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Stefan Delorme

Publications and source records attributed to Stefan Delorme.

36 records · Page 2Linked to original sources

Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: initial results.

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.

Adult↗

Regional lung perfusion: assessment with partially parallel three-dimensional MR imaging.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗

Sensitive noninvasive monitoring of tumor perfusion during antiangiogenic therapy by intermittent bolus-contrast power Doppler sonography.

Intermittent bolus-contrast power Doppler ultrasound was used for noninvasive, quantitative monitoring of tumor perfusion during antiangiogenic therapy. Subcutaneous heterotransplants of human squamous cell carcinoma cells in nude mice were treated with a blocking antibody to vascular endothelial growth factor receptor 2 (DC101) and repeatedly examined at weekly intervals. Using replenishment kinetics of microbubbles (Levovist) tumor vascularization, including capillary blood flow, was clearly visualized by this dynamic ultrasound method allowing the determination of a comprehensive functional status of tumor vascularization (blood volume, blood flow, perfusion, and mean blood velocity) in all examined tumors. DC101 treatment decreased tumor blood flow (-64%) and volume (-73%) compared with untreated controls (+409% and +185%, respectively). Regression of functional vessel parameters was observed early well before reduction of tumor size. The treatment-related amount of reduction in tumor volume was directly correlated for the initial tumor blood flow before start of therapy and the perfusion calculated at the preceding examination. The vessel density (immunofluorescence staining with CD31 antibody at different time points) showed an excellent correlation with the calculated relative blood volume (k = 0.84, P < 0.01), thereby validating intermittent sonography as a useful monitoring method. We conclude that intermittent sonography is a promising tool for comprehensive monitoring of antiangiogenic or proangiogenic therapies, especially during early stages of treatment, thus yielding information regarding a prospective evaluation of therapy effects beyond the follow up of tumor size.

Animals↗

Dynamic T1-weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging.

Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom-developed animal coil in a conventional whole-body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd-DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (k(ep)) were calculated according to a 2-compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High-resolution imaging of small heterotransplants from 100 to 1,000 mm(3) was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and k(ep) values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of k(ep) value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole-body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies.

Anesthesia, Inhalation↗

High-resolution three-dimensional MR angiography of rodent tumors: morphologic characterization of intratumoral vasculature.

PURPOSE: To evaluate high-resolution three-dimensional MR angiography (MRA) for the visualization and morphologic characterization of intratumoral vasculature. MATERIALS AND METHODS: Two subcutaneous rodent tumor models (human skin carcinoma HaCaT-ras-A-5RT3 grown in nude mice and rat prostate carcinoma R3327-AT1 grown in Copenhagen rats) were examined with a clinical 1.5 T MR-system. For MRA a dedicated high-resolution three-dimensional gradient echo pulse sequence with a voxel size of 166 x 206 x 320 microm(3) was performed after injection of Gadomer-17. The image analysis included a correlation of intratumoral vessels with histology. Signal intensity measurements were performed in the vena cava, the tumor underlying muscle, and in various regions of the tumor. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated from this measurement. RESULTS: High-resolution MRA allowed a clear distinction of intratumoral blood vessels. The mouse tumor model tended to be strongly vascularized with several intratumoral blood vessels clearly displayed by MRA. When correlated with histology, these intratumoral blood vessels had a size in the range of 300 to 400 microm. In contrast, rat tumors had only sparse capillary intratumoral blood vessels that could only be demonstrated by histology. In both tumor models, dilated blood vessels were observed in the subcutaneous tissue near the tumor. In general, areas with a strong contrast enhancement correlated with viable, well vascularized tumor regions, whereas non-enhancing tumor areas correlated with tumor necrosis or hypoxic areas. CONCLUSION: High-resolution three-dimensional MRA allows the visualization of intratumoral vasculature in rodent models. With minimal hardware and software modifications, high-resolution MRA could be performed on a clinical 1.5 T MRI scanner. Morphologic characterization of intratumoral blood vessels could add important insights into the process of tumor angiogenesis.

Animals↗

Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients.

PURPOSE: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. PATIENTS AND METHODS: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15-22 Gy). RESULTS: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). CONCLUSIONS: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting.

Brain Neoplasms↗

Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumour perfusion in small animals.

Replenishment kinetics of microbubbles were adapted to a single bolus injection to investigate tumour angiogenesis in small animals with intermittent imaging, and to compare vascularisation parameters from this new approach with conventional power Doppler ultrasound (US). A reformulation of the imaging protocol and the derivation of perfusion parameters was necessary, taking into account the time-dependence of the systemic microbubble concentration after single bolus injection. Using this new method, tumour vascularisation was evaluated in 13 experimental murine tumours. Furthermore, parameters calculated with intermittent imaging after bolus injection of 100 microl Levovist were compared with parameters from the signal intensity-time curve. The results showed that quantifying tumour perfusion, blood volume and flow, as well as the assessment of the mean blood velocity (in m/s), is possible in tumours with a volume of more than 0.1 mL. In larger tumours, a lower perfusion was calculated than in smaller ones (k = -0.88; p < 0.001). Only limited correlations were found between conventional power Doppler US quantities and parameters of intermittent sonography: Perfusion correlated with the maximum signal intensity (k = 0.61, p < 0.05) and the gradient to maximum (k = 0.82, p < 0.01), full width-half maximum was associated with blood volume (k = 0.62, p < 0.05). We conclude that intermittent bolus contrast sonography allows the quantification of tumour perfusion, even in small animals, and the monitoring of basic antiangiogenic studies with perfusion parameters shows a higher significance than conventional power Doppler US.

Animals↗

A multivessel model describing replenishment kinetics of ultrasound contrast agent for quantification of tissue perfusion.

To improve the quantification of tissue perfusion using intermittent sonography, a new model describing replenishment kinetics of microbubbles is proposed. The new approach takes into account the variability of blood flow velocities found in vivo, especially in tumors, and consistently describes the refilling process of microbubbles. Based upon this model, blood volume, blood velocity, blood flow and perfusion in 17 experimental tumors were calculated, and compared with the results obtained with the established, phenomenologically derived exponential kinetic model. In contrast to the existing model, our approach describes tissue vascularization more physiologically and allows deduction of a consistent new hyperbolic model for quantification of intermittent sonography. Blood volume and mean blood velocity did significantly correlate between both the new and the established model (k=0.99; k=0.94, both p<0.001). However, mean tumor blood velocity was lower (-19%, p<0.01) with the established model compared to the newly developed model. In addition, the range and distribution of blood flow velocities found in vivo can be estimated with the new model. Furthermore, it uses simpler mathematical fitting routines and allows easier data acquisition, which may allow a more practicable clinical application of intermittent sonography. In conclusion, a more valid, detailed and accurate calculation of perfusion parameters, especially of tumors, can be derived in vivo with the new multivessel model of intermittent sonography.

Animals↗

Partially parallel three-dimensional magnetic resonance imaging for the assessment of lung perfusion--initial results.

RATIONALE: Contrast-enhanced magnetic resonance imaging (MRI) of lung perfusion requires a high spatial and temporal resolution. Partially parallel MRI offers an improved spatial and temporal resolution. OBJECTIVE: To assess the feasibility of partially parallel MRI for the assessment of lung perfusion. METHODS: Two healthy volunteers and 14 patients were examined with a contrast-enhanced 3D gradient-echo pulse sequence with partially parallel image acquisitions (TE/TR/alpha: 0.8/1.9 milliseconds/40 degrees; voxel size 3.6 x 2.0 x 5.0 mm3, TA: 1.5 seconds). The image analysis included an analysis of the signal-to-noise ratio in the lungs in areas with normal and impaired perfusion. 3D MR perfusion image data were analyzed for perfusion defects and compared with radionuclide perfusion scans, which were available for 10 of 14 patients. RESULTS: The analysis of the 3D perfusion-weighted data allowed a clear differentiation of perfusion abnormalities: MRI showed normal lung perfusion in 9 of 16 cases, whereas perfusion abnormalities were observed in 7 cases. When compared with the radionuclide perfusion scans, a good intermodality agreement was shown (kappa = 0.74). When compared with normally perfused lung a significantly lower signal to noise ratio was observed in hypoperfused lung (7 versus 17; P = 0.02). CONCLUSION: Partially parallel MRI might be used for the assessment of lung perfusion. Future studies are required to further evaluate the diagnostic impact of this technique.

Adult↗

Comparing dynamic parameters of tumor vascularization in nude mice revealed by magnetic resonance imaging and contrast-enhanced intermittent power Doppler sonography.

RATIONALE: Angiogenesis is essential for spread and growth of malignant tumors. Because noninvasive methods for observing tumor vascularization are limited, most of previous results were based on histologic findings alone. In this study, dynamic parameters obtained using intermittent contrast-enhanced Doppler sonography and dynamic MRI were compared and correlated with microvessel density. METHODS: Eleven tumor-bearing nude mice were examined with dynamic T(1)-weighted sequences using Gd-DTPA in a 1.5 T magnetic resonance (MR) scanner and with intermittent power Doppler sonography after a single bolus of galactose based contrast agent. After examination 6 tumors were harvested for immunofluorescence microscopy using a CD31 stain. Using a 2-compartment model, the MR parameters amplitude (reflecting plasma volume) and k(ep) (influenced by the vessel permeability) were calculated and compared with maximal enhancement (max) and perfusion P measured with ultrasound. RESULTS: The MR amplitude correlated with the ultrasound parameter max significantly (r = 0.61; P = 0.01). Max (r = 0.67; P = 0.01), amplitude (r = 0.72; P = 0.01), and perfusion (r = 0.62; P = 0.05) correlated with the microvessel density. k(ep) moderately correlated with max, but not with perfusion and microvessel density. CONCLUSIONS: Dynamic MRI and contrast enhanced ultrasound are supplementing methods for examining perfusion and vascularity of experimental tumors.

Animals↗

Comparison of arterial spin-labeling techniques and dynamic susceptibility-weighted contrast-enhanced MRI in perfusion imaging of normal brain tissue.

OBJECTIVES: To evaluate relative cerebral blood flow (rCBF) in normal brain tissue using arterial spin-labeling (ASL) methods and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance imaging (MRI). METHODS: Sixty-two patients with brain metastases were examined on a 1.5 T-system up to 6 times during routine follow-up after stereotactic radiosurgery. Perfusion values in normal gray and white matter were measured using the ASL techniques ITS-FAIR in 38 patients, Q2TIPS in 62 patients, and the first-pass DSC echo-planar (EPI) MRI after bolus administration of gadopentetate dimeglumine in 42 patients. Precision of the ASL sequences was tested in follow-up examinations in 10 healthy volunteers. RESULTS: Perfusion values in normal brain tissue obtained by all sequences correlated well by calculating Pearson's correlation coefficients (P < 0.0001) and remained unchanged after stereotactic radiosurgery as shown by analysis of variance (P > 0.05). CONCLUSION: Both ASL and DSC EPI MRI yield highly comparable perfusion values in normal brain tissue.

Adult↗

Neural network-based segmentation of dynamic MR mammographic images.

The usefulness of neural networks for the classification of signal-time curves from dynamic MR mammography was recently demonstrated by our group. The multi-layer perceptron under study consists of 28 input, 4 hidden, and 3 output nodes, and was trained to classify signal-time curves into three tissue classes: "carcinoma," "benign lesion," and "parenchyma." Extending this approach, it was the aim of the present study to evaluate the performance of the developed network in the segmentation of dynamic MR mammographic images in comparison to a pixel-by-pixel two-compartment pharmacokinetic analysis. The population investigated in this pilot study comprised 15 women with suspicious lesions in the breast, which were confirmed histologically after the MR examination. The neural network classified the same areas as malignant as those which were marked as being highly suspicious by the pharmacokinetic mapping approach but with the advantage that no a priori knowledge on tissue microcirculation was needed, that computation proved to be much faster, and that it yielded a unique classification into just three tissue classes.

Breast↗

Dynamic MR mammography: three-dimensional real-time visualization of contrast enhancement in virtual reality.

RATIONALE AND OBJECTIVES: In view of the increasing use of breast magnetic resonance (MR) imaging to supplement x-ray mammography. the authors developed a method for fast and efficient analysis of dynamic MR images of the female breast. MATERIALS AND METHODS: The MR image data sets were acquired with a saturation-recovery turbo fast low-angle shot sequence to detect the kinetics of the contrast agent concentration in the whole breast at a high temporal and spatial resolution. A morphologic three-dimensional fast low-angle shot data set was also acquired. The dynamic image data sets were analyzed with tracer kinetic modeling to describe the physiologic processes underlying the contrast enhancement in mathematical terms and enable the estimation of functional tissue-specific parameters, which reflect the status of microcirculation. To display morphologic and functional tissue information simultaneously, the authors developed a multidimensional real-time visualization system (with three-dimensional texture mapping), which enables a practical and intuitive human computer interface in virtual reality. RESULTS: The spatially differentiated representation of the computed functional tissue parameters superimposed on the anatomic information offers several possibilities: (a) more discernible contrast enhancement, (b) inspection of the data volume in three-dimensional space by means of rotation and transparency variation, (c) location of lesions in space and thus faster and more natural recognition of topologic coherencies, and (d) fast and efficient overview in compressed form. CONCLUSION: A feasibility study demonstrated that multidimensional visualization of contrast enhancement in virtual reality is a practicable idea. Detection and location of multiple breast lesions may be an important application.

Breast↗

Interstitial magnetic resonance lymphography with gadobutrol in rats: evaluation of contrast kinetics.

RATIONALE AND OBJECTIVE: To evaluate the contrast kinetics of gadobutrol for interstitial MR lymphography. MATERIALS AND METHODS: In 11 rats, 0.5 mL undiluted gadobutrol was injected subcutaneously into the hind paw. Contrast kinetics were measured in lymph nodes, kidney, liver, muscle, and blood of six animals using a time-resolved 2D GRE sequence. Additionally, high-resolution 3D T1-weighted data sets were obtained in five animals. RESULTS: Immediately after injection, a pronounced signal intensity loss was observed in popliteal, inguinal and aorto-iliac lymph nodes, followed by a continuous signal intensity increase. From the data peak concentrations of up to 78 mmol/L were estimated for selected lymph nodes. A contrast enhancement was also observed in kidneys, liver, muscle, and blood. Regional lymphatic vessels, the thoracic duct, as well as popliteal, inguinal, aorto-iliac, and axillary lymph node groups could be visualized with the high-resolution 3D MRI. CONCLUSION: Gadobutrol is suitable for interstitial MR lymphography, as it rapidly appears in the lymphatic system. Based on estimates of local tissue concentrations future studies have to assess the optimal contrast agent dosage. Furthermore, the investigation of metastatic lymph nodes is required to evaluate the further potential of gadobutrol for interstitial MR lymphography.

Animals↗

Incidental finding of a mucinous carcinoma of the breast by dynamic MRI in a patient with a history of breast trauma (horse bite): incidental mucinous carcinoma after breast trauma.

Occasional reports on the coincidence of previous trauma of the breast and the development of invasive breast cancer have been published. Furthermore, traumatic changes of the breast tissue can clinically and radiographically mimic malignant breast disease. We report of a 52-year-old female presenting with increasing mammographic microcalcifications after a trauma of the breast due to a horse bite. Dynamic MRI was able to exclude malignancy at the site of the trauma but did detect a clinically and radiographically nonsymptomatic mucinous carcinoma of the breast.

Adenocarcinoma, Mucinous↗

Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101.

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

Animals↗