Henry R. Buswell

Contrast-enhanced magnetic resonance angiography of cerebral arteries: A review

The loss of blood vessel visibility due to the signal saturation of slow flow can be partially overcome by the T1 reduction that occurs with the use of contrast agents such as Gd-DTPA during magnetic resonance angiography (MRA) studies. Dynamic-imaging techniques that have been applied successfully in abdominal imaging may also be useful for intracranial applications. However, the time between arterial and venous enhancement is very short during intracranial circulation. This limits the spatial resolution that can be obtained between arterial and venous enhancement. Fortunately, the blood-brain barrier and the relatively long duration of significant decrease in blood T1 has led to the development of very high resolution intracranial MRA techniques. Knowledge of the contrast-agent dilution factors and the ultimate resulting relaxation rates can be used to optimize the imaging parameters to maximize vessel signal relative to the background signal (the signal-difference-to-noise ratio). The additional venous vascular detail in the contrast-enhanced study can be spatially resolved in the 3D image data and determined by incorporating information from both high-resolution precontrast and postcontrast studies. In this article, the history, development and application of contrast agents in MRA are presented.

Extracellular biodegradable macromolecular gadolinium(III) complexes for MRI.

The clinical application of macromolecular gadolinium (Gd) complexes as MRI contrast agents is limited by the slow excretion of Gd(III) complexes and consequent long‐term tissue accumulation of toxic Gd ions. To alleviate the problem of slow excretion, biodegradable polydisulfide‐based macromolecular Gd(III) complexes were designed and prepared based on the disulfide‐thiol exchange to allow degradation of the macromolecules by endogenous thiols and to facilitate excretion of Gd(III) complexes after the MRI examination. The in vitro degradation study showed that the polydisulfide agent was readily degraded by cysteine at plasma thiol concentrations. No cross‐reaction was observed between the cysteine‐34 on human serum albumin (HSA) with the agent. Concentration‐dependent blood pool contrast enhancement was observed for the polydisulfide agents. The agents of both high molecular weight (35,000 Da) and low molecular weight (17,700 Da) produced significant contrast enhancement in the heart and aorta in rats at relatively high doses. Except for the bladder, the signal intensities gradually decreased over time. Significant blood pool contrast enhancement was also observed for the high molecular weight agent at a low dose (0.03 mmol‐Gd/kg), but not for the agent with a lower molecular weight. The contrast enhancement in the urinary bladder increased over time for the polydisulfide agents and Gd(III)‐(DTPA‐BMA). Degradation products were identified by mass spectrometry in the urine samples from the rats administered with both polydisulfide agents, which confirmed that the polydisulfide agents were degraded in vivo and excreted through renal filtration. The preliminary results demonstrated the in vitro and in vivo degradability, superior blood pool contrast enhancement, and rapid clearance through renal filtration of the novel biodegradable macromolecular agent. This agent has a great potential for further preclinical and clinical development with application in contrast‐enhanced blood pool and cancer MR imaging. Magn Reson Med 51:27–34, 2004.

The arthrotropism of macromolecules in adjuvant-induced arthritis rat model: a preliminary study.

AbstractPurpose.To study the accumulation of macromolecules into the arthritic joints and the possible applications of such phenomenon. Methods. The accumulation of plasma albumin in the joints of adjuvant-induced arthritis (AIA) rat model was first visualized with Evans blue injection. A N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer contrast agent was then synthesized and injected into the AIA rats to allow qualitative examination of biodistribution and pharmacokinetics of the injected macromolecule with magnetic resonance imaging (MRI). Vital organs and the diseased joints were isolated and examined histologically to correlate with the MRI findings. Results. Deep blue color developed around the arthritic joints of the AIA rat a few hours after the injection of Evans blue. MR imaging of the AIA rats injected with polymer contrast agent demonstrated a gradual but very strong accumulation of the injected polymer in the arthritic joints, which lasted for 1∼2 days. Observed differences in the concentration of the injected polymer in the joints correlated with disease severity as assessed histologically. Conclusions. Profound arthrotropism of macromolecules in the AIA rat model was demonstrated with various imaging tools. These observations should help in the conceptual and practical design of novel macromolecular delivery systems for the imaging and treatment of rheumatoid arthritis.

A three-coil comparison for MR angiography

The purpose of this work was to compare intracranial magnetic resonance angiography (MRA) image quality using three different radiofrequency coils. The three coil types included a reduced volume quadrature birdcage coil with endcap, a commercially available quadrature birdcage head coil, and a four‐element phased‐array coil. Signal‐to‐noise ratio (SNR) measurements were obtained from comparison studies performed on a uniform cylindrical phantom. MRA comparisons were performed using data acquired from 15 volunteers and applying a thick‐slab three‐dimensional time‐of‐flight sequence. Analysis was performed using the signal difference‐to‐noise ratio, a quantitative measure of the relative vascular signal. The reduced‐volume endcap and phased‐array coils, which were designed specifically for imaging the intracranial volume of the head, improved the image SNR and vascular detail considerably over that obtained using the commercially available head coil. The endcap coil configuration provided the best vascular signal overall, while the phased‐array coil provided the best results for arteries close to the coil elements. J. Magn. Reson. Imaging 2000;11:458–468.

Triple contrast technique for black blood imaging with double inversion preparation

This work reports on the development of a pulse sequence to simultaneously acquire proton density, T1, and T2 weighted images in a single magnetization prepared fast spin echo acquisition. The technique is based upon the application of a magnetization preparation consisting of a global inversion followed by slice‐selective 180° and 90° pulses to prepare the signal of specific slices. Slices are acquired in an interleaved manner with time delays appropriate for the desired image contrasts. Data acquisition is repeated for all combinations of slice interleaving covering the region of interest until images from all slice locations have been acquired with all desired image contrasts. The multiple image contrasts obtained with this technique should be useful in applications where discrimination between different types of tissue components is desired, such as in the analysis of plaque in cervical carotid artery disease. Magn Reson Med 52:1379–1387, 2004.

A direct comparison of adenosine and regadenoson myocardial perfusion reserves measured by MRI

Methods 8 subjects (5 female, 3 male) without ischemia were imaged on a 3 T Siemens Trio system. Imaging was done first at rest, and then during adenosine infusion (140 ug/ kg/min) and 34 ± 4 minutes later with regadenoson injection (0.4 mg/5 ml). A 5 cc/sec injection of Gd-BOPTA (MultihanceTM) was used, with doses of 0.02, 0.03 and 0.03 mmol/kg, respectively. The contrast was injected ~3 minutes after the start of the adenosine infusion, and ~90 seconds after the regadenoson injection. A saturation recovery radial turboFLASH sequence was used with 72 rays acquired after each saturation pulse. Scan parameters were TR = 2.6 msec, TE = 1.14 msec, flip = 14, slice thickness = 8 mm. Reconstruction was performed by iteratively minimizing a cost function as in [1] with total variation constraints in both space and time dimensions. Processing was performed in a manner similar to [2] to convert the arterial input functions into gadolinium concentration to remove the effects of saturation. Images were registered and segmented to give time curves from 6 tissue regions per slice. The curves were fit to a two compartment model and Ktrans used as an index of perfusion.