Methods for studying CNS disorders Flashcards

1
Q

whats the difference between fMRI and DTI?

A

The fMRI BOLD signal is based on the increased blood flow to a brain region that correlates with increased activation of that region (Logothetis, 2002), whereas DTI measures rely on the anisotropy (directionally dependent diffusion) of water molecules within myelinated axons (Emsell, Van Hecke, & Tournier, 2015)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what categories of methods are there for studying CNS disorders?

A
  • Imaging techniques
  • Indirect ‘markers’ for changes in neurotransmitter function
  • Post-mortem studies on human brain
  • Genetic-linkage analysis
  • Animal models
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What imaging techniqes can be used to study CNS disorders?

A
  • Computerised tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Functional Magnetic resonance imaging (fMRI)
  • Diffuse tensor imaging (DTI)
  • Positron emission tomography (PET)
  • Single photon positron emission tomography (SPECT)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is Computerised tomography?

CT scan

A

Computed tomography (CT) provides rapid, noninvasive imaging of the brain and skull

an imaging tool that combines X-rays with computer technology to produce a more detailed, cross-sectional image of your body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Magnetic resonance imaging (MRI)?

A

imaging technique that produces cross-sectional images of your body.
Unlike X-rays and CT scans, MRI works without radiation. The MRI tool uses magnetic fields and a sophisticated computer to take high-resolution pictures of your bones and soft tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

breifly compare CT and MRI

A
  • MRI provides better resolution of neural structures than CT . This difference is most significant clinically for visualizing the following: Cranial nerves, Brain stem lesions, Abnormalities of the posterior fossa, Spinal cord - CT images of these regions are often marred by bony streak artifacts.
  • CT is superior to magnetic resonance imaging (MRI) in visualizing fine bone detail in (but not the contents of) the posterior fossa, base of the skull, and spinal canal.
  • CT may require a radioactive tracer which can have adverse effects, includign allergic reactions and contrast nephropathy.
  • MRI is better for detecting demyelinating plaques, early infarction, subclinical brain edema, cerebral contusions, incipient transtentorial herniation, abnormalities of the craniocervical junction, and syringomyelia.
  • MRI is contraindicated if patients
    Have had a pacemaker or cardiac or carotid stents for < 6 weeks
    Have ferromagnetic aneurysm clips or other metallic objects that may overheat or be displaced within the body by the intense magnetic field
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is functional MRI?

fMRI

A

a specialized form of MRI that is used for measuring and mapping the brain’s functional activity. evaluates blood flow in the brain called the blood oxygenation level dependent (BOLD) contrast technique.
based on the fact that oxyhaemoglobin has different magnetic resonance to deoxyhaemoglobin.

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.
The microvasculature responds by increasing blood flow – this increase the oxyHb to deoxyHb ratio
This reveals patterns of activity in the intact brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Diffuse tensor imaging (DTI)?

A

While DWI refers to the contrast of the acquired images, DTI is a specific type of modeling of the DWI datasets
the basic concept behind DTI is that water molecules diffuse differently along the tissues depending on its type, integrity, architecture, and presence of barriers, giving information about its orientation and quantitative anisotropy
Mapping pathways and investigating aberrant connectivity
Uses water to get a more detailed Image than traditional MRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Diffusion weighted imaging?

A

Diffusion weighted imaging (DWI) is a variant of conventional Magnetic Resonance Imaging based on the tissue water diffusion rate. It is a non-invasive method, with unparalleled sensitivity to water movements within the architecture of the tissues that uses existing MRI technology and requires no new equipment, contrast agents, or chemical tracers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Positron emission tomography?

A

An imaging test that can help reveal the metabolic or biochemical function of your tissues and organs. The PET scan uses a radioactive drug called a tracer to show both typical and atypical metabolic activity.

When the radiopharmaceutical undergoes beta plus decay, a positron is emitted, and when the positron interacts with an ordinary electron, the two particles annihilate and gamma rays are emitted. These gamma rays are detected by gamma cameras to form a three-dimensional image, in a similar way that an X-ray image is captured.

first unstable positron emission isotopes are created in an cyclotron e.g. O15 (half-life 2 min)
when these isotopes are injected they distribute according to the relative activity of the brain regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how does SPECT differ from PET?

A

SPECT is very similar to PET in its use of radioactive tracer and detection of γ-rays. However, unlike PET the radioisotopes used for SPECT emit only a single γ-ray during decay that is measured directly. Moreover, SPECT scans are significantly less expensive than PET scans partly due to that the nuclides used in SPECT have a longer half-life and are relatively easily obtained than PET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the main advantage of SPECT compared to PET?

A

Main advantage does not require on site cyclotron (A cyclotron is a type of particle accelerator which repeatedly propels a beam of charged particles (protons) in a circular path)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is Electroencephalography?

EEG

A

Twenty electrodes are distributed symmetrically over the scalp to detect electrical changes in the brain that are associated with Seizure disorders, Sleep disorders, Metabolic or structural encephalopathies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is Megnetoencephalography?

A

based on detection of the magnetic fields that arise because of the electrical activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are the differences between EEG and MEG?

A
  • In EEG the electrodes are placed on the scalp. MEG is performed using a dewar that contains multiple sensor coils, which do not touch the patient’s head
  • MEG primarily detects the magnetic fields induced by intracellular currents, whereas scalp EEG is sensitive to electrical fields generated by extracellular currents.
  • Although MEG is more sensitive in detecting currents that are tangential to the surface of the scalp, EEG is sensitive to tangential and radial neuronal activities
  • Magnetic fields are not distorted by the tissue conductivity of the scalp, skull, cerebrospinal fluid (CSF) and brain; in contrast, electrical fields may be distorted by the skull and CSF.
  • MEG provides better spatial resolution of source localization (2-3 mm) than EEG (7-10 mm)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what indirect markers are there for changes in neurotransmitter functions?

A

levels of metabolites in
* cerebralspinal fluid
* plasma
* urine

binding to platelets

17
Q

how can platelets be used to detect changes in the brain?

give an example

A

Platelets express interesting proteins when it comes to psychiatric conditions. Platelets harbour mitochondria and these harbour monoamine oxidase. They have a class of receptor 5HT2A. in the platlets this receptor mediates aggregation, this receptor gene is encoded by the same one as in the brain so you can analyse this one to see what variant is in the brain aswell

Eg using binding to monoamine transporters as markers for depression
The majority of studies indicate that the Bmax (maximal binding capacity) of platelet [3H]imipramine binding is lower in depressed, untreated patients than in the control population and that this finding is relatively specific to depression

18
Q

what ways can we detect and monitor neurotransmitters?

5 categories

A

(1) Nuclear medicine tomographic imaging, including positron emission tomography and single-photon emission computed tomography;
(2) Optical sensing, including surface-enhanced Raman spectroscopy, fluorescence, chemiluminescence, optical fiber based biosensors and colorimetry;
(3) Electrochemical detection, including voltammetry and amperometry;
(4) Analytical chemistry techniques, including high performance liquid chromatography; and
(5) Microdialysis. In practice, two or more techniques may be combined for better detection accuracy.

19
Q

what are the limitations of post mortem studies on human brains?

A
  • Protein is labile - may degrade between death and analysis (and agonal delay also has an effect)
  • Patient may have been taking medication that disturbs brain features
  • Lack of well matched controls
20
Q

what disorders have shown differentially expressed miRNA in post mortem brain tissues?

A

Studies that have assessed miRNA expression in postmortem brain tissues have identified differentially expressed miRNA between cases with various neuropsychiatric disorders, such as schizophrenia, bipolar disorder and major depression

21
Q

what are the advantages and disadvantages of animal models for CNS disorders?

A

Advantages – drug screening, therapy,
Disadvantages – not an exact ‘phenocopy’ of the disease