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Frontiers of Optoelectronics

Front. Optoelectron.    2017, Vol. 10 Issue (3) : 239-254     DOI: 10.1007/s12200-017-0724-6
Research and developments of laser assisted methods for translation into clinical application
Ronald SROKA1,2(), Nikolas DOMINIK1,2, Max EISEL1,2, Anna ESIPOVA3, Christian FREYMÜLLER1,2, Christian HECKL1,2, Georg HENNIG1,2, Christian HOMANN1,2, Nicolas HOEHNE1,2, Robert KAMMERER2,5, Thomas KELLERER1,2, Alexander LANG1,2, Niklas MARKWARDT1,2, Heike POHLA2,4, Thomas PONGRATZ1,2, Claus-Georg SCHMEDT1,3, Herbert STEPP1,2, Stephan STRÖBL1,2, Keerthanan ULAGANATHAN1,2, Wolfgang ZIMMERMANN2,4, Adrian RUEHM1,2
1. Laser-Forschungslabor, LIFE-Center, Hospital of University, Ludwig-Maximilians University Munich, Munich, Germany
2. Department of Urology, Hospital of University, Ludwig-Maximilians University Munich, Munich, Germany
3. Department of Vascular Surgery, Diakonie Klinikum, Schwäbisch Hall, Germany
4. Labor für Tumorimmunologie, LIFE-Center, Hospital of University, Ludwig-Maximilians University Munich, Munich, Germany
5. Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald- Insel Riems, Germany
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Biophotonics and laser medicine are very dynamic and continuously increasing fields ecologically as well as economically. Direct communication with medical doctors is necessary to identify specific requests and unmet needs. Information on innovative, new or renewed techniques is necessary to design medical devices for introduction into clinical application and finally to become established after positive clinical trials as well as medical approval. The long-term endurance in developing light based innovative clinical concepts and devices are described based on the Munich experience. Fluorescence technologies for laboratory medicine to improve non-invasive diagnosis or for online monitoring are described according with new approaches in improving photodynamic therapeutic aspects related to immunology. Regarding clinically related thermal laser applications, the introduction of new laser wavelengths and laser parameters showed potential in the treatment of varicose veins as well as in lithotripsy. Such directly linked research and development are possible when researchers and medical doctors perform their daily work in immediate vicinity, thus have the possibility to share their ideas in meetings by day.

Keywords translational biophotonics      thermal laser application      fluorescence diagnosis      on-line monitoring      lithotripsy      phlebology      photodynamic therapy (PDT)      laboratory medicine     
Corresponding Authors: Ronald SROKA   
Just Accepted Date: 04 July 2017   Online First Date: 29 August 2017    Issue Date: 26 September 2017
 Cite this article:   
Ronald SROKA,Nikolas DOMINIK,Max EISEL, et al. Research and developments of laser assisted methods for translation into clinical application[J]. Front. Optoelectron., 2017, 10(3): 239-254.
Fig.1  Prototype ZnPP fluorometer device is shown (a), with the optical fiber attached to the front side. The applicator tip is brought in contact of the lower lip of a patient (b), while the feedback light indicates a measurement site suitable for a reliable ZnPP measurement
Fig.2  Results of a clinical study on 56 women after childbirth. Shown is the comparison of the non-invasive ZnPP fluorescence measurements with the reference HPLC determination
Fig.3  Fluorescence excitation of coproporphyrin I and uroporphyrin I spectrum at (a) pH= 7 and (b) pH= 1.5 at the same molar concentration. The quotient of coproporphyrin to uroporphyrin excitation spectra reveals the ideal excitation wavelength for selective excitation of either porphyrin (green). For the acidic samples, the ratio yields a much higher difference between uroporphyrin and coproporphyrin excitation, which allows for a more precise differentiation between the two porphyrins
Fig.4  Fluorescence spectra of urine spiked with uroporphyrin and coproporphyrin (a). The picture shows, that 397 nm excitation yields a much higher fluorescence than 409 nm excitation, which is indicative of a sample with a higher amount of coproporphyrin than uroporphyrin. From the calibration curves (b), two equations for each excitation wavelength can be derived. With the intensity measured during the two wavelength excitation, the equations can be solved and return the concentration of each porphyrin
Fig.5  (a) Schematic of a central phantom experiment: The opto-mechanical biopsy needle (here: only with side-view fibers) was immerged in a liquid brain phantom at different distances from a blood-filled glass capillary (drawn in red, orange and green, respectively). After adjusting the fiber-to-capillary distance, the needle was moved inz-direction. The capillary orientation was perpendicular to the drawing plane. (b) Experimental results of the remission ratioI578/I650 for the three fiber-to-capillary distances indicated left
Fig.6  Sketch of an opto-mechanical biopsy needle with three integrated glass fibers for light delivery and collection. One bare-end fiber is used to detect tumor tissue via PpIX fluorescence in front of the needle. Two side-view fibers are placed inside the tissue suction window to assess the sucked tissue regarding the presence of tumor tissue (via PpIX fluorescence) and blood vessels (via remission spectrometry)
Fig.7  Schematic representation of interstitially placed light applicators in the treatment planning software. The active portions along the stereotactic trajectories from which radiation emanates are indicated in yellow, the tumor volume to be irradiated is indicated in purple [19]
Fig.8  Light dose dependent survival and caspase 3/7 activation of U87 and U373 cells. For investigation of the transcriptome, sublethal light doses of 1 J/cm2 (U87) and 0.5 J/cm2 (U373) were applied (black lines in the graphs). Adopted from Ref. [32]
Fig.9  Genes upregulated by non-lethal PDT. Adopted from Ref. [32]
Fig.10  Temperature sensor consisting of ruby sphere (outer diamter, OD= 1 mm) attached to an optical fiber (core diameter 400 µm). (a) Front view; (b) side view
laser mode pulse length/ms energy/J frequency/Hz power/W
1 0.25 1.0 10 10
2 1.0
3 1.6
4 1.2
5 0.25 0.5 5 5
6 0.84
7 1.3
8 1.6
Tab.1  List of laser modes used for preliminary fragmentation efficiency measurements using 5 and 10W laser power at different pulse lengths
Fig.11  Preliminary results using different optical pulse lengths, sorted by stone breaking times. The perpendicular lines illustrate the particular breaking times for each laser mode. The total fragmentation time with its standard deviation is the combination of the green bar (time before stone break) and the red bar (chasing fragments). On the right hand side the dust and fragmentation ratios are displayed in percent for each mode
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