerve tissue or major blood vessels. An expansion of this promising field of research is the transfer of optical detection of tumor tissue to an optical guidance for laser tumor resection. In terms of translational aspects of optical technologies towards therapy systems this would allow for a very precise surgical resection of only the carcinoma sparing the surrounding tissue with tremendous advancements for the functional restoration of patients after tumor resection.

Another important and evolving therapeutic field of Optics in Medicine is vision. On the one hand optical technologies can dramatically enhance the possibilities to treat diseases of the eye or – in severe cases – may technically replace the sense of vision in humans: Refractive corneal surgery uses advanced wave-front analysis techniques to provide algorithms, which are used for treatment of refractive errors with excimer and femtosecond lasers. The further development of laser techniques will enable the reliable treatment of myopia as well as hyperopia and astigmatism. Such laser equipment can also be used for curative surgery to treat corneal diseases and to provide for sophisticated cutting techniques for corneal transplantation.

One of the great dreams of mankind is artificial vision, which through opto-mechanical stimulation allows the provision of sight for ocular blindness. The implantation of chips in the subretinal or epiretinal space could allow for supplementation of the visual pathway with useful information in diseases which normally would cause blindness. In the future, direct stimulation of the visual cortex with electrical signals from video systems might even bypass the eye and allow for a new era of artificial vision.

On the other hand optical vision technology can influence and meliorate endoscopic, minimal invasive and robotic surgery. High precision time of flight camera systems and 3-dimensinal imaging systems are developed to be combined with high-end surgical technology to enhance the quality of view during the operation via a minimal invasive approach and the surgical accuracy, hence reducing the operation time and patients’ morbidity.