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Neuroimaging in Mental Health > Week 5 > Flashcards

Week 5 Flashcards

1
Q

Why measure brain function in the context of mental health?

A
  1. Brain disorders may not necessarily show structural deficits (eg addiction).
  2. Timing - functional changes may precede anatomical changes (eg. neurodegeneration in AD).
  3. Functional measurements allow the understanding of the pathological mechanism involved in the disease and direct the development of treatments.
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2
Q

What is a tracer?

A

A small drop, that has certain biochemical properties that will make it move around the body compartments at certain rates.

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3
Q

What is a compartment?

A

Compartments can be distinct physical tissues: blood, extravascular space, cells and so on, or distinct chemical states - the original compounds, their phosphorylated metabolite or so on.

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4
Q

What are the transfer rates?

A

What we call physiological parameters. Typically they can be:

  • perfusion
  • enzymatic

from these rates, we can derive how tracer gets stuck on a target density or affinity.

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5
Q

What are the three strict requirements for tracer measurement?

A
  1. The tracer has to be a drop - a very small mass - in order to affect the system it’s targeting.
  2. It must move between compartments in a well-defined way - tracers are not used to explore systems we don’t know, only to calculate rates between compartments.
  3. Presence of the instrumentation that is able to measure the concentration of the drop through time.
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6
Q

What two components make up a tracer?

A
  1. A substrate - is the biological element that we are interested in tracing.
  2. A label - emits the signal that allows the measurement of the tracer.
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7
Q

What tracer is used for CT?

A

X-ray opaque - iodine.

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8
Q

What paramagnetic tracers are used in MRI?

A

Gadolinium.

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9
Q

What are the problems with the tracers iodine and gadolinium?

A
  1. Molecules are big - they change biochemical properties of the substrates they attach to
  2. They do not cross BBB
  3. In the case of MRI, the amount of tracer needed is substantial - therefore it is likely to interfere with the targeted system.
  4. MRI is also not quantitative.
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10
Q

What are the advantages of PET?

A
  1. Positron is highly energetic so only tiny amounts of the label are needed.
  2. Positron emitters are natural molecules that can be directly incorporated into the substrate.
  3. PET instrumentation is built to allow accurate quantification of radioactivity concentration in the image, but also in blood.
  4. PET technology is designed to accurately fit the three tracer principles.
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11
Q

What is a radioisotope?

A

Radioisotopes are radioactive isotopes of an element. They can also be defined as atoms that contain an unstable combination of neutrons and protons, or excess energy in their nucleus.

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12
Q

How the tracer is produced (2)?

A
  1. The radioisotope is produced.

2. The radioisotope is attached to the substrate.

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13
Q

What is a positron?

A

A positively charged particle with the same mass as an electron.

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14
Q

What happens after positron is emitted by proton-rich nuclei?

A

When released by decay, the positron travels a distance and then annihilates with an electron, generating two gamma rays, travelling in opposite directions.

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15
Q

What is an isotope?

A

Isotopes are members of a family of an element that all have the same number of protons but different numbers of neutrons. The number of protons in a nucleus determines the element’s atomic number on the Periodic Table.

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16
Q

7 criteria for a radiotracer

A
  1. Specific to the target
  2. Able to cross BBB
  3. Should have limited plasma binding
  4. Should not be metabolised too quickly by the liver.
  5. Should be selective to one or two pathways.
  6. Should have suitable kinetics for PET study duration.
  7. Should exhibit non-specific (nor-saturable) binding.
17
Q

Why instrument detect the decaying label?

A

Because it generates the positron which in turn annihilates with gamma emission.

18
Q

How does the PET scanner know whether the gammas come from the same annihilation?

A

PET scanners use timing circuits. If two gammas are detected in the same narrow time window, less than ten nanoseconds, the two gammas will be paired.

19
Q

What are the three problems with gamma detection and how to correct those?

A
  1. Attenuation - as gammas are absorbed by the tissue. Corrected by building attenuation map before tracer injection.
  2. Scatter -. Gammas interact with matter and change direction, creating a false echo. Correction is made by using attenuation maps to simulate a scatter profile.
  3. Random events - that occur when two unrelated gammas are detected in the same time window and erroneously coupled. Correction is achieved by simulation by artificially scrambling events collected during the acquisition.
20
Q

What is the projection?

A

Detection of two gammas that originated from the same positron annihilation.

21
Q

Two methods to reconstruct images from projections

A
  1. Filtered back projection (FBP) - by projecting back on the image the projected data. This recreates the original image plus stripe artefacts that are eliminated with some filtering. FBP is quick and very quantitative, but stripe artefacts are not entirely eliminated.
  2. Iterative reconstruction (IR):
    - makes an initial guess of an object, then uses the computational model to generate the projections that are then compared with the real projection data.
    - if different, hypothetical image is changed and the simulated projections are generated again.
    - the process is repeated until the simulated object generates projections that are close to the original data.
22
Q

What is the Kety-Schmidt method?

A

In 1945 Kety and Schmidt introduced the use of an inert gas as a tracer for the measurement of organ blood flow (1). The method they described is based on inhalation of the gas, e.g. nitrous oxide and on following the rate of tissue uptake by analysis of multiple arterial and venous blood samples.

23
Q

What is by far the main source of energy in the brain?

A

Glucose

24
Q

What are the parameters describing tracer behaviour in the system of interest?

A
  1. Tissue tracer uptake
  2. Tracer accumulation rate
  3. Radiotracer volume of distribution
25
Q

Why quantification in PET is important?

A

Because under specific assumptions by characterising the tracer kinetics it is possible to characterise the ongoing physiological processes of the investigated tissues providing a quantitative measure of the system functioning in vivo. In other words - we measure the tracer behaviour as a proxy to the in vivo system functioning.

26
Q

Three kinetic principles

A

The concentration of a probe that:

  1. does not alter or perturb the system
  2. interacts with the system in a predictable way, informative and reproducible fashion
  3. has a concentration that can be inferred quantitatively
27
Q

Two broad types of PEt studies

A
  1. Research PET studies: designed to maximise the information about a particular process or to extend the knowledge about it.
  2. Diagnostic or clinical PET studies: maximise the detection of a particular PET process in a particular subject with maximum sensitivity and specificity.
28
Q

What does the SUV tell us?

A

It reflects the main process for which the tracer has been designed. For example in the case of FDG PEt SUV is a proxy for tissue glucose metabolism. In the case of PET neuroreceptor system, the SUV is a proxy for the receptor density.

29
Q

The difference between static PET imaging and dynamic PET imaging

A

Participant lies in the PET scan at the moment of the tracer injection.

30
Q

What is dynamic PET imaging?

A

Multiple acquisitions of the target volume of interest over time. Characterisation of acquired image changes over time with the tracer tissue distribution and the tracer activity.

31
Q

What result the PET scanner returns?

A

The measure of the radioactivity in a given volume. This radioactivity is the overall result of multiple sources.

32
Q

What are the four methods that do not use an arterial line?

A
  1. Image derived
  2. Alternative modelling
  3. Population-based input functions
  4. Venous input functions
33
Q

Types of PET image segmentation

A
  1. Anatomical
  2. Functional
  3. Multimodal

Neuroimaging in Mental Health (8 decks)

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