Cancer and inflammation: differentiation by USPIO-enhanced MR imaging.

PURPOSE: To assess ultrasmall superparamagnetic iron oxide particles (USPIO) -enhanced MR imaging for the differentiation of malignant from benign, inflammatory lesions. MATERIALS AND METHODS: In this study, approved by the local animal care committee, VX2 carcinoma and intramuscular abscesses were implanted into the hind thighs of New Zealand White rabbits. MR imaging was performed pre contrast and serially for 24 h after the injection of USPIO. MR findings were compared with histopathologic results based on Prussian blue stains for the presence of iron. RESULTS: Twenty-four hours after the Ferumoxtran-injection, no changes were observed in VX2 carcinomas, whereas a mean reduction of the contrast-to-noise ratio (CNR) of approximately 90% was noticed in abscesses as well as in necrotic tumors. On histopathologic examination, abscess and necrotic parts of the tumor were found to include iron-containing monocytes demonstrating that the reduction in CNR was caused by USPIO-tagged monocytes. CONCLUSION: Our results prove the ability of USPIO-enhanced MRI to differentiate benign, inflammatory from malignant lesions.

Identifying radiological needs of referring clinicians.

To provide prospective information about quality- and satisfaction-related product features in radiology, a customer-centered approach for acquiring clinicians' requirements and their prioritizations is essential. We introduced the Kano model for the first time in radiology to obtain such information. A Kano questionnaire, consisting of pairs of questions regarding 13 clinician requirements related to computed tomography (CT), magnetic resonance imaging (MRI) access and report turnaround time (RTT), was developed and administered. Each requirement was assigned a Kano category, and its satisfaction and dissatisfaction coefficients were calculated and presented in a Kano diagram. The data were stratified based on different clinics and on staff and resident clinicians. The time interval was evaluated between the completion of an examination and the first attempt to access the report by a clinician. Consultation for modality selection and scheduling and access to CT within 24 h and RTT within 8 to 24 h were considered as must-be requirements. Access to CT within 4 h and within 8 h, access to MRI within 8 h and within 24 h, and access to RTT within 4 h were one-dimensional requirements. The extension of operation time for CT or MRI, as well as MRI access within 4 h, was considered attractive. Eight out of nine clinics considered RTT within 8 h as a must-be requirement. There were differences in responses both among different clinics and between staff and resident clinicians. Access attempts to reports by clinicians in the first 4 h after the examination completion accounted for 65 % of CTs and 49 % of MRIs.

Novel approach to complex pulmonary arteriovenous malformation embolization using detachable coils and Amplatzer vascular plugs.

INTRODUCTION: We evaluated the feasibility of a modified embolization technique of pulmonary arteriovenous malformations (PAVM) using venous sac embolization with detachable coils combined with the feeding artery embolization with the Amplatzer vascular plug (AVP). MATERIALS AND METHODS: We retrospectively studied technical and clinical success in the treatment of 11 complexe PAVMs. We recorded number and size of feeding arteries and draining vein, the last prior and post treatment in the follow up CT, size of PAVMs; and the number of devices needed to occlude each PAVM. RESULTS: 11 complexe PAVM were treated with detachable coils to venous sac embolization followed by AVP to embolize feeding arteries. In all but one case a complete occlusion of the PAVM was angiographically achieved. The mean number of feeding vessel was 2.64 ± 0.92 (2-5). The mean number of coils was 7.82 ± 5.09 (3-20 coils). CT-follow-up, that was possible in 8 patients, showed a significant reduction of the draining vein size. The mean diameter reduction of the draining vein was 62 ± 18% varying between 29% and 77%. In all but one case with the complexe angioarchitecture the reduction of draining vein size close to 70% was achieved. CONCLUSIONS: Our study implies that the venous sac embolization using the detachable coils followed by occlusion of the large feeding arteries using the AVP is a highly efficient method for the treatment of the complex PAVMs with large out-flow vessels and short feeding arteries.

Enhancing same-day access to magnetic resonance imaging.

PURPOSE: The aim of this study was to provide better patient access to MRI within 24 hours through process improvement. METHODS: The MRI process in an academic radiology department was examined. Customer value was determined using a Kano questionnaire. Current state process and performance data were measured. Process time and process value mapping were conducted. Underlying root causes that hampered MRI process flow were identified and prioritized using a fishbone diagram and failure mode and effect analysis. Statistical analysis, queuing theory, and statistical process control were used to describe and understand process behaviors, to test hypotheses, to validate solutions, and to monitor results. RESULTS: Timely access to MRI examinations within 24 hours was identified as a key customer value. A total of 33 failure modes leading to process wastes, together with 113 potential failure causes, were worked out, of which 14 failure modes were prioritized and dealt with. Having improved the process, patient access within 24 hours increased from 53% to >90%. The mean cycle time was reduced from 52 to 39 minutes. The monthly throughput increased by 38%. Scanner productivity was increased by 32%. Revenue and savings are estimated to be about €247,000 in the first year, after subtracting all costs. CONCLUSIONS: Patient access to MRI within 24 hours has been granted for >90% of requests. Improved productivity and cost saving are achieved simultaneously.

Hypersensitivity reactions and contrast medium injection: are they always related?

BACKGROUND: Hypersensitivity (allergic or non-allergic) reactions that occur after contrast medium (CM) injection are usually related to the CM. Recent studies, and case reports lack the analysis of alternate causes that could be also responsible in individual cases. PATIENTS AND METHODS: We investigated the individual relevant factor/causative agent of adult patients with hypersensitivity reactions that occurred in radiological units during CM-enhanced procedures (CT, angiography, urography, or MR-examinations). Both immediate and non-immediate (delayed) reactions were included. To find out the relevant agent a detailed patients' history was carefully analyzed. In addition, the records were retrospectively reviewed, and if indicated and possible laboratory (e.g. basophil activation test) and skin tests (e.g. prick) and/or provocations with CM-injections under routine conditions were performed. RESULTS: 38 patients (men n=21) suspected for CM-hypersensitivity reactions were identified. These reactions were in most cases mild (n=21), moderate reactions occurred in 13 cases, and four patients had severe reactions. In 28 patients the reactions were induced by the CM (iodinated CM in 25 cases). Four patients had reactions that were not CM-related (latex allergy, adenosine reaction, vasovagal reaction, unknown cause) and in six cases the reaction was partly CM-related (immunological activation was present due to the patients' diseases). CONCLUSION: Our data support the hypothesis that in CM-enhanced procedures not only contrast materials but also a broad range of other factors may also induce hypersensitivity reactions. Therefore, the number of CM-induced hypersensitivity is smaller than initially suspected. The knowledge of the cause of a reaction is essential to effectively prevent its recurrence and to improve safety aspects in patients undergoing CM-injection. Larger trials should be performed to more specifically assess alternate causes in patients who acquire hypersensitivity reactions in CM-enhanced diagnostic procedures.

Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.

PURPOSE: Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival. PATIENTS AND METHODS: Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis. RESULTS: Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18). CONCLUSION: Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.

Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study.

BACKGROUND: To assess prospectively the safety and efficacy of Yttrium-90 microspheres in patients with unresectable liver metastases from neuroendocrine tumors. MATERIALS AND METHODS: Microspheres were administered via a temporarily placed hepatic catheter. Patients were monitored prospectively. All patients were followed with laboratory and imaging studies at regular intervals to determine response rates. Toxicity and quality of life scores were measured. RESULTS: Nine patients (7 female) with a mean age of 58.8 years were enrolled in this prospective trial. The mean tumor load was 58.8%. The estimated percentage shunting to the lungs on MAA scans was 5.04 +/- 2.4%. Visceral artery embolization of extrahepatic arteries before treatment was performed in 6 patients. The median dose of microspheres was 2.1 +/- 0.4 GBq. A total of 12 therapy sessions was performed. The mean follow-up was 21.7 months. Technical success was 100%. No major complications occurred. Survival rates were 100, 57 and 57% for 1, 2 and 3 years, respectively. Three months after SIRT therapy partial response (PR) was seen in 6 patients (66%). Calculated reduction of liver metastasis volume was 49%. In 3 patients (33%) stable disease was seen with a calculated tumor reduction of 13%. The estimated time to progression was 11.1 months. CONCLUSION: Radioembolization with (90)Y microspheres is safe and produces high response rates even with extensive tumor replacement for up to 1 year. Acute and late toxicity was very low. Further investigations compared with other local ablative techniques is warranted.

[Determination of the arterial input function in mouse-models using clinical MRI]. / Bestimmung der arteriellen Inputfunktion in einem Mausmodell an einem klinischen MRT-system.

Dynamic contrast enhanced Magnetic Resonance Imaging is a promising method for quantitative analysis of tumor perfusion and is increasingly used in study of cancer in small animal models. In those studies the determination of the arterial input function (AIF) of the target tissue can be the first step. Series of short-axis images of the heart were acquired during administration of a bolus of Gd-DTPA using saturation-recovery gradient echo pulse sequences. The AIF was determined from the changes of the signal intensity in the left ventricle. The native T1 relaxation times and AIF were determined for 11 mice. An average value of (1.16+/-0.09) s for the native T1 relaxation time was measured. However, the AIF showed significant inter animal variability, as previously observed by other authors. The inter-animal variability shows, that a direct measurement of the AIF is reasonable to avoid significant errors. The proposed method for determination of the AIF proved to be reliable.

[Dosimetric evaluation of eye lense shieldings in computed tomography examination--measurements and Monte Carlo simulations]. / Dosimetrische Evaluation von Augenlinsen-protektoren in der Computertomographie--Messungen und Monte-Carlo-Simulationen.

The present study aims at the investigation of eye lens shielding of different composition for the use in computed tomography examinations. Measurements with thermo-luminescent dosimeters and a simple cylindrical waterfilled phantom were performed as well as Monte Carlo simulations with an equivalent geometry. Besides conventional shielding made of Bismuth coated latex, a new shielding with a mixture of metallic components was analyzed. This new material leads to an increased dose reduction compared to the Bismuth shielding. Measured and Monte Carlo simulated dose reductions are in good agreement and amount to 34% for the Bismuth shielding and 46% for the new material. For simulations the EGSnrc code system was used and a new application CTDOSPP was developed for the simulation of the computed tomography examination. The investigations show that a satisfying agreement between simulation and measurement with the chosen geometries of this study could only be achieved, when transport of secondary electrons was accounted for in the simulation. The amount of scattered radiation due to the protector by fluorescent photons was analyzed and is larger for the new material due to the smaller atomic number of the metallic components.

Plasma chromogranin A as marker for survival in patients with metastatic endocrine gastroenteropancreatic tumors.

BACKGROUND & AIMS: The prognostic role of plasma chromogranin A in patients with neuroendocrine tumors is unclear. We investigated the role of chromogranin A in predicting survival and hypothesized that chromogranin A mirrors tumor burden and that a rapid increase after a phase of stable plasma chromogranin A levels might predict exploding tumor growth. METHODS: Three hundred forty-four patients with metastatic, well-differentiated neuroendocrine tumors were included. A subsample of 102 patients was investigated to correlate radiologically classified tumor burden with plasma chromogranin A. Hepatic tumor burden (0%, 0%-25%, 25%-50%, >50%) was assessed from computed tomography/magnetic resonance imaging scans. Follow-up information until death was generated in regular intervals. RESULTS: Plasma chromogranin A levels (U/L) vary between tumor entities (Kruskal-Wallis, P < .001) and were associated with survival time (hazard ratio [hours], 2.14 per one unit in the log10 CgA level scale; 95% confidence interval [CI], 1.75-2.62; P < .001). Chromogranin A levels correlated with hepatic tumor burden (Spearman P = .57; 95% CI, 0.44-0.70; P < .001). Additional extrahepatic tumor load did not relevantly affect plasma chromogranin A. A sudden increase observed in individual patients was paralleled by rapid tumor progress and short survival. CONCLUSIONS: Increased plasma chromogranin A in patients with metastatic neuroendocrine tumors is predictive for shorter survival. There was a modest correlation between chromogranin A levels and hepatic tumor burden. We hypothesized further that a sudden increase in individual chromogranin A levels indicates unfavorable outcome.

Localisation and staging of gastrin producing tumours using cross-sectional imaging modalities.

Cross sectional imaging in the assessment of gastrinomas has three major applications: Tumor localization (sporadic gastrinoma, MEN I) in patients undergoing primary or secondary surgery. Staging of metastasized tumors, especially assessment of lymph nodes and liver metastases, possibly including a risk analysis prior to liver resection. Post-surgery follow-up and monitoring of bio- or chemotherapy. Detection of primary tumors is strongly correlated with their size. However, the sensitivity of surgical assessment of the mostly small tumors by experienced surgeons is much higher than that of any imaging modality. Of all imaging modalities, endoultrasonography (EUS) followed by Somatostatin receptor scintigraphy (SRS) is the most sensitive modality for the assessment of pancreatic tumors in asymptomatic patients suffering from a MEN-I syndrome. Scintigraphy has the highest sensitivity in tumors of symptomatic patients and in the assessment of metastases. CT and MRI are only second line diagnostic modalities. Their sensitivity is largely dependent on the selection of patients. As a potential application, 3D reconstruction of nearly isotropic CT data sets for the risk assessment prior to liver resection is currently developing. Due to the absent radiation exposure, MRI is increasingly utilized to monitor the response of metastases under systemic therapy, e.g. in clinical trials.

Effectiveness and renal tolerance of multidetector helical CT with gadobutrol: results of a comparative porcine study.

PURPOSE: To prospectively evaluate the safety and effectiveness of high doses of 1 mol/L gadobutrol as a contrast agent for computed tomography (CT). MATERIALS AND METHODS: Experiments were performed according to guidelines for care of laboratory animals. The local animal care committee approved the study protocol. Unenhanced and contrast material-enhanced CT images of the chest and abdomen were obtained randomly in nine domestic pigs. Gadobutrol was injected (1, 2, or 3 mL per kilogram of body weight; three pigs for each dose). Attenuation was measured in different vascular and parenchymal structures. Changes in blood chemistry and hematologic parameters were monitored before and 1, 2, 3, and 7 days after gadobutrol administration. Urine samples were evaluated before and 7 days after gadobutrol administration. Technetium 99m mertiatide renal scintigraphy was performed before and 7 days after contrast medium injection. Animals were sacrificed 7 days after contrast medium administration, and one kidney was removed from each animal for examination with light microscopy. No serious adverse events occurred. A mixed-model nested analysis of variance was used for statistical evaluation. RESULTS: Mean attenuations for the 1, 2, and 3 mL/kg gadobutrol doses, respectively, were 148 HU +/- 20 (standard deviation), 282 HU +/- 18, and 289 HU +/- 20 in the thoracic aorta; 99 HU +/- 11, 166 HU +/- 9, and 153 HU +/- 18 in the kidneys; and 106 HU +/- 7, 186 HU +/- 18, and 224 HU +/- 24 in the inferior vena cava. No clinically relevant changes in hematologic, blood chemistry, or urine analysis results were detected. Markers for glomerular filtration and tubular function were unaffected in all groups. Scintigraphy revealed no differences between unenhanced and contrast-enhanced results. No morphologic changes of the renal parenchyma were found at histologic analysis. CONCLUSION: Contrast-enhanced CT with a 2 or 3 mmol/kg dose of 1 mol/L gadobutrol resulted in excellent vascular and parenchymal enhancement. A gadobutrol dose of up to 3 mL/kg did not affect renal function.

Accuracy of single-session extracranial radiotherapy for simple shaped lung tumor or metastasis using fast 3-D CT treatment planning.

BACKGROUND: This study is situated in the area of measuring set-up accuracy and time periods of single-session extracranial radiotherapy (SSRT) for simple-shaped targets (e.g., spherical or rotational symmetrical) definitively located in the peripheral lung. METHODS AND MATERIALS: After adaptation of the stereotactic body frame, the patient has to remain in the vacuum pillow during planning computed tomography (CT), fast three-dimensional (3-D) treatment planning, and direct irradiation after verification. Fast preplanning is performed by using virtual simulation software to accelerate the method. RESULTS: In our new procedure, SSRT is applied in approximately 1.5 h. The mean setup accuracy vector was 2.4+/-0.7 mm in the range of 1.34 to 4 mm. Mean intrafractional patient movement in the stereotactic body frame before and after radiation was 0.70 mm+/-0.5 mm and 0.76+/-0.76 mm in the range of 0 to 2.8 mm. Mean time period steps were measured at (1) planning CT with 3-D treatment planning: 76+/-12 min; (2) irradiation and verification: 33+/-7 min; and (3) complete procedure duration: 109+/-11 min (range, 89-169). CONCLUSIONS: The main difference between the positioning technique of SSRT and that of conventional extracranial radiosurgery is the tighter patient fixation, which guarantees minimal patient movement. The main advantages are procedure acceleration and omission of CT simulation. SSRT is a preliminary stage of real-time treatment.

Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial.

BACKGROUND & AIMS: The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure (progression, death, stop of study treatment) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut (mainly pancreatic) and midgut tumors. METHODS: One hundred nine of 125 registered patients were randomized starting in January 1995, and 105 patients (51 monotherapy, 54 combination treatment) were finally analyzed in March 2000. Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging. Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not randomized because of stable disease. RESULTS: Partial tumor regression occurred in 2.9%, 1.9%, and 5.7% and stabilization of tumor growth in 44.8%, 27.6%, and 15.2% at 3, 6, and 12 months, respectively, with no significant differences between both treatment arms. In March 2000, 9.5% of patients were in treatment. Time to treatment failure and long-term survival did not differ significantly between the 2 groups, with a median survival of 32 and 54 months for the octreotide and the combination groups, respectively. Survival was longer in patients not randomized because of stable disease (median, 68 months) and in those with low nuclear Ki-67. A trend toward longer survival was shown for patients with slow spontaneous tumor growth before randomization. Patients responding to treatment lived longer than unresponsive patients. CONCLUSIONS: Combination treatment was not superior to monotherapy concerning progression-free and long-term survival. Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage.

Pathologic breast conditions in childhood and adolescence: evaluation by sonographic diagnosis.

OBJECTIVE: The growing awareness of female breast cancer has led to increased sensitivity toward pathologic breast conditions in children and adolescents. Thus, approximately 15% of patients in child and adolescent gynecology are referred for the first time because of conspicuous features of the breast such as pain, palpable masses, and other findings on visual inspection. The aim of this study was to analyze the underlying diagnoses and diseases and determine the status of breast sonography in the diagnostic process. METHODS: The study population consisted of 62 female patients between 8 weeks and 20 years of age (1997-2002) who were examined clinically, followed by standardized sonography (7.5-13 MHz, conventional B-mode panoramic sonography). Presumed diagnoses were confirmed by biopsy in some patients (n = 16) and by follow-up with clinical examination and sonography in most cases (n = 46). RESULTS: The clinical and sonographic evaluation confirmed 4 main groups of diagnoses: benign tumors (15), developmental disturbances (14), cystic changes (11), and inherent defects (7). In the remaining cases, the findings were no abnormality (9), nipple discharge without evidence of pathologic or morphologic correlates (3), abscesses (2), and epidermoid cyst (1). CONCLUSIONS: Knowledge of regular breast development and its variants is essential for the physician. Given knowledge of the sonographic appearance of physiologic breast development and specific lesions, breast sonography is most helpful in identifying and characterizing abnormalities and guiding further investigation.

Local administration of NF-kappa B decoy oligonucleotides to prevent restenosis after balloon angioplasty: an experimental study in New Zealand white rabbits.

PURPOSE: To evaluate the efficacy of NF-kappa B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. MATERIALS AND METHODS: In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-kappa B in two different concentrations (1 mug: n = 14; 10 mug: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. RESULTS: NF-kappa B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF-kappa B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm(2) using 1 mug NF-kappa B ODN compared to 0.98 mm(2) in the control group. The higher dose resulted in a neointimal area of 0.97 mm(2) compared to 1.07 mm(2) at the control side. CONCLUSIONS: Local drug delivery of NF-kappa B ODN using the "channeled balloon" catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.

Evaluation of a laser system for CT software simulation (EXOMIO) in patients with breast cancer.

PURPOSE: To develop a manually movable laser system connected to the CT table for alignment of the isocenter cross of irradiation fields on the patient's skin directly after CT software simulation. MATERIAL AND METHODS: The specially designed laser system was constructed in the authors' department, and the mean focusing accuracy of isocenter translations was analyzed using Alderson phantom measurements. The mean overall accuracy from setup to treatment of the whole procedure of CT software simulation was measured by the comparison of bone structures and mamma contour of the digitally reconstructed radiograph (DRR) with the verification film. The time taken for the different setup procedure steps was evaluated for 70 breast cancer patients who were treated using tangential fields. RESULTS: The mean focusing accuracy of the manually movable laser system after defined isocenter translation was measured as 0.8 +/- 0.5 mm, the mean patient movement on the CT table as 2.0 +/- 1 mm, and the mean positioning accuracy of the first treatment after patient positioning corresponding to the skin alignments as 3.9 +/- 1.5 mm. The time periods for the different steps of the CT software simulation were measured, and the total duration was found to be 35.8 +/- 3.3 min. CONCLUSION: In general, the main advantage of well-known CT software simulation when compared to conventional simulation is the relief of the real X-ray simulator which is feasible with fast planning software (EXOMIO) and the presented movable laser system.

Effects of altering infusion parameters on intimal hyperplasia following local catheter-based delivery into the rabbit iliac artery.

BACKGROUND: Efficient local gene or drug therapy requires optimized application modalities to avoid vessel damage, which might lead to increased neointimal hyperplasia. Aim of the study was to evaluate different application parameters for local delivery using the channeled balloon catheter in order to minimize vessel trauma induced by local application. METHODS AND RESULTS: Sixty cholesterol fed rabbits were randomly enrolled into twelve groups of different local application parameters: group I, application pressure 2atm/application volume 1ml physiologic saline; group II, 2atm/2ml; group III, 2atm/5ml; group IV, 4atm/1ml; group V, 4atm/2ml; group VI, 4atm/5ml. The other six groups received Ringer's solution instead of saline. Administration of the solution was randomly performed in one iliac artery using the channeled balloon catheter with simultaneous balloon angioplasty (8atm). The contralateral iliac artery served as a control and was treated with balloon angioplasty only. Four weeks after local therapy, calibrated angiography was performed; the animals were sacrificed, vessel segments were excised and quantitative morphometric measurements were obtained. In none of the animals acute complications, e.g. dissection, thrombosis or perforation of the vessel, was noted. Up to an application pressure of 4atm and an application volume of 5ml, no significant neointima formation was seen compared to arteries which underwent angioplasty only. Additionally, no significant differences between saline and Ringer's solution were detected. In a multivariate analysis, neither application pressure nor volume were found to have a statistically significant influence on the amount of neointimal hyperplasia. CONCLUSIONS: Local application of "drugs" using the channeled balloon catheter is safe and feasible without significant induction of neointimal hyperplasia compared to angioplasty, if an application volume of 5ml and a pressure of 4atm is not exceeded.

In vitro MR imaging of regulated gene expression.

PURPOSE: To design and evaluate a construct that allows regulated expression of the magnetic resonance (MR) imaging reporter gene human tyrosinase under control of the tetracycline response element. MATERIALS AND METHODS: A breast cancer cell line (MCF-7) was transfected with a plasmid that codes for the tetracycline-controlled transactivator and a new construct. In this construct, the reporter gene human tyrosinase is under control of the tetracycline response element, thus allowing suppression of gene expression by adding doxycycline (tetracycline switched off). A reverse transcription polymerase chain reaction was conducted to evaluate gene expression. Additionally, immunohistochemical investigation of tyrosinase and melanin staining was undertaken to analyze the presence of these molecules. After culture in an iron- and holotransferrin-enriched medium, cells were imaged in a 1.0-T clinical MR imager by using a surface coil and T1-weighted spin-echo and gradient-echo sequences. RESULTS: Two stable transfected cell clones were established. Cells cultured with doxycycline showed no background expression of the human tyrosinase gene, whereas withdrawal of doxycycline resulted in detectable tyrosinase messenger RNA expression. Gene expression results in a detectable tyrosinase protein level and melanin content. Increased signal intensity on T1-weighted MR images in cells that expressed the reporter gene was observed in comparison to genetically identical cells with the reporter gene switched off. CONCLUSION: Our construct enables MR imaging of regulated tyrosinase gene expression in vitro.

Magnetic resonance urography in pediatric urology.

OBJECTIVE: To evaluate the efficiency of magnetic resonance urography (MRU) in pediatric urology. MATERIAL AND METHODS: We report retrospectively on 12 children who underwent MRU between January 1999 and November 2001. MRU was performed to accurately evaluate the entire urinary tract because of megaureter, ectopic ureter, vesicoureteral reflux, Y-inverted duplication and hydronephrosis because of pyeloureteral stenosis. T1- and T2-weighted images were obtained in the coronal, sagittal and axial planes. The mean age of the children (8 females, 4 males) investigated was 36 months (range 2-140 months). RESULTS: An accurate anatomical picture of the entire urinary tract could be obtained in all children. The obstructive nature of megaureter could be differentiated. The distal orifice of ectopic ureter could be identified in the vagina. Vesicoureteral reflux into the blind-ending ureteral bud of a duplicated system was accurately identified. Hydronephrosis was demonstrated to be the result of pyeloureteral stenosis. The location of stenoses was easily identified in the sagittal and coronal planes. CONCLUSIONS: MRU is an excellent imaging modality for accurately depicting the urinary tract. MRU is superior to conventional intravenous urography because it does not use ionizing radiation, the gadolinium contrast medium used is not nephrotoxic and the imaging quality is excellent, reproducible and not interfered with by gas superposition. Considering the high costs and diagnostic benefit of MRU compared to intravenous urography, MRU should be performed in patients with impaired renal function, in those with an allergy to contrast medium and if anatomic relationships are not clear prior to reconstructive surgery.