Positron Emission Tomography (PET) measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream and uses the data to produce two or three-dimensional images of the distribution of the chemicals throughout the brain (Nilsson 57). The positron emitting radioisotopes used are produced by a cyclotron and chemicals are labelled with these radioactive atoms. The labeled compound, called a radiotracer, is injected into the bloodstream and eventually makes its way to the brain. Sensors in the PET scanner detect the radioactivity as the compound accumulates in different regions of the brain. A computer uses the data gathered by the sensors to create multicolored two or three-dimensional images that show where the compound acts in the brain.
The greatest benefit of PET scanning is that different compounds can show blood flow and oxygen and glucose metabolism in the tissues of the working brain. These measurements reflect the amount of brain activity in the various regions of the brain and allow us to learn more about how the brain works. PET scans were superior in terms of resolution and speed of completion (as little as 30 seconds) when they first came online. The improved resolution permitted better judgments to be made as to the area of the brain activated by a particular task. The biggest drawback of PET scanning is that because the radioactivity decays rapidly, it is limited to monitoring short tasks (Nilsson 60). Before fMRI technology came online, PET scanning was the preferred method of brain imaging, and it still continues to make large contributions to neuroscience.
SPECT is similar to PET. Single photon emission computed tomography (SPECT) uses gamma ray emitting radioisotopes and a gamma camera to record data that a computer uses to construct two- or three-dimensional images of active brain regions (Ball). SPECT relies on an injection of radioactive tracer, which is rapidly taken up by the brain but does not redistribute. Uptake of SPECT agent is nearly 100% complete within 30 – 60s, reflecting cerebral blood flow (CBF) at the time of injection. These properties of SPECT make it particularly well suited for epilepsy imaging, which is usually made difficult by problems with patient movement and variable seizure types. SPECT provides a "snapshot" of cerebral blood flow since scans can be aquired after seizure termination (so long as the radioactive tracer was injected at the time of the seizure). A significant limitation of SPECT is its poor resolution (about 1 cm) compared to that of MRI.
Diffuse optical imaging or diffuse optical tomography is a medical imaging modality which uses near infrared light to generate images of the body. The technique measures the absorption of haemoglobin, and relies on the absorption spectrum of haemoglobin varing with its oxygenation status.
Typical applications include rapid 2D optical topographic imaging of the evoked response following brain activity and tomographic reconstruction of an entire 3D volume of tissue to diagnose breast cancer or neonatal brain haemorrhage
Diffusion tensor imaging (DTI) is a new (mid- to late-1990s) magnetic resonance imaging (MRI)-based technique that allows us to visualize the location, the orientation, and the anisotropy of the brain's white matter tracts. The architecture of the axons in parallel bundles and their myelin shield facilitate the diffusion of the water molecules along their main direction. This diffusion which is preferentially oriented in one direction is called "anisotropic diffusion". The imaging of this white matter property is an extension of diffusion MRI. If we apply diffusion gradients (i.e. magnetic field variations in the MRI magnet) in at least 6 directions, it is possible to calculate, for each voxel, a tensor (i.e. a 3*3 matrix) that describes this diffusion anisotropy. The fiber direction is indicated by the tensor’s main eigenvector. This vector can be color-coded, yielding a cartography of the tracts’ position and direction (red for left-right, blue for superior-inferior, and green for anterior-posterior). The brightness is weighted by the tracts’ anisotropy.
Diffusion tensor imaging data can be used to perform tractography within white matter. Fiber tracking algorithms can be used to track a fiber along its whole length (e.g. the corticospinal tract, through which the motor information transit from the motor cortex to the spinal cord and the peripheral nerves).
The clinical applications of DTI are the tract-specific localization of white matter lesions, the localization of tumors in relation to the white matter tracts (infiltration, deflection), the localization of the main white matter tracts for neurosurgical planning, and the assessment of the white matter maturation in children.
They are tools for investigating the pathophysiology of psychiatric illnesses & the action of psychotropic drugs..
Methodology:
1.. Production & incorporation of a gama-emitting radioisotope into molecule of biological interest to form a radiotracer administered to humans..
2.. Imaging of the sdistribution of the radiotracer, over minutes or hours, in living human brain with PET or SPECT cameras..
3.. Quantification of a physiological parameter of interest..
Radiotracers:
PET radiotracers:
a) C15O2/H2 15O for blood flow, used to map dysfunctional brain areas involved in psychiatric illness..
b) (18F)deoxyglucose for glucose metabolism, used for resting-state studies & yo define anti-psychotic drug effects..
c) (11C)SCH 23390 for Dopamine D1 receptor, for receptor occupancy studies with many neuroleptics..
d) (11C)raclopride for Dopamine D2 receptor, may enable extra-striatal D2 populations to be measures..
e) (11C)RTI 121 & 32 for dopamine reuptake site markers for studies in Parkinson's disease
f) (18F)dopa & (18F) metatyrosine for dopaminergic neurone density & integrity, predominantly imageable in basal ganglia, some application to psychosis studies..
g) (11C)Flumazenil for central benzodiazepine receptors, labels all subtypes of central receptor, studies in aanxiety disorders..
h) (18F)altanserin & (18F)setoperone for 5-HT2 receptor, studies in depressed patients..
j) (11C)MDL-100907 for 5-HT2A receptors, may be most suitable legend for imaging 5-HT2 receptors..
k) (11C)WAY 100635 for 5-HT1A receptors, studies in major depressive disorders..
l) (11C)McN 5652 for serotonin transporter, studies in ecstacy abusers..
m) (11C)methyltryptophan for possible measure of serotonin synthesis rate..
n) (11C)diprenorphine for mue, kappa & delta receptors, studies in depressive disorders..
SPET radiotracers:
a) (99mTc)HMPAO for blood flow, many resting-state & two-scan activation studies in psychosis
b) (123I)iodobenzamide for dopamine D2 receptors, for occupancy & displacement studies..
c) (123I)epidepride for dopamine D2/D3 receptors, studies of schizophrenia, can measure extrastriatal dopamine receptors.
d) (123I)iomazenil for benzodiazepine receptors, for studies in alcoholism..
e) (123I)nor0beta-CIT for dopamine & serotonin transporter, studies in ecstacy abusers..
In functional brain mapping, regional cerebral blood flow or metabolism is measured as an index of locan neuronal activity..
a) studies in normal volunteers in which 'activation' paradigms are used to identify functional Anatomy
that is relevant to psychiatric disorders..
b) activation studies in patients who are compared with matched control subjects..
c) studies in which the biological variable is correlated with a relevan clinical variable within the patient group..
d) the longitudinal comparision of patients before & after various treatments & into clinical recovery..
e) cross-sectional studies of resting-state brain activity in patient groups in comparision with appropriate controls..
In radioligand imaging, the specific uptake & binding of radiolabelled tracer compunds is measured..
a) to estimate baseline radioligand uptake at rest in patient groups in comparision with controls..
b) within-patient group correlations between radioligand uptake & particular signs/symptoms..
c) longitudinal comparision of radioligand uptake in patients before & after various treatments & into clinical recovery..
d) 'displacement' or radioligand activation studies designed to detect changes in the levels of intrasynaptic neurotransmitters in response to a pharmacological or cognitive challenge..
e) investigation of the receptor binding & occupancy characteristics of psychotropic drugs..
Basic principle is if protons are mainly in freely diffusing water molecules, as theya re in CSF, T1 will be prolonged, while if theya re mainly bound to large macromolecules as in fat, T1 will be short. Likewise, liquid tissues will have prolonged T2 times compares with solid tissues..
Relaxation times at 1.5 T for different tissue types:
Grey matter- T1- [snip]-1040 ms (grey matter contains less fat than white matter), T2- 64-71 ms
White matter- T1- 740-770 ms, T2- 64-70 ms
CSF- T1- >2000 ms, T2- >300 ms
Fat (at 1 T)- T1- 180 ms, T2- 90 ms
Repetition time (TR) & time of echo (TE), the parameters of the spin echo pulse sequence, cam be adjusted.
If TR is long (>1000 ms) & TE is short (<20 ms), contrast in the images will e weighted by differences b/w tissues in proton density. Proton-density-weighted images show good contrast b/w relatively hyperintense parenchymal tissue & hypointense CSF..
If TR os short (<1000 ms) & TE is short (<20 ms), contrast in the images will be weighted by tissue-differences in spin-lattice relaxation. T1-weighted images show excellent contrast b/w hyperintense white matter & relatively hypointense grey matter. That's why T1 weighted images are widely used to measure quantitative abnormalities in size or shape of the cerebral cortex..
If TR is long (>1000 ms) & TE is long (>20 ms), contrast in the images will be weighted by tissue differences in spin-spin relaxation. T2-weighted images show strong contrast b/w hyperintense CSF & parenchymal tissues, unless there is congestion or edema of the parenchyma, in which case the T2 weighted signal will be increased. That's why T2 weighted images are widely used to identify acute, inflammatory & ischaemic lesions...
Fast spin echo sequence:
It involves a refinement of the basic spin echo sequence which elicits several signals, an scho-train, by multiple 190 degree pulses after a single 90 degree pulse, instead of eliciting a single signal echo after a 180 degree rephasing pulse in each cycle of length TR..Earlier echoes (TE<20 ms) are used to form a proton-density-weighted image & those arriving later (TE>80 ms) are used to form a T2-weighted image. This pair of dual-echo images provides complementary tissue contrast for no increase in scan time, making fast spin echo a favoured sequence..
Diffusion-weighted imaging:
It can provide information abotu the organization of white matter tracts in the brain that cannot be obtained by other MRI methods..
The principle is the rate of Brownian motion or diffusion of proton will be greatest for the protons that are moving freely throught the CSF & less for protons constrained by physical barriers such as myelinated cell membranes..
White matter is generally hyperintense in diffusion-weighted imaging because closely packed axonal tracts provide the greatest barrier to the free diffusion of water in the brain..
Complications & contraindications:
Absolutely contraindicated in patients with any strongly magnetized object in their heads- aneurysm clips, recontructive metal plates, traumatically embedded metal fragments..
Also in patients with implanted electronic devices- cardiac pacemakers etc...
Static magnetic fields as strong as 2 T cause no harmful effects to biological tissue. Rapid switching of field ingradients can induce electrical currents in tissue, but at the switching speeds used in MRI these induced currents are several times less than needed for muscle contraction...
Artefacts:
Subject motion is the most common artefact, may be voluntary or involuntary (physiological)..
Where two materials with very different susceptibilities are closely adjacent, there may be severe distortion of the magnetic field, causing artefactual loss or exaggeration of the MR signal..
Voxel sizes are larger than some scales of anatomical organization organization in the brain.. This partial volume artefact is particularly evident at the interface b/w cortical grey matter & sulcal CSF & at the interface b/w corical grey matter & central white matter..
Uses:
Structural MRI is most often used in Psychiatryto exclude non-psychiatric causes for psychopathology..., i.e., to exclude tumours, a-v malformations, etc...
It may detect-
hippocampal sclerosis or callosal agenesis suggestive of birth injury or abnormal development..
infarcts or periventricular white matter changes in vascular dementia..
focal grey matter atrophy in frontal lobe in Pick's disease or caudate nucleus & frontal cortex in Huntingtone's disease..
Morphometry:
It is to measure the anatomical structure of the brain.. The area or volume of regions of interest (ROI) can be measured directly by drawing a line around the region on a computerized display of the data & counting the number of voxels enclosed by the line..
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