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Lecture 25 Review. Medical Optics and Lasers Application of optical methods to medicine Why optical...
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Transcript of Lecture 25 Review. Medical Optics and Lasers Application of optical methods to medicine Why optical...
Lecture 25
Review
Medical Optics and Lasers
• Application of optical methods to medicine
• Why optical methods?– Non-invasive– No side-effects– High resolution– Functional information– Real-time information– Cost effective– Portable
Medical Optics and Lasers
• Optical methods based on interactions of light with matter (biological sample)– Basic Principles– Absorption– Scattering
• Multiple scattering/Diffusion• Single scattering
– Fluorescence– Microscopy– Optical Coherence Tomography– Photodynamic therapy
Light as a wave
Period
time
angle) to timeconverts(2
2
)/(1
)(sec
)angle todistance converts(2
)(
frequencyangular
Hzorscyclesfrequencyc
ondsperiod
vectornpropagatiok
meterswavelength
Monochromatic (only onewavelength/frequency)waves traveling in phase
Monochromatic (only onewavelength/frequency)waves traveling out of phase
Phase==t-kz
kzttz o cos,
Matter: Basic principles
• The basic unit of matter is the atom• Atoms consist of a nucleus surrounded by
electron(s)• It is impossible to know exactly both the
location and velocity of a particle at the same time
• Describe the probability of finding a particle within a given space in terms of a wave function,
Particle in a box
• The particle confined in a one-dimensional box of length a, represents a simple case, with well-defined wavefunctions and corresponding energy levels
• n can be any positive integer, 1,2,3…, and represents the number of nodes (places where the wavefunction is zero)
• Only discrete energy levels are available to the particle in a box----energy is quantized
a
xn
axn
sin2
)( 2
22
8ma
hnEn
Atomic orbitals: Quantum numbers
•Principal quantum number, n–Has integral values of 1,2,3…… and is related to size and energy of the orbital
•Angular quantum number, l–Can have values of 0 to n-1 for each value of n and relates to the angular momentum of the electron in an orbital; it defines the shape of the orbital
•Magnetic quantum number, ml
–Can have integral values between l and - l, including zero and relates to the orientation in space of the angular momentum.
•Electron spin quantum number, ms –This quantum number only has two values: ½ and –½ and relates to spin orientation
Molecular orbitals• Molecular orbitals (chemical bonds) originate from the overlap of
occupied atomic orbitals
• Bonding molecular orbitals – are lower in energy than corresponding atomic orbitals (stabilizes the
molecule)
• Anti-bonding orbitals – are higher in energy than corresponding atomic orbitals and destabilizes
the molecule
bonds – involve overlapping s and p orbitals along the line joining the nuclei of
the bond-forming atoms
bonds – involve p and d orbitals overlapping above and below the line joining the
nuclei of the bond-forming atoms
Hybrid orbitals and conjugated bonds
• The four 2p orbitals can combine to form these orbitals, arranged according to energy, with the lowest energy orbital at the bottom.
• Can you think of a set of wavefunctions that may describe what is going on?
• These are similar to the wavefunctions we got for a particle in the box, with the length of the box corresponding to the length of the carbon chain
Principles of laser operation
• Stimulated emission• Population inversion• Laser cavity
– Main components– Gain and logarithmic losses– Two vs. three vs. four-level systems– Properties of laser light– Homojunction/heterojunction semiconductor
lasers
Cell and Tissue basics
• Basic components of a cell– Nucleus– Mitochondria– Lysosomes– ER – Golgi
• Basic components of epithelial tissues– Types of epithelia– Connective tissue– Basement membrane
Light-tissue interactions
• scattering– elastic scattering
• multiple scattering
• absorption
• fluorescence
Epithelium
Connective Tissue
• single scattering
Optical methods are based on different types of light-matter interactions to provide structural, biochemical, physiological and morphological information
Tissue optical properties
• There are two main tissue optical properties which characterize light-tissue interactions and determine therapeutic or diagnostic outcome:– Absorption coefficient: a (cm-1)
a=a*Na =(A/L)*ln10 a=atomic absorption cross section (cm2)• Na=# of absorbing molecules/unit volume (cm-3)• A=Absorbance• L=sample length
– Scattering coefficient: s (cm-1) s=s*Ns s=atomic scattering cross section (cm2)• Ns=# of scattering molecules/unit volume (cm-3)
Tissue absorption
Major tissue absorbers include: Hemoglobin, lipids (beta carotene), melanin, water, proteinsOxy and deoxy hemoglobin have distinct spectra. Optical measurements can provide information on tissue oxygenation, oxygen consumption, blood hemodynamics
Tissue scattering spectra exhibit a weak wavelength dependence
Structural proteins constitute major tissue scattering centers. Cell nuclei and membrane rich organelles (e.g. mitochondria) also scatter light
Fluorescence spectra provide a rich source of information on
tissue state
-1
-0.5
0
0.5
1
1.5
350 400 450 500 550 600300
350
400
450
Emission (nm)
Exc
itatio
n (
nm)
NADH
FAD
Collagen
Trp
Protein expression
Structural integrity
Metabolic activity
Courtesy of Nimmi Ramanujam, University of Wisconsin, Madison
Which optical method to use?
• Three main questions:– What is the required depth of penetration?– What is the acceptable resolution?– What type of information is needed?
1 mm 1 cm 10 cm
Penetration depth (log)
1 m
10 m
100 m
1 mm
Resolution (log)
OCT
Imaging methods
100 nm
100 m10 m1 m
Standardmicrosc
4-Pi/STED
Confocal/multi-photon microscopy
Diffuse optical tomography and spectroscopy
Spectroscopic methods: Functional information• Diffuse reflectance
– Penetration depth: microns to centimeters depending on wavelength, souce/detector separation, light delivery/collection geometry
– Resolution not well defined– Absorption
• Tissue oxygen saturation• Arterial/venus oxygen saturation• Oxygen consumption• Hemodynamics
– Scattering• Structural changes of the matrix• May be nuclear changes
• Light Scattering– Penetration depth: microns to hundreds of microns depending on how highly scattering is the sample– Inelastic scattering (Raman)
• Information: biochemical composition– Elastic scattering
• Information– Size distribution of major cell scattering centers (e.g. nuclei, mitochondria)– Cell/tissue organization
• Resolution– Potential to detect size changes on the order of 100 nanometers
• Fluorescence– Penetration depth: microns to centimeters depending on implementation, i.e. wavelength, sample optical
properties, source/detector geometry– Endogenous fluorescence
• Cell and tissue biochemistry (NADH/FAD, tryptophan, porphyrins, oxidized lipids• Tissue structure (collagen, elastin)
– Induced fluorescent protein expression (molecular specificity)– Fluorescent tags
• Antibodies (antigen expression)• Molecular beacons (enzyme activity)
Diffuse optical tomography and spectroscopy
• Applications– Breast cancer detection– Brain function– Oxygen consumption by muscles– Arthritis– atherosclerosis– Pulse oximeter– Jauntice (billirubin) test for neonates
Light scattering spectroscopy
• Cancer detection
• Detection of pre-cancerous changes– Barrett’s esophagus– Uterine cervix– Oral cancers
• Biopsy guidance
• Non-invasive patient monitoring
Optical coherence tomography
• Non-invasive detection of morphological changes
• Applications– Cancer detection– Eye diseases– Atherosclerosis– Developmental biology
Raman scattering
• Applications– Atherosclerosis– Cancer detection– Blood composition– Bacterial detection
Tissue fluorescence
• Applications– Cancer detection
• Pre-cancer detection• Guide to biopsy• Patient monitoring
– Atherosclerosis detection– Bacterial infection (?)
Microscopy
• Cell microscopy– Understand basic cell functions in healthy and
disease states– Understand role of specific proteins and cell
component interactions
• Tissue/intravital microscopy– Understand cell matrix interactions that govern
disease development, progression and regression
• Drug/therapy development and optimization• Early detection
Multi-modality optical detection
• Goal: Acquire morphological and biochemical information to achieve more sensitive/specific detection
• Combined use of fluorescence, diffuse reflectance and light scattering
• Combined use of Raman and fluorescence• Combined use of OCT and fluorescence• Combined use of reflectance and
fluorescence imaging
Photodynamic therapy
• Example of light-based therapeutic method
• Light used to achieve cytotoxicity
• Optical methods can also be used to tailor dosimetry to patient and monitor/predict therapeutic efficacy
• Used for treating a variety of conditions from cancer to acne to atherosclerosis
Optical methods are a powerful tool for understanding human health and improving
disease detection and treatment
0 2 4 6 8 10
20
18
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10
8
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2
0
y (cm)
x (c
m)0 0.5 1 1.5
0
0.5
1
1.5
EnlargedNuclei, %
mm
mm40-50
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20-30
10-20
Non-dysplasticmucosaAdenoma