Download Biomedical Optics

Biomedical Optics
p
Hsiao Lung Chan,
Hsiao-Lung
Chan Ph.D.
Ph D
Dept Electrical Engineering
Ch
Chang
Gung
G
University, Taiwan
[email protected]
Outline
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Essential optical principle
Light propagation in biological tissue
Blood oxygen concentration
Laser Doppler velocimetry
Fluorescence microscope
Functional near infrared imaging
Optical coherence tomography
Lecture edited by 詹曉龍, 長庚大學電機系, 2010.
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Electromagnetic (EM) waves
The magnetic field oscillates in orthogonal
to the electrical field and in phase
EM fields have
longitudinal as
well as transverse
components.
E x  E0 exp[ j (t  kz )]
H y  H 0 exp[ j (t  kz )]
frequency
wavelength
g
velocity
f   / 2
  2 / k
c  f   / k
n  c0 / c
iindex
d off
refraction of the
medium
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Electromagnetic spectrum
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Polarization

Electromagnetic waves, such as light, and gravitational
waves exhibit polarization; acoustic waves (sound waves)
in a gas or liquid do not have polarization because the
direction of vibration and direction of propagation are the
same.
Plane pressure pulse wave
Propagation of an
omnidirectional pulse wave
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Light polarization

When light travels in free
space, in most cases it
propagates as a transverse
wave—the polarization is
perpendicular to the wave's
wave s
direction of travel.
Transverse plane wave
Propagation
P
opagation of a transverse
t ans e se
spherical wave
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Light polarization (cont.)
(cont )
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The simplest manifestation of polarization is to visualize a
plane wave, which is a good approximation of most light
waves.
waves
The electric field vector of a plane wave may be divided
into two perpendicular components labeled x and y
For a simple harmonic wave, the two components have
exactly the same frequency
E x  ex cos(t  kz )
E y  e y cos(t  kz   )
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Light polarization (cont.)
(cont )

The electric field may be oriented in a single direction (linear
polarization), or it may rotate as the wave travels (circular or elliptical
p
polarization).
)
linear
circular
elliptical
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Light interaction with nonparticipating media

Reflection and refraction
Snell’s law
ni sin  i  nt sin  t
ni
nt
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Light interaction with participating media
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Scattering
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Scattering of light depends
on the wavelength of the
light being scattered.
Since visible light has
wavelength on the order of
a micron, objects much
smaller
ll than
th this
thi cannott be
b
seen, even with the aid of a
microscope
p
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Scattering
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Light interaction with participating media
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Absorption
Beer-Lambert’s law
I ( x  x)  I ( x)  aI ( x)x
dI ( x)

 aI ( x)
dx
 I ( x)  I 0 ( x)e  ax
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Oxygen saturation (SaO2, SpO2) measurement
(1) SaO2 is the relative amount of oxygen
carried by the hemoglobin
(2) The color of Hb is blue, HbO2 is bright red color
(3) Two specific wavelengths :
λ1 : a red wavelength (eg. 660 nm)
λ2 : a near infrared wavelength (eg.
(eg 805 nm)
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Beer-Lambert’s
Beer
Lambert s law
I t  I 0  10 Cd
where It and I0, transmitted and incident light power;
α, C, d, extinction coefficient, concentration of the sample, and
light path length
Define optical density, OD
I
OD  log  t
 Io
SaO 2 

   Cd

C HbO 2
C HbO 2  C Hb
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Light absorption signal
produce AC
output
produce DC
output
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Light absorption signal
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Light absorption in different blood oxygen
concentrations
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SaO2
I IR  I 0  10
I R  I 0  10
HbO 2
Hb
 ( IR
C HbO2  IR
C Hb )( d  d )
 ( RHbO 2 C HbO 2  RHb C Hb )( d  d )
 IR 

log 
HbO 2


I

C HbO 2   RHb C Hb
R
R ( DC ) 
R


 HbO 2
IR
 I IR   IR C HbO 2   IRHb C Hb

log 
I

IR
(
DC
)


SaO 2 
C HbO 2
C HbO 2  C Hb

R
  RHb
IR
R
  IRHbO 2 )
 ( RHb   RHbO 2 )
IR
 IRHb
( IRHb
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SaO2 applications
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Laser Doppler velocimetry

Partially quantify blood flow in human tissues such as
capillary flow
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Laser Doppler velocimetry (cont
(cont.))
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Laser Doppler velocimetry (cont
(cont.))
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Doppler effect
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Example
ν=1014 Hz
v=1 mm/sec
c/n=210
c/n
2108 m/sec
 Δν=500 Hz



v cos 


c/n
v : relative velocity
 : light frequency
n:refraction coefficient
Usingg laser as light
g source
Get “beat” through interference between lights
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Laser Doppler velocimetry (cont
(cont.))
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Fiber optics and waveguides in medicine

An optic fiber with a cylindrical core with index of
refraction (n1) and cladding index (n2) where n2<n1
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Fiber optics
Snell’s law
n2 sin  2  n1 sin 1
Refraction of rays that
escape from wall of fiber
Low refractory index
High refractory index
n1=1.62 for a glass
3 : accepted
angle
l for
f internal
i t
l
reflection in fiber
Internal reflection
within a fiber
when n1 sin  ic  n2 sin 90 0  n2
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Optical fiber type
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Displacement optode
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A thin reflectance
diaphragm for pressure or
temperature measurement
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Fluorescence
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The emission of light by a substance that has absorbed
light of a different wavelength.
I mostt cases, emitted
In
itt d lilight
ht h
has a longer
l
wavelength,
l
th and
d
therefore lower energy, than the absorbed radiation.
Photon energy
E = h
h = Planck's constant
 = frequency of light
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Fluorescence microscope
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The excitatory
Th
it t
lilight
ht is
i
transmitted through the
specimen.
p
The fluorescence in the
specimen gives rise to
emitted
d light.
l h
Only reflected excitatory
light reaches the objective
together with the emitted
light.
The emission filter can filter
out the remaining excitation
light.
light
Fluorescent imaging for dividing human cells
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DNA is stained blue, a
protein called INCENP is
green and the microtubules
green,
are red.
Each fluorophore is imaged
separately using a different
combination of excitation and
emission filters
The images are captured
sequentially
q
y using
g a CCD
camera, then overlaid to give
a complete image.
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Confocal microscope
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increase optical resolution and contrast of a micrograph by
using point illumination and a spatial pinhole to eliminate
out of focus light in specimens
out-of-focus
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Near-infrared
Near
infrared spectroscopy (NIRS)
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Uses the near-infrared region (from 800 nm to 2500 nm)
Applications in pharmaceutical and medical diagnostics
(i l di blood
(including
bl d sugar and
d oximetry).
i t )
OxiplexTS, ISS Inc, USA
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Near-infrared
Near
infrared sensing methods
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Application in peripheral vascular disease (PVD)
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PVD is a narrowing of the vessels carrying blood to the
muscles in the legs and arms.
M t patients
Most
ti t reportt experiences
i
off pain
i iin the
th extremities
t
iti
due to inadequate blood flow and oxygen delivery to the
exercising muscle
muscle.
OxiplexTS, ISS Inc, USA
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Application in brain oxygenation

With 20% of oxygen consumption
occurring in the human brain, any
deficiencyy in oxygen
yg supply
pp y mayy
result in injury
OxiplexTS, ISS Inc, USA
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Functional NIR sensing
An sensor with central emitter
and eight
g surrounding,
g,
detachable detectors
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Functional NIR optical imaging
NIR images of the prefrontal cortex obtained with the
continuous wave device for problem solving showing
blood volume and oxygenation changes (scale is μM).
μM)
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Functional NIR optical imaging
Hemodynamic changes due to emotional stress in
the prefrontal cortex.
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Optical coherence tomography (OCT)
光同調斷層影像
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Captures micrometer-resolution, three-dimensional images
from within optical scattering media (e.g., biological
tissue)
OCT is an interferometric technique.
OCT of a fingertip
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OCT principle
Interferometry
•
•
•
•
•
•
super-luminescent diode (SLD)
convex lens (L1)
b
beamsplitter
li
(BS)
camera objective (CO)
CMOS-DSP camera (CAM)
reference (REF) and sample (SMP).
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OCT principle (cont.)
(cont )
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Display image of light scattering in tissue
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Michelson interferometer
Waves in phase undergo
constructive interference
laser
Superposition of
waves
laser
Out of phase undergo
destructive interference
Traveling
different
distances
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Time-domain
Time
domain OCT
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The pathlength of the reference arm is translated longitudinally in
time.
The interference (series of dark and bright fringes) is achieved when
path difference lies within the coherence length of the light source
(axial resolution).
Thi interference
This
i t f
is
i called
ll d cross-correlation
l ti where
h
the
th peakk off the
th
envelope corresponds to pathlength matching
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Frequency-domain
Frequency
domain OCT
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The broadband interference is acquired with spectrally
separated detectors either by


encoding
di the
th optical
ti l frequency
f
in
i time
ti
with
ith a spectrally
t ll
scanning source
or with a dispersive detector,
detector like a grating and a linear
detector array.
Spectral bandwidth sets
the axial resolution
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Frequency-domain
Frequency
domain OCT
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Due to the Fourier relation between auto-correlation and
spectral power density, the depth scan can be immediately
calculated from the acquired spectra,
spectra without movement
of the reference arm.
This feature improves imaging speed dramatically
dramatically.
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OCT application
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OCT in Oral cancer diagnosis
Normal mucosa
Biopsy:
Pros: Golden‐standard
Cons: Sampling errors
Invasive method
Complicated process
Time‐consuming method OCT‐ Optical biopsy
Pros: Non‐invasive
Real‐time imaging
Multi‐dimensional imaging
Cons: Poorer resolution Provided by Prof. MT Tsai
(J Biomed Opt 2008, 2009)
Cancerous mucosa
Reference
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John Enderle, Susan Blanchard, Joseph Bronzino,
Introduction to Biomedical Engineering, Academic Press,
2000.
2000
生物醫學工程導論，滄海書局，2008.
Wikipedia the free encyclopedia
Wikipedia,
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