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.

Magnetic resonance angiography versus duplex sonography for diagnosing renovascular disease.

Noninvasive testing for renovascular disease is required to identify patients who may benefit from revascularization procedures without exposing an unnecessary amount of patients to the risks of catheter angiography. All available methods of diagnosing renal artery stenosis have significant limitations. We compared a new technique, contrast-enhanced magnetic resonance angiography, with an established technique, duplex ultrasonography, for the detection of renal artery stenosis using catheter angiography as the standard of reference. Eighty-nine patients with clinically suspected renovascular disease underwent duplex renal scanning and contrast-enhanced magnetic resonance angiography. Sixty of these also underwent catheter angiography. All studies were interpreted for the presence of renal artery stenosis blinded to the results of the other imaging modalities. For detection of hemodynamically significant (>/=60% diameter reduction) main renal artery stenosis, sensitivity and specificity were 90% and 86%, respectively, for magnetic resonance angiography and 81% and 87% for duplex sonography. Most false readings involved differential grading of stenoses detected with all 3 techniques. When patients with fibromuscular dysplasia were excluded from the analysis, the sensitivity of magnetic resonance angiography increased to 97%, with a negative predictive value of 98%. Magnetic resonance angiography detected 96% and duplex 5% of accessory renal arteries seen at catheter angiography. Contrast-enhanced magnetic resonance angiography is a useful technique for diagnosing atherosclerotic renovascular disease. It overcomes the major limitations of duplex renal scanning. However, duplex has the advantage of providing hemodynamic information and appears better suited for the assessment of patients with suspected fibromuscular dysplasia.

Fast spin-echo inversion-recovery imaging versus fast T2-weighted spin-echo imaging in bone marrow abnormalities.

RATIONALE AND OBJECTIVES: The purpose of this investigation is to compare a fat-suppressed T2-weighted fast spin-echo (FSE) sequence in bone marrow abnormalities with an FSE STIR sequence that recently has become commercially available. METHODS: Fast spin-echo images (repetition time [TR], 3500-5000 mseconds; echo time [TE], 96-114 mseconds) and FSE STIR images (TR, 3000-5000 mseconds; TE, 32-40 mseconds; inversion time [TI], 140-150 mseconds) were compared quantitatively and qualitatively calculating signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and lesion conspicuity and using a qualitative scoring system. RESULTS: Signal-to-noise ratio (mean +/- standard deviation) was 36.4 +/- 19.3 for the FSE and 29.0 +/- 15.9 for the FSE STIR images (P = .002). Contrast-to-noise ratio (mean +/- standard deviation) was 18.7 +/- 14.3 for the FSE and 20.3 +/- 16.0 for the FSE STIR images (P = .45). Lesion conspicuity (mean +/- standard deviation) was 1.7 +/- 1.5 for the FSE and 3.5 +/- 4.0 for the FSE STIR images (P = .025). The most important difference in the qualitative evaluation related to the better signal homogeneity on the FSE STIR images. CONCLUSIONS: Fast spin-echo STIR images may be preferable to FSE images with fat suppression due to better image homogeneity and lesion conspicuity.

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.

Abdominal pulsatile tumor after endovascular abdominal aortic aneurysm repair.

A 70 years old patient was successfully treated for infrarenal aortic aneurysm by an endovascular bifurcated prosthesis. Three months later, because of dysuria, he underwent urological examination revealing an abdominal pulsatile tumor. Thereafter, the patient was sent to our emergency ward with suspected symptomatical endoleak. Radiological screening by computer tomography and magnetic resonance angiography showed good post-operative results without endoleak. Patient was treated with antispasmodic medication and is doing well today. Because endovascular repair of aortic aneurysm, in contrast to an open approach, does not eliminate the aneurysm itself, post-operative abdominal palpation can be ambiguous. Magnetic resonance angiography--without the need of nephrotoxic contrast medium--compares favourably to CT and provides excellent pictures with less artefacts for post-operative screening of endoleak. If reperfusion can be excluded, pulsation is due to the transmission of the blood-pressure wave to the thrombosed aneurysm.

[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.

[Long-term monitoring]. / Long-Term Monitoring.

The electroencephalography (EEG) keeps its essential role in the differential diagnosis of epileptic and non-epileptic seizure disorders and in the classification of the different types of epilepsies and epileptic seizures, mainly due to its unique capability to directly show epileptic malfunction. The routine EEG usually records the EEG between seizures (interictal EEG) and remains a cost effective, highly specific, but not very sensitive method in epileptology. However, a diagnosis based on clinical data and routine EEG alone if often difficult and 20-30% of patients referred to an epilepsy centre due to medical refractory seizures do not have epilepsy. The different methods of long-term monitoring (cable and radio telemetry, ambulatory EEG monitoring) can continuously record EEG and other biosignals for many hours up to several days and allow a direct assessment of seizures (ictal EEG). In combination with the video-recorded symptomatology, these methods establish a precise diagnosis and follow-up of uncertain seizure disorders in the majority of cases. Although technical and personnel investment is relatively high the method used in expert hands is efficient, accepted and cost effective.

Detection and evolution of rhythmic components in ictal EEG using short segment spectra and discriminant analysis.

An automated method for analysis of ictal EEG is described which aims to reliably detect one or several rhythmic components in short EEG segments (2 sec) and to display their presence, frequency, amplitude, location, and temporal evolution. Spectra were estimated and compared using fast Fourier transform (FFT) and autoregressive modelling (AR). A subsequent linear discriminant analysis decided whether a spectral peak is likely to be caused by rhythmic activity or by the inherent statistical variability. FFT was found to perform better than AR in the detection of rhythmic components, yielding a false-positive rate of 0.825%, a false-negative rate of 2% (signal to noise ratio -4.6 dB), a frequency resolution of 2 Hz, and a temporal resolution of 0.5 sec. Seizure analysis revealed that the ictal scalp EEG of even short seizures can show a complex evolution of rhythmic patterns which are impossible or difficult to recognize by visual inspection or conventional spectral analysis. The following phenomena are demonstrated: superposition of two rhythmic components suggesting two cerebral regions discharging simultaneously and independently with their own pacemakers, sudden and gradual change of frequencies, and gradual development of harmonic frequencies. It is suggested that a more precise correlation between rhythmic generators and seizure symptomatology might allow more predictable pharmacological responses in antiepileptic therapy.

Normal and myopathic propagation of surface motor unit action potentials.

With the aid of a computer-assisted multichannel EMG system, the propagation of motor unit action potentials is analysed during isometric voluntary muscular contraction under normal and myopathic conditions. A linear array of 30 surface electrodes is fixed above the biceps brachii muscle, parallel to the longitudinal muscle axis and centered over the end-plate zone. The EMG is simultaneously recorded on all channels and displays the propagation of surface potentials on both sides of the innervation band. The mean muscle fibre conduction velocity is computed by a cross-correlation technique. Five adult patients in a late stage of progressive muscular dystrophy show a highly altered propagation behaviour of motor unit action potentials without a time shift between potentials of adjacent electrodes. A mathematical model is described which predicts such a behaviour and suggests that it must be due to a pathological longitudinal spread of end-plates in this patient group. In 5 boys with Duchenne muscular dystrophy and only moderate impairment of the biceps muscle the mean muscle fibre velocity was reduced (2.81 +/- 0.34 m/sec) compared to 17 healthy subjects (4.42 +/- 0.37 m/sec). Each myopathic patient examined could be separated clearly from the group of healthy subjects on the basis of the surface EMG analysis.

From clinical observation to long-term monitoring: diagnostic developments in conservative epileptology.

The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary-level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long-term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17.8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, tics, or startle reactions, are frequent (34.9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.

Twenty years of ictal EEG-EMG.

This study aimed to evaluate the use of ictal EEG recordings combined with simultaneous surface EMG in the diagnosis and analysis of motor events, both epileptic and nonepileptic. All ictal registrations were performed utilizing radio/cable telemetry. Routine recordings consisted of 18-channel EEG plus 8-channels bipolar surface EMG in freely moving patients. Combined ictal EEG-EMG recordings in freely moving patients enabled us to identify and define the following pathomechanisms of epileptic drop seizures, epileptic axial spasms, atonic, myoclonic-atonic, and akinetic seizures. Precise differentiation could be made between tonic and nontonic postural seizures and between startle-induced reflex seizures and hyperekplexia. The findings from telemetered ictal recordings in freely moving patients with combined EEG and surface EMG offer the only means of identifying, defining, and differentiating motor events, both epileptic and nonepileptic, of a short duration that cannot be properly differentiated by clinical examination alone.

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.