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J Griebel

Publications and source records attributed to J Griebel.

At least 19 recordsLinked to original sources

Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging.

Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As noninvasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Twenty-four hours after three intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size-matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals. In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.

Animals↗

[Introduction of a mammography screening program in Germany. Consideration of benefits and risks].

For women between 50 and 70 years of age, X-ray mammography presently represents the most effective method for early breast cancer detection. It is commonly accepted that quality assured mammography examinations conducted at regular intervals can reduce mortality from breast cancer. In the year 2002, the German Bundestag agreed to the implementation of a mammography screening program for Germany based on the European guidelines. The effectiveness of a mammography screening program is controversially discussed and two of the most commonly cited hazards are the occurrence of false-positive results and the so-called overdiagnosis. Another issue of criticism is the radiation risk due to the mammography examinations. However, in women aged 50-70 years the radiation risk has no substantial importance. In contrast to the present situation in Germany in which opportunistic screening is widespread, standardized quality assured screening will guarantee that false-positive rates are kept as low as possible and that further assessment diagnostics are effective and minimally invasive.

Adult↗

[Radiation exposure of patients from diagnostic and interventional X-ray procedures. Facts, assessment and trends].

Man-made radiation exposure to the German population predominantly results from the medical use of ionizing radiation. According to the most recent evaluation, the mean effective dose per inhabitant and year from X-ray procedures increased from 1.6 to 1.8 mSv between 1996 and 2001. This rise is mainly caused by the expanding use of CT and reflects the growing importance of this imaging modality. Besides actual data on the frequency and dose of various types of X-ray examinations, patient-specific factors will be highlighted which have to be considered in the assessment of the associated individual and collective radiation risk. Moreover, different concepts to reduce radiation exposure of patients will be discussed as well as some current trends in health service that may affect radiation hygiene -- such as diagnosis-related groups for inpatients and CT screening.

Body Burden↗

Assessment of a theoretical formalism for dose estimation in CT: an anthropomorphic phantom study.

Dose assessment in computed tomography (CT) is challenging due to the vast variety of CT scanners and imaging protocols in use. In the present study, the accurateness of a theoretical formalism implemented in the PC program CT-EXPO for dose calculation was evaluated by means of phantom measurements. Phantom measurements were performed with four 1-slice, four 4-slice and two 16-slice spiral CT scanners. Firstly, scanner-specific nCTDIw values were measured and compared with the corresponding standard values used for dose calculation. Secondly, effective doses were determined for three CT scans (head, chest and pelvis) performed at each of the ten installations from readings of thermoluminescent dosimeters distributed inside an anthropomorphic Alderson phantom and compared with the corresponding dose values computed with CT-EXPO. Differences between standard and individually measured nCTDIw values were less than 16%. Statistical analysis yielded a highly significant correlation (P < 0.001) between calculated and measured effective doses. The systematic and random uncertainty of the dose values calculated using standard nCTDIw values was about -9 and +/- 11%, respectively. The phantom measurements and model calculations were carried out for a variety of CT scanners and representative scan protocols validate the reliability of the dosimetric formalism considered-at least for patients with a standard body size and a tube voltage of 120 kV selected for the majority of CT scans performed in our study.

Head↗

Morpho-functional visualization of dynamic MR-mammography.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The image data sets were acquired with a saturation-recovery-turbo-FLASH sequence facilitating the detection of the kinetics of the contrast agent concentration in the whole breast with a high temporal and spatial resolution. In addition, a morphological 3D-FLASH data set was acquired. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality. The spatially differentiated representation of the computed functional tissue parameters superimposed on the anatomical information offers several possibilities: improved discernibility of contrast enhancement, inspection of the data volume in 3D-space and localization of lesions in space and thus fast and more natural recognition of topological coherencies. In a feasibility study, it could be demonstrated that multidimensional visualization of contrast enhancement in virtual reality is practical. Especially, detection and localization of multiple breast lesions may be an important application

Breast Neoplasms↗

Radiation exposure in multi-slice versus single-slice spiral CT: results of a nationwide survey.

Multi-slice (MS) technology increases the efficacy of CT procedures and offers new promising applications. The expanding use of MSCT, however, may result in an increase in both frequency of procedures and levels of patient exposure. It was, therefore, the aim of this study to gain an overview of MSCT examinations conducted in Germany in 2001. All MSCT facilities were requested to provide information about 14 standard examinations with respect to scan parameters and frequency. Based on this data, dosimetric quantities were estimated using an experimentally validated formalism. Results are compared with those of a previous survey for single-slice (SS) spiral CT scanners. According to the data provided for 39 dual- and 73 quad-slice systems, the average annual number of patients examined at MSCT is markedly higher than that examined at SSCT scanners (5500 vs 3500). The average effective dose to patients was changed from 7.4 mSv at single-slice to 5.5 mSv and 8.1 mSv at dual- and quad-slice scanners, respectively. There is a considerable potential for dose reduction at quad-slice systems by an optimisation of scan protocols and better education of the personnel. To avoid an increase in the collective effective dose from CT procedures, a clear medical justification is required in each case.

Data Collection↗

[Diffusion-weighted MRI--a new parameter for advanced rectal carcinoma?].

PURPOSE: To evaluate the predictive value of apparent diffusion coefficient (ADC) on therapy outcome of combined chemoradiation in patients with primary carcinoma of the rectum. MATERIALS AND METHOD: Prior to standardized, combined, neoadjuvant chemoradiation, 16 patients with primary carcinoma of the rectum (cT3) were examined with magnetic resonance imaging (MRI). Diffusion-weighted spin echo echo-planar images (SE-EPI) and contrast-enhanced T 1 -weighted spin echo (SE) images at 1.5 Tesla were obtained. The mean ADC of the tumor region was calculated and correlated with the therapy outcome substantiated by postsurgical histopathologic staging. RESULTS: Tumor down-staging (pT0-2) occurred in 9 patients (therapy responders) and no down-staging (pT3) in 7 patients (therapy non-responders). The mean ADC measured 0.476 +/- 0.114 x 10(-3) mm 2/s in the responder group and 0.703 +/- 0.085 x 10(-3) mm 2/s in the non-responder group. Comparison of the mean ADC between the groups reached statistical significance (p = 0.001). CONCLUSION: The mean ADC might be a new quantitative parameter to predict therapy outcome of combined preoperative chemoradiation in patients with primary carcinoma of the rectum.

Adenocarcinoma↗

Morphofunctional visualization of MR-mammography in virtual reality.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus to enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality.

Breast Neoplasms↗

Dynamic MR-mammography in virtual reality.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The image data sets were acquired with a saturation-recovery-turbo-FLASH sequence facilitating the detection of the kinetics of the contrast agent concentration in the whole breast with. In addition, a morphological 3D-FLASH data set was acquired. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus to enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality. The spatially differentiated representation of the computed functional tissue parameters superimposed on the anatomical information offers several possibilities: improved discernibility of contrast enhancement; inspection of the data volume in 3D-space using the features of rotation and transparency variation; localization of lesions in space and thus fast and more natural recognition of topological coherencies. In a feasibility study, it could be demonstrated that multidimensional visualization of contrast enhancement in virtual reality is a practicable idea. Especially, detection and localization of multiple breast lesions may be an important application.

Computer Simulation↗

Quantitative imaging of tumour blood flow by contrast-enhanced magnetic resonance imaging.

Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T(1)-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 x 250 microm(2). Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future.

Animals↗

Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma.

Contrast enhanced dynamic studies of malignant tumors performed by computed tomography or magnetic resonance imaging (MRI) are increasingly applied to characterize tumor microcirculation for the prediction of therapy outcome. The aim of our study was to correlate perfusion index (PI) values determined in primary rectal carcinoma before chemoradiation with therapy outcome. In 17 patients with clinically staged T3 primary rectal carcinoma, dynamic MRI was performed before the onset of therapy using an ultrafast T1-mapping sequence. On the basis of the acquired data sets, PI values were calculated on a pixel-by-pixel basis. To characterize the heterogeneity of tumor microcirculation, relative cumulative frequency histograms of PI values within the tumors were computed. Subsequent resection of the tumors allowed correlating PI with histopathological classification. In 12 of 17 patients, T-downstaging as a response to therapy was found, whereas in the remaining 5 patients no therapy response was observed after chemoradiation. A statistically significant difference between both groups was found for the mean PI (P < 0.001; 8.5+/-1.7 ml/min/100 g versus 11.4+/-0.7 ml/min/100 g). Analyzing the cumulative frequency histograms for both groups revealed an optimal discrimination for a P1 value of 12.6 ml/min/100 g. The fraction of pixels in the tumor with PI values larger than 12.6 ml/min/100 g was significantly different (P < 0.001) between therapy-responding (3+/-3.6%) and therapy-nonresponding tumors (21+/-4.3%). The results indicate either a reduced supply of nutrients as well as chemotherapeutic agents attributable to increased shunt flow or highly aggressive tumor cell clusters characterized by increased angiogenic activity. Noninvasive PI measurements by dynamic MRI in rectal carcinoma before therapy seem to be of predictive value for therapy outcome in patients scheduled for preoperative chemoradiation.

Adenocarcinoma↗

Lung volume recruitment in lambs during high-frequency oscillatory ventilation using respiratory inductive plethysmography.

Monitoring lung volume is important in the treatment of acute hypoxemic respiratory failure. However, there are no tools available for lung volume measurement to guide ventilator management during high-frequency oscillatory ventilation (HFOV) and during dynamic changes in conventional ventilation (CV). We studied the performance of a new respiratory inductive plethysmograph (RIP) with modified software. We measured Delta changes in lung volume above end-expiratory volume (V(RIP)) during HFOV and studied whether changes in V(RIP) parallel changes in mean airway pressure. Calibration of the plethysmograph was made by serial injections of a known gas volume in six term (140 d gestation) and eight preterm (125 d gestation) lambs. Linear regression analysis of the relationship between injected gas volume and V(RIP) showed strong correlation (r(2) = 0.93-1.00 term animals, r(2) = 0.86-1.00 preterm animals). The pressure volume curves from the calibration with the injected gas volumes also correlated well with the pressure volume curves extrapolated from changes in V(RIP). Lung hysteresis was clearly demonstrated with RIP after changes in mean airway pressure during HFOV and after changes in positive end-expiratory pressure during CV. We conclude that measurements of lung volume in term and preterm lambs by use of modified RIP correlate well with changes in mean airway pressure during HFOV, with static pressure volume curves and with changes in positive end-expiratory pressure during CV. We speculate that this technique may provide clinically useful information about changes in lung volume during HFOV and CV. However, evaluation of the precision and chronic stability of RIP measurements over prolonged periods will require further studies.

Animals↗

[Perfusion-index values evaluated by dynamic magnetic resonance imaging in advanced rectal carcinoma. A new predictor of response to preoperative radiochemotherapy?].

PURPOSE: The aim of our study was to evaluate in vivo the influence of tumor microcirculation data on therapy outcome. PATIENTS AND METHODS: Tumor perfusion data of primary rectal carcinoma (n = 14, cT3) who underwent preoperative chemoradiation have been analyzed (Table 1). The perfusion data were acquired at the beginning and at the end of therapy by use of an ultrafast T1-mapping sequence on a whole-body magnetic resonance imager. The gadolinium-DTPA concentration-time-curves were evaluated for arterial blood and tumor before, during and after intravenous constant rate infusion and from that the perfusion index (PI) was calculated. Subsequent resection of the tumors allowed for a correlation of perfusion index values with the pathological classification. RESULTS: Nine patients showed a T downstaging (ypT0-2, group 1), 5 patients did not (ypT3, group 2). The initial mean perfusion index value of group 1 (n = 9) was 8.2 ml/min/100 g (+/- 2) and for group 2 (n = 5) 10.4 ml/min/100 g (+/- 0.4). The difference in perfusion index values before chemoradiation between group 1 and group 2 was significant different (p = 0.012, Mann-Whitney test). The perfusion index value at the end of therapy of group 1 (n = 6) was 9.6 ml/min/100 g (+/- 2.8) and for group 2 (n = 4) 10.7 ml/min/100 g (+/- 1.6). The difference in perfusion index values after chemoradiation between group 1 and group 2 was not significant different (Table 2). CONCLUSION: Our used perfusion index value combines 2 parameters: tumor perfusion and extraction fraction. Therefore a significant negative influence on therapy outcome of high perfusion index values could be explained possibly by areas with a high portion of high perfusion (e.g. av-shunts) and a low extraction fraction (= low exchange of nutrients). However, we could show a significant negative influence of high perfusion index values on therapy outcome (p = 0.012). Because the tumor stage has a significant influence on tumor-free survival, there is a possibility for using initial perfusion index values as a new prognostic factor in rectal carcinoma without sphincter infiltration undergoing a preoperative chemoradiation. To examine this hypotheses a prospective trial is in preparation.

Adult↗

[Dynamic MR mammography. Multidimensional visualization of contrast medium enhancement in virtual reality].

BACKGROUND: The purpose of this study was the development of a method for fast and efficient analysis of dynamic MR images of the female breast. The image data sets were acquired with a saturation-recovery turbo-FLASH sequence which enables the detection of the kinetics of the contrast agent concentration in the whole breast with a high temporal and spatial resolution. In addition, a morphologic 3D-FLASH data set was acquired. METHODS: The dynamic image datasets were analyzed by a pharmacokinetic model which enables the representation of the relevant functional tissue information by two parameters. In order to display simultaneously morphologic and functional tissue information, we developed a multidimensional visualization system, which enables a practical and intuitive human-computer interface in virtual reality. DISCUSSIONS: The developed system allows the fast and efficient analysis of dynamic MR data sets. An important clinical application is the localization and definition of multiple lesions of the female breast.

Adult↗

Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implications for therapy.

PURPOSE: To measure microcirculatory changes during chemoirradiation and to correlate perfusion index (PI) values with therapy outcome. MATERIALS AND METHODS: Perfusion data in 11 patients with cT3 (clinical staging, tumor invaded the perirectal tissue) rectal carcinoma who underwent preoperative chemoirradiation were analyzed. Perfusion data were acquired by using a T1 mapping sequence with a whole-body magnetic resonance (MR) imager. After contrast medium was intravenously infused at a constant rate, concentration-and-time curves were evaluated for arterial blood and tumor. All patients underwent MR imaging before and at constant intervals during chemoirradiation. Clinical stages before therapy were compared with surgical stages after therapy. RESULTS: Spatial and temporal resolution on dynamic T1 maps were sufficient to reveal changes in contrast medium accumulation in the tumor. Comparison of PI values and radiation dose showed a significant increase in the 1st (P: =.003) and 2nd weeks (P: =.01) of treatment; values subsequently returned to pretreatment levels or showed a renewed increase. High initial PI values correlated with greater lymph node downstaging (P: =.042). CONCLUSION: Dynamic T1 mapping provides a suitable tool for monitoring tumor microcirculation during chemoirradiation and offers the potential for individual optimization of therapeutic procedures. Furthermore, these results indicate that the PI map may serve as a prognostic factor.

Adenocarcinoma↗

Infant lung function after inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn.

Our objectives were to determine whether the use of inhaled nitric oxide (iNO) for severe persistent pulmonary hypertension of the newborn (PPHN) causes impaired lung function during infancy. We therefore performed a prospective study of lung function in 22 infants after neonatal intensive care unit (NICU) discharge who had been treated for severe persistent pulmonary hypertension of the newborn (PPHN) with (n = 15) or without (n = 7) iNO, and compared these findings in lung function to those of healthy control infants (n = 18). Five infants with interstitial lung disease (ILD) were included to assure that the pulmonary function tests (PFT) were sensitive enough to detect abnormalities of lung function in this age group. We measured passive respiratory mechanics and functional residual capacity (FRC) using a commercially available system. All data were expressed as means and standard deviation. Statistical analysis was performed by analysis of variance (ANOVA). A Bonferroni multiple comparisons test was used for variables that showed overall group differences. Twenty-two infants were studied during follow-up 4-12 months after NICU discharge. None of the infants were actuely ill, and only one infant was on 0.25 L of oxygen per minute at the time of study. We found no differences in lung function between the treatment groups (iNO + mechanical ventilation (MV), or MV alone), or between either treatment group and healthy control infants of the same age. We were able to detect significant differences in functional residual capacity adjusted for weight or height, and compliance of the respiratory system adjusted for weight or lung volume in the ILD infants compared to the healthy controls or infants who had PPHN, indicating that these PFTs were sensitive enough to determine abnormal lung function in this age group. We conclude that inhaled nitric oxide therapy for the treatment of severe PPHN does not alter lung function as determined by lung volume and passive respiratory mechanics measurements during early infancy.

Administration, Inhalation↗

[Development and application of dynamic MR imaging in the evaluation of perfusion changes in rectal carcinoma during radiotherapy in clinical routine. Preliminary results].

PURPOSE: This study was aimed at measuring microcirculatory parameters and contrast medium accumulation within the rectal carcinoma during fractionated radiotherapy in the clinical setting. MATERIAL AND METHODS: Perfusion data were observed in patients with rectal carcinoma (n = 8) who underwent a pre-operative combined chemo/radiotherapy. To acquire perfusion data, an ultrafast T1 mapping sequence was carried out on a 1.5-Tesla whole body imager to obtain T1 maps at intervals of 14 or 120 seconds. The overall measurement time was 40 minutes. The transaxial slice thickness (5 mm) was chosen in such a way that both arterial vessels and the tumor could be clearly identified. The gadolinium-DTPA (Gd-DTPA) concentration time curve was evaluated for arterial blood and tumor after intravenous constant rate infusion. The method allows a spatial resolution of 2 x 2 x 5 mm and a temporal resolution of 14 seconds. Patients underwent MR imaging before and at constant intervals during fractionated radiotherapy. RESULTS: Spatial and temporal resolution of dynamic T1 mapping was sufficient to reveal varying CM accumulation levels within the tumor and to identify the great arteries in the pelvis. In 6 patients Gd-DTPA concentration-time-curves were evaluated within the tumor during radiation. Pi index of Gd-DTPA versus radiation dose showed a significant increase in the first or second week of treatment, then either returned slowly to pretreatment level or a renewed increase was observed. The average Pi-value at the beginning was 0.16 (+/- 0.049), reaching highest level of 0.23 (+/- 0.058). In all groups the rise from the Pi-value to the Pi-maximum was statistically significant. The relative increase in perfusion ranged between 20 to 83%. CONCLUSION: The results show, that the ultrafast MR-technique described above provide a suitable tool for monitoring tumor microcirculation during therapeutic interventions and offers the potential for an individualized optimization of therapeutic procedures.

Aged↗