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Biomedical subjects

V M Runge

Publications and source records attributed to V M Runge.

At least 19 recordsLinked to original sources
PubMed2001

[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↗
PubMed2001

[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↗
PubMed2001

Central nervous system: review of clinical use of contrast media.

The clinical utility of intravenous contrast administration for magnetic resonance imaging in neoplastic disease of the brain, non-neoplastic disease of the brain, and in disease of the spine is reviewed. Magnetic resonance imaging (MRI) is the modality of choice for the evaluation of most suspected intracranial and spinal pathology. Contrast use substantially improves lesion detection and differential diagnosis. Applications are discussed in neoplastic disease, infection, vascular disorders, demyelinating disease, and trauma (specifically including in the spine disk herniation). Gadolinium chelates play as important a role in magnetic resonance imaging as do iodinated agents in computed tomography. Contrast administration facilitates time-efficient and cost-effective diagnosis.

Central Nervous System Diseases↗
PubMed2001

Safety of magnetic resonance contrast media.

Intravenous contrast media, specifically the gadolinium chelates, are well accepted for use in the clinical practice of magnetic resonance imaging. The gadolinium chelates are considered to be very safe and lack (in intravenous use) the nephrotoxicity found with iodinated contrast media. Minor adverse reactions, including nausea and hives, occur in a low percentage of cases. The four agents currently available in the United States cannot be differentiated on the basis of these adverse reactions. Severe anaphylactoid reactions are also known to occur with all agents, although these are uncommon. This review discusses the safety issues involved with intravenous administration of the gadolinium chelates and off-label use. The latter is common in clinical practice and permits broader application of these agents.

Anaphylaxis↗
PubMed2001

A clinical comparison of the safety and efficacy of MultiHance (gadobenate dimeglumine) and Omniscan (Gadodiamide) in magnetic resonance imaging in patients with central nervous system pathology.

RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

Brain Neoplasms↗
PubMed2001

A review of contrast media research in 1999-2000.

Contrast media research published during the years 1999 and 2000 is reviewed in this article, in terms of relevance to developments within the field of diagnostic radiology. The primary focus is on publications from the journal Investigative Radiology, which publishes much of the clinical and laboratory research performed in this field. The journals Radiology and the American Journal of Roentgenology are dominant in the field of diagnostic radiology and together publish more than 10 times the number of articles as appear each year in Investigative Radiology. However, in 1999 for example, these two journals together published fewer articles than did Investigative Radiology alone that concerned basic (animal) research with contrast media. Thirty-six percent of the articles in Investigative Radiology in 1999 had a primary focus on contrast media and 18% on basic (animal) research with contrast media. To make this review more complete, articles from other major journals are cited and discussed, as needed, to provide supplemental information in the few areas not well covered by articles in Investigative Radiology. The safety of contrast media is always an important topic and research continues to be performed in this area, both to explore fundamental issues regarding iodinated contrast media and also to establish the overall safety profile of new magnetic resonance (MR) and ultrasound agents. In regard to preclinical investigations, most of the work performed in the last 2 years has been with MR and ultrasound. In MR, research efforts continue to be focused on the development of targeted agents. In ultrasound, research efforts are split between studies looking at new imaging methods and early studies of targeted agents. In regard to the clinical application of contrast media, the published literature continues to be dominated by MR. Investigations include the study of disease in clinical trials and in animal models. A large number of studies continue to be published in regard to new techniques and applications within the field of contrast-enhanced magnetic resonance angiography. This field represents the single, largest new clinical application of contrast media in MR to emerge in the last decade. New clinical research continues to be published regarding the use of contrast media in computed tomography (CT), ultrasound, and x-ray angiography. The introduction of spiral CT (together with the multidetector scanners) has led to greater utilization of this modality, as well as intravenous iodinated contrast media. The number of publications regarding clinical applications of intravenously injected ultrasound contrast agents remains low, with the high expectations in regard to growth (in terms of number of exams using contrast) of the last decade yet to be fulfilled.

Animals↗
PubMed2000

Phase II double-blind, dose-ranging clinical evaluation of gadobenate dimeglumine in focal liver lesions: with analysis of liver and kidney signal change on early and delayed imaging.

To evaluate the effect of contrast dose using gadobenate dimeglumine, 30 patients with focal liver lesions documented by computed tomography or ultrasound were studied by magnetic resonance imaging at 1.5 T. Patients received one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, or 0.2 mmol/kg) or saline. The order of dosage was randomized, with both the physician and patient blinded to the administered dose. Scans were obtained before, immediately following injection, and after 80 minutes of delay. Enhancement effects were quantified by region of interest measurements. Films were also reviewed in a randomized prospective fashion by an abdominal radiologist blinded to contrast dose and diagnosis. Higher doses led to a statistically significant improvement in enhancement of normal liver, both on immediate (P = 0.01 for the comparison of 0.1 and 0.2 mmol/kg immediately post-contrast) and delayed scans (P = 0.003 for the same comparison). Liver-lesion contrast-to-noise ratio also increased with dose, although results for most comparisons by dose were not statistically significant. Scans following gadobenate dimeglumine injection were judged to provide additional diagnostic confidence sufficient to affect patient management in 10 of 24 cases. In seven cases this information was provided by dynamic scans, in one case by delayed scans, and in two cases by both dynamic and delayed scans. In 2 of the 10 cases the dose was 0.025 mmol/kg, in 2 cases 0.05 mmol/kg, in 3 cases 0.1 mmol/kg, and in 3 cases 0.2 mmol/kg. Gadobenate dimeglumine is effective for imaging of focal liver lesions at a range of doses, with trends toward improved diagnostic information at higher doses.

Adult↗
PubMed2000

Safety of approved MR contrast media for intravenous injection.

In the last 10 years, the use of intravenous contrast media in magnetic resonance (MR) has become well-established clinical practice. Contrast media provide critical additional diagnostic information in many instances. The gadolinium chelates constitute the largest group of MR contrast media and are considered to be very safe. These agents are thought to be safer than nonionic iodinated contrast agents. Unlike x-ray agents, the gadolinium chelates are not nephrotoxic. Minor adverse reactions, including nausea (1%-2% for all agents) and hives (<1% for all agents), occur in a very low percent of cases. Health care personnel should be aware of the (extremely uncommon) potential for severe anaphylactoid reactions in association with the use of MR contrast media and be prepared should complications arise. The four gadolinium chelates currently available worldwide, gadopentetate dimeglumine, gadoteridol, gadodiamide, and gadoterate meglumine, cannot be differentiated on the basis of adverse reactions. Far fewer patients have been examined to date with the two other agents that have widespread approval, mangafodipir trisodium and ferumoxides. These latter two agents are considered to be very safe but have a higher percentage of associated adverse reactions (7%-17% with mangafodipir trisodium and 15% with ferumoxides). This review discusses the safety issues involved with administration of intravenous contrast media in MR imaging, focusing on the six agents (four gadolinium chelates, one manganese chelate, and the last a large iron particle) with widespread use world-wide.

Anaphylaxis↗
PubMed2000

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Adult↗
PubMed2000

Synthesis, characterization, and imaging performance of a new class of macrocyclic hepatobiliary MR contrast agents.

RATIONALE AND OBJECTIVES: To investigate the effect of substituent lipophilicity, substituent position, and overall charge on the hepatobiliary clearance and tolerance of a series of aromatic ring-containing macrocyclic Gd chelates to select a candidate compound for evaluation as a hepatobiliary imaging agent. METHODS: Hepatobiliary clearance was studied in rats. Tissue distribution and tolerance were studied in mice. Imaging was performed in cats, rabbits, and Rhesus monkeys using T1-weighted pulse sequences or T1-weighted breath-hold pulse sequences. RESULTS: All the compounds were excreted bimodally. Gd-2,5-BPA-DO3A (15d) was found to have the optimal combination of hepatobiliary clearance (47% in rats, 29% in mice) and tolerance (minimum lethal dose 5.0 mmol/kg). Initial imaging studies in cats demonstrated the feasibility of Gd-2,5-BPA-DO3A for hepatic imaging. In rabbits with implanted VX-2 adenocarcinoma as a model for metastatic liver disease, Gd-2,5-BPA-DO3A provided sustained hepatic signal intensity (SI) enhancement and lesion conspicuity over a 120-minute imaging time course. In Rhesus monkeys with normal liver function, Gd-2,5-BPA-DO3A afforded sustained hepatic SI enhancement and a time-dependent increase in gallbladder SI over the entire 90-minute imaging time course. CONCLUSIONS: Gd-2,5-BPA-DO3A provides dramatic and sustained SI enhancement of hepatic tissue in cats, rabbits, and Rhesus monkeys that was superior in all respects to the extracellular space MRI agent, Gd-HP-DO3A, that was employed as a control.

Animals↗
PubMed1999

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data.

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.

Contrast Media↗
PubMed1999

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Abdomen↗
PubMed1999

Changes in the approval process for contrast media.

This paper discusses, from an academic perspective, the changes proposed by the Food and Drug Administration (FDA) regarding the approval process for contrast media. The proposed changes are extensive, covering indications, safety and efficacy assessments, and image acquisition and handling. The draft guidance unfortunately grouped together therapeutics and diagnostics. Indications were divided into the following categories: a) structure delineation, b) functional physiological, or biochemical assessment, c) disease or pathology detection/assessment, and d) diagnostic or therapeutic patient management. Such a division would greatly complicate the approval process, requiring multiple trials to gain approval. The draft guidance also disregarded that indications for imaging agents are often general and not disease specific. As issued, it implied that separate trials would be required for each clinical setting where lesions might be important. As the standard of truth, blinded reads with no clinical information were proposed as the primary endpoint. This ignores how diagnostic exams are interpreted and the value of medical history.

Contrast Media↗
PubMed1999

Off-label use and reimbursement of contrast media in MR.

Use of an approved contrast agent for a clinical purpose not contained in the package insert is not in violation of current U.S. Acts providing that it is in the course of routine medical practice, not part of an investigation into safety or effectiveness and not commercialized through advertising. The Food and Drug Administration does not have the authority to regulate the use of approved contrast media in any manner that radiologists believe, in their professional judgment, would best serve the patient. Moreover, the use of an approved contrast agent for a clinical purpose not explicitly contained in the labeling does not expose the radiologist to malpractice liability. Regarding reimbursement, there is no guarantee that any payer will reimburse a provider for use of a contrast agent outside of package insert indications. The best way to influence reimbursement is to provide the payer with detailed information prior to claim submission.

Contrast Media↗
PubMed1999

MR imaging of tumor microcirculation: promise for the new millennium.

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is a method of imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE MRI can measure and predict tumor response to therapy. Recent advances in MR technology provide the enhanced spatial and temporal resolution that allow the application of this methodology in the management of cancer patients. The September issue of this journal provided a microcirculation section to update readers on this exciting and challenging topic. Evidence is mounting that DCE MRI-based measures correlate well with tumor angiogenesis. DCE MRI has already been shown in several types of tumors to correlate well with traditional outcome measures, such as histopathologic studies, and with survival. These new measures are sensitive to tumor physiology and to the pharmacokinetics of the contrast agent in individual tumors. Moreover, they can present anatomical images of tumor microcirculation at excellent spatial resolution. Several issues have emerged from recent international workshops that must be addressed to move this methodology into routine clinical practice. First, is complex modeling of DCE MRI really necessary to answer clinical questions reliably? Clinical research has shown that, for tumors such as bone sarcomas, reliable outcome measures of tumor response to chemotherapy can be extracted from DCE MRI by methods ranging from simple measures of enhancement to pharmacokinetic models. However, the use of similar methods to answer a different question-the differentiation of malignant from benign breast tumors-has yielded contradictory results. Thus, no simple, one-size-fits-all-tumors solution has yet been identified. Second, what is the most rational and reliable data collection procedure for the DCE MRI evaluation? Several groups have addressed population variations in some key variables, such as tumor T(1)0 (T(1) prior to contrast administration) and the arterial input function C(a)(t) for contrast agent, and how they influence the precision and accuracy of DCE MRI outcomes. However, despite these potential complications, clinical studies in this section show that some tumor types can be assessed by relatively simple dynamic measures and analyses. The clinical scenario and tumor type may well determine the required complexity of the DCE MRI exam procedure and its analysis. Finally, we suggest that a consensus on naming conventions (nomenclature) is needed to facilitate comparison and analysis of the results of studies conducted at different centers. J. Magn. Reson. Imaging 10:903-907, 1999.

Arteries↗
PubMed1999

Contrast media research.

This selective review highlights research in contrast media development and application in the field of diagnostic radiology in 1998 and 1999. The focus is on research published in Investigative Radiology, supplemented with work from other publications in the few areas not extensively covered by the journal. Studies continue to be performed, although at a low level, examining safety issues. Most preclinical investigations have focused on MR and ultrasound agents. In MR, the research effort is concentrated on the development of targeted agents; in ultrasound, work is focused on the characterization of basic contrast mechanisms. The demonstration of clinical applications is still dominated by work with MR, both in disease models and human investigations. The use of extracellular gadolinium chelates to enhance visualization of blood vessels (the field of contrast-enhanced MR angiography) is the largest single new clinical application of contrast media to emerge in several years. New clinical applications continue to be pursued with contrast media in CT, ultrasound, and x-ray angiography. As intravenously injected ultrasound contrast agents come to market, trials demonstrating clinical applications and subsequent scientific publications will increase in number.

Angiography↗