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Purpose The purpose of this work was to develop and evaluate a system consisting of an insertable gradient, RF coils, and animal positioning hardware to enable imaging of the internal structure of the cochlea and other inner ear structures of a guinea pig model at 3T. Methods Transmit and receive RF coils, and an animal positioning system, were developed and integrated with an insertable gradient and animal monitoring system for improved guinea pig cochlea imaging when compared to a standard clinical 3T MRI system. A resolution phantom with 120 μm line separations was used to assess the contrast improvements with the insertable gradient. A homogeneous phantom was used to assess the SNR and homogeneity of the RF coils. FLASH imaging was used to observe the temporal passage of gadolinium contrast through the guinea pig cochlea. Results The insertable gradient enabled increased resolution imaging with nearly twice the contrast-to-noise ratio. The small animal array had better SNR for imaging the guinea pig cochlea (about 14 mm deep) than the commercial Siemens wrist coil (2.2×) and the small birdcage coil (1.6×). The positioning device kept the animal secure and stationary. Injected gadolinium contrast allowed visualization of the internal cochlear structures with FLASH image acquisition, which achieved 100 μm isotropic resolution images in 33 min. Conclusion The specialized RF coils and animal holding equipment designed to operate within the composite gradient enabled higher resolution images than could be obtained from the available RF coils operating in the conventional gradients on the clinical MRI system. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 44B: 89–101, 2015

Purpose: This work compared peripheral nerve stimulation (PNS) thresholds for the MRI scanner body gradients (BODY), a head/neck insert gradient (INSERT), and the combination of both gradient sets used simultaneously (COMPOSITE). Methods: For BODY, INSERT and COMPOSITE gradients, PNS thresholds were determined by exposing subject volunteers to stepped increases in gradient strength. For COMPOSITE mode, the INSERT was applied at equal (experiment 1) or double (experiment 2) the BODY gradient strength. Results: The locations and thresholds of peripheral nerve stimulation depended on the gradient system configuration, gradient axis, and gradient strength. Stimulation in the body occurred when using the BODY Y-gradient axis either singly (110 T/m/s) or in COMPOSITE mode (315 T/m/s experiment 2) and adding the insert gradient had negligible effect on stimulation. Stimulation in the head/sinus area generally occurred when using the INSERT X-gradient either singly (213 T/m/s) or in COMPOSITE mode (320 T/m/s) and adding the body gradient had negligible effect on stimulation. In the COMPOSITE mode, both the location of stimulation and the limiting gradient strength matched location and strength of the limiting component gradient. Conclusion: Stimulation, to a first-order approximation, is independent for the two gradient systems. In COMPOSITE mode, PNS can be dominated by either of the individual gradient components, indicating that the contribution of each component can be increased until the threshold limit of each component gradient is reached. COMPOSITE gradients provide increased gradient performance with PNS thresholds higher than either component gradient system operating alone. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 44B: 66–74, 2015

Purpose: To design and build a head insert gradient coilto use in conjunction with body gradients for superiorimaging.Materials and Methods: The use of the boundary ele-ment method to solve for a gradient coil wire pattern onan arbitrary surface allowed us to incorporate engineeringchanges into the electromagnetic design of a gradient coildirectly. Improved wire pattern design was combined withrobust manufacturing techniques and novel coolingmethods.Results: The finished coil had an efficiency of 0.15 mT/m/A in all three axes and allowed the imaging region toextend across the entire head and upper part of the neck.Conclusion: The ability to adapt an electromagneticdesign to necessary changes from an engineering perspec-tive leads to superior coil performance.Key Words: gradient coil; boundary element method; elec-tromagnetics; cooling; vacuum pot; head imagingJ. Magn. Reson. Imaging 2014;39:1088–1095.

We have constructed a small-bore insertable gradient coil with two linear gradient imaging regions and interfaced it with an MRI scanner. We have also constructed an RF system capable of transmitting or receiving in both regions simultaneously.Designs for conductor placement for two-region X-, Y- and Z-gradient coils were optimized by simulated annealing. Wire patterns for each axis were chosen that gave low inductance, reasonable homogeneity over a large imaging volume and high efficiency (gradient field per-unit-current).Imaging was performed on a Siemens 3T TIM Trio scanner equipped with three additional gradient amplifier channels and a second RF/gradient array controller. Phantoms were placed in the two imaging regions as well as the central non-imaging region to test gradient homogeneity and crosstalk between regions. Images acquired simultaneously in the two regions showed very little signal crosstalk between imaging regions and even less signal from the central, non-imaging region.When combined with an overlapping single-region gradient insert, extended field-of-view (FOV) imaging will be possible without moving the table or the subject and without increasing nerve stimulation. Construction and testing of a two-region gradient coil insert is a necessary intermediate step as a proof of concept for an extended field of view, contiguous, three-region human-sized gradient system.

Many magnetic resonance imaging applications require high spatial and temporal resolution. The improved gradient performance required to achieve high spatial and temporal resolution may be achieved by using local gradient coils such as planar gradient inserts. The planar gradient set provides higher gradient performance because it is placed inside of the imaging bore of the magnet (within the body gradients) in close proximity to the imaging region. Although the wire patterns for planar gradients can be designed using two dimensional stream functions and simulated annealing, optimization of the two dimensional stream functions can be much more computationally intensive and time consuming than optimizing the one dimensional stream functions required for cylindrical gradients. To address this problem, we have developed a simple and rapid method for the design of planar gradient inserts to produce a high strength local gradient field and a reasonably uniform imaging region. By using conformal mapping, the two dimensional problem can be simplified to a faster and more easily calculated one dimensional problem. The mapping transforms the magnetic field and wire patterns in the cylindrical system into a magnetic field and wire patterns in the bi-planar geometry providing a tool for bi-planar gradient coil design using a one dimensional stream function. © 2009 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 35B: 23–31, 2009

Chronic hemodialysis requires a vascular access that provides high flow rates for the extracorporeal recirculation of blood. Although the arteriovenous (AV) fistulas created by the anastomosis of a native artery to a native vein is the preferred access, synthetic polytetrafluoroethylene (PTFE) AV grafts are also widely used in the U.S. Both access types succumb to premature failure due to clotting caused by underlying neointimal hyperplasia formation, although synthetic grafts have a higher rate of failure. The construction or revision of hemodialysis accesses are among the most commonly performed vascular surgery procedures in the U.S (1). Access failure results in significant morbidity in the hemodialysis patient population and currently there is no effective therapy to prevent access failure (2, 3). Synthetic AV grafts could be the preferred access for hemodialysis if the high occurrence of hyperplasia could be prevented, as they generally have larger luminal diameters and shorter waiting times before use than native fistulas. Thus research is ongoing to develop strategies to inhibit hyperplasia and prevent graft failure. Porcine models of AV graft have been developed for the study of the pathogenesis of hyperplasia and treatment modalities. These models recapitulate the pattern of hyperplasia development observed in clinically failed AV grafts, with hyperplasia developing in an accelerated manner (4–7). Thus these models are very useful for studying strategies to prevent AV graft hyperplasia. Analysis of hyperplasia development in the pig model typically involves survival of the animals for 4–8 weeks after graft placement followed by euthanasia and histological analysis of the graft-vessel anastomoses. Hyperplasia occurs most often at the juncture of the graft and vessel but it is also observed within the native vessels, upstream, and downstream of the anastomoses (8). Therefore, histological sampling of multiple sections of the anastomosis and attached vessels is required for a thorough evaluation of hyperplasia development and of treatment effects. Histological analysis provides information regarding the cellular nature of the lesion. Histology from our group and others has shown the lesion consists primarily of cells with smooth muscle cell-like properties, and numerous macrophages and macrophage-derived foreign body cells. The lesion is also a site of conspicuous angiogenesis and deposition of extracellular matrix (4, 5, 9–11). Unfortunately, histological analysis suffers from a number of shortcomings (12). Because of its labor-intensive nature and expense, only a limited number of samples are typically obtained around the graft/vessel anastomosis. Thus, the access region is generally not completely evaluated. Also, the fixation of tissue for histology results in shrinkage and some distortion of vessel structure from the in vivo condition. In addition, artifacts often occur during preparation of thin histology slices due to differences in cutting resistance between the soft vascular tissues and the more resilient sutures and grafts. The graft often becomes detached from the tissue during processing, making the tissue histology difficult to analyze. Another obvious disadvantage to histological analysis is that the animals must be euthanized to obtain the tissue, precluding any further in vivo studies. For these reasons, a technique that readily yields information regarding hyperplasia development throughout the graft and attached vessels in vivo is needed. Development of such a technique could prove useful for evaluating hyperplasia development in patients as well. Some investigators have used intravascular ultrasound or contrast (x-ray) angiography to characterize hyperplasia development in animal models (7, 13–15). Angiography usually requires intravascular catheter placement, and involves exposure of staff to some levels of radiation, as well as the administration of contrast agent to the animal. It also usually provides only two-dimensional images. More importantly, it provides information on the lumen diameter but not the tissues that cause the stenosis. Intravascular ultrasound provides excellent images of the vessel wall with fairly detailed information about the intimal and medial layers but is also invasive, requiring intravenous catheter placement, significant technical skill and expensive non-reusable ultrasound probes. Computed tomography (CT) can provide 3 dimensional images of the lumen but again this technique involves radiation exposure and provides limited information about the hyperplastic tissue. Magnetic resonance imaging (MRI) has previously been used to detect stenoses within AV fistulas and grafts in patients (16–24). These previous investigations used contrast enhanced-MRI to yield luminal images of the vascular tree but no attempts were made to visualize the hyperplastic tissues per se. Recently, MRI has been used to visualize angioplasty-induced coronary lesions in a porcine model and the images were compared to ex vivo MRI and histological specimens from the same animals (25). Good agreement was observed for measurements of vessel wall thickness and area from the MR images and matched histology sections. Here we report the use of MRI to visualize not only the lumen, but also the development of hyperplastic tissue itself in hemodialysis AV grafts in vivo in a porcine model of AV graft failure.

A methodology using magnetic resonance angiography (MRA) is presented for identifying thermally significant blood vessels in isolated kidneys, specifically for use in biothermal model development with application to high intensity focused ultrasound (HIFU). A combination of a proven preservation technique, newly developed MR-compatible experimental procedures and the refinement of MR pulse sequence parameters was used to determine vascular characteristics using high-resolution three-dimensional time-of-flight MRA image of flow through isolated kidneys. Results presented are twofold. First, improved vessel visibility was attained through decreasing the magnetic resonance imaging bandwidth from 150 to 30 Hz ∕ pixel while simultaneously increasing the echo time, repetition time, and flip angle; vascular center line extraction showed an 18% improvement in the number of vessel segments detected and a 23% increase in length of the terminal segments over a base line technique without improvements. Second, the overall system was shown to be practical to determine vascular flow effects during HIFU heating; testing results from heating the kidney with HIFU are presented, showing a decrease of average kidney temperature with an increase of flow rate through the kidney with localized cooling demonstrated surrounding known vessel locations.

Sensitivity encoding (SENSE) was combined with keyhole and selective line acquisition mode (SLAM) techniques to acquire a time series of images during contrast passage. The acquisition speed of the dynamic time frames was improved by a factor of 8 in total. The high spatial frequencies were sampled during the steady state and combined with the dynamic time frames to construct a series of high-resolution time-resolved contrast-enhanced 3D images. Filtered temporal correlation analysis was used to separate the arteries and veins.

The clinical application of macromolecular Gd(III) complexes as MRI contrast agents is impeded by their slow excretion and potential toxicity due to the release of Gd(III) ions caused by the metabolism of the agents. A polymer Gd(III) chelate conjugate with a cleavable spacer has been designed to solve this problem. Poly(l-glutamic acid)-cystamine-[Gd(III)-DOTA] was prepared by the conjugation of DOTA to PGA (MW = 50,000) via cystamine, a cleavable disulfide spacer, followed by the complexation with GdCl(3). A Gd(III) DOTA chelate derivative was readily released from the polymer conjugate in the incubation with cysteine, an endogenous plasma thiol. The conjugate produced significant MRI blood pool contrast enhancement in nude mice bearing OVCAR-3 human ovarian carcinoma xenographs. Less significant contrast enhancement was observed for a small molecular contrast agent, Gd(DTPA-BMA). The pharmacokinetic MRI study showed that the Gd(III) chelate from the conjugate accumulated in the urinary bladder in a similar kinetic pattern to Gd(DTPA-BMA), suggesting that the chelate was released by the endogenous thiols and excreted through renal filtration. The preliminary results suggest that this novel design has a great potential to solve the safety problem of macromolecular MRI contrast agents.

Purpose 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. Materials and Methods Two techniques to reduce the artifact, tri-directional flow compensation (3DFC) and elliptical-centric (EC) phase-encoding order, are investigated in five volunteer studies. Results 3DFC eliminates the pulsation-related artifacts and the vessel distortion. A residual amplitude variation artifact is observed. EC phase encoding nearly eliminates the pulsatile motion-related artifact, but it does not eliminate vessel distortion. Conclusion The combination of 3DFC and EC phase encoding appears to provide the greatest artifact reduction in the five volunteer studies performed. J. Magn. Reson. Imaging 2003;18:121–127. © 2003 Wiley-Liss, Inc.

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. © 2003 Wiley-Liss, Inc.

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.

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.

We studied the time course of changes in the Hahn spin-echo decay (Hahn-T2) in lungs of spontaneously breathing living rats at 1 hour, 3 hours, and 7 days following oleic acid injection. Motion artifacts were minimized by using the motion-insensitive interleaved rapid line scan (ILS) imaging technique. Prior to injury, the lungs exhibited two resolvable exponential Hahn-T2 components. One and 3 hours after injury the decay showed a regionally nonuniform behavior, which was fit with one, two, or three exponential components. The short and medium components increased at 1 and 3 hours after injection. The third, much longer, component is probably due to intraalveolar pulmonary edema. After 7 days the Hahn decay was similar to that observed before injury, probably reflecting resolution of the edema. Our data suggest that Hahn-T2 measurements can be used to characterize the time course and regional distribution of lung injury in living animals. J. Magn. Reson. Imaging 2000;11:215–222. © 2000 Wiley-Liss, Inc.

In this paper, we report on the development of a novel multiple thin-slab projection-reconstruction acquisition technique. To eliminate the slab boundary artifact, the slabs are highly overlapped and only a small fraction of the projection view angles are sampled at each slab position. After Fourier transformation in the slice direction, there are sufficient numbers of projection measurements at each slice position to obtain very high resolution MR angiograms. The technique presented has all of the advantages of multiple overlapping thin slab acquisition (MOTSA) with no evidence of slab boundary artifact. J. Magn. Reson. Imaging 1999;10:569–575. © 1999 Wiley-Liss, Inc.

CNR studies were performed for human intracranial vessels in 3D MRA data sets. The CNR dependency of different imaging parameters, such as flip angle, field of view, echo time, repetition time, and echo readout symmetry, was studied for vessels in the region of the circle of Willis. A theoretical model was developed for MR vascular imaging based on the Bloch equations and Fourier imaging theory. This model predicts the MR image intensity of vessels from basic subject parameters, such as the relaxation times of blood and stationary tissue, vessel dimension, and flow velocity, and the parameters of the imaging technique, such as flip angle, voxel volume, repetition time, and echo time. For most experiments, the model was found to fit the experimental results well. The validity of this model allows the optimization of imaging parameters to maximize vessel CNR in MR angiography.

Many Magnetic Resonance Imaging (MRI) applications such as Dynamic Contrast Enhanced MRI (DCE-MRI) of the breast require high spatial and temporal resolution, and can benefit from improved gradient performance, e.g. increased gradient strength, and reduced gradient rise time. The improved gradient performance required to achieve high spatial and temporal resolution for this application may be achieved by using local insert gradients specifically designed for a target anatomy. Current flat gradient systems cannot create an imaging volume large enough to accommodate both breasts, further, their gradient fields are not homogeneous, dropping off rapidly with distance from the gradient coil surface. To attain an imaging volume adequate for bilateral breast MRI, a planar local gradient system design has been modified into a superellipse shape, creating homogeneous gradient volumes (HGVs) that are 182% (Gx), 57% (Gy), and 75% (Gz) wider (left/right direction) than those of the corresponding standard planar gradient. Adding an additional field-modifying (FM) gradient winding results in an additional improvement of the homogeneous gradient field near the gradient coil surface over the already enlarged HGVs of the superelliptical gradients (67%, 89%, and 214% for Gx, Gy, and Gz respectively). A prototype y-gradient insert has been built to demonstrate imaging and implementation characteristics of the superellipse gradient in a 3T MRI system.

The tradeoff between gradient performance factors, size of the imaging region, and physiological factors such as nerve stimulation typically leads to compromises in gradient design and ultimately suboptimal imaging performance. Local gradient systems can add some performance flexibility, but are cumbersome to set up and remove. In nearly all conventional MRI systems, the use of local gradients precludes the use of the more homogeneous whole body gradients. This paper presents the concept of dynamically selectable composite gradient systems where local gradients and whole body gradients can be selected independently and simultaneously. The relative performance of whole body, insert, and composite gradients is predicted for echoplanar (EPI), turbo spin echo (TSE), and steady state free precession (SSFP). A realization of the concept is presented.

We compared in vivo and in vitro Hahn echo T2 measurements in rat lungs in both imaging and nonimaging modes. All measurements could be characterized by multiexponential functions consisting of either two or three exponentials. Essentially the same values of the time constants were observed for spontaneously breathing rats and for excised lungs. © 1991 Academic Press, Inc.

A methodology using magnetic resonance angiography (MRA) is presented for identifying thermally significant blood vessels in isolated kidneys, specifically for use in biothermal model development with application to high intensity focused ultrasound (HIFU). A combination of a proven preservation technique, newly developed MR-compatible experimental procedures and the refinement of MR pulse sequence parameters was used to determine vascular characteristics using high-resolution three-dimensional time-of-flight MRA image of flow through isolated kidneys. Results presented are twofold. First, improved vessel visibility was attained through decreasing the magnetic resonance imaging bandwidth from 150 to 30 Hz/pixel while simultaneously increasing the echo time, repetition time, and flip angle; vascular center line extraction showed an 18% improvement in the number of vessel segments detected and a 23% increase in length of the terminal segments over a base line technique without improvements. Second, the overall system was shown to be practical to determine vascular flow effects during HIFU heating; testing results from heating the kidney with HIFU are presented, showing a decrease of average kidney temperature with an increase of flow rate through the kidney with localized cooling demonstrated surrounding known vessel locations.

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. © 2005 Wiley-Liss, Inc.

To study the accumulation of macromolecules into the arthritic joints and the possible applications of such phenomenon.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.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.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.

Biodegradable PEGylated Gd-DTPA l-cystine copolymers, PEG-g-poly(GdDTPA-co-l-cystine), were prepared and tested as a blood pool contrast agent in mice. The biodegradable macromolecular agent was designed to be broken down into smaller Gd complexes by endogenous thiols via the disulfide-thiol exchange reaction to facilitate the clearance of Gd complexes after the contrast-enhanced MRI examination. Gd-DTPA l-cystine copolymers were synthesized by condensation polymerization of l-cystine and DTPA-dianhydride in water followed by chelating with Gd(OAc)(3). MPEG-NH(2) (MW = 2000) was then conjugated to the polymeric backbone in different ratios. The macromolecular contrast agent was readily degraded with the incubation of l-cysteine. It also demonstrated superior contrast enhancement in the heart and blood vessels as compared to a low molecular weight control agent, Gd-(DTPA-BMA). At 1 h postcontrast, the PEGylated macromolecular agent still showed prominent enhancement, while little contrast enhancement was detectable in the blood pool by the control agent. PEG-g-poly(GdDTPA-co-l-cystine) shows promise as an MR blood pool imaging agent.

Purpose Computer simulations and measurements on human volunteers were used to test the extent to which the quality of carotid imaging might be improved by coil arrays that are not limited by a constraint on the number of RF coil receiver ports. Methods Analytic near-field equations for the magnetic and electric fields of a rectangular loop resonator were used to estimate the relative signal-to-noise ratio (rSNR) along the length of a simulated carotid artery as a function of loop size, loop position and vessel depth. The sizes, positions and number of elements in a linear coil array that resulted in the maximum composite SNR along the length of a simulated carotid artery were then estimated. The linear array results were used to predict the total number of elements needed for optimal imaging of the carotid arteries. Also, three normal volunteers were imaged with a variety of RF coils, and the rSNR measurements along the lengths of the carotid artery were evaluated for each coil combination. Results The analytic simulation and the human volunteer measurements both show that improved SNR (e.g., >300% at the bifurcation) can be obtained with coils tailored to each specific region of the carotid artery in comparison to that obtained with four-element arrays designed and used to image the entire carotid artery. Conclusions The resulting number of coil ports, 16 to 24, required for full coverage of the carotid arteries is consistent with the number of channels just becoming available on recently developed clinical scanners.

Purpose To evaluate the ability of high-resolution MRA to monitor changes in intracranial aneurysm volume, and devise a highly reliable technique for obtaining these measurements. Materials and Methods To obtain a baseline estimate of the repeatability of MRA scans and validate the statistics-based technique for aneurysm volume measurement, multiple scans were obtained on individual subjects over a period of up to 1 year. These 3D MRA data sets were coregistered and then analyzed using the volumetric analysis of segmented data and the proposed statistical method. Results It was shown that high-resolution MRA provides highly repeatable data sets. Both methods used for the aneurysm volume measurements showed consistent results. However, the proposed statistical method had lower error and was much less sensitive to the choice of segmentation parameter than the volumetric analysis of segmented data. A change of 1 mm in the average radius of the aneurysm was detectable with the statistics-based technique. Conclusions This study demonstrates that the statistical method of aneurysm volume measurement in high-resolution MRA allows reliable and accurate assessments of aneurysm volume changes. J. Magn. Reson. Imaging 2004;20:340–346. © 2004 Wiley-Liss, Inc.

We evaluate three measures of technical image quality for intracranial magnetic resonance angiography (MRA): (1) a two-alternative forced choice (2AFC) evaluation of vessel visibility, (2) vessel-to-background signal-difference-to-noise ratio (SDNR), and (3) observer ranking of the fidelity of vessel morphology compared to that in a gold standard image. The gold standard used for both the 2AFC and ranking measures is intraarterial catheter angiography. These measures are applied to healthy arterial segments. The 2AFC and SDNR measures directly evaluate the visibility of artery segments for which the existence is known from the gold standard images. We argue that (1) 2AFC evaluates the carrier signals on which any vascular disease process is modulated and provides an upper bound on the detectibility of vascular lesions, (2) SDNR is a predictor of 2AFC, and (3) ranking may be used to predict the relative performance of techniques in the detection of vascular lesions.

In this study, the problem of small vessel visualization in magnetic resonance angiography is addressed. The loss of vessel contrast due to slow flow-related signal saturation can be compensated by the T, reduction obtained from the use of an MR contrast agent, such as Gd-DTPA. The vessel/background signal-difference-to-noise ratio (SDNR) is shown to strongly depend on the imaging parameters, as well as on the time course of the blood T, values obtained from the contrast injection. Specifically, it was found that vessel SDNR increases almost linearly with TR, if the sampling bandwidth is reduced proportionately.

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.

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.

The water–biopolymer cross-relaxation model, proposed by H. E. Rorschach and C. F. Hazlewood (RH) [ J. Magn. Reson. 70, 79 (1986)], explains the Larmor frequency dependence of T 1 in many biological systems. However, the RH theory fails at low Larmor frequencies. In this paper, a more general version of the RH theory has been developed. This theory is valid at all frequencies. Use of the new expression for the spin–lattice relaxation rate (1/ T 1 ), earlier published experimental data in H 2 O/D 2 O bovine serum albumin, which had been measured over a wide frequency range (10 kHz to 100 MHz), were fitted over the entire frequency range. The agreement between theory and the experimental data is excellent. Theoretical expressions for the rotating-frame spin–lattice relaxation rate (1/ T 1ρ ) were also obtained.

To determine the possibility of using nuclear magnetic resonance imaging to study experimentally induced lung injury, we measured in the lungs of spontaneously breathing living rats the time course of both the Hahn spin-echo decay (T2) and the proton density after endotoxin injury. In order to minimize artifacts arising from motions of the nearby chest wall and heart, we used a motion-insensitive technique (the interleaved line scan). A typical Hahn T2 measurement was obtained over a region of interest from a series of images each with a different echo time, which ranged from 16 to 110 ms. Lung water content was determined by integrating the proton density over the region of interest. The Hahn T2 and proton density were measured before and at 1, 3, 6, and 9 h after intravenous injection of endotoxin. The effects of the treatment administered before and after endotoxin injection were also evaluated. Endotoxin treatment caused lengthening of both fast (T2f) and slow (T2s) Hahn T2 components but had no significant effect on the proton density, consistent with the notion that endotoxin causes lung injury without significant lung water accumulation in rats. However, the methylprednisolone treatment prevented the lengthening of T2s but did not seem to have a significant effect on T2f. Our results suggest that NMR imaging can be used to detect and monitor experimental lung injury in intact living animals, even in the absence of variations of lung water content.

The spin–lattice relaxation time T 1 was measured in excised degassed (airless) rat lungs over the frequency range 6.7 to 80.5 MHz. The observed frequency dependence was fitted successfully to the water–biopolymer cross-relaxation theory proposed by H. E. Rorschach and C. F. Hazlewood (RH) [ J. Magn. Reson. 70, 79 (1986)]. The rotating frame spin–lattice relaxation time T 1ρ was also measured in rat lung fragments over the frequency range 0.56 to 5.6 kHz, and the observed frequency dependence was explained with an extension of the RH model. The agreement between the theory and the experimental data in both cases is good.