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.

Therapeutic elastase inhibition by alpha-1-antitrypsin gene transfer limits neointima formation in normal rabbits.

PURPOSE: Alpha-1-antitrypsin (AAT) is the major circulating elastase inhibitor. Deficiency of elastase inhibition leads to emphysema and vascular abnormalities including accelerated neointima. Because recent evidence suggests that tissue AAT levels determine inhibitory function, the authors hypothesize that local tissue-based expression of AAT limits elastase activity sufficiently to guide arterial response to injury. MATERIALS AND METHODS: Rabbit common femoral arteries were injured by mechanical overdilation and treated with buffer, viral control, or an adenovirus expressing AAT (Ad/AAT). After 3 and 28 days, intima-to-media (I/M) ratios were evaluated. Additionally, early changes in elastase inhibition potential (3 d), extracellular elastin and collagen content (3 d), and local macrophage and neutrophil infiltration (7 d) were determined. RESULTS: Ad/AAT significantly decreased neointima formation after mechanical dilation injury after 28 days: buffer controls exhibited mean I/M ratios of 0.76 +/- 0.06, whereas viral controls reached 0.77 +/- 0.09; in contrast, Ad/AAT reduced I/M ratios to 0.44 +/- 0.06. Both early elastin and collagen content were preserved in the Ad/AAT group relative to controls. The Ad/AAT group also reversed the local inflammation that characterized viral controls. CONCLUSIONS: This strategy demonstrates that local increases in elastase inhibition potential promote a neointima-resistant small-caliber artery, which may offer new promise in management of patients undergoing angioplasty.

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.

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.

Enhancement of neointima formation with tissue-type plasminogen activator.

PURPOSE: Indirect evidence suggests that tissue plasminogen activator (tPA) either limits or does not alter restenosis. However, tPA enhances tumor invasiveness through matrix remodeling, and several elements of degraded matrix enhance smooth muscle cell mitogenesis. We use either local adenoviral-mediated overexpression of tPA or systemic infusion of recombinant tPA combined with mechanical overdilation of rabbit common femoral arteries to evaluate the impact of tPA on neointima formation. METHODS: Left common femoral arteries of New Zealand white rabbits were transfected in situ either with an adenoviral-construct-expressing tPA or a viral control (adenoviral-construct-expressing beta-galactosidase) or nonviral (buffer) control after balloon angioplasty injury. At 7 and 28 days, left common femoral artery segments were harvested (n = 4 for each group and time point). Vessel segments were examined for intimato-media ratio, smooth muscle cell proliferation, extracellular matrix, and inflammatory response. Thrombus formation was evaluated after 3 days (n = 3 for each group). In a second experiment, New Zealand white rabbits (n = 3 per group, per time point) underwent mechanical dilation followed by buffer treatment or systemic tPA infusion according to a widely clinically used accelerated infusion protocol. Treated artery segments were harvested after 7 or 28 days and processed for intima-to-media ratio determination and class-wide histochemical determination of collagenous extracellular matrix and collagen content. RESULTS: Both rate and degree of neointima formation increase dramatically with overexpression (250%-461% relative to controls at 7 and 28 days). Substantial early matrix degradation is observed in vessels treated with local overexpression of tPA, although no increases in local inflammation or in smooth muscle proliferation occur. Late enhancement of smooth muscle proliferation emerges, consistent with secondary impact of perturbed matrix components. Systemic infusion of tPA according to clinical protocols also results in early and late enhancement of neointima formation in this model (34%-52% relative to controls at at 7 and 28 days), with significant early collagenous matrix degradation. Systemic infusion, although significant, did not attain the degree of neointima formation present with overexpression. CONCLUSION: With some evidence of dose-dependence, tissue plasminogen activator enhances neointima formation after angioplasty in a rabbit model. Early matrix degradation precedes change in rates of proliferation and underlies this effect in spite of several antirestenotic actions including decreased thrombus and decreased macrophage recruitment in this model.

Stair-step artifacts with single versus multiple detector-row helical CT.

PURPOSE: To compare the effects of acquisition parameters on the magnitude and appearance of artifacts between single and multiple detector-row helical computed tomography (CT). MATERIALS AND METHODS: A cylindric (12.7 x 305.0-mm) acrylic rod inclined 45 degrees relative to the z axis was scanned at the isocenter and 100 mm from the isocenter with single detector-row (single-channel) helical CT (beam width, 1-10 mm; pitch, 1.0, 2.0, or 3.0) and multiple detector-row (four-channel) helical CT (detector width, 1. 25, 2.5, 3.75, and 5 mm; pitch, 0.75 or 1.5). The SD of radius measurements along the rod (SD(r)) was used to quantify artifacts in all 72 data sets and to analyze their frequency patterns. Volume-rendered images of the data sets were ranked by six independent and blinded readers; findings were correlated with acquisition parameters and SD(r) measurements. RESULTS: SD(r) was smaller in four- than in single-channel helical CT for any given table increment (TI). In single-channel helical CT, SD(r) increased linearly with beam width and geometrically with pitch. In four-channel helical CT, SD(r) measurements were directly proportional to the TI, regardless of the detector width and pitch combination used. Off-center object position on average increased SD(r) by a factor of 1.6 for single-channel helical CT and by a factor of 2.0 for four-channel helical CT. Subjective rankings of image quality correlated excellently with SD(r) (Spearman r = 0.94, P <.001). CONCLUSION: Artifacts are quantitatively and subjectively smaller with four- compared with single-channel helical CT for any given TI.

Partial fat-saturated contrast-enhanced three-dimensional MR angiography compared with non-fat-saturated and conventional fat-saturated MR angiography.

Abdominal three-dimensional magnetic resonance angiography was performed in 35 patients in the equilibrium phase without fat saturation, with conventional fat saturation, and with fast partial fat saturation. Qualitative and quantitative evaluation demonstrated significantly better vessel visualization with both fat-saturated techniques. The partial fat-saturated technique provided water-specific images within a breath hold, reducing motion artifacts significantly.

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.

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.

[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.

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.

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.

Comparison of three dimensional magnetic resonance imaging in conjunction with a blood pool contrast agent and nuclear scintigraphy for the detection of experimentally induced gastrointestinal bleeding.

BACKGROUND AND AIMS: To compare the performance of 3D magnetic resonance imaging (MRI) in conjunction with an intravascular contrast agent with that of scintigraphy, with respect to detection and localisation of gastrointestinal haemorrhage in vivo in pigs. METHODS: Intraluminal bleeding sites were surgically created in the small bowel and colon of six pigs. The animals underwent scintigraphy with (99m)Tc labelled red blood cells and 3D MRI following administration of an intravascular contrast agent (NC100150) at five minute intervals over 30 minutes. For analysis, the intestinal tract was divided into six segments. Based on the two evaluated methods, each segment was characterised on a five point scale regarding the presence of a bleed. At autopsy, the surgically manipulated bowel segments were inspected for the presence of haemorrhage. RESULTS: Bleeding was confirmed at autopsy in 18/36 segments. Contrast extravasation with subsequent movement through the bowel could be documented on MRI data sets. All segments were correctly characterised, resulting in 100% sensitivity and specificity for MRI. Based on scintigraphy, interpretation of seven segments (19%) was false (sensitivity/specificity of 78%/72%). Differences in diagnostic performance were evident in the receiver operator characteristic (ROC) analysis, with an area under the MRI curve of 0.99 and under the scintigraphy curve of 0.85. CONCLUSION: In conjunction with an intravascular contrast agent, 3D MRI permits accurate detection and localisation of gastrointestinal bleeding. The extent and evolution of intestinal bleeding can be determined with repeated data acquisition.

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.