This document discusses optical coherence tomography (OCT), which uses light to perform high-resolution, non-invasive imaging of tissue microstructure. OCT works by measuring echoes of backscattered light to generate histopathology images without biopsy. It has applications where standard biopsy is difficult or has sampling errors. OCT performs cross-sectional and 3D imaging using interferometry to measure echo time delays of backscattered light. Time-domain OCT scans a reference mirror, while Fourier-domain OCT detects interference spectra to image faster.

2. Introduction
 OCT performs high-resolution imaging of tissue
microstructure and pathology by measuring echoes of
backscattered light.
 Results in histopathology images without biopsy.
 Also called ‘optical biopsy’. (Light is used instead of
knife)
 Tissue pathology can be imaged with resolutions of 1–15
µm, one to two orders of magnitude finer than
conventional ultrasound.
 Is particularly suited to ophthalmic applications and other
tissue imaging requiring micrometer resolution and
millimeter penetration depth.

3. Introduction
 OCT has applications in situations:
 where standard excisional biopsy is hazardous or
impossible.
 Applications include the eyes, arteries, or nervous tissues.
 where standard excisional biopsy has sampling error.
 Excisional biopsy and histopathology is used for diagnosis of
many diseases including cancer; however, if the biopsy misses
the lesion, this causes a false negative.

4. A-scan, B-scan, and 3D-scan
 OCT performs cross-sectional and volumetric imaging by
measuring the magnitude and echo time delay of
backscattered light.
 Axial scans or A-scans: axial measurements of echo time
delay
 B-scans: 2D cross-sectional images generated by transversely
scanning the incident optical beam and performing
sequential axial measurements of echo time delay (0.02 –
0.04 sec).
 3D-scans: Three dimensional, volumetric data sets generated
by scanning the incident optical beam in a two-dimensional
pattern to generate a series of B-scans.

7. OCT and Other Imaging Modalities
OCT fills a gap between ultrasound and microscopy.
 OCT technologies have axial resolutions ranging from 1 - 15
µm, approximately 10–100 times finer than standard
ultrasound imaging.
 Light attenuation due to optical scattering in most tissues limits
OCT imaging depth to 2–3 mm.
 Confocal microscopy has submicron resolution, but imaging
depth is only a few hundred microns in most tissues
 Although the imaging depth of OCT is limited, OCT can be
integrated with devices such as catheters or endoscopes to
access luminal organ systems such as the GI tract.

9. OCT and Ultrasound
 Light is used instead of sound waves.
 Ultrasound and OCT are analogous: Images are obtained by
measuring
 echo time delay, and
 intensity of backreflected sound or light from structures having
different acoustic or optical properties, as well as from boundaries
between structures.
 OCT is effectively ‘optical ultrasound’
 Images show optical properties of tissues, not a true histological
section

10. OCT and Ultrasound
 A principal difference: The speed of sound is 1,500 m/s,
while the speed of light is approximately 3 x 108 m/s.
 In order to measure distances with a 100 µm resolution, as for
ultrasound imaging, a time resolution of 100 ns is required.
This resolution is well within the limits of electronic
detection.
 The measurement of distances with a 10 µm resolution, a
typical resolution for OCT imaging, requires a time resolution
of 30 fs (30 x 10-15 sec). Direct electronic detection is
impossible with this time resolution.
 Thus, measurement methods such as high-speed optical
gating, optical correlation, or interferometry must be used.

11. Principle
 Interference is the addition of two waves mathematically.
 Interferometry makes use of the principle of superposition
to combine waves in a way so that the resulting interference
pattern have some meaningful property diagnostic of the
waves original state.
 Interferometry
 measures correlation b/w physical quantities of a single wave
(autocorrelation), or b/w several waves (cross-correlation).

12. Interferometry
 When two waves with the same frequency combine, the resulting
intensity pattern is determined by the phase difference between the
two waves:
 Waves that are in phase will undergo constructive interference,
 Waves that are out of phase will undergo destructive interference,
 Waves which are not completely in phase nor completely out of
phase will have an intermediate intensity pattern, which can be
used to determine their relative phase difference.

13. Michelson interferometer
 A single incoming beam of coherent light is
split into two identical beams by a beam
splitter (a partially reflecting mirror).
 Each of these beams travels a different
route, called an optical path, and they are
recombined before arriving at a detector.
 The optical path difference, the difference
in the distance traveled by each beam,
creates a phase difference between them.
 This introduced phase difference creates an
interference pattern between the initially
identical waves.
 The resulting interference fringes give
information about the difference in optical
path lengths.
 The exact distances between the three
mirrors determines the length of the two
optical paths.
The light path through a Michelson
interferometer.

14. Michelson interferometer
 Use of white light will result in a pattern of colored
fringes.
 Different patterns depend on the relative phase
difference between the two beams.

15. Coherence..?
 Two wave sources are perfectly coherent if they have a
constant phase difference and the same waveform and
frequency.
 Generally, coherence describes the correlation (or degree of
similarity) between physical quantities of a single wave, or
between several waves or wave packets.
 Coherence is an ideal property of waves that enables stationary
or “meaningful” interference.

16. Coherence..?
 Types : Spatial & Temporal
 Spatial coherence describes the correlation between
waves observed at different points in space.
i.e., at the same moment in time, but at different points in
space
 Temporal coherence describes the correlation between
waves observed at different moments in time.
i.e., correlation of phase at the same point in space but at
different time moments.

17. Coherence..?
(a) Perfectly coherent beam. All the
constituent waves are in phase at all
times.
(b)Spatially coherent beam, but
exhibits only partial temporal
coherence. Waves simultaneously
change their phases by an identical
amount every few oscillations.
(c) Completely incoherent beam
where the phases of each wave
change randomly at random times.

18. Coherence..?
 Coherence time τc is the time over which a propagating wave
may be considered coherent.
 Or, it is the time above which the wave phase or amplitude
changes by a significant amount (and hence the correlation
decreases by significant amount).
 The coherence length Lc is defined as the distance the wave
travels in time τc.

19. Coherence..?
 Coherence length is inversely proportional to the frequency
bandwidth of the light.
 A wave with a longer coherence length is closer to a perfect
sinusoidal wave.
 The larger the range of frequencies Δf a wave contains, the faster the
wave decorrelates (and hence the smaller τc is).

20. Coherence..?
 Wave interference is strong when the optical paths taken by the
interfering waves differ by less than the coherence length.
 When two identical waves of length Lc travel different distances L1
and L2 , then are recombined, they can only interfere over a length
Lc – (L1 –L2)

21. Types of OCT
 Time-domain OCT
 Fourier-domain OCT

22. Time-domain OCT
Scanned
reference path

23. Time-domain OCT
 OCT is based on low-coherence interferometry.
 OCT uses a low-coherence light source (or broad-bandwidth light
source), i.e., sources that emit light over a broad range of
frequencies.
 White light is an example of a broadband source with lower power.
 The core of a typical OCT system is a Michelson interferometer.
 One interferometer arm is focused onto the tissue sample.
 The other interferometer arm is bounced off a reference mirror.
 Reflected light from the tissue sample is combined with reflected
light from the reference giving rise to an interference pattern.

24. Time-domain OCT
 Interferometry essentially measures correlation between light
backscattered from the tissue with light that has traveled through a
reference path with a known time delay.
 The optical pathlength of the reference arm is varied (the reference
mirror is translated longitudinally). The interferometer output is
detected as the reference path length is scanned.
 The envelope of this modulation changes as pathlength difference is
varied, where the peak of the envelope corresponds to pathlength
matching.
 This peak represents the location of the microstructure of the
sample under test.
 The echo magnitude versus time delay or axial scan is obtained by
demodulating, or detecting the envelope of the interference signal.

25. Time-domain OCT
 A cross-sectional tomograph (B-scan) may be achieved by laterally
scanning the sample and combining a series of these axial depth scans
(A-scans).
 Because of the low coherence of the light source used (or broad-
bandwidth light source), interference is only observed when the
measurement and reference path lengths differ by less than the
coherence length of the light source.
 Therefore, interferometric signal is observed only over a small range
of path length differences corresponding to scanning a limited
depth of sample.
 The coherence length of the light source determines the axial image
resolution.
 Shorter coherence lengths from broadband light sources provide
finer axial resolution.

26. Time-domain OCT

27. Fourier-domain OCT
 Spectral/Fourier-domain OCT uses a broad bandwidth
light source and detects the interference spectrum from the
interferometer using a spectrometer and a line scan
camera.
 It essentially measures all of the echoes of light
simultaneously, leading to an increase in imaging speed.

28. Fourier-domain OCT
 Spectrometer:
 uses a prism or a grating to spread the light from a light
source into a spectrum.
 often used in spectroscopy for producing spectral lines,
measuring their intensities versus wavelengths.

29. Fourier-domain OCT
 The position of the reference mirror is fixed, i.e., reference arm has a
fixed known time delay.
 The signal beam and the reference beam have a relative time delay
determined by the path length difference ΔL, which is related to the
depth of the structure in the tissue.
 The interference of the two beams shows spectral modulation
versus frequency , i.e., a periodic output spectrum, which can be
measured using a spectrometer.
 The frequency of this modulation is related to the echo time delay.
 Different echo delays will produce different frequency modulations.

31. Fourier-domain OCT
 Fourier transforming the interference spectrum yields
axial scan information (echo magnitude vs. time
delay).
 The technique is somewhat analogous to MR imaging
in that spatial information is encoded as spatial
frequency.

35. OCT
Advantages Disadvantages
Non-invasive Best for optically transparent tissues
Non-contact Limitations in cases of
retinal/subretinal hemorrhage, cornea
opacities
Near-microscopic resolution
Axial resolution ~ 10 µm
Diminished penetration depth 2-4mm
No preparation of the sample or subject
No ionizing radiation

36. Selected Applications
Intravascular OCT
 OCT is used to image coronary arteries in order to
visualize vessel wall lumen morphology and
microstructure at a resolution 10 times higher than
other existing modalities such as intravascular
ultrasounds (IVUS)and x-ray angiography.
 For this type of application, approximately 1 mm in
diameter fiber-optics catheters are used to access
artery lumen through semi-invasive interventions.

37. Early OCT image of a human artery in comparison with intravascular
ultrasound (IVUS). The OCT image has 15 mm axial resolution and
enables the differentiation of the intima, media, and adventitia. IVUS
has deeper image penetration, but lower resolution.

38. Selected Applications
Ophthalmology
 Ocular (or ophthalmic) OCT is used heavily
to obtain high-resolution images of the retina
and anterior segment.
 OCT is important for the diagnosis and
monitoring of diseases such as glaucoma, age-
related macular degeneration, and diabetic
retinopathy because it provides quantitative
information on retinal pathology which is a
measure of disease progression or response to
therapy.
 Images can be analyzed quantitatively and
processed using intelligent algorithms to
extract features such as retinal thickness.

39. Schematic of OCT instrument design for retinal imaging

40. Time-Domain OCT of the macular area of a retina at
800 nm, axial resolution 3 μm