An introduction to functional and molecular imaging with MRI
Section snippets
Background
Molecular and functional imaging using MRI is based on the established principles of nuclear magnetic resonance (NMR), which have been used to analyse molecular structures since the 1940s.1, 2, 3 Throughout the 1950s and the 1960s, NMR was used to evaluate a wide variety of substances and tissues, but it was not until the 1970s that the medical applications of NMR became realized.4 The major breakthrough for medical imaging came in 1973 when Paul Lauterbur demonstrated that the origin of the
Dynamic contrast-enhanced MRI (DCE-MRI)
DCE-MRI is performed following injection of intravenous contrast medium and is used to assess tissue vascularity. Most MRI contrast agents use gadolinium, which shortens the T1 relaxation time of the adjacent protons in water and produces increased signal on T1-weighted imaging (the T2 relaxation time will also be shortened).7 Free gadolinium ions are toxic and therefore they are combined with a chelate such as diethylene triamine penta-acetic acid (DTPA).7 DCE-MRI uses either low molecular
Diffusion-weighted imaging (DWI)
DWI is based upon the thermal movement of molecules, which is random and often referred to as Brownian motion.8 If the diffusion constant is high, then the molecules will diffuse further in a fixed time interval compared to molecules with a lower diffusion constant.7 Conversely, by measuring how far a molecule moves in a fixed time interval, the diffusion constant can be calculated. DWI usually employs magnetic field gradients, which sensitize a spin-echo sequence to these small molecular
Magnetic resonance spectroscopy (MRS)
Certain nuclei will resonate in a magnetic field at a frequency that is determined by the local chemical environment around them. For example, the two hydrogen nuclei (1H or protons) in each molecule of water have a different resonant frequency from the hydrogen nuclei in fat and this can be exploited in fat-suppressed imaging. This principle allows MRS to probe many metabolites simultaneously; the relative size of each peak in a spectrum acquired from a volume of tissue is proportional to the
Targeted contrast agents and CEST agents
Water-soluble contrast media are used in DCE-MRI, which consequently reflects the movement of free water. An alternative approach is to link a gadolinium chelate to a probe that will target a specific molecule of biological interest. A relatively high concentration of contrast agent (0.01–0.1 mm) is necessary to produce a local alteration in the water signal intensity and, therefore, amplification strategies are required to accumulate a large number of gadolinium ions at the site of interest;
Cell labelling and gene expression with MRI
Contrast agents incorporating superparamagnetic iron oxide (SPIO) nanoparticles have shown promise as a means to image labelled cells using MRI.54 They are usually injected as carbohydrate-coated particles measuring approximately 50–100 nm in diameter that can be transported across cell membranes.55 Even at very low concentration, SPIOs create magnetic field inhomogeneity; this dephases the protons which reduces the signal intensity seen on T2*- or T2-weighted images.7 Cells can be labelled by
PET-MRI
Recently, there has been an interest in combining the high sensitivity of metabolic imaging using PET with the high spatial and contrast resolution of MRI. PET-CT is now an important clinical tool but PET-MRI would have a number of advantages, including a reduction in radiation dose and improved soft-tissue resolution.66, 67 The major problem for PET-MRI is that conventional photomultiplier tubes (PMTs) are very sensitive to even weak magnetic fields.67 To overcome this, optical fibres have
Hyperpolarization techniques
Although MRI has many advantages for molecular imaging, its major disadvantage is low sensitivity to detection. To put this into context, when protons are placed into a magnetic field they enter one of two energy levels; approximately half will enter the lower energy level and approximately half will enter the higher energy level. There is a small difference between these two pools, which is typically of the order of a few parts per million, and it is this small number of protons that is used
Conclusion
The basic principles of NMR have allowed MRI to be exploited for molecular and functional imaging. MRI is a versatile technique that can be used to image tissue anatomy, probe vascularity and water diffusion, as well as to image specific molecular targets on or within cells. In general, functional and molecular techniques probe processes that require amplification for detection. Therefore, they represent a compromise between spatial resolution and sensitivity; instead of traditional high
Acknowledgements
The author holds funding from Cancer Research UK, the Royal College of Radiologists UK, the National Institute for Health Research Cambridge Biomedical Research Centre, and the School of Clinical Medicine at the University of Cambridge. The author is grateful to Dr James O’Connor of the University of Manchester, for providing helpful comments on the manuscript.
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