Vascular endothelial growth factor enhances atherosclerotic plaque progression.

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.

Thrombomodulin overexpression to limit neointima formation.

BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.

Effect of human recombinant vascular endothelial growth factor165 on progression of atherosclerotic plaque.

OBJECTIVES: This study was designed to evaluate the impact of recombinant human vascular endothelial growth factor165 (rhVEGF) on atherosclerotic plaque progression. BACKGROUND: Therapeutic angiogenesis represents a promising treatment for ischemic diseases. However, angiogenesis may impact atherosclerosis. METHODS: Albumin or rhVEGF was administered by a single intramuscular injection (2 microg/kg body weight) to New Zealand White rabbits fed with a 0.25% cholesterol diet beginning three weeks before therapy. Subsets of rabbits from each group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analyses at 7 or 21 days. RESULTS: The mean plaque area was 15.75+/-2.28% and 22.00+/-3.24% with VEGF and 0.67+/-0.22% and 1.17+/-0.34% with albumin at 7 and 21 days, respectively. The plaque circumference was 13.00+/-2.58% and 23.75+/-2.86% with VEGF and 2.50+/-0.65% and 6.25+/-1.88% with albumin at 7 and 21 days, respectively. The maximal plaque thickness was 0.11+/-0.002 and 0.15+/-0.007 mm with VEGF and 0.04+/-0.009 and 0.07+/-0.003 mm with albumin at 7 and 21 days, respectively. The endothelial density (reported as percent total plaque area) was 31.75+/-4.42% and 63.00+/-8.45% with VEGF and 7.75+/-1.65% and 12.75+/-1.93% with albumin at 7 and 21 days, respectively. The macrophage density was 4.5+/-0.86 and 19.25+/-1.54 with VEGF and 4.26+/-0.75 and 6.00+/-1.08 with albumin at 7 and 21 days, respectively. CONCLUSIONS: Recombinant human VEGF increases the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.

Assessment of peritoneal tolerance of a new MR blood pool contrast agent in rabbits.

OBJECTIVE: Fast 3D MR angiography in conjunction with a new blood pool contrast agent (iron oxide crystals) is a recently described method for detection and localization of intra-abdominal bleeding sites with high sensitivity and specificity. However, peritoneal reactions to the contrast agent have not yet been investigated. The purpose of this study was to assess the peritoneal tolerance of the contrast agent in an animal experiment. METHODS: Eleven rabbits were intraperitoneally injected with 5 mL diluted NC100150 Injection; two rabbits were used as the control group. Rabbits injected with NC100150 Injection were imaged in pairs at 12, 24, and 48 hours and 3 weeks, and a single rabbit was imaged at 72 hours and 1 and 2 weeks after the intraperitoneal administration of the agent. Immediately after imaging, the rabbits were killed and an autopsy was performed. Samples of peritoneal surfaces and intra-abdominal organs were harvested for histology. MR imaging, gross pathology, and histology were evaluated. RESULTS: MR imaging and gross pathology demonstrated the presence of intraperitoneal contrast agent up to 24 hours after administration. Histology revealed a considerable amount of iron in the peritoneum, mesenteric fat, and lymph nodes within the first 24 hours. In most cases, iron was rapidly cleared from these sites within 2 days; in one animal, however, iron was detectable up to 1 week. No signs of inflammation or fibrosis were detected. CONCLUSIONS: This study shows no evidence of inflammatory reactions or signs of fibrosis after the intraperitoneal application of NC100150 Injection.

Optimization of contrast dosage for gadolinium-enhanced 3D MRA of the pulmonary and renal arteries.

To determine the minimal contrast dosage required for diagnostic contrast-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) image quality of the pulmonary (PAs) or renal arteries (RAs). In 12 volunteers (10 females, 2 males; mean age 24 years) imaging was performed with 4 different dosages: 0.05, 0.1, 0.2 and 0.3 mmol/kg of body weight (BW) 0.5 M gadolinium (Gd) contrast agent. The PAs and RAs were evaluated separately each in groups of six volunteers. Qualitative and quantitative signal-to-noise ratio (SNR) image analysis was performed. For the PAs, the increases in signal-to-noise ratio were paralleled by increases in image quality ratings. For the PAs, with the use of 0.05 mmol/kg, only 50.3% of all segments were rated diagnostic, whereas with higher dosages the percentage rose to 89.2% for 0.1 mmol/kg, 98.2% for 0.2 mmol/kg. and 99.1% for 0.3 mmol/kg. For the RAs, 0.3 mmol/kg provided no significant increase in singal-to-noise ratio compared to 0.2 mmol/kg (p = 0.4). Only by a dosage of 0.2 and 0.3 mmol/kg, all evaluated segments were diagnostic evaluable. A dose of 0.2 mmol/kg is required for proper assessment of the RAs or PAs.

Multi-detector row CT: effect of iodine dose reduction on hepatic and vascular enhancement.

PURPOSE: To evaluate the impact of different iodine concentrations of intravenous contrast agent on hepatic and vascular enhancement during arterial and porto-venous phase imaging using a 4-channel multi-detector row CT (MDCT). MATERIAL AND METHODS: One hundred consecutive patients referred for triphasic abdominal MDCT were randomly assigned into four groups receiving different iodine concentration (200, 250, 300 or 350 mg/ml). Non-contrast, arterial, and porto-venous phase 4-channel MDCT imaging was performed (VolumeZoom, Siemens, Germany). A fixed volume of 150 ml intravenous contrast agent at a rate of 3 ml/s was injected using an automatic bolus-tracking system (Care Bolus, Siemens, Erlangen). Hepatic and vascular enhancement values were measured over time and non-contrast values were subtracted in order to compute arterial and porto-venous mean hepatic (MHE) and mean aortic (MAE) enhancement for each group. Mean change of enhancement > 80 HU for the aorta and > 40 HU for the liver during porto-venous phase imaging was considered as sufficient enhancement. RESULTS: All groups achieved sufficient vascular enhancement during arterial phase imaging; MAE with 350 mg/ml (222 HU) and 300 mg/ml (213HU) was significantly better than with 250 mg (196HU) and 200 mg/ml (169 HU), whereas MHE showed no statistically significant difference between the groups (range 16 - 25 HU). Porto-venous MHE showed increased enhancement with larger concentrations, with significant differences among the groups. Only the higher concentration groups (350 mg/ml und 300 mg/ml) fulfilled in every individual the guidelines for sufficient porto-venous MHE. In the lower concentration groups, 8 patients with 200 mg/ml and 3 patients with 250 mg/ml showed enhancement values below the required minimum. CONCLUSION: A decrease in iodine contrast agent down to 200 mg/ml concentration is only tenable for propose of vascular aortic and hepatic arterial enhancement, whereas hepatic porto-venous phase imaging still requires concentrations at or above the level of 300 mg/ml.

[Intravascular MR imaging: the first in-vivo experiences in an animal arteriosclerosis model]. / Intravaskuläre MR-Bildgebung: erste in-vivo-Erfahrungen in einem Arteriosklerose-Tiermodell.

PURPOSE: To evaluate intravascular MR imaging in normal New Zealand rabbits and hereditary hyperlipidaemic Watanabe rabbits (WHHL) with histological correlation. MATERIAL AND METHODS: The suprarenal abdominal aortas of two normal and two WHHL rabbits were examined by conventional angiography, high resolution MRT with a surface coil and intravascular MRT in a 1.5 T system. The intravascular reception coil consisted of a copper wire loop built into the balloon of an angioplasty catheter. The findings were correlated with histological examinations. RESULTS: Excellent spin echo images with a resolution of 78 x 156 microns were obtained in less than 4 minutes. The arteriosclerotic changes in the vessels of the WHHL rabbits could not be recognised angiographically. High resolution MRT with surface coils showed mural thickening but a detailed demonstration of arteriosclerotic lesions was possible only by means of high resolution intravascular imaging. There was good histological correlation. CONCLUSION: Arteriosclerotic lesions can be demonstrated in vivo by high resolution intravascular imaging.

[Ultrasound-guided biopsy of non-palpable breast lesions: correlation with the results of fine-needle aspiration biopsy]. / Ultraschallgesteuerte Schneidbiopsien nicht palpabler Mammaläsionen: Korrelation mit den Ergebnissen der ultraschallgesteuerten Feinnadelpunktion.

PURPOSE: The purpose of this study was the clinical evaluation of ultrasound-guided biopsy in comparison with ultrasound-guided fine-needle aspiration biopsy of identical, non-palpable breast lesions. MATERIALS AND METHODS: From August 1997 until July 1998, 73 ultrasound-guided biopsies were performed in 66 patients with non-palpable lesions of the breast. In 18 patients (age 33-77 years) with 20 non-palpable lesions, fine-needle aspiration biopsy (20-G needle) and biopsy (18-G biopsy needle) were performed on a single occasion. This was the patient selection of our retrospective study. RESULTS: One malignant neoplasm was found among the 20 biopsied lesions, while the remaining 19 lesions were of a benign nature. In 20% of the cases, the material obtained by fine-needle biopsy was not sufficient for a cytologic diagnosis, while biopsy allowed a diagnosis in 19/20 cases. No complications were observed. CONCLUSIONS: Ultrasound-guided biopsy using an 18-G needle is a suitable method for the evaluation of non-palpable lesions that are only visible on ultrasound. It represents an attractive alternative to fine-needle aspiration in the absence of experienced cytologic diagnosticians.

Transcaval biopsy of retroperitoneal fibrosis.

An additional use of the transjugular hepatic Tru-cut biopsy needle is reported. A periaortic mass was biopsied with this device inserted through the femoral vein under fluoroscopy guidance. Based on the sampled tissue, a diagnosis of idiopathic retroperitoneal fibrosis was made. The procedure was well tolerated, and long-term follow-up confirmed the diagnosis. Transcaval retroperitoneal biopsy may represent an alternative to surgical biopsy of diffuse retroperitoneal disease in high operative-risk patients.

Plain and covered stent-grafts: in vitro evaluation of characteristics at three-dimensional MR angiography.

PURPOSE: To evaluate the characteristics of various plain and covered stents as regards demonstration of the contained lumen with simulated contrast material-enhanced fast three-dimensional (3D) magnetic resonance (MR) angiography. MATERIALS AND METHODS: Six stents (Easy Wallstent, Cragg, Palmaz, Cragg EndoPro System 1, Corvita, Passager) were implanted in plastic tubes and integrated into a closed-tubing circuit driven by a pulsatile roller flow pump. The circulating water was spiked with gadopentetate dimeglumine. Three-dimensional MR angiograms were obtained with an echo time of 1.4 or 2.1 msec and with partial (0.5 signal acquired) or full (one signal acquired) k-space sampling. The size of the stent-associated artifact was determined relative to the tube diameter. RESULTS: The Easy Wallstent and Palmaz stent caused complete obliteration of the stent lumen with all sequences. The Cragg, Cragg EndoPro System 1, and Passager stents allowed good visualization of the stent lumen. The Corvita stent demonstrated major artifacts. The magnitude of the stent-associated artifact was related to the echo time (P < .01) but not to the type of k-space sampling (P = .35). CONCLUSION: The luminal patency of selected plain and covered stents can be assessed with contrast-enhanced 3D MR angiography.

In vitro image characteristics of an abdominal aortic stent graft: CTA versus 3D MRA.

Percutaneous stent-grafting is increasingly employed as a less invasive alternative to surgery for the treatment of infrarenal abdominal aortic aneurysms. It requires long-term imaging follow-up, to document the structural integrity of the device, to exclude perigraft channels and endograft leakages, as well as the shrinkage of the aneurysmal sac. The expectation of severe stent induced artifacts and safety concerns have prevented 3D MRA from being used. The purpose of this in vitro study was to investigate the imaging characteristics of a bifurcated stent graft with 3D MRA (3D Fourier transform fast spoiled GRE) at 1.5 T in comparison to those of CTA. Measurement of the stent wall thickness and luminal diameter were made on a agar gel embedded stent graft at five locations on both CTA and MRA images. The stent graft was depicted as a dark ring on MR images. Wall thickness measurements at the five locations of the stent graft overestimated the true stent thickness, while luminal diameters were slightly underestimated. Measurement differences between MR and CT were not statistically significant (P = 0.67; P = 0.85). Artifacts emanating from the platinum markers were considerably less severe on the MR-images. A wider area of signal loss was seen only at the insertion of the iliac stent leg into the aortic stent portion due to the overlap of two radio-opaque platinum markers. 3D MRA images should permit a comprehensive assessment of the arterial lumen, and of perivascular tissues.

Virtual MR arthroscopy: new insights into joint morphology.

Evaluation of the feasibility of virtual magnetic resonance (MR) arthroscopy was performed on 10 patients referred for MR arthrography of the shoulder, the elbow, or the knee. A fast spoiled contrast-enhanced three-dimensional gradient-echo sequence was combined with image postprocessing to render arthroscopic views. Virtual MR arthroscopy was successfully demonstrated in all 10 joints. Determination of added diagnostic benefit will require further study.

Pulmonary hemorrhage: imaging with a new magnetic resonance blood pool agent in conjunction with breathheld three-dimensional magnetic resonance angiography.

PURPOSE: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. METHODS: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30 degrees ) were acquired breath-held over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. RESULTS: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. CONCLUSION: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.

Three-dimensional MR angiography of a nitinol-based abdominal aortic stent graft: assessment of heating and imaging characteristics.

OBJECTIVE: To assess heating- and 3D MRA imaging characteristics of a commonly used aortic stent graft in a 1.5T MR-environment. MATERIALS AND METHODS: A bifurcated stent graft (Vanguard; Boston Scientific, Oakland, N. J.) was evaluated in vitro regarding localized heating effects as well as imaging appearance using fast 3D GRE sequences. To quantitate stent related artifacts, stent wall thickness and luminal diameters were measured. Subsequently eight patients were imaged three months following placement of an aortic stentgraft with 3D MRA. Images were assessed for the presence of stent leaks, luminal patency, and stent configuration. RESULTS: There were no temperature changes associated with the stent during scanning. Wall thickness measurements overestimated true stent thickness, resulting in minimal underestimation of luminal diameters on 3D MRA images. In vivo imaging confirmed these results. Stent patency was confirmed in all 8 patients. CONCLUSION: Contrast-enhanced 3D MRA appears well suited for the evaluation of the abdominal and pelvic vasculature following aortic implantation of a Vanguard stent.

Real-time MR-guided joint puncture and arthrography: preliminary results.

The purpose of this study was to evaluate interactive MR-guided joint puncture with intra-articular application of contrast agent. MR-guided arthrography of the shoulder joint was successfully performed in three patients using an interactive guidance system implemented in an open-configuration MR system. Visualization of the needle pathway and contrast inflow was comparable to that with conventional X-ray fluoroscopy. The position of the intra-articular needle tip was accurately confirmed and subsequent MR arthrography was diagnostic in all cases.

Intestinal and peritoneal bleeding: detection with an intravascular contrast agent and fast three-dimensional MR imaging--preliminary experience from an experimental study.

PURPOSE: To assess the ability to detect and localize intestinal and peritoneal bleeding with an intravascular contrast agent and fast three-dimensional (3D) magnetic resonance (MR) imaging. MATERIALS AND METHODS: An intravascular contrast agent (NC100150 Injection) was administered into small-bowel specimens at five flow rates; the specimens were imaged with a 3D gradient-echo (GRE) sequence at 1-minute intervals. Radionuclide studies with technetium-99m pertechnetate were performed in the same manner. Subsequently, the MR imaging technique was assessed in vivo. Two intraluminal intestinal and one hepatic bleeding sites were created in an anesthetized pig. Three-dimensional GRE imaging data sets were acquired after intravenous injection of the contrast agent. Imaging findings were confirmed with macroscopic inspection. RESULTS: Contrast material injected at 0.5-2.0 mL/min was detected with both radionuclide and MR imaging after 1 minute. An accumulated volume of 0.2 mL was necessary to demonstrate the bleeding site. In vivo, all bleeding sites were readily detected on MR images. Contrast material accumulated in the intestines and peritoneal space. CONCLUSION: In conjunction with an intravascular contrast agent, 3D MR imaging allows detection and localization of gastrointestinal bleeding. The extent of the bleeding can be determined with repeat data acquisitions.

Stent-graft therapy for subclavian artery aneurysms and fistulas: single-center mid-term results.

PURPOSE: To evaluate the potential of covered stents to replace surgery in the treatment of subclavian artery aneurysms and traumatic injuries. MATERIALS AND METHODS: Nine patients (five men, four women; age range, 20-83 years; mean, 54 years) with subclavian artery aneurysms (n = 5) or fistulas (n = 4) were treated with stent-grafts. All devices used were custom-made, consisting of polytetrafluoroethylene (PTFE)-covered Palmaz (n = 5), Wallstent (n = 2), Z stents (n = 8), or a polyester-covered Z stent (n = 1). One patient was lost to follow-up after 2 months. All others were followed up with clinical evaluation, computed tomography (CT), and/or ultrasound. RESULTS: All devices were deployed successfully with exclusion of the aneurysms and fistulas. There were two procedure-related complications (22%), consisting of groin pseudoaneurysms requiring surgical repair 3 and 9 days after the procedure. One of those patients required additional oral antibiotic therapy for a postsurgical groin wound infection. One patient developed a stenosis at 12 months, which required angioplasty. The stent-graft thrombosed in one patient because of a kink 2 months after placement, which was successfully treated by thrombolysis and placement of a Wallstent. The primary and secondary patencies are 89% and 100%, respectively, after a mean follow-up of 29 months (2-66 mo). CONCLUSION: Mid-term results of stent-graft therapy of subclavian artery aneurysms and fistulas are encouraging, with low morbidity and excellent clinical outcome.

MR versus fluoroscopic guidance of a catheter/guidewire system: in vitro comparison of steerability.

Our purpose in this study was to evaluate the steerability of a combined catheter guidewire system with MR tracking in an open-configuration .5T MR system and compare it with fluoroscopic guidance. Experiments were performed with an aorta-shaped glass phantom with different-size branches connected to a roller flow pump to simulate pulsatile flow. A .035" guidewire was used in conjunction with a 5F Cobra 2-shaped catheter. For active MR guidance, a small RF coil was incorporated into the tips of all devices. In addition to fluoroscopic guidance, we used MR tracking devices to selectively catheterize all branches in the .5T open magnet (Signa SP, GEMS). Time requirements for the latter were compared with those needed under conventional angiographic conditions using standard catheters and guidewires. Active MR tracking permitted the simultaneous real time (4 updates/sec) guidance of both guidewire and catheter. Under MR guidance, all branch vessels were successfully catheterized. We found no significant differences in time requirements between guidance with the MR tracking device and fluoroscopic guidance. However, cannulation under fluoroscopic guidance with standard angiography devices required significantly less time (P < .05). Selective catheterization of small branch vessels is possible with active MR tracking of a combined catheter/guidewire system. Limitations of MR tracking device material and design result in a considerable lengthening of the cannulation procedures.