[Ad multos annos. 30 years of sonographic tissue characterization].
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Publications and source records attributed to I Zuna.
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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.
A program of computer-assisted texture analysis was applied to evaluate its usefulness for objective description of changes in tumor architecture due to primary medical treatment in patients with locally advanced breast cancer. Changes in values of parameters of the statistical pattern recognition technique were compared to ultrasonographically depictable, subjectively recorded changes in echogenicity and echotexture (brightness, homogeneity) and reviewed with regard to histopathologic evaluation of tumor regression. Characteristic trends of defined quantitative texture parameters (mean gradient, mean gray value, contrast from the co-occurrence matrix) corresponded to visually depictable changes of the B-mode image and underlying histopathologic changes. The results indicate that quantitative texture analysis may aid in noninvasive monitoring of tumor response to neoadjuvant chemotherapy.
We aimed to evaluate objectively the value of color Doppler flow imaging in the assessment of response of locally advanced breast cancer to primary medical treatment by using a computer assisted semiquantitative method. Prior to and after neoadjuvant treatment, 17 patients with locally advanced breast carcinoma were prospectively evaluated by physical examination and computer assisted semiquantitative color Doppler ultrasonography. The results of clinical and color Doppler examination were finally correlated to the histopathologic evaluation of tumor response. The degree of concordance between posttherapeutic histopathologic results, clinical examination, and color Doppler assessment was evaluated by kappa statistics. Concordance was 0.474 (0.135-0.813) between histopathologic results and clinical posttherapeutic assessment and 0.870 (0.627-1.113) between histopathologic results and semiquantitative color Doppler examination. Objective semiquantitative assessment of tumor vascularity as displayed by color Doppler ultrasonography has potential as a functional tool for measuring tumor response to neoadjuvant chemotherapy.
The kinetics of local drug uptake and metabolism of the anticancer drug 5-fluorouracil (5-FU) has been monitored by means of 19F nuclear magnetic resonance spectroscopy in 17 patients with neck tumors during concurrent radiochemotherapy. All of the patients underwent an accelerated hyperfractionated, concomitant-boost radiochemotherapy with 5-FU [600 or 1000 mg/m2 of body surface (b.s.)] and carboplatin (70 mg/m2 of b.s.). Serial 19F nuclear magnetic resonance spectra were obtained during and after the administration of 5-FU in a 15-T scanner with the use of a 5-cm diameter surface coil positioned on a cervical lymph node metastasis. Examinations were performed at day 1 of therapy and, in 13 patients, also after 43.5 Gy of irradiation at day 1 of the second chemotherapy cycle. Resonances of 5-FU and the catabolites 5,6-dihydro-5-fluorouracil (DHFU) and alpha-fluoro-beta-alanine (FBAL) were resolved in the tumor spectra. The median of the 5-FU and FBAL levels was significantly higher (more than 2-fold) at the second compared with the first examination, whereas the level of DHFU did not change. This effect could indicate an increased delivery of 5-FU into the interstitial space of the tumor in the course of the combined treatment, which would result in an enhanced exposure of the tumor cells to the drug. A potential mechanism for synergy between radio- and chemotherapy is discussed, but alternative mechanisms are also being considered. The findings indicate that a method is available to rationally address the design of dosing schedules in concurrent therapy regimens.
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 < 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.
The purpose of this study was to estimate the size required for small vessels to become detectable with color Doppler sonography. A murine experimental tumor was examined with color Doppler sonography after injection of 1.5 mL of the contrast medium Levovist. Histologically, we measured vessel diameters inside the tumor, as well as in its direct neighborhood. With color Doppler at a transmit frequency of 7 MHz, vessels were only detected in the tumor's environment, but not inside. By histology, the 95% quantile of the vessel diameter distribution was found to be 21 microm inside the tumor, 37 microm in the underlying muscle, and 73 microm in the directly adjacent connective tissue. Vessels in the upper range of the size distribution in the muscle and connective tissue are probably detectable. Using the 95% quantile as an estimate, and correcting the values for possible shrinkage, using a factor of 1.91 reported in the literature, vessels in the 74-134 microm range may be detected under the given conditions, whereas vessels measuring 38 microm or less are inaccessible to color Doppler.
BACKGROUND: Cigarette smoking accelerates progression of renal failure in diabetic and nondiabetic renal disease. Renal hemodynamics during smoking are characterised by a reversible decrease in glomerular filtration rate (GFR) and filtration fraction (FF) accompanied by increased renovascular resistance (RVR), systemic blood pressure, heart rate and plasma catecholamine concentrations. MATERIALS AND METHODS: To further assess the role of sympathetic overactivity we compared the effects of different pharmacological interventions on smoking-induced changes of renal hemodynamics in occasional smokers. In a first series, placebo pretreatment plus smoking was compared to Prazosin pretreatment (3 mg) plus smoking. In a second study, placebo pretreatment plus smoking was compared to Atenolol pretreatment (50 mg) plus smoking. RESULTS: Basal blood pressure was significantly lower with Prazosin and Atenolol. On placebo, GFR and FF decreased significantly during smoking and RVR increased. With Prazosin pretreatment compared to placebo pretreatment no statistically significant differences for the changes of GFR, FF, RPF and RVR were seen. In contrast, with Atenolol pretreatment compared to placebo pretreatment, the smoking-induced changes in active renin, GFR and RVR were significantly smaller. CONCLUSION: It is suggested that the acute renal hemodynamic effects of smoking are mediated, at least in part, via increased sympathetic activity operating mainly through beta-1 adrenergic mechanisms.
RATIONALE AND OBJECTIVES: Tumor volume is an important parameter for clinical decision making. At present, semiautomatic image segmentation is not a standard for tumor volumetry. The aim of this work was to investigate the usability of semiautomatic algorithms for tumor volume determination. METHODS: Semiautomatic region- and volume-growing, isocontour, snakes, hierarchical, and histogram-based segmentation algorithms were tested for accuracy, contour variability, and time performance. The test were performed on a newly developed organic phantom for the simulation of a human liver and liver metastases. The real tumor volumes were measured by water displacement. These measured volumes were used as the gold standard for determining the accuracy of the algorithms. RESULTS: Variability of the segmented volumes ranging from 3.9 +/- 3.2% (isocontour algorithm) to 11.5 +/- 13.9% (hierarchical segmentation) was observed. The segmentation time per slice varied between 32 (volume-growing) and 72 seconds (snakes) on an IBM/RS6000 workstation. CONCLUSIONS: Only the region-growing and isocontour algorithms have the potential to be used for tumor volumetry. However, further improvements of these algorithms are necessary before they can be placed into clinical use.
PURPOSE: To compare two different three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiographic techniques. MATERIALS AND METHODS: In 26 patients suspected of having renal artery stenosis, results with fast multiphase 3D MR angiography were compared to those with standard 3D MR angiography in 37 patients. With both techniques, 31-second breath-hold acquisitions were performed. Multiphase angiography comprised five discrete 6.4-second acquisitions without bolus timing, and standard angiography comprised a single acquisition based on test-bolus timing. Two readers evaluated images obtained with both techniques in terms of image quality, artifacts, and vessel conspicuity. Accuracy of findings on the multiphase 3D MR angiograms for assessment of renal artery stenosis was determined by comparing them to digital subtraction angiograms and surgical findings. RESULTS: In the early arterial phase, multiphase 3D MR angiograms showed no image degradation by venous overlay, whereas standard 3D MR angiograms depicted at least minor overlay in 53 of 83 renal arteries (P < .001). Less parenchymal enhancement in the early arterial phase resulted in a higher vessel conspicuity for the divisions and segmental arteries (P < .001). Both readers detected and correctly graded 18 of 20 stenoses on the multiphase angiograms with almost perfect interobserver agreement (kappa > 0.89). CONCLUSION: Renal multiphase 3D MR angiography is an accurate technique requiring no bolus timing. The performance of early arterial phase imaging leads to improved depiction, particularly of the distal renovascular tree, compared to that with standard single-phase 3D MR angiography.
OBJECTIVE: The maximal tumor diameter of cervical cancer is one of the most important prognosis factors concerning patients' survival. The purpose of this study was to investigate the efficiency of different MRI-procedures in relation to clinical palpation concerning pretherapeutic tumor diameter assessment. MATERIAL AND METHODS: Thirty-one patients with biopsy proven primary cervical cancer and its recurrence (n = 10), respectively, underwent dynamic and conventional MRI before further treatment. The results of maximal tumor diameters were compared to palpatory findings and then correlated to the whole mount specimen as gold standard. RESULTS: The contrast-enhanced dynamic and T2-weighted MRI allows a significantly better (p < 0.05) assessment of maximal tumor diameter of cervical cancer than the conventional T1-weighted MRI. The T2-weighted MRI showed the highest correlation (r = 0.83) in respect to the whole mount specimen up to FIGO-IIB disease. The contrast-enhanced dynamic MRI and the palpation were characterized by the highest correlation coefficients of r = 0.77, r = 0.70 respectively, in advanced cervical cancer > FIGO-IIB disease. CONCLUSIONS: The MRI procedures offer no evident advantage in relation to clinical palpation to determine the maximal tumor diameter of cervical cancer or its recurrency and seems not to be indicated generally.
IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. It is characterized by recurrent gross hematuria, microhematuria and/or proteinuria and diffuse mesangial IgA deposits in glomeruli. It is predominantly a disease of young males. Apart from primary IgAN (Berger's disease), IgA deposits in the glomeruli are also seen in Henoch-Schönlein purpura and in association with various of other diseases, particularly liver cirrhosis. Originally it was thought that IgAN was a benign disease, but it is now known that approximately 20-40% of patients develop progressive renal disease 5 to 25 years after diagnosis and progress to end-stage renal disease. Clinical predictors of progressive disease are elevated serum creatinine concentration at presentation, increased systemic blood pressure, persistent protein excretion > 1.0 g/day and histological predictors are glomerulosclerosis, tubular atrophy/interstitial fibrosis, extension of immune deposits to the perivascular space and crescent formation. Progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions. These features of IgAN reported in literature were mostly, but not completely, confirmed by analysis of all consecutive patients with biopsy proven IgAN and follow-up > 12 months in the renal units of Heidelberg and Prague using univariate analysis, multiple range test and multiple regression analysis.
Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.
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 tumor biological aggressiveness in terms of lymphatic spread. MATERIAL AND METHODS: Pharmacokinetic MR imaging parameters (amplitude A, exchange rate constant k21) 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, k21) showed a weak but significant (p < 0.05) correlation with microvessel density counts. Lymphatic involvement was more comprehensively assessed by the pharmacokinetic parameter k21 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 tumor biological 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.
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.
This paper demonstrates the statistical processing of data from a multicentric study. Seventy-seven patients with a suspicious, solid breast mass were included in a two-center study, using clinical breast examination, mammography, and ultrasound. The assessment was formalized using a uniform evaluation sheet. The prospective results of the examinations were compared with the histologic report. The degree of interdependence between an examiner's diagnosis and diagnostic criteria used was assessed using the kappa statistics. We found that despite standardized assessment, the criteria used for differential diagnosis were at least partially different. The criteria valid for diagnosis at both centers were whether a mass fitted well into the surrounding tissue or led to destruction or architectural distortion, whether it was fixed to the surrounding tissues, as assessed by sonopalpation maneuvers, and whether it borders were sharp or unsharp.
Findings in previous investigations have indicated that contrast-enhanced colour Doppler can be used to improve the demonstration of characteristic features of neovascularization in malignancies. However, the quantification of the increase in colour Doppler signals after Levovist in the cited study relied only on descriptive criteria defined by the investigator, resulting in a subjective scoring system. A computer-assisted method for quantitative analysis of colour pixel density is a novel approach for objective assessment of colour Doppler signal after contrast media administration. After microbubble contrast medium injection in 47 patients, carcinomas and benign lesions behaved differently regarding degree, onset and duration of Doppler enhancement. However, the high interindividual variability and the temporal variations of the Doppler signal still limit the value of these criteria for prospective diagnosis. Rapid image-acquisition techniques are needed in order to apply the necessary mathematical processing before the contrast kinetics can be used for diagnostic purposes.