K. Craig Goodrich

Improved efficiency in double-inversion fast spin-echo imaging

Double‐inversion fast spin‐echo (FSE) pulse sequences can be designed to provide excellent suppression of blood signal in black‐blood MRI. However, because a nonselective inversion is used, these sequences typically have been highly inefficient. In this work it is demonstrated that the efficiency of double‐inversion sequences can be greatly improved by a form of interleaving in which all of the slices to be imaged in a single pass are reinverted each time a signal is obtained from any single slice. To date, several studies have demonstrated a high level of blood suppression with these more efficient techniques. Magn Reson Med 47:1017– 1021, 2002.

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.

Contrast-enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor-bearing mice

The structures of polydisulfide‐based biodegradable macromolecular Gd(III) complexes were modified to improve their in vivo retention time and MRI contrast enhancement. Steric hindrance was introduced around the disulfide bonds to control their access to free thiols in order to alter the degradation rate of the copolymers. Two new macromolecular agents, (Gd‐DTPA)‐cystine copolymers (GDCP) and (Gd‐DTPA)‐cystine diethyl ester copolymers (GDCEP), were prepared. Both agents were readily degraded in vitro and in vivo by the disulfide‐thiol exchange reaction, but at a slow rate. The introduction of COOH and COOEt groups slowed down the degradation of the copolymers in the incubation with 15 μM cysteine. Metabolic degradation products were identified by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry in the urine samples from rats injected with the agents. The T1 relaxivity (r1) was 5.43 mM−1s−1 for GDCP, and 5.86 mM−1s−1 for GDCEP, respectively, at 3T. MRI contrast enhancement of both agents was studied in nude mice bearing MDA‐BM‐231 human breast carcinoma xenografts, on a Siemens Trio 3T scanner. The modified agents resulted in more significant contrast enhancement in the blood pool and tumor periphery than (Gd‐DTPA)‐cystamine copolymers (GDCC) and a low‐molecular‐weight control agent, Gd‐(DTPA‐BMA), at a dose of 0.1 mmol‐Gd/kg. The results demonstrate that the structural modification of the biodegradable macromolecular Gd(III) complexes resulted in a relatively slow degradation of the macromolecules and significantly improved in vivo contrast enhancement. The modified agents show promise for use in investigations of blood pool and cancer by contrast‐enhanced (CE) MRI. Magn Reson Med 53:835–842, 2005.

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.

Longitudinal Assessment of Hyperplasia Using Magnetic Resonance Imaging without Contrast in a Porcine Arteriovenous Graft Model

RATIONALE AND OBJECTIVES Chronic hemodialysis requires a vascular access that provides high blood-flow rates for the extracorporeal recirculation of blood. Synthetic arteriovenous (AV) grafts often fail because of clotting caused by underlying hyperplasia formation. The authors report the use of magnetic resonance (MR) imaging (MRI) without contrast agent to monitor tissue hyperplasia formation as well as luminal area in a porcine model of AV graft stenosis. MATERIALS AND METHODS Expanded reinforced polytetrafluoroethylene grafts were surgically placed between the common carotid artery and the external jugular vein, bilaterally, in pigs. Animals underwent MRI in a 3-T scanner at 3, 4, or 6 weeks after graft placement, followed by euthanasia and the collection of grafts and adjacent tissues for histologic analysis. Two animals underwent sequential scanning at 1, 2, 3, 5, and 7 weeks after graft placement, followed by histologic analysis. RESULTS Measurements of hyperplasia obtained from the MR images were compared with, and correlated well with, measurements obtained from the histologic cross-sections (r = 0.932, P = .02). The MR images provided a more complete view of the venous hyperplasia throughout the graft compared with histology. The MR images could be examined from multiple angles and were unaffected by histologic preparation artifacts. CONCLUSION Unlike histology, MRI provided longitudinal 3-dimensional views of hyperplasia within the AV grafts. This ability of MRI to more completely identify the geometry of hyperplasia and to quantify the tissue volume in vivo could provide benefits over histologic analysis in assessing the pathology of AV graft failure and the efficacy of antihyperplasia interventions.

The need for phase-encoding flow compensation in high-resolution intracranial magnetic resonance angiography

To demonstrate that the time delay between phase and frequency encoding and the presence of pulsatile blood flow in high‐resolution time‐of‐flight (TOF) imaging of the intracranial arteries (especially near the circle of Willis) can distort the appearance of blood vessels and result in a cross‐hatch—appearing artifact in surrounding tissue.

A quantitative study of ramped radio frequency, magnetization transfer, and slab thickness in three-dimensional time-of-flight magnetic resonance angiography in a patient population

RATIONALE AND OBJECTIVES The authors compare the effectiveness of various magnetic resonance (MR) angiography acquisition strategies in enhancing the visibility of small intracranial vessels. METHODS Blood vessel contrast-to-noise ratio (CNR) in time-of-flight MR angiography was studied as a function of vessel size and several selectable imaging parameters. Contrast-to-noise measurements were made on 257 vessel segments ranging in size from 0.3 mm to 4.2 mm in patients who recently had undergone intraarterial cerebral angiography. Imaging parameters studied included magnetization transfer, spatially variable radio frequency (RF) pulse profile (ramped RF), and imaging slab thickness. RESULTS The combination of thin slabs (16 slices/slab), ramped RF, and magnetization transfer resulted in the highest CNR for all but the smallest vessel sizes. The smallest vessels (< 0.5 mm) had the highest CNR, using the thick slab (64 slices/slab) with ramped RF and magnetization transfer. Magnetization transfer always improved vessel CNR, but the improvement diminished as the slab thickness was reduced. The CNR increased with a decrease in slab thickness for all but the smallest vessel sizes. CONCLUSIONS Overall, the results provide a quantitative demonstration that inflow enhancement of blood is reduced for small vessels. Thus, whereas magnetization transfer is important at all vessel sizes, it becomes the primary factor in improving the visibility of the smallest vessels.

Velocity measurement based on bolus tracking with the aid of three- dimensional reconstruction from digital subtraction angiography

The problem of blood flow measurement in x-ray angiography using measurements of the leading edge of the contrast bolus as it traverses the vascular bed is considered. A new technique for velocity measurement is presented based upon the ratio of the temporal derivative to the spatial derivative of the contrast bolus in the direction of flow. With the addition of a small correction factor, the value obtained is shown to reflect the transport velocity, or the velocity at which the contrast is transported down the vessel of interest. Most blood flow measurements based on bolus tracking techniques are actually using the contrast transport velocity to represent the blood flow velocity. Because of the streaming that occurs due to laminary flow conditions, the measured transport velocity is found to be somewhere between the average and the peak (central) fluid velocities for measurements taken during the traversal of the bolus leading edge. The spatial and temporal variation of the transport velocity are found to be consistent with the bolus motion expected in the presence of laminar flow. From x-ray images of contrast passage through simple tubes, we find that the derivative method measures the transport velocity during passage of the bolus leading edge. In most cases of laminar blood flow, the leading edge transport velocity can be 20%-40% higher than the average blood velocity.