Dept Electrical Engineering Chang Gung University, Taiwan

Transcription

1 Biomedical Optics Hsiao-Lung Chan, Ph.D. Dept Electrical Engineering Chang Gung University, Taiwan

2 Outline Essential optical principle Light propagation in biological tissue Blood oxygen concentration Laser Doppler velocimetry Fluorescence microscope Functional near infrared imaging Optical coherence tomography Lecture edited by 詹曉龍, 長庚大學電機系, Biomedical Optic 2

3 Electromagnetic (EM) waves EM fields have longitudinal as well as transverse components. The magnetic field oscillates in orthogonal to the electrical field and in phase E x H y E0 exp[ j( t kz)] H 0 exp[ j( t kz)] frequency wavelength velocity f / 2 2 / k c f / k index of refraction of the medium n c / c 0 Biomedical Optic 3

4 Electromagnetic spectrum Biomedical Optic 4

5 Polarization Electromagnetic waves, such as light, and gravitational waves exhibit polarization; acoustic waves (sound waves) in a gas or liquid do not have polarization because the direction of vibration and direction of propagation are the same. Plane pressure pulse wave Propagation of an omnidirectional pulse wave Biomedical Optic 5

6 Light polarization When light travels in free space, in most cases it propagates as a transverse wave the polarization is perpendicular to the wave's direction of travel. Transverse plane wave Propagation of a transverse se spherical wave Biomedical Optic 6

7 Light polarization (cont.) The simplest manifestation of polarization is to visualize a plane wave, which is a good approximation of most light waves. The electric field vector of a plane wave may be divided into two perpendicular components labeled x and y For a simple harmonic wave, the two components have exactly the same frequency E E x y e e x y cos(t kz) cos( t kz ) Biomedical Optic 7

8 Light polarization (cont.) The electric field may be oriented in a single direction (linear polarization), or it may rotate as the wave travels (circular or elliptical polarization). linear circular elliptical Biomedical Optic 8

9 Light interaction with nonparticipating media Reflection and refraction Snell s law n i sin i n t sin t n i n t Biomedical Optic 9

10 Light interaction with participating media Scattering Scattering of light depends on the wavelength of the light being scattered. Since visible light has wavelength on the order of a micron, objects much smaller than this cannot be seen, even with the aid of a microscope Biomedical Optic 10

11 Scattering Biomedical Optic 11

12 Light interaction with participating media Absorption Beer-Lambert s law I( x x) I( x) ai( x) x di( x) ai( x) dx ax I x) I ( x) e ( 0 Biomedical Optic 12

13 Oxygen saturation (SaO 2, SpO 2 ) measurement (1) SaO 2 is the relative amount of oxygen carried by the hemoglobin (2) The color of Hb is blue, HbO 2 is bright red color (3) Two specific wavelengths : λ 1 : a red wavelength (eg. 660 nm) λ 2 : a near infrared wavelength (eg. 805 nm) Biomedical Optic 13

14 Beer-Lambert s law I t I 10 0 Cd where I t and I 0, transmitted and incident light power; α, C, d, extinction coefficient, concentration of the sample, and light path length Define optical density, OD OD log I t I o Cd SaO 2 C C HbO HbO 2 2 C Hb Biomedical Optic 14

15 Light absorption signal produce AC output produce DC output Biomedical Optic 15

16 Light absorption signal Biomedical Optic 16

17 Light absorption in different blood oxygen concentrations Biomedical Optic 17

18 SaO 2 SaO 2 ) ( ) ( d d C C IR Hb Hb IR HbO HbO IR I I ) ( ) ( 2 d d C C Hb HbO ) ( ) ( d d C C R Hb R HbO R I I I Hb Hb IR HbO HbO IR Hb Hb R HbO HbO R DC R R C C C C I I I IR R ) ( log Hb IR HbO IR DC IR IR C C I I 2 ) ( log R ) ( ) ( HbO R Hb R HbO IR Hb IR Hb R Hb IR Hb HbO HbO R IR R C C C SaO ) ( ) ( 2 R R IR IR IR Biomedical Optic 18

19 SaO 2 applications Biomedical Optic 19

20 Laser Doppler velocimetry Partially quantify blood flow in human tissues such as capillary flow Biomedical Optic 20

21 Laser Doppler velocimetry (cont.) Biomedical Optic 21

22 Laser Doppler velocimetry (cont.) Doppler effect Example ν=10 14 Hz v=1 mm/sec c/n=210 8 m/sec Δν=500 Hz Using laser as light source v cos c / n v : relative velocity : light frequency n: refraction coefficient Get beat through interference between lights Biomedical Optic 22

23 Laser Doppler velocimetry (cont.) Biomedical Optic 23

24 Fiber optics and waveguides in medicine An optic fiber with a cylindrical core with index of refraction (n 1 ) and cladding index (n 2 ) where n 2 <n 1 Biomedical Optic 24

25 Fiber optics Snell s law n 2 sin2 n1 sin 1 Refraction of rays that escape from wall of fiber Low refractory index High refractory index n 1 =1.62 for a glass Internal reflection within a fiber 3 : accepted angle for internal reflection in fiber when n 0 1 sinic n2 sin 90 n 2 Biomedical Optic 25

26 Optical fiber type Biomedical Optic 26

27 Displacement optode A thin reflectance diaphragm for pressure or temperature measurement Biomedical Optic 27

28 Fluorescence The emission of light by a substance that has absorbed light of a different wavelength. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation. Photon energy E = h h = Planck's constant = frequency of light Biomedical Optic 28

29 Fluorescence microscope The excitatory t light is transmitted through the specimen. The fluorescence in the specimen gives rise to emitted light. Only reflected excitatory light reaches the objective together with the emitted light. The emission filter can filter out the remaining excitation light.

30 Fluorescent imaging for dividing human cells DNA is stained blue, a protein called INCENP is green, and the microtubules are red. Each fluorophore is imaged separately using a different combination of excitation and emission filters The images are captured sequentially using a CCD camera, then overlaid to give a complete image. Biomedical Optic 30

31 Confocal microscope increase optical resolution and contrast of a micrograph by using point illumination and a spatial pinhole to eliminate out-of-focus of focus light in specimens Biomedical Optic 31

32 Near-infrared spectroscopy (NIRS) Uses the near-infrared region (from 800 nm to 2500 nm) Applications in pharmaceutical and medical diagnostics (including blood sugar and oximetry). OxiplexTS, ISS Inc, USA Biomedical Optic 32

33 Near-infrared sensing methods Biomedical Optic 33

34 Application in peripheral vascular disease (PVD) PVD is a narrowing of the vessels carrying blood to the muscles in the legs and arms. Most patients t report experiences of pain in the extremities due to inadequate blood flow and oxygen delivery to the exercising muscle. OxiplexTS, ISS Inc, USA Biomedical Optic 34

35 Application in brain oxygenation With 20% of oxygen consumption occurring in the human brain, any deficiency in oxygen supply ppy may result in injury OxiplexTS, ISS Inc, USA Biomedical Optic 35

36 Functional NIR sensing An sensor with central emitter and eight surrounding, detachable detectors Biomedical Optic 36

37 Functional NIR optical imaging NIR images of the prefrontal cortex obtained with the continuous wave device for problem solving showing blood volume and oxygenation changes (scale is μm). Biomedical Optic 37

38 Functional NIR optical imaging Hemodynamic changes due to emotional stress in the prefrontal cortex. Biomedical Optic 38

39 Optical coherence tomography (OCT) 光同調斷層影像 Captures micrometer-resolution, three-dimensional images from within optical scattering media (e.g., biological tissue) OCT is an interferometric technique. OCT of a fingertip Biomedical Optic 39

40 OCT principle Interferometry super-luminescent diode (SLD) convex lens (L1) beamsplitter (BS) camera objective (CO) CMOS-DSP camera (CAM) reference (REF) and sample (SMP). Biomedical Optic 40

41 OCT principle (cont.) Display image of light scattering in tissue Biomedical Optic 41

42 Michelson interferometer Waves in phase undergo constructive interference laser Superposition of waves laser Traveling different distances Out of phase undergo destructive interference Biomedical Optic 42

43 Time-domain OCT The pathlength of the reference arm is translated longitudinally in time. The interference (series of dark and bright fringes) is achieved when path difference lies within the coherence length of the light source (axial resolution). This interference is called cross-correlation where the peak of the envelope corresponds to pathlength matching Biomedical Optic 43

44 Frequency-domain OCT The broadband interference is acquired with spectrally separated detectors either by encoding the optical frequency in time with a spectrally scanning source or with a dispersive detector, like a grating and a linear detector array. Spectral bandwidth sets the axial resolution Biomedical Optic 44

45 Frequency-domain OCT Due to the Fourier relation between auto-correlation and spectral power density, the depth scan can be immediately calculated from the acquired spectra, without movement of the reference arm. This feature improves imaging speed dramatically. Biomedical Optic 45

46 OCT application Biomedical Optic 46

47 OCT in Oral cancer diagnosis Normal mucosa Biopsy: Pros: Golden standard Cons: Sampling errors Invasive method Complicated process Time consuming method OCT Optical biopsy Pros: Non invasive Real time imaging Multi dimensional imaging Cons: Poorer resolution Provided by Prof. MT Tsai (J Biomed Opt 2008, 2009) Cancerous mucosa

48 Reference John Enderle, Susan Blanchard, Joseph Bronzino, Introduction to Biomedical Engineering, Academic Press, 生物醫學工程導論, 滄海書局,2008. Wikipedia, the free encyclopedia Biomedical Optic 48