The major goal of molecular imaging is the spatiotemporal imaging of genomic and proteomic events. Molecular imaging encompasses the fields of chemistry, biology, physics, and medicine, and brings experts in these scientific fields together to determine means of visualizing molecular and cellular events 1, 2
Molecular imaging includes several imaging modalities, such as, bioluminescence, fluorescence, positron emission tomography (PET), single photon emission computed tomography (SPECT), computed tomography (CT), optical imaging, ultrasound, and magnetic resonance imaging (MRI). The advantages and disadvantages of these modalities have been discussed extensively in the literature 1
. MRI is well known for its superior three-dimensional resolution, and can be used to acquire physiological and ultra-fine anatomical information using different pulse sequences. Unlike other cross-sectional modalities, such as, PET, SPECT, and CT, MRI is free from the issue of ionizing radiation with arbitrary imaging planes and provides multiplanar imaging capabilities. Ultrasound and optical imaging are limited in their ability to detect signals through deep tissue. CT provides anatomical maps for PET/SPECT; however, its role in molecular imaging is restricted due to its low sensitivity and limited contrast resolution of soft tissue. One of the biggest advantages of MRI is its ability to provide images of deep tissues in a background of superb anatomical detail. Furthermore like CT and ultrasound, MR scanners are widely available that can accommodate large animals.
The disadvantages of MRI are difficult interpretation among complex background signal intensity and its relatively low sensitivity. According to Massoud et al, the sensitivity of MRI probe detection is 106
times lower than PET and 1010
times lower than bioluminescence. However, thanks to the development of high field MRI and improved hardware and software designs, the signal to noise ratio of MRI has been improved significantly 1
, and novel approaches used for reporter gene imaging may further increase its sensitivity and specificity.
In a typical MRI, the signal provided by the smallest image element is a function of mobile proton in hydrogen molecule and the relaxation time. There are two types of relaxation times, that is, a T1 spin-lattice relaxation time, and a T2 spin-spin relaxation time. Different pulse sequences exploit localized variations in these relaxation times, so that a given element (a voxel) takes on different signal intensities according to physiological conditions. “Enhancement” is used to increase voxel contrast by perturbing the local environment. Gadolinium, the most commonly used MR contrast “enhancement” material, shortens T1 and produces bright voxels corresponding to gadolinium-containing region on T1-weighted images. On the other hand, iron, the second most common contrast agent, shortens T2, and produces dark voxels on T2-weighted images. T1-shortening agents are more useful clinically because target lesions are imaged at high signal-to-background ratios, whereas T2-shortening agents have higher sensitivity at the molecular level 3
Two types of labeling mechanisms can be used to target a biological process or a cell using MRI. Direct labeling involves the binding of gadolinium or an iron-containing compound to the cell surface or internalized intracellularly. The other mechanism involves reporter gene techniques that induce specific genetic cascades. The major benefits of reporter gene techniques are that cells must be viable to produce an imaging signal, and that imaging signal does not dilute with cell division 4
. Research is being undertaken to find safe transgene strategies for reporter gene imaging.