Biomedical subjects

K Craig Goodrich

Publications and source records attributed to K Craig Goodrich.

10 recordsLinked to original sources

PubMed2005

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↗

PubMed2005

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↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

High-resolution time-resolved contrast-enhanced 3D MRA by combining SENSE with keyhole and SLAM strategies.

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.

Carotid Arteries↗

PubMed2004

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

PURPOSE: 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.

Animals↗

PubMed2003

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

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.

Adult↗

PubMed2002

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.

Aged↗

PubMedDate not supplied

Poly(l-glutamic acid) Gd(III)-DOTA conjugate with a degradable spacer for magnetic resonance imaging.

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.

Animals↗

PubMedDate not supplied

PEG-g-poly(GdDTPA-co-L-cystine): a biodegradable macromolecular blood pool contrast agent for MR imaging.

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.

Animals↗