Introduction to Medical Imaging

Instructors: Brian Fleming and Ioana Fleming

flembri@pha.jhu.edu, ioana@cs.jhu.edu

Lecture 1

In the Beginning…

Where to put the Leeches

• Hippocrates (460 - 377 BCE)– Muscles, skeleton, kidneys– Observation only

• Pesky “Oath” prevented human dissection

• Aristotle and Friends (4th century BCE)– Animals aren’t people

• Herophilos and Erasistratus (4th century BCE)– First human cadavers– Criminals aren’t people either

Where to put the Leeches

• Dark Ages - Europe– Balance the “humors”– Bleed, burn, drown, or exorcise

• Dark Ages – Arabia/Persia– Avicenna (1020 AD) Canon of Medicine

• Premier book of medicine everywhere for 500 years

– Ibn Zuhr (1100 AD) • Invented Autopsy and discovered parasites • Would have killed the idea of humors if logic and fact had

been considered a valid argument

Where to put the Leeches

• Printing Press – 17th century– Sharing of ideas brings renaissance (murder?)

History of Medical Imaging

Wilhelm Röntgen (Roentgen)

• The father of diagnostic radiology• German physicist (1845-1923)• Discovered x-rays in 1895• X was for "unknown“• First Nobel Prize in physics 1901

Discovery of X-rays

How to Irradiate Yourself

• Step 1 – Force electrons to go where no electron would ever want to go

– In air, would cool by giving off light

How to Irradiate Yourself

• Step 2 – Get rid of the air– Air quenches electron escape

• Unless you really ramp up the voltage…

– Try Neon

– Or try nothing…

How to Irradiate Yourself

• Step 3 – Run those electrons into a target

“Instant” Success

• Nov 8, 1895: Accidental discovery of x-rays• Dec 22, 1895: Bertha’s hand• Dec 28, 1895: first publication of results• Jan 1, 1896: Roentgen mailed copies to

leading scientists• Jan 5, 1896: Austrian newspaper story• Jan 23, 1896: society presentation• Feb 8, 1896: 1st clinical use (in US!)

Within One Year ...

• 49 serious books on x-rays• 1,044 scientific papers• Known to:

– spot cancer– treat cancer– cause cancer

• Numerous patents

What it REALLY Did…

Fluoroscopy

Fluorescence

Filmed in X-ray!

Early Popularity of Fluoroscopy

• Simple fluoro equipment:– x-ray tube– electrical generator– scintillation screen

• Convenience of real-time• Note: early film required 1-

2 hours of exposure– (where was intensifier

screen????)

Red Goggles

• Fluoroscopy images were dim• 1899: Beclere showed that dark adaptation is

a function of the retina• 1901: Williams suggested 10-minute dark

adaptation• 1916: scientific basis of sensitivity of retinal

rods in the range of red light• 1916-1950’s: red goggles standard gear

X-ray Hazards

• Early 1896: reports of hair falling out• Early 1896: skin reddening, inflammation• Early 1896: some severe burns (attributed to high

voltage in tubes)• Early 1896: delayed burns• 1902: Edison clear on dangers of x-rays

– Clarence Dally’s oozing ulcers, lost fingers, left hand, died in 1904 (Edison never x-rayed again)

• The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis

Some More Landmarks

• 1896: Becquerel discovered radioactivity• 1896: stereoradiography developed

• 1901: contrast agents described• 1904: lead glass protection devised• 1904: exposure badge invented

First angiogram

Coolidge X-ray Tube: 1913

• Properties of new tube:– high vacuum– hot cathode– tungsten-target

• Five outstanding properties– accurate adjustment– stable– reproducible– range of x-ray energies– less scattered radiation

William Coolidge

(expense prevented routine use until 1930’s)

Potter-Bucky Grid: 1913-1920

• Scattered x-rays cause blurring• 1913: Gustav Bucky: metal collimator grid

– reduce scatter blur

• 1920: Hollis Potter: movable grids– reduce image of grid

Conventional Tomogram: 1929

• Overlapping tissues blur tissue of interest• Jean Kieffer invented conventional tomogram

to image an interior slice – to help diagnose his own TB!

Only amateur in >100years to make a significantdiscovery in medicalimaging

Tomography

• Much as any light/camera, there is a focal plane

• My moving source and camera in opposite directions, focal plane becomes sharp

• Basis for almost all modern medical 3-D devices except Ultrasound.– CAT = Computed Axial Tomography

– PET = Positron Emission Tomography

Tomography (Again!)

Tomography was hard

• So it really wasn’t used all that much…

• Until 1972, when computers and motors led to the development of CAT

Impact of X-rays

• Widespread detection of tuberculosis in 1917

• 1898: American Roentgen Ray Society

• 1927: proof of cell damage caused by x-rays

• 1935: radiologist required to interpret radiograph in court (anybody could previously)

• Shoe fluoroscopes from 1920’s to 1960’s

Out with the old, In with the nukes

• X-rays were (and still are) limited.– Dim, for one (unless subject already dead)– Cannot track temporal events well

• Blood flow• Brain activity• Etc

• Enter nuclear medicine

Radioactive Decay

• Antoine Henri Becquerel (1852 – 1908)

• Shared Nobel Prize of 1903 with Marie and Pierre Curie for discovery of radioactivity

– Studying phosphorescence in Uranium salts on one side of his desk and the effect of bright sunlight on fluorescent coated photographic plates on the other.

Nuclear Physics in a Slide

Isotope Mass

C12 12

C13 13.00335

N13 13.0057

N14 14.0031

N15 15.0001

O15 15.0031

Neutron 1.0087

Proton 1.0073

Electron 0.00055

Alpha (He) 4.0026

Spontaneous Decay

• Every atom in the universe has a chance of spontaneously decaying– p+ π0 + e+

• Happens about once every universe

• Generally, large isotopes ( > Fe) Alpha decay– Nucleus binding energy is unstable– Mass products have lower mass than parent– 238U 234Th + 4He

• Beta Decay = emission of electron or positron– p+ n0 + e+ + ν– Electronic Transmutation – 15O 15N- + e+ + ν

• Gamma Decay – excess from β decay

Back to Nuclear Imaging

• Radiopharmaceuticals are injected• Biodistribution process causes

– absorption, distribution, metabolism, excretion

• Radioactive decay occurs, producing:– gamma rays (single photons), or

• Single Photon Emission Computed Tomography (SPECT)

– positrons (which yield paired photons)• Positron Emission Tomography (PET)

• Location and counts are recorded as images

Positron Annihilation

• Positrons are Anti-matter (anti-electrons)– When matter and anti-matter collide, they

annihilate– Mass energy of electron + positron released as

two photons– Total energy = 2*0.511 MeV + extra conserved

energy

Nuclear Medicine

Gallium scintigraphy looks for recurrence of malignant melanoma

• Step 1 – Inject patient with a radioactive substance

•Alpha, Beta, or Gamma?•PET, SPECT

•Step 2 – Wait for body to distribute

•Choose radiopharmaceutical depending on target

• Step 3 – Take photos, make scrapbook

Radiopharmaceuticals?

Isotope Beta Decay Gamma Decay

Half Life Product

15O Β+ N* 122 s 15N234Th Β- Y 24 d 234Pa18F Β+ N* 110 m 18O111In Β- Y 122 s 111Sn14C Β- N* 5730 y 14N99mTc N Y 6 h 99Tc

Tc = Technitium, In = Indium

Nuclear Medicine LandmarksSingle-photon imaging

• 1896: Becquerel discovered radioactivity• 1930’s: Hevesy mapped internal organs• late 1930’s: discovery of technetium• 1946: AEC allowed isotopes for medical use• 1950’s: Anger invented gamma camera• 1968: SPECT introduced by Kuhl• 1980’s: Dual/triple headed SPECT systems

Gamma Camera

For:•planar imaging•SPECT imaging

SPECT = single photon emission computed tomography

Commercial Gamma Cameras

ToshibaSiemens

For planarimaging andSPECT

[Normal male, Tc-99m HMPAO, for cerebral blood flow, Brighamrad]

normal Tc-99m MDP bone scintigram (5 mCi injected dose).

Commercial PET Scanners

CTI/Siemens

PET Images

Parkinson's Disease

Huntington's disease

Myocardial perfusionDopamine receptors

Ultrasound Imaging

Medical Ultrasound

• 1940’s – Ultrasound used to ease pain– Dr. George Ludwig, Naval Medical RI, Bethesda

• 1949 - Dr. John Wild measures how thick your colon (wall) is– “Father of Medical Ultrasound”

• 1953 – Inge Edler asks Carl Hertz if he can use radar to see inside the body.– No, but they use ultrasound to measure heart

activity, published in 1954

Medical Ultrasound

• 1958 – Prof. Ian Donald treats the wife of one of the directors of Babcock and Wilcox– Asks to visit with R&D to see their toys– Asks to play with ultrasound– Uses it on volunteers to measure ultrasonic

properties of various people with illnesses– Publishes "Investigation of Abdominal Masses by

Pulsed Ultrasound”• The most important medical imaging paper… EVER

– Goes on to study the growth rate of fetuses, first use of US in obstetrics

Medical Ultrasound

• 1965: First real-time ultrasound scanner• 1970: commercial systems widespread• mid-1970’s: grayscale and Doppler systems• early-1980’s: phased-array systems• mid-1990’s: 3-D ultrasound

How Does Ultrasound Work?

• Send a pulse -- receive the pulse• Map time-of-arrival to round-trip distance• Scan transducer in a plane

Ultrasound

Sound Propagation

• Sound travels through different things at different speeds– Speed of sound = cs

– Simple Version :

Material Cs (m/s)

Air 343

Water 1482

Steel 5960

Muscle 1482

Bone ?

Ultrasound Images

heart

Fetal head

kidneyCorotid artery

Fetalspine

3D Ultrasound

Kretztechnik AG

Voluson 530D Gallbladder stone

prostate

Fetal face

Back to X-Ray

• 1955 – Ronald Bracewell did some maths• X ray source and detector move together• Pencil thin beam which fans out in 2D• Each image is a projection of all tissue in beam• Take images at a full 360 degrees• Reconstruct using Fourier image analysis

• 1956 – Allan Cormack gives it a try, succeeds in 1963

• 1972 – Godfrey Hounsfied demonstrates first CT scanner

• Hounsfield and Cormack share Nobel prize

Computerized Tomography

CT Landmarks

• 1971: Hounsfield scanned first patient (4min)• 1972: EMI dominated Chicago RSNA• 1974: 26 EMI scanners worldwide• 1974: Shepp-Stein reconstruction formula• 1975: Commercial 2G, 3G, 4G CT scanners• 1979: Hounsfield and Cormack win Nobel Prize• 1985: Imatron, 50-100ms per slice• Late 80’s: Slip-ring technology • 1989: first commercial helical CT scanner• 1990s: multislice technology (<30s head-toe)

Early Commercial CT Scanner

Siemens Siretom CT Scanner, 1975 Compareto modernCT image

Fast and High Resolution CT

• 2 revs/s• 8 slices/s• 2.5mm slices• 58 s total time

Data collected usingusing Picker Mx8000TM

This image followsimage processing and 3D rendering

3D Anatomy from CT

Facial fractures Lumbar spine CT endoscopy

Magnetic Resonance Imaging

CT MRI

Same patient:

acute cerebral infarct

How Does MRI Work?

• Human are “ugly bags of mostly water”• H2O has protons which have magnetic moments

• Protons also spin• Step 1 – Make protons all spin one way• Step 2 – Use radio waves at the resonant frequency

to make all the protons suddenly spin the other way• Step 3 – Turn off radio and let spins go back to

normal• Energy difference between spin up and spin down

states released as a photon • B-field strength dictates resonance frequency

• Tuned to select individual areas at a time• Relaxation time, intensity, all Fourier transform

into an image with very high contrast

MRI Landmarks

• 1924: Pauli proposed nuclear magnetism• 1937: Rabi measured magnetic moments• 1946: Bloch and Purcell described relaxation• 1971: Lauterbur invented MRI (published 1973)• 1973: Mansfield introduced k-space• 1975: Ernst invented NMR Fourier imaging• 1977: Damadian’s first whole-body MR scanner• 1980: Margulis takes lead at UCSF• 1997: Damadian wins patent lawsuit against GE• 2003: Lauterbur and Mansfield win Nobel Prize

Some Modern Systems

[Siemens, MAGNETOM 42SP]

GE 0.5T open magnet(“double donut”)

MR Images

Tagged MRI

Breast implants

knee

heart

What is Next?

• MEG: magneto-encephalography• EEG: electro-encephalography• fMRI: functional magnetic resonance• micro-PET• optical imaging• molecular imaging• Photo acoustic imaging

Why We’re are Afraid to Fly