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General Information

OS7137
Class: Mon. 9:00-12:00 am (17 weeks in this semester)
Scopes:
The most important imaging modalities for biomedical
researches and clinical applications

Principles and instruments

Image characteristics and analysis
Advantages and limitations
Applications and recent progress

Contents:

Introduction to biomedical imaging

X-ray imaging and computed tomography (CT)
Nuclear medicine
Ultrasound imaging
Magnetic resonance imaging
Optical imaging
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General Information

Reference:
A. Webb, Introduction to Biomedical Imaging, WileyInterscience (2003).
P. N. Prasad, Introduction to Biophotonics, WileyInterscience (2003).
D. E. Chandler, R. W. Roberson, Bioimaging - Current
Concepts in Light and Electron Microscopy, Jones and
Bartlett (2009).

Grades:
5 Quizzes (one for each chapter): 20 %
Oral report: 20 %
Final project:
Oral presentation: 25 % (group)
Paper report: 35 % (personal)
Bonus
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General Information

Final project:

Date: 6/11, 6/18

Grouping: 2 students in a group
Subject: SCI journal papers ( 3 papers)
Presentation (per group): 15 mins (with 2-3-mins Q & A)
Report (per student): due on 6/25
Abstract
Introduction
Content (methods, advances, comparisons, limitations,
possible solutions, etc.)
Conclusion

Office: Rm529
Email: sychen@dop.ncu.edu.tw
Notes and class information are available at BB Learn

Course Schedule
Date

Content

Note

2/20

Syllabus + Introduction

2/27

X-ray imaging (I)

Report 1 (Make up lecture on 3/3)

3/5

X-ray imaging (II)

Report 2

3/12

Nuclear medicine (I)

Report 3 / Quiz 1

3/19

Nuclear medicine (II)

Report 4

3/26

Ultrasound imaging (I)

Report 5 / Quiz 2

4/2

--

No class

4/9

Ultrasound imaging (II)

Report 6

4/16

Magnetic resonance imaging (I)

Report 7 / Quiz 3

4/23

Magnetic resonance imaging (II)

Report 8

4/30

Optical microscopy (I)

Report 9 / Quiz 4

5/7

Optical microscopy (II)

Report 10

5/14

Optical microscopy (III)

Report 11

5/21

Optical microscopy (IV)

Report 12

5/28

Optical microscopy (V)

Report 13

6/4

Optical microscopy (VI)

Report 14

6/11

Term project presentation (I)

Quiz 5

6/18

Term project presentation (II)

Brief Introduction

Human Anatomy
Integumentary System

Circulatory System

Skeletal System

Endocrine System

Muscular System

Reproductive System

Respiratory System

Circulatory System

http://www.3dscience.com/

Lymphatic System

Nervous System

To do disease diagnosis
How to see inside?
How to see small?
How to see 3-dimensionally?
How to see diseases?

Biomedical Imaging System

Ex vivo modalities

Advantages

Physical biopsy
Histopahtology staining
Optical microscopy
Electron microscopy

H & E stain

High resolution
Molecular information

Disadvantages

Painful
Scar formation
Metastasis (cancer)
Information loss
Time-consumed
High cost

In vivo imaging modalities

Physical biopsy

Electron microscopy

Biomedical Imaging System

In vivo modalities

X-ray imaging (projection)

X-ray computed tomography (CT)
Nuclear medicine
Ultrasonic imaging
Magnetic resonance imaging
Optical imaging

Goals

Diagnostic significance
Noninvasiveness (safety)
High penetrability
High spatial resolution
High speed
High stability
Low cost
Etc.

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X-ray Imaging (projection radiography)

Dental X-ray imaging

http://aquantumofknowledge.wordpress.com/

http://medenco.com/

http://starmedvl.ro/

Image contrast: different attenuation of X-ray

Good for hard tissues but not in soft tissues
Overlapping layers hard to interpret
X-ray imaging

http://www.dicts.info/

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X-ray Imaging and Computed Tomography

(CT)
Spatial resolution:
X-ray angiography: ~100 m
CT: ~1 mm
Limited energy dosage
tissue damages due to ionizing radiation
X-ray angiography

http://bryanking.net/medical-tests/

X-ray CT

http://radlink.com.sg/

http://www.worldculturepictorial.com

http://www.metacafe.com/watch/1637214/head_to_toe/

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Nuclear Medicine

http://emedicine.medscape.com/

http://www.neurology.org/

99
42

1/2 66h
1/2 6h
Mo
+ 9943m Tc
9943g Tc +

123
53

http://www.radiopharmaceuticals.com.sg/

13h
123
I + 10 e
52Te +
73h
201
Tl + 10 e
80 Hg + + X-ray

201
81

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Positron Emission Tomography (PET)

http://health.howstuffworks.com/

Study of Alzheimer disease

http://health.howstuffworks.com/

http://www.nia.nih.gov/

Issues of tissue damages exist!!

http://kuims.blogspot.com/

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Ultrasonic Imaging

http://www.microscopesblog.com/
http://en.wikipedia.org/wiki/Ultrasound

No ionizing radiation
noninvasive
Poor resolution (cm)
Poor contrast
Higher penetrability than light
http://www.medicexchange.com/

3D imaging: XZT

http://www.medicexchange.com/

4D imaging: XYZT

Not for gas and bone

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Ultrasonic Imaging

http://www.indiamart.com/

Doppler ultrasonic imaging of blood flow

http://victorybreastimaging.com/

Brest imaging

http://www.sportsmedicine.pro/

Musculoskeletal structure

http://conradweiseranimalhospital.com/

Cardiac disease

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Magnetic Resonance Imaging (MRI)

Spinning hydrogen atoms small magnets

Large static magnetic field precession
Radiofrequency (RF) field
changes of magnetic fields
RF coil & Faradays law detect the changes

http://www.cardiff.ac.uk/

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Magnetic Resonance Imaging (MRI)

Different viewing angle

http://www.magnet.fsu.edu/

Noninvasive but side effects may exist!

Angiography

Brain function

Stronger contrast for soft tissues than CT

Brain tumor diagnosis

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Optical Imaging

Bio-tissue

Light

Bio-tissue

Reflection
Refraction
Transmission
Scattering
Absorption

Detector
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Optical Microscopy
Hooks microscope

Bright-field microscopy

H & E stain
http://filebox.vt.edu/
http://www.yourbeautyinfo.com/

Dark-field microscopy

Noninvasive?
Stronger contrast?
Higher resolution?
Higher penetrability?
Molecular information?

http://www.ruf.rice.edu/

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Phase, Interference, and Polarization

Bright-field

Phase contrast

http://electron9.phys.utk.edu/

http://www.currentprotocols.com/

Phase contrast

Differential Interference
contrast (DIC)
http://micro.magnet.fsu.edu/

http://micro.magnet.fsu.edu/

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Confocal Microscopy
Human cornea
Incoherent light source (halogen lamp)

M. Bohnke et al. Retinal and Eye Research 18, pp.553-628 (1999)

Coherent light source (laser)

Laser Scanning Confocal Microscopy (LSCM)
http://www.bio.brandeis.edu/

Spatial filtering of PSF

Good for thick tissues!
Only reflected signals?

R. L. Niederer et al. Br. J. Ophthalmol. 91, pp.1165-1169 (2007)

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Fluorescence Microscopy

http://research.stowers-institute.org/

http://zeiss-campus.magnet.fsu.edu/

http://serc.carleton.edu/

http://www.olympusfluoview.com/

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Confocal + Fluorescence Microscopy

http://www.lbb.ethz.ch/

http://zeiss-campus.magnet.fsu.edu/

Spinning disc confocal microscopy

Wide-field fluorescence microscopy

http://www.olympusfluoview.com/

LSCM
Confocal fluorescence microscopy

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Multicolor Fluorescence Microscopy

How to chose fluorophores?
Overlapping of emission spectra
Issues of photodamages
Issues of photobleaching

http://micro.magnet.fsu.edu/

http://jhc.sagepub.com/

How to reduce off-focus photodamages and increase resolution simultaneously?

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Nonlinear Microscopy
Single photon excitation (blue-green CW light)

Two photon
fluorescence

Single photon
fluorescence
http://www.loci.wisc.edu/

Two photon excitation (fs pulses @ 800 nm)

Confined excitation volume
improved resolution
Reduced off-focus excitation
reduced off-focus damages
http://obel.ee.uwa.edu.au/

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Two Photon Microscopy (TPM)

SHG

TPF
http://www.pnas.org/

Second Harmonic Generation (SHG)

No energy deposition
Only virtual transition
Type I collagen fibers

SHG + TPF

http://www.pnas.org/

Two Photon Fluorescence (TPF)

Energy deposition
Real-level transition
http://pubs.acs.org/

Elastin fibers

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Harmonic Generation Microscopy (HGM)

Linear optics
P() = 0 (1) E()

Nonlinear optics
P = 0 (1) E() + P(2)(2) + P(3)(3) + ...

h1

h2

h1

= 0 (1) E() + 0 (2) E()E() + 0 (3) E()E()E() + ...

= Fundamental + SHG + THG +
Second Harmonic Generation
(SHG)

In vivo images of human skin

h1
h1

h3

h1

Third Harmonic Generation

(THG)

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Fluorescence Resonance Energy Transfer (FRET)

http://commons.wikimedia.org/

http://commons.wikimedia.org/

http://www.lin.com.tw/

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Fluorescence Lifetime Imaging Microscopy (FLIM)

http://www.iss.com/

Fluorescence lifetime imaging

Molecular information
Disease diagnosis
http://microscopy.berkeley.edu/

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Raman Imaging & Coherent Anti-Stoke Raman

Scattering
CARS imaging

http://www.engineering.unl.edu/

Raman imaging

http://www.mdpi.com/

http://www.nist.gov/

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4Pi Microscopy

Use interference to modify the PSF

Improved axial resolution
But only for thin samples
http://zeiss-campus.magnet.fsu.edu/

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Structured Illumination Microscopy (SIM)

http://zeiss-campus.magnet.fsu.edu/

http://online.physics.uiuc.edu/

Saturated Structured
Illumination Microscopy
(SSIM)
http://zeiss-campus.magnet.fsu.edu/

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Depletion Microscopy
Ground-State Depleted Microscopy (GSD)

http://zeiss-campus.magnet.fsu.edu/

Stimulated Emission
Depletion Microscopy
(STED)

http://zeiss-campus.magnet.fsu.edu/

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Localization Microscopy
Photoactivated localization microscopy (PALM)
Stochastic optical reconstruction microscopy (STORM)

http://zeiss-campus.magnet.fsu.edu/

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Near-Field Scanning Optical Microscopy (NSOM)

http://www.i-aps.org/

http://www.olympusmicro.com/

http://zeiss-campus.magnet.fsu.edu/

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Optical Coherence Tomography (OCT)

http://www.absoluteastronomy.com/

http://www.oct-ophtalmo.fr/

Diabetic Macular Edema

Post-Cataract Complications

Glaucoma

Age-related Macular Degeneration

http://www.ticgroup.com.tw/

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Thats all?
Not even close!!

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