optical coherence tomography lecture 3 – parametric ... · optical + biomedical engineering...
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Optical coherence tomography Lecture 3 – Parametric contrast, and delivery
systems: endoscopes and needles David Sampson
Optical + Biomedical Engineering Laboratory School of Electrical, Electronic and Computer Engineering,
& Centre for Microscopy, Characterisation & Analysis
The University of Western Australia
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Take home messages • Basic imaging technology in place
- Speed and sensitivity have enabled 3D
• 3D opens up many possibilities
• Imaging protocols – take care to avoid artefacts
• Accurate comparison with histology is vital but still rare
• Many impediments, but two stand out… - Scattering contrast is low
- Speckle corrupts image
• Speckle – the interplay of wavefront aberration and multiple scattering not well understood
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Roadmap for what OBEL does • Medical microscopy
Optical coherence tomography
• What you can do on the surface “Atlas” studies: lymph nodes, parametric methods: attenuation, PS-OCT, lymph nodes, burns vasculature
• What you can do with catheters Human upper and lower airways
• What you can do with needles Needle design, OCT+fluorescence multimodality, animal airways, tumour margins: breast cancer
• Elastography – alternative contrast Emerging methods, phantoms, modelling, breast cancer
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
How much does the scattering coefficient of tissues typically vary by?
μs = 2-20 mm-1
…which is a mean free path 50-500 μm
Scattering contrast is modest
Contrast, contrast, contrast
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
OCT of human axillary lymph nodes Involved lymph node - ductal carcinoma
– Well delineated metastasis – Remainder of node is uninvolved – T: tumour, C: cortex, PC: paracortex, M: medulla
Histology (H&E stain) OCT
McLaughlin et al., Cancer Research 79, 2579-2584, 2010
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Involved lymph node − ductal carcinoma – Diffuse malignant cells – T: Tumour, dark in OCT – C: Residual cortex, light grey in OCT
Histology (H&E stain) OCT
OCT of human axillary lymph nodes McLaughlin et al., Cancer Research 79, 2579-2584, 2010
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• How can we get more constrast?
• If we have 3D, try imaging an optical parameter, parametric imaging
• This trades off depth for enhanced sensitivity
• Flavours of optical properties include:
- Scattering and absorption – μs, μa, g
- Birefringence – Δn = ne – no
Contrast, contrast, contrast
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Parametric OCT imaging to enhance contrast
McLaughlin et al., MICCAI 2009: Proc. Medical Image Computing and Computer-assisted Intervention; Lecture Notes in Computer Science 5762:657-664, 2009; and J. Biomed. Opt. 15, art. 046029, 2010
OCT Parametric OCT H&E histology
1mm 1mm 1mm
Cancer
Map A scan slope – Measures local attenuation – Info in 3D volume mapped to
2D to improve sensitivity to…
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Cancerous lymph node – Parametric images show better contrast of healthy vs cancerous
tissue – Circled areas show residual healthy cortex
H&E histology μ parametric image OCT en face – best match
McLaughlin et al., “Parametric imaging of cancer with optical coherence tomography”, Journal of Biomedical Optics, 15(4):046029, 2010
Scale bar 1mm
Parametric OCT – qualitative contrast
Optical pathlength 0.5 mm
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Cancerous lymph node – Cancerous areas – high attenuation (bright) – Healthy cortex – low attenuation (dark)
H&E histology Parametric image OCT en face – best match
McLaughlin et al., “Parametric imaging of cancer with optical coherence tomography”, Journal of Biomedical Optics, 15(4):046029, 2010
500 m
• Images shown are qualitative – reflectance not calibrated • Can we convert parametric imaging to a quantitative modality?
Parametric OCT – qualitative contrast
Optical pathlength 0.5 mm
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Contrast mechanism – attenuation in depth – Given a 3D data set, estimate μt at each x,y over a range z – If tissue is homogeneous, single scattering will follow
modified “Beer’s Law”
Core idea: Condensing 3D data to 2D to enhance sensitivity to detecting cancer
Parametric attenuation
image
Parametric OCT – quantitative contrast
McLaughlin et al., MICCAI 2009: Proc.
Medical Image Computing and
Computer-assisted Intervention; Lecture
Notes in Computer Science 5762:657-664,
2009
R(z) = ρe-2μtz
loge R(z)
Slope μt
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
How to generate parametric attenuation images
Parametric image − extract μ (x,y)
Moving window (x,y)
Assume homogenous: apply fit over (e.g., 200 μm) window
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Moving window (x,y)
Parametric image − extract μ (x,y) Assume homogenous: apply fit over (e.g., 200 μm) window
How to generate parametric attenuation images
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Moving window (x,y)
Select depth(z)
Parametric image − extract μ (x,y) Assume homogenous: apply fit over (e.g., 200 μm) window
How to generate parametric attenuation images
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
How to generate parametric attenuation images
Moving window (x,y)
Select depth(z)
Parametric image − extract μ (x,y) Assume homogenous: apply fit over (e.g., 200 μm) window
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Method to extract attenuation coeffiction μt
1. A-scan 2. Reflectance profile R(z)
Pre-processing+
Fit to model Calibration
+Correction
3. Extract μt
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT 17
Method: Axial calibration and correction Confocal axial response CCCCCCCCoonnffooccaall aaxxiiaaaaaaaaaa
Reference scan function
OCT objective lens focus function
Reference arm coupling efficiency
Microsphere suspension,
0.46 μm diameter,
μs ≈ 0.7 mm-1, g = 0.7
Correction profiles
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Quantitative parametric OCT - Signatures • Healthy lymph node • Calibrated reflectance profile
R(z) • Extract absolute μt
240 μm
μt
H&E histology OCT (en face)
• Pathologist identifies pure
tissue types – Paracortex – Medullary sinuses – Fibrous capsule
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Axillary lymph node Paracortex Medullary sinuses
Fibrous capsule Inactive primary follicular tissue
Scale bars: 1 mm
OCT
Quantitative μt(x,y) Segmented by μt(x,y) H&E histology
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Axillary lymph node, Example #2 Paracortex Medullary sinuses
Necrosis Calcification
Histology OCT μt(x,y)
Fibrous capsule Cortex
Scale bars: 1 mm
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Lymph node – measured attenuation coefficients
Lymphoid tissues can be distinguished with quantitative parametric imaging of the attenuation coefficient
L. Scolaro et al. “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography” Biomed. Opt. Express 3(2), 366–379, (2012)
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
OCT (en face)
Paracortex Medullary sinuses Fibrous capsule
Scale bars: 1 mm
Quantitative μt(x,y) Segmented by μt(x,y)
Quantitative parametric OCT L. Scolaro et al. “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography” Biomed. Opt. Express, vol. 3, no. 2, pp. 366–379, (2012)
Take home: Promising, not yet convincing
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Parametric attenuation imaging of burn scars
• Removing effect of vessels important • Scars are more transparent than normal skin • Because their collagen contains more water
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Roadmap for what OBEL does • Medical microscopy
Optical coherence tomography
• What you can do on the surface “Atlas” studies: lymph nodes, parametric methods: attenuation, PS-OCT, lymph nodes, burns vasculature
• What you can do with catheters Human upper and lower airways
• What you can do with needles Needle design, OCT+fluorescence multimodality, animal airways, tumour margins: breast cancer
• Elastography – alternative contrast Emerging methods, phantoms, modelling, breast cancer
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• How can we get more constrast?
• If we have 3D, try parametric imaging
• Trade off depth for enhanced sensitivity
• Flavours of optical properties include:
- Scattering and absorption – μs, μa, g
- Birefringence – Δn = ne – no
Contrast, contrast, contrast
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
What can PS-OCT be used for?
• Birefringence – magnitude and orientation – Large-scale information on “micro-order of nanostructure”
Examples – Nerve fibre layer in the retina (glaucoma) – Collagen: Scarring in skin, cornea; in atherosclerotic plaque,
abnormality in the cornea, organisation in cartilage – Muscle: dystrophies, airways
• Scattering (less evidence)
– Small-scale information about scatterers and their local environment
Examples – Dental caries – Oesophagus – distinguishing normal, neoplastic and scar tissue
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Musculoskeletal tissues exhibit birefringence
Jacoby et al., Development, 2009, 136, 3367-3376
Normal, undamaged, muscle
Necrotic muscle
Decreases when disease processes damage tissue
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Duchenne muscular dystrophy (DMD)
• Can we characterise tissue necrosis or regeneration in the mdx mouse model in vivo?
• If so, a single animal could be tracked in time – needs fewer animals, less variability
• Can we characterise DMD in humans?
C57 control mouse
Collaboration: Grounds Lab School of Anatomy, Physiology & Human Biology, The University of Western Australia
Normal Dystrophic
100μm 100μm
The Jackson Laboratory www.jax.org
DMD patient 12 years
mdx dystrophic mouse
Optical coherence tomography imaging of muscle
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Klyen et al., J. Biomed. Opt., 13(1) 011003, 2008
EDL
EDL
TA
TA
x
x y
y
Histology:
Haematoxylin and Eosin-stained 5-μm tissue section
Optical coherence tomography:
en face, from 3D section
TA EDL
Tissue damage model – whole muscle autograft
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
100μm
250μm
500μm
Autograft surgical model of muscle damage
B. R. Klyen et al., JBO, 13(1): 011003 (2008)
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
mdx mouse model of muscular dystrophy – bulk
z
y x
B. R. Klyen et al., J. Biomedical Optics 16(7), 076013, 2011
Photograph 3D-OCT H&E-histology EBD-fluorescence
histology
Necrotic lesion
Disruption region EBD
accumulation
EBD fluorescence
EBD-fluorescence Microscopic indication of
permeable (leaky or necrotic) myofibres
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Does the degree of polarisation change? – DOP is a measure of the amount of polarised versus
unpolarised light – If we illuminate with polarised light and detect single
backscattering, the DOP should remain unity – Affected by many factors, but especially multiple scattering
Polarisation-sensitive OCT
What affects the polarisation state? – Birefringence along optical path – Scattering
Typical retardation over image – few radians, a small effect Δn = 10-3, λ = 1 μm, l = 1 mm, 2kΔnl = 4π
Orientation of axis of birefringence can also be important
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Some points – Stokes formalism or Jones calculus can be used – To determine retardation/birefringence need only two independent measurements – To determine birefringent axis orientation need another two
Could be full set of Stokes parameters
Could be amplitude and phase in orthogonal polarisations
– To determine parameters at a given depth assumes parameters at shallower depths are known
Scenarios – Determine full Müller matrix of tissue
• Requires 16 independent measurements
– Determine Stokes parameters of received light knowing Stokes parameters of input light
• Requires 4 independent measurements
– Determine Jones matrix • Requires 4 independent measurements
How is polarisation described? Jones calculus ⎥
⎦
⎤⎢⎣
⎡=
in
inin
,
,
y
x
EE
Ε
⎟⎟⎟⎟⎟
⎠
⎞
⎜⎜⎜⎜⎜
⎝
⎛
=
in
in
in
in
in
VUQI
SStokes calculus
⎥⎦
⎤⎢⎣
⎡=
43
21in path, JJ
JJJ =in path,M
⎥⎥⎥⎥
⎦
⎤
⎢⎢⎢⎢
⎣
⎡
44434241
34333231
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14131211
MMMMMMMMMMMMMMMM
Jscatterer Mscatterer
out path,out path, MJininpath,scattereroutpath,out ΕJJJΕ =
Sout = Mpath,outMscattererMpath,inSin
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Poincaré sphere
Polarisation state described by Stokes parameters Q,U,V Normalised Stokes vectors lie on the unit (Poincaré) sphere Linear states on the equator, circular states at the poles
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Polarisation on the Poincaré sphere • Jones vector representation: complex amplitude and phase
• Stokes vectors: Relative intensities Normalised
• We can represent as a point in 3-D space – the Poincaré sphere
[ ]I,Q,U,V=S[ ]V,U,QI ˆˆˆˆ == SS
⎥⎦
⎤⎢⎣
⎡=
⎥⎥⎦
⎤
⎢⎢⎣
⎡=⎥
⎦
⎤⎢⎣
⎡Δ
−−
−
θ
θφ
φφ
φ
sincosi
ii
y
ix
y
x
eae
eaea
EE
xy
x
S
Partiallypolarised
1ˆ <S
Elliptical polarisationFully polarised
1ˆ =S
Right circularpolarisation
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Instrumentation • Ref path – equal signal on
both detectors • Sample – independent of
axis orientations
{ }( ){ }⎟
⎟⎠
⎞⎜⎜⎝
⎛
−−−
−=
θδπδ
δδ
2expsinexpcos
S jj
RE
nretardatio=δnorientatio axis=θ What is the difficulty with a
fibre? Unknown polarisation state Varies with time
• What happens in an ordinary OCT system and a birefringent sample?
• Intensity modulation with retardation – why??
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Polarisation-sensitive OCT – fibre optics
PBS: Polarising beam splitter PC: Polarisation controller PD: Photodetector
Co- (left) and cross- (right) polarised signal components
Be aware that there are various approaches trading off complexity with completeness in polarisation state
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
OCT v PS-OCT B-scan images OCT Retardance
φ(z) =2πn
λ2zΔn
• Polarisation sensitive OCT B scan intrinsically an integral from the surface
• A natural fit for parametric imaging
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Straight OCT does not have enough contrast
• In muscle tissue, try imaging birefringence
• Birefringence depends on disease
• Try parametric imaging of birefringence
Parametric polarisation-sensitive OCT
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Parametric imaging requires automation
• Clinical motivation – muscular dystrophy
• PS-OCT to measure birefringence – Undamaged muscle high birefringence – Necrotic muscle low birefringence
• Automated quantification algorithm – Calculates percentage of necrotic tissue – Addresses issues of:
• Phase wrapping • Phase noise
• Pre-clinical validation
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Birefringence Rate of change of phase retardation, φ, with depth, z
Phase retardation Angle between points on the Poincaré sphere
Birefringence from changes in polarisation
Δn =φ(z)
2z
λ2πn
Phase retardation, ϕ(z)
Stokes vector at depth z
Stokes vector at depth z0
φ(z) =2πn
λ2zΔn
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Phase retardation • Does not increase
monotonically with depth • Wraps between [0, π]
Phase retardation – phase wrapping
Stokes vector at depth z1
Phase retardation, ϕ(z1)
Phas
e re
tard
atio
n, ϕ
(z)
Stokes vector at depth z0
Stokes vector at depth z2
Phase retardation, η(z2)
z0 z2z1 z4z3
z3
η(z3)
z4z8
z5 z6 z7 z8
z5
ϕ(z5)
z6
η(z6)
z7
η(z7)
Depth into tissue, z
Stifter et al., Opt. Express, 2010, 18, 25712-25725
Unwrap using a Hilbert-transform based technique
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Phase precision Variance of phase retardation inversely related to OCT SNR
Noise reduction Averaging with kernel K(size m, n, o)Weighting by
Phase retardation – phase noise
)(SNR/2)(2 zz ≈φσ
)(/1)( 2 zzw φσ=
)),,(SNR/(22av zyxKmno ⊗×≈σ
Park et al., Opt. Lett., 2005, 30, 2587-2589
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Quantification algorithm
For each A-scan in the imaging volume • Spatially average Stokes vectors • Calculate the phase-retardation • Hilbert transform recover phase • Perform phase unwrapping • Weighted least squares linear fit
slope of phase with depth • Calculate birefringence
Applying this over the whole volume gives a 2D map of birefringence
Δn =φ(z)
z
λ4π
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Birefringence depends on health/pathology of muscle • Can differentiate necrotic from undamaged tissue
Polarisation-sensitive OCT on muscle
Necrotic
Undamaged
Necrotic
Undamaged
Necrotic
Undamaged
Mdx mouse model, left gluteus L. Chin, X. Yang, R. A. McLaughlin, P. B. Noble, D. D. Sampson, “En face parametric imaging of tissue birefringence using polarization-sensitive optical coherence tomography”, J. Biomedical Optics, 2013
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Polarisation-sensitive OCT on muscle
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
2D colour-coded map of birefringence • Undamaged muscle high
birefringence • Necrotic muscle low
birefringence
Threshold to distinguish between undamaged and necrotic
47
Calculation of percentage of necrotic tissue
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Percentage area of muscle necrosis agrees well
48
Results from dystrophic mdx and control C57 mice: quadriceps (1, A), triceps (2, 3, 4, B, C) and tibialis anterior (5, D, E) muscles
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Muscles – birefringence
• Burn scars – birefringence and attenuation
• Access – combine PS in a needle
Where are we going next in this area?
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
30G OCT needle images of muscle
Tendon Tendon
Connective tissue
Connective tissue
Myofiber Myofiber
@1300 nm
OCT Histology
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
30G OCT needle images of muscle
Myofibers Tendon
Connective tissue
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• OCT needle probes have limited resolution
• Can we improve the resolution using confocal?
Confocal microscope in a needle
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Confocal microscope in a needle
Imaged at 15-mm depth in bovine muscle tissue with 700 nm resolution
Pillai et al., Optics Express 19, 7213, 2011 Laser
488 nm
PMTBS
SMF (angle cleaved) Band-pass
filter
GRIN microendoscope
Scan actuator xy
GRIN fiber
Notch filter
Microscope objective
Sample
22 G needle Guiding needle
350 μm-diameter optics in a 22-gauge needle (700 μm diameter) Deep tissue – ultimate resolution
Low-NA/high-NA GRIN doublet with proximal GRIN fibre scanning
10 μm
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• We can get more constrast from parametric imaging
• We need 3D, and we trade off depth resolution – new problem
• Flavours of optical properties:
- Scattering and absorption – μs, μa, g
- Birefringence – Δn = ne – no
• Need to target applications, not just be empirical
Contrast, contrast, contrast
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Roadmap for what OBEL does • Medical microscopy
Optical coherence tomography
• What you can do on the surface “Atlas” studies: lymph nodes, parametric methods: attenuation, PS-OCT, lymph nodes, burns vasculature
• What you can do with catheters Human upper and lower airways
• What you can do with needles Needle design, OCT+fluorescence multimodality, animal airways, tumour margins: breast cancer
• Elastography – alternative contrast Emerging methods, phantoms, modelling, breast cancer
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Upper airway
– Obstructive sleep apnea
– Asthma
• Lower airway
– Obstruction - stenoses, lung cancer, COPD
– Airway remodelling - asthma, COPD, bronchomalacia, bronchiectasis
Anatomical optical coherence tomography
J. J. Armstrong et al., Opt. Express 11 (1817-1826) 2003 J. J. Armstrong et al., Am J. Respir. Crit. Care Med. 173 (226-233) 2006
Internal dimensions of hollow organs
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Scanning Michelson interferometer
• Long range low-coherence axial sectioning
• Rotational point beam scanning
• Elastic single back-scattering
(Anatomical) optical coherence tomography
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Long radial range
• Pullback axial scanning
(Anatomical) optical coherence tomography
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Anatomical OCT – Upper airway anatomy
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Armstrong et al., Am. J. Respir. Crit. Care Med., p. 226, 2006
Clinical measurements – Pullback scan
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Able to quantitatively observe sleep apnoea events – previously not routinely possible
Leigh et al., IEEE Trans. Biomed. Eng., p. 1438, 2008
Clinical measurements – Apnoea events
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Respiratory phase gating in the pharynx
– Images show movement of airway wall with respiratory phase
– Threshold loading used to increase inspiratory effort
– Greater inspiratory effort → larger movement
– First examples of OCT breath-gated images
– Important for 3D acquisitions
Deep breathing
Breathing against inspiratory threshold load of 20 cm H2O
Oropharynx
Velopharynx
See also VJBO, Vol. 4, Issue 6, 26 May 2009, cover
R. A. McLaughlin, J. J. Armstrong, S. Becker, J. H. Walsh, A. Jain, D. R. Hillman, P. R. Eastwood, D. D. Sampson, Respiratory gating of anatomical optical coherence tomography images of the human airway , Opt. Express, vol. 17, no. 8, pp. 6568-6577, 2009.
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Clinical sleep research
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Why is it useful?
– Stent size selection in tracheo-bronchial disease
– Airway patency beyond obstructing lung cancers/tumour extent
– Quantifying tracheobronchomalacia
– Regional compliance - research tool in airway diseases
Delivered through bronchoscope working channel (3 mm)
Trachea
Middle lobe
Main broncus
Lower lobes
J. J. Armstrong, S. Becker, R. A. McLaughlin, M. S. Leigh, J. H. Walsh, D. R. Hillman, P. R. Eastwood, and D. D. Sampson, Anatomical optical coherence tomography – a safe and effective tool for quantitative long-term monitoring of upper airway
size and shape, Proc. SPIE 6842, 68421N (2008).
Trachea to intermediate size
airways (3-4 mm)
aOCT in the lower airway
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
J. P. Williamson et al, Measuring airway dimensions during bronchoscopy using optical coherence tomography , Eur. Respir. J. 35(1), 34-41, 2010
P. B. Noble et al., Distribution of airway narrowing responses across generations and at branching points, assessed in vitro by anatomical optical coherence tomography , Respiratory Research 11, doi:10.1186/1465-9921-11-9, 2010
P. B. Noble et al., Airway narrowing assessed by anatomical optical coherence tomography in vitro: Dynamic airway wall morphology and function , J. Appl. Physiol.108, 401-411, 2010
Validation in a pig model
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
• Operating theatre • Through bronchoscope
operation - working channel
Human lower airway – bronchoscopy suite
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
aOCT-CT validation – Pre-operative CT – Intra-operative aOCT – Strong correlation in
airway diameter
– Data available online – See Optics Express website
http://www.opticsinfobase.org/oe/
R. A. McLaughlin et al, Applying anatomical optical coherence tomography to quantitative 3D imaging of the lower airway , Optics Express, 16(22), 2008
Axial
Coronal
Human lower airway – CT data
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
R. A. McLaughlin et al, Applying anatomical optical coherence tomography to quantitative 3D imaging of the lower airway , Optics Express, 16(22), 2008
aOCT-CT validation – Pre-operative CT – Intra-operative aOCT – Strong correlation in airway
diameter
– Data available online – See Optics Express website
http://www.opticsinfobase.org/oe/
3D reconstruction of trachea using OSA s Interactive Science Publishing
VolView (VTK based from Kitware, NY)
Human lower airway – aOCT data
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
R. A. McLaughlin et al, Applying anatomical optical coherence tomography to quantitative 3D imaging of the lower airway , Optics Express, 16(22), 2008
Intra-operative imaging – Imaging from larynx to trachea – Surgical instrument visible in
scan – Laryngeal mask
(Used to introduce bronchoscope into airway)
– Data available online – See Optics Express website
http://www.opticsinfobase.org/oe/
aOCT – larynx to trachea
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Clinical history – 51 yo female previously intubated
during severe asthma attack – Prolonged ventilation via a
tracheostomy – One month later developed
breathing problems
Imaging CT scan revealed subglottic tracheal stenosis
Case study – stenosis
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
CT/aOCT cross-comparison shows good correlation
Pre-op CT reconstruction 3D aOCT reconstruction
Outcome - Enabled accurate intraoperative stent sizing
Case study – stenosis
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Question Had the airway completely collapsed? Problem CT may be out of date Unable to push bronchoscope past stenosis Solution Image with anatomical OCT probe
Bronchoscopic view of a tumour in the proximal left main bronchus as viewed from above the main carina
The aOCT probe was advanced between the tumour and airway wall into the left lower lobe
Case study – tumour occlusion
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Left main bronchus obstructed by tumour; a patent airway, distal to the tumour, is seen
Left main bronchus, now fully patent, following endoscopic tumour resection and chemoradiotherapy
– Follow-up bronchoscopy two months later – Airway free of tumour
J. P. Williamson et al., Using optical coherence tomography to improve diagnostic and therapeutic bronchoscopy , Chest 136(1), 272-276, 2009
Tumour occlusion – outcome
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
In vivo human airway local compliance – aOCT Elastic Properties of the Central Airways in ObstructiveLung Diseases Measured Using Anatomical OpticalCoherence Tomography
Jonathan P. Williamson1,2, Robert A. McLaughlin3, William J. Noffsinger1, Alan L. James1,4, Vanessa A. Baker1,4,Andrea Curatolo3, Julian J. Armstrong3, Adrian Regli5, Kelly L. Shepherd2,4, Guy B. Marks6, David D. Sampson3,7,David R. Hillman1,4,5, and Peter R. Eastwood1,2,4
Central Airway Compliance in AsthmaUp or Down? Good or Bad?
In this issue of the Journal, Williamson and coworkers (pp. 612–619) report on the use of anatomical optical coherence tomogra-phy (OCT) to measure the luminal area of central intrathoracicairways (generations 0–5) (1). By coupling this dynamic, in vivomeasurement with simultaneously measured transpulmonary pres-sure, they derived area–pressure relationships of these airwaysand calculated airway compliance (Caw) and specific compliance(sCaw). They then compared these values in control subjects andthose with obstructive lung diseases: asthma, chronic obstructivepulmonary disease (COPD), and bronchiectasis. This is an excit-ing use of a new technology, and their results are surprising.
March 2011
First measurements of local airway elastic properties in situ shows surprising findings in lung disease
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Roadmap for what OBEL does • Medical microscopy
Optical coherence tomography
• What you can do on the surface “Atlas” studies: lymph nodes, parametric methods: attenuation, PS-OCT, lymph nodes, burns vasculature
• What you can do with catheters Human upper and lower airways
• What you can do with needles Needle design, OCT+fluorescence multimodality, animal airways, tumour margins: breast cancer
• Elastography – alternative contrast Emerging methods, phantoms, modelling, breast cancer
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
In vivo microscopy in medical imaging
Deep-tissue microscopy requires: – Optical sectioning
– Current best is a few millimetres in depth
– Endoscopic delivery in hollow organs
– Needle delivery in solid tissues
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
OCT microscope-in-a-needle
23-gauge
Mirror
Optical adhesive
SMF No-core fiber
GRIN fiber
30-gauge 23-gauge
30-gauge
140 μm hole drilled with fs-laser
0.31 mm
125 μm
GRIN NCF SMF
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
3D OCT-in-a-needle imaging engines 840-nm SD-OCT System:
– 840-nm SLD, 6.2 μm axial resolution – Spectrometer-based, 140 kHz Basler Sprint – Common-path sample arm
1300-nm SS-OCT System: – 1310-nm Axsun swept source, 12 μm
axial resolution, 50-kHz sweep rate – High sensitivity, >110 dB – Common-path and dual-arm probes
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Sheep lung scanning Alveoli and bronchioles
– In-tact lung, saline filled – 23-gauge needle, 0.64 mm hole
– Marked areas excised for histology
Quirk et al., J Biomedical Optics, Art. 0036009, 2011
Haematoxylin and eosin-stained
histology
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Sheep lungs – 3D views
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Breast tumour margin – OCT and histology
R. A. McLaughlin, B. C. Quirk, A. Curatolo, R. W. Kirk, L. Scolaro, P. Robbins, B. A. Wood, C. M. Saunders, D. D. Sampson, “Imaging of breast cancer with optical coherence tomography needle probes: Feasibility and initial results”, IEEE J. Selected Topics on Quantum Electronics, In press
H&E section
OCT
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Roadmap for what OBEL does • Medical microscopy
Optical coherence tomography
• What you can do on the surface “Atlas” studies: lymph nodes, parametric methods: attenuation, PS-OCT, lymph nodes, burns vasculature
• What you can do with catheters Human upper and lower airways
• What you can do with needles Needle design, OCT+fluorescence multimodality, animal airways, tumour margins: breast cancer
• Elastography – alternative contrast Emerging methods, phantoms, modelling, breast cancer
Abbe School of Photonics, 11 June 2013 Sampson, Lecture 3, OCT
Take home messages • 3D opens up possibilities to explore new contrast
• Parametric imaging offers niche opportunity
• Attenuation requires nothing new
• Birefringence requires polarisation sensitive-OCT
• Endoscopy with OCT presents many opportunities
• Anatomical OCT presents opportunities in airways
• Needle-based OCT opens up many possibilities
- For much more on this see my Friday colloquium 2pm
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