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    This region corresponds to the blind spot.  The figures below illustrate a picture of the human fundus (back of the eye) taken through an ophthalmoscope, in which the optic disc is seen as a pale yellow spot from which numerous retinal arteries (red blood vessels) emerge.  The person whose fundus is being observed was obviously gazing at the girl holding the telephone, whose own image is upside down on the retina.  The thick lines in sketch diagram on the right are retinal blood vessels; the thin lines are the axons of retinal ganglion cells, which bundle together to form the optic nerve).  The far right figure illustrates very clearly the paths of Golgi-stained retinal ganglion cell axons as they arc across the retina, avoiding the fovea, toward the optic nerve head.
    The Blind Spot
    The "blind spot" is a region on the back of the eye where there are no photoreceptors.  Hence, at this location in each eye, and at the spatial location "out there" where the blind spot happens to be pointed, there is no visual sensation.  King Henry IIX, it is said, was fond of "beheading' his dinner guests by locating the image of their heads in his blind spot (of course, beheadings were a hobby of sorts for Henry).
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    Her ses det mobile system i klinikken på Onkologisk Afdeling i Lund.
    Og det her er den håndholdte probe.
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    1. 1. BMI2 SS08 – Class 4 “OCT” Slide 1 Bio m e dicalIm ag ing 2 Class 4 – Optical Coherence Tomography (OCT) 02/19/08
    2. 2. BMI2 SS08 – Class 4 “OCT” Slide 2 O pticalbio psy – de finitio n • The in situ imaging of tissue microstructure with a resolution approaching that of histology, but without the need for tissue excision and processing • A ballistic optical imaging modality – Analogous to ultrasonography
    3. 3. BMI2 SS08 – Class 4 “OCT” Slide 3 O pticalco he re nce to m o g raphy • Three-dimensional imaging technique with ultrahigh spatial resolution, even in highly scattering media • Based on measurements of the reflected light from tissue discontinuities – e.g., the epidermis-dermis junction – i.e., principal contrast mechanism is the tissue scattering coefficient μs • To a lesser extent, polarization is a contrast mechanism • Based on interferometry – involves interference between the reflected light and the reference beam.
    4. 4. BMI2 SS08 – Class 4 “OCT” Slide 4 Co m po ne nts o f NIR Pro pag atio n in Tissue • Light propagation (Monte Carlo simulation) Incident light Ballistic component “Snake” component Diffuse reflectance Absorption Diffuse transmittance Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    5. 5. BMI2 SS08 – Class 4 “OCT” Slide 5 Co nce pt o f Inte rfe ro m e try ( ) ( ) 20 20 0 0 -1 -1 sample arm reference arm , electric field amplitudes , propagation constants [cm ] , arm lengths [cm] angular frequency [s ] time [s] R R S S i k l t R R i k l t S S R S R S R S E E e E E e S R E E k k l l t ω ω ω − − = = → → = = = = =
    6. 6. BMI2 SS08 – Class 4 “OCT” Slide 6 Co nce pt o f Inte rfe ro m e try E = ER + ES ( ) ( ) ( ) ( ) 2 2 2 0 0 0 0 2 cos 2 2 R S R S R S s s R R I t E E E E E E k l k l µ + = + + −
    7. 7. BMI2 SS08 – Class 4 “OCT” Slide 7 The O CT se tup Broadband source Detector Fiber-optic beamsplitter Tissue Scanning reference mirror Computer Amplifier Bandpass filter Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    8. 8. BMI2 SS08 – Class 4 “OCT” Slide 8 Ho w To Achie ve a De pth Pro file Tissue Reference mirror
    9. 9. BMI2 SS08 – Class 4 “OCT” Slide 9 So urce spe ctrum and e nve lo pe Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    10. 10. BMI2 SS08 – Class 4 “OCT” Slide 10 Sig nificance o f Sho rt Co he re nce Le ng th/Tim e 0 2 4 6 8 10 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 Time FieldStrength
    11. 11. BMI2 SS08 – Class 4 “OCT” Slide 11 1 mm 1 cm 10 cm Penetration depth (log) 1 µm 10 µm 100 µm 1 mm Resolution (log) OCT Confocal microscopy Ultrasound Standard clinical High frequency O CT vs. standard im ag ing Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    12. 12. BMI2 SS08 – Class 4 “OCT” Slide 12 Co nstructio n o f im ag e Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    13. 13. BMI2 SS08 – Class 4 “OCT” Slide 13 Cho o sing the lig ht so urce • Four primary considerations – wavelength, – bandwidth, – power (in a single-transverse-mode), – stability; • portability, ease-of-use, etc. Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    14. 14. BMI2 SS08 – Class 4 “OCT” Slide 14 Cho o se lig ht so urce – wave le ng th Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    15. 15. BMI2 SS08 – Class 4 “OCT” Slide 15 Cho o se lig ht so urce – wave le ng th Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    16. 16. BMI2 SS08 – Class 4 “OCT” Slide 16 Late ralre so lutio n (2/2) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    17. 17. BMI2 SS08 – Class 4 “OCT” Slide 17 Lig ht pro pag atio n in sam ple • The sample – need to describe light-tissue interaction taking temporal and spatial coherence properties into account; • can transport theory be used? • Light-tissue interaction may be modelled by using, for example, the extended Huygens-Fresnel principle • correlation between tissue, state of tissue (lesions) and optical properties? Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    18. 18. BMI2 SS08 – Class 4 “OCT” Slide 18 Sche m atic o f fitting alg o rithm D. Levitz et al., Opt. Express 12, 249-259 (2004) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    19. 19. BMI2 SS08 – Class 4 “OCT” Slide 19 AnalyticalO CT m o de l • Mean square heterodyne signal current – general expression – μs scattering coefficient – w spot size (H, absence, & S, presence of scattering) σb effective backscattering cross section – P optical power (R: reference; S: sample) α conversion from optical power to current Ψ heterodyne efficiency factor ( ) ( ) ( ) ( ) 2 2 222 22 2 2 2 0 4 1 1 1 Ψ s s s s z z z zR S b H SH S H e eP P w i z e e ww w w i z µ µ µ µα σ π − − − −    −  = + + −   +    ≡ Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    20. 20. BMI2 SS08 – Class 4 “OCT” Slide 20 O CT in no n-invasive diag no stics • Ophthalmology – diagnosing retinal diseases. • Dermatology – skin diseases, – early detection of skin cancers. • Cardio-vascular diseases – vulnerable plaque detection. • Endoscopy (fiber-optic devices) – gastrology, – … • Functional imaging – Doppler OCT, – spectroscopic OCT, – optical properties, – PS-OCT. • Guided surgery – delicate procedures – brain surgery, • knee surgery, • … Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    21. 21. BMI2 SS08 – Class 4 “OCT” Slide 21 Co m m e rcialsyste m s • Ophthalmology – Humphrey (division of Zeiss), US; • www.humphrey.com, – Ophthalmic Technologies Inc., Can. – … • Cardio-vascular diseases – Lightlab Imaging, US; • www.lightlabimaging.com. • Dermatology – Isis Optronics, D; • www.isis-optronics.de, – OCT Innovation, Den, – … Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    22. 22. BMI2 SS08 – Class 4 “OCT” Slide 22 Humphrey® Optical Coherence Tomography scanner at Herlev Hospital. Applicatio ns: O phthalm o lo g y Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    23. 23. BMI2 SS08 – Class 4 “OCT” Slide 23 Applicatio ns: O phthalm o lo g y Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    24. 24. BMI2 SS08 – Class 4 “OCT” Slide 24 Applicatio ns: O phthalm o lo g y Department of Ophthalmology, The New York Eye & Ear Infirmary, New York, NY 10003, USA Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    25. 25. BMI2 SS08 – Class 4 “OCT” Slide 25 No rm alEye Nominal width of scan: 2.8 mm 250 micronsHumphrey Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    26. 26. BMI2 SS08 – Class 4 “OCT” Slide 26 mµ mµ UHR-O CT ve rsus co m m e rcialO CT W. Drexler et al., “Ultrahigh-resolution ophthalmic optical coherence tomography”, Nature Medicine 7, 502-507 (2001) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    27. 27. BMI2 SS08 – Class 4 “OCT” Slide 27 Applicatio ns: O phthalm o lo g y • Assessment of treatment (choroid) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    28. 28. BMI2 SS08 – Class 4 “OCT” Slide 28 Clinically adapte d syste m s Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    29. 29. BMI2 SS08 – Class 4 “OCT” Slide 29 Applicatio ns: De rm ato lo g y • Dermatology – Medical Laser Center Lübeck GmbH, Lübeck, Germany. sub-epidermal blister (in vivo) at the forearm (3 by 1.5 mm2 ) sub-dermal blister (in vivo) at the forearm (2 by 1.5 mm2 ) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    30. 30. BMI2 SS08 – Class 4 “OCT” Slide 30 Applicatio ns: De rm ato lo g y Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    31. 31. BMI2 SS08 – Class 4 “OCT” Slide 31 Applicatio ns: De rm ato lo g y Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    32. 32. BMI2 SS08 – Class 4 “OCT” Slide 32 Basics o f dise ase From Essential Pathology, Emanual Rubin & John L. Farber, second edition, J. B. Lippincott Company, 1995, p. 252 Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    33. 33. BMI2 SS08 – Class 4 “OCT” Slide 33 Applicatio ns: Cardio lo g y • Imaging inside veins OCT Ultrasound Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    34. 34. BMI2 SS08 – Class 4 “OCT” Slide 34 O CT vs. histo lo g y D. Levitz, L. Thrane, M. H. Frosz, P. E. Andersen, C. B. Andersen, J. Valanciunaite, J. Swartling, S. Andersson-Engels, and P. R. Hansen, Opt. Express 12, 249-259 (2004). Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    35. 35. BMI2 SS08 – Class 4 “OCT” Slide 35 Extract scatte ring co e fficie nt Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    36. 36. BMI2 SS08 – Class 4 “OCT” Slide 36 Extract geff Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    37. 37. BMI2 SS08 – Class 4 “OCT” Slide 37 In-vitro clinicalstudy – sam ple s • Analysis of the scattering properties at 1300 nm of the human arterial intima – 4 normal, 4 lipid-rich, 3 fibrous, and 3 fibrocalcific aortic segments, – imaged with OCT in Phosphate Buffered Saline, – routine histological processing – intima identified in histology first, then in the corresponding OCT image. • Reference – D. Levitz, L. Thrane, M. H. Frosz, P. E. Andersen, C. B. Andersen, J. Valanciunaite, J. Swartling, S. Andersson-Engels, and P. R. Hansen, Optics Express 12, 249-259 (2004). Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    38. 38. BMI2 SS08 – Class 4 “OCT” Slide 38 Im ag e inte rpre tatio n • OCT images are divided into transverse blocks (~200-300 µm): – normal: 41 – lipid-rich: 40 – fibrous: 34 – fibrocalcific: 36 Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    39. 39. BMI2 SS08 – Class 4 “OCT” Slide 39 Applicatio n: re sults Normal arterial blocks 15 – 39 mm-1 : ∼95% Lipid-rich and fibrocalcific arterial blocks < 15 mm-1 : ∼60% Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    40. 40. BMI2 SS08 – Class 4 “OCT” Slide 40 Applicatio n: re sults (2) Normal arterial blocks 0.95 - 1: 87.8% Atherosclerotic arterial blocks < 0.95: > 50% Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark
    41. 41. BMI2 SS08 – Class 4 “OCT” Slide 41 O CT: sug g e ste d re ading • OCT – D. Huang et al., Science 254, 1178 (1991) – A. Fercher, J. Biomed. Optics 1, 157 (1996) – J. M. Schmitt, “Optical coherence tomography (OCT): A review”, IEEE J. Select. Topics Quantum Electron. 5, 1205-1215 (1999) – J. G. Fujimoto et al., “Optical coherence tomography: An emerging technology for biomedical imaging and optical biopsy”, Neoplasia 2, 9-25 (2000) – W. Drexler et al., “Ultrahigh-resolution ophthalmic optical coherence tomography”, Nature Medicine 7, 502-507 (2001) – W. Drexler, “Ultrahigh-resolution optical coherence tomography”, J. Biomed. Opt. 9, 47-74 (2004) Courtesy of Prof. P.E. Andersen, Risø, Technical University of Denmark

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