Aus dem Laser-Forschungslabor der Laser-Immunologie-Forschungs-Einrichtung (LIFE-Zentrum) Ludwig-Maximilians-Universität München Bereichsleitung: PD Dr. rer. biol. hum. Ronald Sroka Direktor: Prof. Dr. med. Christian Stief UNTERSUCHUNGEN ZUR LASERINDUZIERTEN LITHOTRIPSIE Dissertation zum Erwerb des Doktorgrades der Humanbiologie an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Maximilian Eisel aus München 2019 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: PD Dr. rer. biol. hum. Ronald Sroka Mitberichterstatter: PD Dr. med. Markus Bader Prof. Dr. med. Alexander Karl Mitbetreuung durch den promovierten Mitarbeiter: Dr. rer. nat. Adrian Rühm Dekan: Prof. Dr. med. dent. Reinhard Hickel Tag der mündlichen Prüfung: 17.12.2019 a b Inhaltsverzeichnis Publikationsliste ............................................................................................................................................ 1 Abstract .......................................................................................................................................................... 3 Zusammenfassung ........................................................................................................................................ 5 Untersuchungen zur laserinduzierten Lithotripsie .................................................................................. 7 Pathogenese & Pathophysiologie humaner Harnsteine ................................................................. 7 Diagnose der Urolithiasis .................................................................................................................... 9 Therapie der Urolithiasis ................................................................................................................... 10 Originalmanuskripte................................................................................................................................... 13 In vitro investigations of propulsion during laser lithotripsy using video tracking .................. 14 Holmium:yttrium-aluminum-garnet laser induced lithotripsy: in-vitro investigations on fragmentation, dusting, propulsion and fluorescence ................................................................... 23 Investigation of optical properties of dissected and homogenized biological tissue ............... 39 Literaturverzeichnis .................................................................................................................................... 51 Danksagung ................................................................................................................................................. 61 Lebenslauf ................................................................................................................................................... 62 Persönliche Daten .............................................................................................................................. 62 Berufserfahrung .................................................................................................................................. 62 Schule & Studium .............................................................................................................................. 62 Wissenschaftliche Lehre .................................................................................................................... 63 Eidesstattliche Versicherung ..................................................................................................................... 65 c d PUBLIKATIONSLISTE Veröffentlichungen in begutachteten Fachmagazinen: Maximilian Eisel, Stephan Ströbl, Thomas Pongratz, Frank Strittmatter, Ronald Sroka, „In vitro investigations of propulsion during laser lithotripsy using video tracking“, Lasers Surg. Med., 50: 333-339. doi:10.1002/lsm.22770 (2018), JIF: 2.726 Maximilian Eisel, Stephan Ströbl, Thomas Pongratz, Frank Strittmatter, and Ronald Sroka, „Holmium:yttrium-aluminum-garnet laser induced lithotripsy: in-vitro investigations on fragmen- tation, dusting, propulsion and fluorescence", Biomed. Opt. Express 9, 5115-5128 (2018), JIF: 3.482 Maximilian Eisel, Stephan Ströbl, Thomas Pongratz, Herbert Stepp, Adrian Rühm, Ronald Sroka, "Investigation of optical properties of dissected and homogenized biological tissue", J. Bi- omed. Opt. 23(9) 091418 (24 September 2018), JIF: 2.367 Sroka, Ronald; Dominik, Nikolas; Eisel, Maximilian; Esipova, Anna; Freymüller, Chris- tian; Heckl, Christian; Hennig, Georg; Homann, Christian; Höhne, Nicolas; Kammerer, Robert, Kellerer, Thomas; Lang, Alexander; Markwardt, Niklas; Pohla, Heike; Pongratz, Thomas; Schmedt, Claus-Georg; Stepp, Herbert; Ströbl, Stephan; Ulaganathan, Keer- thanan; Zimmermann, Wolfgang; Rühm, Adrian; Research and developments of laser assisted meth- ods for translation into clinical application; Frontiers of Optoelectronics 10(3) 239-254 (2017) Maximilian Eisel, Frank Strittmatter, Stephan Ströbl, Christian Freymüller, Thomas Pongratz, Ronald Sroka, “Comparative investigation of multiple-used and single–use flexible endo- scopes for urological interventions” (Im Revisionsprozess) Markus Bader, Maximilian Eisel, Frank Strittmatter, Abdulmajeed Alghamdi , Christian Stief, Thomas Pongratz, Ronald Sroka, “Endoscopic clearance lithotripsy devices bench comparison of stone elimination capacity and drilling speed” (geteilte Autorenschaft) (In Bearbeitung) Maximilian Eisel, Thomas Pongratz, Frank Strittmatter, Stephan Ströbl, Ronald Sroka, “Comparison of 1.94 µm Thulium fiber laser, 2.1 µm Ho:YAG laser and 2.94 µm Er:YAG laser: Applicability and efficiency for laserinduced lithotripsy“ (In Bearbeitung) Alexander Kretschmer, Abdulmajeed Alghamdi, Maximilian Eisel, Christian Stief, Ronald Sroka, Frank Strittmatter “Evaluation of a single use ureterorenoscope in patients with kidney stones” (In Bearbeitung) 1 Veröffentlichungen in „Conference Proceedings“: Maximilian Eisel, Keerthanan Ulaganathan, Frank Strittmatter, Thomas Pongratz, Ronald Sroka, "Investigations to improve laser induced lithrotripsy (Conference Presentation)," Proc. SPIE 10038, Therapeutics and Diagnostics in Urology: Lasers, Robotics, Minimally Inva- sive, and Advanced Biomedical Devices, 100380E (19 April 2017); Ronald Sroka, Maximilian Eisel, Thomas Pongratz, Keerthanan Ulaganathan, Frank Strittmatter, "Investigations on the fluorescence of urinary stones: how to assist the MD (Conference Presentation)," Proc. SPIE 10038, Therapeutics and Diagnostics in Urology: Lasers, Robot- ics, Minimally Invasive, and Advanced Biomedical Devices, 1003804 (19 April 2017); Ronald Sroka, Thomas Pongratz, Frank Strittmatter, Maximilian Eisel, Stephan Ströbl, "In-vitro investigation on fragmentation/dusting and fluorescence during Ho:YAG-Laser induced litho- tripsy (Conference Presentation)," Proc. SPIE 10468, Therapeutics and Diagnostics in Urology 2018, 1046807 (14 March 2018); weitere Konferenzbeiträge: Mündlicher Vortrag: In-vitro investigation on fragmentation and dusting effects during Ho:YAG- Laser induced lithotripsy auf der European Conferences on Biomedical Optics (ECBO) EW4D.4, Medical Laser Applications and Laser-Tissue Interactions (MLA), München, 2017 Erfindungsmeldungen: Eisel, Maximilian; Ströbl, Stephan; Sroka, Ronald Vorrichtung zur bildgestützten, objektiven Quantifizierung und Bewegungsanalyse bei laserinduzierter Lithotripsie, 29. April 2017, Aktenzei- chen 20 2017 002 293.1, Erfindung freigegeben Eisel, Maximilian; Ströbl, Stephan; Sroka, Ronald Vorrichtung zum Schutz endoskopischer Komponenten vor ungewollter Laserapplikation, 6. Juli 2017, Aktenzeichen 20 2017 003 565.0, Erfindung freigegeben 2 ABSTRACT The ureterorenoscopy (URS) with laser induced lithotripsy is a preferred endoscopic method for the treatment of lithiasis and is in direct competition to extracorporeal shockwave lithotripsy (ESWL) and percutaneous nephrolitholapaxy (PCNL). During the laser induced lithotripsy pulsed laser light is guided to the urinary calculus via a light guide wire through the working channel of an endoscope, the stone hence is fragmented by photothermal and mechanical effects. The Ho:YAG laser (λ: 2.1 µm) ranks as gold standard for therapy of urolithiasis, due to the high absorption of this wavelength in water (α: 2.78 mm-1) and good transmission in low OH light guide wire systems. The applied laser energy causes a force to the stone and adjacent fragments, whereby stone move- ment (propulsion) is induced. Repelled fragments can be hardly detectable or may lead to an in- creased operation time due to tracking of lost fragments with the endoscope. For one thing re- maining fragments potentially result in increased recurrence rates or secondly to overall longer operation time. To address this medical need, a measurement set-up was constructed for the quantification of the fragmentation rate and propulsion at different laser parameters (optical pulse length, energy per pulse and repetition rate). With the objective to improve the locating of stones and fragments, the spectral fluorescence characteristics of human kidney stones were investigated via fluorescence microscopy using different excitation wavelength. The systematic evaluation of ablation rates at different laser parameters (Energy (E): 0.5 J/pulse - 2.5 J/pulse, repetition rate (f): 10 Hz - 80 Hz, optical pulse length (t): 0.3 ms - 4 ms) were investi- gated by shredding artificial calculi (Bego, mixture 15:4, edge