LASERS IN MEDICINE: SURGICAL & THERAPEUTIC APPLICATIONS PIER GIORGIO GOBBI UNIVERSITY HOSPITAL SAN RAFFAELE

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1 LASERS IN MEDICINE: SURGICAL & THERAPEUTIC APPLICATIONS PIER GIORGIO GOBBI UNIVERSITY HOSPITAL SAN RAFFAELE

2 LASER TIMELINE A solution looking for a problem 1966: Dye (Sorokin) 1962: GaAs (GE, IBM, MIT) 1964: Nd:YAG (Geusic) 1974: Alexandrite 1982: Ti:sapphire (Moulton) 1960: Ruby (Maiman) 1964: CO 2 (Patel) 1970: Excimer (Basov) 1976: F.E.L. (Madey) 1964: Ar + (Bridges)

3 LASER & CLINICAL TIMELINE 1965: oncology (McGuff, ruby) 1964: retinal coagulation in men (Zweng, ruby) 1966: vessel anastomosis (Yahr, CO 2 ) 1968: retinal coagulation (L Esperance, Ar + ) 1975: endoscopy (Dwyer, Ar + ) 1983: photoablation (Trokel, ArF) 1961: retinal coagulation in rabbits (Zaret, ruby) 1967: dermatology (Goldman, Ar + ) 1973: gastroenterology (Nath, Nd:YAG) 1980: photodisruption (Aron Rosa, Nd:YAG) 1966: Dye (Sorokin) 1962: GaAs (GE, IBM, MIT) 1964: Nd:YAG (Geusic) 1974: Alexandrite 1982: Ti:sapphire (Moulton) 1960: Ruby (Maiman) 1964: CO 2 (Patel) 1970: Excimer (Basov) 1976: F.E.L. (Madey) 1964: Ar + (Bridges)

4 LASER MARKETPLACE Materials Processing 26 % Medical & Aesthetic 7 % Excimer litography 11 % Image recording 1 % Data storage 11 % Scientific & Military 5 % Instrumentation & Sensors 4 % Pumps 4 % Communications 31 % Total revenues: 7.5 G$ (2011)

5 MEDICAL LASER MARKETPLACE Revenues (M$)

6 LASER PROCEDURES SURGERY: tissue removal in open procedures / surgical precision and control / laser-assisted procedures ENDOSCOPY: optical fibers non invasive procedures / insertion through body opening or small incision / less trauma & faster recovery LITHOTRIPSY: fragmentation of stones and calculi ANGIOPLASTY: recanalization of blood vessels blocked by plaques CANCER THERAPY: photodynamic therapy / laser hyperthermia TISSUE WELDING & ANASTOMOSIS: sealing or joining of tissues / small structures PAIN CONTROL / RELIEF: laser induced analgesia / treatment of chronic pain BIOSTIMULATION: alteration of metabolism of living tissue in therapeutically useful way

7 1 ST LAW OF PHOTOBIOLOGY Light must be absorbed before photobiological interaction can occur Corollary: Light which is not absorbed by a system is safe for that system

8 PRIMARY LIGHT-TISSUE INTERACTIONS SPECULAR REFLECTION TISSUE TRANSMISSION INCIDENT RADIATION ABSOR PTION SCATTERING: - Backward - Internal - Forward

9 ABSORPTION: CHROMOPHORES WATER: transparent in [400, 800] nm absorption peaks: 1450; 1930; 2940 nm present in all tissues: skin 70%; cartilage 75%; arteries 80%; bone 10 30%; dentin 13%; enamel 3%

10 WATER ABSORPTION Absorption coefficient [cm -1 ] Wavelength [μm]

11 ABSORPTION: CHROMOPHORES WATER: transparent in [400, 800] nm absorption peaks: 1450; 1930; 2940 nm present in all tissues: skin 70%; cartilage 75%; arteries 80%; bone 10 30%; dentin 13%; enamel 3% HEMOGLOBIN: wide diffusion (except cartilage and dental tissue) strong absorption of blue and green, reflection of red higher red absorption for oxygenated hemoglobin BLOOD: water + hemoglobin MELANIN: biological pigment of skin and other soft tissues absorption monotonically increases from 1000 to 400 nm XANTHOPHILL: pigment localized in neural fiber layers (macula) strong absorption of blue

12 CHROMOPHORE ABSORPTION EXTINCTION COEFFICIENT (cm -1 ) XANTHOPHYLL 10 MELANIN OXYHEMOGLOBIN RED. HEMOGLOBIN WAVELENGTH [nm]

13 ABSORPTION: CHROMOPHORES COLLAGEN: structural component of most tissues fibrils unravel and become sticky under mild heating (welding and anastomosis) and expand at coagulation (hemostasis) CARTILAGE: water + collagen BLOOD VESSELS: hollow soft tissue, effectively cooled by blood flow hemostasis: coagulation of proteins in blood (increased viscosity) and denaturation of collagen hemostasis improves at higher power density, longer exposure and deeper penetration BONE: composite material, collagen matrix + calcium phosphate (hydroxyapatite 45%) DENTAL TISSUE: enamel, dentin, cementum, plaque, caries water + collagen + hydroxyapatite (70-95 %)

14 ABSORPTION: CHROMOPHORES ATHEROSCLEROTIC PLAQUE: soft plaque: fatty deposit fibrous plaque: fatty deposit + collagen calcified plaque: fatty deposit + calcium phosphate white-yellowish color low absorption in VIS-NIR CALCULUS: stone-like deposit of inorganic salts and organic materials accumulated in organs, gland, ducts variety of pigmentation and mechanical properties: very hard (calcium oxalate) hard but not brittle (uric acid) soft and crumbly (struvite) CARBON: may develop in tissues heated in presence of oxygen strong absorption at any wavelength (blackbody) minimized with proper irrigation

15 RELEVANT FACTORS * Laser parameters: wavelength λ power P / energy E exposure duration Δt spot size on tissue A * Bio-optical parameters: absorption coefficient μ a scattering coefficient μ s

16 RAYLEIGH SCATTERING Φ S λ Ar 488 Ar 514 Nd:YAG 532 Kr 647 Semic 810 Nd:YAG

17 IRRADIANCE (W/cm 2 )

18 EYE TRANSMISSION PERCENTAGE ABSORPTION WAVELENGTH [nm]

19 EYE

20 LASER-TISSUE INTERACTIONS PHOTOCHEMICAL: optical radiation chemical energy optical activation of singlet oxygen from specific molecules with specific λs PHOTOMECHANICAL (PHOTODISRUPTION): pulsed laser energy acoustic energy mechanical action dependent on peak power not on λ PHOTOABLATIVE (PHOTODECOMPOSITION): pulsed laser energy chemical energy breaking of chemical bonds, short λs PHOTOTHERMAL: optical radiation heat temperature rise absorption wavelength dependent BIOSTIMULATION: low power irradiation highly controversial

21 PHOTO-CHEMICAL INTERACTION Non thermal process: low irradiance + long time exposures PDT: Photo Dynamic Therapy of tumors Infusion of a sensitizing agent S (chromophore photochemically active to non absorbing molecules) Selective retention of S by neoplastic tissue Irradiation with proper optical radiation ( 1 W/cm 2 ; 1 to 500 s; VIS near IR) Resonant excitation of S: S + hν S* Multiple sequential decays: intramolecular transfer reactions Production of highly cytotoxic reactive species (singlet oxygen) Irreversible oxidation of cell structures

22 PHOTO-CHEMICAL INTERACTION 1.1 PDT of Age Related Macular Degeneration (Diode 689 nm) 1.2 Endoscopic PDT of esophageal cancer (Dye 630 nm) 1.3 PDT in Neurosurgery (schematic proposal)

23 PHOTO-MECHANICAL INTERACTION Non thermal process: high fluence + short time exposures Focused giant pulse Φ = E p /(t p w 2 ) High electric field E 10 6 V/cm E laser E ion. mol. High irradiance Φ W/cm 2 Free electron generation Photon absorption Inverse Brehmsstralung Avalanche ionization hν + e - + A + e - ΔEk + A+ Plasma formation (optical breakdown) N E cm -3 ; T > 2 ev Spherical shock wave p [bar] 13 E p [mj]/r 3 [mm 3 ] Onset and collapse of cavitation bubbles Localized mechanical disruption p > tissue resistance Chromophore independent!

24 PHOTO-MECHANICAL INTERACTION 2.1 Capsulotomy, iridotomy (Q-S Nd:YAG) 2.2 Lithotripsy (Dye 504 nm)

25 PHOTO-ABLATIVE INTERACTION UV radiation; short exposures Short pulse ( s) of UV radiation on tissue Strong absorption (proteins, amides, peptides, polymers): AB + hν (AB)* Promotion to repulsive state (if hν > E bond ) Photodissociation for Φ > Φ th : (AB)* A + B + E k Ejection of fragments Non necrotic ablation with well defined thickness: d = L opt ln(φ/φ th )

26 PHOTO-ABLATIVE INTERACTION 3.1 Photo-Refractive Surgery (ArF)

27 PHOTO-THERMAL INTERACTIONS T < 43 C: NO EFFECT T 45 C: HYPERTHERMIA: enzyme activation, cell death if sustained (cancer therapy) T 55 C: COLLAGEN MELTING (tissue welding) T 60 C: COLLAGEN SHRINKAGE (skin resurfacing, LTK) T 70 C: COAGULATION: protein denaturation, tissue whitening (haemostasis, necrosis) T 100 C: VAPORIZATION: boiling of cellular water, tissue removal and cutting T > 100 C: CARBONIZATION and ABLATION SPALLATION: explosive phase transition and mechanical disruption SELECTIVE PHOTOTHERMOLYSIS

28 PHOTO-THERMAL INTERACTIONS 4.1 Retinal Photocoagulation (Ar nm) 4.2 Transurethral Prostate Coagulation (Nd:YAG 1064 nm) 4.3 Laser Assisted Microvascular Anastomosis (diode 810 nm) 4.4 Plastic Surgery (CO μm)

29 LASER or STD INSTRUMENTS? Example: soft tissue surgery - Knife - Electrosurgical unit (ESU) - Laser (CO 2 )

30 PERFORMANCE KNIFE ESU LASER Surgical precision (lateral) Surgical control (depth) Vaporization NO Cutting Spot coagulation NO Area coagulation NO + ++ Compatibility with irrigation Neuromuscolar stimulation Tactile feedback Endoscopic procedures Patient safety Operator safety OR personnel safety Ancillary hazards (fire, explosion, burns, EM interference) Ergonomy (portability & quick use) Costs Marketing Training

31 HOMEWORK 1 Discuss the relevance of coherence (spatial / temporal) in each interaction 2 Discuss the Goldfinger laser, intended to cut 007 s body into 2 parts: fiction or reality?

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