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Dennis L Parker

Publications and source records attributed to Dennis L Parker.

At least 19 recordsLinked to original sources

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PURPOSE: The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. METHODS: Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. RESULTS: The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. CONCLUSION: These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

Animals↗

Biodegradable cystamine spacer facilitates the clearance of Gd(III) chelates in poly(glutamic acid) Gd-DO3A conjugates for contrast-enhanced MR imaging.

Poly(L-glutamic acid) (PGA)-cystamine-[gadolinium (Gd)-DO3A] was prepared in high yield with a high Gd-DO3A conjugation efficiency. Approximately 55% of the carboxylic groups in PGA were loaded with Gd-DO3A via cystamine as the spacer. Cystamine can be readily cleaved by endogenous thiols to release the Gd(III) chelates from the conjugate facilitating Gd(III) excretion after the magnetic resonance imaging (MRI). The contrast-enhanced MRI with PGA-cystamine-(Gd-DO3A) was investigated in mice bearing MDA-MB-231 breast carcinoma xenografts. PGA-1,6-hexanediamine-(Gd-DO3A), a paramagnetic polymer conjugate of a nondegradable spacer, was used as a control. Both conjugates resulted in similar contrast enhancement in the heart, vasculature, liver and kidneys in the first hour post injection. More substantial signal intensity reduction was observed for PGA-cystamine-(Gd-DO3A) in these organs than PGA-1,6-hexanediamine-(Gd-DO3A) due to release of the Gd chelates from PGA-cystamine-(Gd-DO3A) after the cleavage of the disulfide spacer by the endogenous thiols. Both conjugates resulted in similar tumor enhancement with approximately 70% increased signal intensity in the tumor periphery and 10-40% increased signal intensity in tumor interstitium. No cross-reaction was observed between PGA-cystamine-(Gd-DO3A) and human serum albumin, a plasma protein containing a cysteine residue. PGA-cystamine-(Gd-DO3A) resulted in significantly lower Gd(III) tissue retention than PGA-1,6-hexanediamine-(Gd-DO3A) 10 days after the injection in the mice (P<.05). The conjugation of Gd(III) chelates to biomedical copolymers via the degradable disulfide spacer resulted in significant contrast enhancement in the blood pool and tumor tissue but minimal long-term Gd(III) tissue retention.

Absorbable Implants↗

Effect of size and charge on pharmacokinetics and in vivo MRI contrast enhancement of biodegradable polydisulfide Gd(III) complexes.

The purpose of this study is to investigate how the structures of polydisulfide Gd(III) complexes affect their pharmacokinetics and in vivo contrast enhancement as biodegradable macromolecular MRI contrast agents. A negatively charged polydisulfide Gd(III) complex, (Gd-DTPA)-cystine copolymers (GDCP), and a neutral agent, (Gd-DTPA)-cystine diethyl ester copolymers (GDCEP), with different molecular weights were prepared and characterized. The MRI contrast enhancement of the agents was studied in mice. Neutral GDCEP showed more rapid degradation than negatively charged GDCP in the blood plasma. Consequently, GDCP resulted in more significant and prolonged contrast enhancement in the blood pool and liver than GDCEP. The size of GDCEP did not significantly affect its in vivo contrast enhancement due to rapid degradation and clearance from the blood circulation. The increase in the molecular weight of GDCP resulted in prolonged in vivo contrast enhancement in the blood pool. The structural modification of polydisulfide Gd(III) complexes resulted in biodegradable macromolecular MRI contrast agents with different degradability and in vivo contrast enhancement.

Animals↗

k-space inherited parallel acquisition (KIPA): application on dynamic magnetic resonance imaging thermometry.

In this study, a novel method for dynamic parallel image acquisition and reconstruction is presented. In this method, called k-space inherited parallel acquisition (KIPA), localized reconstruction coefficients are used to achieve higher reduction factors, and lower noise and artifact levels compared to that of generalized autocalibrating partially parallel acquisition (GRAPPA) reconstruction. In KIPA, the full k-space for the first frame and the partial k-space for later frames are required to reconstruct a whole series of images. Reconstruction coefficients calculated for different segments of k-space from the first frame data set are used to estimate missing k-space lines in corresponding k-space segments of other frames. The local determination of KIPA reconstruction coefficients is essential to adjusting them according to the local signal-to-noise ratio characteristics of k-space data. The proposed algorithm is applicable to dynamic imaging with arbitrary k-space sampling trajectories. Simulations of magnetic resonance thermometry using the KIPA method with a reduction factor of 6 and using dynamic imaging studies of human subjects with reduction factors of 4 and 6 have been performed to prove the feasibility of our method and to show apparent improvement in image quality in comparison with GRAPPA for dynamic imaging.

Algorithms↗

Multiple-region gradient arrays for extended field of view, increased performance, and reduced nerve stimulation in magnetic resonance imaging.

This article presents a novel design for magnetic resonance imaging (MRI) gradient systems. This design may allow the development of MRI scanners that are capable of imaging large regions with high performance while minimizing the potential for nerve stimulation. The general concept of the gradient system is that spatial oscillation is incorporated such that each gradient coil creates multiple, approximately linear gradient regions that oscillate in gradient polarity. Separate radiofrequency (RF) coil arrays are designed to be sensitive to the signals within each linear region and thus allow signal measurements to be obtained separately from each region. Enabling image acquisition in the transition region that separates each pair of adjacent linear regions requires a second gradient system with imaging regions that overlap and coincide with the transition regions of the first gradient system. Imaging the extended field of view (FOV) is accomplished by interleaved operation of the two gradient systems. Simulated annealing is used to create designs for both longitudinal and transverse gradient systems with two imaging regions.

Computer Simulation↗

High-resolution DTI of a localized volume using 3D single-shot diffusion-weighted STimulated echo-planar imaging (3D ss-DWSTEPI).

Diffusion tensor MRI (DTI) using conventional single-shot (SS) 2D diffusion-weighted (DW)-EPI is subject to severe susceptibility artifacts. Multishot DW imaging (DWI) techniques can reduce these distortions, but they generally suffer from artifacts caused by motion-induced phase errors. Parallel imaging can also reduce the distortions if the sensitivity profiles of the receiver coils allow a sufficiently high reduction factor for the desired field of view (FOV). A novel 3D DTI technique, termed 3D single-shot STimulated EPI (3D ss-STEPI), was developed to acquire high-resolution DW images of a localized region. The new technique completes k-space acquisition of a limited 3D volume after a single diffusion preparation. Because the DW magnetization is stored in the longitudinal direction until readout, it undergoes T(1) rather than T(2) decay. Inner volume imaging (IVI) is used to limit the imaging volume. This reduces the time required for EPI readout of each complete k(x)-k(y) plane, and hence reduces T(2)(*) decay during the readout and T(1) decay between the readout of each k(z). 3D ss-STEPI images appear to be free of severe susceptibility and motion artifacts. 3D ss-STEPI allows high-resolution DTI of limited volumes of interest, such as localized brain regions, cervical spinal cord, optic nerve, and other extracranial organs.

Algorithms↗

Pharmacokinetics, biodistribution and contrast enhanced MR blood pool imaging of Gd-DTPA cystine copolymers and Gd-DTPA cystine diethyl ester copolymers in a rat model.

PURPOSE: To investigate plasma pharmacokinetics and biodistribution of biodegradable polydisulfide Gd(III) complexes, Gd-DTPA cystine copolymers (GDCP) and Gd-DTPA cystine diethyl ester copolymers (GDCEP) and their efficacy as blood pool MRI contrast agents in comparison with a nondegradable macromolecular agent, Gd-DTPA 1,6-hexanediamine copolymers (GDHC). METHODS: The pharmacokinetics and biodistribution of GDCP and GDCEP with molecular weight of 35 KDa were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. GDHC with the same molecular weight was used as a control. The Gd content in the plasma and various tissues and organs were determined by the ICP-OES. Plasma pharmacokinetic parameters were calculated by using a two-compartment model. The contrast enhanced blood pool MR imaging of the agents was evaluated in Sprague-Dawley rats on a Siemens Trio 3T MR scanner. RESULTS: The biodegradable macromolecular agents, GDCP and GDCEP, had faster blood pool clearance than the nondegradable GDHC. The long-term Gd(III) tissue retention of the biodegradable polydisulfide agents was substantially lower than the nondegradable macromolecular agent. Both GDCP and GDCEP resulted in significant blood pool enhancement for the first 2 min post-injection and more rapid disappearance of the enhancement over time than GDHC. The negatively charged GDCP had prolonged enhancement duration as compared to GDCEP. The structure and biodegradability of the macromolecular contrast agents significantly affected their pharmacokinetics and blood pool contrast enhancement. CONCLUSION: Both GDCP and GDCEP provided effective contrast enhancement for MR imaging of the blood pool. The accumulation of toxic Gd(III) ions in the body was greatly reduced with GDCP and GDCEP as compared to the nondegradable control.

Animals↗

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 microM 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 T(1) relaxivity (r(1)) was 5.43 mM(-1)s(-1) for GDCP, and 5.86 mM(-1)s(-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.

Animals↗

High-resolution DTI with 2D interleaved multislice reduced FOV single-shot diffusion-weighted EPI (2D ss-rFOV-DWEPI).

Diffusion tensor MRI (DTI), using single-shot 2D diffusion weighted-EPI (2D ss-DWEPI), is limited to intracranial (i.c.) applications far from the sinuses and bony structures, due to the severe geometric distortions caused by significant magnetic field inhomogeneities at or near the tissue-air or tissue-bone interfaces. Reducing these distortions in single-shot EPI by shortening the readout period generally requires a reduced field of view (and the potential of wraparound artifact) in the phase-encoding direction and/or reduced spatial resolution. To resolve the problem, a novel 2D reduced FOV single-shot diffusion-weighted EPI (2D ss-rFOV-DWEPI) pulse sequence applicable for high resolution diffusion-weighted MRI of local anatomic regions, such as brainstem, cervical spinal cord, and optic nerve, has been developed. In the proposed technique, time-efficient interleaved acquisition of multiple slices with a limited FOV was achieved by applying an even number of refocusing 180 degrees pulses with the slice-selection gradient applied in the phase-encoding direction. The two refocusing pulses used for each slice acquisition were separated by a short time interval (typically less than 45 ms) required for the 2D EPI echotrain acquisition. The new technique can be useful for high resolution DTI of various anatomies, such as localized brain structures, cervical spinal cord, optic nerve, heart, or other extra-cerebral organ, where conventional 2D ss-DWEPI is limited in usage due to the severity of image distortions.

Algorithms↗

3D multi-scale vessel enhancement filtering based on curvature measurements: application to time-of-flight MRA.

In this paper we evaluate the use of voxel intensity curvature measurements to enhance vessels in 3D MRA images. We compare a multi-scale discrete kernel filter (MaxCurve) to the Hessian matrix based filter proposed by Frangi and co-workers. The MaxCurve filter is based on the maximum difference between the negative curvature computed along orthogonal lines defined by a 3x3x3 kernel. Filter performance is assessed using measures of vessel and background separation (contrast and the area under the ROC curve). Filter parameters are optimized using a training set of four typical time-of-flight MRA images and tested on a separate set of ten MRA images with the same acquisition parameters. The filters tended to provide good MIP image contrast enhancement. The filters are applied to MRA images acquired with different parameters and field strengths indicating potential usefulness for a variety of images. Overall the discrete kernel and Hessian matrix filter performed quite similarly.

Algorithms↗

Relative RF coil performance in carotid imaging.

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.

Adult↗

Application of phase consistency to improve time efficiency and image quality in dual echo black-blood carotid angiography.

There is a considerable similarity between proton density-weighted (PDw) and T2-weighted (T2w) images acquired by dual echo fast spin-echo (FSE) sequences. The similarity manifests itself not only in image space as correspondence between intensities of PDw and T2w images, but also in phase space as consistency between phases of PDw and T2w images. Methods for improving the imaging efficiency and image quality of dual echo FSE sequences based on this feature have been developed. The total scan time of dual echo FSE acquisition may be reduced by as much as 25% by incorporating an estimate of the image phase from a fully sampled PDw image when reconstructing partially sampled T2w images. The quality of T2w images acquired using phased array coils may be significantly improved by using the developed noise reduction reconstruction scheme, which is based on the correspondence between the PDw and T2w image intensities and the consistency between the PDw and T2w image phases. Studies of phantom and human subject MRI data were performed to evaluate the effectiveness of the techniques.

Algorithms↗

Automatic detection of three-dimensional vascular tree centerlines and bifurcations in high-resolution magnetic resonance angiography.

OBJECTIVES: We sought to develop a simple and robust algorithm capable of automatically detecting centerlines and bifurcations of a three-dimensional (3D) vascular bed. MATERIALS AND METHODS: After necessary preprocessing, an appropriate cost function is computed for all vessel voxels and Dijkstra's minimum-cost-path algorithm is implemented. By back tracing all the minimum-cost paths, centerlines and bifurcation are detected. The detected paths are then split into segments between adjacent nodes (bifurcations or vessel end-points) and smoothed by curve fitting. RESULTS: Application of the algorithm to both simulated 3D vessels and 3D magnetic resonance angiography (MRA) images of an actual intracranial arterial tree produced well-centered vessel skeletons. Quantitative assessment of the algorithm was performed. For the simulated data, the root mean square error for centerline detection is about half a voxel. For the human intracranial MRA data, the sensitivity, positive predictive value (PPV), and accuracy of bifurcation detection were calculated for different cost functions. The best case gave a sensitivity of 91.4%, a PPV of 91.4%, and an RMS error of 1.7 voxels. CONCLUSIONS: To the extent that imperfections are eliminated from the segmented image, the algorithm is effective and robust in automatic and accurate detection of centerlines and bifurcations. The cost function and algorithm used are demonstrated to be an improvement over similar algorithms in the literature.

Algorithms↗

Determination of carotid artery atherosclerotic lesion type and distribution in hypercholesterolemic patients with moderate carotid stenosis using noninvasive magnetic resonance imaging.

BACKGROUND AND PURPOSE: The aims of this study were to noninvasively determine carotid atherosclerotic lesion type and distribution and to evaluate the reproducibility of determining lesion types in asymptomatic patients with moderate hypercholesterolemia and moderate carotid artery (CA) stenosis using MRI. METHODS: Forty-two asymptomatic patients with moderate CA stenosis underwent bilateral carotid MRI in a 1.5-T scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MRI-modified American Heart Association criteria were used to evaluate lesion types at 3 locations (common and internal CA [CCA and ICA, respectively] and CA bifurcation) and at the minimum lumen area. Two identical MR scans were conducted to evaluate reproducibility of lesion types. RESULTS: Lesion types were obtained from 230 locations. Type III (39%) occurred most commonly, followed by types IV-V (25%), I-II (20%), VI (12%), and VII (4%). Type III was more commonly distributed in the CCA (n=35, 39%) and ICA (n=32, 36%). Type IV-V was more commonly distributed in the CCA (n=24, 41%) and at the bifurcation (n=21, 36%). Forty-two lesions were available at the site of minimum lumen area: type III (33%), IV-V (33%), VI (29%), and VII (5%). There was good agreement of lesion types between both MRI scans (Cohen's kappa=0.73; 95% CI: 0.65 to 0.81). CONCLUSIONS: MRI can determine lesion types reproducibly as well as the distribution of lesions in hypercholesterolemic patients with moderate CA stenosis. A wide range of lesion types, including advanced lesions, were found in these patients.

Aged↗

Statistics-based approach for aneurysm volume measurements.

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.

Cerebrovascular Circulation↗

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.

Animals↗

POCSENSE: POCS-based reconstruction for sensitivity encoded magnetic resonance imaging.

A novel method for iterative reconstruction of images from undersampled MRI data acquired by multiple receiver coil systems is presented. Based on Projection onto Convex Sets (POCS) formalism, the method for SENSitivity Encoded data reconstruction (POCSENSE) can be readily modified to include various linear and nonlinear reconstruction constraints. Such constraints may be beneficial for reconstructing highly and overcritically undersampled data sets to improve image quality. POCSENSE is conceptually simple and numerically efficient and can reconstruct images from data sampled on arbitrary k-space trajectories. The applicability of POCSENSE for image reconstruction with nonlinear constraining was demonstrated using a wide range of simulated and real MRI data.

Brain Mapping↗

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, T(1), and T(2) 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 degrees and 90 degrees 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.

Arteriosclerosis↗