Biophotonics and medical imaging

Biophotonics and medical imaging
Johannes F. de Boer*
Director Institute LaserLaB
Professor Physics Department, VU University,
Amsterdam and Rotterdam Ophthalmic Institute
*Commercial interest: Intellectual property
The impact of physics on imaging
in healthcare
Anna Berthe Röntgen: Hand mit Ringen
Wilhelm Röntgen's first "medical" x-ray,
of his wife's hand,
taken on 22 December 1895
X-Ray, CT, MRI, PET, Ultrasound
These techniques are a
mainstay of medical imaging
Currently used medical imaging
methods
Radiology
1 mm
1 cm
Radio nucleotide
DOT
PET
MRI
CT
US
Pathology
10 µm
1 µm
100 µm
LIGHT, e.g.,
Microscopy
OCT
HFUS
MRI
X-Ray, CT
Diagnostic capability
Low resolution
Organ Level
Organ Level
Tumor Staging
Architectural, Cellular,
Optical Biopsy
Histopathology is the golden standard
especially for cancer diagnosis
DOT: Diffuse Optical Tomography;
PET: Positron Emission Tomography;
MRI Magnetic Resonance Imaging;
CT: Computed Tomography;
US: Ultra Sound;
HFUS: High Frequency Ultra Sound;
OCT: Optical Coherence Tomography.
OCT is analogous to ultrasound imaging
Uses infrared light in stead of sound
Speed of sound ~ 1480 m/sec (in water)
Speed of light – 3x108 m/sec
Human skin
5 mm wide x 1.6 mm deep
Resolution: 10-30 µm
Interferometry
is used to measure
small time delays
of scattered photons
Principle of OCT
B-Scan
A-line
Low-Coherence Interferometry
Reference
Sample
Source
Detector
Low-Coherence Source!
Detector!
Detector!
Coherent Source!
λ!
Mirror Displacement!
Coherence!
Length!
Mirror Displacement!
Low Coherence Fringe
2λ ln 2 0.44 λ0
FWHM = Lc = 0
=
π Δλ
Δλ
2
λ3
λ2
λ1
0
ΔL
2
The human eye
OCT in ophthalmology: Fercher and Fujimoto groups
(early 1990’s)
High resolution OCT: Fujimoto, Drexler (late 1990’s)
Measurements
Example:
•  1 OCT B-scan in 6 s
•  1536 A-lines per B-scan
•  1024 pixels / A-line
•  dynamic range ~35 dB
•  resolution in depth 6 !m
•  resolution in width ~ 20-30 !m
•  32 video frames / 6 s
•  B-scans post processed to remove
motion artifacts
Time Domain and Spectral Domain OCT
configurations
Fujimoto (1991)
Huang, D., Swanson, E.A., Lin, C.P., Schuman, J.S., Stinson, W.G., Chang,
W., Hee, M.R., Flotte, T., Gregory, K., Puliafito, C.A., and Fujimoto, J.G.,
Optical coherence tomography. Science, 1991. 254(5035): p. 1178-81.
Fercher (1995)
Source
Fiber
50/50 Reference arm
Splitter
Sample arm
Grating
Detector array
Lens
mirror
Spectrum to PC
for processing
Lens
Grating
A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. El-Zaiat, “Measurements of intraocular
distances by backscattering spectral interferometry,” Opt. Comm. 117, 43-48 (1995).
Detector
Array (CCD)
SD-OCT
I (k ) = I r (k ) + 2 I s (k ) I r (k ) ∑ α n cos( k z n ) + I s (k )
n
FFT
[
]
⎧
2
2
2
2 ⎫
FT [ I (k )] = Γ ( z ) ⊗ ⎨δ (0) + ∑ α n δ ( z − z n ) +∑α n δ ( z + z n ) + O I s I r ⎬
n
n
⎩
⎭
−1
2
2
FFT
SNRSD =
ηPsampleτ i
Eν
Experimental verification of sensitivity
Experimental SNR
TD = 44.3 dB
SD = 50 dB
50
TD-OCT 4msec/depth profile
SD-OCT 100µsec/depth profile
Theoretical prediction
TD = 46.7 dB
(QE=0.85, BW = 100kHz
SD = 51.9 dB
(QE = 0.28, τi = 100 µs)
Signal [dB]
40
Sample arm power = 1.27 nW
30
20
10
SNR difference = 5.7 dB
0
SNR benefit =
5.7 + 16 = 21.7 dB
0
200
400
600
Depth [µm]
Demonstrated SNR improvement of 21.7 dB (factor of 150)
N. Nassif et al. Optics Letters 29 (5), 480 (2004)
First video rate images of the human retina (2003-2004)
Width 6.4 mm, depth 1.7 mm, 1000 depth profiles
2x
Magni
fied
N. A. Nassif et al., Opt. Express 12, 367-376 (2004)
UHR-SD-OCT Fovea
6 x 6 mm
6 x 1.1 mm
B. Cense et al. Opt. Express 12, 2435-2447 (2004)
Age related Macular Degeneration (AMD)
AMD is the leading cause of blindness in people over
age 65 years in Western countries
8 million people affected in the US alone
10% of AMD patients will develop neovascularization
under the retinal pigmented epithelium or in the
subretinal space
Current treatment: anti VEGF therapy
Current diagnosis: include Fluorescein Angiography
(FA), indocyanine green angiography (ICG), and OCT
70-year-old male, presenting with
blurred vision (OD)
70-year-old
male (OD)
Location 1
A: Drusen, B: Blood clot, C: Subretinal fluid, D: RPE detachment. Image
size 7.55 mm x 1.95 mm.
70-year-old
male (OD)
Location 2
A: Cystic changes, B: Blood clot, C: Weak scattering in photoreceptors, D:
Subretinal Fluid, E: Strong scattering in photoreceptors, F: RPE detachment,
G: confirmed CNV from FA. The OCT image suggests this is type 1 CNV.
70-year-old
male (OD)
Location 3
A: Strong scattering from photoreceptors in the periphery of the subretinal
fluid. Image size 7.55 mm x 1.95
Optical Doppler Tomography
Velocity component parallel to beam = v x cos(θ)
Doppler frequency shift:
Δf = 2vcos(θ)/λc
Velocity:
v = Δf λc /2cos(θ)
First ODT demonstration: T. Milner
First flow measurement in the eye: Izatt Group
High Resolution Doppler OCT (ODT)
Sequential A-lines
A-line 1
ΔT
A-line 2
ω=Δφ/ΔT
Δφ
Y. Zhao et al. Optics Letters 24: 114-116, 2000.
Phase-resolved OCT angiography
B. Braaf, K.A. Vermeer, K.V. Vienola, J.F. de Boer, Optics Express, 20,
20516-20534 (2012)
Acknowledgement JFdB group members
Boy Braaf
Jianan Li
Mattijs de Groot
Joshua Mo
Koen Vermeer
Frank Helderman
Miriam Moester
Clinical collaborators
Glaucoma: Hans Lemij
AMD: Jan van Meurs
Lung: Joop de Langen, Hans Daniels
Fluorescence: Guus van Dongen
Past group members
Ki Hean Kim
Hyle Park
Many more
Funding: NWO Groot, FOM NIG project grant, NIH R21,
VICI (ZonMW), CORR research funds (ROI), MS
foundation (VU/ROI)