LASER APPLICATIONS IN MEDICINE AND BIOLOGY

LASER APPLICATIONS IN MEDICINE AND BIOLOGY Volume 2 Edited by M. L. Wolbarsht Professor of Ophthalmology and Director of Research Department of Ophthalmology Duke University Medical Center Durham, North Carolina PLENUM PRESS NEW YORK AND LONDON

Contents Chapter 7 Microbeams 1 by Michael W. Berns 1. Introduction 1 2. Instrumentation 2 2.1. General Considerations 2 2.2. Ruby Laser Microbeams 3 2.3. Argon Laser Microbeams 5 2.4. Neodymium Laser Microbeams 9 2.5. Other Laser Microbeam-Like Systems 9 2.6. Available Laser Wavelengths 13 3. Methodologies Employed with Microbeam Irradiation... 14 3.1. Cell Culture 14 3.2. Vital Dye Sensitization 16 3.3. Light Microscopy 20 3.4. Electron Microscopy 21 3.5. Biochemical Analysis 22 4. Studies on Cell Function and Structure 22 4.1. Multicellular Plants 22 4.2. Unicellular Organisms 23 4.3. Embryos and Eggs 25 4.4. Tissue Culture Cells Ruby and Neodymium Lasers 26 4.5. Tissue Culture Cells Argon Laser 27 4.6. Microbeam Studies on the Nervous System 37 5. Conclusion 37 Acknowledgments 38 References 38 xi

xii Contents Chapter 2 Lasers in Ophthalmology 41 by B. F. Hochheimer 1. Introduction 41 2. Coherence 41 3. Consequences of Coherence 45 3.1. Fringe Visibility 45 3.2. Beam Collimation 47 3.3. Resolution 49 4. Lasers 49 4.1. Ideal and Real Lasers 49 4.2. Lasers Used in Ophthalmology 52 5. The Eye 53 6. The Laser Refractor 56 7. Laser Acuity Testing 59 7.1. The Acuity of the Eye 59 7.2. Modulation Transfer Function 60 7.3. Laser Visual Acuity Tester 61 8. Retinal Visual Acuity in the Case of Cataracts 63 9. The Laser Cane 65 10. Laser Treatment for Corneal Ulcers 67 11. Laser Photocoagulation 68 11.1 Ruby Laser Coagulator 68 11.2. Argon Ion Laser Coagulator 69 12. Conclusion 73 References 74 Chapter 3 Holography of the Eye: A Critical Review 77 by K. D. Vaughan and R. A. Laing in collaboration with R. L. Wiggins 1. Introduction 77 2. Applications 80 2.1. Three-Dimensional Records 80 2.2. Detection of Abnormalities 80 2.3. Measurement of Abnormalities in Three Dimensions 80 2.4. Information Storage 80

Contents xiii 2.5. Retrospective Study of the Entire Eye 81 2.6. Contour Mapping 81 2.7. Measurement of Changes Within the Eye 81 2.8. High Resolution of Fundus 81 2.9. Measurement of Optical Constants of the Eye... 81 3. Possible Methods of Hologram Formation 81 3.1. Fresnel Hologram 82 3.2. Fraunhofer Hologram 82 3.3. Fourier Transform Hologram 83 3.4. Lensless Fourier Transform Hologram 83 4. Methods of Achieving Magnification 84 4.1. Magnification Due Solely to the Holographic Process 85 4.2. Holography of a Premagnified Object 86 4.3. Magnification Subsequent to the Holographic Process 87 5. Special Holographic Techniques 90 5.1. Holographic Interferometry 90 5.2. Holographic Contour Generation 91 6. Choice of Parameters 91 6.1. Wavelength 91 6.2. Retinal Energy Density 97 6.3. Exposure Duration 99 6.4. Recording Materials 101 7. Speckle 109 8. Holograms of the Eye Ill 9. Proposed Applications of Ocular Holography 120 9.1. Holographic Interferometry 120 9.2. High-Resolution Image of the Optic Fundus... 122 9.3. Measurement of Optical Constants of the Eye... 124 10. Summary 124 Acknowledgments 125 Appendix Information Content of Eye Holograms 126 References 128 Chapter 4 Quantitative Laser Microprobe Analysis 133 by I. Harding-Barlow 1. Introduction 133

xiv Contents 2. Instrumentation 134 2.1. Laser Head 134 2.2. Microscope Head 136 2.3. Emission Spectrography 137 2.4. Mass Spectrometry 140 2.5. Atomic Absorption 141 3. Standardization 141 4. Sample Preparation 142 5. Applications 143 5.1. Forensic and Toxicological Applications 143 5.2. Applications to Tissues 144 5.3. Applications to Teeth, Bones, and Skin 145 5.4. Applications to Body Fluids 146 5.5. Applications to Plants 146 5.6. Applications to Nonmammalian Biology 146 6. Sensitivity 146 7. Laser Microprobe vs. Other Probes 147 8. Conclusions 147 References 147 Chapter 5 Laser Flow Microphotometers for Rapid Analysis and Sorting of Individual Mammalian Cells 151 by P. F. Mullaney, J. A. Steinkamp, H. A. Crissman, L. S. Cram, and D. M. Holm 1. Introduction 151 2. Flow Microphotometry 153 2.1. General Considerations 153 2.2. Laminar Flow Chamber 153 2.3. Input Beam Optics 155 2.4. Light Collection Systems 156 2.5. Electronic Signal Processing 157 3. Flow Microfluorometry (FMF) 161 3.1. FMF II 162 3.2. Beam Optics 162 3.3. Signal Processing 163 3.4. Results 163 3.5. Resolution 165

XV 4. Biological Applications of FMF II 166 4.1. Life Cycle Analysis and Relative DNA Quantitation. 166 4.2. Chemotherapeutic Agent Effects 170 4.3. Cell-Surface Architecture Studies 171 4.4. Fluorescein-Labeled Antigen-Antibody Measurements 172 5. Preparation of Cell Samples for FMF Analysis 173 5.1. Cell Dispersal and Fixation 173 5.2. DNA Staining Procedures 174 5.3. Protein Staining 175 6. Multiparameter Cell Analysis and Sorting 177 6.1. Description of the Multiparameter Cell Sorter (MPS-1) 178 6.2. Electronic Cell Sensing 181 6.3. Fluorescence Detection 181 6.4. Light Scattering 183 6.5. Multiparameter Signal Processing 183 6.6. Multiparameter Analysis and Sorting Applications. 186 6.7. Tumor Cell Identification and Separation 188 6.8. White Blood Cell Differential 189 7. Light Scattering 192 7.1. Models for Mammalian Cells 193 7.2. Exact Electromagnetic Theory Considerations... 194 7.3. Experimental Verification for Live Mammalian Cells in Suspension 194 7.4. Flow Microphotometric Measurements 196 8. Future Applications 198 8.1. Instrumentation 199 8.2. Biological Applications 199 Acknowledgments 200 References 200 Chapter 6 Biological Damage Resulting from Thermal Pulses 205 by Frank Stephenson Barnes 1. Introduction 205 2. Calculation of the Temperature Distribution 207

xvi Contents 3. Chemical Rate Equations 214 4. Biological Results at Elevated Temperatures 218 Acknowledgments 220 References 220 Chapter 7 Laser Protective Eyewear 223 by David H. Sliney 1. Introduction 223 2. Applications 224 3. Laser Viewing Enhancement Goggles 225 4. Parameters of Laser Eye Protection 226 4.1. Wavelength 226 4.2. Optical Density 226 4.3. Laser Beam Irradiance or Radiant Exposure 227 4.4. Visual Transmittance of Eyewear 228 4.5. Laser Filter Damage Threshold (Maximum Irradiance) 229 4.6. Filter Curvature 230 5. Methods of Construction 230 6. Selecting Appropriate Eyewear 231 7. Commercial Sources of Laser Eye Protection 234 8. Testing Laser Eye Protection 234 9. Marking of Eye Protection 236 10. Eye Protection for Infrared Lasers 236 11. Eye Protection for Pump Lamps and Tunable Wavelength Lasers 237 12. Polarizing Filters 237 13. Dynamic Eye Protection Devices 238 14. Future Developments 239 References 239 Chapter 8 Lasers in Surgery 241 by Stanley Stellar, Thomas G. Polanyi, and Herbert C. Bredemeier 1. Introduction 241 1.1. Scope of Review 242

xvii 1.2. Characteristics of Lasers 242 1.3. Interaction of Radiation with Tissue 246 2. Critical Review and History of Laser Surgery 249 2.1. Pulsed Ruby and Neodymium Laser Surgery... 250 2.2. Carbon Dioxide Laser Surgery 252 3. Carbon Dioxide Laser Surgery 254 3.1. Instrumentation 254 3.2. Surgical Applications Clinical and Experimental. 263 4. Surgical Applications of Other Lasers 285 4.1. Ruby Laser 285 4.2. Argon Ion Laser 286 4.3. Neodymium in Yttrium, Aluminum, Garnet (Nd YAG) 287 5. The Future of Lasers in Surgery 288 6. Summary and Conclusions 289 Acknowledgments 290 References 290 Chapter 9 The Carbon Dioxide Laser in Clinical Surgery 295 by Isaac Kaplan, Uzi Sharon, and Ralph Ger 1. Introduction 295 1.1. Skin Healing 298 1.2. Skin Grafts 298 1.3. Hemostatic Effect 298 1.4. Postoperative Pain 299 2. Observations on the Applicability of the Carbon Dioxide Laser in Specific Clinical Conditions 299 2.1. Burns 299 2.2. Mastopathy 300 2.3. Hemangioma 300 2.4. Cervical Erosions 300 2.5. Hemorrhoids 300 2.6. Malignant Tumors 301 2.7. Rectal Carcinoma 301 3. Design and Development of a New Carbon Dioxide Surgical Laser 301 3.1. The Laser and Optical Bench 302 3.2. The Articulated Arm and Balancing System 302

xviii Contents 3.3. The Manipulator 305 3.4. Safety Measures 305 3.5. Mobility and Compactness of the System 305 3.6. Remote Control 306 3.7. Attachments for Specific Surgical Procedures... 306 4. Conclusions 307 References 308 Chapter 10 The Formulation of Protection Standards for Lasers 309 by M. L. Wolbarsht and D. H. Sliney 1. Introduction 309 1.1. Application of the Protection Standards 310 1.2. The Need for Regulations 311 2. Analysis of Safety Regulations in Massachusetts 312 2.1. Philosophy of Laser Regulation and Registration..313 2.2. Definitions 314 2.3. Exemptions and Exceptions 314 2.4. Data Collection 314 2.5. Protection Standards 316 2.6. Measurements for Conformance and Survey 316 2.7. Regulation 317 2.8. Specific Precautions for Outdoor Installations... 318 2.9. Personnel Protection 318 2.10. Medical Surveillance 319 2.11. Appendix to Massachusetts Board of Health Rules and Regulations 321 3. The Outlook for Federal Regulations 321 4. State Regulations in the United States 322 5. Protection Standards for Retinal Hazards: Considerations of Biological Data 322 5.1. Useful Presentation of Biological Data 323 5.2. Sources of Error in the Biological Data 326 5.3. Laser Accident Data 328 5.4. Combining Data Points 329 5.5. Standards for Different Wavelengths 330 6. The Selection of Proper Format and Levels Neither Too Detailed Nor Too Conservative 331 6.1. The Degree of Safety 331

xix 6.2. Military Protection Standards 332 6.3. Specification of Protection Standards 333 6.4. Retinal Exposure Levels and Corneal Exposure Levels 333 6.5. Specification of Pupil Size 333 7. Extrapolation 334 7.1. Interpreting the Biological Data 335 7.2. From Cornea to Retina and Back Again 335 7.3. Relation Between Different Retinal Image Sizes and Associated Retinal Injury Thresholds 337 7.4. Thermal Models 338 7.5. Retinal Detachment 339 7.6. Melanin Granules in Pigment Epithelium as Local Hot Spots 340 7.7. Other Factors Influencing Laser Injury Spot Size: Biological and Physical Amplification... 341 7.8. Infrared and Ultraviolet Laser Protection Standards 342 8. The ANSI-Z-136 Standards 343 8.1. Formulation of Protection Standard Exposure Levels 343 8.2. Limiting Apertures 344 8.3. Extended Sources 344 8.4. Correction Factor Л (С А ) 344 8.5. Repetitively Pulsed Lasers 348 8.6. Laser Hazard Classification 353 9. Other Standards 354 10. Present Problems and Future Plans 354 References 356 Chapter 11 Dentistry and the Laser 361 by Ralph H. Stern 1. Introduction 361 1.1. Anatomy of Dental Structures 361 1.2. Dental Diseases 363 2. Early Laser Investigations 363 3. Investigations Leading to Laser-Induced Caries Inhibition 367

Contents 3.1. Ruby Laser 367 3.2. Pulsed Carbon Dioxide Laser 369 4. Laser Effects on Dental Soft Tissue 380 5. Potential Applications 384 6. Summary 386 Acknowledgments 386 References 387 Author Index 389 Subject Index 399