Laser-advanced new methods for diagnostics and therapeutics

Medical laser applications are manifold. They include advanced technologies, which meet current challenges in clinical diagnostics and therapeutics, and are capable of addressing a wide range of health care issues that could have an impact on large sectors of the population. Recent research activities and ongoing innovative developments pave the way for short- to mid-term improvement of both clinical diagnostics and therapeutic procedures as well as for the extension of the applicability of established techniques for new medical indications. Novel biomedical laser applications based on new laser types or novel energy delivery systems could increase the usable range of laser-tissue interactions, and thus improve target-oriented, high precision application of laser radiation in clinical practice. Starting with basic research and development (R&D), these new energy delivery techniques, combined with innovative key medical techniques, are now at the translational stage into the clinics. Conferences with a special focus on medical laser applications and laser-tissue interactions have been established worldwide and not only cover the great diversity of these laser applications but also provide the necessary interdisciplinary forum for scientists, engineers, technicians, and medical practitioners (see Conference calendar in this issue) [1].

This issue of Photonics & Lasers in Medicine reflects a broad range of laser-assisted diagnosis and treatment modalities, and highlights the efforts to bridge the gap between institutional R&D and clinical application and/or clinical observations, which subsequently impact improvements in medical devices or techniques. Laser-advanced medical applications are presented which are either close to or have already become part of the clinical practice [2].

From a clinician’s point of view, optical biopsy and non-destructive diagnosis techniques still face challenges on their way towards recognition as routine techniques in daily practice. Although histopathology of excised tissue samples is still the gold standard for diagnosis, various new non-invasive photonics-based diagnostic techniques are being developed continuously. In oncology, these techniques rely on the physical and biochemical changes that precede or mirror malignant changes within tissue [3–8] and involve simple optical tissue interrogation techniques. Their accuracy, expressed in terms of sensitivity and specificity, was reported in a number of studies and suggests the potential for a cost-effective, real-time, in-situ diagnosis for specific diseases and conditions.

Non-destructive testing or clinically non-invasive diagnosis is a R&D field that uses photons of the electromagnetic (EM) spectrum of longer wavelengths compared to the wavelength of photons with ionization capacity. The spectrum between 0.1 THz and 10 THz or the wavelength spectrum between 30 μm and 3 mm is known as the “THz band” or “millimeter-submillimeter band”, and physicists call it the “far infrared” region [9]. In comparison to optical and radiofrequency techniques, the THz spectrum represents a relatively young R&D activity which emulates these techniques [10–12]. From the biological point of view, the application of the THz waves is limited to less than a millimeter in depth. Trevino-Palacios [13] from the Instituto Nacional de Astrofísica, Optica y Electronica of Mexico presents an overview of THz developments and THz devices with regard to possible medical applications. Medical and non-medical applications are described together with the fundamental limitations of THz studies, which have to be overcome before the possible clinical impact of this technique can be assessed.

Within the EM spectrum, there is considerable use of the near-infrared region for non-destructive diagnostic and imaging techniques, of which optical coherence tomography (OCT) features the most prominently. OCT as an imaging modality is often considered the optical analog of ultrasound. High-resolution cross-sectional imaging of the internal structure of biological tissues can be performed depending on the tissue’s optical properties of the target and the wavelength employed. Thus, OCT is a promising biomedical imaging method because it can function as a (non-invasive) optical biopsy method, enabling imaging of pathologies in real-time providing three-dimensional and en-face images. Although OCT is already used routinely in ophthalmology [14], dermatology [15] and cardiology [16], in-vivo studies and clinical investigations are still under way to find new diagnostic indications for this technique. A promising approach could be for monitoring late radiation effects in head and neck cancer patients who have been treated with radiotherapy. These patients often suffer from late radiation effects, sometimes months and even years after the original therapy. Currently, diagnosis and monitoring of the later effects, such as oral toxicities, are performed by simple visual inspection by the attending physician. Subsurface imaging and image processing could be useful for monitoring these late effects more effectively. Davoudi et al. [17], from the Department of Medical Biophysics at the University of Toronto, Canada, demonstrated the ability of OCT, combined with newly developed image processing techniques, to reveal subsurface microstructural changes in the oral mucosa in a clinical study. The data extracted from the OCT images demonstrated significant microstructural and microvascular differences between the two test groups under investigation, made up of either healthy volunteers or patients after treatment with ionizing radiation therapy. As a result, OCT, combined with the specific image analysis platform, could be used as a non-invasive, in-vivo diagnostic tool for subsurface investigation of late oral radiation toxicity. It remains to prove whether an OCT-based clinical diagnosis tool can precede the current clinical diagnosis and if this would have an impact on patient management.

Surgery in gynecology involves a wide range of energy sources (monopolar and bipolar electro surgery, laser and ultrasonic technologies). It appears that CO₂, Nd:YAG, and KTP lasers provide alternative methods for achieving similar results, when compared to traditional endoscopic techniques, such as cold-cutting monopolar and bipolar energy [18]. Gynecologists using these tools should be aware of both the potential benefits and risks of all these energy deposition-based therapies. While laboratory-based studies have reported differences between various energy sources, these differences may not be clinically significant or relevant. Rather, the choice of instrumentation may depend on the nature of the surgical task being performed. It is important that surgeons have an understanding of the biophysical basics of these technologies not only to understand the limitations and potential dangers but also to enable them to utilize the most appropriate energy source(s) in an appropriate clinical setting [19]. For example, leiomyomas are benign soft-tissue neoplasms that arise from smooth muscle. Symptom relief management is the major goal for treatment of women with significant clinical symptoms. For symptomatic myomas, hysterectomy is a definitive solution; however, less-invasive operation techniques are emerging [20]. Fürst et al. [21] from the University Hospital of Munich, Germany, describes ex-vivo investigations based on using a diode laser emitting a wavelength of 1470 nm and a fiber-assisted handling procedure for enucleation of myomas from human uteri myomatosus [21].

Tattoos, or pe’a (the popular name of the traditional male tattoo of Samoa), demonstrate the strong ties many Samoans feel for their culture. Samoans, both men and women, practice the art of tattooing. The Samoan word for tattoo is “tatau” which means “correct or workmanlike”. It also signifies the correct quadrangular figures with reference to the fact that Samoan tattoo designs do not include circular lines. Early Englishmen mispronounced the word “tatau” and borrowed it into popular usage as tattoo [22]. Tattooing has been practiced across the globe since at least Neolithic times, as has been found in mummified preserved skin, ancient art, and archeological records [23]. However, direct evidence for tattooing on mummified human skin only goes back to the 4th century BC. The oldest discovery of tattooed human skin to date was found on the body of Ötzi, the Iceman, dating to between 3370 and 3100 BC [24]. Even though traditional tattooing is a painful process, tattooing is nowadays in widespread use for beautification of the body. Therefore, there is a growing need for investigations on complications occurring during the placement or removal of tattoos [25], which includes skin reactions associated with tattoos [26]. Pedrol et al. [27] from the Clinical Research Unit in Barcelona, Spain, presents a study with a description of the evolution of skin lesions induced by tattooing. Images of skin damage are shown caused by contemporary professional tattooing techniques, with and without ink. The authors conclude that knowledge of the tattooing procedure could lead to a better understanding of its potential complications.

Laser-light delivery for interstitial, thermal, hyperthermal, non-thermal, biomodulating and photodynamic purposes is the domain for fiber techniques with cylindrical and radial scattering characteristics [28]. The light distribution patterns were initially generated by using scattering bodies, which were attached to the distal part of the fibers, resulting in a limited resistance to temperature and laser power. Additionally, the large outer diameter and short active length limited the indications that these fiber types could be used for. Delivery fiber applicators based on photosensitive quartz optical fibers with scattering centers inscribed by a structured beam from an excimer laser were realized previously as cylindrical diffusers with high performance [29]. In this issue, Köcher et al. [30] from the Laser- und Medizin-Technologie GmbH, Berlin (LMTB), Germany, report on the requirements and development of a manufacturing procedure for cylindrical diffusers by means of internal structuring of silica glass fibers for use in medicine. In this context, another article by Pantaleone et al. [31] from Sweden describes the path to commercialization of these scattered light application systems for laser ablation of tissue and immunostimulating interstitial laser thermotherapy.

Optical fiber technology has significantly enhanced photonics applications in basic life sciences research and in biomedical diagnosis, therapy, monitoring, and surgery. The unique operational properties of fibers have been used to realize advanced biomedical functionality for areas such as illumination, imaging, minimally invasive surgery, tissue ablation, biological sensing, and tissue diagnosis [32]. Optical fiber sensing principles and techniques, and in particular, their multitasking potential, can be exploited for biological and medical applications. For example, a change in the refractive index within the fiber components is a possible source of signals for identification of specific biomolecules. Mohsenirad et al. [33] from the Nano-photonic and Optoelectronic Research Laboratory in Teheran, Iran, propose the construction of a two-dimensional, photonic crystal biosensor based on two waveguides and a nanocavity with a hexagonal lattice of air holes in a silicon slab. The proposed structure was designed for the wavelength range of 1.5259–1.6934 μm, with a sensitivity of ~83.75 nm/RIU.

The original research papers within this issue illustrate the encouraging efforts in R&D, commercialization and application of the advanced photonics techniques used in light-assisted diagnostic and therapeutic interventions. It also demonstrates that previous technical developments can be improved upon to enable commercialization and that traditional applications should be reconsidered due to new insights into their potential side effects.

Last but not least we would like to draw your attention on the press release on the this year’s winner of the Innovation Award Berlin Brandenburg [34]. The LMTB was awarded for the development of a sensor for the non-destructive determination of hemoglobin in blood products, a good example for the successful development of non-invasive optical detection systems.