Rudolf Steiner

Institut für Lasertechnologien in der Medizin und Meßtechnik an der Universität Ulm

Determination of the iron oxide nanoparticles (IONPs) local temperature during laser heating is important in the aspect of laser phototherapy. We have carried out theoretical modeling of IONPs local electromagnetic (EM) field enhancement and heating under the laser action near individual IONPs and ensembles of IONPs with different sizes, shapes and...

The main problem in the photodynamic therapy (PDT) of tumors is insufficient light exposure to tissue or the appearance of undesirable surface effects. The reason is the irregular distribution of the absorbed light dose by depth. The influence of the spot diameter on the relative fluence rate in the near-surface layer of the cervical tissue was stu...

The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, o...

Nanoparticles are used as drug carriers to increase the selectivity and effectiveness of therapy, as well as for combined therapy that utilizes different effects. Iron oxide nanoparticles are promising in this aspect. Due to magnetic properties, they can be used as a contrast agent for magnetic resonance imaging. Also, iron oxide nanoparticles coul...

The monocyte/macrophage cell lineage reveals an enormous plasticity, which is required for tissue homeostasis, but is also undermined in various disease states, leading to a functional involvement of macrophages in major human diseases such as atherosclerosis and cancer. We recently generated in vivo evidence that crystalline, nonfluorescent nanopa...

Background: Organic crystalline nanoparticles (NPs) are not fluorescent due to the crystalline structure of the flat molecules organized in layers. In earlier experiments with Aluminum Phthalocyanine (AlPc)-derived NPs, the preferential uptake and dissolution by macrophages was demonstrated [3]. Therefore, inflamed tissue or cancer tissue with acc...

The development and the spectral research of unique coating as crystalline nanoparticles of IR photosensitizers were performed for the creation of hydroxyapatite implants with photobactericidal properties. It has been proved that by the interaction of nanoparticles covering implant with the polar solvent, which simulates the interaction of the impl...

Einsteins Idee von der stimulierten Emission von Strahlung (Einstein 1917) bildete die Grundlage für die Erfindung des LASERs (Akronym für „Light Amplification by Stimulated Emission of Radiation“, eingeführt von Gordon Gould). Albert Einstein entwickelte das theoretische Konzept für die Lichtausbreitung in Wellenpaketen (Photonen) und für die sog....

In this present study we applied Raman and fluorescence microscopy to investigate the internalisation, cellular distribution and effects on cell metabolism of photosensitizer nanoparticles for photodynamic therapy in fibroblasts and macrophages.

Nanoparticles made from aluminum phthalocyanine (AlPc) raw material are non-fluorescent because of fluorescence quenching due to the molecular crystalline structure forming a stack of flat molecular layers. However, when AlPc molecules become detached from the particle, fluorescence occurs. First observations demonstrated the benefit of using alumi...

In der Ästhetischen Chirurgie sind Laser nicht mehr wegzudenken: Narben, Falten und Tätowierungen, Facial Rejuvenation, Nasen- und Blepharoplastik oder zahnärztlich-ästhetische Behandlungen – vielfältig sind die Indikationen, bei denen Laser Mittel der Wahl oder eine erfolgversprechende Alternative zur klassischen Chirurgie sind. Laserbehandlungen...

In this present study we applied Raman and fluorescence microscopy to investigate the internalisation, cellular distribution and effects on cell metabolism of photosensitizer nanoparticles for photodynamic therapy in fibroblasts and macrophages.

The group of editors would like to express their thankfulness to all the contributing authors for submitting their valuable and informative manuscripts. We would like to wish all the authors success in their researches.

Using the energy transfer kinetics probe we found that –OH acceptors are distributed in the volume of the Nd3+:YPO4 nanoparticles as crystal structure defects or in the mesopores.

The diagnosis of tissue alterations by fluorescence spectroscopy or different modalities of fluorescence imaging is widely used to detect precancerous or cancerous lesions. Demarcation of such lesions supports the efficient treatment either by photodynamic therapy (PDT) or conventional surgical intervention. Autofluorescence of tissue intrinsic chr...

Das Verständnis der Laser-Gewebe-Wirkungen und der optimale Gebrauch des Lasers ist der wichtigste Hinweis in diesem Kapitel. Die wellenlängenabhängige Eindringtiefe des Laserlichts in das Gewebe bestimmt die Wärmeentwicklung und die Nekrosezone. Das Konzept der Photothermolyse, das von Rox Anderson eingeführt wurde, verbesserte die Spezifität der...

Blitzlampen (IPL) sind hochenergetisch gepulste Lichtquellen, die polychromatisches, inkohärentes Licht mit einem breiten Wellenspektrum emittieren. Bei IPL-Geräten kann mittels wechselbarer Filtersätze das von der Blitzlampe emittierte Licht auf den gewünschten Spektralbereich eingeengt werden. Der Spektralbereich des emittierten Lichtes wird dabe...

Verfolgt man die Geschichte der Laserentwicklungen und parallel dazu die medizinischen Anwendungen, so ist ein kontinuierlicher Fortschritt bei den Laserwirkungen und den Geräteentwicklungen zu beobachten. Das Verständnis der charakteristischen Eigenschaften des Photons und des Lichts bildet die Grundlage für alle Anwendungen zur medizinischen Diag...

Although several treatment options are available for hepatocellular carcinoma (HCC), their application is mostly restricted to early diagnosed cases or includes liver transplantation, which is rarely available due to donor scarcity. The attractiveness of PDT as a cancer treatment does not only come from its minimal invasiveness, but also from the h...

The functionalization of dental implants, aiming at the improvement of long-term acceptance, is of pivotal interest in dental research. Bone, connective tissue, and oral epithelium are in direct contact to the implant surface and exhibit distinct requirements for proper growth and differentiation. The authors applied direct laser writing and atomic...

Intense pulsed light (IPL) systems are high intensity pulsed sources that emit polychromatic light in a broad wavelength spectrum, which can differ between flash lamps and manufacturers. IPL can be configured for different emission spectra by varying filtration, lamp type, or current density. The waveband of light emitted by IPL is chosen so that i...

Understanding laser-tissue interactions and using the laser in an optimal way are the most important messages in this chapter. The wavelength-dependent penetration depth of laser light into tissue determines heat flow and the thickness of the zone of necrosis. The concept of photothermolysis, introduced by Rox Anderson, improved specificity of lase...

Following the history of lasers and, in parallel, the applications in medicine demonstrates the continuous improvement of insight into laser reactions and development of devices. Understanding the characteristics of photons and light is the basis for all applications in medical diagnosis and therapy. Knowledge about the physical principle of lasers...

Hintergrund Die Bestrahlung eines Photosensibilisators mit sichtbarem Licht, vorzugsweise Laserlicht im roten Spektralbereich, und in Gegenwart von molekularem Sauerstoff führt zu einer photochemischen Reaktion, die als photodynamische Therapie (PDT) bezeichnet wird. Die PDT wird zunehmend für die Behandlung von Hauttumoren eingesetzt. Für den Erfo...

The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell c...

Novel gadolinium-based mifepristone conjugates were synthesised using various synthetic routes. Moderate antiprogestagenic activity of the new conjugates was observed in human breast cancer cells (T47-D cells) using AP (alkaline phosphatase) assay. The amount of incorporated Gd determined by inductively coupled plasma mass spectroscopy (ICPMS) indi...

Presbyopia is a wide spread phenomenon in elder people and is caused by the hardening of the lens in human eyes. Research is performed to make such lenses again more flexible by application of geometrically optimised cuts through the lens with a femtosecond-laser. Different protein agglomerations are responsible for the flexibility reduction of the...

Summary Laser-induced interstitial thermotherapy (LITT) is a method which has become a promising alternative for the palliative treatment of non-resectable metastases. At an early stage, a bare fibre was inserted, e.g. into liver metastases. Sophisticated applicators, with an integrated cooling system, are now used to increase the coagulated volume...

A series of mifepristone derivatives with different "linker groups" in position 4' of the phenyl ring in the 11beta-position of the steroid scaffold (2-41) have been synthesized. Their antigestagenic activites were determined in a cell-based assay (alkali phosphatase assay in T47-D breast cancer cells) and compared with that of the parent compound...

This paper reports on the content of an international training course on “Lasers and Light in Urology”, which was organized by the International Center for Advanced Studies in Health Sciences and Services (ICAS) of the University of Ulm and the ‘Institut für Lasertechnologien in der Medizin und Meßtechnik’ (ILM) an der Universität Ulm. This report...

Spectral fluorescence lifetime imaging (SLIM) is an advanced imaging technique, which combines spectral with time resolved detection. Real spectral information is achieved by using a grating in front of a PML-array, which allows time-correlated single photon counting (TCSPC). Whereas spectrally resolved fluorescence imaging alone has a reasonable s...

Aim of this study was to evaluate the potential of denaturation of hormone active tissue in the thyroid gland by laser induced interstitial thermotherapy (LITT) as a treatment of autonomous hyperthyroidism. An interstitial thyroid laser application (Nd:YAG 1064 nm, 5W, 2 min) was performed in 5 pigs. During laser application, the laryngeal recurren...

The potential of medical applications of Mid-IR lasers is still not at its end. Continuous research of laser-tissue interactions steadily opened new fields of medical applications for the Er:YAG laser at 2,94 nm wavelength, due to the high absorption of this wavelength in water, biological soft and hard tissue. Lasers with emission at 2 μm had no r...

The investigation of living cells at physiological conditions requires very sensitive, sophisticated and non-invasive methods. In this study, Raman spectroscopy, a chemically and structurally sensitive measuring technique is combined with high-resolution confocal microscopy to investigate different biomolecules inside of cells. In Raman spectral im...

Objective: Over 2 million people in Germany suffer from chronic wounds. Only few patients underwent a surgical debridement, because this treatment is painful and has to be performed mostly under general anaesthesia, which is a risk in particular for elderly patients. The aim of this project was to establish a feedback-controlled ablation system ded...

The investigation of living cells at physiological conditions requires very sensitive, sophisticated, non invasive methods. In this study, Raman spectral imaging is used to identify different biomolecules inside of cells. Raman spectroscopy, a chemically and structurally sensitive measuring technique, is combined with high resolution confocal micro...

To test the effects of a continuous medium flow inside DegraPol scaffolds on the reepithelialization and revascularization processes of a tissue-engineered trachea prosthesis. In this proof-of-principle study a continuous medium flow was maintained within a tubular DegraPol scaffold by an inserted porous catheter connected to a pump system. The imp...

We used spectrally resolved fluorescence lifetime imaging (SLIM) to investigate the mitochondria staining dye rhodamine 123 and binding of DAPI to RNA and DNA in cells. Moreover, different components of the photosensitizer Photofrin were resolved in cell cultures by SLIM. To record lifetime images (tau-mapping) with spectral resolution we used a la...

SLIM (spectral fluorescence lifetime imaging) is a highly sophisticated new technique, which combines spectral resolved and time resolved detection. Real spectral information is achieved by using a grating in front of a PML-array, which allows time-correlated single photon counting (TCSPC). Whereas spectrally resolved fluorescence imaging alone has...

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartil...

High resolution optical coherence tomography (OCT) has become a new diagnostic tool for the evaluation of structural changes of the skin. The instrumental resolution (3 μm lateral and 5 μm axial) was determined by the point spread function of 1nm particles. OCT now offers diagnosis of inflammation processes in deeper skin layers, not detectable by...

During the last decades laser technology has continuously developed. New types of lasers as ultra-short pulsed lasers in the femtosecond regime entered medical applications in ophthalmology. Diode lasers became more powerful and smaller with a broader range in wavelengths. In future new sources will also be used in medicine, fibre lasers, LEDs and...

In animal lab experiments with pigs we evaluated the use of laser-induced thermotherapy (LITT) on thyroid tissue. A laser application using the Nd:YAG-Laser (1064nm) was performed for 2min with 5W on both lobes of the thyroid gland in 5 pigs. This resulted in spheroid coagulation zones of 5–8mm in diameter. No impairment of the conduction rate of t...

One of the most promising clinical applications of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PP IX) is the fluorescence diagnosis and photodynamic treatment of malignant brain tumours. In order to obtain a deeper understanding of the cellular processes involved, U373-MG human glioblastoma cells were used as model system to study intr...

Flash-photolysis measurements were performed on normal and on chemically modified human adult hemoglobin solutions in the concentration range between 1 to 100 μM (for complete molecule) and in the pH range between pH 5 and pH 9. The energy of the irradiating flash was varied continuously from 20 to 400 Joules. It is shown that the fast reaction obs...

Background: The potential application of TOOKAD(®)-PDT for the treatment of blood vessels was investigated. TOOKAD(®) (WST09), a novel palladium-bacteriopheophorbide absorbs light in the near IR with a high quantum yield of intersystem crossing. Our study assessed the efficacy of this drug in inducing vascular damage with a view to its possible us...

The present paper describes the chemical synthesis and in vitro characterization of a novel, high-affinity, fluorescent progesterone receptor (PR) antagonist. The three-step synthesis was carried out starting from mifepristone. After demethylation with calcium oxide, the methylamino group was alkylated with 6-bromohexanol, and the resulting compoun...

We developed a new surgical procedure to improve the recurrence rate using an Er:YAG laser as dissection tool for the carpal ligament with the objective to ablate a small amount of the carpal ligament and to denaturate its ends. The Er:YAG Laser was transmitted to the applicator via a GeO fiber. With this system we proceeded 10 carpal ligament diss...

An overview on some advanced techniques of fluorescence spectroscopy and fluorescence microscopy is given. These techniques include time-resolved fluorescence spectroscopy, energy transfer spectroscopy (FRET), total internal reflection fluorescence microscopy (TIRFM) and fluorescence lifetime imaging (FLIM). The principle of these methods is explai...

Optical Coherence Tomography (OCT), a promising new and non invasive technology for diagnosis of tissue is on the cusp of being introduced in clinical dermatology. OCT instrumentations are commercially available (e.g. ISIS Optronics GmbH, Mannheim) which provide two dimensional images of high resolution (lateral 3μm, axial 5μm) of morphological mic...

A novel compact illumination device in variable-angle total internal reflection fluorescence microscopy (VA-TIRFM) is described. This device replaces the standard condensor of an upright microscope. Light from different laser sources is delivered via a monomode fibre and focused onto identical parts of a sample under variable angles of total intern...

A setup consisting on a laser scanning microscope equipped with appropriate detection units was developed for time-resolved intracellular fluorescence spectroscopy and fluorescence lifetime imaging (FLIM) for online detection of structural changes of various biomolecules. Short-pulsed excitation was performed with a diode laser which emits pulses a...

A setup consisting on a laser scanning microscope equipped with appropriate detection units was developed for time-resolved intracellular fluorescence spectroscopy and fluorescence lifetime imaging (FLIM) for on-line detection of structural changes of various biomolecules. Short-pulsed excitation was performed with a diode laser which emits pulses...

This work describes the time-resolved fluorescence characteristics of two different photosensitizers in single cells, in detail mTHPC and 5-ALA induced PPIX, which are currently clinically used in photodynamic therapy. The fluorescence lifetime of the drugs was determined in the cells from time-gated spectra as well as single photon counting, using...

An infrared laser system was developed based on a diode pumped YLF : Er-crystal emitting continuously at a wavelength of 2.8 gm. In order to irradiate biological samples at a microscopic scale, the laser was adapted to an inverse microscope using an IR-transmitting reflecting microscope objective. The TEM00 output beam can be focused on biological...

To develop a new ab externo technique for glaucoma trabecular surgery using the infrared Er:YAG laser radiation (2.9 micrometer) guided into Schlemm's canal by an optical fiber. In order to create a drainage canal to the anterior chamber, a quartz fiber (core diameter: 100 micrometer) coupled to an Er:YAG laser was shielded by a metal canula (diame...

This work describes the time-resolved fluorescence characteristics of 5-ALA induced PPIX in living cells. The intracellular fluorescence lifetime was determined from time-gated spectra as well as single photon counting, using a ps pulsed diode laser for fluorescence excitation. The diode laser which emits pulses at 398 nm with 70 ps duration was co...

Intraoperative graft patency verification is of major clinical importance for quality control after coronary artery bypass grafting (CABG). The purpose of this study was assessment of graft patency and stenosis of variable severity by fluorescence angiography (FA) using indocyanine green (ICG). For this purpose 32 domestic pigs (40–70 kg) were exam...

Intracellular location of photosensitizers (meso- tetraphenylporphyrin tetrasulfonate (TPPS4), meso-tetraphenylporphyrin monosulfonate (TPPS1)) was examined in endothelial cells using fluorescence microscopic and fluorescence spectroscopic techniques. For fluorescence excitation, total internal reflection (TIR) illumination or epi-illumination was...

This article describes a setup for subcellular time-resolved fluorescence spectroscopy and fluorescence lifetime measurements using a confocal laser scanning microscope in combination with a short pulsed diode laser for fluorescence excitation and specimen illumination. The diode laser emits pulses at 398 nm wavelength with 70 ps full width at half...

Development of minimal invasive diagnostics methods is of great importance in today's healthcare. The present work deals with the measurements of glucose concentration in small drops, its volume being in the range of 1 (mu) L and its glucose concentration being in the range of 1-10 mM. The aim of the work was to develop robust quantitative method o...

 Selenium dioxide oxidation allows the selective introduction of a hydroxyl group at position 6 of the steroid skeleton of the antihormone (11β, 17β)-11-(4-dimethylamino-phenyl)-17-hydroxyl-17-(1-propynyl)-estra-4,9-dien-3-one (mifepristone, RU 486) and leads in a one-step procedure to two diastereomeric oxidation products. Their structure (6α- and...

We studied theoretically and experimentally the luminescence decay from excited erbium levels and laser action at 2.8 micrometers of lithium-yttrium double-fluoride LiYF4:Er3+ (YLF:Er3+) crystals. Experimental studies of the luminescence decay curves were carried out using selective laser excitation at 4I13/2 level by Q-switch pulsed Yb-Er glass la...

The chorioallantoic membrane (CAM) of the fertilized egg allows grafting of human melanomas for short-term investigations and offers the opportunity to investigate the behavior of metastasizing cells and the release of S100β into peripheral blood. Tissue from one primary melanoma as well as cutaneous and subcutaneous metastases of 10 melanoma patie...

This article describes a setup for subcellular time-resolved fluorescence spectroscopy and fluorescence lifetime measurements using a confocal laser scanning microscope in combination with a short pulsed diode laser for fluorescence excitation and specimen illumination. The diode laser emits pulses at 398 nm wavelength with 70 ps full width at half...

Photodynamic therapy (PDT) is a form of cancer treatment based on the selective accumulation of a photosensitizer in neoplastic tissue. The fluorescent properties of a photosensitizer permit diagnostic localization of primary tumours and/or metastasis. Occult lesions are hard to detect and can easily be missed during routine laparoscopy. Fluorescen...

For hair removal commonly lasers are used with wavelengths being selectively absorbed by melanin .As a consequence, laser radiation leads to an increase of the temperature not only in melanin containing structures of the hair but also in the epidermis. Therefore, we simulated and studied the laser induced temperature development in tissue for vario...

For hair removal lasers are used with wavelengths being selectively absorbed by melanin. As a consequence, laser radiation leads to an increase of the temperature not only in melanin containing structures of the hair, but also in the epidermis. Therefore, we simulated and studied the laser induced temperature rise in tissue for different laser wave...

Purpose: Examination of morphology in corneal ablation induced by a q-switched Er:YSGG (2.79 microm) laser and a free-running Er:YAG laser (2.94 microm). Methods: Defined ablation of 6-mm diameter and 15, 30, 55, 90, and 120-microm depth was performed on freshly enucleated swine eyes. Er:YSGG laser parameters: fluence 1.6 J/cm2, frequency 6 Hz,...

Sulfonated meso-tetraphenylporphyrins of different hydrophilicity were microspectrofluorimetrically examined in endothelial cells using total internal reflection (TIR) illumination or epi-illumination. Since the penetration depth of the evanescent field during TIR illumination is limited to a few hundred nanometers, photosensitizers were almost sel...