Nuclear Medicine Imaging

04/19/23 VII.2

Overview• Nuclear medicine:

Therapeutic and diagnostic use of radioactive substances• Radioactivity:

• Naturally occurring radioisotopes (radioactive isotopes) discovered 1896 by Becquerel

• First artificial radioisotopes produced by the Curies 1934 (32P) “Radioactivity,” “Radioactive”

• 1947 - Kohman: “Radionuclide” = nucleus of measurable half-life • 1935 - Hevesy uses 32P for metabolic studies with Geiger-Muller

counter• 1949 - First radionuclide imaging by Cassen of 131I uptake in thyroid

gland(scintillator+PMT, scanner, collimator,1/4” spatial resolution)

• 1957 - Anger camera (planar imaging)• 1960 - Kuhl & Edwards construct Mark IV scanner (~10 years before x-

ray CT)• 1977 – Kayes & Jaszczak develop SPECT independently• 1950 – first PET attempts • 1976 – First commercial PET (Phelps & Hoffman at CTI)

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Radionuclide Imaging

• Characteristics:• The distribution of a radioactive agent inside the body is imaged• Projection and CT imaging methods• Imaging of functional or metabolic contrasts (not anatomic)

– Brain perfusion, function– Myocardial perfusion– Tumor detection (metastases)

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Nuclear Stability

• The neutrons and protons which form the nucleus of an atom are held together by a combination of forces such as gravitational and electrostatic forces. The protons tend to repel each other. This means that, as bigger atoms are but together, it becomes more difficult for the nucleus to be stable as one collection of particles.

• The only reason that the nucleus is stable is that neutrons bind the other particles together, which is why the heavier atoms have more and more neutrons.

• As a general rule, there are about equal number of neutrons and protons in a nucleus. But, in heavier atoms, a greater proportion of neutrons have to be added to maintain the stability of the atom.

• The nucleus of many atoms is not stable. Nuclei with infavourable neutron/proton ratio will disintegrate or decay into stable nuclei by spontaneous emission of nuclear particles.

• Example:

energy

energy

e

e

n p e

p n e

neutron rich nucleus :

proton rich nucleus :

electron neutrion

positron

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Nuclear Stability

Neutron rich

unstable element

Proton rich

unstable element

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Definitions

• Isotope: Nuclides of same atomic number Z but different N (and A) same element

• Nuclide: Species of atom characterized by the constitution of its nucleus (in particular N, Z)

• Radionuclide: Nuclide of measurable half time

• Radioactive decay : the process by which an unstable nucleus is transformed into a more stable daughter nucleus by emitting nuclear particles.

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Examples of Radioactive Decay

04/19/23 VII.8

Nuclear Activity

• Radioactive decay is described by

• N(t), N0: number of radionuclide at time t = 0 and t, resp.

: decay constant [1/t]

• Activity A = average decay rate [decays per second]

• Nuclear activity is measured in curie: 1 [Ci] = 3.7 1010 decays/sec(orig.: activity of 1 g of 226Ra)

• Practical: 1 mCi, Ci. SI unit is becquerel [Bq] = 1 decay/second

0( ) tN t N e

1/ 2

0.693T

99mTc

0tdN t

A t N t A t A edt

04/19/23 VII.9

Interaction of Nuclear Particles and Matter

• Alpha particles• Helium nucleus (4He++), mostly occurring for parent with Z > 82• ~ 3-9 MeV (accounts for the kinetic energy of the alpha particle

+ kinetic energy of the product nucleus)• + 2 charge large mass strong interaction (ionisation: attracts

eşectrons from other atoms which become cations)

• Mean range in air: Rm = 0.325 Ealpha3/2

• Beta particles• Causes Bremsstrahlung (white, characteristic)

• “Wiggly” motion in matter (low mass)

• Gamma rays• Electromagnetic waves produces in nuclear processes ( < 0.1

nm, E > 10 keV)• Identical to x-ray interaction (for E > 1.02 MeV: pair production

and photo disintegration [emission of alpha, n, or p from nucleus])

04/19/23 VII.10

Radionuclides in Clinical Use

• Most naturally occurring radioactive isotopes not clinically useful (long T1/2, charged particle emission)

• Artificial radioactive isotopes produced by bombarding stable isotopes with high-energy photons or charged particles

• Nuclear reactors (n), charged particle accelerators (Linacs, Cyclotrons)

1/ 2 2.5d99 99T mMo Tc e

04/19/23 VII.11

Radionuclide Generator• On-site production of 99mTc

• 99mTc is the single most important radionuclide in clinical use (gamma @ 140 keV)

1/ 2 6 h99 99 140 keVTmTc Tc

Al2O3

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Radiopharmaceuticals and their uptake in the body

In nuclear medicine imaging a radioactive isotope is introduced into

the particular part of the body which is to be investigated.

Ex: in order to follow heart, introduce the activity into the blood stream.

Ex: In order to follow tyroid gland, introduce radioactive iodine (as tyroid

absorn iodine)

In some cases, neither of the two methods are possible.

attach the radioactive subtance to another chemical which is chosen

because ıt is preferentially absorbed by part of the body. The chemicals to

which radipactive labels are attached are called radiopharmaceuticals.

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Radiopharmaceuticals (cont.)

If a chemical compound has one or more of its atoms substituted by

a radioactive atom then the results is a radiopharmaceutical.

For more detailed information: see Belcher & Velter “Radionuclides in

medical diagnosis”, 1971

Selection of isotopes:

1) choose an isotope so that the resultant radiopharmaceutical is in the correct

chemical form which will allow it to be absorbed by the particular organ to be

imaged.

2) the energy of radiation must be suitable to the detectors to be used. Optimum

energy range for gamma cameras is 100-300 keV. Efficiency drops beyond this

range

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Selection of isotopes (cont.)

3) T1/2 must not be too short, otherwise it will decay before the radiopharmaceutical

can be delivered. It must not be too long, otherwise the patient will be unnecessarily

exposed to ionization.

T1/2 (ideal) is a few hours.

Exception: Se is used for pancreas scanning. T1/2 is 120 days.

4) radiation dose delivered to patient must be as low as possible

5) radiopharmaceutical must be available, it should be cheap.

The radionuclide that fulfills most of the above criteria is Technetium _ 99m (99m Tc),

which is used in more than 90% of all nuclear medicine studies.

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Properties of 99mTc:

• T1/2 = 6 h

• radiates 140 keV gamma ray• the short half time and absence of Beta emission allows low

radiation dose to patient.• The 140 keV gamma radiation allows for 50% penetration of

tissue at a thickness of 4.6 cm.

Applications:

• 99mTc-Sestamibi (myocardial perfusion, cancer)• 99mTc-labeled hexamethyl-propyleneamine (brain perfusion)

Other gamma emitters:

123 I, 111 In, 67 Ga, 201 Tl, 81 Kr m

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Positron emitters:

• 11 C , T1/2 = 20 min – many organic compounds (binding to nerve receptors, metabolic

activity)

• 13 N , T1/2 = 10 min

– NH3 (blood flow, regional myocardial perf.)

• 15 O , T1/2 = 2.1 min

– CO2 (cerebral blood flow), O2 (myoc. O2 consumption), H2O (myoc. O2 consumption & blood perfusion)

• 18 F , T1/2 = 110 min – 2-deoxy-2-[18F]-fluoroglucose (FDG, neurology, cardiology, oncology,

metabolic activity)

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Imaging

As long as the photons emanating from the radionuclide have sufficient energy

to escape from the human body in significant numbers, images can be generated

that portray in vivo distribution of the radiopharmaceutical.

Nuclear medical imaging may be divided into three categories:

1) conventional or planar medical imaging,

2) Single photon emission computed tomography (SPECT),

3) Positron emission tomography (PET).

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Conventional or planar imaging

The three-dimensionally distributed radiopharmaceutical is imaged onto a planar or

two-dimensional surface producing a projection image.

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Detection of Gamma Radiation

• Scintillation detectors most commonly used• Crystals: NaI(Ti), BGO, CsF, BaF2 • Criteria: Stopping power, response time, efficiency, energy

resolution

• Ion collection detectors (ionization chambers) not used because of low efficiency, slow response

• Semiconductor detectors (diodes): very high energy resolution, fast but small and high cost

04/19/23 VII.20

Scintillation Camera (Anger Camera)

• Imaging of radionuclide distribution in 2D• Replaced “Rectilinear Scanner”, faster, increased efficiency,

dynamic imaging (uptake/washout)• Application in SPECT and PET• One large crystal (38-50 cm Dia.) coupled to array of PMT

1. Enclosure2. Shielding3. Collimator4. NI(Ti) Crystal5. PMT

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Anger Logic

The Anger camera is a system for achieving a large number of resolvable elements with a limited number of detectors. It thus overcomes the previous difficulty of having the resolution limited by the number of discrete detectors.

The principle is based on estimating the position of a single event by measuring the contribution to a number of detectors.

GAMMA-RAY PHOTON

x1

x2

I1 I2

SCINTILLATING CRYSTAL

LIGHT PHOTONS

PHOTODETECTOR

x I1x1+ I2x2

I1+I2

Cameras of this general

type have a single crystal

viewed by arrays of detectors

with the detected outputs

followed by a position computer

to estimate the position of

each event.

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Applications

1. Thyroid imaging: The thyroid gland is situated in the lower part of the neck at a

depth of about 1 cm. The purpose of thyroid is to secrete the hormone thyroxin

which is carried in the blood stream and controls a number of body functions:

• stimulate metabolism

• influence growth

• control mental development

• store iodine

underactive thyroid :

• mental dullness,

• low temperature

• decrease in metabolism

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Imaging of thyroid can be useful for the following purposes:

1. To determine the amount of thyroid tissue left after surgery or radiotherapy for thyroid disease,

2. To detect thyroid metastases associated with thyroid cancer,

3. To show the comparative function of different parts of the glands,

4. To measure the size and position of the thyroid prior to surgery or other treatments of the disease.

To obtain images, the patient is given an oral dose of 30Ci 131I in the form of KI (potassium iodide). The scan is taken 24hrs later.

131 I emits rays (336 keV).

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Collimators I

Collimator restricts

the acceptance angle

Geometry

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Single Photon Emission Computed Tomography (SPECT)• If one or more gamma cameras

are attached to a computer controlled gantry, which allows the detectors

to be rotated around a patient, multiple views (or 2D projections) of the 3D pharmacutical distribution can be acquired.

• First SPECT 1963 (Mar IV) used array of detectors• Rotation, Translation• High count rates• Many components• Mostly single-slice

• Rotating camera:• Multiple slices• Multi-camera systems

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SPECT Image

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SPECT Artifacts

• Reconstruction methods similar to x-ray CT• X-ray attenuation: X-ray from source is attenuated by tissue

unknown concentration of tracer and unknown distribution of tissue absorption.• Corrective measures:

1) Transmission measurement with external source to determine tissue absorbtion

2) Assume constant absorption and use geometric mean of two measurements 180 apart, which is independent on d

3) Iterative reconstruction

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Using the Geometric MeanLet there be an activity A at depth d from detector I. Assume that the object has

a constant attenuation coefficient. Then the fraction of photons reaching that

detector (C1) is proportional to e-x, that is

dAeC 1

Survival

probability

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Geometric mean (cont.)

The fraction of photons reaching the second detector (C2) is:

)(2

xTAeC

If the geometric mean is used, then

2/

2/1)(

2/121

))((

)(

T

dTd

GM

Ae

AeAe

CCC

which is totally independent of source depth. Provided an outline of the body,

a simple correction can be applied to the combined opposed projections.

04/19/23 VII.30

Iterative Reconstruction method

dxdytyxeyxA

dxdyetyxyxAtp

dss

dss

)sincos(),(

)sincos(),()(

)(

)(

04/19/23 VII.31

,,

),(

)(kjjl

i

k

kii eAfkp

The image domain can be discretized and acquired ray sums can be expressed by:

where

Ai : activity contained in the ith voxel,

p(k) : projection data at angle , the sum of weighted activity (or ray sum) along the kth ray at angle of view ,

fi k, : fractional volume of the ith element that is contained within the

kth ray,

i : the attenuation coefficient of the ith element (corresponding to the energy of the photon),

lj k, : length of the portion of the kth ray that is contained within the ith element

exp(- j lj k, ) : attenuation factor for radiation originating from the ith element.

The index j denotes elements lying along the kth ray between the ith element and the boundary of the object nearest the detector.

04/19/23 VII.32

Iterative method

• Assume attenuation distribution, find Ai

• Calculate attenuation distribution using Ai

• Find new estimate for Ai using the calculated attenuation coefficients,

04/19/23 VII.33

Positron Emission Tomography

• Use with positron emitters (beta-plus) • Positron annihilates with electron of nearby

atom two gamma quanta each at 511 keV leave under 180

• “Tagging” of radiation:• Windowing• Coincidence detection (“electronic

collimation”)

04/19/23 VII.34

PET Detectors• Individual Coupling:

Expensive, packing problematic, high count rate

• Block Design:Digital encoding, longer dead time, more economic, somewhat reduced resolution

04/19/23 VII.35

PET Image Resolution

04/19/23 VII.36

PET Resolution compared to MRI

• Modern PET ~ 2-3 mm resolution

MRI

PET

04/19/23 VII.37

Functional Imaging