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Biomedical subjects

M E Moseley

Publications and source records attributed to M E Moseley.

At least 19 recordsLinked to original sources

Hypercarbia-induced changes in cerebral blood volume in the cat: a 1H MRI and intravascular contrast agent study.

Cerebral blood volume changes with arterial carbon dioxide were monitored by proton T1-weighted MR images following administration of the intravascular contrast agent Gd-DTPA labeled with human serum albumin. Without MR contrast, no significant image intensity changes were observed with PaCO2. Following contrast, regional brain image intensities increased significantly over control (0% inspired CO2) in cortical gray, white, and basal ganglia regions with increasing PaCO2 and returned to control intensities upon return to 0% inspired CO2. Imaging of through-plane and in-plane phantoms was performed to assess flow effects. Signal losses of 2 and 6% (relative to no flow) were observed for bulk velocities of 5 mm/s at TE values of 15 ms. An intravascular contrast agent may be useful for MRI monitoring of local cerebral blood volume changes during cerebral perturbations.

Adipose Tissue

Iron-dextran as a magnetic susceptibility contrast agent: flow-related contrast effects in the T2-weighted spin-echo MRI of normal rat and cat brain.

Iron-dextran (1 mmol Fe/kg) was used as an intravascular, paramagnetic contrast agent in rat and cat brain in conventional spin-echo T2-weighted (TR 2800/TE 100) 1H magnetic resonance imaging. The resulting images displayed differential decreases (30-50%) in intensity whose pattern was similar to that obtained with the superparamagnetic particulate iron oxide AMI-25 (0.18 mmol Fe/kg). Postcontrast images displayed improved anatomic detail, and contrast effects were observed to be greater in cortical and subcortical gray matter than in adjacent white matter. Intravenous injection of acetazolamide after administration of iron-dextran caused a small additional decrease in image intensity. Measurement of whole blood and plasma at 5 min postinjection of either contrast agent revealed significant increases in their volume magnetic susceptibilities. The contrast effect appears to be related to magnetic susceptibility changes brought about by the iron-dextran; it has both blood volume and blood flow components. The static model of magnetic susceptibility effects in brain capillaries is modified to include bolus flow of erythrocytes, providing a mechanism for the observed flow effects.

Acetazolamide

Real-time observation of transient focal ischemia and hyperemia in cat brain.

Gradient-recalled echo-planar (T2*-weighted) imaging was used to noninvasively monitor regional blood oxygenation state changes in real time during transient episodes of focal ischemia in cat brain. Varying ischemic intervals (12 s to 30 min) were caused by middle cerebral artery occlusion. A rapid signal drop was noted upon occlusion, due to deoxygenation of static blood in the ischemic tissues. Upon successful reperfusion, the signal intensity recovered immediately and increased above (overshot) the baseline level before slowly returning to normal. The "overshoot" response was strongly dependent on the duration of the ischemic interval and is thought to reflect reactive hyperemia.

Animals

Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40.

RATIONALE AND OBJECTIVES: This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects. MATERIALS AND METHODS: Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin. RESULTS: Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved. CONCLUSION: Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.

Animals

Magnetic resonance imaging demonstration of pharmacologic-induced myocardial vasodilatation using a macromolecular gadolinium contrast agent.

RATIONALE AND OBJECTIVES: Adenosine is a potent vasodilator used clinically in nuclear scintigraphy to assess coronary artery reserves. The potential to identify this vasodilating effect of adenosine using magnetic resonance imaging (MRI), which is superior in spatial resolution to nuclear scintigraphy, combined with a blood-pool MRI contrast agent, was investigated in normal rats. METHODS: Groups of Sprague-Dawley rats received successive infusions of either adenosine (3 mg/kg/minute; n = 7) or dipyridamole (negative control; up to 1.0 mg/kg/minute; n = 9), both before and after contrast enhancement, with a macromolecular blood-pool MRI contrast agent, albumin-gadolinium-DTPA35 (Gd-DTPA35) (4.0 mumol Gd per kilogram). Electrocardiographically (ECG) gated MRIs (2.0 Tesla), acquired serially before and after contrast enhancement, and with and without either adenosine or dipyridamole infusions, to monitor potential pharmacologic responses. RESULTS: During repeated infusions of adenosine, the postcontrast myocardial enhancement, reflecting blood volume, increased significantly (P < .05), up to 150%, compared with pre-adenosine enhancement. Infusions of dipyridamole, pharmacologically inactive in rats, produced no change in myocardial enhancement. CONCLUSIONS: The increased myocardial signal intensity observed during adenosine infusions after enhancement of the blood pool can be attributed to increased blood volume accompanying coronary vasodilatation. The method, which does not require a continuous infusion of contrast agent, has potential for the clinical evaluations of coronary artery reserves.

Adenosine

Contrast-enhanced MR imaging of the lung: assessments of ventilation and perfusion.

The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine-(gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine-(gadopentetate dimeglumine)40.

Aerosols

Cytotoxic brain edema: assessment with diffusion-weighted MR imaging.

To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging.

Animals

Comparison of diffusion- and T2-weighted MRI for the early detection of cerebral ischemia and reperfusion in rats.

The sensitivity of diffusion-weighted MRI was compared to that of T2-weighted MRI following temporary middle cerebral artery occlusion (MCA-O) for 33 min followed by 4 h of reperfusion in rats. Diffusion-weighted spin-echo images using strong gradients (b value of 1413 s/mm2) demonstrated a significant increase in signal intensity in ischemic regions as early as 14 min after onset of ischemia in comparison to the normal, contralateral hemisphere (p less than 0.05). This hyperintensity returned to baseline levels during reperfusion. T2-weighted images showed no evidence of brain injury during the temporary occlusion. In three rats subjected to permanent MCA-O, diffusion-weighted MRI demonstrated an increased signal intensity on the first image following occlusion and continued to increase during the 4-h observation period. T2-weighted images failed to demonstrate significant injury until approximately 2 h after MCA-O. Signal intensity ratios of ischemic to normal tissues were greater in the diffusion-weighted images than in the T2-weighted MR images at all time points (p less than 0.05). Close anatomical correlation was found between the early and sustained increase in diffusion-weighted MRI signal intensity and localization of infarcts seen on post-mortem histopathology.

Animals

Diffusion-weighted MR imaging of extraaxial tumors.

The clinical usefulness of the application of spin-echo diffusion-weighted imaging in the evaluation of extraaxial cysts and epidermoid tumors is demonstrated in a series of 15 patients. Apparent diffusion coefficient (ADC) images based on intravoxel incoherent motion (IVIM) were obtained with a maximum gradient b value = 100 s/mm2. Lesion ADC was qualitatively compared to external phantoms. In all cases, epidermoid tumors revealed reduced ADC values similar to that of normal brain tissue. On the other hand, all cysts had ADC similar to the stationary water phantom. Lesion delineation was improved due to the replacement of normal pulsatile (very high ADC) cisternal CSF. Direct quantitative measurements of ADC using this technique may not be possible due to unavoidable motion artifact.

Brain

Anisotropy in diffusion-weighted MRI.

Diffusional anisotropy of water protons, induced by nonrandom, directional barriers which hinder or retard water motion, is measurable by MRI. Faster water diffusion was observed when the diffusion-sensitizing gradient direction paralleled the long axes of white matter tracts, indicative of fewer barriers to water motion. Diffusion perpendicular to this axis was as much as four times slower. Anisotropy was seen pre- and postmortem in all axial, sagittal, and coronal planes, with and without cardiac gating. Ordering has also been observed in feline optic nerve and in human peripheral nerves. Utilization of this technique can greatly improve understanding and assessment of demyelinating disorders, of white matter infarcts and neoplasms, and of neonatal brain and spinal cord development.

Animals

Ferrioxamine B derivatives as hepatobiliary contrast agents for magnetic resonance imaging.

Succinyl (SDF), phenylsuccinyl (PSDF), glutaryl (GDF), and phenylglutaryl (PGDF) derivatives of desferrioxamine B (DF) have been synthesized. In rats given the 59Fe(III) chelates of each these ligands at tracer levels, 82-94% of the 59Fe was eliminated within 1-2 days. 59Fe given as DF, SDF, and GDF chelates was excreted primarily in the urine, while nearly 50% of that given as PSDF and PGDF was excreted in the feces. Correspondingly, Fe-DF, Fe-SDF, and Fe-GDF (0.2 mmol/kg) produced early, marked renal, but no gastrointestinal magnetic resonance imaging (MRI) enhancement. Fe-PSDF and Fe-PGDF (0.2 mmol/kg) produced marked and rapid MRI enhancement of the upper small intestine. In animals with cannulated bile ducts, 59Fe from 59Fe-PGDF (carrier added, 0.1 mmol/kg) appeared rapidly in the collected bile, but not in the intestinal contents, proving that the contrast agent reaches the bowel via the bile. These changes in the excretion and MRI enhancement patterns brought about by the presence of a phenyl substituent apparently were not related to changes in lipophilicity or protein binding.

Animals

Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476.

A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.

Animals

Differentiation of capillary leak and hydrostatic pulmonary edema with a macromolecular MR imaging contrast agent.

The ability of a macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]40) to allow distinction of pulmonary capillary leak from hydrostatic pulmonary edema was investigated. Capillary leak edema was induced in 12 rats by means of venous injection of oleic acid; hydrostatic pulmonary edema was induced in 10 rats by means of continuous infusion of 0.9% sodium chloride. In the oleic acid pulmonary edema model, the signal intensity continued to increase for 12 minutes after administration of contrast material, indicating a leak of paramagnetic molecules from the intravascular to the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in the hydrostatic edema model, as would be expected in the absence of endothelial damage. Hydrostatic edema tended to be distributed homogeneously throughout the lung, while capillary leak edema tended to occur predominantly in the peripheral portions of the lung. These findings indicate that macromolecular contrast agents can facilitate differentiation between edema caused by elevated intravascular pressure and edema induced by abnormal capillary permeability.

Animals

Recent advances in MR imaging/spectroscopy of cerebral ischemia.

Recent advances in high-resolution MR imaging and multinuclear spectroscopy have stimulated studies of the functional relationships between tissue hypoperfusion, cellular energy depletion, and brain edema associated with cerebral ischemia. The very slow (microns/sec) random translational motion of water protons in various brain tissues and intracranial fluid compartments can now be assessed with MR diffusion imaging. More slowly diffusing protons in ischemic tissues can be differentiated from normal parenchyma, CSF, and flowing blood, enabling the detection and localization of ischemic regions within minutes of the onset of stroke. Perfusion imaging "snapshots," obtained in as little as 25 msec with echoplanar MR methods, permit the evaluation of tissue washin/washout kinetics of contrast agents in the microvasculature, and thus the quantification of brain perfusion on a regional basis. Also, delineation of major intra- and extracranial arterial and venous structures with MR angiography, acquired with two- or three-dimensional Fourier transformation techniques, has enabled accurate noninvasive assessments of vascular occlusive disease. Finally, improvements in MR spectroscopic techniques have facilitated investigations of metabolic regulation and bioenergetics in experimental animal models of cerebral ischemia, as well as in stroke patients. Combined MR imaging and spectroscopy will likely play an important role in differentiating reversibly from irreversibly ischemic brain tissues and in the investigation of various neuroprotective pharmaceuticals.

Animals

Ultrafast magnetic resonance imaging: diffusion and perfusion.

Echo-planar magnetic resonance imaging (MRI) can be used to measure apparent diffusion coefficients noninvasively in vivo, with scan times of 150 milliseconds or less, and to assess early ischemic effects in the feline experimental model, which has an occluded middle cerebral artery (MCA). The apparent diffusion coefficient in ischemic regions, which are identified later from vital staining, is significantly decreased from normal values within 1 hour after the MCA becomes occluded. A series of 10 echo-planar images that are progressively diffusion-weighted can be collected in 1 minute (effective TR of 6 seconds). Semilogarithmic plots of image intensity versus gradient strength factors (b values) were linear. Collecting sequential gradient echo-planar images during the passage of a bolus of contrast medium is also useful when assessing perfusion or vascular integrity before and during ischemic episodes. After intravenous injection of dysprosium-diethylene triamine penta-acetic acid-bis(methylamide), typical signal losses of 40% to 80% were observed and were dose-dependent. Areas of possible ischemia identified from diffusion-weighted images did not lose signal intensity with the use of contrast medium and were seen as regions of relative hyperintensity, clearly discernible from normally perfused tissues.

Animals