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MIMS > Imaging Tumours > Flashcards

Imaging Tumours Flashcards

1
Q

What umbrella does most hospital imaging come under

A

Structural

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2
Q

Name 6 imaging techniques

How can all these methods be used

A 
Fluorescence
Ultrasound 
X Ray (including CT)
PET
SPECT
MRI

By injecting an imaging agent into the blood stream and imaging that

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3
Q

Define molecular imaging

A

Imaging molecules that are undergoing biological processes at the cellular or subcellular level

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4
Q

What is functional imaging

A

Imaging properties of tissues beyond their anatomical structure such as the size of their cells or the leakiness of blood vessels

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5
Q

How is energy transferred through space

A

Electromagnetic radiation

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6
Q

What form is the energy in electromagnetic radiation

A

Photons

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7
Q

What is an electromagnetic wave

A

A stream of photons all with the same frequency

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8
Q

What is the most common C isotope

How many neutrons and protons

What is another C isotope

A

C-12

6 protons and 6 neutrons

C-13 and C-14

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9
Q

Is C-13 stable

A

Yes

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10
Q

What do unstable C isotopes emit

What are the associated molecules

A

Gamma rays (Tc-99m) or positrons (F-18)

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11
Q

Name 2 imaging techniques that use MRI machines

A

MRI

and Magnetic Resonance Spectroscopy

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12
Q

Give the 4 key features of an MRI machine

A
  1. A super conducting magnet that provides a strong permanent magnetic field
  2. Radio frequency antennae (coils)
  3. Gradient coils to spatially vary the magnetic field
  4. Console
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13
Q

What do coils do in an MRI machine

A

Send and receive radio waves of the MRI signal

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14
Q

What is a pulse sequence

A

The specific set of pulses and timings of radio waves sent from the coil of the MRI machine into the patient

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15
Q

Do all isotope nuclei have spin

A

No

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16
Q

Name a common isotope that has spin

A

Hydrogen - 1 which makes up 99.98% of the hydrogen in water

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17
Q

What is the most common isotope of P

Does it have spin

A

P-31

Yes

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18
Q

Which carbon molecule has spin

A

C-13

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19
Q

How common is C-13

A

1% of all C molecules in the universe

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20
Q

What is chemical shift

A

Different chemicals in the body have NMR signals at different frequencies

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21
Q

What is the unit of the frequency axis in an NMR graph

A

ppm (part per million) NOT Hz

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22
Q

Why do we use ppm not Hz in NMR

A

The actual frequency of peaks is proportional to the static magnetic field of the MRI/NMR instrument

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23
Q

What does part per million mean

A

How many millionths of the static magnetic field the peak is from 0

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24
Q

How might your use C-13 glucose to image muscles

How many peaks would you see when doing this imaging on a resting muscle

A

Tune the coils of the MRI machine to send and detect C-13 nuclei frequencies
Inject the patient with C-13 glucose and watch its peaks

3 peaks: α-glucose, β-glucose, and glycogen

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25
Q

How is MRS an insensitive technique (2)

A

A large amount of muscle is used for each spectrum

Results take hours to acquire

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26
Q

Other than water, what molecule is very commonly imaged with clinical scanners

A

Fat

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27
Q

Why do the 2 H atoms in water only give 1 peak

A

The water molecule is symmetrical so they have the same frequency

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28
Q

What does turning on a gradient do when imaging water

A

It changes the magnetic field so it is smaller on the left and larger on the right

1 gradient turning on allows a 1 dimension image to be formed

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29
Q

What are the 3 dimensions produced by using 3 gradient coils in the bore of the MRI

A

Up down

Left right

In out

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30
Q

What is the main cause of an MRI signal appearing brighter in some places on the scan

What is another cause

A

Relaxation

Also some tissues have more water than others

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31
Q

What is relaxation

A

The way NMR signals decay after excitation by a pulse of radio waves

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32
Q

What are the 2 types of relaxation

A

T1 and T2

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33
Q

What kind of material is paramagnetic

A

Metal ions

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34
Q

What is the effect of paramagnetic materials on relaxation

A

A strong shortening effect on both T1 and T2

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35
Q

How can imaging exploit paramagnetism

A

Contrast agents containing Gadolinium ions can be injected into the blood stream and their presence can be images with MRI

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36
Q

What is fMRI and what is it used for

A

Functional magnetic resonance imaging

It is a method of detecting the brain’s response to different stimuli

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37
Q

What is the magnetism of Oxy haemoglobin and deoxy haemoglobin

A

Oxy - diamagnetic

Deoxy - paramagnetic

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38
Q

What does the paramagnetic property of deoxy haemoglobin mean

A

It changes the relaxation properties of the water in the blood, so MRI pulse sequences can be designed to be very sensitive to the paramagnetism caused by the deoxy Hb/ Oxy Hb ratio

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39
Q

What is the MRI technique that utilises the paramagnetism of the deoxy/Oxy Hb ratio

A

Blood oxygen Level Dependent MRI

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40
Q

Why does the BOLD signal follow a time lag of a few seconds

A

This is where neurons are processing an incoming signal from an AP

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41
Q

Why does blood flow increase to allow BOLD MRI

A

The neurons processing APs in the brain is energetically expensive so local blood flow is increased in this region to raise the amount of glucose and oxygen

Oxy Hb is in excess so the local paramagnetic signals from deoxy haemoglobin gives BOLD signal

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42
Q

What is PET

A

Position Emission Tomography is a molecular imaging technique that uses an injected tracer molecule which is radioactive and released positrons

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43
Q

What are positrons

A

Anti matter equivalents of the electron

Ie they are the same size and mass as e- but are only emitted by unstable radioactive nuclei

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44
Q

What happens after a position emitting nucleus has emitted a positron

Eg?

A

It turns into a different nucleus

F-18 decays to oxygen -18

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45
Q

Does the position emitting substance release positrons at a constant rate?

A

No it steadily decreases

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46
Q

Where does the positron emitting substance accumulate

A

In tumours but it does diffuse around the body as well

47
Q

What happens when positrons are emitted

A

They pass through the patient’s tissue until it hits an e- (within a few mm of where the positron was emitted

48
Q

What happens when a positron and e- collide

A

Both particles are annihilated to produce to produce 2 gamma rays that travel in opposite directions which are detected by the PET detector, showing that the source is somewhere along this straight line

This is specified as many different positrons and straight lines are produced and the cross over point is where the positrons are emitted from

49
Q

Name 3 positron emitting nuclei

A

F-18
Carbon-11
Iodine -125

50
Q

How long is F-18 half life

A

2 hours

51
Q

What does F-18 replace when used in PET tracers

A

Hydrogen or OH groups

52
Q

What is the most commonly used PET tracer in the clinic

A

Fluorodeoxyglucose

FDG

53
Q

Why is FDG used as a PET tracer

A

It is essentially glucose just with an OH replaced by F-18

This means it can be taken up by cells and phosphorylated to fluorodeoxyglucose-6-phosphate

54
Q

Which cells give a strong PET signal when FDG is used as the tracer

A

Cells with high levels of the glucose transporter and hexokinase

55
Q

How long do you do a PET scan after injection of FDG

A

30-60 mins

56
Q

Why can you see the general structure of different tissues in a PET scan

What are the 2 key areas that usually show up

A

FDG uptake is variable between tissues

Brain, bladder

57
Q

Why does brain always has high signals in a PET scan

A

It takes up a lot of glucose to fuel thinking

58
Q

Why is it difficult to use FDG for brain tumour imaging

A

The brain always has strong signals

59
Q

What does SPECT stand for

What radiation does it use

A

single photon emission computed tomography

Gamma emission

60
Q

What does SPECT detect

A

A single gamma ray emission

61
Q

What nuclei are required for SPECT

Why these

How does their half lives compare to those in PET scans

A

Technetium-99m
Indium - 111

They are gamma emitters

Longer half lives than PET but weaker signals

62
Q

What does SPECT rely on to define the direction of the line

What is the apparatus used for this called

A

Gamma rays passing through a narrow gap and hitting a detector some distance behind it

Collimator

63
Q

How do the dimensions of the collimator effect it’s efficiency

A

The narrow the gap, the better the resolution but the worse the signal noise

64
Q

How does SPECT detect neuroendocrine tumours

A

Covalent linking of In- 111 to octreotide which binds to the somatostatin receptor

This receptor is over expressed in neuroendocrine tumours

65
Q

How is glucose converted to pyruvate

What happens to pyruvate now

A

Glycolysis

It is transferred to mitochondria and passes through the TCA cycle to fuel oxidative phosphorylation
OR
pyruvate can be converted to lactate and exported from the cell

66
Q

Which are the 2 key enzyme in glycolysis do cancer cells
Upregulate

How do they do this

A

Hexokinase and Lactate dehydrogenase

Over expressing particular isoforms of these enzymes, often Hexokinase II and LDH-A

67
Q

How is glucose transported into cancer cells

A

Via GLUT1 mainly

68
Q

How is lactate transporter out of cancer cells

A

By monocarboxylate transporters (mostly MCT1 and 4)

69
Q

What is the net production of ATP from glycolysis

A

2 per glucose

70
Q

As glycolysis produces fewer ATP molecules alone than if the pyruvate went onto the TCA cycle and oxidative phosphorylation, why would the cancer cell up regulate glycolysis specifically

A

Lots of carbon flowing into glycolysis allows the tumour to use glycolytic intermediates to synthesise building blocks for lipid and DNA synthesis

This allows cell growth and division

71
Q

What does the export of lactate from the cancer cell promote?

A

Invasive growth of the tumour through neighbouring tissue

72
Q

What is used to stage lymphoma patients

A

FDG PET

73
Q

Why is FDG PET good for imaging lymphoma tumours

A

The cancer cells are highly glycolytic and up regulate GLUT and hexokinase expression and therefore take up lots of FDG and phosphorylate it to FDG-phosphate And it is metabolically stuck here

Therefore FDG-phosphate builds up within tumours

74
Q

How does FDG get metabolically stuck in tumour cells

A

FDG-phosphate is not a substrate for the 2nd enzyme in glycolysis so cannot progress down the glycolysis pathway

Hexokinase uses ATP to make the phosphorylation one way so won’t convert FDG phosphate back to FDG and tumour cells don’t have a lot of glucose-6-phosphatase (the usual enzyme for the reverse reaction)
Thus FDG-phosphate is stuck

75
Q

Does FDG labelling work on dying tumours

A

No as dying tumours have low hexokinase activity and will not accumulate FDG labelling

76
Q

Why can we use FDG PET fo monitor tumour response to therapy

A

Dead / dying tumour cells don’t accumulate FDG labelling so you can see the number of living cancer cells rather than just the size of the tumour (which may have swollen during therapy but actually many cells have died)

77
Q

How can lactate dehydrogenase activity be assessed

A

Using MRI and hyperpolarised [1-13C] pyruvate

78
Q

What is a hyperpolariser

A

A separate machine to an MRI that sits in an adjacent room and it can enhance normal insensitive NMR signals 10,000 times

This is called Dynamic Nuclear Polarisation

79
Q

What is DNP

A

Dynamic Nuclear Polarisation

80
Q

How is DNR achieved

A

By irradiating a sample, which has nuclear spin, with microwaves whole it sits at a very low temperature

This gives a v large NMR signal which will relax with the time constant T1 until the signal is almost nothing. This means very large signals will decay away over the course of seconds

81
Q

Are all nuclei with spin suitable for DNP

A

Yes but some are better than others

82
Q

What kind of pyruvate is most suitable for DNP

Why

A

[1-13C] pyruvate

It has a long T1 relaxation time so hyperpolarisation lasts for minutes

Its metabolic product ([1-13C] lactate) also has a long relaxation time

83
Q

What is [1-13C] pyruvate

A

Pyruvate with a single 13-C nucleus at the first carbon

84
Q

How does pyruvate enter cancer cells

A

Through the same monocarboxylate transporters that allow lactate out of the cell

These are generally up regulated

85
Q

What does it mean if cancer cell gave up regulated lactate dehydrogenase

A

[1-13C] pyruvate is converted to [1-13C] lactate at a higher rate than surrounding tissue

This allows DNP to be used effectively

86
Q

Why is DNP MRI often done as a dynamic series of measures

A

It images enzymatic conversion

87
Q

What does apoptosis cause cells to do (which is useful for imaging)?

What about for necrosis

A

Causes cells to shrink and bud

Necrosis leads to cell swelling, leakiness and cell lysis

88
Q

What does it mean if an apoptotic cell buds

A

It turns into an apoptotic body

89
Q

What will happen to cancer cells that have been treated

How are these changes detected

A

It will change from a tightly packed mass of cells of a similar size to being a mixture of tiny shrunken and budding cells and large leaky cells and lysed necrotic regions

Using diffusion weighted MRI

90
Q

How do water molecules move

A

According to Brownian motion

Molecules collide with each other constantly and move randomly
The sphere of possible positions increases with the time the water is moving

91
Q

Do MRI pulse sequences use gradients to get positional information?

A

Yes they use varying magnetic fields caused by currents flowing in specifically shapes wire loops

92
Q

What does a DW-MRI do

A

Uses a gradient to “label” each water molecule with a position and then a second gradient to read the new position

93
Q

What is each pixel in the final image of a DW- MRI machine

A

An average of billions of water molecules

94
Q

What would the signal on a DW MRI machine be if none of the water molecules moved in the time between the gradients

A

The signal would be at a maximum

If the molecules move the signal will be smaller

95
Q

Why is the signal decrease of DW MRI machines calculable

A

Water at a known temperature is expected to have a highly predic stable diffusion speed

96
Q

Why is the measured diffusion in the DW MRI sequence always less than the predicted diffusion speed

A

The molecules in tissues are always bumping into plasma membranes, organelles, extracellular matrix etc

97
Q

What is ADC

A

Apparent Diffusion Coefficient how restricted the water diffusion is in tissue

98
Q

How can ADC be used to measure treatment effectiveness

Will the ADC value increase or decrease

A

A reduced cell density will be detected after effective treatment and cell lysis will remove restrictions on water diffusion, leading so a higher ADC value

As both apoptosis and necrosis are occurring both increases and decreases are detected

99
Q

If an ADC value of a tumour remains unchanged, what does it say about the therapy

A

Therapy is ineffective

100
Q

What is the apoptotic “eat me” signal for phagocytes

A

Externalisation of phosphatidylserine

101
Q

What is phosphatidylserine

What happens in apoptosis to them

A

A phospholipid that usually sits in the inner leaflet of the bilayer of the PM

They are shifted to the outer layer where they are recognised and bound by receptors on macrophages

102
Q

What is Annexin V

How is it used in imaging

A

A protein that binds specifically to phosphatidylserine

It is covalently linked to a gamma emitting nucleus eg Tc-99m

103
Q

What do you do with Annexin V -Tc-99m

A

Inject after her soy and the Annexin V will bind to the apoptotic cells increases local concentration

The Tc-99m emits gamma rays that are detected by a SPECT machine

104
Q

How is apoptosis imaged by PET

A

By combining Annexin with a positron emitter eg Iodine 125

105
Q

How far can oxygen diffuse

A

2mm

106
Q

How do tumours grow new blood vessels

A

Using VEGF

This binds to endothelial cells and activates them to grow new blood vessels
The endothelial cels then secrete PDGF, which attracts smooth muscle cells to form

107
Q

What feature if tumour vasculature allows us to image them

What technique is used

A

The leaky quality

MRI

108
Q

What perfusion contrast agents are used to image tumour vasculature

A

Gadolinium ion chelates in MRI

109
Q

Give 5 facts about Gd ion chelates that Make them appropriate for MRI

A

They bind to Gd tightly so free toxic Gd is not released into the body

They are water soluble so can be cleared by the kidney within hours

They are not transported into cells so remain in the blood or ECF

They cross the ECF faster in regions of leaky vasculature

Gd ions are paramagnetic meaning MRI pulse sequences can exploit its relaxation to make it appear bright

110
Q

Are blood vessels equally permeable across the body to large molecules

A

No

They are v impermeable in the brain thanks to the blood brain barrier

111
Q

What is used to diagnose aggressive brain tumours

How can we see if it worked

A

Contrast Enhanced MRI which images the break down of the blood brain barrier

Prevention of angiogenesis shows reduced CE MRI signal

112
Q

What is used in anti angiogenic therapy

How does it work

A

Bevacizumab

Binds to VEGF-A to stop the growth factor binding to the receptor on endothelial cells

113
Q

What is TTP

A

Time to progression

They were free from a worsening of their condition for longer

114
Q

Does Magnetic resonance require ionising radiation

A

No

MIMS (12 decks)

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