Download Biomedical Optics

Coordinators
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Göran Salerud, [email protected]
Biomedical Optics
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Maria Ewerlöf, [email protected]
Introduction
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Neda Haj-Hosseini, [email protected]
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Marcus Larsson, [email protected]
E. Göran Salerud
Department Biomedical Engineering
Course layout
Course Content
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Lectures
40 h
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Introduction, general optics
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Tutorials
12 h
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Safety
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Laboratory exercise
12 h
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Optical definitions and calculations
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Self-studies
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Tissue optical properties
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Oral seminars
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Optical transport
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Written exam
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Monte Carlo simulation
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Measurement of optical parameters
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Applications
xh
2016-10-28
2017-01-07
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PPG & Spectroscopy
Flourescence, multiphoton, Raman and more
Hyper Spectral Imaging
OCT, LDF
Photoacoustics
Why use optical methods?
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Motivation
Probes structures as well as molecules associated with disease
progression already present in tissue
1.
Optical photons provide non-ionizing and safe radiation for
medical applications.
2.
Optical spectra--based on absorption, fluorescence, or Raman
scattering--provide biochemical information because they are
related to molecular conformation.
3.
Optical absorption, in particular, reveals angiogenesis and
hypermetabolism, both of which are hallmarks of cancer; the
former is related to the concentration of hemoglobin and the
latter to the oxygen saturation of hemoglobin. Therefore,
optical absorption provides contrast for functional imaging.
4.
Optical scattering spectra provide information about the size
distribution of optical scatterers, such as cell nuclei.
Non-invasive
Fast
Automated
Optical
Signal
Light Source
Tissue
Motivation cont..
Why should you learn about Biomedical Optics?
5.
Optical polarization provides information about structurally anisotropic tissue components, such as collagen and muscle fiber.
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Working understanding of absorption, fluorescence and
scattering properties
6.
Optical frequency shifts due to the optical Doppler effect provide
information about blood flow.
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To understand how these interactions can be modeled in tissue
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How they can be implemented in diagnostic tools
7.
Optical properties of targeted contrast agents provide contrast
for the molecular imaging of biomarkers.
8.
Optical properties or bioluminescence of products from gene
expression provide contrast for the molecular imaging of gene
activities.
9.
Optical spectroscopy permits simultaneous detection of multiple
contrast agents.
10.
Optical transparency in the eye provides a unique opportunity
for high-resolution imaging of the retina.
What is Biomedical Optics
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Tissue - typical” physics for using light in Medicine
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Interaction of light and tissue (“tissue optics”)
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Development of methods and (bio) medical instrumentation
based on these interactions
The Biophotonic Field
Therapeutic Use of Light
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Diagnostic Use of Light
Photophysical
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X-ray
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Medical infrared imaging
Photochemical
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Contrast microscopy
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Oxygen radicals
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Blood gas analysis
Photocoagulation
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Temperature
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Treating smallpox
Conversion of photon energy into mechanical energy
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Spectral imaging
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Photodynamic therapy
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Fluorescent imaging
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Photobiological irradiation
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Ballistic photon imaging
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Optical coherence tomography
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Multiphoton imaging
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Optoacoustic imaging
Use of light in Medicine
Diagnosis:
- Tumor detection
- Vascular malformation
- Burn wounds classification
Monitoring:
- Pulse oximetry
- Brain oxigenation
- Glucose monitoring
- Perfusion after transplantation
Interaction of Light with Molecules
Treatment:
- Surgery: cutting, welding
- PWS removal, tattos, wrinkles
- Light theraphy: bilirubin, depression
- Photodynamic theraphy (PDT)
Interaction of Light with Matter
Skin fluorescence
Picosecond laser for oxygen measurements
Fluorescence of retina, Diabetic patient
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OCT
The fluorescence mapping of the retina of a diabetic patient.
The red areas take the least amount of time to reach maximum
fluorescence, whereas the blue areas take the longest.
Brain tissue of frog
OCT radar
PDT
Spectroscopy
Basal cell carcinoma
Time resolved microscopy
The Interaction of Light and Matter: a and n
The interaction of light and matter is what makes life interesting.
Everything we see is the result of this interaction. Why is light
absorbed or transmitted by a particular medium?
Light causes matter to vibrate. Matter in turn emits light, which
interferes with the original light.
Destructive interference means absorption.
~ ±90° out-of-phase interference
Refractive
changes the phase velocity of light,
index
or refractive index.
Absorption
coefficient
a
w
n–1
Light – Tissue Interaction
Optical Properties of Tissue
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Absorption cross section
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Absorption coefficient
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Scattering cross section
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Scattering coefficient
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Phase function
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Scattering –anisotropy
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Reduced Scattering coefficient
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(Reduced) albedo
Optical Contrast in Biological Systems
Absorption
Elastic Scattering
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Absorption
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Fluoresence Spectroscopy
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Angiogenesis
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Metabolism
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Raman Spectroscopy
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Low Coherence Spectroscopy
Water
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Lipids
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Exogeneous dyes
Flourescence
Nonlinear Effects
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§ Two photon excited
fluorescence
Reflection spectroscopy
Oxy and deoxy hemoglobin
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Optical Contrast in Biological Systems
Autofluorescence (native
chromophores)
§ FAD, NAHD, Collagen
§ Lifetime
§ Anisotropy (rotational diffusion)
§ Exogenous Contrast
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Indocyanine green
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Methylene blue
Absorption - Beer-Lambert law
§ The decline of irradiance of the
amount dI0 of EM radiation is
proportional to the incident
quantity I0 and the distance dl
§ I0 at l (I0(l)),
§ Amount of absorption (a),
§ Thickness layer (dl)
∂I = −I ⋅ α ⋅ ∂l
I1 = I 0 e − α l
§ Dimension of a?
§ a = ec
§ Effects of scattering?
§ Second and Third harmonic
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Fluorescent dyes
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Photosensitizers
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Cyanine dyes
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Nanoparticles
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Nanospheres
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Quantum dots
Raman Scattering
Bioluminiscence
Optical Properties of Tissue Constituents
Tissue optics - Scattering
Tissue Spectroscopy
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Discrimination between tissue types
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Assessment of tissue components → functional info
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Reflectance spectroscopy
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Tissue Absorption and Scattering
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Absorption properties of different components and scattering properties of
bulk tissue.
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Broad band light source
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Broad band detection
Fluorescence Spectroscopy
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Absorption and fluorescent properties of different tissue components and
scattering properties of bulk
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Short excitation wavelength
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Energy down conversion to longer wavelengths; broad band detection
Imaging : Spatial information: e.g. tumor bounderies, tissue
oxygenation etc
Optical Spectroscopy: Oxygenation
First approach for the quantification of spectroscopic
measurements: modified Lambert Beer with estimated or
measured pathlength
Absorption
Outgoing light
Incident light
Diffuse
reflectance
Diffuse
transmittance
I (λ )
−dDPF (µ atotal ( λ ))
=e
I0 (λ )
Transmission
Reflection
I (λ )
−dDPF (µ atotal ( λ ))
=e
I0 (λ )
Method
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Time-of-flight or
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Phase resolved measurements
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Disadvantage:
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large volumes are measured,
unknown optical pathlength
Depth resolution
[µm]
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Imaging Methods in Tissue
Depth resolution
[mm]
Determination of the optical pathlength in tissue
www.liu.se
100
C(M) : (confocal)
microscopy
10
TOF / FM
1
PA:
NIR
100
10
OCT/
OPS
PA:
green
(C)M
10
100
Depth [µm]
OPS: orthogonal
polarization spectral
imaging
PA: photoacoustics
TOF: time-of-flight
tomography
FM: frequencymodulated tomography
1
1
OCT: optical coherence
tomography
1
10
100
Depth [mm]