生醫影踽導論 Introduction to Biomedical Imagingmlli/courses/CourseIntro_EE... · 2012. 3....

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生醫影像導論生醫影像導論生醫影像導論生醫影像導論Introduction to Biomedical Imaging

Meng-Lin Li ( 李夢麟李夢麟李夢麟李夢麟), Ph. D.mlli@ee.nthu.edu.tw

Department of Electrical EngineeringNational Tsing Hua University, Taiwan

http://www.ee.nthu.edu.tw/~mlli – 2

生醫影像導論生醫影像導論生醫影像導論生醫影像導論Introduction to Biomedical Imaging

Meng-Lin Li ( 李夢麟李夢麟李夢麟李夢麟), Ph. D.mlli@ee.nthu.edu.tw

Department of Electrical EngineeringNational Tsing Hua University, Taiwan

http://www.ee.nthu.edu.tw/~mlli – 3

Imaging, What? Why?

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Imaging – “ Making ” Pictures

� Beauty/Cute is skin deep (Devil inside @_@)

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Why Biomedical Imaging?

� To less-invasively or non-invasively see inside of human body, animals, which is in-visible to the naked eyes

� 講簡單一點講簡單一點講簡單一點講簡單一點，，，，就是在做特別一點的就是在做特別一點的就是在做特別一點的就是在做特別一點的照相機照相機照相機照相機

http://www.ee.nthu.edu.tw/~mlli – 6

How to Do Imaging?

� Matthew O'Donnell: " heat , sound , light , electric field , magnetic field --those are your senses." These are the ways that you can see inside of something. Any time that you can monitor change--the way that heat, sound, light, electric field, magnetic field intera cts with the body--you can take that information backwards then to figure out what is going on local ly.

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For Example

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How to Do Imaging?

� Matthew O'Donnell: " heat , sound , light , electric field , magnetic field --those are your senses." These are the ways that you can see inside of something. Any time that you can monitor change--the way that heat, sound, light, electric field, magnetic field intera cts with the body--you can take that information backwards then to figure out what is going on local ly.

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Ultrasound Imaging ( 超音波造影超音波造影超音波造影超音波造影)

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不知道，你們會不會稍稍感動一下 (Demo)

(這是我兒子…)

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High Resolution? ( 造影對象: 小動物):Cardiac Imaging of Mice

From NTU EE

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Photoacoustic Imaging ( 光聲造影光聲造影光聲造影光聲造影)

(1) Laser pulse (<ANSI limit:e.g., 20 mJ/cm 2)

(4) Ultrasonic detection

(Wideband)

(3) Ultrasonic emission( KPa to MPa)振動產生超音波

(2) Local heating(~ mK)

造成熱脹冷縮

熱脹冷縮產生振動

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可以拿來看燒傷程度

30-second burnin porcine skin

B-scan

mmBurn depth: ~1.75 mm

Depth

Depth: 0 mm Depth: 0.60 mm Depth: 1.08 mm

C-scans

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回歸正題回歸正題回歸正題回歸正題

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Goals

� To foster an understanding/concepts of the differen t biomedical imaging signals, their relative advantag es and disadvantages, and a familiarity with first principles.

� To provide hands-on experience with biomedical imaging data

� Most important of all, hopefully, to arise your int erests in biomedical imaging and to provide basic knowledg e and skills for further study

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Course Description

� This is an introductory course of biomedical imagin g with emphasis on the “signals and systems” and “physics” aspects.

� Basic principles, instrumentation, image characteristics, clinical applications, recent progress, and applications in molecular imaging of the state- of-the-art imaging modalities will be discussed.

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生醫造影生醫造影生醫造影生醫造影 佔佔佔佔 生醫工程拼圖的哪幾塊生醫工程拼圖的哪幾塊生醫工程拼圖的哪幾塊生醫工程拼圖的哪幾塊????

生醫電子生醫電子生醫電子生醫電子((((Bio-electronics ))))

生醫訊號處理及造影生醫訊號處理及造影生醫訊號處理及造影生醫訊號處理及造影((((Bio-signal processing ))))

生醫影像分析生醫影像分析生醫影像分析生醫影像分析((((Bio-image analysis ))))

生醫光電生醫光電生醫光電生醫光電((((Bio-photonics ))))

電機工程電機工程電機工程電機工程EE

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Covered Topics

� Introduction� Basic Imaging Principles

� Signals and Systems, and General Imaging Characteristics

� Ultrasound Imaging� Magnetic Resonance Imaging� X-Ray Imaging� X-Ray Computed Tomography� Nuclear Medicine Imaging (Simplified)

� Positron Emission Tomography (PET)� Single Photon Emission Computed Tomography

(SPECT)� Optical Imaging � Site Visit: NTHU Brain Research Center (For sure, D ate:

TBD), Mackay Memorial Hospital(TBD)

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General Imaging System Blocks ( 這是我師祖的手稿這是我師祖的手稿這是我師祖的手稿這是我師祖的手稿)

感想感想感想感想: 師祖的字師祖的字師祖的字師祖的字跟跟跟跟我的一樣醜我的一樣醜我的一樣醜我的一樣醜

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Course Information

� Time: T6T7T8� Place: 台達台達台達台達211� Prerequisits: Signals and Systems (at least knowledge of

Fourier transform and sampling), or Consent of Instructor

� Textbook:� P. Suetens, “Fundamentals of Medical Imaging,” Cambri dge

University Press, 2002. (in NTHU library, you can loc ate the newest version)

� Class notes and related material (i.e., PowerCam files) will be announced on NTHU iLMS elearning system (http://lms.nthu.edu.tw )

� Office hour: by appointment� TAs: TBD� Contact: EECS R524A (ext. 62179 )

Email: mlli@ee.nthu.edu.tw

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Grading

� 50% Computer (Matlab) and written homework and report (~ 4 HWs, 1-2 page report)

� 25% Midterm� 25% Final� Note that these weights are approximate; we reserve

the right to change them later

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Delay Penalty

� To encourage you not to give up and to solve your homework on your own, delay is allowed but with som e penalty

� 10% deduction for up to two-day delay (i.e., *0.9)� 20% deduction for up to four-day delay (i.e., *0.8)� 30% deduction for up to six-day delay (i.e., *0.7)� 40% deduction at most (i.e., *0.6) before the gradi ng is

announced.

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On-line Matlab Tutorial

� http://www.ieee-uffc.org/ultrasonics/software.asp?n ame=matlab� http://www.math.ufl.edu/help/matlab-tutorial/index. html#SEC6� MIT open courseware� Manual of Matlab� 資工系張智星老師網頁資工系張智星老師網頁資工系張智星老師網頁資工系張智星老師網頁

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Zero tolerance to academic plagiarism and dishonest y!

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上完課上完課上完課上完課你應該要知道你應該要知道你應該要知道你應該要知道…

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在正式開始前給你們一點點感覺在正式開始前給你們一點點感覺在正式開始前給你們一點點感覺在正式開始前給你們一點點感覺，，，，影像是如何掃瞄影像是如何掃瞄影像是如何掃瞄影像是如何掃瞄(Scan)出來的出來的出來的出來的?掃瞄掃瞄掃瞄掃瞄(Scanning) == Sampling

Time

Ultr

ason

icsi

gnal Surface

Strong scatterer

Strong scatterere.g., certain cells

Time-resolved signal(depth = time x speed of sound/2 )

Depth

Modified from Prof. L. V. Wang’s slide

Raw data/ RF dataTissue

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我們最在乎影像系統的哪些特性我們最在乎影像系統的哪些特性我們最在乎影像系統的哪些特性我們最在乎影像系統的哪些特性?

� 1. Safety� 2. Contrast source� 3. Resolution

� Spatial resolution� Contrast resolution� Temporal resolution

� 4. Penetration� 沒有生物醫學的生醫工程是沒用的沒有生物醫學的生醫工程是沒用的沒有生物醫學的生醫工程是沒用的沒有生物醫學的生醫工程是沒用的!!!

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No Contrast, No Diagnosis

lateral [cm]

axia

l [cm

]

original

-0.5 0 0.5

1

1.5

2

2.5

3

3.5

4

4.5

lateral [cm]

Correlation based

-0.5 0 0.5lateral [cm]

GCF

-0.5 0 0.5

� Ultrasonic imaging of cyst in breast (Age: 66)

CNR 3.07 2.98 4.33

From NTUEE

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典型的核醫影像典型的核醫影像典型的核醫影像典型的核醫影像 ((((什麼器官什麼器官什麼器官什麼器官 ?)?)?)?)

(Myocardial perfusion imaging)

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核子醫學影像核子醫學影像核子醫學影像核子醫學影像

� Nuclear medicine ?� Unclear medicine ?� 沒那麼嚴重啦沒那麼嚴重啦沒那麼嚴重啦沒那麼嚴重啦 ! 「「「「清不清晰清不清晰清不清晰清不清晰」」」」不是醫學影像最重要的考量不是醫學影像最重要的考量不是醫學影像最重要的考量不是醫學影像最重要的考量

� 核醫的重要目的核醫的重要目的核醫的重要目的核醫的重要目的:� 功能性檢測功能性檢測功能性檢測功能性檢測，，，，不是只看器官形態不是只看器官形態不是只看器官形態不是只看器官形態

� 能看到何種能看到何種能看到何種能看到何種「「「「功能功能功能功能」，」，」，」，並非完全取決於影像清晰程度並非完全取決於影像清晰程度並非完全取決於影像清晰程度並非完全取決於影像清晰程度

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Spatial Resolution (Nomenclature)

x

z

y

Good focusing Poor focusing

x: Lateral, azimuthal, scany: Elevational, non-scanz: Axial, range, depth

Axial, Lateral, Elevational (Slice thickness) Resolu tion

Each pixel represents a “voxel”

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Concept of Sample Volume?Relationship with Point Spread Function

(i.e., Impulse Response)?

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為什麼為什麼為什麼為什麼Beauty Is Skin Deep? Intravital Microscopy 顯微術顯微術顯微術顯微術

J. Biomed. Optics 10, 044004 (2005)

Hyperspectral imaging

RFP GFP

Truman Show == True Man Show?

Trans-illumination

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有些醫學影像會欺騙醫生的眼睛有些醫學影像會欺騙醫生的眼睛有些醫學影像會欺騙醫生的眼睛有些醫學影像會欺騙醫生的眼睛

1.5 cm

Open skull photo

Glioma

Macro-fluorescence

Micro-fluorescence sliceThionine stained slice

min

max

(~2 mm from scalp)

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有些醫學影像有有些醫學影像有有些醫學影像有有些醫學影像有””””種族歧視種族歧視種族歧視種族歧視””””

� Adaptive array beamforming for technically difficult bodies (e.g., overweight people and breast imaging)

(a) (b) (c)

(e) (f) (g)

(正常人正常人正常人正常人) (有點胖有點胖有點胖有點胖) (蠻胖的蠻胖的蠻胖的蠻胖的)

Orig

inal

Sid

elob

eR

educ

ed

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我的我的我的我的MRI機器出了什麼問題機器出了什麼問題機器出了什麼問題機器出了什麼問題? Inaccurate FOV Setting

別人掃瞄這樣 而我掃瞄成這樣？!

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Electro magnetic Spectrum

PET, SPECT(1 – 2 mm)

CT (50-200 µµµµm)X-ray

MRI(25 – 100 µµµµm)

From “Fundamentals of Medical Imaging,” Cambridge University Press, 2002.

Optical Imaging(? µµµµm or mm)

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Classification

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Ionizing Radiation vs. Non-ionizing Radiation

� Ionizing radiation ( 游離輻射游離輻射游離輻射游離輻射)� X-Ray Imaging� X-Ray Computed Tomography� Positron Emission Tomography

(PET)� Single Photon Emission

Computed Tomography (SPECT)

� Non-ionizing radiation� Ultrasound Imaging� Magnetic Resonance

Imaging� Optical Imaging

Ionization:The conversion of neutral atoms or molecules into ions by the removal of electrons(>13.6 eV)

Risk free?Less invasive

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Morphological , Functional, Molecular Imaging

� X-Ray Imaging – Morphological � X-Ray Computed Tomography – Morphological � Nuclear Medicine Imaging

� Positron Emission Tomography (PET) –Functional + Molecular

� Single Photon Emission Computed Tomography (SPECT) – Functional + Molecular

� Ultrasound Imaging – Morphological + Functional + Molecular

� Magnetic Resonance Imaging – Morphological + Functional + Molecular

� Optical Imaging – Morphological + Functional + Molecular

http://www.ee.nthu.edu.tw/~mlli – 41

所以所以所以所以…不用上課也可以知道這麼多種生醫造影不用上課也可以知道這麼多種生醫造影不用上課也可以知道這麼多種生醫造影不用上課也可以知道這麼多種生醫造影

� 絕對在不同疾病上各有千秋絕對在不同疾病上各有千秋絕對在不同疾病上各有千秋絕對在不同疾病上各有千秋

� 雖有消長雖有消長雖有消長雖有消長，，，，但仍難互相取代但仍難互相取代但仍難互相取代但仍難互相取代

� $ : PET > MRI > CT > X Ray > US� 第一線診斷第一線診斷第一線診斷第一線診斷 ? 追加檢查追加檢查追加檢查追加檢查 ?

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當紅炸子雞當紅炸子雞當紅炸子雞當紅炸子雞 Molecular Imaging

� The ultimate goal is to look at molecular processes . � We are moving toward imaging not necessarily one

molecular event, but a collection of a single type of molecular event, which signifies that a particular process is turned off.

� OK. I know the molecular process; then so what? Clinical value? (my own opinions)

http://www.ee.nthu.edu.tw/~mlli – 43

Molecular Imaging Modalities(see MIPS: http://mips.stanford.edu/CMIR: http://cmir.mgh.harvard.edu/ )

Rat shoulder with tumors transaxial

image (Dept. of Neurology,

Memorial Sloan-Kettering cancer

center)

Rat brain with U87

tumor(Dept. of

Neurosurgery &. Cardiovascular division, U. of

Virginia school of medicine)

Normal V.S.transgenic &.

knockout mice

transverse images

(Oak Ridge national lab.)

Neuronal death in rat

brain(Hoechst Marion

Rousel, Core research, FRG)

Fluorescence rat head with

U87 brain tumor

(Optical imaging lab, Biomedical

Engineering Dept., TAMU)

Mouse brain with U87

tumor(Optical imaging lab,

Biomedical Engineering Dept.,

TAMU)

Positron Emission

TomographyUltrasound

Micro-Computed

Tomography

Magnetic Resonance

Imaging

Optical Imaging

Photo-Acoustic

Tomography

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Imaging of Gene Expression

T. F. Massoud and S. S. Gambhir, Genes & Development , 17, 2003

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History (If Interested)

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References

� “Fundamentals of Medical Imaging,” P. Suetens, Cambridge University Press, 2002.

� “Medical Imaging,” A. Macovski, Prentice Hall, 1983. � “Introduction to Biomedical Imaging,” A. Webb, IEEE

Press, 2003. � “Principles of Medical Imaging,” K. K. Shung, M. B.

Smith, and B. Tsui, Academic Press, 1992.� “Foundation of Medical Imaging,” Z. H. Cho, J. P.

Jones, and M. Singh, John Wiley &Sons, Inc., 1993.� http://www.cis.rit.edu/htbooks/mri/index.html (The

Basics of MRI), J. P. Hornak.� Course material of “Introduction to Biomedical

Engineering” from Prof. Hsiao-Wen Chung (NTUEE)

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Are You Ready?

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正式開始前正式開始前正式開始前正式開始前，，，，先來做個簡單的測驗先來做個簡單的測驗先來做個簡單的測驗先來做個簡單的測驗

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你知不知道你知不知道你知不知道你知不知道?

� 1. 你了解Sinusoidal Signal，其Phase與Time Shift的關係嗎?影像上Sinusoidal Pattern，其Phase與Space Shift的關係嗎?

� 2. 為什麼我們這麼愛Delta function/Dirac impulse?� 3. 何謂Spatial Frequency?� 4. 大部分影像系統都是Low Pass Filter� 5. What we want from so many different kinds of Fourier transform?� 6. Phase對造影/影像的重要性� 7. Fourier transform pair和Sampling theory/Nyquist criterion� 8. 有聽過Hilbert transform嗎? FFT?

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How Many Fourier Transforms You Have Learned?

� Continuous-time Fourier transform (CTFT)� Continuous-time Fourier series (CTFS)� Fourier series (FS)� Discrete-time Fourier transform (DTFT)� Discrete Fourier transform (DFT)� Discrete-time Fourier series (DTFS)� Fast Fourier transform (FFT)

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對做對做對做對做Imaging而言而言而言而言，，，，答案是答案是答案是答案是… Just One

� Fundamental: Continuous-Time Fourier Transform (Real World)

� All other Fourier-based transforms are derivable fr om CTFT under specific signal conditions

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1D Fourier Transform

dttf tfi ⋅⋅⋅−∞

∞−⋅= ∫

π2e)f()F(

Inverse Fourier Transform:

dfft tfi ⋅⋅⋅+∞

∞−⋅= ∫

π2e)F()f(

))(f()F()f( tFTft =↔Fourier Transform:

You may have seen the Fourier transform and its inverse written as:

dtt ti ⋅⋅−∞

∞−⋅= ∫

ωω e)f()F( ωω ωπ dt ti ⋅⋅+

∞

∞−⋅= ∫ e)F()f(

21

Generally complex-valued

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Where in f( x,y), x and y are real, not complex variables.

Two-Dimensional Inverse Fourier Transform:

∫ ∫∞

∞−

+⋅−⋅=

)(2e ),(f),F( dxdyyxvu vyuxi π

∫ ∫∞

∞−

+⋅+⋅=

)(2e ),F(),( dudvvuyxf vyuxi π

↑ ↑amplitude basis functionsand phase of required basis functions

Two-Dimensional Fourier Transform:

2D Fourier Transform

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Time/Space Shift

][][,)()( 00 nnxnxttxtx −→−→

(t0 < 0)

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Sinusoidal Signal

� FREQUENCY� Radians/sec� or, Hertz (cycles/sec)

� PERIOD (in sec)

� AMPLITUDE� Magnitude

� PHASE

)cos( ϕω +tA

f)2( πω =

ωπ21 ==

fT

A

ϕ

ω

by FT

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Sinusoidal Signal: Phase ���� Time Shift

� Equate the formulas:

� and we obtain:

� or,

� Phase is ambiguous: 0 to 2 ππππ

)cos())(cos( ϕωω +=− tAttA m

ϕω =− mt

ωϕ−=mt

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Magnitude and Phase

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Magnitude & Phase Angle in Images

http://www.ee.nthu.edu.tw/~mlli – 59

Continous/Discrete Time/Space Signals

Sampling

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Signals Types

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Signal Types

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Signal Types

t/ x

Dirac impulse/unit impulse