2016/4/26 No. 1 Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo) based on M. Niemz, “Laser-Tissue Interactions,” Springer Quantum Beam Engineering E 量子ビーム発生工学特論E Laser-tissue interaction and its medical applications Kenichi Ishikawa (石川顕一) http://ishiken.free.fr/english/lecture.html [email protected]レーザーの生体組織への影響と医療応用
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2016/4/26 No. 1
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
based on M. Niemz, “Laser-Tissue Interactions,” Springer
Quantum Beam Engineering E 量子ビーム発生工学特論E
Laser-tissue interaction and its medical applications
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Interaction mechanismsn Photochemical interaction
n Thermal interactionn Photoablationn Plasma-induced ablation
n Photodisruption
All these seemingly different interaction types share the energy density (fluence) ranges between 1 and 1000 J/cm2 → Exposure duration largely matters!
Map of laser-tissue interactions
2016/4/26 No. 3
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Photochemical interactionLight can induce chemical effects and reactions within macromolecules or tissues.• In nature → photosynthesis• Medical application → significant role during photodynamic therapy (PDT)• takes place at very low intensity ~ 1 W/cm2 and long exposure (seconds to
CW)• in the visible ranges – high efficiency and optical penetration depth
Photodynamic therapy (PDT)
Tumor Injection of photosensitizer
Laser irradiation
Excitation of photosensitizer
Production of highly cytotoxic reactants through intramoleculartransfer reactions
Oxidation of essential cell structures
Necrosis
chromophore compound causing light-induced reactions in other non-absorbing molecules
2016/4/26 No. 4
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Kinetics of photosensitizationExcitation• Singlet state absorptionDecays• Fluorescence• Nonradiative singlet decay• Intersystem crossing• Phosphorescence• Nonradiative triplet decayType I reactions• Hydrogen transfer• Electron transfer• Formation of HO2 radicals• Formation O2
- radicalsType II reactions• Intramolecular exchange• Cellular oxidation
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1S + hν ⇒ 1S*
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1S* ⇒ 1S + h # ν
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1S* ⇒ 1S
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1S* ⇒ 3S*
FIG.3.6
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3S* ⇒ 1S + h # # ν
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3S* ⇒ 1S
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3S* + RH ⇒ SH• + R•
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3S* + RH ⇒ S•− + RH•+
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SH• + 3O2 ⇒ 1S+ HO2•
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S•− + 3O2 ⇒ 1S+ O2•−
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3S* + 3O2 ⇒ 1S + 1O2*
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1O2* + cell⇒ cellox
cytotoxic
Energy level diagram of hematoporphyrin derivative(HpD)
2016/4/26 No. 5
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Photodynamic therapy (PDT)
method
• Intravenous injection of photosensitizer (typically porfimer sodium, sold as photofrin)– Photofrin concentration in tumor is ca. four times higher than in healthy tissues.
– Photofrin stays in tumor longer than 48 hours.– Photofrin is excreted from healthy tissues (except for liver and kidney) within 24
hours.
• Laser irradiation after 48-72 hours after Photofrin injection – 630 nm wavelength– introduced to the tumor by optical fiber
a form of cancer therapy using nontoxic light-sensitive compounds that are exposed selectively to light, whereupon they become toxic to targeted tumor cells.
Photofrin
2016/4/26 No. 6
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
on an outpatient basis using a gentle, relaxing medicineand local anesthetic
STEP 1 : After some anesthetic is injected to numb thearea, a thin needle called a cannula is inserted throughthe back and into the herniated disc.STEP 2 : A small laser probe is carefully insertedthrough the cannula and into the disc. Pulses of laserlight are shined into the problem area of the disc.STEP 3 : The laser light creates enough heat to shrinkthe disc wall area.END OF PROCEDURE : The probe and needle areremoved, and the insertion area in the skin is coveredwith a small bandage. Because no muscles or bone arecut during the procedure , recovery is fast and scarringis minimized.
2016/4/26 No. 17
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Summary of thermal interaction• Main idea: Achieving a certain temperature which leads to the desired thermal effect
Advantages• Precision of the etching process • Excellent predictability• No thermal damage to adjacent tissueMedical application• Laser-Assisted in situ Keratomileusis (LASIK) - myopia,
hypermetropia, and astigmatism.
2016/4/26 No. 19
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Mechanism of photoablation
1. Absorption of a UV photon 2. Excitation of repulsive states
• AB + hν→ (AB)*3. Dissociation
• (AB)* → A + B + Ekin4. Ejection of fragments
C-C bond : 3.5 eVC-N bond : 3.0 eV
Polymethyl-metacrylate (PMMA)
needs UV light
~ 3 – 7 eV
2016/4/26 No. 20
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Summary of photoablation• Main idea : direct breaking of molecular bonds by UV
photons• Observations : very clean ablation, associated with
audible report and visible fluorescnece• Typical lasers : excimer lasers such as ArF, KrF, XeCl,
XeF
• Pulse duration : 10~100 ns
• Intensity : 107~1010 W/cm2
• Medical application : vision correction (LASIK)
2016/4/26 No. 25
Quantum Beam Engineering E (Kenichi ISHIKAWA) for internal use only (Univ. of Tokyo)
Plasma-induced ablation• Optical breakdown at laser intensity exceeding 1011W/cm2 in solid and
1014 W/cm2 in air• Ablation is primarily caused by plasma ionization itself.• Very clean and well-defined removal of tissue without evidence of thermal
or mechanical damage by choosing appropriate laser parameters.