Mechanisms of contrast enhancement in magnetic resonance imaging

The use of contrast agents has increased the sensitivity and specificity of magnetic resonance imaging (MRI). Contrast in MRI is multifactorial, depending not only on T1 and T2 relaxation rates, but also on flow, proton density and, in gradient-echo sequences, on the angle of the induced field. The use of contrast agents in MRI changes the T1 and T2 relaxation rates, producing increased signal intensity on T1-weighted images or decreased signal intensity on T2-weighted images, or both. All contrast agents produce changes in magnetic susceptibility by enhancing local magnetic fields. These effects are caused by interactions between nuclear and paramagnetic substance magnet moments, which produce accentuated transitions between spin states and cause shortening of T1; the paramagnetic substance causes accentuated local fields, which lead to increased dephasing and thus shortening of T2 or T2* relaxation time. The efficacy of shortening of T1, T2 or T2* relaxation time depends on the distance between the proton nucleus and the electronic field of the paramagnetic compound, the time of their interaction (correlation time) and the paramagnetic concentration. The MRI contrast agents currently in use cause shortening of T1, T2 or T2* relaxation time. Metal chelates (e.g., gadolinium-diethylene triamine penta-acetic acid [Gd-DTPA]) in low concentration cause shortening of T1 relaxation times, and the superparamagnetics (e.g., ferrite) cause shortening of T2 relaxation times.     

Perfusion magnetic resonance imaging and magnetic resonance spectroscopy of cerebral gliomas showing imperceptible contrast enhancement on conventional magnetic resonance imaging

The purpose of the present paper was to evaluate the utility of perfusion MRI in cerebral gliomas showing imperceptible contrast enhancement on conventional MRI, and to evaluate the relationships of perfusion MRI and magnetic resonance (MR) spectroscopic results in these tumours. Twenty-two patients with histopathologically proven cerebral gliomas and showing insignificant contrast enhancement on conventional MR were included in the present study. All patients underwent perfusion MRI and MR spectroscopy on a 1.5-T MR system. Significant differences of the relative cerebral blood volume (rCBV) values and the choline : creatine ratios were noted between low-grade and anaplastic gliomas (P < 0.01). Good correlation was found between the rCBV values and the choline : creatine values (y = 0. 532x + 1.5643; r = 0.67). Perfusion MRI can be a useful tool in assessing the histopathological grade of non-contrast-enhancing cerebral gliomas. Along with MR spectroscopic imaging it can serve as an important technique for preoperative characterization of such gliomas, so that accurate targeting by stereotactic biopsies is possible.     

The impact of partial-volume effects in dynamic susceptibility contrast magnetic resonance perfusion imaging

PURPOSE: To demonstrate the degree of the cerebral blood flow (CBF) estimation bias that could arise from distortion of the arterial input function (AIF) as a result of partial-volume effects (PVEs) in dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI). MATERIALS AND METHODS: A model of the volume fraction an artery occupies in a voxel was devised, and a mathematical relationship between the amount of PVE and the measured baseline MR signal intensity was derived. Based on this model, simulation studies were performed to assess the impact of PVE on CBF. Furthermore, the effectiveness of linear PVE compensation approaches on the concentration function was investigated. RESULTS: Simulation results showed a nonlinear relationship between PVE and the resulting CBF measurement error. In addition to AIF underestimation, PVE also causes distortions of AIF frequency characteristics, leading to CBF errors varying with mean transit time (MTT). An uncorrected AIF measured at a voxel with a partial-volume fraction of 相似文献   

Contrast agent dose effects in cerebral dynamic susceptibility contrast magnetic resonance perfusion imaging

Purpose

To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC‐MRI).

Materials and Methods

Sequential DSC‐MRI (1.5T gradient‐echo echo‐planar imaging using an echo time of 61–64 msec) was performed using contrast agent doses of 0.1 and 0.2 mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12 stroke patients.

Results

1) Arterial signal showed the expected doubling in relaxation response (ΔR2*) to dose doubling. 2) The brain signal showed a less than doubled ΔR2* response to dose doubling. 3) The 0.2 mmol/kg dose studies subtly underestimated cerebral blood volume (CBV) and cerebral blood flow (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF, the 0.2 mmol/kg studies overestimated the CBV and CBF compared with the 0.1 mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in stroke.

Conclusion

Subtle but statistically significant dose sensitivities were found. Therefore, it is advisable to carefully control the contrast agent dose when DSC‐MRI is used in clinical trials. The study also suggests that a 0.1 mmol/kg dose is adequate for hemodynamic measurements. J. Magn. Reson. Imaging 2009;29:52–64. © 2008 Wiley‐Liss, Inc.     

Safety of magnetic resonance imaging contrast agents.

Many of the MR examinations performed in the world each year are accompanied by administration of one of these frequently used intravenous contrast agents: Magnevist, Omniscan, and ProHance. Accordingly, MR practitioners must understand the basic pharmacokinetics, side effects, and the potential for adverse events for these contrast agents. Additionally, MR practitioners must know how to manage side effects and adverse events that may occur in association with the administration of contrast agents. Notably, the use of MR imaging contrast agents in special patient populations must be understood. This article discusses each of these important issues.     

Paramagnetic contrast agents in nuclear magnetic resonance medical imaging

Relaxation time differences are the sources of most of the contrast observed in proton NMR images, not only among normal organs and tissues but between lesions and the adjacent tissue. Although these differences are often large, there are low-contrast situations in which it would be desirable to increase the visibility of an organ or region. The study of time-dependent phenomena would also be aided by the ability to change selected relaxation times deliberately. One way to achieve these goals is to administer substances that change proton relaxation times in tissues without causing significant toxic effects or other physiologic changes. Paramagnetic ions and molecules, those with unpaired electrons, may be useful for this purpose because the very large magnetic effects associated with such electrons can drastically decrease water proton relaxation times at concentrations of the order of 100 to 1000 microM, which may be reached in certain organs after doses of 10 to 100 microM/kg. The general characteristics of such paramagnetic substances are described, and specific animal experiments with manganous ion and its complexes, and with stable nitroxide free radicals and molecular oxygen, are reviewed. The paramagnetic contrast agents already studied are effective, and many more are potentially possible, but the most important questions to be answered are whether acute and chronic toxicity are low enough to permit research and diagnosis on humans.     

Intravascular contrast agents suitable for magnetic resonance imaging

Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging (MR) using a 0.5-T superconducting scanner. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.     

Image contrast and pulse sequences in urinary tract magnetic resonance imaging

Since image contrast in urinary tract proton magnetic resonance imaging (MRI) depends on both intrinsic properties of the imaged tissue and the imaging technique, it is important to understand the principles underlying image production, both while performing urinary tract MRI and when interpreting the images. This paper reviews briefly the major characteristics of tissue that can produce image contrast: mobile proton density, tissue motion, and relaxation times. It also describes the principles by which these factors, together with the choice of pulse sequence, affect image appearance. The specific pulse sequences described include the spin-echo and inversion recovery sequences; the influence of repetition time, echo delay, and inversion time are also described. Although empiric data regarding the best pulse sequences to use for all types and sites of pathology in the urinary tract are not complete, knowledge of the characteristics of normal tissue and the major sorts of pathologic change permit one to make general conclusions about the appropriate choice of pulse sequences.     

T1rho contrast in functional magnetic resonance imaging.

The application of T1 in the rotating frame (T1rho) to functional MRI in humans was studied at 3 T. Increases in neural activity increased parenchymal T1rho. Modeling suggested that cerebral blood volume mediated this increase. A pulse sequence named spin-locked echo planar imaging (SLEPI) that produces both T1rho and T2* contrast was developed and used in a visual functional MRI (fMRI)experiment. Spin-locked contrast significantly augments the T2* blood oxygen level-dependent (BOLD) contrast in this sequence. The total functional contrast generated by the SLEPI sequence (1.31%) was 54% larger than the contrast (0.85%) obtained from a conventional gradient-echo EPI sequence using echo times of 30 ms. Analysis of image SNR revealed that the spin-locked preparation period of the sequence produced negligible signal loss from static dephasing effects. The SLEPI sequence appears to be an attractive alternative to conventional BOLD fMRI, particularly when long echo times are undesirable, such as when studying prefrontal cortex or ventral regions, where static susceptibility gradients often degrade T2*-weighted images.     

Image contrast and pulse sequences in urinary tract magnetic resonance imaging

Since image contrast in urinary tract proton magnetic resonance imaging (MRI) depends on both intrinsic properties of the imaged tissue and the imaging technique, it is important to understand the principles underlying image production, both while performing urinary tract MRI and when interpreting the images. This paper reviews briefly the major characteristics of tissue that can produce image contrast: mobile proton density, tissue motion, and relaxation times. It also describes the principles by which these factors, together with the choice of pulse sequence, affect image appearance. The specific pulse sequences described include the spin-echo and inversion recovery sequences; the influence of repetition time, echo delay, and inversion time are also described. Although empiric data regarding the best pulse sequences to use for all types and sites of pathology in the urinary tract are not complete, knowledge of the characteristics of normal tissue and the major sorts of pathologic change permit one to make general conclusions about the appropriate choice of pulse sequences.     

Off-resonance experiments and contrast agents to improve magnetic resonance imaging

The effect of off-resonance irradiation on the water proton NMR signal intensity has been investigated as follows: (a) in the presence of a paramagnetic probe like manganese(II); (b) in the presence of bovine serum albumin (BSA) and two gadolinium(III) complexes, Gd-DTPA and Gd-BOPTA; (c) in the presence of cross-linked BSA and the two above-mentioned gadolinium(III) complexes. The experimental data have been rationalized on the basis of the available theoretical models. The effectiveness of the two complexes as contrast agents for MRI has been predicted. It is shown that contrast agents providing comparable longitudinal and transverse relaxation rate enhancements are those of general interest for off-resonance magnetization transfer-MRI.     

Long-circulating liposomal contrast agents for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a dynamic technique for imaging vasculature. However, the currently used gadolinium (Gd) chelates, such as Gd-DTPA, restrict the time window for image acquisition due to their rapid elimination from blood and their rapid diffusion into the extravascular space, which prevents their use in steady-state imaging, particularly for MR angiography (MRA). The goal of this study was to prepare long-circulating polyethylene glycol-bearing ((PEG)ylated) liposomes encapsulating Gd chelate, and characterize and demonstrate their utility for MRA. The liposomes were prepared by hydrating a mixture of lipids with gadodiamide (Omniscan). The liposomes were sized down to around 100 nm by extruder and exhaustively dialysed to remove the unencapsulated gadodiamide. The Gd liposomes exhibited a significant sustained (>4 hr) contrast enhancement of the vasculature with improved spatial details in a rat model with little leakage relative to Gd-DTPA controls as shown by MRI. We suggest that such long-circulating liposomal formulations allow for high spatial resolution imaging without the confounding effects of clearance and extravascular diffusion of the agent complicating the data and image analysis.     

Gadolinium contrast agent is of limited value for magnetic resonance imaging assessment of synovial hypertrophy in hemophiliacs

Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring.

Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol.

Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy.

Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.     

Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles.

Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.     

Effect of b value on contrast during diffusion-weighted magnetic resonance imaging assessment of acute ischemic stroke

PURPOSE: To examine the effect of varying the diffusion encoding strength (b value) on the contrast (signal difference, Delta S) between damaged and normal tissue during diffusion-weighted magnetic resonance imaging (DWI) assessment of acute ischemic stroke. MATERIALS AND METHODS: Phantoms with diffusion values approximating those expected in acutely infarcted and normal tissue were constructed from a mixture of agar and formaldehyde and imaged at varying b values (0-3000 mm(-2) second). Ten patients were imaged with multiple b values (500-2500 mm(-2) second) within 12 hours of stroke onset. RESULTS: Theoretical calculations showed that for any combination of diffusion coefficients there existed an optimal b value that was higher than the standard setting of 1000 mm(-2) second, and this was confirmed by the phantom studies. In the patients, increasing b from 1000 to 1500 mm(-2) second increased Delta S (average, 22.4%; P = 0.001), but no consistent benefit was seen at b = 2000 mm(-2) second (P = 0.408). This compared favorably with the average optimal b value of 1662 mm(- 2) second calculated from the patients. CONCLUSION: These results suggest that increasing the b value from 1000 to 1500 mm(-2) second would increase contrast between infarcted and normal tissue in the setting of acute ischemic stroke.