Elsevier

Clinical Radiology

Volume 65, Issue 7, July 2010, Pages 557-566
Clinical Radiology

An introduction to functional and molecular imaging with MRI

https://doi.org/10.1016/j.crad.2010.04.006Get rights and content

Magnetic resonance imaging (MRI) has been applied to many aspects of functional and molecular imaging. Many of the parameters used to produce image contrast in MRI are influenced by the local chemical environment around the atoms being imaged; these parameters can be exploited to probe the molecular content of tissues and this has been shown to have many applications in radiology. Diffusion-weighted imaging is a well-established method for measuring small changes in the molecular movement of water that occurs following the onset of ischaemia and in the presence of tumours. Exogenous contrast agents containing gadolinium or iron oxide have been used to image tissue vascularity, cell migration, and specific biological processes, such as cell death. MR spectroscopy is a technique for measuring the concentrations of tissue metabolites and this has been used to probe metabolic pathways in cancer, in cardiac tissue, and in the brain. Several groups are developing positron-emission tomography (PET)-MRI systems that combine the spatial resolution of MRI with the metabolic sensitivity of PET. However, the application of MRI to functional and molecular imaging is limited by its intrinsic low sensitivity. A number of techniques have been developed to overcome this which utilize a phenomenon termed hyperpolarization; these have been used to image tissue pH, cellular necrosis, and to image the lungs. Although most of these applications have been developed in animal models, they are increasingly being translated into human imaging and some are used routinely in many radiology departments.

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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