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Introduction: This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced urothelial cancer. Methods: Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP). Results: A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.

Background: Pulmonary function may decline after induction chemotherapy and predict perioperative complications in non-small cell lung cancer (NSCLC). The influence of adjuvant chemotherapy is largely indeterminate. Objective: To assess whether adjuvant chemotherapy alters pulmonary function and impacts on treatment-related adverse events. Methods: In a trial on adjuvant chemotherapy (the TREAT trial), 132 patients with R0-resected NSCLC were randomised to 4 cycles of cisplatin-vinorelbine (CVb, n = 65) or cisplatin-pemetrexed (CPx, n = 67). Pulmonary function tests (forced expiratory volume in 1 s, FEV1, forced vital capacity, FVC, total lung capacity, TLC, diffusing capacity for carbon monoxide, DLCO, and blood gas analyses, BGA) were analysed before and 30 days after the last chemotherapy, and changes were calculated (Δ = mean differences). Results: Overall, FVC increased significantly (Δ +290 ml, n = 76; p < 0.0001), while TLC did not change (Δ +220 ml, n = 41; p = 0.174). For CPx, FEV1 increased significantly (Δ +150 ml, n = 47; p = 0.0017), but not for CVb (Δ +30 ml, n = 30). DLCO decreased only for CVb (-8%, n = 6) but not for CPx (-0.39%, n = 17; p = 0.58). BGA did not change (p = 0.99). In a Cox regression analysis, baseline pulmonary function did not influence treatment failure. Conclusions: Adjuvant chemotherapy seems not to result in a decrease of pulmonary function parameters. A significant FVC increase was probably due to ongoing postoperative improvement. Decline of DLCO was noted with CVb but not with CPx. Pulmonary function does not impact on treatment failure.

Increased echogenicity is one of the major diagnostic criteria for the subjective evaluation of liver echograms. In our approach to ultrasonic tissue characterisation by B-scan image analysis echogenicity is expressed by parameters deriving from the grey-level histogram. In this study the grey level histograms of a group of normals and patients with diffuse parenchymal liver disease are analysed. When employing the two parameters mean grey level (G) and standard deviation of grey levels (SG) the diagnostic accuracy was 90% (specificity 95%, sensitivity 85%). For subjective evaluation the liver echograms of a randomly selected sub-group of normals and patients were blindly evaluated by three observers who positively correlated the finding of increased echogenicity with the diagnosis of a pathological liver echogram. As demonstrated by our results the two-parameter analysis of the grey-level histogram leads to a quantification of the subjective diagnostic criterion of echogenicity, thus providing useful information for image interpretation.

Purpose In postmenopausal women with estrogen receptor–positive early breast cancer, surgery is usually followed by a 5-year course of tamoxifen. This report presents results of a prospective, open-label, randomized study, designed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment, compared with continuing on tamoxifen for 5 years. Patients and Methods After receiving tamoxifen treatment for 2 years, eligible patients (n = 979) were randomly assigned to switch to anastrozole (1 mg/d) or continue tamoxifen (20 or 30 mg/d) for an additional 3 years. Patients were monitored every 6 months during years 1 to 3 and annually thereafter. The primary efficacy variable was disease-free survival, including local or distant recurrence, new contralateral breast cancer, or death. Secondary variables were overall survival and assessment of safety. Results Switching to anastrozole resulted in a significant reduction in the risk of disease recurrence (hazard ratio [HR], 0.66; 95% CI, 0.44 to 1.00; P = .049), and improved overall survival (HR, 0.53; 95% CI, 0.28 to 0.99; P = .045) compared with continuing on tamoxifen. Fewer patients who switched to anastrozole reported serious adverse events (22.7% v 30.8%) compared with those who continued on tamoxifen, mainly due to more patients in the tamoxifen group with endometrial events. The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified. Conclusion Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen.

This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/alpha/ST: 600 ms/28 ms/180 degrees /6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/alpha: 0.8/1.9 ms/40 degrees ), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P0.0001). Severe morphological changes led to perfusion defects (97%, P0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients.

The study consisted of two treatment arms comparing the effects of CLDR (continuous low dose rate) and PDR (pulsed dose rate) brachytherapy on cell cycle progression in a radioresistant rat prostate tumour model.Interstitial PDR and CLDR brachytherapy (both 192-Ir, 0.75 Gy/h) were administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to 40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell subpopulations were determined at 4 h (3 Gy), 24 h (18 Gy), 48 h (20 and 36 Gy), as well as during the subsequent redistribution period (20 and 40 Gy) at 72, 96, and 120 h. Tumours either implemented with an empty tubing system (n=5) or under undisturbed growth (n=5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal.The aneuploid cells possessed a constant DNA-Index of 1.9+/-0.06. In contrast to sham-treated controls, the aneuploid cell fraction with G2/M DNA content was significantly increased (p0.05) after initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p0.05) with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but then more pronounced cell cycle changes, particularly expressed during the redistribution period after both 20 and 40 Gy.CLDR and PDR brachytherapy showed differential effects on cell cycle progression. The induction of a significantly earlier but also less persistent G2/M cell cycle arrest after CLDR compared to PDR brachytherapy implies that a substantially higher fraction of tumour cells are irradiated in G2/M after CLDR.

To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion.Lung and chest wall motion of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP (true fast imaging with steady-state precession) dMRI and a small inductively coupled marker coil on either the abdomen or thorax. Three different breathing maneuvers were performed (predominantly "abdominal breathing," "thoracic breathing," and unspecific "normal breathing"). The craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) lung distances were correlated (linear regression coefficient) with marker coil position during forced and quiet breathing.Differences of the CC distance between maximum forced inspiration and expiration were significant between abdominal and thoracic breathing (p0.05). The correlation between CC distance and coil position was best for forced abdominal breathing and a marker coil in the abdominal position (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03, respectively). In quiet breathing, a lower correlation was found.A fiducial marker coil external to the thorax in combination with dMRI is a new technique to yield quantitative information on the correlation of internal organ and external chest wall motion. Correlations are highly dependent on the breathing maneuver.

We sought to intraindividually compare computed tomography angiographies (CTAs) acquired at 80 kVp and 120 kVp with respect to vessel contrast, noise level, and radiation dose.CTA was performed on a single-slice CT scanner using tube voltages of 80 kVp and 120 kVp in 29 patients with arteriovenous malformations. Mean Hounsfield Units (HU) were evaluated for different vessels and brain parenchyma. To determine contrast-to-noise ratios (CNRs), noise levels were estimated from phantom measurements.The calculated effective dose to male/female patients was 0.4/0.5 mSv for 80 kVp and 0.7/0.8 mSv for 120 kVp. CT density in blood vessels was between 297 and 458 HU for 80 kVp and 152 and 229 HU for 120 kVp (P0.0001). Despite an increased noise level in the low-voltage images, the CNR was 26-59% higher at 80 kVp than at 120 kVp (P0.05).The use of a reduced tube potential leads to improved CNR in CTA of the cerebral vasculature and a markedly reduced radiation exposure to patients.

Rationale and objectives: To objectively quantify the effects of a microbubble contrast agent to differentiate breast tumors with power doppler ultrasound and to compare these results with color doppler ultrasound (CD US). Methods: In 47 patients a microbubble contrast agent was injected intravenously. Computer-assisted quantitative assessment of the color pixel density was performed to evaluate the increase in Doppler signals. Results were compared to previously published results of a color Doppler ultrasound study. Results: Peak color pixel density at contrast-enhanced power Doppler ultrasound was higher for carcinomas than for benign tumors (P < 0.03). Time to peak enhancement was shorter in carcinomas than in benign tumors (P < 0.01). For both parameters, diagnostic accuracy of power Doppler ultrasound was 69 and 78%, and for color Doppler ultrasound 62 and 76%, respectively. Conclusions: Quantitative assessment of contrast-enhanced power Doppler ultrasound showed significant differences in malignant and benign breast tumors. Diagnostic accuracy of contrast-enhanced power Doppler ultrasound was higher compared to color Doppler ultrasound.

Objective To evaluate the accuracy of multidetector computed tomography (CT) and magnetic resonance imaging (MRI) in staging and estimating renal carcinomas with caval thrombus. Methods Initially, 23 patients with suspected caval thrombi were admitted into this prospective study. Triphasic CT imaging was performed using a multidetector CT with a reconstructed slice thickness of 2 mm. 3D CT reconstructions were used to improve surgical planning. MRI protocol included: a transversal T1-weighted GE sequence with and without Gd-DTPA, a transversal T2-weighted respiratory-gated TSE, and a coronal T1-weighted GE sequence with Gd-DTPA and fat saturation. In addition, a multiphase 3D angiography was performed after Gd-DTPA injection. Patients were divided into 3 groups: caval thrombus below the insertion of the hepatic veins, within the intrahepatic vena cava, and intra-atrial extension. The results the tumor thrombus extension and staging results of 2 independent readers were correlated with surgical and histopathological staging. Results Of the 23 patients admitted, CT and MR scans of 14/13 patients respectively were correlated with histopathological workup. CT thrombus detection sensitivity and specificity for both readers was 0.93 and 0.8 respectively. MRI sensitivity and specificity for both readers was 1.0/0.85 and 0.75. Readers I and II evaluated the uppermost extension of the cranial tumor thrombus by both CT and MRI. CT and MR accuracy was 78% and 72%, 88% and 76% respectively. Conclusion In cases of a suspected tumor thrombus, MRI and multidetector CT imaging showed similar staging results. Consequently, these staging modalities can be used to assess the extension of the tumor thrombus.

To assess the influence of tumor diameter on tumor mobility and motion of the tumor bearing hemithorax during the whole breathing cycle in patients with stage I non-small-cell lung cancer (NSCLC) using dynamic MRI.Breathing cycles of thirty-nine patients with solitary NSCLCs were examined using a trueFISP sequence (three images per second). Patients were divided into three groups according to the maximal tumor diameter in the transverse plane (3, 3-5 and5 cm). Continuous time-distance curves and deep inspiratory and expiratory positions of the chest wall, the diaphragm and the tumor were measured in three planes. Motion of tumor-bearing and corresponding contralateral non-tumor bearing regions was compared.Patients with a tumor3 cm showed a significantly lower diaphragmatic motion of the tumor bearing compared with the non-tumor bearing hemithorax in the craniocaudal (CC) directions (tumors 3-5 cm: 23.4+/-1.2 vs 21.1+/-1.5 cm (P0.05); tumors5 cm: 23.4+/-1.2 vs 20.1+/-1.6 cm (P0.01). Tumors5 cm in the lower lung region showed a significantly lower mobility compared with tumors3 cm (1.8+/-1.0 vs 3.8+/-0.7 cm, P0.01) in the CC directions.Dynamic MRI is a simple non-invasive method to differentiate mobility of tumors with different diameters and its influence on the surrounding tissue. Tumor diameter has a significant influence on tumor mobility and this might be taken into account in future radiotherapy planning.

A prospective controlled clinical study was performed to compare fluoroscopic guidance with fluoroscopy-based surgical navigation for distal locking of intramedullary implants. Forty-two patients with fractures of the lower extremity treated by intramedullary nailing were divided in two groups: distal locking either with fluoroscopic guidance (group I) or with surgical navigation (group II). The average fluoroscopic time to insert one interlocking screw with fluoroscopic guidance was 108 s compared with 7.3s in the navigation group. The average procedure time to insert one interlocking screw in group I was 13.7 min compared with 17.9 min in group II. The drill bit failed to pass through the interlocking hole in one patient from group II. There was no significant difference in the technical reliability between both groups. Fluoroscopic times to achieve equivalent precision are reduced with fluoroscopy-based surgical navigation compared with fluoroscopic guidance. Fluoroscopy-based surgical navigation is recommended for intraoperative guidance in situations where reduction of exposure to radiation is considered advantageous over the increase of procedure time.

Rationale and Objectives: To assess if preradiation and early follow-up measurements of relative regional cerebral blood flow (rrCBF) can predict treatment outcome in patients with cerebral metastases and to evaluate rrCBF changes in tumor and normal tissue after stereotactic radiosurgery using arterial spin-labeling (ASL) and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI. Methods: In 25 patients with a total of 28 brain metastases, DSC MRI and ASL perfusion MRI using the Q2TIPS sequence were performed with a 1.5-T unit. Measurements were performed prior to and at 6 weeks, 12 weeks, and 24 weeks after stereotactic radiosurgery. Follow-up examinations were completely available in 25 patients for Q2TIPS and 17 patients with 18 metastases for DSC MRI. The rrCBF of the metastases and the normal brain tissue was determined by a region-of-interest analysis. rrCBF values were correlated with the treatment outcome that was classified according to tumor volume changes at 6 months. Results: The alteration of the rrCBF at the 6-week follow-up was highly predictive for treatment outcome. A decrease of the rrCBF value predicted tumor response correctly in all metastases for Q2TIPS and in 13 of 16 metastases for DSC MRI. The pretherapeutic rrCBF was not able to predict treatment outcome. The rrCBF values in normal brain tissue affected by radiation doses less than 0.5 Gy remained unchanged after therapy. Conclusion: These preliminary results suggest that ASL and DSC MRI techniques determining rrCBF changes in brain metastases after stereotactic radiosurgery allow the prediction of treatment outcome.

Aim of this study was to evaluate the role of pre-therapeutic and follow-up MRI in the clinical treatment and outcome in patients with astrocytoma WHO grade II after fractionated stereotactic radiation therapy (FSRT). One hundred thirty-nine patients with histologically proven astrocytoma WHO grade II were treated with FSRT and retrospectively evaluated. All patients had follow-up MRI studies (Gd-DTPA-enhanced T1- and T2-weighted MR images). Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed on five potential MRI related prognosticators. Median follow-up was 3.8 years. Positive contrast enhancement (CM+) prior to FSRT proved to be a significant prognosticator for PFS and OS (p

Rationale and Objectives: To investigate diaphragm and chest wall motion during the whole breathing cycle using magnetic resonance imaging (MRI) and a volumetric model in correlation with spirometry. Materials and Methods: Breathing cycles of 15 healthy volunteers were examined using a trueFISP sequence (5 slices in 3 planes, 3 images per second). Time-distance curves were calculated and correlated to spirometry. A model for vital capacity (VC), continuous time-dependent vital capacity (tVC), and investigating the influence of horizontal and vertical parameters on tVC was introduced. Results: Time-distance curves of the breathing cycle using MRI correlated highly significant with spirometry (P < 0.0001). VC calculated by the model was similar to VC measured in spirometry (5.00 L vs. 5.15 L). tVC correlated highly significantly with spirometry (P < 0.0001). Vertical parameters had a more profound influence on tVC change than horizontal parameters. Conclusions: Dynamic MRI is a simple noninvasive method to evaluate local chest wall motion and respiratory mechanics. It widens the repertoire of tools for lung examination with a high temporal resolution.

To evaluate partially parallel three-dimensional (3D) magnetic resonance (MR) imaging for assessment of regional lung perfusion in healthy volunteers and patients suspected of having lung cancer or metastasis.Seven healthy volunteers and 20 patients suspected of having lung cancer or metastasis were examined with 3D gradient-echo MR imaging with partially parallel image acquisitions (fast low-angle shot 3D imaging; repetition time msec/echo time msec, 1.9/0.8; flip angle, 40 degrees; acceleration factor, two; number of reference k-space lines for calibration, 24; field of view, 500 x 440 mm; matrix, 256 x 123; slab thickness, 160 mm; number of partitions, 32; voxel size, 3.6 x 2.0 x 5.0 mm(3); acquisition time, 1.5 seconds) after administration of 0.1 mmol/kg of gadobenate dimeglumine. In volunteers, 3D MR perfusion data sets were assessed for topographic and temporal distribution of regional lung perfusion. Sensitivity, specificity, accuracy, and positive and negative predictive values for perfusion MR imaging for detecting perfusion abnormalities in patients were calculated, with conventional radionuclide perfusion scintigraphy as the standard of reference. Interobserver and intermodality agreement was determined by using kappa statistics.Topographic analysis of lung perfusion in volunteers revealed a significantly higher signal-to-noise ratio (SNR) of up to 327% in gravity-dependent lung areas. Temporal analysis similarly revealed much shorter lag time to peak enhancement in gravity-dependent lung areas. In patients, perfusion MR imaging achieved high sensitivity (88%-94%), specificity (100%), and accuracy (90%-95%) for detection of perfusion abnormalities. Interobserver agreement (kappa = 0.86) was very good and intermodality agreement (kappa = 0.69-0.83) was good to very good for detection of perfusion defects. A significant difference (P.0001) in SNR was observed between normally perfused lung (14 +/- 7 [SD]) and perfusion defects (7 +/- 4) in patients.Partially parallel MR imaging with high spatial and temporal resolution allows assessment of regional lung perfusion and has high diagnostic accuracy for detecting perfusion abnormalities.

Long fluoroscopic times and related radiation exposure are a universal concern when C-arm fluoroscopy is used to guide percutaneous procedures. Fluoroscopy-based surgical navigation has been proposed as an alternative guidance method requiring limited fluoroscopic times to achieve precision. The purpose of this experimental study was to compare fluoroscopy-based surgical navigation with C-arm fluoroscopy for guidance with respect to the precision achieved, the fluoroscopic time, and the resources needed. 114 guide wires were placed in 38 synthetic bone models using either C-arm fluoroscopy (group A) or fluoroscopy-based surgical navigation (group B) for guidance. Precision of guide wire placement was rated on the basis of an individual CT scan on all fracture models of both groups. The fluoroscopic time, the procedure time, and the number of attempts required to place the guide wires were documented as well. An average fluoroscopic time of 26 s was needed with C-arm fluoroscopy to place three guide wires compared with an average fluoroscopic time of 2 s that was needed when fluoroscopy-based surgical navigation was used for guidance (p < 0.0001). Precision of guide wire placement and procedure times required to place the guide wires did not differ significantly between both groups. The number of attempts required for correct placement was found significantly reduced with fluoroscopy-based surgical navigation when compared with fluoroscopic guidance (p = 0.04). Fluoroscopic times to achieve precision are reduced with fluoroscopy-based surgical navigation compared with C-arm fluoroscopy. The impact of this new technique on minimally invasive, percutaneous procedures has to be evaluated in controlled prospective clinical studies.

Purpose To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd-DTPA for time-resolved three-dimensional pulmonary magnetic resonance angiography (MRA). Materials and Methods Thirty-one patients and five healthy volunteers were examined with a contrast-enhanced time-resolved pulmonary MRA protocol (fast low-angle shot [FLASH] three-dimensional, TR/TE = 2.2/1.0 msec, flip angle: 25°, scan time per three-dimensional data set = 5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd-DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol using two different flip angles and once with 0.2 mmol/kg bw Gd-DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality. Results In patients, significantly higher SNR and CNR were observed with Gd-DTPA compared to both doses of gadobutrol (SNR: 35–42 vs.17–25; CNR 33–39 vs. 16–23; P ≤ 0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd-DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol-enhanced MRA with an increased flip angle of 40°. Image quality was rated equal for both contrast agents. Conclusion No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd-DTPA were observed for time-resolved pulmonary MRA in this study. Potential explanations are T2/T2*-effects caused by the high intravascular concentration when using high injection rates. J. Magn. Reson. Imaging 2004;19:202–208. © 2004 Wiley-Liss, Inc.

To investigate the feasibility of raster scanned heavy charged particle therapy in the treatment of prostate cancer (PCa,) with special regard to the influence of internal organ motion on the dose distribution.The CT data of 8 patients with PCa who underwent three-dimensional conformal radiotherapy (RT) were chosen. In addition to the routine treatment planning scan, three to five additional positioning control CT scans were performed. The organs at risk and the target volumes were defined on all CT scans. Primary and boost carbon ion plans were calculated to deliver 66 Gy to the clinical target volume/planning target volume, with an additional 10 Gy to the gross tumor volume (GTV). To estimate the influence of internal organ motion on plan quality, the dose was recalculated on the basis of the control CT scans. The comparative analysis was based on the dose-volume histogram-derived physical parameters.The average 90% target coverage was 99.1% for the GTV. The maximal dose to the rectum was 71.8 Gy. The average rectal mean dose was 19 Gy. The volume of the rectum receiving 70 and 68 Gy was 0.1 and 0.3 cm3. The average difference in the 90% coverage for the GTV on control CT cubes was 3.6%. The maximal rectal dose increased to 76.2 Gy. The deviation in the mean rectal dose was1 Gy on average. The rectal volume receiving 70 and 68 Gy increased to 2.5 and 3.3 cm3.The investigation demonstrated the feasibility of raster scanned carbon ions for PCa RT. Excellent coverage of the target volume and optimal sparing of the rectum were acquired. The combination of photon intensity-modulated RT and a carbon ion boost to the GTV is the most rational solution for the gain of clinical experience in heavy ion RT for PCa patients.

Tumor doses > 70 Gy are needed for local control in adenoid cystic carcinomas. These tumor doses cannot be delivered if the tolerance doses to neighboring organs at risk (OAR) are respected. This treatment planning study investigates the physical advantage of combined photon intensity-modulated radiation therapy (IMRT) plus carbon ion boost compared to photon IMRT alone. Patients and Methods: For nine patients, treatment plans were generated using a) photon IMRT alone (integrated boost concept), and b) sum plans consisting of a photon IMRT plan and a carbon ion boost plan. 54 Gy were prescribed to the planning target volume 1 (PTV1), the boost volume (PTV2) received 72 Gy. The tolerance doses of the delineated OAR were strictly adhered to. Plan quality of IMRT plans and sum plans was compared using adequate physical parameters. Results: Both therapy techniques lead to highly conformal dose distributions that allow the prescription of the desired target doses. Target conformality and heterogeneity as well as target coverage for PTV1 are comparable for both techniques. The target coverage for PTV2 can be significantly improved using carbon ion beams (median 95% coverage 93.7% vs 87%; p = 0.039). Furthermore, the mean doses to the OAR can be reduced by 8.3% (median % reduction of mean doses to OAR; p = 0.00001) using carbon ions. Conclusions: The combination of photon IMRT with carbon ions improves the target coverage for the boost volume and offers better sparing of OAR close to the PTV2 (gross tumor volume) in comparison with photon IMRT alone. A clinical study has been initiated to evaluate whether these potential advantages translate into clinical benefit.

A restrospective study of patients with brain metastases from non-small cell lung cancer (NSCLC) is performed to identify patients who benefit from radiosurgery and to determine prognostic factors for survival. Eighty-six consecutive patients with a total of 110 brain metastases from NSCLC were treated with linac-based radiosurgery. Six patients with eight brain metastases who received radiosurgery as a focal boost to whole brain radiotherapy where excluded. Median age at treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used to identify potential prognostic factors for local control of brain metastases and survival of the patients. Median follow-up was 6 months (range 1 1/2-77 months) with 17/80 patients still alive. Median actuarial survival was significantly longer (P0.004) in patients with metachronous onset of brain metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was significantly increased after radiosurgery in the absence of extracranial tumor progression (P0.03). Eleven patients (14%) developed new brain metastases after radiosurgery after a latency of median 5 months. Actuarial local control rate was 96% after 3 months. Local control was significantly increased with a prescribed doseor=18 Gy/80%-isodose (P0.01). We conclude that especially patients with poor prognostic factors and a limited number of brain metastases may be palliatively treated with radiosurgery alone. This approach allows to effectively control CNS manifestation of the disease and can be integrated into chemotherapeutic protocols.

OBJECTIVE: For nephron sparing surgery of renal cell carcinoma knowledge of the intrarenal extension of the tumor and infiltration of the renal pelvis, the intrarenal vessels and the perinephric fat is essential. This question is much more difficult to answer compared to the description of staging parameters. Aim of this study is to evaluate the value of multi-slice CT in planning of nephron sparing surgery. MATERIAL AND METHODS: In a prospective study 46 patients with suspected renal cell carcinoma underwent a triphasic multi-slice CT (unenhanced, delay 30 s and 120 s). A reconstructed slice thickness of 2 mm in the arterial and parenchymal phase was used to create volume rendered 3D-reconstructions. Based on the source data and multiplanar reconstructed images the extent of the renal cell carcinoma was assessed in terms of size, hilar infiltration, arterial and venous invasions, capsula infiltration and perirenal growth. The results of two blinded readers were correlated with histopathological staging and intraoperative findings. RESULTS: 36 carcinomas were evaluated histopathologically. 10 patients showed no renal cell carcinoma histopathologically. Multi-slice CT allowed us to diagnose the localization and size of all tumors correctly. Infiltration into perinephric fat was correctly excluded in 24/30 and 8/30 cases. Infiltration of the renal pelvis could be excluded in 17/24 and 12/24 cases. The state of venous infiltration could be correctly diagnosed in 29/30 and 27 /30 carcinomas. CONCLUSION: Despite of the high temporal and spatial resolution of multi-slice CT, which allows the delineation of intrarenal arteries as well as renal hilus and the veins, the evaluation of tumor infiltration into the renal hilus, the intrarenal vessels and the perinephric fat remains a diagnostic problem. For planning of nephron sparing surgery, a knowledge of the infiltration in these structures is essential.

Purpose: To evaluate survival rates and side effects after stereotactically-guided radiotherapy (SRT) in patients with recurrent medulloblastoma of the brain.

The combination of etoposide, folinic acid, and 5-fluorouracil (5-FU) (ELF regimen) has been proved to be an active chemotherapy in patients with advanced gastric cancer. The aim of this study was to confirm the efficacy in the clinical setting and to correlate response with different parameters like serum tumor markers. We treated 60 patients with advanced gastric cancer with 120 mg/m2 etoposide, 300 mg/m2 folinic acid, and 500 mg/m2 5-FU, on d 1-3. The cycle was repeated on d 21. Objective response was obtained in 23% of all patients with measurable disease. Stable disease was obtained in 37%. The tumor-growth-control rate in patients with proximal carcinoma was significantly higher than in those with distal carcinoma (85% vs 48%, p = 0.04). Median survival for all patients was 8.0 mo (95% confidence interval [CI] 7.0-8.5). In responsive patients, survival was more than two-fold longer than in patients with progressive disease. The administration of ELF could be performed safely on an outpatient basis. Toxicity was rather mild. The most frequently elevated serum tumor marker was CA 72-4 (55% of the patients). An elevated level of carcinoembryonic antigen before treatment was significantly correlated with progressive disease. A more than two-fold elevation of at least one marker under treatment was significantly correlated to progressive disease (p < 0.002). A reduction of at least one marker under treatment was significantly correlated to tumor growth control (p < 0.00015). The results of the present trial confirm the efficacy and low toxicity of the ELF regimen in advanced gastric carcinoma. Serum tumor markers proved suitable parameters for assessing response to treatment.

PURPOSE: Large skull-base meningiomas are difficult to treat due to their proximity or adherence to critical structures. We analyzed the long-term results of patients with skull-base meningiomas treated by a new approach with high-precision fractionated stereotactic radiotherapy. PATIENTS AND METHODS: One hundred eighty-nine patients with benign meningiomas were treated with conformal fractionated stereotactic radiotherapy between 1985 and 1998. Patients were undergoing a course of radiotherapy either as primary treatment, following subtotal resection, or for recurrent disease. The median target volume was 52.5 mL (range, 5.2 to 370 mL). The mean radiation dose was 56.8 Gy (± 4.4 Gy). Follow-up examinations, including magnetic resonance imaging, were performed at 6-month intervals thereafter. RESULTS: The median follow-up period was 35 months (range, 3 months to 12 years). Overall actuarial survival for patients with World Health Organization (WHO) grade I meningiomas was 97% after 5 years and 96% after 10 years. Local tumor failure was observed in three of 180 patients with WHO grade I tumors and was significantly higher in two of nine patients with WHO grade II tumors. A volume reduction of more than 50% was observed in 26 patients (14%). Preexisting cranial nerve symptoms resolved completely in 28% of the patients. Clinically significant treatment-induced toxicity was seen in 1.6% of the patients. No treatment-related deaths occurred. CONCLUSION: The results of this study demonstrate that fractionated stereotactic radiotherapy is safe and effective in the therapy of subtotally resected or unresectable meningiomas. The overall morbidity and incidence subacute and late side effects of this conformal radiotherapy approach were low.

Ziel. Ziel der Studie war die Bestimmung der Strahlenexposition des Patienten durch intraoperative Bildgebung mit dem Bildverstarker bei Marknagelosteosynthesen. Material und Methode. 39 Patienten mit pertrochanterer Femurfraktur (n=32) oder Unterschenkelfraktur (n=7) wurden mit Marknagelosteosynthesen versorgt. Die dabei auftretende Strahlenexposition des Patienten wurde auf Grundlage intraoperativ gemessener Durchleuchtungsparameter durch Dosisberechnung bestimmt. Ergebnisse. Die mittlere Durchleuchtungszeit fur die Osteosynthese pertrochanterer Frakturen mit dem PFN® war mit 3,3 min deutlich kurzer als diejenige fur die Osteosynthese von Unterschenkelfrakturen mit dem UTN® (im Mittel 8,2 min Durchleuchtungszeit). Die berechnete effektive Dosis lag fur die stammnahe pertrochantere Fraktur bei 14 mSv, fur die Versorgung von stammfernen Unterschenkelfrakturen ergaben sich effektive Dosen kleiner 0,1 mSv. Schlussfolgerung. Die Strahlenbelastung des Patienten durch intraoperatives Rontgen bei Marknagelosteosynthesen lasst sich aufgrund der o. g. Daten abschatzen. Beobachtungen wahrend des operativen Vorgehens (kleine Fokus-Haut-Abstande, fehlendes Einblenden des Strahlungsfeldes) legen nahe, dass eine Reduktion der Strahlenbelastung bei Osteosynthesen u. a. durch verbesserte Ausbildung des Unfallchirurgen auf dem Gebiet des Strahlenschutzes erreicht werden kann.

We aimed to evaluate whether the histopathologic variability of fibroadenomas accounts for their varied appearance in contrast enhanced power Doppler (PD). Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler ultrasound (US) prior to and following IV bolus injection of a microbubble contrast agent. A 3-min computer-assisted assessment of the color pixel density (CPD) was used for objective evaluation of the increase in color Doppler signals. Enhancement characteristics were correlated to histopathologic features of microvessel density and epithelial hyperplasia, patient's age, tumor size, use of exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in 19 patients. Compared to baseline values, patients with epithelial hyperplasia showed a significant increase in mean CPD following contrast media administration (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal status. Microvessel counts did not show a significant correlation to CPD at baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial hyperplasia, primarily occurring in young patients, may contribute to the differential diagnostic overlap in some fibroadenomas and thus limit the ability of PD to distinguish between benign and malignant masses on the basis of enhancement characteristics.

We aimed to evaluate the differential diagnostic value of a method of computer-assisted texture analysis in comparison to established ultrasonographic B-mode characteristics in the examination of solid breast masses. At two centers, 77 patients presenting with a solid mass on B-mode scan were studied at 7.5 MHz. Description of B-mode appearance included assessment of tumor shape, borders, presence of an echogenic rim, tissue architecture, internal echo structure, absorption and elasticity. For statistical pattern recognition, the following parameters were used: form factor, mean grey level, signal-to-noise ratio, mean gradient and correlation from the co-occurrence matrix. At center 1, the most decisive parameter for differential diagnosis was distortion of tissue architecture (sensitivity, SN, 83%; specificity, SP, 92%) and, at center 2, relation to the adjacent tissue (SN 93%, SP 92%). Among texture parameters, best discrimination was achieved for correlation from the co-occurrence matrix at center 1 (SN 58%, SP 73%) and for form factor at center 2 (SN 93%, SP 77%). Among sonographic criteria, the highest contribution to the diagnosis was found for an unsharp border (odds ratio, OR, 12.2), architectural distortion (OR, 8.6), fixation to skin or chest wall (OR, 9.0) and fixation to adjacent breast parenchyma (OR, 8.8), according to texture analysis for parameters form factor (OR 4.0) and correlation from the co-occurrence matrix (OR 4.7). Ultrasonographic texture analysis can be helpful as an additional parameter in differential diagnosis of breast tumors, but did not reach differential diagnostic accuracy of sonomorphologic features.

To compare contrast-enhanced power Doppler (PD) harmonic imaging (CHI) with contrast-enhanced power Doppler fundamental imaging (CPD) in the depiction of renal cortical vessels, 20 healthy volunteers were subjected to PD imaging and HI assessment of the kidney after bolus injection of Levovist(R) (SH U 508A). System settings were standardized and the pulse-repetition frequencies (PRF) systematically toggled from 750 to 500 and 250. Videotapes were independently reviewed by three readers with regard to the presence of artefacts, the degree of Doppler signal enhancement, demarcation of vessels and the extent of visualization. The assessments were graded separately for each PRF in accordance with a multistage scoring system. In comparison to contrast-enhanced PD, artefacts were significantly lower with CHI for all PRF (p = 0.0001). Vessels were better visualized (p = 0.002) and less blurred (p = 0.006) with CHI than with CPD. There was no significant difference in the extent of Doppler signal increase between CPD and the contrast-enhanced harmonic mode. Combination of the contrast-enhanced harmonic method and PD allows the PRF to be lowered and, by balancing the greater susceptibility of PD to interference from clutter, increases the likelihood of detection of flow in small vessels.

Exercise renography makes it possible to subdivide essential hypertensives (EHs) into two distinct populations. Fifty to 60% develop exercise-mediated renal dysfunction and a transitory, severe reduction of glomerular filtration. The other subset of EHs does not have exercise-mediated renal dysfunction. We hoped to learn whether the disturbance is also present while EHs rest. Twenty-six EHs and 21 normotensive controls were studied with a resting sequential renogram using Tc-99m-mercaptoacetyl-triglycine (MAG3), a tracer excreted primarily by proximal tubular cells. EHs also had an exercise renogram. All persons had three consecutive 10-min dual-tracer infusion clearance determinations with 111In–DTPA and 131I–hippurate, for the simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). To demonstrate the accuracy of the clearance procedure we sought to reproduce Hollenberg’s results which show greater flow variability in EH than in normotension. Following this, the variability (VAR) of the GFR and ERPF as well as the variability fraction (VF), the ratio of GFR variability divided into the ERPF variability, were calculated. Hollenberg’s results were reproduced. Sixteen of 26 essential hypertensives developed exercise-mediated renal dysfunction. GFR-VAR in EH differed from controls. The VF suggests that EHs with a bilateral abnormal exercise renogram have a more pronounced GFR variability than those EH with a normal exercise renogram. The results point to intraglomerular pressure fluctuations in patients with EH, and the VF suggests that this may be more pronounced in EHs with a bilateral abnormal exercise renogram than in those with a normal exercise renogram. It is hypothesized that the variable GFR provokes renin secretion in EH.

Objective: The objective of this trial was to examine the degree of tumor vascularity in lymph node metastases as depicted by computer-assisted color Doppler sonography and the tumor volumes associated with prognosis in carcinomas of the oropharynx and hypopharynx after primary radiochemotherapy. Patients And Methods: In a prospective trial, 25 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx (stage IV UICC 1997) were treated with radiochemotherapy. The color Doppler findings were quantified with a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD). As important prognostic cofactor, total tumor volume (TTV) was calculated from CT sections and related to the degree of vascularity. Results: Low CPD in neck metastases showed a correlation with better overall survival. A high-CPD group and a high-TTV group (median survival 10.1 months) were determined and were compared with all other CPD/TTV combinations (median survival 28.4 months); the difference in survival was significant ( P = 0.002). Conclusion: The results indicate that high tumor vascularity in combination with high TTV indicates a particularly bad prognosis in patients treated with primary radiochemotherapy for head and neck cancer. (Otolaryngol Head Neck Surg 2000;122:596-601.)

While the diagnostic benefits of gadolinium (Gd)-chelate contrast agents are firmly established in magnetic resonance imaging (MRI) of tumors, the pathophysiologic basis of the enhancement observed and its histopathologic correlate remained vague. Tumor angiogenesis is fundamental for growth and metastasis and also of interest in new therapeutic concepts. By correlative analysis of a) histology; b) vascular density (CD31); and c) vascular permeability (vascular permeability factor/vascular endothelial growth factor [VPF/VEGF]), we found a) significantly (P F 0.001) faster exchange rates in malignant compared with benign breast lesions; b) distinct differences in enhancement characteristics between the histologic types (invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ); and c) dependence of enhancement kinetics on the VPF/VEGF expression. The pathophysiologic basis for the differences in contrast enhancement patterns of tumors detectable by MRI is mainly due to vascular permeability, which leads to more characteristic differences than vascular density. MRI is able to subclassify malignant breast tumors due to their different angiogenetic properties. J. Magn. Reson. Imaging 1999; 10:260‐266. r 1999 Wiley-Liss, Inc.

To evaluate objectively the effects of a microbubble contrast agent on the color Doppler ultrasound (US) examination of breast lesions.Forty-seven patients aged 23-71 years underwent color Doppler US before and after intravenous injection of a microbubble contrast agent. A 3-minute computer-assisted assessment of the color pixel density (CPD) was used to evaluate objectively the increase in the number of color Doppler US signals, the transit time of the microbubble bolus, and the potential additional differential diagnostic information.Peak CPD at contrast agent-enhanced color Doppler US was 14.3% +/- 8.1 (mean +/- 1 standard deviation) for carcinomas and 9.3% +/- 4.9 for benign lesions (P = .04). The time to peak enhancement was shorter in carcinomas (38 seconds +/- 20) than in benign tumors (71 seconds +/- 48, P = .02). Final CPD was close or equal to baseline values. With the median of 13% for peak CPD as a threshold, the sensitivity for this parameter was 55%, the specificity was 79%, and the accuracy was 62% (P = .04). For a median time to peak of 50 seconds, the sensitivity was 84%, the specificity was 57%, and the accuracy was 76%.After microbubble contrast agent injection, carcinomas and benign lesions behave differently in degree, onset, and duration of Doppler US enhancement. High interindividual variability and temporal variations in the Doppler US signal still limit the value of these criteria for prospective diagnosis.

Aus fruheren Untersuchungen ist bekannt, das die kontrastmittelgestutzte Farbdopplersonographie zur verbesserten Darstellung von Gefasen in malignen Veranderungen eingesetzt werden kann. Allerdings beruht die Quantifizierung der Farbdopplersignalzunahme nach Levovist bislang ausschlieslich auf subjektiver Einschatzung durch den Untersucher. Diese Arbeit beschreibt die Anwendung eines computergestutzten Verfahrens, mit dessen Hilfe die Dichte erkennbarer Gefase im Farbdopplerbild quantifiziert wird. Durch sequentielle Bildaufnahme ist auf diesem Wege eine objektivere Erfassung der An- und Abflutung von Doppler-Signalverstarkern moglich. Hiermit zeigten Karzinome und benigne Veranderungen bei insgesamt 47 Patientinnen nach Injektion von Ultraschallkontrastmittel unterschiedliches Verhalten hinsichtlich Ausmas, Beginn und Dauer der Signalzunahme. Allerdings erweist sich die Datenerfassung mit dem bisher verfugbaren System als zu grobmaschig, um zufallig bedingte, zeitliche Schwankungen des Dopplersignals angemessen mathematisch glatten zu konnen. Soll die Dynamik der Kontrastmittelanflutung fur diagnostische Zwecke genutzt werden, mussen Verfahren entwickelt werden, die eine Datenerfassung mit hoher Abtastrate ermoglichen.

Purpose: To review important aspects of study design in clinical radiology and to introduce the reader to the requirements of Good Clinical Practice (GCP). Methods: The European guidelines for GCP, the Declaration of Helsinki, the differentiation into study phases and the authors' own experience in open and sponsored clinical trials are the basis of this analysis. Results: Guideline such as GCP do not limit scientific freedom in research but define high standards for the well-being of patients and volunteers as well as guaranteeing scientific honesty. The benefits of defined data monitoring and the necessity of a prospective statistical concept are frequently underestimated. Conclusion: Correct study design has to be expected in radiology too. High standards guarantee accuracy and honesty of scientific studies. Only this can warrant the value for the patient of radiological diagnostics and therapy.

The diagnostic impact and reproducibility of the different methods used within the concept of functional MR-Mammography (FMRM) was assessed by a multi-reader-analysis. By four experienced readers, 100 histologically confirmed cases were evaluated in six different sessions. Per session, one of the following components was analyzed: clinical history (I), static MRM (II), color-coded projection images (III), time-signal curves of contrast enhancement within a large ROI (IV) and the strongest enhancing pixel (V) obtained from the histologically confirmed lesion and the complete FMRM reading (VI). The functional methods (IV-VI) revealed significantly (p < 0.05) higher specificities than the others (I-III). The highest reproducibility between the readers was observed for (IV) phi chi = 0.80, (V) phi chi = 0.76 and FMRM (VI) phi chi = 0.63. These three methods also presented the best ROC-curves and showed the highest complementarity with respect to the false positive classifications in x-ray mammography. FMRM is a reader independent, reproducible method. The analysis of the contrast enhancement time-intensity curves with high temporal resolution allows an improved differentiation of malignant and benign findings.

The aim of this study was to evaluate image quality of spiral CT of the brain as compared with incremental CT using identical scanning parameters. Incremental or spiral cranial CT was performed on 46 consecutive, randomized patients with non-traumatic disease of the brain on a Siemens (Erlangen, Germany) Somatom Plus 4. Evaluation was done in a randomized blinded way by two experienced radiologists. Different anatomical structures, image noise, and artifacts were scaled 1 (bad) to 4 (very good). Statistical analysis was done using the F-test of variance for partial sums of squares as well as Student's t-test. Incremental CT was superior to spiral CT for evaluation of the internal capsule, supratentorial artifacts, gray/white matter differentiation, and image noise. No statistically significant differences were seen for evaluation of the pons, infratentorial artifacts, and eye muscles. With identical scanning parameters incremental CT is superior to spiral CT in the assessment of small, complex structures in a low-contrast setting. No differences are seen for larger structures or small structures in a medium-contrast range. Artifacts localized close to the skull in spiral CT can easily mimic hemorrhage in traumatized patients. Spiral CT should therefore only be used for CT angiography and if 3D reconstructions are needed.

The aim of our study was to reassess the diagnostic performance of image-based, computer-assisted colour Doppler quantification under routine conditions. We used a computer-assisted protocol that quantitatively characterises a colour Doppler image by the relative amount of colour pixels (colour pixel density, CPD) and the colour hues (numerically expressed by the mean colour value, MCV) in 44 patients with breast carcinoma and 49 patients with benign breast lesions. Studies were carried out over two periods by two examiners, subsequently in charge of breast ultrasound. During the first period, the sensitivity of the MCV was 92 %, the specificity 75 %; the sensitivity of the CPD was 80 %, the specificity 81 %. During the second period, the sensitivity of the MCV was 58 %, the specificity 77 %; the sensitivity of the CPD was 68 %, the specificity 71 %. Despite measures to create uniform examination conditions, the diagnostic performance of this method may decline under routine conditions.

Purpose: It was the aim of this project to examine (i) the relationships between contrast-enhanced dynamic MR imaging derived characteristics and histologic microvessel density counts – a recognized surrogate of tumor angiogenesis – from tumors in patients with primary or recurrent cancer of the uterine cervix, and (ii) to correlate these parameters with lymphatic involvement (i. e. lymphatic channels) to assess tumorbiological aggressiveness in terms of lymphatic spread. Materials and methods: Pharmacokinetic MR imaging parameters (amplitude A, exchange rate constant k 21) were derived from contrast-enhanced dynamic MR imaging in thirty-three patients with biopsy proven cancer of the uterine cervix. The pharmacokinetic MR imaging characteristics were correlated to histologic capillary density counts obtained from whole mount specimen. In addition, these data were correlated to the angiogenic activity as a marker for lymphatic system involvement. Results: Pharmacokinetic MR imaging derived parameters (A, k 21) showed a weak but signifikant (p < 0.05) correlation with microvessel density counts. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k 21 compared with histologic microvessel density, resulting in a significantly (p < 0.05) higher overall accuracy (85 % vs. 64 %), sensitivity (83 % vs. 54 %), and comparable specificity (89 % vs. 89 %), respectively. Conclusion: Our first results show that the signal-time curves measured by contrast-enhanced MR imaging are only in part influenced by microvessel density. In addition, MR imaging derived characteristics may assess tumorbiological aggressiveness in terms of lymphatic spread (i. e. lymphatic channels) more comprehensively than histologic microvessel density in patients with primary or recurrent cancer of the uterine cervix.

The authors developed a texture-based pattern recognition and segmentation tool for the quantitation of high-resolution computed tomography (HRCT) findings in usual interstitial pneumonia (UIP).In HRCT images of five patients with UIP and five patients without UIP, 1022 regions of interest (ROIs) of 5 x 5 pixels were classified by the examiner to be normal, emphysematous, ground-glass lesion, intralobular fibrosis, vessel, or bronchus section. The classes and the texture parameters calculated in the ROIs were the basis for the decision rule, using a multivariate discrimination analysis. The classification was compared with the examiner's diagnosis in 1889 new randomly selected ROIs.Depending on the structure, the sensitivity (the probability that a structure would be recognized correctly) was 68.7% to 80.7%. If the system classified a structure as normal, ground glass or fibrotic region, this was correct in 77.3% to 88.1%. However, the system's diagnosis of a bronchus section was correct in only 16.2%. The overall accuracy was 70.7%.Texture-based segmentation may be a valuable tool to aid the quantitative assessment of parenchymal disease in HRCT images.

Purpose: To evaluate the use of high-temporal resolution cine MR phase-contrast flow measurements for assessment of flow dynamics in renal artery stenosis (RAS). Material and methods: In a dog model, cine MR flow measurements were validated by comparing the MR flow data to an invasive transit-time ultrasound reference technique for different degrees of RAS. Cardiac-gated MR flow curves were recorded in 56 renal arteries of 28 patients with a temporal resolution of at least 32 ms. In all cases RAS was confirmed by digital subtraction angiography (DSA). Abnormalities of flow dynamics were assessed in the calculated flow curves using the MR parameters mean flow, maximum velocity, and time to systolic maximum. Results: By means of the MR blood flow parameters high-grade stenoses ( >50 %, n = 23) were detected with sensitivity of 100 % and specificity of 94 % with reference to DSA. The overall differentiation between stenoses (n = 37) and non-stenosed vessels (n = 19) revealed a sensitivity of 87 % and a specificity of 100 %. Conclusion: Analysis of cardiac-gated MR flow curves provides a non-invasive method to assess the hemodynamic significance of RAS and thus allows a functional evaluation in relation to the morphologic characteristics of the stenosis.

PURPOSE: To compare staging of advanced primary cervical carcinoma (pT2b-pT4a) by conventional and pharmacokinetic magnetic resonance imaging (MRI) with the giant cross section specimen and histopathological findings. MATERIALS AND METHODS: Seventeen patients with biopsy-proven cancer of the cervix and clinically suspected invasive cancer (FIGO IIB-IVA) were prospectively examined by conventional (T2 and contrast-enhanced T1-weighted spin echo images) and pharmacokinetic MRI. All MRI findings were compared with the giant cross section specimen and histopathology as the standard of reference. For pharmacokinetic MRI, a saturation recovery TurboFLASH sequence was used with a high temporal resolution of 13 s per ten sections. Signal time changes were analyzed using a pharmacokinetic model and the computed parameter values were visualized by color-coded overlay. RESULTS: Analysis of parametrial invasion on T2-weighted images resulted in an accuracy of 85% and 73% on contrast-enhanced T1-weighted images and on pharmacokinetic MR images respectively. Accuracy of analysis of bladder and/or rectal wall invasion was significantly (P < 0.05) higher on pharmacokinetic MR images (88%) than on T2-weighted images (67%). Contrast-enhanced T1-weighted spin-echo images improved staging accuracy compared with T2-weighted images (76% vs 67%). CONCLUSION: At present, conventional T2-weighted SE images are superior to contrast-enhanced T1-weighted SE and pharmacokinetic MR images in depicting infiltration of the parametrium. However, suspected infiltration of the bladder and/or rectum (pT4a) is diagnosed more accurately on pharmacokinetic images than on conventional MR images.

The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to ( n = 20) and at 6 ( n = 17), 18 ( n = 17), and 50 wk ( n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T 1 -weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k 21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k 21 (median, 5.7 min −1 ; range, 1.9–23.0 min −1 ) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1–2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant ( p k 21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group ( n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm 3 . For this group, we found a significant drop ( p A and a decrease of the exchange rate constant k 21 . In the nonresponder group ( n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm 3 . The pharmacokinetic analysis revealed a decrease of the amplitude A and an increase of the exchange rate constant k 21 . The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.

We examined whether or not the degree of tumor vascularity in lymph node metastases as depicted by color Doppler is associated with a patient's prognosis. Cervical lymph node metastases in 25 patients with head and neck cancer were examined before combined accelerated radiotherapy and chemotherapy. The findings were quantified using a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD) and the color hues, which are numerically expressed by the mean color value (MCV). We found that, in the patient group with a CPD below median, the median survival was 958 days and, in the group with a higher CPD, it was 423 days (p = 0.05). The time to detection of distant metastases was 18 months with a low CPD, and 6 months with a high CPD (p = 0.05). However, the time to local or nodal progression was not different between the groups. The MCV was not correlated with prognostic data. These results indicate that, in patients with metastatic head and neck cancer, highly vascularized lymph nodes detected with color Doppler sonography may indicate a shorter survival and earlier occurrence of distant metastases.

Purpose: To evaluate the spatiotemporal evolution of radiosurgical induced changes both in metastases and in normal brain tissue adjacent to the lesions by serial magnetic resonance (MR) imaging. Methods and Materials: Thirty-five intracranial metastases of different primaries were treated in 25 patients by single high-dose radiosurgery. MR images acquired before radiosurgery were available in all patients. Sixty-three follow-up MR studies were performed in these patients including T2- and contrast-enhanced T1-weighted MR images. The average follow-up time was 9 ± 5 months (mean ± standard deviation [SD]). Based on contrast-enhanced T1-weighted MR images, tumor response was radiologically classified in the following four groups: stable disease was assumed if the average tumor diameter after treatment did not show a tumor shrinkage of more than 50% and an increase of more than 25%, partial remission as a shrinkage of tumor size of more than 50%, a disappearance of contrast-enhancing tumor as a complete remission, and an increase of tumor diameter of more than 25% as tumor progress. Moreover, we analysed signal changes on T2-weighted images in brain parenchyma adjacent to the enhancing metastases. Results: The overall mean survival time was 10.5 ± 7 months, with a 1-year actuarial survival rate of 40%. Stable disease, partial or complete remission of the metastatic tumor was observed in 22 patients (88%). Central or homogeneous loss of contrast enhancement appeared to be a good prognostic sign for stable disease or partial remission. This association was statistically significant (p < 0.05). Three patients (12%) suffered from tumor progression. In eight patients (32%) with stable disease or partial remission, signal changes on T2-weighted images were observed in tissue adjacent to the contrast enhancing lesions. A progression of the high signal on T2-weighted images was seen in seven of the eight patients between 3 and 6 months after therapy, followed by a signal regression 6–18 months after irradiation. Conclusion: MR imaging is a sensitive imaging tool to evaluate tumor response as well as the presence or absence of adjacent parenchymal changes following radiosurgery. Loss of homogeneous or central contrast enhancement on Gd-enhanced MR images appeared to be a good prognostic sign for tumor response. Tumor shrinkage seems not to be dependent on time. In addition, most cases of radiation induced changes in normal brain parenchyma observed on T2-weighted images seem to be self limited.

Infection with Helicobacter pylori is associatedwith the development of gastric cancer. To study whetherthe infection with H. pylori strains expressing thevacuolating cytotoxin (VacA) and/or thecytotoxin-associated protein (CagA) is associated with an increasedrisk of developing gastric adenocarcinoma, sera of 90patients with gastric cancer and 90 matched controlswith cardiovascular diseases were investigated for the presence of antibodies to VacA and CagA byimmunoblot. Although no significant difference in theoverall H. pylori seropositivity was found betweencancer patients and controls, antibodies against VacA or CagA were significantly more frequent incancer patients than in control subjects. Seventyfive(97.4%) of 77 H. pylori-positive patients in the cancergroup, but only 60 (84.5%) of 71 H. pylori-positive control patients had antibodies against eitherVacA or CagA (χ2 6.63; relative risk,2.00; 95% confidence interval, 1.18–3.39; P =0.01). The presence of antibodies against VacA or CagAalone was also associated with an increased cancer risk (92.2%vs 80.3%; χ2 = 5.30; relative risk, 1.74;95% confidence interval, 1.08–2.78; P = 0.021, forVacA; and 87.0% vs 74.6%; χ2 4.90;relative risk, 1.61; 95% confidence interval, 1.06–2.45; P =0.037, for CagA). The relative risk for gastric cancerwas mainly elevated in patients under 65 years, but notin patients at or over 65 years. There is evidence that infection with VacA- or CagA-producing H.pylori strains increases the risk of developing gastriccancer, especially in younger patients.

To stage advanced cervical carcinoma with conventional or pharmacokinetic magnetic resonance (MR) imaging by correlating imaging findings with whole-mount specimens and histopathologic findings.Twenty-six adult patients with primary cervical cancer (stages IIB-IVA) underwent T2-weighted turbo spin-echo (SE) MR imaging; gadolinium-enhanced, T1-weighted SE MR imaging; and gadolinium-enhanced, saturation-recovery, turbo fast low-angle shot MR imaging. All imaging findings were correlated with the whole-mount specimens and histopathologic findings. Signal intensity changes versus time were analyzed by using a pharmacokinetic model and parameter values displayed as a color-coded overlay.Histopathologic stages were IIB (n = 9), IIIB (n = 1), and IVA (n = 16). The overall accuracy for tumor staging was 73% for T2-weighted, 81% for T1-weighted, and 92% for pharmacokinetic MR imaging. Pharmacokinetic MR imaging was accurate (90%) in the diagnosis of tumor extension into the bladder and/or rectal wall but inaccurate (69%) in that of parametrial invasion. T2-weighted images were most accurate (86%) in the assessment of parametrial tumor extension but less accurate (69%) in that of bladder or rectal invasion.T2-weighted turbo SE images are still superior to contract medium-enhanced T1-weighted SE or pharmacokinetic MR images in the diagnosis of parametrial infiltration by uterine cervical carcinoma. However, pharmacokinetic MR imaging is a promising method for demonstrating and staging IVA disease.

Dynamic MR image series were analyzed with a pharmacokinetic two-compartment model. To preserve the spatial resolution of the dynamic MR images, the pharmacokinetic parameters were computed pixel by pixel, color coded, and superimposed on conventional MR images (pharmacokinetic mapping). The efficacies of pharmacokinetic mapping and conventional MR imaging in distinguishing between recurrent tumors and benign conditions in patients who have pelvic lesions after treatment of cervical carcinoma were compared.Twenty-one women with 24 suspected pelvic lesions and a history of treated cervical carcinoma (stages IB-IIIA) were included in this study. Patients had been treated before MR imaging with surgery or irradiation alone (eight patients) or a combination of the two (13 patients). Patients were referred because of our findings from CT examinations and/or clinical examinations. Of 24 suspected lesions, 17 were histologically verified as tumor recurrences and seven were classified as benign masses (histologically diagnosed as fibrosis and granulation tissue). T1- and T2-weighted spin-echo images were interpreted by three observers. During and after constant-rate infusion of gadopentetate dimeglumine, the kinetics of lesion response were determined with a strongly T1-weighted saturation recovery turbo-fast low-angle shot sequence. The signal-time curves for the suspected lesions were analyzed within the framework of a pharmacokinetic two-compartment model and displayed as color-coded images. The calculated pharmacokinetic parameters (amplitude [A] and tissue distribution time [t21]) were evaluated retrospectively to obtain optimal threshold values for differentiating malignant lesions from benign lesions.Analysis of the pharmacokinetic mapping data showed significantly shorter (p.005) and stronger (p.001) contrast medium enhancement of malignant lesions (t21, 24 sec; A, 1.5 arbitrary units) than of benign lesions (t21, 65 sec; A, 0.7), resulting in a sensitivity of 100%, a specificity of 88%, and an accuracy of 96%. Interpretation of the lesions on conventional T2-weighted MR images resulted in a sensitivity of 90%, a specificity of 38%, and an accuracy of 74%.Analysis of color-coded pharmacokinetic maps is more effective than conventional MR imaging in distinguishing between malignant and benign conditions in patients who have pelvic lesions after treatment of cervical carcinoma.

To determine the most effective means by which to apply the combined treatments of local tumour hyperthermia (LTH) with interstitial low dose-rate irradiation (IRT) we examined the significance of such factors as dose-rate of radiation, and the sequence and frequency of hyperthermia applications in the anaplastic Dunning prostate tumour subline R3327-AT1. IRT was carried out by the insertion of a single Ir-192 seed into the center of the tumour. For LTH treatments, the tumour-bearing leg was positioned in a circulating constant temperature water bath (43.5 +/- 0.1 degrees C) for 35 min. Neither LTH treatment alone nor the insertion of a dummy seed produced any change in tumour growth compared with sham-treated controls. With regard to the sequence of heating and IRT our results showed that during a 72-h treatment time (30 Gy, 40 cGy/h) a single heat treatment given just before the start of IRT was more efficient (TER = 1.47) in terms of growth delay than LTH given in the middle or the end of radiation treatment (TER approximately 1.0). The growth delay for both the 20 and 40 cGy/h groups appear to be linear with increasing dose for the IRT as well as the IRT + LTH groups. The higher dose-rate was more effective especially with respect to long-term delay in tumour growth in some of the animals. As TER at 40 cGy/h decreased subsequently with increasing treatment time from 1.47 to 1.25 at 60 Gy, we conclude that for treatment times72 h, one LTH just before IRT might not be sufficient. If multiple heat treatments are applied during a comparable time course, two LTH treatments one just before the start, the other at the end yielded the greatest local tumour control. In contrast, three LTH given daily were not more effective than the one LTH given just before the start of IRT. These data indicate a clear thermal enhancement of low dose-rate irradiation, with maximal sensitization when hyperthermia was given just before IRT. For multiple heatings a better understanding of the underlying mechanisms of sequencing and timing hopefully provides guidelines how to apply optimally both modalities in the treatment of cancer.