Biomedical subjects

Edward C Parsons

Publications and source records attributed to Edward C Parsons.

9 recordsLinked to original sources

PubMed2006

Temporal diffusion spectroscopy: theory and implementation in restricted systems using oscillating gradients.

The theory of temporal diffusion spectra is reviewed. In contrast to q-space spectroscopy, which measures the displacement spectrum of spins in a spatial domain, the spectral density of the velocity correlation function (VCF) in the temporal domain is considered. It is demonstrated that casting diffusion in this domain may facilitate measurements of microscopic geometry and the decomposition of the diffusion signal into components due to disperse flow and restricted diffusion. An oscillating gradient (OG) method of diffusion spectroscopy was developed and implemented. Microscopic pore sizes, surface-to-volume ratios (S/Vs), and diffusion path tortuosities were extracted from model systems using this method. Cases are discussed in which this type of experiment may allow the characterization of pore geometry when spatial domain experiments fail. OGs may be combined with imaging sequences to map complex patterns of diffusion and flow. Moreover, scalar apparent diffusion coefficient (ADC) measurements in complex biological systems may be subtly dependent on specific pulse sequence parameters. Thus, scalar ADC measurements using gradient pulses with different frequency spectra may give different results. Conversely, the frequency dependence of motion-sensitizing gradient pulses may be exploited to deduce the origin of ADC changes.

Diffusion Magnetic Resonance Imaging↗

PubMed2005

Molecular magnetic resonance imaging of atrial clots in a swine model.

BACKGROUND: The detection and differentiation of intracardiac masses is still challenging and may include neoplasms and thrombi. The aim of this study was the investigation of a targeted, fibrin-specific contrast agent (EP-2104R) for molecular targeted magnetic resonance imaging (MRI) of left atrial clots. METHODS AND RESULTS: Chronic human thrombi were surgically implanted in the left atrial appendage of 5 swine. Molecular MRI was performed with a navigator-gated, free-breathing, cardiac-triggered 3D inversion-recovery, black-blood, gradient-echo sequence before and after systemic administration of 4 micromol/kg EP-2104R. MR images were analyzed by 2 investigators, and the contrast-to-noise ratio was calculated. Location of clots was confirmed by autopsy, and the gadolinium concentration in the clots was assessed. Before contrast agent administration, thrombi were not visible on black-blood MR images. After contrast administration, all atrial clots (n=5) were selectively visualized as white spots with a high contrast-to-noise ratio (clot/blood, 29.7+/-8.0). The gadolinium concentration in the clots averaged 74+/-45 micromol/L. CONCLUSIONS: The fibrin-specific MR contrast agent EP-2104R allows for selective and high-contrast visualization of left atrial clots by means of molecular targeted MRI.

Animals↗

PubMed2005

Molecular magnetic resonance imaging of pulmonary emboli with a fibrin-specific contrast agent.

RATIONALE AND OBJECTIVES: The detection of pulmonary embolism is still challenging due to the often nonspecific clinical findings. The aim of this study was to investigate the potential of molecular targeted magnetic resonance imaging (MRI) of pulmonary emboli using low-dose application of a fibrin-specific contrast agent (EP-2104R; Epix Pharmaceuticals, Cambridge, MA). METHODS: Fresh clots from human blood were engineered ex vivo and delivered in the lungs of 11 swine. Subsequently, a T1-weighted breath-hold three-dimensional gradient-echo sequence was performed before as well as 5 minutes, 1 hour, and 2 hours after systemic administration of 7.5 (n = 5) or 4 (n = 5) micromol/kg EP-2104R. One swine that did not receive any contrast agent served as a control. MR images were analyzed by two investigators and contrast-to-noise ratio between the thrombus and the surrounding tissue (blood pool and lung parenchyma) was assessed. Localization of thrombi was compared with 16-row multislice computed tomography. Finally, the animals were killed and thrombi were removed for assessment of gadolinium concentration. MAIN RESULTS: Before contrast media application, thrombi were not visible on MR images. At 1 and 2 hours after contrast media injection, pulmonary emboli were selectively visualized with high-signal intensity foci, independent of the dosage used. A high gadolinium concentration in thrombi was found after both dosages (83 +/- 41 microM for 4 micromol/kg and 130 +/- 57microM for 7.5 micromol/kg), resulting in a similar high contrast-to-noise ratio on MR images (between 11 and 13). CONCLUSION: Systemic low-dose application of EP-2104R allows for selective molecular MRI of fresh pulmonary thromboembolism in a swine model.

Animals↗

PubMed2005

Molecular magnetic resonance imaging of coronary thrombosis and pulmonary emboli with a novel fibrin-targeted contrast agent.

BACKGROUND: The differential diagnosis of acute chest pain is challenging, especially in patients with normal ECG findings, and may include coronary thrombosis or pulmonary emboli. The aim of this study was to investigate the novel fibrin-specific contrast agent EP-2104R for molecular targeted MR imaging of coronary thrombosis and pulmonary emboli. METHODS AND RESULTS: Fresh clots were engineered ex vivo from human blood and delivered in the lungs and coronary arteries of 7 swine. Subsequent molecular MR imaging was performed with a navigator-gated free-breathing and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence before and after systemic administration of 7.5 micromol/kg EP-2104R. Two swine served as the control group. MR images were analyzed by 2 investigators, and contrast-to-noise ratio and gadolinium concentration in the clots were assessed. Before contrast media application, no thrombi were visible. After contrast administration, all 32 pulmonary emboli, 3 emboli in the right heart, and 5 coronary thrombi were selectively visualized as white spots with a mean contrast-to-noise ratio of 32+/-19. The average gadolinium concentration from all 3 types of thrombi was 144+/-79 micromol/L. CONCLUSIONS: Molecular MR imaging with the fibrin-targeted contrast-agent EP-2104R allows selective visualization of acute coronary, cardiac, and pulmonary thrombi.

Angiography↗

PubMed2004

In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding molecular magnetic resonance contrast agent.

BACKGROUND: The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis. METHODS AND RESULTS: Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA-labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray-guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 micromol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (approximately 250 micromol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 micromol/L Gd. CONCLUSIONS: We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.

Animals↗

PubMed2004

In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent.

BACKGROUND: Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis. METHODS AND RESULTS: Fifteen male New Zealand White rabbits (weight, approximately 3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology. CONCLUSIONS: We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.

Acute Disease↗

PubMed2003

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

Animals↗

PubMed2002

Early postexercise muscle glycogen recovery is enhanced with a carbohydrate-protein supplement.

In the present study, we tested the hypothesis that a carbohydrate-protein (CHO-Pro) supplement would be more effective in the replenishment of muscle glycogen after exercise compared with a carbohydrate supplement of equal carbohydrate content (LCHO) or caloric equivalency (HCHO). After 2.5 +/- 0.1 h of intense cycling to deplete the muscle glycogen stores, subjects (n = 7) received, using a rank-ordered design, a CHO-Pro (80 g CHO, 28 g Pro, 6 g fat), LCHO (80 g CHO, 6 g fat), or HCHO (108 g CHO, 6 g fat) supplement immediately after exercise (10 min) and 2 h postexercise. Before exercise and during 4 h of recovery, muscle glycogen of the vastus lateralis was determined periodically by nuclear magnetic resonance spectroscopy. Exercise significantly reduced the muscle glycogen stores (final concentrations: 40.9 +/- 5.9 mmol/l CHO-Pro, 41.9 +/- 5.7 mmol/l HCHO, 40.7 +/- 5.0 mmol/l LCHO). After 240 min of recovery, muscle glycogen was significantly greater for the CHO-Pro treatment (88.8 +/- 4.4 mmol/l) when compared with the LCHO (70.0 +/- 4.0 mmol/l; P = 0.004) and HCHO (75.5 +/- 2.8 mmol/l; P = 0.013) treatments. Glycogen storage did not differ significantly between the LCHO and HCHO treatments. There were no significant differences in the plasma insulin responses among treatments, although plasma glucose was significantly lower during the CHO-Pro treatment. These results suggest that a CHO-Pro supplement is more effective for the rapid replenishment of muscle glycogen after exercise than a CHO supplement of equal CHO or caloric content.

Adult↗

PubMedDate not supplied

Modified oscillating gradient pulses for direct sampling of the diffusion spectrum suitable for imaging sequences.

A variation of the oscillating gradient spin echo method had been developed, which isolates temporal frequencies of the dephasing spectrum. This allows sampling of the diffusion spectrum, the Fourier transform of the velocity correlation function (VCF). It has been shown that restriction and flow alter this function in ways that can be mathematically characterized, yielding quantitative information on restriction geometry and flow parameters. It is demonstrated that in many systems of interest, dispersion of velocity will produce a peak in the VCF spectrum near omega=0, while restricted diffusion will manifest itself in the spectrum at higher frequencies. The method, therefore, may be useful for decoupling their effects on the apparent diffusion coefficient (ADC), as well as in revealing the physics of both phenomena. This method has been implemented in model systems of packed beads, yielding data consistent with theoretical models of restricted diffusion spectra and data from one previous study. The method may have significant application to biology and medicine, as well as the study of transport phenomena in porous media and complex flow.

Diffusion↗