Contrast-enhanced sonography of tumor neovascularity in a rabbit model.

This project was designed to detect the development of tumor neovascularity and determine if intravenous microbubble contrast improves visualization of otherwise undetectable tumors in an animal model. VX-2 carcinoma was implanted into one thigh of 10 New Zealand white rabbits. Tumors were assessed without and with contrast at 1- to 4-day intervals from day 3-19 postimplantation, using gray scale, color flow, pulse Doppler and power Doppler imaging. Tumor vascularity was compared with the contralateral thigh muscle, so each animal was its own control. Contrast injection improved visualization of tumor neovascularity. Early tumors had homogeneous vasculature but, with time, the centers became less vascular, while the periphery increased. Following contrast injection, color gain was decreased by 40% without compromising color intensity. Neovascularity was detected by contrast injection before the tumor could be palpated or visualized by gray scale. Based on these data, we conclude that enhancement of neovascularity by intravenous contrast permits earlier detection and improved visualization of soft tissue tumors in rabbits.

Contrast enhanced sonography of visceral perfusion defects in dogs.

The purpose of this study was to assess the utility of an intravenous contrast agent (FS069) for visualization of normal visceral perfusion compared with perfusion after segmental infarction in a canine model. Six mongrel dogs were used as subjects. Splenic, renal, hepatic, and small bowel perfusion was assessed without and with intravenous microbubble contrast material using gray scale, color Doppler, pulsed Doppler, and color power Doppler sonography. Each organ was then reassessed after ligation of a segmental vessel. Imaging was again performed without and with contrast material using all four ultrasonographic modalities. In all organs color and spectral Doppler signals were significantly enhanced from normally perfused tissue after intravenous contrast agent injection. Ischemic areas were more conspicuous after contrast medium injection except in the liver. Hepatic perfusion was maintained by portal flow in the liver despite arterial ligation. Ligation of collateral arcades was required to produce bowel ischemia. Intravenous injection of FS069 improves evaluation of visceral perfusion and identification of focal visceral ischemia in dogs. These results suggest that this agent may increase sensitivity for detection of blood flow in small and deep vessels.

Contrast-enhanced ultrasonographic visualization of gonadal torsion.

The purpose of this study was to investigate the effect of use of intravenous ultrasonographic contrast agent in the diagnosis of gonadal torsion in an animal model. After examination of perfusion of normal gonads in male and female dogs, torsion was produced and maintained mechanically. Presence and pattern of blood flow was then reassessed before and after administration of varying doses of perfluorocarbon-filled microsphere intravenous contrast agent. Modes of examination included gray scale, color flow, color power, and spectral analysis using a transducer placed directly on the surgically exposed gonads. Although no enhancement was perceptible on gray scale images, color and spectral Doppler signals were significantly stronger after injection of contrast agent in both normal and rotated gonads. Perfusion asymmetry was more obvious. Some residual flow was seen in partially rotated testes, and absence of flow was documented in both partially and fully rotated ovaries. Use of intravenous contrast medium improves demonstration of altered flow patterns in ischemic gonads, allowing more confident diagnosis.

Volumetric flow estimation in vivo and in vitro using pulsed-Doppler ultrasound.

The measurement of volumetric blood flow in small vessels in vitro and in vivo poses a significant technological challenge. In this study, two pulsatile flow models were developed, one with a 3.2-mm lumen diameter and one with a 12.7-mm lumen diameter, to assess the accuracy of volumetric flow estimation of two pulsed-Doppler devices, a Crystal Biotech VF1 20-MHz system with either a cuff-mounted or a needle-mounted probe and an Advanced Technology Laboratories Ultramark 9 High Definition Imaging system with a 5-MHz linear array transducer. The VF1 volumetric flow error was measured in the 3.2-mm phantom over a variety of pulsatile and continuous waveforms. The accuracy of the VF1 was also tested in porcine femoral and renal arteries. VF1 volumetric flow error ranged from 4.8% to 54.3% in the in vivo studies. The ATL demonstrated similar volumetric flow errors in the porcine femoral artery (approximately 3.2 mm diameter), but these errors were reduced to < or = 17.4% in the 12.7-mm-diameter in vitro flow model.

Direct evidence of cavitation in vivo from diagnostic ultrasound.

Recent increases in the pressure output of diagnostic ultrasound scanners have led to an interest in establishing thresholds for bioeffects in many organs including the lungs of mammals. Damage may be mediated by inertial cavitation, yet there have been no such direct observations in vivo. To explore the hypothesis of cavitation-based bioeffects from diagnostic ultrasound, research has been performed on the thresholds of damage in rat lungs exposed to 4.0-MHz pulsed Doppler and color Doppler ultrasound. A 30-MHz active cavitation detection scheme complementing these studies provides the first direct evidence of cavitation in vivo from diagnostic ultrasound pulses.

Changes in regional vascular capacitance during prostacyclin-induced cardiac vagal reflex in pigs.

The purpose of this study was to determine the effects of the prostaglandin I2 (prostacyclin; PGI2)-induced cardiac vagal reflex on intestinal and liver blood volumes and the intestinal vascular pressure-volume (P-V) relationship. In anesthetized pigs, blood volumes were measured by blood-pool scintigraphy. Portal venous pressure was varied by graded inflation of a portal vein constrictor to determine the intestinal vascular P-V relationship. Proximal right coronary infusion of PGI2 at a rate of 0.15 micrograms.kg-1.min-1 for 6 min increased intestinal blood volume by 7.0 +/- 1.2% (P < 0.01, means +/- SE) and shifted the intestinal vascular P-V relationship away from the pressure axis (i.e., a volume increase at a given venous pressure). This change was associated with decreases in liver blood volume and left ventricular end-diastolic pressure by 4.5 +/- 1.2 (P < 0.01) and 17 +/- 2% (P < 0.05), respectively. PGI2 also reduced central venous pressure by 16 +/- 2% from 3.2 +/- 0.5 mmHg (P < 0.05) and portal venous pressure by 7.0 +/- 0.6% from 7.6 +/- 0.6 mmHg (P < 0.05). These responses were abolished by bilateral vagotomy. The results demonstrate that intracoronary PGI2 infusion increases intestinal blood volume. This increase is mediated by a cardiac vagal reflex. The PGI2-induced shift in the intestinal vascular P-V relationship suggests that intestinal blood volume increases by an active change in vascular capacitance, whereas reductions in liver blood volume and left ventricular end-diastolic pressure appear to be due to passive mechanisms related to the shift of blood volume to the intestinal circulation.

Catecholamine alterations attending spinal cord injury: a reanalysis.

The catecholamine response of injured tissue after severe spinal cord injury (SPI) remains a puzzling controversy. This study was undertaken in an attempt to resolve that controversy. The influence of the biochemical assay method, the magnitude of injury, and the spinal cord region injured on catecholamine levels was determined in the cat spinal cord. It was found that the concentration of norepinephrine (NE) in the traumatized spinal cord is dependent on both the magnitude and the region of injury. The relatively large tissue samples necessitated by the older, less sensitive assay methodology show little or no change in NE levels after a 500-g/cm injury in the cat. When regional samples are analyzed with more sensitive methods, a net depression in the NE level of local tissue is observed. The results of earlier studies from this laboratory indicating an increase in tissue NE after trauma were apparently artifactual, presumably due to the nonselective nature of the biochemical assay used at that time. Dopamine levels were not elevated after SCI, and previous reports from other laboratories indicating an increase in dopamine levels were probably also errant due to methodology-related problems.

Role of adrenergic nerves in blood-induced cerebral vasospasm.

Cerebral arteries have an abundant supply of adrenergic nerve fibers which are believed to release vasoactive substances responsible for the induction of cerebral vasospasm. To assess the importance of adrenergic nerves in this phenomenon, high doses (600 microgram/ml) of 6-hydroxydopamine (6-OHDA) were used to produce in vitro chemical sympathectomy in bovine middle cerebral artery. 6-OHDA reduced catecholamine fluorescence to undectable limits. H3-norepinephrine re-uptake was reduced to 1.5% of intact controls. Arterial norepinephrine content was reduced by 92%. Contractile responses to norepinephrine, serotonin, and fresh human whole blood were modestly reduced after denervation. This reduction was probably due to alpha receptor inactivation by 6-OHDA, because after protection of the alpha receptors with phentolamine the vessel response was the same as in untreated controls. Contractions in response to aged human whole blood were not affected by denervation. The results suggest that the endogenous release of catecholamines does not play a major role in the initiation or spread of blood-induced vasospasm in large cerebral arteries.

Influence of arterial blood pressure upon central hemorrhagic necrosis after severe spinal cord injury.

To determine the influence of systemic arterial blood pressure upon the pathogenesis of spinal cord injury, we eliminated the increase in systemic blood pressure normally observed after trauma to the spinal cord with the ganglionic blocker chlorisondamine. Blockade of the pressure response did not influence the development of hemorrhagic necrosis in the spinal cord. We conclude that the transient pressure response accompanying spinal cord injury is probably not a major factor in the pathogenesis of hemorrhagic necrosis at the site of the spinal cord injury.