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M V Knopp

Publications and source records attributed to M V Knopp.

At least 19 recordsLinked to original sources

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Angiogenesis Inhibitors↗

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI.

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4 +/- 0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k(ep) and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k(ep) decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.

Animals↗

A comparison of Gd-BOPTA and Gd-DOTA for contrast-enhanced MRI of intracranial tumours.

A two-centre intra-individual crossover study was performed in 23 patients with suspected high-grade glioma or metastases to assess and compare the safety and enhancement characteristics of two different MRI contrast media (gadobenate dimeglumine, Gd-BOPTA and gadoterate meglumine, Gd-DOTA) at equivalent doses of 0.1 mmol/kg body weight. T1-weighted spin-echo (SE) and T2-weighted fast SE images were obtained before and T1-weighted images 0, 2, 4, 6, 8 and 15 min after injection. T1-weighted images with magnetisation transfer contrast were acquired 12 min after injection. Qualitative assessment by blinded, off-site readers (reader 1:19 patients; reader 2:21) and on-site investigators (23) revealed significant (P< or =0.005) overall preference for Gd-BOPTA over Gd-DOTA for contrast enhancement (Gd-BOPTA preferred in 18, 15 and 18 cases; Gd-DOTA in 0, 1 and 1 and no preference in 1, 5 and 4; off-site readers 1 and 2, and on-site investigators, respectively). A similar significant preference for Gd-BOPTA was expressed by off-site readers and on-site investigators for lesion-to-brain contrast, lesion delineation, internal lesion structure, and overall image preference. Quantitative assessment by off-site readers revealed significantly (p<0.05) greater lesion enhancement with Gd-BOPTA than with Gd-DOTA at all times from 2 min after injection.

Aged↗

[Clinical high- and ultrahigh-field MR and its interaction with biological systems].

The field strength of the static field in MRI has increased from 0.015 to 12 Tesla (T) during the last 25 years, which is about an 800 fold increase. In addition to low- and high field systems (1.5-4 T), ultra-high field systems with field strengths above 4 T are now available for human MRI. The extension of non-significant risk status for clinical fields up to 8 T by the FDA in July 2003 facilitates the further growth of this technology. The increase in field strength creates the need for a better understanding of the safety challenges to ensure safety for human imaging applications. This encompasses understanding the effects of the strong magnetic field at the atomic and molecular level and from biological tissue to organ systems. Moreover, in addition to the effects of a static magnetic field, the effects of radio-frequency- and gradient-fields have to be considered. This paper reviews the safety relevant issues for high- and ultrahigh field MR.

Equipment Safety↗

[Clinical MR at 3 Tesla: current status].

Clinical MRI is mostly performed at field strengths up to 1.5 Tesla (T). Recently, approved clinical whole-body MR-systems with a field strength of 3 T became available. Its installation base is more rapidly growing than anticipated. While site requirements and operation of these systems do not differ substantially from systems with lower field strength, there are differences in practical applications. Imaging applications can use the gain in signal-to-noise for increased spatial resolution or gain in speed. This comes at a trade off in increased sensitivity to field inhomogeneities and changes in relaxation times, which lead to changes in image contrast. The benefit of high field for spectroscopy consists in increased signal-to-noise-ratio and improvement in frequency resolution. The increase in energy deposition necessitates the use of special strategies to reduce the specific absorption rate (SAR). This paper summarizes the current state of MR at 3 T.

Artifacts↗

[Dynamic magnetic resonance tomography (dMRT). It's value in advanced head-neck tumors treated with radiochemotherapy].

PURPOSE: With the help of dynamic magnetic resonance tomography (dMRT) the status of tissue microcirculation can be visualized. METHODS: Dynamic MRI was performed in 13 patients with advanced, nonresectable oro- or hypopharynx carcinoma at the beginning and the end of therapy. Maximal signal intensity and exchange rate constant in the tissue of the tumor and the lymph node metastases were analyzed using a pharmacokinetic two-compartment model. RESULTS: In all six patients with clinical complete response (CR), the maximal signal intensity increased after therapy in the tissue of the primary tumor and the lymph node metastases. Furthermore, a high decrease in the parameter k(21) was associated with a better prognosis and could be observed especially after combined radiochemotherapy. CONCLUSION: Our first results indicate that contrast-enhanced dynamic MRI studies before and after radio- or combined radiochemotherapy offer important information about the changes of microcirculation in the tissue of the tumor and lymph node metastases. Furthermore, this information seems to be a promising predictor for clinical outcome of therapy.

Adult↗

[Multiphasic MR angiography as an intra-individual comparison between the contrast agents Gd-DTPA, Gd-BOPTA, and Gd-BT-DO3A].

QUESTION: The availability of new MR contrast agents having either a protein binding effect or higher concentration leads to the question if they differ from standard compounds in their vascular contrasting properties. METHODS: By intraindividual comparison five volunteers were examined (1.5 T MR system) with a multi-phasic MRA of the abdomen each receiving three different contrast agents (gadopentetate dimeglumine 0.5 M; gadobenate dimeglumine 0.5 M, and gadobutrol 1.0 M). The dose (0.15 mmol/kg body weight) and flow rate (3.0 ml/s) were kept identical. All images were quantitatively and qualitatively evaluated by blinded assessment. RESULTS: Significantly higher maximum signal intensity was found in the arteries for the protein interacting gadobenate dimeglumine (p = 0.05). No significant difference in vascular enhancement was demonstrated in the comparison of gadobutrol to gadopentetate dimeglumine. CONCLUSION: Gadobenate dimeglumine was shown to be a favorable contrast agent for multi-phasic MRA. A higher concentrated Gd-chelate does not automatically lead to improved vascular contrast if standard imaging protocols are used.

Abdomen↗

Assessment of brain metastases with dynamic susceptibility-weighted contrast-enhanced MR imaging: initial results.

PURPOSE: To assess if preradiation and early follow-up regional cerebral blood volume (CBV) measurements can help predict treatment outcome in patients with cerebral metastases and to evaluate regional CBV changes in tumor and normal tissue after radiosurgery. MATERIALS AND METHODS: In 18 patients, dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging was performed with a 1.5-T unit, which allowed an absolute quantification of the regional CBV. Measurements were performed prior to and at 6 weeks and 3 months after therapy. Treatment outcome was classified according to tumor volume changes at 6 months. The regional CBV of the metastases and the normal adjacent brain tissue were determined with a region-of-interest analysis. Regional CBV values were correlated with the patient outcome to assess the sensitivity and specificity of dynamic susceptibility-weighted contrast-enhanced MR imaging. RESULTS: The pretherapeutic regional CBV was not able to help predict a treatment outcome; however, the method proved to be highly sensitive and specific for treatment outcome prediction at the 6-week follow-up. A decrease of the regional CBV value helped predict the treatment outcome with a sensitivity of more than 90%. The tumor volume change alone had a sensitivity of only 64%. The measured regional CBV values of normal brain tissue and their ratio were comparable to physiologic data and remained unchanged with therapy. CONCLUSION: The results suggest that dynamic susceptibility-weighted contrast-enhanced MR imaging is a useful method for the assessment of radiosurgically treated brain metastases. The implemented technique with determination of the arterial input function enables an absolute quantification of the regional CBV and prediction of tumor response.

Adult↗

Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution.

The aim of this study was to evaluate changes in both size and contrast enhancement of breast tumors during neoadjuvant chemotherapy, using dynamic MRI with high temporal resolution. Patients with advanced breast cancer (n=21) underwent a 1.5-T MRI scan prior to and following neoadjuvant chemotherapy with four cycles. Dynamic contrast enhancement was measured using a fast turbo-FLASH sequence and quantified using a two-compartment model with the parameters k(ep) and amplitude. Image analysis was done on images overlayed with a color map of parameters. The correlation between tumor diameter measured by histopathology and MRI was 0.7 (p<0.003). A reduction of tumor size after chemotherapy of more than 25% was associated with a decrease of both analyzed contrast enhancement parameters (k(ep): p<0.002; amplitude: p<0.006), where k(ep) began to drop already after the first cycle of chemotherapy (p<0.008). A clear reduction of tumor size was only noted after the third cycle (p<0.008). In patients without tumor regression there was also a trend towards an early reduction of contrast enhancement. We assume that MRI with high temporal resolution and color mapping is a novel tool to assess therapeutic effects of neoadjuvant chemotherapy in breast tumors, which deserves further prospective evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

Cerebral arteriovenous malformations: morphologic evaluation by ultrashort 3D gadolinium-enhanced MR angiography.

The purpose of this study was to evaluate the usefulness of a new ultrashort contrast-enhanced (CE) MR angiography (MRA) for the morphologic evaluation of cerebral arteriovenous malformations (AVMs). The method was compared with conventional X-ray digital subtraction angiography (DSA) and time-of-flight (TOF) MRA in 22 patients to assess the angioarchitecture of the malformations which is essential for treatment planning and follow-up. Two experienced MR readers independently evaluated both techniques with regard to the assessment of feeding arteries, AVM nidus, and venous drainage patterns. Contrast-enhanced MRA was able to detect all AVMs seen on DSA, whereas the TOF MRA failed in 1 patient with a very small AVM. In the assessment of the different vessel components of the AVM there was no difference for the detection and delineation of feeding arteries and the AVM. The venous drainage patterns could always be clearly delineated in the CE MRA, whereas TOF MRA could demonstrate the exact venous drainage in only 9 patients. Contrast-enhanced MRA was found to be superior to conventional TOF MRA in the assessment of the angioarchitecture of cerebral AVMs especially regarding the assessment of the venous drainage patterns. The superiority is supported by the improved vessel-to-background contrast and contrast-to-noise ratios. The major limitations of this new technique consist of a low spatial resolution at the used time resolution which can be improved by further sequence modifications. Contrast-enhanced MRA is thus an important additional imaging technique for treatment planning and follow-up of AVMs.

Adult↗

[Comparison of methods for quantifying contrast enhancement exemplified by dynamic MRI mammography].

AIM: Aim of this study was to demonstrate and compare different quantification techniques to assess contrast enhancement in dynamic MRI studies. The diagnostic potential of dynamic MRI studies is increasingly appreciated and already used in different organ systems. METHOD: A patient population of 314 histologically verified breast lesions (138 malignant, 176 benign) were evaluated using a high temporal resolved dynamic sequence. Different quantification techniques such as the use of a cutoff line, time dependent and pharmacokinetic assessment were comparatively evaluated. RESULTS: Time dependent quantification methods revealed higher diagnostic potential which was further improved by in vivo normalization of the contrast availability in the vascular system. Significant differences in the enhancement characteristics were determined between malignant and benign as well within the different histological entities. CONCLUSION: Time dependent quantification methods enable an angiogenic characterization of lesions to improve diagnostic interpretation as well as monitoring during therapy. They are also the basis for automated, color-coded visualization of dynamic studies.

Breast↗

Dynamic susceptibility contrast-enhanced echo-planar imaging of cerebral gliomas. Effect of contrast medium extravasation.

PURPOSE: To assess the influence of the degree of contrast medium extravasation on different DSC EPI MR sequences for perfusion MR imaging. MATERIAL AND METHODS: 60 patients with cerebral gliomas were examined by either an FID EPI or an SE EPI DSC MR sequence. The acquired images were evaluated on a qualitative and quantitative basis. For qualitative assessment, the homogeneity of the signal time curve, image artifacts, the degree of signal drop and the degree of enhancement were evaluated. The quantitative assessment included the percentage of signal drop and the contrast-to-noise ratio of the different EPI sequences was analyzed. RESULTS: FID EPI presented a more homogeneous signal time curve and a more pronounced susceptibility effect than the SE EPI sequence. Due to the lesser susceptibility effect, the SE EPI sequence was not as sensitive to contrast media extravasation. The signal returned to baseline in all patients. In patients with strongly enhancing lesions, the FID EPI sequence suffered from considerable T1 effects, causing problems in the quantification of perfusion data. CONCLUSION: FID EPI sequences were preferred for perfusion MR imaging in patients without strong enhancing lesions, e.g. in ischemia or tumors with intact blood-brain barrier. In patients with suspected strong enhancing lesions, an SE EPI sequence should be used.

Brain Neoplasms↗

Assessment of gadobenate dimeglumine for magnetic resonance angiography: phase I studies.

RATIONALE AND OBJECTIVES: To assess the vascular contrasting properties of a new MR contrast agent (gadobenate dimeglumine [Gd-BOPTA]), which presents higher relaxivity because of reversible, weak protein interaction, and, to compare these properties with a standard gadolinium agent. MATERIALS AND METHODS: Two phase I trials compared intraindividually: (A) the vascular contrasting properties of Gd-BOPTA at three doses (0.0125, 0.05, and 0.2 mmol/kg body weight) and two flow rates (0.5 and 2.0 mL/s) in 10 volunteers; and (B) 0.1 mmol/kg body weight doses of Gd-BOPTA and Gd-DTPA at 2.0 mL/s using a modified magnetic resonance angiography (MRA) sequence with a temporal resolution of 1 s/f. Quantitative (ROI analysis) and fully blinded qualitative (reader review) assessment of images was performed. RESULTS: A dose of 0.2 mmol/kg resulted in higher maximum intensities, longer median peak widths, and larger areas under the curve than did the lower doses (0.0125 mmol/kg and 0.05 mmol/kg). In the intraindividual comparison, Gd-BOPTA demonstrated significantly better vascular enhancement characteristics in terms of signal peak duration (p < 0.05), maximum signal intensity (p < 0.05), and area under the enhancement curve (p < 0.01). The multireader assessment for overall vascular contrast preferred Gd-BOPTA at p < 0.03. CONCLUSIONS: Gd-BOPTA was shown to exhibit preferential and different vascular enhancement properties as compared with Gd-DTPA for MRA.

Adult↗

Dynamic contrast-enhanced MRI using Gd-DTPA: interindividual variability of the arterial input function and consequences for the assessment of kinetics in tumors.

Gd-DTPA kinetics in arterial blood was investigated by dynamic MRI in 47 patients with malignant and benign mammary tumors. Signal enhancement was monitored for 10 min after the beginning of a 1-min infusion of 0.1 mmol/kg Gd-DTPA. Kinetics in blood was biexponential with median half-lives of 21 sec and 11.1 min, respectively. Peak signal enhancement and the area under the signal enhancement-time curve varied 2.5- and 3.7-fold between patients. The shortest mean residence time in one of up to three tumor compartments, MRT*, was estimated using either the individual (reference) or a mean population (surrogate) arterial input function (AIF). MRT* (reference estimate) was 1.0 (0-1.5), 1.9 (1.5-2.3), and 2.5 (2.3-2.8) min in carcinomas, fibroadenomas, and mastopathies, respectively (median and interquartile distance). Surrogate estimates were unbiased but differed from the reference estimates 1.5-fold or more in 23% of cases. AIFs should be monitored individually if accurate estimates of individual MRT* are desired.

Breast Neoplasms↗

[Administration of MR contrast agents outside of approved indications (off-label use].

PURPOSE: The use of MRI contrast agents outside their labeled indications is routine in radiology. However, physicians feel frequently at unease. It is the aim of this paper to introduce the medical, juridicial and billing relevant issues in order to improve the knowledge on this topic. METHODS: The basis for off-label use is the physician's prerogative, which finds its basis in the "declaration of Helsinki". RESULTS: Off-label use is allowed under special conditions and might be even the medical state of the art. CONCLUSION: The necessity for off-label use will continue to increase for MR-contrast agents, as clinical trials for registration purpose are quite costly and manufactures continuously will concentrate on the essential indications.

Clinical Trials as Topic↗

[Comparison of contrast behavior of gadobenate-dimeglumine and Gd-DTPA in intra-axial brain tumors. A double-blind randomized intraindividual cross-over study].

The purposes of the study was to assess intra-axial brain tumors by a blinded comparison of gadobenat-dimeglumine and Gd-DTPA. 27 patients with known cerebral gliomas or metastases were included into an intra-individual randomized double-blinded cross-over study. The protocol included T1 SE, T2 FSE and after contrast a series of five T1 SE sequences followed by T1 SE with MT, T1 SE, and 3D GRE sequences. Imaging data acquired at two centers were assessed on-site by the investigators and off-site by two experienced readers using quantitative and qualitative criteria. For a quantitative analysis tumor contrast and contrast-to-noise ratios were determined out of ROI in tumor, unaffected white matter, a region outside the head, and an external reference tube. For the qualitative assessment on- and off-site readers were asked to compare both MR scans for lesion contrast, lesion delineation and information upon the internal morphology and structure. In the quantitative analysis lesions examined with gadobenat-dimeglumine present a maximal 26% increase of the lesion contrast. In both, the on-site, as well as the off-site assessment the intensity of enhancement and the lesion contrast were found to be significantly better with gadobenat-dimeglumine enhanced MRI. There was a trend towards gadobenat-dimeglumine for the delineation of the lesion from the surrounding tissue and the internal lesion morphology. Based on our observations gadobenat-dimeglumine proved to be a safe and valuable contrast media for the assessment of CNS neoplasms. Compared with Gd-DTPA it provides a more intense contrast enhancement and a better tumor contrast which might be of importance for the further management of these patients.

Brain↗

Postoperative fluid-attenuated inversion recovery MR imaging of cerebral gliomas: initial results.

Fluid-attenuated inversion-recovery (FLAIR) imaging has shown to be a valuable imaging modality in the assessment of intra-axial brain tumors; however, no data are available about the role of this technique in the clinically important postoperative stage. The purpose of this study was to evaluate the diagnostic potential of FLAIR MR imaging in residual tumor after surgical resection of cerebral gliomas. Fifteen patients with residual cerebral gliomas were examined within the first 18 days after partial surgical resection of cerebral gliomas. The imaging protocol included T1-weighted spin echo, T2- and proton-density-weighted fast spin echo, and FLAIR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media application. Detection and delineation of residual tumor were the primary parameters of the image analysis. Additionally, the influence of image artifacts on the image interpretation was assessed. On FLAIR images residual signal abnormalities at the border of the resection cavities were observed in all patients, whereas T2- and T1-weighted images present residual abnormalities in 13 of 15 and 10 of 15 patients, respectively. The FLAIR imaging was found to be superior to conventional imaging sequences in the delineation of these changes and comparable to contrast enhanced T1-weighted imaging in the delineation of residual enhancing lesions. Because of protein cell components and blood byproducts within the resection cavity, FLAIR imaging was unable to suppress the cerebrospinal fluid (CSF) in 4 patients. After the decomposition of proteins and blood, CSF could again be completely suppressed and residual or recurrent tumors were clearly identified. Our preliminary study has shown that FLAIR may be a valuable diagnostic modality in the early postoperative MR imaging after resection of cerebral gliomas due to its better delineation of residual pathologic signal at the border of the resection cavity. It should therefore be integrated into the early and/or intraoperative MR imaging protocol.

Adolescent↗