Neuro: past, present and future/ OTHER HALF IN TOPIC 1 NEUR531 Flashcards
What is radiography?
Using radiation to provide images of tissues, organs, bones and vessels
What is catheter angiography?
A radiopaque (meaning a substance that is opaque, or cannot be seen through under radiation) liquid injected into one of the carotid, vertebral arteries shows the branches of these vessels
What is the chief value of catheter angiography?
Detecting arterial disease or displacement of blood vessels by lesions such as tumours
What is computed tomography?
Non-invasive. Uses X-ray rotated around the head at desired plane and is based on scanning the head with a narrow, moving beam of radiographs and measuring the attenuation (reduction of amplitude) of the emerging beam. There are sensitive electronic sensors of X-irradiation. The information about relative radiopacity obtained with different viewing angles is fed to a computer that executed a mathematical algorithm on the data.
What happens to the density reading from “sections” (tomographs) of the head, in CT scan
Processed by a computer to generate an image whose brightness depends on the absorption values of the tissues
Why is CT technique useful?
It is valuable in clinical diagnosis because the density of many cerebral lesions is greater or lesser than the density of normal brain tissue
What is MRI?
Magnetic resonance imaging (MRI) uses the protons (H+ ions) of water molecules in biological tissues
How does MRI work?
In a strong static magnetic field, the protons align with the direction of the magnetic field, creating a net magnetization. Then radio waves cause these aligned atoms to produce faint signals, hydrogen atoms emit energy that is detected and integrated in a computer to produce MR images
Why is radiofrequency applied to tissue? In MRI
Protons absorb energy and change their alignment
What is the significance of switching off the radiofrequency applied in MRI?
Immediately after turning off the radiofrequency energy, protons return to their equilibrium distribution (relaxation) and emit energy. Protons in different tissues have different relaxation rates
What exactly is the computer detecting an integrating in MRI?
The hydrogen atoms emitting energy
What is the resolution of images dependent on in MRI?
Strength of magnetic field, the time used for scanning, and the required signal to noise ratio
How thick are the slices typically for MRI?
1 to 5 mm
What is the strength that is used at most MRI facilities?
1.5 to 3.0 Tesla
What is the typical in-plane resolution (xy plane) (aka voxel dimension)
0.5 to 1.0 mm
What does a T1-weighted image do? in MRI
Emphasizes the difference between CNS tissue (brighter) and other fluids and tissues (dark) and gives some discrimination between white matter (brighter) and gray matter (less bright)
What does a T2-weighted image do? in MRI
Emphasizes the cerebrospinal fluid (CSF; bright) in the subarachnoid space and ventricles, providing crisp anatomical resolution but with less contrast between gray and white matter
What does a proton density image do?
A MRI technique that emphasizes the difference between gray matter (bright) and white matter (dark)
What does an apparent diffusion coefficient (ADC) image do?
MRI technique that produces contrast based on the diffusion of water molecules and show areas with diffusivity such as ventricles or an infarcted (tissue death or necrosis due to inadequate blood supply to the affected area) area as bright
What are ADC images commonly used for?
diagnosis of acute stroke
What does fluid-attenuated inversion recovery (FLAIR) sequence provide?
It’s a MRI technique that provides images in which the CSF signal is completely nulled
what are FLAIR images commonly used in?
In the investigation of white matter abnormalities
What are the advantages of MRI?
Non-invasive, avoidance of potentially harmful radiation, anatomical resolution that is greatly superior to that obtainable with radiographs
What is the main disadvantage of MRI?
The slow process, requiring approx. 30-40 mins for a typical examination, contrast with CT which takes a few minutes
What accompanies neuronal activity?
Increases blood flow and oxygen usage
Which of Deoxyhaemoglobin and oxyhaemoglobin is paramagnetic (paramagnetic materials are slightly attracted by a magnetic field and do not retain the magnetic properties when the external field is removed)?
Deoxyhaemoglobin
What does blood oxygen level-dependent (BOLD) signal?
Relates to deoxyhaemoglobin concentration in the tissue being examined
What does high levels of metabolic activity translate to?
High intensity of an image, thus rendering prominent any parts of the brain that are more acute than the surrounding regions
What are the 2 primary types of BOLD signals?
T2 BOLD (fMRI)
and
Hahn spin-echo (HSE) BOLD fMRI
What is T2 BOLD fMRI?
Most frequently used type (relative to HSE BOLD fMRI). Signal is due to deoxygenated haemoglobin, and “activation” is commonly imaged in large veins as well as in nervous tissue
What is HSE BOLD fMRI?
More accurate localization, detects movement of water into and out of red blood cells, with much stronger signals arising from capillaries than longer vessels, spatial resolution of approx. 0.1mm
How do molecules move?
Using their thermal energy
Molecular movement in biological tissues is restricted by…
Cell membranes, macromolecules and fibrous structures, therefore movement may be anisotropic (exhibiting properties with different values when measured along axes in different directions)
What is isotropic and anisotropic?
isotropic –> properties of material independent of direction
anisotropic –> is direction dependent
How can you encode water diffusion?
using strong magnetic field gradient
What happens if water molecules experience same diffusion gradient in both applications of pair (little diffusion) as opposed to water molecule diffusing far?**
The MR signal is refocused and images appears bright, as opposed to experiencing different gradients and is not refocused well
In compact bundles of axons in white matter, the anisotropic movement of water is…?
accentuated
Is the rate of diffusion of the axon bundle higher along or across axon bundle?
Along
What is diffusion tensor imaging (DTI)
Form of diffusion MRI enables visualization of large bundles of axons in the brain. Compare position of hydrogen atoms in water molecules at discrete time intervals.
In DTI, how is rate and preferred direction of diffusion of water molecules calculated?
Can be calculated from 6 or more scans of each voxel obtained by the application of different orientations (directions) of diffusion gradients
What is DTI data be used for?
Identify connectivity between brain areas (tractography)
What is DTI used for in diagnosing?
Demyelination and myelin abnormalities (e.g., multiple sclerosis (MS))
What is diffusion-weighted imaging (DWI)?
Form of diffusion MRI
What does DWI measure?
Measures the mean diffusivity of water in a given voxel
Give an example where DWI would be useful relative to CT
DWI very sensitive to early changes following stroke e.g., DWI changes might be evident only 10 mins after first manifestation of stroke, cf. CT detects changes after several hours
How can radioactive tracers be used for in the brain?
Structure can be related to function by mapping the distribution of a metabolically significant substance that has been labelled with a radioactive isotope
What is the relationship between blood flow and activity of neurons?
Transient but conspicuous local increases in blood flow are associated with activity of neurons
How do you monitor regional cerebral blood flow with radioactive tracer?
A radioactive tracer such as Xe is introduced into the blood and the intensities of the emitted gamma rays are measured by an array of detectors at the surface of patient’s head
How does intensity of radiation vary?
With vascular perfusion of underlying tissues. (The passage of fluid through tissue)
How is regional cerebral blood flow used in clinical setting?
To identify cortical regions in which the circulation is inadequate
How can you study regional cerebral blood flow? With tracers
By single-photon emission computed tomography (SPECT) and positron emission tomography (PET)
What are some of the tracers used in SPECT?
Xe or Tc
What is some of the tracers PET use?
carbon, nitrogen, oxygen
How does SPECT work?
Each disintegrating atom of an ordinary gamma-emitting isotope emits one photon. SPECT makes sectional maps based on the uptake into tissue and subsequently dispersal of radiolabelled compounds that have been introduced into blood
How is regional blood flow represented in SPECT?
As variations of intensity in the resulting images.
What is the resolution and time for a SPECT? and cost relative to PET
Low resolution (2-3mm) but they are obtained in only a fraction of the time needed for a PET scan and at a much lower cost
How does PET work?
Positrons are emitted by certain radioactive isotopes (15O, 13N, 11C, 18F). A positron is immediately annihilated when it encounters an electron and 2 gamma-ray photons are emitted. Detection of these pairs of photons enables the computation of sites of concentration of isotopes which is incorporated into metabolically significant compound
What is the resolution and time for PET?
Superior resolution to that of SPECT. 5 to 10 mm. But inferior to CT (2mm) or MRI (0.5 to 1.0 mm).
Positron-emitting isotopes have half-lives ranging from 2 mins - 2 hours –> that is time frame to complete process depending on the isotope
What is Marchi technique?
Oldest staining method for anterograde degeneration (process in which an axon is damage).
Selectively stains degenerating myelin with osmium tetroxide in the presence of an oxidising agent.
What is silver method?
Can show degenerating unmyelinated axons and synaptic terminals
How long after lesion is placed in animals do degenerating axons demonstrable for silver methods and marchi techniques appear?
4-8 days
How is a tracer used?
A tracer substance is injected in a region of gray matter. Tracer taken up by axonal terminals or neuronal cell bodies (or both) and transported within the cytoplasm
What is retrograde tracers?
Accumulation of tracers in the cell bodies of neurons whose axons end in the injected region
What is anterograde tracers?
Tracers enter cell bodies and are transported to the presynaptic terminals at the destination of the axons
What could be a tracer?
Radioactively labelled amino acid, a fluorescent dye, a histochemically demonstrable enzyme [HRP], or a protein that has been chemically linked to a fluorecent dye or HRP.
What is membrane probes? and timespan in which it occurs
Hydrophobic fluorescent compound (e.g., Dil), enter lipid domains of cell membranes, including neuronal axolemma (cell membrane of axon). Then diffuse in the plane of membrane. Allowing the tracing of fibres tracts from a site of application of dye.
Slow, over several months
How can viruses be used for experimental neuronal tracing?
Certain viruses replicate within neurons, are transported within, and are passed from one cell to another at synapses. These viruses can be modified to make cells synthesize histochemically detectable enzyme, or viral protein may be stained immunochemically
How can an analogue of ordinary d-glucose, 2-deoxy-D-glucose, be used for revealing structures?
2-deoxy-D-glucose, enters cell but is not metabolized. Radioactively labelled 2-deoxyglucose accumulates in cytoplasm of metabolically active cells, detected by autoradiography
What does deoxyglucose show?
Reveal structures in brain that are active when particular system of pathway in use.
How is cytochrome oxidase used histochemically?
Used for determining catalytic function of cytochrome oxidase used in metabolic activities. in regions that contain active neurons, the activity of this enzyme is higher than in adjacent quiescent areas
What is electrophysiology?
Explore electrical activity of living neurons. Electrically stimulating neurons and recording potentials evoked elsewhere
What is optogenetics?
Genetically tag subsets of neurons with microbial opsins and activate or silence them using brief pulses of light
What are excitotoxins?
analogues of excitatory transmitter glutamic acid. When excitotoxin binds to glutamate receptors there is unusually long activation of nonspecific ligand-gated cation channels of the postsynaptic cells
What happens after the binding of excitotoxins
Calcium ions diffuse into the neuron and activate proteolytic enzyme that destroy the cytoplasm. (Proteolytic enzymes breakdown proteins)
How are cells that use monoamines selectively intoxicated?
By analogues of these substances or their metabolic precursors. E.g., neurons that make use of dopamine or noradrenaline selectively poisoned by 6-hydroxydopamine, and serotonin cells –> 5,6-dihydroxytryptamine
What is suicide transport?
Some toxic lectins (proteins that bind to carbs, e.g., ricin-60, from castor beans) and other compounds (e.g., antibiotic doxorubicin) taken up by axonal endings and by injured axons of passage and transported retrogradely to the neuronal cell bodies, where they inhibit nucleic acid and protein synthesis
How can suicide transport be useful?
Produces selective lesions that can provide experimental models of diseases in which certain populations of nerves degenerate.
What do both PET and fMRI methods detect?
changes in regional blood flow and metabolism within the brain. Neurons that are active demand more glucose and oxygen. Thus, by detecting changes in blood flow, PET and fMRI reveal the regions of the brain that are most active under different circumstances
