Radionuclide Imaging Flashcards

1
Q

What are the radionuclide imaging principles?

A
  1. Radiochemistry - Label small amounts of molecules with a radionuclide
  2. Administer the radiotracer to the biological system
  3. Detect the signal of radionuclide decay
  4. Convert the signal into a meaningful biomedical image
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2
Q

What are the features of a tracer?

A

It is used to measure concentration
The tracer is unstable
It allows you to determine function
It does not change the biology of the material

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3
Q

Why is it important that only small amounts of molecules are labelled with a radionuclide?

A

If it is not a small amount, it will damage DNA. This can change cell biology. Also, do not want competitive behaviour.

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4
Q

What are the components of radiochemistry involved in radionuclide imaging?

A
  • Label molecules with radionuclides*
  • Radiotracer amounts are very small (pico/nano molar)
  • The radionuclide is PURE
  • Consider radiotracer half-life range
  • The radiotracer is PURE
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5
Q

What does it mean to say a radionuclide is pure?

A

There are no alternative ways of decay
Will decay in the way that you want them to
Will be alpha OR beta OR gamma
Otherwise there will be a lot of background radiation

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6
Q

What are the features of the radiotracer half life that should be considered?

A

It should be as low as is reasonable.
Needs to be in the range of the biological and experimental requirements
Normal half life is between 1 and 2 hours

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7
Q

What are the components of pharmokinetics involved in radionuclide imaging?

A
  • Administer the radiotracer to the biological system*
  • All tracer molecules need to travel quickly to the abnormal area (through the blood stream)
  • Then they need to stay there to allow for imaging to occur
  • Needs to have very few radiometabolites created, otherwise you can stop following the tracer and start following the radio-metabolite (and get a signal from it)
  • These metabolites DO NOT compete with the tracer or it can suppress biological processes
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8
Q

What are the components of nuclear engineering involved in radionuclide imaging?

A
  • Detect the signal of radionuclide decay*
  • Emitted particle should pass through the body (some won’t due to interaction with body matter)
  • It should arrive at the detector in a predictable manner in order to detect where the gamma ray came from (usually straight if no interaction with matter
  • The detector should be able to discriminate each decay event
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9
Q

What are the components of biomathematics involved in radionuclide imaging?

A

Convert the signal into a meaningful biomedical image

2D = planar imaging, gamma camera
3D = Tomography/PET and SPECT
4D = image changes with time due to pharmokinetics
5D = image changes with time due to pharmokinetics and subject motion
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10
Q

What does SPECT stand for?

A

Single Photon Emission Computed Tomography

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11
Q

What are the common radionuclides used in SPECT?

A

99m-Tc
123-I
111-In
67-Ga

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12
Q

What is the main feature of radiotracers used in SPECT?

A

They are photo-emitting

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13
Q

What is the half life of 99m-Tc?

A

6 hours

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14
Q

What is the half life of 123-I?

A

13 hours

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15
Q

What is the half life of 111-In?

A

67 hours

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16
Q

What is the half life of 67-Ga?

A

78 hours

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17
Q

What is an example of a SPECT tracer that uses 99m-Tc as the nuclide?

A

HMPAO

Hexa Methyl Propylene Amine Oxime

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18
Q

What is an example of a SPECT tracer that uses 123-I as the nuclide?

A

Iodine

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19
Q

What is HMPAO used for clinically?

A

Cerebral perfusion

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20
Q

What is an example of a SPECT tracer that uses 67-Ga as the nuclide?

A

Gallium nitrate

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21
Q

What is 67-Gallium nitrate used for in SPECT clinically?

A

Osteomyelitis

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22
Q

What are the features of SPECT tracers?

A
  • Photo emitting

- Relatively low energy gamma photons

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23
Q

What are the features of SPECT tracers?

A
  • Photo emitting
  • Relatively low energy gamma photons
  • Heavy nuclides
  • Label large molecules (peptides)
  • Not commonly organic molecules
  • Majority use 99m-Tc
  • Can see single molecules within the body
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24
Q

What is the average gamma photon energy from a SPECT tracer?

A

100-400keV

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25
Q

What is the main feature of a PET tracer?

A

They are positron emitting

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26
Q

What does PET stand for?

A

Positron emitting tomography

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27
Q

What are nuclides used most commonly in PET?

A

15-O
11-C
13-N
18-F

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28
Q

What is the half life of 15-O?

A

2 minutes

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29
Q

What is the half life of 11-C?

A

20 minutes

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30
Q

What is the half life of 13-N?

A

10 minutes

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31
Q

What is the half life of 13-N?

A

10 minutes

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32
Q

What is the half life of 18-F?

A

110 minutes

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33
Q

What does FDG stand for?

A

Fluoro-Deoxy-Glucose

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34
Q

What are the features of PET tracers?

A
  • Short half life
  • Cyclotron required for production
  • Relatively low energy gamma photons
  • Biological elements
  • Has a wide range of clinical applications
  • Mainly used in oncology
  • More natural elements
  • Most research and investigations are carbon based
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35
Q

What are the consequences of the short half life of PET tracers?

A

Less time to do imaging
Expensive
Cyclotron needs to be close to the scanner

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36
Q

What are the 3 elementary particles?

A

alpha
beta
gamma

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37
Q

Describe an alpha particle and its properties

A

4He
2
Travel straight but has a coulomb interaction with tissue the stops them within a few micrometres of travel
Not possible to image

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38
Q

Describe an alpha particle and its properties

A

4He
2
Travel straight but has a coulomb interaction with tissue the stops them within a few micrometres of travel
Not possible to image

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39
Q

Describe a beta particle and its properties

A

0 e OR 0 beta+
-1 +1
Interact with coulomb force but because they are small, they do not travel straight
Average tissue range is 1-5mm
In vivo imaging possible
Positrons annihilate and create 2 gamma particles (511kev)

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40
Q

Describe a gamma particle and its properties

A
Interact with matter through the photoelectric effect and compton scattering
High energy (100-500KeV) helps them escape human tissue
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41
Q

What are the layers within a gamma camera?

A
Collimator
Scintillation crystal
Light Guide
PMTs
Processing electronics
Lead casing
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42
Q

What are the layers within a gamma camera?

A
Collimator
Scintillation crystal
Light Guide
PMTs
Processing electronics
Lead casing
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43
Q

What are the features of an image generated by a gamma camera?

A

Creates a 2D image
It is a projection image
No depth information
Can determine direction not location

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44
Q

What are the basics behind a gamma camera?

A
Emits gamma ray
Collimators stop any non parallel rays
Scintillator absorbs gamma photons
Emits optical photons
Converted to electrical current
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45
Q

What are the 4 steps in that occur in the scintillator crystal?

A

Absorption: gamma ray ejects electrons (via Compton or photoelectric effect)

Excitation: the electron is excited to the conduction band (can move through the crystal)

Relaxation: the electron relaxes back to valence band

Emission: subsequent emission if visible light (characteristic) radiation

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46
Q

What are the scintillation crystals in gamma cameras commonly made of?

A

Sodium iodide
NaI
Doped in thallium

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47
Q

What are the scintillation crystals in gamma cameras doped in? Why?

A

Doped in thallium to achieve efficient scintillation at room temperature.

Without this, it only scintillates at liquid nitrogen temperatures

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48
Q

What are the basics behind a gamma camera?

A
Emits gamma ray
Collimators stop any non parallel rays
Scintillator absorbs gamma photons
Emits optical photons
Converted to electrical current
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49
Q

What are the 4 steps in that occur in the scintillator crystal?

A

Absorption: gamma ray ejects electrons (via Compton or photoelectric effect)

Excitation: the electron is excited to the conduction band (can move through the crystal)

Relaxation: the electron relaxes back to valence band

Emission: subsequent emission if visible light (characteristic) radiation

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50
Q

What are the scintillation crystals in gamma cameras commonly made of?

A

Sodium iodide
NaI
Doped in thallium

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51
Q

What are the scintillation crystals in gamma cameras doped in? Why?

A

Doped in thallium to achieve efficient scintillation at room temperature.

Without this, it only scintillates at liquid nitrogen temperatures

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52
Q

What are the basics behind the workings of a gamma camera?

A
Gamma ray emitted
Collimators block out non-parallel rays
Scintillator absorbs gamma rays
Converts to optical photons
Optical photons are converted to electrical current
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53
Q

What are the 4 steps that occur in a scintillation crystal?

A

Absorption: gamma ray ejects electrons (via Compton or photoelectric effect)

Excitation: the electron is excited to the conduction band (can move through the crystal)

Relaxation: the electron relaxes back to the valence band

Emission: with subsequent emission of characteristic frequency radiation (visible light)

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54
Q

What are gamma camera scintillation crystals commonly made of?

A

NaI
Sodium iodide
Doped with thalium

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55
Q

What are the ideal properties of a scintillation crystal?

A
  1. High scintillation efficiency (high gamma to light conversion)
  2. Linear conversion (light yield is proportional to deposited energy)
  3. Low optical absorption (optically transparent crystal)
  4. Short decay time of induced luminescence
  5. Able to be manufactured in large sizes to image patients
  6. Index of refraction = glass for efficient coupling to PMTs
  7. Low cost
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56
Q

What are the advantages of using NaI for gamma camera scintillators?

A

Very cheap to produce
Puts it into the visible light range
Allows it to occur at room temperature

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57
Q

What happens if you increase the thickness of the scintillation crystal in a gamma camera?

A

Stops more gamma rays

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58
Q

What happens if you do not use grease for optical coupling?

A

The air/solid interface between the scintillation crystal and the PMT photocathode would cause total internal refractions

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59
Q

How does a photomultiplier tube work

A

In an vacuum
Incident light photons enter the PMT through the photocathode
Light strikes the photocathode
A photoelectron is emitted
The electron strikes anodes of ascending voltages
It gains energy and it ejects further electrons from the next dynode
It produces an amplified signal

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60
Q

What is optical coupling?

A

It ensures that there is little leakage of light from the crystal before it reaches the PMT

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61
Q

How is efficient optical coupling achieved?

A

Silicon grease or oil of a similar optical index to the crystal and photocathode should be used as a light guide between the surfaces.

Regular re-greasing at services

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62
Q

What happens if you do not use grease for optical coupling?

A

The air/solid interface between the scintillation crystal and the PMT photocathode would cause total internal refractions

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63
Q

How does a photomultiplier tube work

A

Incident light photons enter the PMT through the photocathode
Light strikes the photocathode
A photoelectron is emitted
The electron strikes anodes of ascending voltages

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64
Q

How is the location of a gamma photon emission calculated in a gamma camera?

A

For each event, a signal is generated in each PMT
The information is used to work back the initial location
There will be more signal at some PMTs due to the position - light will hit multiple PMTs are light does not travel in a straight line

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65
Q

What are the methods used in gamma cameras to remove scatter?

A

Pulse height analyser

Collimation

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66
Q

What is a pulse height analyser?

A

Excludes scatter
Scattered photons will generally have lower energy than non-scattered
It measures the energy and only accepts those that fall within a certain range +/- X%

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67
Q

What needs to be determined in a pulse height analyser?

A

Bandwidth - the range of energies that will be accepted

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68
Q

Why do you need a range of values in a pulse height analyser?

A

It is experimental
There are small inaccuracies
If the range is too small, may exclude some primary rays

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69
Q

What is the purpose of a collimator in gamma cameras?

A

Excludes all radiation not parallel to the detector

Reduces scatter

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70
Q

In SPECT what radioisotope is used most commonly and what is its energy?

A

99m-Tc

140keV (low energy)

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71
Q

What collimator properties need to be considered?

A
Needs to be made of lead
Size
Septal thickness
Hole depth
Hole size
Distance from detector

Different radioisotopes need different collimators

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72
Q

What happens if you increase the amount of collimation?

A

Get a decrease in resoltion

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73
Q

Why does PET provide a higher resolution than SPECT?

A

Many photons are absorbed by the collimators and this results in a loss of information and a reduction in resolution

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74
Q

In SPECT what radioisotope is used most commonly and what is its energy?

A

99m-Tc

140keV (low energy)

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75
Q

What happens if you increase the septal thickness of a collimator?

A

Increased thickness =
Increased imaging energy
Decreased sensitivity

Septa must be thick enough to stop radiation with the energy of the imaged isotope

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76
Q

What are the properties of a shallow holed collimator?

A

High sensitivity - allows most rays through
Low resolution
Decrease radiation for the same count

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77
Q

Why is the resolution increased by using smaller holes in a collimator?

A

Each collimator hole sees a smaller region.

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78
Q

What are the consequences of increasing the hole depth of a collimator?

A
Increased hole depth = 
Increase resolution
Decrease specificity
Increase radiation dose required
No change in the imaging energy
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79
Q

What are the consequences of decreasing collimator hole size?

A

Decrease hole size =
Decrease sensitivity
Increased resolution
No change in imaging energy

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80
Q

Why is the sensitivity of a collimator decreased when using smaller holes?

A

Smaller holes means more holes

This means more area is taken up from lead septa which decreases sensitivity

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81
Q

Why is the resolution increased by using smaller holes in a collimator?

A

Each collimator hole sees a smaller region.

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82
Q

What is the effect of increasing the distance between the collimator and the detector?

A

Increasing the distance
Increased noise in the image
Decreased image quality

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83
Q

Describe the basic mechanism of PET imaging

A

Positron emitted
Finds nearby electron and annhiliates with it
This creates 2 gamma photons (511kEV) that spreads in opposite directions

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84
Q

What is the energy of the gamma photons in PET imaging?

A

2 x 511keV

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85
Q

What determines spatial resolution in PET? What is the usual resolution?

A

The size of the crystal

3mm

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86
Q

In PET what is a coincidence?

A

The gamma rays hit 2 detectors at the same time

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87
Q

Describe the detector blocks used in PET imaging

A

4x4 array of crystal elements each of dimensions 4mmx4mmx30mm
They are segmented
The cuts in the crystal serve to distribute scintillation light between the 4 square PMTs
PMTs from all crystals

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88
Q

How is the location of the gamma event determined in PET?

A

The interaction crystal is identified by comparing light collected by each PMT as in gamma camera
Can determine which crystal event it occurred in

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89
Q

What determines spatial resolution in PET? What is the usual resolution?

A

The size of the crystal

3mm

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90
Q

In PET what is a coincidence?

A

The gamma rays hit 2 detectors at the same time

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91
Q

In PET how are coincidences determined?

A

There is uncertainty in coincidences due to the resolving time (approx 1ns)
A coincidence window ‘gate’ is set
Take events that occur within a window

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92
Q

In PET how many events are there per s?

A

Roughly 1000s per s

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93
Q

What is the probability of a random coincidence occurring?

A

R = 2 x S1 x S2

This occurs when 2 gates overlap by chance and these need to be accounted for

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94
Q

What is the result of not using attenuation correction?

A

Artefacts

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95
Q

Describe the attenuation in PET

A

Most gamma photons will not leave the body
Most interactions with matter are through Compton scattering
Both gamma rays need to escape to register a coincidence
There is increased attenuation in larger objects and it appears there is an activity reduction
Thinner parts of the body would emit more radiation

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96
Q

What are the advantages of fusing PET with MR?

A

Allows for imaging with less radiation

Combines functional and anatomical information

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97
Q

How are attenuation problems fixed in PET?

A

Attenuation correction using CT
CT measures the attenuation factor
The true count rate measured by the emission scan is divided by the attenuation factor

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98
Q

What is the result of not using attenuation correction?

A

Artefacts

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99
Q

What are the advantages of fusing PET with CT?

A

CT provides anatomical information
PET provides functional information
Can do attenuation correction

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100
Q

What are the advantages of fusing PET with MR?

A

Allows for imaging with less radiation

Combines functional and anatomical information

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101
Q

What are the disadvantages of PET and SPECT?

A
  • Biological hazard, uses ionising radiation
  • Complicated chemistry
  • Need CT and/or MRI (increase in expense and training)
  • Complex physics and inverse mathematical problems
  • Complex logisitcs: radiation decay and protection
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102
Q

What is the concept behind a 2m body PET scanner?

A
Measures all photons at once
Get 40x more photons
Less radiation
Uses short life isotopes
No gaps 
Decrease in time
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103
Q

What is the basic method used for image reconstruction?

A

Back projection
Can be filtered or unfiltered
It projects backwards the data and uses an analytical approach

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104
Q

What are the advantages used in filtered back projection?

A

Fast = approximately 1 minute
Linear
Well-known

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105
Q

What are the disadvantages used in filtered back projection?

A

Low resolution

Streak artefacts

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106
Q

Describe the nuclides used for beta minus decay?

A

Neutron excess nuclides

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107
Q

Why does decay occur?

A

Decay occurs due to an imbalance between protons and neutrons
Unstable nuclides do no not necessarily exist in nature as their decay is rapid

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108
Q

What are the disadvantages of iterative reconstruction?

A

Relatively slow = 10 mins
Stopping criteria can be hard to determine
Get salt and pepper noise

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109
Q

Describe the nuclides used for beta plus decay?

A

Neutron deficient nuclides

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110
Q

Describe the nuclides used for beta minus decay?

A

Neutron excess nuclides

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111
Q

Why does decay occur?

A

Decay occurs due to an imbalance between protons and neutrons
Unstable nuclides do no not necessarily exist in nature as their decay is rapid

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112
Q

How are unstable nuclides produced?

A

Nuclear reactions

Cyclotrons

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113
Q

How is an unstable nuclide created in a nuclear reaction?

A

Add a proton to a stable atom

Proton goes inside the nucleus

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114
Q

Give an example of a nuclear reaction to produce an unstable atom

A

14 N + 1 H –> 11 C + 4 He
7 1 6 2

15 N + 1 H –> 15 O + 1 n
7 1 8 0

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115
Q

How does a cyclotron work?

A

It gives energy to protons by accelerating them
This creates a proton beam which bombards the target to produce PET radionuclides
Particle is confined to a circular path by a magnetic field
Energy increases with each rotation
High energies possible with compact design
Within a vacuum chamber

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116
Q

What is the energy of the proton beam in a cyclotron?

A

15MeV

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117
Q

What are the pros and cons of a shielded room vs. self shielded cyclotron?

A

Shielded room - expensive, easy to access for maintenance and target development

Self-shielded - compact, can work nearby, cheap, but more difficult to access

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118
Q

What is the disadvantage of cyclotrons?

A

Very expensive to run and build

Cost 1-1.5 million

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119
Q

How is the circular motion created in a cyclotron?

A

A charged particle in a magnetic field has a circular motion

The oscillator changes the direction

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120
Q

What is the advantage of the circular design of a cyclotron?

A

Can be more compact than linear

Increase in rotations causes an increase in energy

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121
Q

What are the pros and cons of a shielded room vs. self shielded cyclotron?

A

Shielded room - expensive, easy to access for maintenance and target development

Self-shielded - compact, can work nearby, cheap, but more difficult to access

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122
Q

Give examples of cyclotron produced nuclides

A
Mainly beta + decay:
18F
11C
13N
15O

Mixed decay:
124I
64Cu

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123
Q

What is the branching ratio and half life of: 18F?

A

97% beta +

109.6 minutes

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124
Q

What is the branching ratio and half life of: 11C?

A

99% beta +

20.3 minutes

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125
Q

What is the branching ratio and half life of: 13N?

A

100% beta +

9.96 minutes

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126
Q

What is the benefit of a long half life?

A

You have to isolate the patient :(
Can see longer biological pathways and process
Also allows for repeat scanning from the same radiation does to see a process in stages

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127
Q

Why can multiple types of decay be useful?

A

Can combine radionuclide therapy with imaging

For example if mixed alpha and beta +

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128
Q

What does Emax mean in relation to cyclotron produced nuclides?

A

Maximum energy a positron can have

Different nuclei have different energies

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129
Q

What is the effect of increasing the energy a positron has?

A

Decreases resolution

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130
Q

What is the benefit of a long half life?

A

You have to isolate the patient :(
Can see longer biological pathways and process
Also allows for repeat scanning from the same radiation does to see a process in stages

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131
Q

What occurs in a nuclear reactor?

A
  • Uranium decays and creates neutrons
  • Reaction increases exponentially
  • Target of heavy elements in reactor core
  • Nuclei absorb THERMAL NEUTRONS and undergo FISSION
  • Fission products are neutron rich and decay via beta minus decay
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132
Q

What radionuclides are produced in a nuclear reactor (fission)?

A

131 I
99 Mo
137 Cs
133 Xe

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133
Q

What is the problem with fission?

A

It is unpredictable - it is uncertain how it will split

There are many branches and potential fission biproducts

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134
Q

What is a nuclear generator and how does it work?

A
  • Generators serve as a source of a short lived radionuclides
  • Constructed on a decay-growth relationship
  • Product a daughter nuclide from a parent nuclide (both of which must be distinctly different)
  • Makes SPECT cheaper
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135
Q

Give an example of radionuclides (beta plus decay) that can be created in a generator

A

82Sr -> 82Rb
68Ge -> 68Ga
62Zn -> 62Cu

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136
Q

Describe the decay of 99Mo

A

99Mo –> decays via beta negative decay with a half life of 67 hours to –> 99mTc

99mTc –> decays via gamma decay with a half life of 6 hours to 99Tc

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137
Q

What are the regulations in place for the generation of radionuclides?

A
  • Radiochemistry quality control
  • Good manufacturing practice
  • Manufacturing licence

Meeting all regulations is expensive and hard to set up

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138
Q

How common are generators for beta plus radionuclides?

A

Several PET nuclides can be generator produced but they are not commonly used
Likely to change

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139
Q

Give an example of radionuclides (beta plus decay) that can be created in a generator

A

82Sr -> 82Rb
68Ge -> 68Ga
62Zn -> 62Cu

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140
Q

Describe the formation of a radioactive molecule to be injected into the patient

A

Radionuclide needs to be attached to another molecule
This needs to be done quickly with minimal human interaction
Generate more than you need to allow for the decay
Needs to be made as automatic as possible and needs to be a quick process

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141
Q

What are the regulations in place for the generation of radionuclides?

A
  • Radiochemistry quality control
  • Good manufacturing practice
  • Manufacturing licence

Meeting all regulations is expensive and hard to set up

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142
Q

What does radiopharmaceutical quality control state?

A

Need good reproducibility of these factors:

  • Radiochemical purity
  • Chemical purity
  • pH
  • Sterility
  • Apyrogenicity
  • Very low toxicity
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143
Q

Define radiochemical purity

A

The fraction of a specific radionuclide present in the desired chemical form and in the specified molecular position

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144
Q

What causes radiochemical impurities?

A

Incomplete reactions
Side reactions
Incomplete removal of protecting groups

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145
Q

What are the design considerations for creating a radio-molecular?

A
  • FUNCTION: a platform that meets the radiochemists requirements
  • SAFETY: radiation, remote processing, health and safety regulations
  • QUALITY: reliability, reproducibility, validation
  • FINANCE: funding, manufacturing costs, running costs, resources
  • DELIVERABLES: synthesis yield, synthesis speed, size, simplicity
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146
Q

What are the features of tracer synthesis that needs to be considered?

A
  • Large amounts of radioactivity are needed (need shielding and robotics)
  • Radioactive half life
  • Very small molar quantities
  • High specific activity is usually required
  • Very high radiochemical yield and reliability
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147
Q

Why is it important to ensure chemical purity?

A

Mandatory for tracers to avoid adverse reactions and pharmacological or toxic effects.
Impurities result in poor quality images due to the high background in surrounding tissues

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148
Q

What is outlined by Good Manufacturing Practice with regards to radionuclide creation?

A

Ensures the products are consistently produced and controlled to the quality standards appropriate to their intended use:

  • Personel
  • Premises and equipment
  • Documentation
  • Production
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149
Q

What are the design considerations for creating a radio-molecular?

A
  • FUNCTION: a platform that meets the radiochemists requirements
  • SAFETY: radiation, remote processing, health and safety regulations
  • QUALITY: reliability, reproducibility, validation
  • FINANCE: funding, manufacturing costs, running costs, resources
  • DELIVERABLES: synthesis yield, synthesis speed, size, simplicity
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150
Q

What are the features of tracer synthesis that needs to be considered?

A
  • Large amounts of radioactivity are needed (need shielding and robotics)
  • Radioactive half life
  • Very small molar quantities
  • High specific activity is usually required
  • Very high radiochemical yield and reliability
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151
Q

What are microfluidic devices (MFD)?

A
Reactions take place in very small places
Fully automated syntheses can be conducted 
Very advanced technology 
Used for fast FGD production
40% 18-FDG yield in 10-12 minutes
- 6 mins drying
- 2 minutes radiolabelling
- 2 minutes purification
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152
Q

What are the steps involved in tracer distribution?

A
  1. Fixed site with cyclotron and scanner
  2. Tracer sent to sites with a fixed scanner and no cyclotron
  3. Tracer sent to mobile scanner
  4. Stand alone production facility to support mobile scanners OR fixed sites
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153
Q

What are the benefits and negatives of mobile PET scanners?

A

Very complicated procedure to control
Planes can be used to transport FDG
Allows for PET scanning in remote areas

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154
Q

Describe the kinetic rates of FDG

A

Measure the change of radioactivity over time to calculate kinetic parameters

Transport and phosphorylation of de-oxy glucose differs only a term from glucose *.

This is termed the lump constant (0.89)

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155
Q

What is FDG?

A

Fluoro-deoxy glucose

Deoxyglucose is an analogue of glucose with H replaced by OH
Deoxyglucose is then labelled with 18F.
It cannot be isomerised to fructose-6-phosphate and metabolised further and is trapped in mitochondria

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156
Q

What is the decay time of 18FDG?

A

2 hours

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157
Q

What happens to FDG in tissue?

A

It is trapped within the cells.
This is at a rate proportional to glucolysis.
Tracer amount accumulates and get a higher intensity signal.

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158
Q

Describe the kinetic rates of FDG

A

Measure the change of radioactivity over time to calculate kinetic parameters

Transport and phosphorylation of de-oxy glucose differs only a term from glucose *.

This is termed the lump constant (0.89)

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159
Q

What are the 3 possible scanning protocols in PET?

A

Static: Inject, wait, scan an area
Whole body: Inject, wait, scan in sections by moving the bed
Dynamic: Inject then scan in sections

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160
Q

What is the normal scanning protocols for using FDG?

A

Inject and leave for 1 hour
Scan for 20 minutes
This allows FDG time to accumulate

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161
Q

Why are shallow breathing protocols used in CT?

A

1-3cm variation with breathing
Large discrepancy in liver and lungs
Can create a strong artefact in PET (due to attenuation correction)

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162
Q

How is a whole body SPECT or PET generated?

A

7-8 bed movements with approximately 3 minutes at each

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163
Q

What are the new advances in PET/CT?

A

Multiple passes per bed position
Possible continuous bed motion
Respiratory motion correction (track motion mathematically or externally)

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164
Q

How is a CT scan acquired in a PET-CT?

A
  • First have a scout scan to determine body position
  • CT at lower dose than diagnostic CT and is used for localisation. Can do full dose if you require the CT
  • Used for CT attenuation correction
  • Normally without contrast agents
  • Normally with shallow breathing protocols
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165
Q

Why are shallow breathing protocols used in CT?

A

1-3cm variation with breathing
Large discrepancy in liver and lungs
Can create a strong artefact in PET (due to attenuation correction)

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166
Q

What methods are used to standardise SUV?

A

Lean body mass
Geometric body surface area
Ideal body weight
18FDG body surface area

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167
Q

What are the new advances in PET/CT?

A

Multiple passes per bed position
Possible continuous bed motion
Respiratory motion correction (track motion mathematically or externally)

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168
Q

How do you calculate a SUV?

A

Standardised Uptake Value

SUV = tissue concentration (MBq/ml) /
Injected dose (MBq) / Body weight in kg

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169
Q

What is SUV?

A

Standardised uptake value
- Standardised way of comparing different patients
- Changes day to day, scan to scan, hard to tell accuracy
It doesnt include an error estimate

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170
Q

What methods are used to standardise SUV?

A

Lean body mass
Geometric body surface area
Ideal body weight
18FDG body surface area

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171
Q

What is SUV max?

A

Maximum SUV value in a region

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172
Q

What is SUV mean?

A

Average SUV in a region

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173
Q

What are the difficulties with defining the region of a tumour?

A
  1. Manual deliniation (variations between individuals)
  2. Automatic thresholding (e.g. include all voxels 40% SUVmax)
  3. 3D imaging can be time consuming to delineate

SUV max is commonly used

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174
Q

What are the disadvantages of using SUV?

A

Rough description of tracer kinetics
Limits on testing drug efficacy
Doesnt fully exploit characteristics of different tracers
Semi-quantitative
Only works for tracers of flux (e.g. FDG) where uptake is not too influenced by perfusion

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175
Q

What is the advantages of dynamic PET imaging?

A

Offers a more complete framework of analysiss
Tracks tracer over time and use this for SUV
Can do kinetic modelling to determine the chemistry of the biological process
Can do volumetric chemistry over time
Parametric imaging
Has units - not an arbritary number

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176
Q

What is required for dynamic pet imaging?

A

Need to measure radioactivity in plasma
Need multiple snap shots
Need to know how fast the process is (number of counts per s)

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177
Q

What radionuclides are used in bone imaging?

A

99m-Tc- diphosphonates
Organic phosphate compounds

MDP = methylene diphosphonates
HDP = hydroxyl-methylene diphosphonates

Can choose which

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178
Q

In terms of bone imaging what does tracer uptake depend on?

A

Blood flow - lesion must have blood flow
Activity of osteoblasts - bone turnover
Local Ca2+/PO4 2-

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179
Q

What the indications for bone imaging?

A
Suspected metastases
Radiographic lesion
Persistent pain with normal radiograph
Acute symptoms
Assessment of joint disease
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180
Q

What legislations must be met for NM imaging?

A

IRMER
ARSAC
Local rules
Quality control

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181
Q

What radionuclides are used in bone imaging?

A

99m-Tc- diphosphonates
Organic phosphate compounds

MDP = methylene diphosphonates
HDP = hydroxyl-methylene diphosphonates

Can choose which

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182
Q

In terms of bone imaging what does tracer uptake depend on?

A

Blood flow - lesion must have blood flow
Activity of osteoblasts - bone turnover
Local Ca2+/PO4 2-

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183
Q

What the indications for bone imaging?

A
Suspected metastases
Radiographic lesion
Persistent pain with normal radiograph
Acute symptoms
Assessment of joint disease
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184
Q

What is the protocol used for bone imaging?

A

20-25 minutes in the scanner
Wait 2-4 hours after injection
Need to wait as a low percentage of cardiac output to the bone
Allows time for tracer to collect in bones
Children have active growth rates and therefore there are increased tracer at plates

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185
Q

What are the radionuclides used in lung imaging?

A

99mTc- MAA (macroaggregated albumin) for perfusion

99mTc- technegas for ventilation

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186
Q

How is 99mTc-MAA administered?

A

Used for lung perfusion
It is injected
Particles 10-30um in size, blocks 0.1-0.3% of pre-capillary arteries

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187
Q

How is 99mTc-technegas administered?

A

Used for lung ventilation
It is inhaled
Particles 0.1-0.5um in size and are deposited on bronchoalveolar cell lining

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188
Q

What are the indications for lung imaging?

A

Suspected PE
Relative lung function
Suspected right to left shunts

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189
Q

What are the reasons for VQ imaging over CT?

A

When CT can’t be done:
Allergic to contrast
Renal failure (from contrast)
Pregnancy

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190
Q

What is the process for determining renal function using imaging?

A
Draw ROI over organ
See how radioactivity decays in the area
Plot time activity curve
Done with diuretic 
Can determine: shape, morphology, function and split function (%R&%L)
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191
Q

What is 99mTc-MAG3 used for?

A

Renal imaging
Used for dynamic renal function and drainage
It is cleared by tubular secretion
Can see drainage and whether there is an obstruction

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192
Q

What is 99mTc-DMSA used for?

A

Used for static renal function

Localises to the cortex (proximal tubular cells)

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193
Q

What are the indications of renal imaging?

A

MAG3: dilated collecting system or obstruction

DMSA: relative renal function and scarring

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194
Q

What is the process for determining renal function using imaging?

A
Draw ROI over organ
See how radioactivity decays in the area
Plot time activity curve
Done with diuretic 
Can determine: shape, morphology, function and split function (RvL)
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195
Q

What are the radionuclides used in cardiac imaging?

A

99mTc-pertechnetate

99mTc-tetrofosmin (sestamibi)

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196
Q

What is 99m-Tc pertechnetate used for?

A

Cardiac image
Tracer stays in blood
Can be used to look for LV ejection fraction
Reserved only for patients on chemotherapy that is cardiotoxic.
Very producible and not user dependent

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197
Q

How does 99mTc- sestamibi work (tetrofosmin)?

A

Tracer is taken up where there is a high concentration of mitochondria
Lipophilic cation which diffuses across the cell membrane and localises in mitochondria

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198
Q

What is the use of 99Tc- sestamibi and what are its indications for use?

A

Measures myocardial perfusion at rest and at stress

Indications: IHD, function significance of known CAD, risk stratification

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199
Q

What radionuclide is used for heptaobiliary imaging?

A

99mTc- HIDA

200
Q

What is 99mTc HIDA used for?

A

Hepatobiliary imaging
It shows the formation, excretion and drainage of bile,
It is a bile salt analogue and it allows you to calculate a GB ejection fraction under stress (meal)

201
Q

What the indications for hepatobiliary imaging using 99mTc-HIDA?

A

Biliary dyskinesia
Sphincter of Oddi dysfunction
Biliary atresia or biliary leaks

202
Q

What radionuclide is used for gastric imaging?

A

99m-Tc labelled solid component meal

Give the patient a standard meal - need to be aware of the effect of other drugs on stomach emptying

203
Q

What is the purpose of gastric imaging?

A

Allows the study of the rate of gastric emptying

204
Q

What radionuclides are used in thyroid imaging?

A
Benign = 99mTc-pertechnetate
Cancer = 123I and 131I
205
Q

How does 99mTc-pertechnetate work in thyroid imaging and what are the indications/

A

It is trapped by the thyroid in follicular cells. It measures uptake.
Indications: demonstration of functioning thyroid tissue and investigation of thyrotoxicosis

206
Q

What radionuclides are used when imaging thyroid cancer and how do they work?

A

123I and 131I
It relies on trapping and organification
123I is used for imaging
131I is used for imaging and therapy

207
Q

What are the indications for thyroid imaging using I?

A

Treatment - complete ablation with high dose radiation (GBq) of 131I

Imaging residual disease and metastases (MBq) doses with either 123 or 131

Need to remove all thyroid cells to allow for more effective recurrance detection

208
Q

What radionuclide is used in lymphatic imaging?

A

99mTc labelled nanocolloid

209
Q

How is lymphatic imaging done?

A

99mTcc labelled nanocolloid is injected either intradermally or subcutaneously.
Intradermal is quicker as there is a greater lymphatic network.
Nuclide then cleared by lymphatic channels.

210
Q

What are the indications for lymphatic imaging

A

Sentinel node imaging in cancer

lymphoedema

211
Q

What radionuclide is used in brain imaging?

A

99mTc-HMPAO - cerebral perfusion

123I - ioflupane = dopaminergic pathways

212
Q

What is 99mTc-HMPAO used for?

A

Brain imaging
Used to measure cerebral perfusion
Need to by hydrophilic to cross the BBB

213
Q

What are the indications for brain imaging using 99mTc-HMPAO?

A

Cognitive impairment
Dementia image - diagnosis
Epilepst
Stroke imaging

Moving towards PET

214
Q

What radionuclide would you use to image dopaminergic pathways in the brain? What are the indications

A

123I -ioflupane (DaTSCAN)
The uptake depends on selective binding to pre-synaptic dopamine receptors
Indications: investigation of suspected Parkinsons (90% accurate)

215
Q

What radionuclide is used for oncological imaging?

A

18F-FDG

Glucose analogue labelled with positron emitting isotope

216
Q

What are the main applications of SPECT imaging?

A

Brain
Heart
Musuloskeletal
Endocrine

217
Q

What are the physical limitations of SPECT?

A

Scatter
Attenuation
Partial volume effects

218
Q

Describe an original SPECT/CT system?

A

15 years ago
Rudimetary CT using xray tube
Low quality CT - used for localisation not characterisation

219
Q

Describe a new generation SPECT/CT scanner

A

Latest multidetector CT technology - diagnostic CT, 64 detector rows
Allows for more accurate localisation and characterisation
Advanced gamma camera and CT = facilitates low dose imaging and faster data acquisition
Iterative reconstruction (lower dose or speed up)
Mulit-modality work station and additional PACS software required

220
Q

How can SPECT/CT improve clinical utility of nuclear medicine examinations?

A
  1. Providing more accurate localisation
  2. Detecting additional lesions
  3. Excluding physiological tracer uptake
  4. Charactering equivocal anatomical lesions
  5. Providing reliable CT based attenuation correction
  6. Facilitating one stop shop imaging
  7. Reducing the need for multi-layered testing
221
Q

What are the consequences of specificity and sensitivity with using SPECT/CT>?

A

Increase specificity = increased localisation
Increased sensitivity = increased lesions detected

The increase in specificity is greater than sensitivity

222
Q

What are the clinical applications of SPECT/CT?

A
Bone imaging
Neuroendocrine tumour imaging
Parathyroid imaging
Thyroid imaging
Hepatobiliary imaging
RBC imaging
Infection/inflammation imaging
223
Q

In SPECT/CT how long does each component take?

A
SPECT = approx 10 mins
CT = seconds
224
Q

What is a blood pool image?

A

Initial phase = tracer is in the blood and it is mainly used for looking at soft tissue uptake e.g. hyperaemia

225
Q

What is a dual phase scan?

A

Scans at an initial and delayed phase - common in bone scans.

226
Q

What is the protocol for suspected scaphoid fracture?

A

No clear guidance.
After X ray, MR recommended but there are problems with availability
If a bone scan is negative - 99% confident no fracture
It can miss if done in elderly or within 24 hours

227
Q

When in bone imaging is SPECT/CT suggested?

A

When it affects the axial skeleton or proximal long bones as plain X-ray is poor here
It is also good for pathology of the ankle
When there is metal work (new CT have minimal artefacts)

228
Q

What are neuroendocrine tumours?

A

Diverse group of rare neoplasms accounting for 2% of all cancers.

229
Q

What are the 3 subtypes of neuroendocrine tumours?

A
  1. Neural crest origin - phaechromocytoma, paraganglionoma, neuroblastoma
  2. Meduallry thyroid cancer (MTC) - rare and complex to image
  3. Gastroenteropancreatic (GEP) tumours - carcinoid and endocrine pancreatic tumours (EPTs) they are hormonally active and hard to diagnose
230
Q

How are neuroendocrine tumours imaged?

A

They express somatostatin receptors (SSR) subtypes 2 and 5
Imaged with SSR analogues e.g. 111-Indium labelled pentreotide (octreoscan)
Must use SPECT/CT

Neural crest tumours are imaged with guanethidine analogues e.g. 123Iodine-mIBG

231
Q

What is the protocol for thyroid cancer imaging?

A

Done after resection and ablation
Allows more effective monitoring of thyroiglobulin
131-I kills all thyroid cells
Image 3 days after administration due to very high radiation levels
Can pick up any metastases

232
Q

What radionuclide is used in parathyroid imaging?

A

99mTc- sestamibi

233
Q

What is the purpose of parathyroid imaging?

A

Used for primary parathyroid cancers
Allows for more specific localisation of adenoma to have minimally invasive surgery
Parathyroid holds onto radiation longer than thyroid which washes out

234
Q

What are the reasons for doing sentinel node imaging?

A

It is the first draining node of an area

  • well esablished in breast cancer and adenoma
  • prevents resecting multiple lymph nodes
  • prevents long term morbidity
235
Q

How is WBC imaging done?

A

Label the patients own WBCs and inject back into the patient

Useful in infection and inflammation

236
Q

Why is RBC imaging used?

A

Used for GI blood loss
Can find source of bleeding
Can find smaller bleeding rates than CT angiography

(High uptake in spleen due to sequestering)

237
Q

In PET/CT what are the variables that can be changed in CT?

A
  • Can acquire diagnostic level CT
  • If not required can have low dose CT
  • Non-contrast
  • Shallow breathing protocol
238
Q

In PET/CT what are the variables that can be changed in PET?

A
  • Number of bed positions (7-8)
  • Time per bed position (2-5 mins)
  • Movement artefact (increases with scan time)
  • Dual time point
  • Decrease dose and increase scan time or VV
239
Q

What are the common PET radioisotopes?

A

18F
11C
13N
15O

240
Q

Describe PET tracers

A

Different tracers for different purposes
Location of cyclotron limits what procedures you can do
Most produced in cyclotron
Short half life
Measures physiological processes e.g. glucose metabolism, blood flow, hypoxia, proliferation etc

241
Q

What is the most common PET tracer?

A

FDG - most cancers demonstrate an increased glucose uptake

Cancers upregulate GLUT1 receptors

242
Q

What is the Warberg effect?

A

Most cancers demonstrate an increased glucose uptake

Cancers upregulate GLUT1 receptors

243
Q

What is the basics behind PET imaging?

A

Administer tracer (positron emitting)
Positron annihilates with electron
This produces 2x511keV gamma photons
Use coindence to detect locations

244
Q

What are the features of FDG?

A

It competes with glucose for transport and into cancer cells

It becomes phosphorylated and trapped within the mitochondria

245
Q

What are the benefits of PET/CT?

A
  • Combines functional and anatomical info
  • More accurate localisation
  • Better detection
  • Increased sensitivity and specificity
  • has significant impact on patient management
  • Able to see disease not on normal CT
  • Fused data sets increase correct imaging reading
246
Q

Where is PET/CT commonly used?

A
Lung
Colorectal
Lymphoma
Head and Neck
Oesophageal
247
Q

What is the networking strategy?

A

Aim to have 1 PET/CT scanner per 1.5 million population
Funded by the department of health
National program
Spread throughout country

248
Q

What is the cost of an average PET/CT scan compared to just CT?

A
PET/CT = = £1000
CT = £150
249
Q

What are the most common PET/CT uses?

A
47% lung
16% lymphoma
10% oesophagus
8% colorectal
6% head and neck
250
Q

What are the established uses of 18F-FDG PET/CT in oncology?

A
Lung
Lymphoma
Head and Neck
Oesophagus
Colorectal
Melanoma
Breast
Thyroid
Cervical
Heptaobiliary 
Unknown primary malignancy
251
Q

What are the emerging uses of 18F-FDG PET/CT in oncology

A

Neuroendocrine tumours
Brain tumours
Bone and soft tissue sarcomas

252
Q

What are the 7 steps in the role of FDG PET/CT in oncology?

A
  1. Characterisation
  2. Staging
  3. Re-staging
  4. Response assessment
  5. Recurrence detection
  6. Radiotherapy planning
  7. One stop shop imaging
253
Q

What is characterisation in relation to pet/ct?

A

It is determining the nature of lesions detected on imaging

hard to tell if a mass is malignant or benign without pet/ct

254
Q

What is staging and how is it done with pet/ct

A

It is determinig the extent of disease

PET/CT increases the sensitivity and specificity
Can guide appropriate treatment
Can change the risk profile of nodules/findings
Can detect multiple sites which a CT can miss

255
Q

What is restaging and how is it done with pet/ct

A

Determining the extent of disease (again) after treatment to determine efficacy

Can pick up sites miseed on ct
lymphoma not normally seen on ct

256
Q

What is response assessment using pet/ct

A

Checks if a treatment has worked and this is a rapidly growing area

Guides treatment decisions - tailored therapy
- Can change therapy, stop chemo, track effectiveness, change midway if prognosis poor

PET/CT FDG shows changes before anatomical changes

Can predict overall response and disease free survival

Can determine end of treatment response: Can’t tell residual disease vs fibrosis with just ct

257
Q

What is recurrence detection and how is done using pet/Ct

A

Differentiating fibrosis from recurring disease

Can tell with multiple CT scans over time but not with just one CT.

Adds metabolic activity

Can pick up occult disease missed on anatomical imaging

258
Q

What does radiotherapy planning using pet/ct involve?

A

It allows for a more targeted therapy - to get higher doses to smaller areas

Outline the::
GTV - gross tumour volume
CTV - clinical target volume
PTV - planning target volume
TV - treated volume
IV - irradiated volume

Increases accuracy. It decreases toxicity by decreasing the area

259
Q

What are the newer applications for 18F-FDG PET/CT

A

Infections
Inflammation
Cardiology
Neurology

260
Q

What are the new applications in PET/CT not using FDG?

A

Oncology (choline)
Cardiology (rubidium)
Neurology (amyloid plaques)

261
Q

What is 18F used for?

A

Waste product of FDG
Marker of osteoblastic activty
Good for imaging bone mets
PET has better resolution than SPECT

262
Q

What is 18F-Choline used for?

A

Marker of membrane synthesis
Useful in prostate cancer
Prostate is not very metabolically active so has limited glucose uptake - can be picked up with choline
Can also be used for occult node involvement and bone mets
Can image the process you are targeting

263
Q

What non fdg radionuclides are used in PET oncology?

A

68Ga-DOTA-ocreotate
Used in neuroendocrine tumour receptor imaging
Can use 111 Indium octeotide

264
Q

How is infection and inflammation imaged using PET?

A

FDG uptake is non-specific and is increased in infection and inflammation - can’t distinguish from cancer
Needs confirming with tissue samples

  • Can measure baseline and treatment response
  • Can be used to image large vessel vasculitis as this can’t be seen on CT
  • Can be used to find pyrexia of unknown origin e.g. aortic graft rejection
  • Can be used for sarcoidosis (uncommon as benign)
265
Q

What radionuclides are used in cardiology PET?

A

Oxygen - research
nitrogen - research
rubidium
FDG

266
Q

What are the uses of cardiology PET?

A

Myocardial perfusion and myocardial viability

PET perfusion = rubidium
SPECT perfusion = 99mTc

PET viability = FDG

267
Q

What are the uses of neurology PET?

A

FDG

  • Epilepsy - hypometabolism
  • Dementia
  • Neuro-oncology

Non FDG
- amyloid plaque imaging in Alzheimers

268
Q

How is dementia imaging done in PET?

A

Image if the causes is unknown
Assessed metabolic activity in the brain - hypometabolism

Aims to detect patients early e.g. pre-symptomatic and use therapies to delay onset

Can pick amyloid deposition

Can pick up whether they are 11C - PIB positive or negative. 82% of those who are positive go on to get Alzheimers

Amyvid can assess amyloid plaques but it very expensive

269
Q

What are the technical difficulties of PET/MR?

A
MRI doesnt give density map
MR needs attenuation correction
Scan times are longer
Decreased quality of MR to shorten time
Can have artefacts in mR
very expensive
270
Q

What are the clinical applications of PET/MR?

A
Paediatrics
Oncology
Gynae imaging
Multiparametric assessment
Neurology
Cardiology
271
Q

What is the definition of molecular imaging?

A

Measuring/locating a molecular process or gene expression
It does not image anatomy or structure
it does not image function processes like perfusion

272
Q

What imaging techniques are best for molecular imaging?

A

PET

Optical

273
Q

What is optical imaing?

A

Used in preclinical research and detects light rather than gamma rays
Useful for molecular imaging

274
Q

What are the different types of ionising radiation??

A
beta +
beta - 
alpha
gamma
X-ray
275
Q

What ionising radiation does PET imaging use?

A

Beta + (positron)

2 gamma rays

276
Q

What ionising radiation does SPECT imaging use?

A

Gamma

277
Q

What ionising radiaition foes radionuclide therapy use?

A

beta minus and alpha

278
Q

What are the key attributes to radionuclide imaging (PET and SPECT)?

A
  1. Tracer quantities are pico or nano molar (much lower than CT and MR)
  2. Should not ellicit physiological response
  3. Low risk of toxicity
  4. Radiation risks should be calcuable (radiation purely from tracer)
  5. Rapidly translated to clinical studyy
  6. Quantitative
  7. Non- invasive
  8. Whole body
  9. Molecular rather than anatomical
279
Q

What are the advantages of pet over spect?

A

Pet has better resolution (5-10mm)
Pet has better sensitivity
Pet has better quantification of images
Uses lower levels of radiation as it does not need to over Collimators

280
Q

What are the advantages of spect over pet?

A

Spect is cheaper
It is more widely available
Multitracer imaging is possible
Improving performance imaging

281
Q

What is the principle behind radionuclide therapy?

A

It turns toxicity to your advantage.
It is the selective delivery of radiation to the tumour using the same principles as imaging
Uses beta or alpha emission
Low penetration and therefore create a high local dose and kills the cells

282
Q

Give examples of radionuclide therapy

A

Thyroid cancer 131- I
Bone metastasis 188-Re or 153-Sm or 233-radium (alpha)
Lymphoma
Neuroblastoma

283
Q

What are the 7 steps involved in creating a new radionuclide?

A
  1. Find a molecular target
  2. Consider chemistry - attach radionuclide to particle
  3. Consider molecular biology/cell biology
  4. Small animal models
  5. Imaging
  6. Computer modelling
  7. Clinical imaging

Repeat 1-6 until suitable for clinical

284
Q

Give examples of molecular targets

A

Sodium iodide symporter (iodine or pertechnetate)
Tumour specific antigen
Neuropeptide receptor (somatostatin or calcitonin)
Glucose transporter (FDG)
Amino acid transporter (f18 tyrosine)
Angiogenesis (rgd peptides)
Transferrin receptor (Ga 67)

285
Q

What are the uses for molecular imaging?

A
Clinical diagnosis and decision making
Location and detection of disease 
Molecular characterisation of disease
Bio markers to predict or measure therapy outcome
Drug development tool
Basic biomedical research 
Therapy
286
Q

What are the advantages of using radioactivity for imaging?

A

Tissue penetration is greater than light
Increased sensitivity
Risk generally very small - risk of not scanning greater

287
Q

What are the disadvantages of using radioactivity for imaging?

A
Increased radiation dose
Cost of radioisotopes and technology
Development is expensive 
Avoid in children and pregnant women
Needs to be avoided if unnecessary
288
Q

How is the thyroid imaged using molecular imaging?

A

Human sodium iodine symporter hNIS is imaged
It is essential for thyroid function (production of thyroid hormone) and is over active or under active in some cancers
Useful for staging and shows loss of thyroid and any metastatic spread

289
Q

Where is hNIS present?

A

Thyroid
Stomach
Mammary glands

290
Q

What are the substrates used to image hNIS?

A
123 I iodide. Spect
131 I iodide. Therapy
124 I iodide. Pet
Perchlorate (competitive inhibitor) 
99m Tc pertechnetate. Spect
F18 tetrafluoroborate. Pet
291
Q

What do all hNIS substrates have in common?

A

They all have a single negative charge
Very similar size
Body can’t differentiate molecules

I-, At-, TcO4-, BF4-

292
Q

What can FDG and glucose metabolism be used to detect?

A

High metabolism and replication
Low oxygen
Anaerobic metabolism
Increased glucose consumption

293
Q

What happens in tissues that have increased glucose uptake?

A

Increased glycolysis requires increased glucose
Glut1 expression is increased
Glut1 is translocated to cell membrane
Hexokinase is increased

294
Q

What happens to FDG in the cells?

A

It is an analogue of glucose and is a substrate for glut1 and hexokinase
It enters the cell and is phosphorylated by hexokinase to FDG-6P
It cannot be broken down further and is trapped with in the cell

295
Q

Why are somatostatin receptors imaged?

A

It is a hormone that regulates the endocrine system and is involved in neuro transmission and cell proliferation

It is switched on in neuroendocrine tumours and is not strongly expressed in adults

Target for therapy and imaging

296
Q

How are somatostatin receptors imaged?

A

Using 68Ga octreotide - it has the same binding area as somatostatin.
Somatostatin is very unstable and breaks down rapidly.
Octreotide has a DOTA chelate which makes it more stable.
It is broken down slower

297
Q

What is the principle behind hypoxia imaging?

A

It is an oxygen deficiency that causes changes in cell biology.
These changes can be detected using molecular imaging.
Hypoxia cells have increased free electrons and this breaks down the molecule.
This causes an accumulation of copper/radionuclide in the cell and causes the copper to dissociate from the molecule

298
Q

Why is hypoxia imaging useful?

A

Hypoxia can cause resistance to radiotherapy and chemotherapy.
It is also an indicator that a tumour is more aggressive.
It can also be used in IHD and stroke

299
Q

What is the pet imaging agent used in hypoxia?

A

Cu-ATAM

18F-FMISO

300
Q

What is the spect imaging agent used for hypoxia imaging?

A

99m Tc HL91

301
Q

What is angiogenesis and what is it associated with?

A
It is the formation of new blood vessels and is associated with:
Tumour growth
Wound healing 
Tissue remodelling
Inflammation
302
Q

What is metastasis?

A

It is when cancer cells are transported by the circulatory system to distant sites. It requires angiogenesis.
Cancerous tumour cells release molecules that send signals to surrounding tissue and this activates certain genes that encourage blood vessel growth.

303
Q

When does angiogenesis occur in normal development?

A

Vasculogenesis - creates the primary network of vascular endothelial cells that will become the major blood vessels

Angiogenesis - remodels the network into the new small vessels that complete the system

304
Q

When is angiogenesis normal in adults?

A

Menstrual cycle

Necessary for repair and regeneration of tissue during would healing

305
Q

What contributes to rare cell division?

A

Inhibitors are high

Activators are low

306
Q

What contributes to frequent cell division?

A

Inhibitors low

Activators high

307
Q

What are the molecular targets for imaging angiogenesis?

A

Integrins alphav beta3 - they are present on the surface of endothelial cells. They bind matrix macromolecules and proteinase a

VEGF- affects permeability

Ang 1 and ang 2 - stabilises the vessels

Plasminogen activators

308
Q

What radionuclide is used to image angiogenesis, what does high uptake indicate?

A

18F-galacto-RGD

Binds to avb3 integrins
Very high in angiogenic tumours - sign of an aggressive tumour

309
Q

How does multidrug resistance occur in chemotherapy?

A

Cells have machinery to export potentially toxic substances
Example: MDR1 gene product, this is found in bbb, liver and tumour cells.
This is a problem for chemotherapy
Increased expression of MDR1 can lead to increasing amount of drugs being exported out of the cell

310
Q

Describe the function of MDR1/ PgP

A

It recognises a wide range of molecules, especially lipophilic cations.
It is located in the cell membrane and the presence can be induced by hypoxia and chemotherapy.
It captures the drug inside the cell and transports it out
Imaging this can be used to measure quantity and make decisions about chemotherapy

311
Q

How do you image PgP?

A

Label with 99mTc or 64Cu
Measure uptake - it is trapped in mitochondria
Then measure clearance - clearance is faster with PgP, this requires dynamic sampling
Can repeat the scan after injection of a PgP inhibitor to check (verapamil)

312
Q

What is transferrin?

A

It transports iron in the blood to deliver it to cells

313
Q

How are transferrin receptors imaged?

A

Ga3+ binds to transferrin and it mimics iron due to its similar size and charge.
Inject 67 or 68 Ga and it binds to transferrin and receptors

314
Q

Why is imaging transferrin receptors useful?

A

Transferrin receptors are over expressed in lymphoma and prostate cancer.
The Ga is internalised and it shows cells with increased iron requirement
Increased fe in melanoma

315
Q

What is the normal distribution of gallium in the body when administered?

A

It is where lactoferrin is present: milk, saliva, tears and nasal secretions.
Also high in liver as this is where radio metals are metabolised

316
Q

What are the usual nonmetallic PET tracers?

A

15O
13N
11C
18F

317
Q

What are the usual metallic PET tracers?

A

64Cu
86Y
89Zr
94mTc

318
Q

What is the half life of 64Cu?

A

12.7 hours

319
Q

What is the half life of 86Y?

A

14.7 hours

320
Q

What is the half life of 89Zr?

A

78hours

321
Q

What are the features of metallic tracers used in pET?

A
Long half life (days-hours)
Produced via cyclotron or generator
Have redox chemistry 
Bio metal mimics
Label large molecules, not small
322
Q

What are the features of nonmetallic pet tracers?

A
Short half life (mins to hours)
Produced in cyclotron
No redox chemistry
Label small molecules
Can label large molecules but they have very short half life
323
Q

What does it mean when a tracer has redox chemistry?

A

Metallic elements have a very rich redox chemistry
This is the addition or removal of electrons
They have several states available

324
Q

What are the advantages or disadvantages of tracers having redox chemistry?

A

Advantage: used in hypoxia imaging using copper
Disadvantages: problems with stability

325
Q

What are the disadvantages of metallic tracers?

A
  • Higher energy particle bombardment, but several are still in the cyclotron range
  • labelling is simpler but the processing is more complex
  • inorganic - it is not easily used with small organic molecules and the uses reflect this
  • needs a chelator to increase stability
326
Q

What are the uses of metallic tracers?

A
Peptides
Antibodies
Nano particles
Processes that needs a long half life 
Biological and radiological half life need to be matched
327
Q

What is a bio metal mimic?

A

It can be used to look at where the metal goes normally

328
Q

What is the chelate effect?

A

When 1 ligand is bound it increases the probability of the 2nd and 3rd binding etc.
this increases the stability constant
It requires specific geometry and needs to be designed

329
Q

Describe metal ligand bonding

A

It is not a one way reaction
It is in equilibrium
Increasing the stability constant decreases the likelihood of being broken down

330
Q

What are the problems with chelators?

A

It causes a significant modification of molecule
Increases the size
If it was a small molecule the change will be significant and it will no longer behave as the original
If the molecule is large e.g. Antibodies, the change is insignificant

331
Q

What are the requirements for a radio metal PET imaging agent?

A
  1. Half life needs to be matched to biological half life
  2. Chelator is required to increase stability (need to be specifically designed)
  3. Emission properties - beta plus range, beta plus emission dose
  4. Effect of labelling and or chelating - on bio distribution or pharmokinetics
  5. Specific activity - increased specific activity is increased radioactivity per gram
332
Q

What are the applications of using radio metals in pet imaging?

A
Mimicking bio metals
82Rb mimics K+ (myocardial imaging)
52Fe to see iron metabolism
64Cu to see Copper metabolism
83Sr to see bone metabolism (calcium analogue)
333
Q

What are the important features and uses of 82Rb?

A

Rubidium 82 is injected as an atom
It is produced from a Sr generator (half life of 25 days)
It is used in myocardial perfusion and it identifies regions of poor blood flow
Half life -76s
It is a potassium analogue and can be used to image Na/K pump

334
Q

What are the important features and uses of 64Cu?

A

It uses oxidation and reduction states of copper
Half life - 13hours
Small cation +1 or 2

335
Q

What is the chemistry of 68Ga?

A
Used for SSR imaging 
Hard small cation
\+3 charge
Similar to iron
No redox 
Binding to Ligands is weak
336
Q

Why can chelators be a problem?

A

Change the shape and stop working
Hard to design
Expensive to develop
Can involve heating which can damage the molecule e.g. Antibodies

337
Q

What is the chemistry of 89Zr?

A
Long half life 78hours
Suitable for imaging antibodies
Zr 4+
Binds readily to oxygen
It is very selective
Binds to prostate cancers
338
Q

How can radionuclides be used as a therapy?

A

Beta emitters with a long half life can be delivered to the area
Drug loaded nano particles can deliver chemo drugs to a specific area via receptors
If beta and gamma can image and treat at the same time

339
Q

What are the advantages of using radio metals in pet imaging?

A

Generator availability
Longer half life for transportation
Longer half life to image longer biological processes
Specific metabolic and chemical properties
Linked with therapeutic analogues

340
Q

What are the advantages of molecular imaging?

A

Non invasive
Real time
In living tissues and cells
Allows you to study in the natural environment

341
Q

Why are animals used in preclinical imaging?

A

It is transferable to humans

Saves a lot of lives

342
Q

What are the steps involved to producing a new imaging technique?

A
  1. Select biochemical process
  2. Find a molecular target
  3. Choose imaging modality
  4. Chemistry
  5. Labelling
  6. Molecular/cell biology
  7. Small Animal models
  8. Large animal models
  9. Imaging
  10. Computer modelling
  11. Clinical imaging
343
Q

What are the features to consider when choosing the modality for preclinical imaging?

A
Spatial resolution
Sensitivity
Whether it is dynamic
Whole body or region
Temporal resolution required
Penetration depth
Quantitative
Can repeat studies be done
Is it clinically relevant
344
Q

What are the features of CT?

A
Excellent spatial resolution
Poor sensitivity
Not dynamic
Whole body or region
Ok temporal resolution
Limitless depth of penetration 
Quantitative
Can repeat but dose
High clinical relevance
345
Q

What are the features of MR?

A
Excellent spatial resolution
Very poor sensitivity 
Not dynamic
Whole body or region
Poor temporal resolution
Limitless depth of penetration
Semi quantitative 
Can repeat
High clinical relevance
346
Q

What are the features of a PET scan? Preclinical

A
Lowest spatial resolution
Highest sensitivity
Dynamic
Whole body or region 
Very good temporal resolution 
Limitless depth of penetration
Fully quantitative 
Repeats but dose
High clinical relevance
347
Q

What are the features of a spect scan? Preclinical

A
Low spatial resolution 
Good sensitivity 
Dynamic
Whole body and region
Very good temporal resolution
Limitless depth of penetration 
Quantitative
Repeat but dose
High clinical relevance
348
Q

What staff are involved in the development of preclinical imaging techniques?

A

MDT
Radiochemist, chemist, molecular biologist, geneticist, cell biologist, immunologist, animal model expert, medical physicist, clinician

349
Q

What is the normal development time for a preclinical imaging technique?

A

Between 12 weeks and 3 years

350
Q

What are the steps involved in producing new preclinical imaging technique?

A
Target or ligand discovery
DNA cloning
Expression system
Protein production
Imaging agent development
In vitriol studies
Preclinical imaging
351
Q

What are the pros and cons of cone beam ct?

A

Faster
More expensive so not used preclinically
Image quality limited due to noise
HU less accurate

352
Q

What corrections need to be done in preclinical ct?

A
Offset
Gain
Bad pixel
Geometrical calibration
HU
Beam hardening
353
Q

In spect how many photons make it through the Collimators?

A

1 in 1000

354
Q

What is different about preclinical spect?

A

Uses pin hole Collimator

Increase resolution

355
Q

What is a pin hole collimator?

A
It either magnifies or shrinks the image
It flips the image upside down 
Has much smaller field of view 
6x the resolution
Better sensitivity
356
Q

What determines spect resolution?

A

Intrinsic - noise in pmt signal, spread of energy deposition in detector due to scattering
Acceptance angle In which incident photons are accepted
Septal penetration
Septal scatter

357
Q

What determines the resolution in Pet?

A
Crystal pitch
Positron range
Ring diameter
Location of source
Optical encoding error
358
Q

What is the resultant change in pet resolution as you increase pixel pitch?

A

Increase pitch = decrease resolution

359
Q

What happens to pet resolution as positron range increases?

A

Decreases

360
Q

What happens to pet resolution as ring diameter increases?

A

Decreases

361
Q

What can be done to increase pet resolution?

A

Decrease pixel pitch

Use computer correction for positron range

362
Q

What are urge consequences of decreasing pixel pitch in pet?

A

Increase resolution
Increase inter crystal error
Increase cost

363
Q

What is the partial volume effect?

A

It is when organs of different sizes appear different with the same activity concentration.
Smaller objects look colder

364
Q

What can be done to increase sensitivity of pet?

A

Increase length of crystals
Increased the solid angle
Increase detector surface

365
Q

Describe preclinical pet mr

A

Very expensive
Very recent due to production of mr compatible detectors
Currently sequential, mr then pet or vv

366
Q

What are the key differences between preclinical pet and spect

A

Pet has decreased resolution than spect

Pet has increased sensitivity than spect

367
Q

What are the uses of preclinical imaging in oncology

A
Angiogenesis 
Hypoxia
Proliferation
Tumour metabolism
Apoptosis
Metastasis
368
Q

What are the uses of preclinical imaging in neurology

A

FDG uptake in seizures

Dopamine system

369
Q

What are the challenges in preclinical imaging?

A
Need new imaging agents
Biomarker discovery
Production is not very efficient
Technology
Communication between different fields
Clinical translation
Sensitivity
Practical aspects
370
Q

Why use pinhole for preclinical spect?

A

Increased magnification
Increase sensitivity
Increased resolution

371
Q

What new technologies could appear in the future?

A

Pet mr

Spect mr

372
Q

What modality would you use to view mouse lymph nodes?

A

Pet mr due to soft tissue and sensitivity
Can do pet ct with contrast
Spect

373
Q

Describe radio labelling for theragonostics

A

Combine gamma with beta
Beta is highly energetic and is absorbed by tissue and damages DNA
Can track therapy with gamma and measure response
Use Lut177 16% gamma 84% beta
Can predict outcome to treatment and indicate level of response

374
Q

What are the features of functional imaging?

A

Images physiological function e.g. Glucose metabolism
Spatial resolution 4-15mm
Physiology nor always correlated with anatomy
More specific but not useful without anatomy

375
Q

What are the features do anatomical imaging?

A

Images anatomical properties e.g. Attenuation or t1/t2 times
Spatial resolution is around 1mm
Can take a long time to detect anatomical changes

376
Q

What are the features doe selecting an ideal spect isotope?

A

Type of emission - is it a pure photon emission
Energy of emitted photons - 100-200keV
Half life - allows Imaging and chemistry to take place. Needs to be long enough to view the process but as short as possible to reduce dose
Production - cyclotron or generator

377
Q

What are the features of 99mTc?

A
99mTc --> gamma + 99Tc
6hour half life
Produced from 99Mo
Gamma are 140keV
It is reactor produced 
Can be kept in the hospital and alluded when needed 
Only gamma, no therapeutic doses
378
Q

What are the features of 201 Tl, thallium

A

201Tl –> gamma + 210Hg
Cyclotron produced
K analogue so can see sodium potassium pump
Gamma emission is 167keV and 135 keV
Most are X-ray rang 69-80kev from 210Hg
Images are noisier as you have to use less dose

379
Q

What is the consequence of a high dose per unit activity?

A
Have to use less dose so less units of activity
Decreased quality image
Needs increasing smoothing
Increased blurring
Decreased contrast
380
Q

How much restriction do the Collimators apply?

A

Restrict the direction of photons
1%
Can be less depends on Collimators

381
Q

How is the position of the event determined in spect?

A

The position is calculated by the weighted position of each pmt based on the amount of light detected
Anger logic - uses the coordinates of the centre of each pmt x amount of light at each / total light

382
Q

Describe the pmt array in spect?

A

Closely packed to increase effectiveness at collecting light

Some use hexagonal pmts to increase coverage of the NaI(Tl) crystal

383
Q

What is pulse height analysis?

A

Reads z pulses to determine the energy of each gamma ray
If photons are scattered they lose energy
Don’t want to include as they provide false information
Use a narrow energy window, usually 20% centred at the peak
99mTc 126-154keV

384
Q

What is uniformity correction?

A

It is done by applying an inverse image to all subsequent images

385
Q

What is the spect spatial resolution?

A

6-7mm better in preclinical

Depends on the type of collimator

386
Q

Describe a parallel hole collimator

A

Image is the same size as object
Fov is independent of the distance from the face of the collimator
Count rate is independent of the distance from the face of collimator

387
Q

What type of collimator is used for 99mTc imaging?

A

Low energy

388
Q

Describe a high energy collimator

A

Thick septa to stop high energy photons
Increased hole diameter
Used for iodine

389
Q

What happens to resolution with collimation as you increase the distance from the source?

A

Increases dispersion and decreases resolution

390
Q

Describe the spect crystal

A

NaI(TI) crystal
Detects individual rays by gamma scintillation
Converts to light
Thickness is 9.5mm or 12.7mm

391
Q

When is vq imaging done using nuclear medicine?

A

99mTc is done for perfusion
Inhaled gas is used for ventilation
Normally done with ct not possible e.g. Pregnancy or allergic to contrast agent

392
Q

How does whole body scanning work in nm?

A

A window or ramp opens up along the camera face and scans down the body slowly.
It ramps down as the camera reaches the end of the body
Sensors ensure it stays close to the patient

393
Q

How does dynamic imaging work in nuclear medicine?

A
Inject radio pharmaceutical
Want to know how fast it arrives and is cleared
Plot time activity curve in ROI
Can quantify degree of abnormality 
Scan at repeated periods
394
Q

How is ventricular function determined?

A

Using ventricular ejection fraction
Ef = edv-esv / edv
Can measure regional wall motion to check for abnormalities
Can label RBCs or track the wall edge

395
Q

What is the spatial resolution , temporal resolution and sensitivity of spect?

A

Spatial is 8-16mm
Temporal 2-10mins
Sensitivity 0.15%

396
Q

What is the spatial resolution , temporal resolution and sensitivity of pet?

A

Spatial resolution 3-8mm
Temporal sec-min
Sensitivity 0.5-5%

397
Q

How is spect different from gamma camera?

A

Rotates the gamma camera around to get multiple projections

Sums all data into a matrix -SINOGRAM

398
Q

Why do you use a sinogram in spect

A

Easier for calculation and slice reconstruction
Can use FBP or iterative reconstruction
Can reorient set to get a standard view

399
Q

How are multimodality images combined?

A

Image registration - minimise the distance between landmarks on the 2 images
If the patient moves it alters alignment
Can use cross correlation, mutual information, landmarks and similarity criteria
In pet,ct or spect,ct the centroid displacement between the 2 is calculated and applied to all subsequent images

400
Q

Why is attenuation important?

A

Different depths have different levels of attenuation
If there is no correction then the internal or thicker areas has lower uptake due to increased absorption. Values are underestimated at the centre.
Ct allows you to correct this

401
Q

What are the 3 methods for applying attenuation correction in pet?

A

Image segmentation
Bilinear scaling
Hybrid scaling

402
Q

How is ct attenuation correction done using image segmentation?

A

The HU image is segmented into regions and pixel values are replaced with the expected values for 511keV mu for the region

403
Q

How is ct attenuation correction done using Bilinear scaling?

A

A scaling factor is applied to all hu values to convert to u values at 511
There are 2 separate scaling factors
-1000 to 0
Hu greater than 0

404
Q

How is ct attenuation correction done using hybrid scaling?

A

Apply a scaling factor to HU to get u 511.

2 separate scales, one for soft tissue and one for bone

405
Q

What must be done to apply ctac to pet?

A

Spatial resolution in ct must be adjusted to that of pet

Must use iterative reconstruction

406
Q

What are the problems with iterative reconstruction?

A

It can take a long time
Need to optimise the number of iterations to the application
Increasing iterations increases noise - however it also creates a uniform resolution
Safest to over iterate and smooth

407
Q

What is the current idea to replace collimators in spect?

A

Solid state detectors
Get the energy of the incident photon
You know the angle of incidence
Can potentially reconstruct using advanced mathematics

408
Q

What is DSPECT?

A

New design in cardiology
Small multiple gamma camera can rotate and align with the ROI
Increases scan time over ROI and increases sensitivity
Also decreases resolution due to the wide collimation
You know the percentage decrease in resolution so can correct

409
Q

What happens when you increase the distance of the subject from the gamma camera?

A

Decrease resolution

Increase sensitivity

410
Q

What is resolution recovery

A

It is the mathematical calculation that aims to correct for a decrease in resolution due to using wide collimators

It takes into account specific performance characteristics like knowledge of system and user control

411
Q

What are the common agents used in radionuclide therapy.

A
131 I (NaI) for thyroid
131 I mIBG for neuroblastoma 
177Lu-DOTA for neuroendocrine tumours
90Y-DOTA for neuroendocrine tumours
90Sr for bone mets
412
Q

Who is involved in delivering radionuclide therapy?

A
Nurses
Clinicians
Radio pharmacy
Physicists 
Technicians
413
Q

What is peptide receptor radionuclide therapy?

A

pRRT

Somatostatin receptors are targeted by peptides e.g. 111 In DTPA octreotide to deliver harmful radioactivity to the area

414
Q

What shielding should be used for beta producing radionuclides?

A

Perspex as you want to minimise the production of secondary X-rays

415
Q

What shielding should be used for gamma producing radionuclide?

A

Lead

416
Q

What are the features of X-ray and gamma in terms of radiation protection?

A

Range in air is many metres
Can transverse the body
Relative harmfulness 1

417
Q

What are the features of Beta radiation in terms of radiation protection?

A

Range in air is 10s of cm
Range in tissue is mm
Relative harmfulness is 1

418
Q

What are the features of neutrons in terms of radiation protection?

A

Range in air is many m
Can transverse the body
Relative harmfulness is 5-10

419
Q

What are the features of alpha particles in terms of radiation protection?

A

Range in air is cm
Range in tissue is less than 1mm
Relative harmfulness 20

420
Q

Define absorbed dose

A

Energy absorbed per unit mass

Gy

421
Q

Define effective dose

A

Absorbed dose X factors for radiation type and tissue sensitivity
Sv

422
Q

Define dose rate

A

Measure do how quickly you are receiving radiation dose

mSvh-1

423
Q

What are the effect of radiation?

A

Can have no effect, kill cell or damage the cell and it can be incorrectly repaired
Stochastic is long term
Deterministic is short term

424
Q

What are the effects of a radiation dose greater than 1000mSv?

A

Skin damage
Radiation sickness
Decreased fertility
Death

425
Q

What is the consequence of 1mSv of radiation?

A

Fatal cancer risk of 1 in 20,000

426
Q

What are the 2 main principles of radiation protection?

A

Justification - exposure to ionising radiation should only occur to produce a net benefit

Optimisation - dose, the number of people and the likelihood of exposure should be kept ALARP

427
Q

Define ALARP

A

As low as reasonably practicable

428
Q

What are the standard dose limits?

A

Should be reduced to acceptable levels
Employee is 20mSv per year
Trainees 6, general public 1
1mSv to the foetus during the declared term of pregnancy

429
Q

What is the normal exposure for a chest x ray and a nuclear medicine bone scan

A

Chest X-ray 0.02mSv

Nuclear bone scan 3mSv

430
Q

Describe the care of sealed sources

A

Must be kept secure
Any losses to be reported to police, health and safety executive and the environment agency
Damage should be checked using leak tests

431
Q

What are external radiation hazards?

A

X-ray sets
Linear accelerates
Sealed and unsealed sources

432
Q

What are internal radiation hazards?

A

Unsealed sources

433
Q

What are the 3 main steps to reduce radiation dose

A

Time
Distance (inverse square law)
Shielding

434
Q

What is the photon energy from 99mTc?

A

140keV

435
Q

Compare radionuclide for pet and spect in terms of radiation protection

A

SPECT has lower energy
SPECT has lower TVL and HVL
Spect has a lower dose rate

436
Q

What are the protection steps involved in dispensing radionuclides?

A

Controlled area
Enclosed prep cabinet
Shielding for generator and eluted cavity
Washing, changing and monitoring facilities

437
Q

What are the protection steps involved in dispensing and injecting?

A
Shielded container to carry the syringe
Syringe shield
Spill tray with absorbent material
Control of waste materials 
Room may be a controlled area
438
Q

How do you protect against internal hazards?

A

Containment
Prevent ingestion
Decontamination
Procedures and monitoring

439
Q

How should spills of radioactivity be dealt with.

A

According to local rules
Use decontamination kit
Isolate, decontaminate, report

440
Q

What legislation is in place for radiation protection?

A

Ionising radiation regulations 1999
Ionising radiation (medical exposures) regulations 2000
Medicines (administration of radioactive substances) regulations 1978

441
Q

What is outlined in IRR 1999?

A
Ionising radiation regulations 1999
Protection of workers and public
Enforced by health and safety executive 
Controlled and supervised areas
Radiation protection advisor
Radiation protection supervisor
Local rules
Personal dosimeter
Instructions and training
442
Q

What is outlines in the ionising radiation (medical exposures) regulation 2000?

A

Protection of patients
Justifying medical exposures
Optimising medical exposures
Adequately trained staff

443
Q

What is quality assurance?

A

System to maintain and verify expected performance
It compares performance with other scans using standardised tests
It characterises any deterioration in performance

444
Q

What is quality control?

A

Specific aspects of quality assurance e.g. Equipment tests

445
Q

What are the quality control parameters checked at acceptance and 6 monthly in SPECT?

A
Spatial resolution
Spatial linearity
Uniformity
Count rate capability
System sensitivity
Energy resolution
Whole body scanning performance
Multiple window spatial registration

Shield leakage - only at acceptance

446
Q

Define spatial linearity

A

Parameter which characterises the amount of positional distortion caused by the camera with respect to incident gamma events entering the detector

A line source will appear wavy without correction due to positioning of PMTs

447
Q

How is intrinsic uniformity tested?

A

Measure the repsonse of the camera to a homogeneous flux of radiation WITHOUT collimator
Point source 5 x FOV away

448
Q

How is system uniformity tested?

A

Sheet source (57Co) 122keV throug a collimator

Measure the ability of the overall system to respond correctly to a homogenous flux of radiation

449
Q

How do you calculate integral non-uniformity?

A

Max pixel - min pixel / (max pixel + min pixel)
x100
For whole image

450
Q

How do you calculate differential non-uniformity?

A

For all groups of 5 adjacent pixels

Max pixel - min pixel/ max pixel + min pixel x100

451
Q

What do you need to do to test gamma camera uniformity?

A

Acquire enough counts per pixel to allow the system non-uniformities to be seen as distinct from Poisson noise - around 10000 counts per pixel

452
Q

How do you test spatial linearity

A

Phantom with lines is place on top of sheet source - if straight then correction is working
qualitiative
also gives you an idea of spatial resoltion

453
Q

What is intrinsic uniformity testing?

A

The optical coupling between the crystal and the PMT
If poor - regrease
USE A POINT SOURCE

454
Q

What are collimators made out of?

A

Most are made of lead

Can be tungsten - better performance but more expensive

455
Q

What is the difference between integral and differential non-uniformity?

A

Integral is max and min pixel from anywhere in the image

Differential, they must be within 5 pixel of each other

456
Q

Why is uniformity so important in SPECT?

A

In spect any errors are magnified in the reconstruction process

457
Q

What is the main phantom used to test SPECT?

A

Jaszczak phantom
Industry standard for SPECT testing

It assessed uniformity and spatial resolution

Tank of Tc with cold object within e.g. spheres, parallel rods of varying sizes and pitch

458
Q

What is the centre of rotation?

A

The computer assumes that the gamma camera will rotate in a smooth manner around the postition
Computer must know where the cameras are in order to reconstruct

459
Q

How do you test centre of rotation?

A

Place a point source in the centre and it should execute a sinusoidal pattern

460
Q

What is the typical PET/CT QC schedule?

A

Acceptance and annually - NEMA tests *count rate performance, image quality, spatial resolution and sensitivty)

Daily - CT warm up, air calibration, SUV check (PET)

Weekly - PET/CT alignment

Quarterly SUV calibration and check

461
Q

What are the daily PET detector checks?

A

Expose PET crystal to positron emitting point source

Check uniformity and energy peaking/resolution and coincident timing

SUV check

462
Q

How do you check SUV daily?

A

test using a uniform cylinder containing known activity and mass

Calculate SUV daily to monitor
Check fit for use

463
Q

What are the features of the flat source that should be considered

A

Appropriate emission to the modality

Known decay method and activity and mass

Long half life so don’t have to replace often

464
Q

How do you calculate SUV?

A

SUV = activity concentration from the image / (injection activity/patient body mass)

465
Q

How do you check PET/CT alignment

A
Weekly 
CT moves so could get misregistered
Use phantom with some attenuation characteristic of tissue with 5 radioactive sealed sources on them.
metallic encapsulation so show up on CT
Check they overlap
466
Q

How do you check SUV quarterly

A

Check calibration is right
need to check dose calibrator corresponds correctly to the dose seen by the camera

Update and check correction factors

467
Q

What is the annual NEMA tests required? in PET

A
Sensitivty
Spatial resolution
Image quality
Count rate performance
Accuracy of cont loss corrections
468
Q

What is the NEMA definition of sensitivty? PET

A

Mean cps/kBq from an un-attenuated line source at the centre of FOV and offset 10cm.

Low activity count so count losses are insignificant

Sensitivty decreases linearly as you move out of the centre

469
Q

How do you test for spatial resolution annually in PET?

A

Small sources infiedl of view and determine how big they look

NEMA: 1 source 1cm off axis and 2x10cm off axis

Line sources - look at line spread function - measure FWHM
If it is wide will decrease quality of the image

470
Q

How is overall image quality checked inPET

A

6 coplanar spheres - hot background. they are fillable.

  • Some hotter than background
  • Some colder (no activity)

Check attenuation correction by filling one with sample representing lung tissue - challenge attenuation correction

Put object with activity around it to represent the body to challenge the scatter correction

Can measure contrast, variability and whether they appear to have same concentration

471
Q

why does attenuation correction matter more in pet?

A

It has double the distance to go

Therefore increases attenuation

472
Q

How do you test count rate in PET?

A

Fill line source with high activity (GBq)
Line source scanned in centre
All profiles should be summed to get integrated counts for sinogram

Any events outside width of line = scatter
True count rate (remove scatter and random) = assume linear interpolation from outside the line.

473
Q

How do you analyse count rate?

A

From testing:
Get scatter and random counts
Get total counts
Get system measures of random counts

Calculate scatter fraction and noise equivalent count rate

474
Q

How do you Calculate scatter fraction?

A

A measure of the liely effect of scatter on images

Counts from random+scatter - random counts / (total counts - random counts)

475
Q

How do you calculate noise equivalent count rate (NECR)

A

A global measure of the likely image SNR

NECR = (total counts - counts from scatter and random)^2 / total counts

476
Q

How do you test for correction accuracy in count losses and randoms in PET?

A

Net error is computed which expresses the error in count rate after the corrections are applied

477
Q

What material is a pet scintillator crystal made of.

A

Bismuth germanate

478
Q

List clinical applications of spect/ct

A
Hyperparathyroidism (sestamibi)
Infection/inflammation (white cells)
Bleeding studies (red blood cell)
Hepatobiliary (hida)
Neuroendocrine tumours (octreotide)
Thyroid cancer (iodine)
479
Q

Describe the manufacturing of 99mTc

A

It is produced from 99mo which is primarily obtained from nuclear reactors

480
Q

What is anticipated to be the major issue with respect to 99mTc scanning in the global market?

A

as the number of nuclear generators reduces globally there will be limited access and high price of 99mTc, therefore cost of scanning is expected to increase significantly

481
Q

Define a kinetic constant

A

Defined as the rate of molecular exchange from one compartment to another

482
Q

What are the advantages of using SUV in pet?

A

Simple and versatile
Suitable for clinical use
Useful for diagnosis, staging and therapy

483
Q

What are the disadvantages of using SUV in pet?

A

Only works for tracers of flux
Limited efficacy of drug testing
Semi quantitative
Rough description of tracer kinetics
Doesn’t exploit the characteristics of different tracers
SUV use has to be alway a priori validated

484
Q

Outline the main physical processes that take place between the emission of positron and the formation of an electric signal in a pet

A

Positron emission
Positron travelling /scattering with range mm
Collide with electron
Annihilation producing 2x511keV gamma rays in opposite directions
Travels through body, some will be attenuated via Compton scatter, some will leave the body.
Those that leave the body will hit the scintillator crystal
This produces an optical photon from the gamma
This passes into pmt where signal is amplified and produces an electrical signal
Then calculate position based on light and coincidences

485
Q

What are the reasons for expanding the use of PET

A

Can be combined with Ct to combine anatomical and functional data
FDG is oncology to stage cancer
Novel indications (treatment assessment )
Better access to tracers (now cyclotron and generator)
Cost reduction

486
Q

What are the difficulties with expanding pet imaging

A
Cost is expensive
Development of new tools are expensive 
New tracers are slow and expensive to develop
Lag in patient referrals
Complexity of reporting
Logistics 
Current economic climate
487
Q

What is the main difference of the FDG molecule compared to glucose with respect to their biochemical pathways inside the human body?

A

FDG is phosphorylated and the product is trapped in the cell at a rate proportional to glycolysis. The glucose is not trapped and moves through the cycle

488
Q

What are the advantages of hybrid imaging systems.

A

Combines functional and anatomical
Can correct for attenuation problems in nuclear imaging
Provides more accurate localisation of lesions
Detects additional lesion
Assists in the exclusion of physiological tracer uptake thereby improving accuracy of image interpretation
Better identification of inflammatory lesions
Reduce time imaging by combining

489
Q

What are the disadvantages of using hybrid imaging systems?

A

Longer scanning time
Increased radiation dose
Increased cost of development and production
Increase cost per scan
Artefacts which affects images if there is misalignment or incorrect attenuation provided
Increased staff training
Increased quality control requirements

490
Q

What is the most common clinical indication for FDG pet/ct?

A

Oncology cancer

491
Q

Which part of the body of a normal person scanned with FDG would show most physiological uptake?

A

Brain

492
Q

What kind of cell function is measured with 18F fluorothymidine and 18f choline?

A

Cell membrane proliferation
FLT - imaging Biomarker do cell proliferation
FCH- choline. Imaging Biomarker of malignancy induced over expression of choline kinase

493
Q

Give an example of a particular disease that imaging with FLT or f-choline may be more useful than FDG?

A

Prostate cancer
Has low glucose metabolism/requirement but high cell proliferation (f-choline)

FLT: brain tumour. FDG has a high uptake in the brain and cancer can’t be easily distinguished from normal. FLT does not have high uptake in the brain as standard

494
Q

What the properties of an ideal generator.

A
Parent free
Sterile
Easy to use
High yield of daughter nuclide
Compact
Daughter decays to stable nuclide 
Parent free
495
Q

How does a technicium generator work?

A

Saline (NaCl) is washed through to obtain 99mTc
This runs through an exchange column
The molybdenum decays and it attached to alumina.
99TcO4- binds with sodium to give 99m Tc o4na (pertechnetate) which can then be eluted