18.2. Imaging Flashcards
1
Q
What are some different methods of imaging the brain in vivo?
A
- Positron Emission Tomography (PET)
- Magnetic Resonance Imaging (MRI), Spectroscopy (MRS) and Functional (fMRI)
- X-ray Computed Tomography (CT)
- Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (TDCS) - non-invasive procedure
- Magneto and Electro - Encephalography (MEG/EEG/ERP)
2
Q
What different features of the brain can we look at through imaging?
A
- Anatomy
- Blood flow or perfusion
- Brain metabolism
- Receptor density
- White matter tracts
- Brain biochemistry
- Essentially: Strucure and Function
3
Q
Summarise how different imaging methods range from covering anatomy to biology, and what the relative scales of resolution are.
A
4
Q
What are the features of MRI?
[EXTRA?]
A
- Magnetic Resonance Imaging
- Invented in the early 1970’ s
- Uses the established technique of nuclear magnetic resonance (NMR) to generate images of the human body
- NMR is an old term for MRI
- Does not involve ionising radiation
- Images can be sensitised to physiology
- e.g. Blood flow, free water diffusion, blood oxygenation levels.
- As these features can differ between different brain regions, it can give an insight into their properties
- Nobel Prize for Medicine 2003 Sir Peter Mansfield (English physicist) for inventing MRI
- MRI measures signals from protons in water and fat
- How the protons react to the magnetic field informs us about their surrounding environment, so different signals can be perceived and associated with different structures
- High water concentration (55M) allows for small pixels (~1mm^3 - fairly high resolution)
5
Q
What is the resolution of MRI and what allows this?
A
- Small pixels of ~1mm^3 are allowed
- This is through the high water concentration of the body (55M)
6
Q
What are some measurements enabled by MRI?
A
- Morphometry (lesion size, cartilage volume)
- Relaxometry (T1, T2)
- Pathology (tumour, MS lesions, joint damage)
- Perfusion (tumour, stroke, depression)
- Flow (angiography, cardiac output, velocity)
- Diffusion (stroke treatment, white matter disorders)
- Hyper-polarized gas (Lung)
- functional MRI (focal injury, psychiatric, pain)
- Spectroscopy (pathology, metabolism)
7
Q
What are some applications for MRI?
A
8
Q
How are MR signals generated?
[EXTRA]
A
- When protons are placed in a magnetic field they oscillate
- The frequency at which they oscillate depends on the strength of the magnetic field
- 3-5 Tesla scale used in hospitals, but the larger the magnetic field, the higher the resolution of the image (as it will ensure that more protons change energy states/oscillate, therefore a larger signal is generated - 7 Tesla MRI machine in the lab)
- Unpaired spin in protons allows them to interact with the magnetic field and oscillate
- Protons are capable of absorbing energy if exposed to electromagnetic energy at the frequency of oscillation (radiofrequency)
- The energy put in is non-ionising, and only flips the spins of the protons so that they now oppose the magnetic field
- After they absorb energy, the nuclei release or reradiate this energy so that they return to their initial state of equilibrium (as they always tend towards the lowest energy state)
- The energy is provided in a pulsing manner
- This re-radiation or transmission of energy by the nuclei as they return to their initial state is what is observed as the MRI signal and can be converted into an image
- As the proton changes from one energy state to another, the vectors of its amplitude change (one decreasing, one increasing) - it is these two different vectors that are the ‘relaxation times’ that give T1 and T2 signals on MRI scans
- This return of nuclei to their equilibrium state not instantaneous – occurs over time
- The strength of the MRI signal depends primarily on three parameters:
- Density of protons in a tissue: The greater the density of protons, the larger the signal will be
- T1 relaxation time
- T2 relaxation time
- THESE PARAMETERS FORM THE BASIS OF T1-WEIGHTED, T2-WEIGHTED AND PROTON DENSITY WEIGHTED MRI
- The contrast between brain tissues is dependent upon how these 3 parameters differ between tissues
- For most “soft” tissues in the body, the proton density is very homogeneous and therefore does not contribute in a major way to signal differences seen in a image
- However, T1 and T2 can be dramatically different for different soft tissues, and these parameters are responsible for the major contrast between soft tissues.
- T1 and T2 are strongly influenced by the viscosity or rigidity of a tissue
- Generally speaking, the greater the viscosity and rigidity, the smaller the value for T1 and T2
- Contrast is important for a good image, so when targeting particular structures it can be beneficial to consider whether T1 or T2 weighting will provide a better contrast
- It is possible to manipulate the MR signal by changing the way in which the nuclei are initially subjected to electromagnetic energy
- This manipulation can change the dependence of the observed signal on the three parameters: proton density, T1 and T2
- Hence, one has a number of different MR imaging techniques (“weightings”) to choose from, which accentuate some properties and not others
9
Q
What features are bright and which are dark on a T1 weighted MRI image?
[IMPORTANT]
A
Bright on a T1 weighted image:
- Fat
- Subacute hemorrhage
- Melanin
- Protein-rich fluid
- Slowly flowing blood
- Paramagnetic substances: gadolinium, manganese, copper
- Calcification (rarely)
- Laminar necrosis of cerebral infarction
Dark on a T1 weighted image:
- Increased water, as in edema, tumor, infarction, inflammation, infection, hemorrhage (hyperacute or chronic)
- Low proton density, calcification
- Flow void
10
Q
Which features are bright and which are dark on a T2 weighted MRI image?
[IMPORTANT]
A
Bright on T2 weighted image:
- Increased water, as in edema, tumor, infarction, inflammation, infection, subdural collection
- Methemoglobin (extracellular) in subacute hemorrhage
Dark on T2 weighted image:
- Low proton density, calcification, fibrous tissue
- Paramagnetic substances: deoxyhemoglobin, methemoglobin (intracellular), iron, ferritin, hemosiderin, melanin
- Protein-rich fluid
- Flow void
11
Q
What are some simple tissue characteristics when being imaged in MRI T1, MRI T2 and X-ray/CT for normal tissue?
[IMPORTANT]
A
12
Q
What are some simple tissue characteristics when being imaged in MRI T1, MRI T2 and X-ray/CT for abnormal tissue?
[IMPORTANT]
A
13
Q
What are some issues with imaging pathology using MRI?
A
- The relationship between the signal change, current underlying pathology and clinical status
- This means that it can be difficult to predict so it is frequently best to take a range of weightings and observe what results are obtained
- Conventional MRIs can also be slow in showing some pathology - for example, MRI imaging is frequently not overly beneficial during the acute phase of a stroke
14
Q
What is the pathology shown in these images?
A
- NB that if relaxation agents (contrast agents) such as gadolinium are used, there are huge changes in local relaxation parameters at specific areas of interest/abnormal tissue
- E.g. if there is a BBB leak, gadolinium will exit the brain and affect the local conditions
- Due to its unpaired spin, Gd will distort the magnetic field at its location and change how surrounding protons relax
15
Q
What is the best weighting to view MS lesions?
[EXTRA]
A
- T2 weighted images provide the best contrast to detect white matter tract lesions
16
Q
What can be seen in this scan?
[EXTRA? Possible MCQ]
A
- Sudden onset = likely stroke
- If similar presentations but slower onset, consider degeneration or tumour
17
Q
What can be seen in this scan?
[EXTRA? Possible MCQ]
A
- NB MR is not great at showing strokes in the acute phase
- This lead to the development of diffusion-weighted imaging, which looks at the diffusion of water within the brain and is thought to be more sensitive
18
Q
What can be seen in this scan?
[EXTRA? Possible MCQ]
A
- Anaplastic astrocytoma
- Left parietal lesion, found at biopsy to be an anaplastic astrocytoma
- The T2-weighted image shows poorly circumscribed mass with core of mixed high and low signal, a rounded periphery of higher signal, and a component of infiltrating edema, appearing as somewhat lower signal
- Tumour appears to centered in white matter underlying the left post-central gyrus
19
Q
What can be seen in this scan?
[EXTRA? Possible MCQ]
A
- Anaplastic astrocytoma (Gd contrast)
- The core of lesion contains elements which enhance with gadolinium
- Note extension of enhancing portion of the mass to right hemisphere
- T1-weighted image - highest signal comes from water whose relaxation time shortened due to proximity to injected contrast agent gadolinium-DTPA
- Such signal generally seen from water which is either intravascular or within regions of breakdown of the blood-brain barrier
20
Q
How can radioligands be used to visualise the brain (e.g. BBB breakdown or tumours)?
[EXTRA?]
A
- If radioligand is used (e.g. Thalium-201, a potassium analogue), it can ‘leak’ into regions of the brain in which there are active tumour growth
- Multimodal imaging (e.g. in combo with MRI) can improve localisation of lesions
- Note on the image: two large foci of red-coloured activity in the sites of 201-Tl uptake
21
Q
What do these scans show?
(Pathology on left scan, right scan is an age-matched control)
A
- Can see shrinkage of sulci in left image, lots of (white) CSF filling the gap
- Age matched control still shows a small amount of shrinkage, but this is normal/associated with the ageing process
22
Q
How can diffusion imaging be used?
[EXTRA]
A
- Connectivity-based grey matter segmentation
- Use diffusion of H2O, as it is constrained to white matter tracts/cannot simply move throughout the entire brain
- Using analysis, water can therefore be tracked throughout the brain and it can be observed whether its movement is restricted
- If restricted, it is more likely to be from white matter tracts
- Using this, can use tools to investigate white matter tract connectivity and integrity
- For example, this method has been used to observe brain changes over time
25
Q
What is the normal presentation of a proton MR spectrum of the brain? What are the metabolites most commonly used as signals?
[EXTRA]
A
- N-acetyl aspartate (NAA)
- Chemically hidden
- Marker of viable neurons, but is not present in glial cells
- Levels decrease when there is neuronal damage
-
myo-inositol
- Marker of glial cells
- Choline
- Marker of membrane changes/disturbances
- Creatine
- Often used as an internal reference for energy/metabolic measure
27
Q
How can you relate MRS to function in MS?
[EXTRA]
A
- Large voxel studies indicate that metabolite concentrations are altered in normal appearing brain
- NAA is decreased and Choline is increased
- Reduced NAA correlates well with a disability score (EDSS)
- De Stefano et al, Brain 121, 1469-1477, (1998)
- Biochemical changes seen before those in imaging
28
Q
What is the typical spectra in blunt head injury?
[EXTRA]
A
- Can see dramatic reduction in NAA
- As this marker is only found in neurons, these results suggest that there are now fewer neurons
29
Q
What is a typical proton MRS in the hippocampus of an early dementia patient?
[EXTRA]
A
32
Q
What is positron emission tomography (PET)?
[EXTRA?]
A
- Positron is an anti-electron; given off during decay of the nuclei of specific radioisotopes (e.g. radioactive fluorine 18F)
- When positron meets electron, collision produces two gamma rays with same energy but going opposite directions
- Gamma rays leave patient’s body - detected by PET scanner
- Use positron emitting radioligands introduced into subject’ s blood and their resultant BINDING or METABOLISM/SEQUESTERING in the brain measured using computerised tomography to reconstruct spatial location of emission
- e.g. Local cerebral glucose consumption measured this way using FLUORODEOXYGLUCOSE (18FDOG)
- Glucose used as tumours need this and so will readily take up the radioligand
- Can also make radioligands specific to certain receptors for more targeted imaging
- e.g. Local cerebral glucose consumption measured this way using FLUORODEOXYGLUCOSE (18FDOG)
34
Q
What are some examples of brain receptor PET ligands?
[EXTRA]
A
- These can measure more precise receptor distribution
- Can then compare these between disease and health to further understand pathology
35
Q
What condition is shown in these PET images (control on the left)? What radioligand has been used?
A
- PK11195 binds to inflammatory mediators, e.g. those involved in macrophage-microglia interactions
- Can see huge inflammatory response in the AD patient
- Radioligands allow us to visualise this in vivo
36
Q
What condition is shown in these PET images? What radioligands have been used and what are they for?
[EXTRA]
A
37
Q
Give a brief summary of functional mapping methods.
A
- There is no one perfect technique
- For the highly invasive procedures, they frequently cannot be carried out on humans (or, if they are, can only be done once)
38
Q
What is the Bayesian view of the brain?
[EXTRA]
A
- We are taught to think of the brain in a ‘bottom-up’ manner, using inputs such as light, sound, taste, touch, smell, nociception to then create responses
- However, this is not necessarily the case - the brain is NOT a simple ‘receipt’ organ producing perceptions and experiences by processing bottom up sensory inputs as sole contributor
- This led to the conception of ‘priors’ and the Bayesian view of the brain
- This is a probalistic explanation of how events are contingent/dependent on how things were before, and it is these factors that shape what happens next
- Priors act almost like a probability and can bias how something might be perceived subsequently
- This involves a reasonable degree of anticipation and memory
- If the priors are wrong/biased, then they can have a huge impact on the perception of actual inputs - this is true for senses such as pain and vision
- E.g. if you expect something to hurt, pain can be exacerbated
- Videos were taken during inactivity, and it could be seen that there was still a lot of activity
- See lecture for full video, but activity was colour coded and it was shown that spatial areas were activated together
- These were the resting state/housekeeping networks
- We are not yet sure of their exact function, but they do help to indicate where different networks lie
- Experiment showed that even without inputs, functional networks prefer to fire together - indicates independance from sensory input
39
Q
Provide a summary of the physiological correlates of brain electrical activity.
A
- EEG = electroencephalography
- MEG = magnetoencephalography
- NB PET has been largely superceded by fMRI in functional imaging
40
Q
Who proposed the coupling of cerebral blood flow (CBF) and metabolism?
[EXTRA]
A
Roy and Sherrington, 1890
41
Q
Summarise the magnetic properties of haemoglobin.
[EXTRA]
A
- Deoxyhaemoglobin becomes paramagnetic/similar to a contrast agent, therefore influencing the relaxation of protons in MRI
42
Q
What is fMRI and how does it work?
A
- Functional magnetic resonance imaging measures brain activity by detecting changes associated with blood flow.
- This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases.
- Electrical activity is stimulated in pulses
- It is possible to detect a difference in the image intensity between ‘on’ and ‘off’ states
- The contrast created by this can be used to create an image
49
Q
A
CT
50
Q
A
MRI
51
Q
A
Ultrasound
52
Q
A
X-ray
