Molecular imaging
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The field of molecular imaging originated from the field of radiopharmacology due to the need to better understand the fundamental molecular pathways inside organisms in a noninvasive manner.
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[edit] Molecular imaging
Molecular imaging differs from traditional imaging in that probes known as biomarkers are used to help image various targets or pathways, particularly in vivo. Biomarkers interact chemically with their surroundings and in turn alter the image according to the molecular changes occurring within the area of interest. This is markedly different from previous methods of imaging which primarily imaged differences in qualities such as densities or water content. This ability to image very fine molecular changes opens up an incredible number of exciting possibilities for medical application, including early detection and treatment of disease as well as for basic pharmaceutical development. Furthermore, molecular imaging allows for quantitative tests, which adds a level of objectivity to the study of these areas.
There are many different areas of research being conducted in the field of molecular imaging. Much research is currently centered around detecting what is known as a predisease state or molecular states that occur before typical symptoms of a disease are detected. Other important veins of research are the imaging of gene expression and the development of novel biomarkers.
[edit] Imaging modalities
There are many different modalities that can be used for noninvasive molecular imaging. Each have their different strengths and weaknesses and some are more adept at imaging multiple targets than others.
[edit] Magnetic resonance imaging (MRI)
MRI has the advantages of having very high spatial resolution and is very adept at morphological imaging and functional imaging. MRI does have several disadvantages though. First, MRI has a sensitivity of around 10-3 mol/L to 10-5 mol/L which compared to other types of imaging can be very limiting. This problem stems from the fact that the difference between atoms in the high energy state and the low energy state is very small. For example at 1.5 teslas the difference between high and low energy states is approximately 9 molecules per 2 million. Although with the use of small animal scanners much higher strength magnets can be used which can detect much lower concentrations than weaker magnets.
[edit] Optical imaging
There are several different types of optical imaging.
Optical imaging's most valuable attribute is that it and ultrasound do not have strong safety concerns like the other medical imaging modalities. The downside of optical imaging is the lack of penetration depth.
[edit] Single photon emission computed tomography (SPECT)
The main purpose of SPECT when used in brain imaging is to measure the regional cerebral blood flow (rCBF). The development of computed tomography in the 1970s allowed mapping of the distribution of the radioisotopes in the brain, and led to the technique now called SPECT.
The imaging agent used in SPECT emits gamma rays, as opposed to the positron emitters (such as fdg) used in PET. There are a range of radiotracers that can be used, depending on what is to be measured.
Xenon (133Xe) gas is one such radiotracer. It has been shown to be valuable for diagnostic inhalation studies for the evaluation of pulmonary function; for imaging the lungs; and may also be used to assess rCBF. Detection of this gas occures via a gamma camera—which is a scintillation detector consisting of a collimator, a NaI crystal, and a set of photomultiplier tubes.
By rotating the gamma camera around the head, a three dimensional image of the distribution of the radiotracer can be obtained by employing filtered back projection. The radioisotopes used in SPECT have relatively long half lives (a few hours to a few days) making them easy to produce and relatively cheap. This represents the major advantage of SPECT as a brain imaging technique, since it is significantly cheaper than either PET or fMRI. However it lacks good spatial (i.e., where exactly the particle is) or temporal (i.e., did the contrast agent signal happen at this millisecond, or that millisecond) resolution. Additionally, due to the radioactivity of the contrast agent, there are safety aspects concerning the administration of radioisotopes to the subject, especially for serial studies.
[edit] Positron emission tomography (PET)
The theory behind PET is simple enough. First a molecule is tagged with a positron emitting isotope. These positrons annihilate with nearby electrons, emitting two 511,000 eV photons, directed 180 degrees apart in opposite directions. These photons are then detected by the scanner which can estimate the density of positron anhilations in a specific area. When enough interactions and annihilations have occurred, the density of the original molecule may be measured in that area. Typical isotopes include 15O, 18F, 64Cu, 62Cu, 124I, 76Br, 82Rb and 68Ga. One of the major disadvantages of PET is that most of the probes must be made with a cyclotron. Most of these probes also have a half life measured in hours, forcing the cyclotron to be on on site. These factors can make PET prohibitively expensive. PET imaging does have many advantages though. First and foremost is its sensitivity: a typical PET scanner can detect between 10−11 mol/L to 10−12 mol/L concentrations.
[edit] Ultrasound
Explanation of how it works basics how it would be used in imaging multiple targets.
[edit] Probes and the imaging of molecular interactions
In order to image multiple targets you must first identify and develop the interactions of which you are trying to take advantage. Developing good probes is often difficult and is an area of intense research.
[edit] See also
[edit] References
- Fuchs V.R.,Sox H.C. Jr., Health Affairs 2001: 20(5), 30–42
- Weissleder R, Mahmood U. Molecular imaging, Radiology 2001: 219:316-333
- Piwnica-worms D, Luker KE. Imaging Protein-protein interactions in whole cells and living animals. Ernst Schering Res Found Workshop. 2005;(49):35-41.
- Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light, Genes & Development 2003: 545-580
