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OCT原理及在眼科的應用

   科林儀器股份有限公司
       金守仁
內容
• Tomography 斷層掃描儀
• OCT原理
• OCT發展歷史
• OCT在眼科的應用
Tomography 斷層掃描儀
OCT
• Optical Coherence Tomography
• Tomography的概念
現有Tomography的技術
現有Tomography的技術
現有Tomography的技術
• 限制:X-ray CT, MRI, PET為目前醫療診斷主力且發
 展相當成熟,但受限於解析度只達mm等級,因此希
 望能有更細微的影像技術來做檢測

• 更高解析度的技術產生
  • Fluorescence microscopy
  • Confocal Microscope
  • Ultrasound
  • OCT
現有Tomography的技術
• Fluorescence microscopy
  • 1. 以短波長光源激發螢光物質而發出較長波長的螢光
  • 2. 螢光光譜的變化可以檢測組織的變異
  • 3. 橫向解析度可達0.5 mm


• Confocal microscopy
  • 1. 共焦掃描顯微的原理在1957年由Marvin Minsky所提出,並於
       1969年由 P. Davidovits與M. D. Egger利用雷射而發展出第一
       套共焦掃描顯微鏡
  • 2. 具有空間光學切片的能力
  • 3. 橫向與縱向解析度分別可達0.5與 1um
  • 4. 可與螢光顯微術搭配
  • 5. 與超快雷射搭配做非線性光學的檢測
穿透力 v.s.解析度

      超音波影像系統      共焦掃瞄顯微術       光學同調斷層掃瞄技
                    (Confocal)      術(OCT)
穿透力    最佳(10cm)     最弱(1mm)        中(2-8mm)
解析度      最差           最佳              中
      (數十至數百個μm)      (1 μm)        (1-15um)
Biological measurement
                                                                 Electron Microscopy

             MRI                  Optical Microscopy

        Ultrasound                                        Confocal

         X-ray CT                 SLD           OCT              Femtosecond laser

10 mm         1 mm       100 µm          10 µm             1 µm          0.1 µm



                     Retina          Intra-retinal structure

                                             Individual Cell

                                                               Nucleus
Tomography技術參數比較
OCT原理
OCT 定義
• Optical coherence tomography (OCT) is an
 interferometric, non-invasive optical tomographic
 imaging technique offering millimeter penetration
 (approximately 2--3 mm in tissue) with sub-
 micrometre axial and lateral resolution.
    --From Wikipedia

• (Optical Coherence Tomography, OCT)是採用光
 學造影的方法,主要是利用低同調波長與寬頻光
 源之光學特性,結合反射式干涉技術之原理,來
 解析待測組織之縱向結構,其影像解析度甚至可
 達次微米等級
同調光與低同調光
• 同調性光源:具有近似於單一波長、單一相位的窄頻光譜,
        使光束中波前上每點的光相位相等,為同調
        光
• 低同調性光源:具有一波長範圍的光譜,也就是由不同波
         長的光所組合而成的寬頻光源
OCT 頻寬與波長的選擇
• 提高解析度的方式:
  • 增加頻寬
  • 在相同的頻寬下,波長較短的解析度較佳
• 波長的選擇上得配合待測物適用波長的範圍。
  • 以醫療上的應用為例,人體組織適用的光波長範圍在約700nm
    到1300nm米間,波長小於700nm的光易被蛋白質以及黑色素所
    吸收,長於1300nm的則容易被水吸收。
  • 因此若OCT 系統要應用於人體組織的量測時,就得選擇在這之
    間的波段,稱為生物窗(Biological window)。
• 1300nm的光較不易被散射,可以收集到較深的光訊號,
觀察到較深的區域(前房OCT)。
Optical Source
Michelson Interferometer
 • 組成
   • A monochromatic source
   • A detector
   • Two mirrors
   • One beam splitter
 • 簡單,常見
 • 用途
   • astronomical interferometers
   • gravitational wave detectors
Optical Coherence Tomography
  Basic Principle
                                 Reference Mirror




                                Beam Splitter
Light
Source




                               Detector
 To computer & display
                         OCT Signal
TIME DOMAIN OCT
                      Reference Mirror




 Superluminescent   Beam splitter
   Diode (SLD)




                      one signal return



   To computer
   and display      Photodetector
Time Domain OCT                                 Reference mirror
                                                                   moves back and forth
                                                         Lens
       Broadband
      Light Source
                                                                    Distance determines
            SLD                                                       depth in A scan
                         Interferometer

        Detector          Combines light
                          from reference
                           with reflected
Creates                  light from retina
 A-scan
                                  Scanning mirror
 1 pixel
                                    directs SLD
at a time
                                  beam on retina
Each A-
 scan
has 400                                                                     Process
 pixels           Data Acquisition                                       repeated many
                                                                         times to create
                  Processing                                                 B-scan
                                                    Final A-scan
SPECTRAL DOMAIN OCT
                      Reference Mirror




 Superluminescent   Beam splitter
   Diode (SLD)




                      Multiple signal return (up to 200)




 To computer
 and display           Spectrometer & CCD
Fourier Domain OCT
                                                                   Reference mirror
                                                                      stationary
   Broadband
  Light Source
    SLD
                   Interferometer

                    Combines light
                    from reference
    Grating          with reflected
  splits signal    light from retina
        by
  wavelength


Spectrometer
  analyzes
  signal by
 wavelength                                    FFT

                             Spectral     Fourier transform    Entire A-scan
                          interferogram   converts signal to    created at a
                                            typical A-scan      single time
OCT發展歷史
OCT的問世
    • 西元1991 年由 James G. Fujimoto首先發表出
    來
                              Professor James G. Fujimoto
                              Professor of Electrical Engineering
                              Massachusetts Institute of Technology
                              USA

                              Research:
                              1. Application of femtosecond laser technology
                              2. Studies of ultrafast phenomena
                              3. Laser medicine and surgery
                              4. Development of optical coherence tomography


   James G. Fujimoto, Science, 1991
   What is OCT: Diagnostic medical imaging techonology
   Why OCT: better diagnose and treat disease
   Main application areas: Retinal disease, heart disease and
    cancer
眼科OCT編年史- 華人之光
• 1991, David Huang的論文刊登於Science
• 1994, 第一個臨床原型機
           (Jay Wei - Ziess OCT Tech. Leader)
•   1996, OCT1 生產 (100 A掃描/秒, 16um 解析
          度)
                                                黃大衛(David Huang)
•   1999, OCT2 生產 (OCT1 技術)
•   2001, OCT3 生產 (400 A掃描/秒, 10um 解析
          度)
•   2004, FD-OCT技術 (>20,000 A掃描/秒)
•   2005, Visante前節OCT(30um分辨率)
•   2006, RTVue (第一個透過FDA的FD-OCT)
•   2007, RTVue前節傅立葉OCT(解析度5um)
           & 全球常態數據庫完成
                                                  魏傑(Jay Wei)
At first, OCT was slow




• First OCT image taken by Huang and Schuman
  over night in James Fujimoto’s laboratory, MIT
• Huang D et al. Science, 254:1178 (1991).
OptoVue
                                                RTVue 2006
 A generational leap
 26,000
                          Fourier domain
  Speed
(A-scans
    /sec)


                                             Time domain
     400     Zeiss
            OCT1/2
     100                     Zeiss Stratus
             1996
                                 2002
              16                   10                5
                     Resolution   (µm)


 • RTVue has 65x speed & 2x resolution of Stratus
Evolution of Commercial OCT
Time Domain OCT                  Fourier Domain OCT
• Sequential                     • Simultaneous
• 1 pixel at a time              • Entire A-scan at once
• 400 pixels per A-scan          • 2048 pixels per A scan
• 0.25 seconds per A scan        • .00000385 sec per A scan
• 512 A-scans in 1.28 sec        • 1024 A-scans in 0.04 sec
• Slower than eye movements      • Faster than eye movements


         Motion artifact                       Small blood vessels

                                              IS/OS


                                                Choroidal vessels
  512 A-scans in 1.28 sec
                                       1024 A-scans in 0.04 sec

                            Higher speed, higher definition and higher signal.
診斷設備的設計原則
• 安全性
• 非侵入性
• 非接觸性
• 準確性及再現性
• 使用方便性
現有眼科OCT設備
OCT在眼科的應用
眼睛的構造
眼底構造
臨床應用
• 視網膜
• 青光眼
• 角膜
• 白內障
視網膜常用掃描模式
• Cross line scan
  • 0.156 seconds
  • 2 x 1024(16 scans in
    each direction are
    then averaged)
• 結構的觀察
Retina
CME
高度近視
ERM
Epiretinal membrane
DM
Diabetic Maculopathy
Macular Hole
Polypoidal Choroidal Vasculopathy
AMD Advanced
視網膜常用掃描模式
• EMM5 scan
  • 1.30 seconds
  • 13 horizontal lines
     with 6mm scan length
     + 8 horizontal lines
     with 4mm scan length
  • 13 vertical lines
     with 6mm scan length
     + 8 vertical lines
     with 4mm scan length
• 訊息量化
Analyze Manu

• EMM5
• 數據提供
• 與正常值比較
Analyze Manu
• EMM5
Analyze Manu
• EMM5-Progression Overview
視網膜常用掃描模式
• 3D scan
   • 2.4 seconds
   • 141 B-scans equally
     spaced to cover
     7mm x 7mm volume
• 3D圖像觀察
Macular PVD
Auto scan
Auto play
RPE-Auto play
青光眼常用掃描模式
• ONH scan
  • 0.55 seconds
  • 12 radial line scans 3.4mm
    length & 13 concentric rings
     (1.3 - 4.9mm diameter)
      All centered on disc
• 視神經頭
LOCALIZED NERVE FIBER BUNDLE
DEFECTS
Glaucoma Samples




 ppRNFL TSNIT
 NFL Thickness Map
 ONH Analysis        Ganglion Cell Complex Analysis
Normal vs Glaucoma
                                     Enlarged Cup
              Cup
              Rim
                                     RNFL thinning
              RNFL




           Inner Retina
           Macula Map                 Ganglion
                                      cell loss in
                                      macula



  Normal                  Glaucoma
Optic Nerve Head / RNFL Trend Analysis


  Optic Disc and RNFL Thickness
  Maps in order first to last.
                                    TU


    TSNIT Deviation Maps
    Each visit has separate color
    and is plotted on the same
    graph with normal range
    shown. Color Legend is next
    to graph.

   RNFL parameter trend analysis
   shows graphically changes in
   RNFL parameters, Avg RNFL,
   Sup Avg, and Inf Avg.


RNFL & Optic Disc parameter table
for all exams. Color coded
according to database comparison.
Final column gives change from                 58
most recent visit to baseline.
64/M, POAG (OS)
20120927 台科大 oct原理及在眼科的應用 (1)
青光眼常用掃描模式
• GCC scan
  • 0.58 seconds
  • 1 horizontal line with 7mm scan
    length, followed by 15 vertical
    lines with 7mm scan length and
    0.5mm interval, centered 1mm
    temporal to fovea
• 黃斑部周邊視神經纖維
Ganglion Cell Complex: Thickness / Deviation
from Normal / Significance of Deviation
                 • GCC Thickness


                       •Deviation from
                               Normal




                 •Significance of
                 Deviation
GCC Glaucoma

GCC Thickness Map –
Large area of superior t
thinning OS, inferior thinning
OD




Deviation Map shows 50%
GCC loss in affected areas




Regions with damage are
highly significant



Parameters are outside
normal limits
                                                64
3D
Comprehensive
Presentation

-Precise Disc
margin
verification

-Visit-to-visit
registration

-Sum of C-scans

-User defined
depth of C-scan

-Auto animation
presentation
(Lower right or
full screen)
青光眼常用掃描模式
• 3D Disc scan
   • 2.2 seconds 101 frames
     equally spaced B-scans to
     cover a square volume
   • fixation at 20o nasal
• 視神經頭3D圖像觀察
3D Optic Disc Auto-Animation
3D Optic Disc Auto-Animation
角膜常用掃描模式
• Pachymetry scan
  • 0.32 seconds
  • 8 x 6mm x 2.0mm
    Radial Scans
• 角膜厚度
Pachymetry Maps
Cornea power
角膜常用掃描模式
• Angle scan
  • 0.04 seconds
  • 1 x 3mm x 2.3mm
• 隅角結構觀察與測量
Angle measurement
OCT is useful in the measurement of
tear meniscus in dry eye
Analyze Manu
• 3D Auto Play
  Demo
Q&A
20120927 台科大 oct原理及在眼科的應用 (1)

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20120927 台科大 oct原理及在眼科的應用 (1)

  • 1. OCT原理及在眼科的應用 科林儀器股份有限公司 金守仁
  • 2. 內容 • Tomography 斷層掃描儀 • OCT原理 • OCT發展歷史 • OCT在眼科的應用
  • 4. OCT • Optical Coherence Tomography • Tomography的概念
  • 7. 現有Tomography的技術 • 限制:X-ray CT, MRI, PET為目前醫療診斷主力且發 展相當成熟,但受限於解析度只達mm等級,因此希 望能有更細微的影像技術來做檢測 • 更高解析度的技術產生 • Fluorescence microscopy • Confocal Microscope • Ultrasound • OCT
  • 8. 現有Tomography的技術 • Fluorescence microscopy • 1. 以短波長光源激發螢光物質而發出較長波長的螢光 • 2. 螢光光譜的變化可以檢測組織的變異 • 3. 橫向解析度可達0.5 mm • Confocal microscopy • 1. 共焦掃描顯微的原理在1957年由Marvin Minsky所提出,並於 1969年由 P. Davidovits與M. D. Egger利用雷射而發展出第一 套共焦掃描顯微鏡 • 2. 具有空間光學切片的能力 • 3. 橫向與縱向解析度分別可達0.5與 1um • 4. 可與螢光顯微術搭配 • 5. 與超快雷射搭配做非線性光學的檢測
  • 9. 穿透力 v.s.解析度 超音波影像系統 共焦掃瞄顯微術 光學同調斷層掃瞄技 (Confocal) 術(OCT) 穿透力 最佳(10cm) 最弱(1mm) 中(2-8mm) 解析度 最差 最佳 中 (數十至數百個μm) (1 μm) (1-15um)
  • 10. Biological measurement Electron Microscopy MRI Optical Microscopy Ultrasound Confocal X-ray CT SLD OCT Femtosecond laser 10 mm 1 mm 100 µm 10 µm 1 µm 0.1 µm Retina Intra-retinal structure Individual Cell Nucleus
  • 13. OCT 定義 • Optical coherence tomography (OCT) is an interferometric, non-invasive optical tomographic imaging technique offering millimeter penetration (approximately 2--3 mm in tissue) with sub- micrometre axial and lateral resolution. --From Wikipedia • (Optical Coherence Tomography, OCT)是採用光 學造影的方法,主要是利用低同調波長與寬頻光 源之光學特性,結合反射式干涉技術之原理,來 解析待測組織之縱向結構,其影像解析度甚至可 達次微米等級
  • 14. 同調光與低同調光 • 同調性光源:具有近似於單一波長、單一相位的窄頻光譜, 使光束中波前上每點的光相位相等,為同調 光 • 低同調性光源:具有一波長範圍的光譜,也就是由不同波 長的光所組合而成的寬頻光源
  • 15. OCT 頻寬與波長的選擇 • 提高解析度的方式: • 增加頻寬 • 在相同的頻寬下,波長較短的解析度較佳 • 波長的選擇上得配合待測物適用波長的範圍。 • 以醫療上的應用為例,人體組織適用的光波長範圍在約700nm 到1300nm米間,波長小於700nm的光易被蛋白質以及黑色素所 吸收,長於1300nm的則容易被水吸收。 • 因此若OCT 系統要應用於人體組織的量測時,就得選擇在這之 間的波段,稱為生物窗(Biological window)。 • 1300nm的光較不易被散射,可以收集到較深的光訊號, 觀察到較深的區域(前房OCT)。
  • 17. Michelson Interferometer • 組成 • A monochromatic source • A detector • Two mirrors • One beam splitter • 簡單,常見 • 用途 • astronomical interferometers • gravitational wave detectors
  • 18. Optical Coherence Tomography Basic Principle Reference Mirror Beam Splitter Light Source Detector To computer & display OCT Signal
  • 19. TIME DOMAIN OCT Reference Mirror Superluminescent Beam splitter Diode (SLD) one signal return To computer and display Photodetector
  • 20. Time Domain OCT Reference mirror moves back and forth Lens Broadband Light Source Distance determines SLD depth in A scan Interferometer Detector Combines light from reference with reflected Creates light from retina A-scan Scanning mirror 1 pixel directs SLD at a time beam on retina Each A- scan has 400 Process pixels Data Acquisition repeated many times to create Processing B-scan Final A-scan
  • 21. SPECTRAL DOMAIN OCT Reference Mirror Superluminescent Beam splitter Diode (SLD) Multiple signal return (up to 200) To computer and display Spectrometer & CCD
  • 22. Fourier Domain OCT Reference mirror stationary Broadband Light Source SLD Interferometer Combines light from reference Grating with reflected splits signal light from retina by wavelength Spectrometer analyzes signal by wavelength FFT Spectral Fourier transform Entire A-scan interferogram converts signal to created at a typical A-scan single time
  • 24. OCT的問世 • 西元1991 年由 James G. Fujimoto首先發表出 來 Professor James G. Fujimoto Professor of Electrical Engineering Massachusetts Institute of Technology USA Research: 1. Application of femtosecond laser technology 2. Studies of ultrafast phenomena 3. Laser medicine and surgery 4. Development of optical coherence tomography  James G. Fujimoto, Science, 1991  What is OCT: Diagnostic medical imaging techonology  Why OCT: better diagnose and treat disease  Main application areas: Retinal disease, heart disease and cancer
  • 25. 眼科OCT編年史- 華人之光 • 1991, David Huang的論文刊登於Science • 1994, 第一個臨床原型機 (Jay Wei - Ziess OCT Tech. Leader) • 1996, OCT1 生產 (100 A掃描/秒, 16um 解析 度) 黃大衛(David Huang) • 1999, OCT2 生產 (OCT1 技術) • 2001, OCT3 生產 (400 A掃描/秒, 10um 解析 度) • 2004, FD-OCT技術 (>20,000 A掃描/秒) • 2005, Visante前節OCT(30um分辨率) • 2006, RTVue (第一個透過FDA的FD-OCT) • 2007, RTVue前節傅立葉OCT(解析度5um) & 全球常態數據庫完成 魏傑(Jay Wei)
  • 26. At first, OCT was slow • First OCT image taken by Huang and Schuman over night in James Fujimoto’s laboratory, MIT • Huang D et al. Science, 254:1178 (1991).
  • 27. OptoVue RTVue 2006 A generational leap 26,000 Fourier domain Speed (A-scans /sec) Time domain 400 Zeiss OCT1/2 100 Zeiss Stratus 1996 2002 16 10 5 Resolution (µm) • RTVue has 65x speed & 2x resolution of Stratus
  • 29. Time Domain OCT Fourier Domain OCT • Sequential • Simultaneous • 1 pixel at a time • Entire A-scan at once • 400 pixels per A-scan • 2048 pixels per A scan • 0.25 seconds per A scan • .00000385 sec per A scan • 512 A-scans in 1.28 sec • 1024 A-scans in 0.04 sec • Slower than eye movements • Faster than eye movements Motion artifact Small blood vessels IS/OS Choroidal vessels 512 A-scans in 1.28 sec 1024 A-scans in 0.04 sec Higher speed, higher definition and higher signal.
  • 30. 診斷設備的設計原則 • 安全性 • 非侵入性 • 非接觸性 • 準確性及再現性 • 使用方便性
  • 36. 視網膜常用掃描模式 • Cross line scan • 0.156 seconds • 2 x 1024(16 scans in each direction are then averaged) • 結構的觀察
  • 38. CME
  • 45. 視網膜常用掃描模式 • EMM5 scan • 1.30 seconds • 13 horizontal lines with 6mm scan length + 8 horizontal lines with 4mm scan length • 13 vertical lines with 6mm scan length + 8 vertical lines with 4mm scan length • 訊息量化
  • 46. Analyze Manu • EMM5 • 數據提供 • 與正常值比較
  • 49. 視網膜常用掃描模式 • 3D scan • 2.4 seconds • 141 B-scans equally spaced to cover 7mm x 7mm volume • 3D圖像觀察
  • 54. 青光眼常用掃描模式 • ONH scan • 0.55 seconds • 12 radial line scans 3.4mm length & 13 concentric rings (1.3 - 4.9mm diameter) All centered on disc • 視神經頭
  • 55. LOCALIZED NERVE FIBER BUNDLE DEFECTS
  • 56. Glaucoma Samples ppRNFL TSNIT NFL Thickness Map ONH Analysis Ganglion Cell Complex Analysis
  • 57. Normal vs Glaucoma Enlarged Cup Cup Rim RNFL thinning RNFL Inner Retina Macula Map Ganglion cell loss in macula Normal Glaucoma
  • 58. Optic Nerve Head / RNFL Trend Analysis Optic Disc and RNFL Thickness Maps in order first to last. TU TSNIT Deviation Maps Each visit has separate color and is plotted on the same graph with normal range shown. Color Legend is next to graph. RNFL parameter trend analysis shows graphically changes in RNFL parameters, Avg RNFL, Sup Avg, and Inf Avg. RNFL & Optic Disc parameter table for all exams. Color coded according to database comparison. Final column gives change from 58 most recent visit to baseline.
  • 61. 青光眼常用掃描模式 • GCC scan • 0.58 seconds • 1 horizontal line with 7mm scan length, followed by 15 vertical lines with 7mm scan length and 0.5mm interval, centered 1mm temporal to fovea • 黃斑部周邊視神經纖維
  • 62. Ganglion Cell Complex: Thickness / Deviation from Normal / Significance of Deviation • GCC Thickness •Deviation from Normal •Significance of Deviation
  • 63. GCC Glaucoma GCC Thickness Map – Large area of superior t thinning OS, inferior thinning OD Deviation Map shows 50% GCC loss in affected areas Regions with damage are highly significant Parameters are outside normal limits 64
  • 64. 3D Comprehensive Presentation -Precise Disc margin verification -Visit-to-visit registration -Sum of C-scans -User defined depth of C-scan -Auto animation presentation (Lower right or full screen)
  • 65. 青光眼常用掃描模式 • 3D Disc scan • 2.2 seconds 101 frames equally spaced B-scans to cover a square volume • fixation at 20o nasal • 視神經頭3D圖像觀察
  • 66. 3D Optic Disc Auto-Animation
  • 67. 3D Optic Disc Auto-Animation
  • 68. 角膜常用掃描模式 • Pachymetry scan • 0.32 seconds • 8 x 6mm x 2.0mm Radial Scans • 角膜厚度
  • 71. 角膜常用掃描模式 • Angle scan • 0.04 seconds • 1 x 3mm x 2.3mm • 隅角結構觀察與測量
  • 73. OCT is useful in the measurement of tear meniscus in dry eye
  • 74. Analyze Manu • 3D Auto Play Demo
  • 75. Q&A