Lecture 1 01/04/2019
Biomedical optics
• Physics: light tissue interaction
• Engineering: instrumentation
• Biology: monitoring disease in vivo
• Medicine: apply new technology in clinical care
Absorption and scattering are the two most
important parameters to describe light-tissue
interaction. It determines where the light
goes to and how much energy is being
transmitted.
A laser beam that passes through water does
(almost) not undergo any absorption or
scattering.
When the absorption increases, the penetration of light decreases.
When the scattering increases, the more light goes in every direction. The number of places
where light is located increases.
High scattering, low absorption: transfer of energy is relatively spread.
High absorption, low scattering: large part of energy is captured in the beginning.
There are two important ways to use light:
• To quantify tissue structure and metabolism; for example the oxygen content in blood.
• To influence tissue function; for example surgery or the stimulation of nerves.
The first is more subtle than the second. The biggest difference is the power that is being
used. The first one adds an energy that is just on the boundary of being safe, however the
second one is used to really damage material.
Absorption
Medical imaging techniques cover a large part of the electromagnetic spectrum.
• SPECT, PET, CT, X-ray (short wavelength)
• Optical medical imaging (between short-long wavelength)
• MRI (long wavelength)
These techniques that use longer
wavelengths, like infrared light, are
mostly used in clinical diagnostics.
,The energy decreases if the wavelength increases.
The absorption of water is very important as 70% of the human body consists of water. If we
want to measure something in tissue, the question is if we can measure something in water.
Optical techniques work in the regions where the absorption of water is not as strong.
For example visible light has a large peak where water is strongly absorbed.
Optical techniques are used in medical imaging. Depth is
related to the resolution. The deeper a light can travel, the
lower the resolution.
A microscope cannot go that deep, but has a high
resolution. An OCT can go deeper, but the resolution
worsens a bit. SPECT/PET can go deep, but the resolution
is not good. We cannot observe individual cells, only
larger structures.
Scattering
Scattering depends on the ratio of the wavelength of light that you are using and the structures
you are looking at. For example with cancer we want to look at a cellular level. The cells
divide as a result of mutations and this process is at another level. Also, to be able to divide
the cells need nutrients. Therefore, the mitochondria start working harder and more nutrients
will be available. This example illustrates that many cells begin at subcellular level.
The scope of this course is closely aligned with our research lines: the emphasis is on optical
characterization of tissue diagnostics.
,My motivation
Optical Coherence Tomography → echography with light. OCT is an image technique that
uses light to capture images from within optical scattering media. It is a key diagnostic
method in ophthalmology today.
With OCT light-sensitive receptors on the retina (individual cones and rods in the eye) can be
seen; 2D/3D imaging down to the cellular level. Also, we can quantify the cell layer
thicknesses associated with development of diseases.
OCT can be a key diagnostic method in other disciplines. For example, color-coding of lipid
content in atherosclerotic tissue based on optical properties. When the inside of an artery
narrows due to the accumulation of plaque, the cap can become loose and rips off. Then, the
fat from the plaque comes into contact with the bloodstream (which is usually not present in
the blood) and as a result a blood clot is formed. When this blood clot travels to the heart or
the brain, an infarct can develop. The speed of signal decay can be measured with OCT.
Recent progress: cancer typing in gynecology,
urology, gastro-enterology, dermatology, etc.
Important is the use of this technique in the pre-
phase of cancer screening; in sex organs, vocal
chords, etc. With this technique we can prevent
that too many (healthy tissue) biopsies are
taken.
C. The OCT signal against the depth; this graph
describes how much the signal decays as a
function of the depth. The decay can be
expressed as the attenuation coefficient.
D. This graph shows that the healthy biopsies
have a lower attenuation coefficient than the
biopsies that contain tumor cells.
My motivation: to understand all this
1. How do changes in tissue functionality, morphology during disease development and
progression translate into ‘changes in optical properties?’
2. How can I measure these optical properties quantitatively?
3. How can I translate my optical measurement into a meaningful diagnostic?
, The faith of absorbed energy
Absorbance
The first transition in the Jablonski diagram is the absorbance of a photon of a particular
energy by the molecule of interest. Absorbance is the method by which an electron is excited
from a lower energy level to a higher energy level. The energy of the photon is transferred to
the particular electron. That electron then transitions to a different eigenstate corresponding to
the amount of energy transferred. Only certain wavelengths of light are possible for
absorbance, that is, wavelengths that have energies that correspond to the energy difference
between two different eigenstates of the particular molecule. Absorbance is a very fast
transition, on the order of 10-15 seconds.
1. Heating
Once an electron is excited, there are a multitude of ways that energy may be dissipated. The
first is through vibrational relaxation, a non-radiative process. In vibrational relaxation the
energy deposited by the photon into the electron is transformed into kinetic energy which
causes variations in the length of chemical bonds or the angles between atoms within the
molecule.
However, if vibrational energy levels strongly overlap electronic energy levels, a possibility
exists that the excited electron can transition from a vibration level in one electronic state to
another vibration level in a lower electronic state. This process is called internal conversion
and mechanistically is identical to vibrational relaxation.
For regional heating of tissue (for example for therapy) we typically need to solve equations
like this to calculate the spatiotemporal temperature distribution in the tissue:
The absorption coefficient and fluence rate can be changed; what laser do we need to use?
Heat can also be used for photo-acoustic imaging.
A laser or RF pulse is given, whereafter a photon is absorbed. This
leads to a fast thermal expansion and also to a fast decay which
leads to acoustic waves. This wave propagates from the point
where the pulse is initiated. Thereafter, this pulse can be detected
and an image can be formed.
