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Bernd Misselwitz

Publications and source records attributed to Bernd Misselwitz.

15 recordsLinked to original sources
PubMed2006

MR contrast agents in lymph node imaging.

The detection of tumor metastases in lymph nodes is clinically important for tumor staging and therapy planning in cancer patients. However, differentiating between malignant and benign lymph nodes is still a problem because current imaging modalities rely only on the size and shape of the lymph nodes. Thus, small metastases in normal-sized lymph nodes can be missed, and it is difficult to differentiate enlarged nodes (benign hyperplasia versus malignant disease). Therefore, a specific lymphotropic contrast agent is needed to obtain a high contrast between functional and metastatic tissue. Contrast-enhanced MR lymphography is a noninvasive method for the analysis of the lymphatic system after interstitial (intracutaneous or subcutaneous) or intravenous application of contrast media. Interstitial MR lymphography using extracellular, liposomal, polymeric, lipophilic or particulate contrast agents results in high accumulation in regional lymph nodes. The systemic administration of a lymphotropic contrast medium is needed to address each individual lymph node. Ultrasmall superparamagnetic iron oxide particles are in late-stage clinical development for this indication, but they take 24h to show sufficient contrast. Recently, a gadolinium-type contrast agent (Gadofluorine M) was described that detected lymph node metastases within 60 min of intravenous injection.

Contrast Media↗
PubMed2006

Improvement of quantification of myocardial first-pass perfusion mapping: a temporal and spatial wavelet denoising method.

Mapping of myocardial blood flow (MBF) with first-pass perfusion imaging is becoming an important tool in the study of coronary artery disease. In this study a wavelet-based denoising method was developed to improve the accuracy of pixel-by-pixel MBF maps. We performed an in vivo study in five stenotic dogs with 70% stenosis in the left coronary arteries. First-pass perfusion imaging sessions were performed by administering the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Color microspheres (MS) were injected into the dogs to measure MBF at the same time. After denoising was performed, the signal-to-noise ratio (SNR) of the first-pass perfusion image improved by approximately 180%, whereas spatial variation of MBF maps decreased 38%. It was also found that the correlation of MBFs measured by MRI with the MS method indicates a significant improvement with the denoising method (R2 increased from 0.24 to 0.78, P < .001). This suggests that the wavelet denoising method may be an effective way to increase the accuracy of pixel-by-pixel MBF quantification and reduce spatial variation, and may be applicable to other forms of noise-sensitive image analysis.

Animals↗
PubMed2006

Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine.

OBJECTIVE: The aim of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. METHODS: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n=3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 micromol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall. Histopathology was performed to verify the presence and composition of the atherosclerotic plaques imaged with MRI. RESULTS: Gadofluorine was found to enhance LCA atherosclerotic lesions relative to RCA wall by 21% (P<0.025) 24 hours after contrast injection. Enhancement of healthy LCA wall relative to healthy RCA wall was not observed. CONCLUSION: Gadofluorine selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Gadofluorine appears to be a promising MR contrast agent for detection of atherosclerotic plaques in vivo.

Animals↗
PubMed2005

In vivo evaluation of gadolinium hydroxypyridonate chelates: initial experience as contrast media in magnetic resonance imaging.

The effect of ligand structure on the magnetic resonance (MR) imaging and biodistribution of six gadolinium (Gd) chelates based on a hydroxypyridonate-terephthalimide (HOPO-TAM) ligand design was investigated. Modifications to the molecular structure of the Gd-HOPO-TAM chelates (hydrophilicity and aromatic group substitution) significantly influence the efficacy of imaging and biodistribution. MR imaging was performed on female mice after intravenous (iv) injection of 100 micromol of Gd/kg of body weight of the different complexes. The biodistribution results indicate that the liver uptake of the complexes is enhanced by a short poly(ethyleneoxy) (PEO) chain, while blood pool localization is facilitated by a very long PEO chain. There is a direct correlation between the blood pool localization of the complexes and the signal intensity of blood vessels in the MRI. The imaging results are consistent with in vitro NMR measurements that indicate long PEO chains increase image enhancement capabilities in the presence of serum albumin.

Animals↗
PubMed2005

Assessment of nerve degeneration by gadofluorine M-enhanced magnetic resonance imaging.

Nerve injury represents a major cause of disability. In the peripheral nervous system, nerves have the capacity to regrow but within weeks after injury, it is impossible to clarify whether proper regeneration is under way or is failing. In this experimental study, we report on a novel tool to assess nerve outgrowth in vivo. After systemic application, the novel gadolinium-based magnetic resonance (MR) contrast agent Gadofluorine M (Gf) selectively accumulated and persisted in nerve fibers undergoing Wallerian degeneration causing bright contrast on T1-weighted MR images. Gf enhancement on MR imaging was present already at 48 hours within the entire nerve segments undergoing Wallerian degeneration, and subsequently disappeared from proximal to distal parts in parallel to regrowth of nerve fibers. Most importantly, Gf enhancement persisted in nonregenerating, permanently transected nerves. Our novel Gf-based MR imaging methodology holds promise for clinical use to bridge the diagnostic gap between nerve injury and completed nerve regeneration, and to determine the necessity for neurolysis and engraftment if spontaneous regeneration is not successful.

Animals↗
PubMed2005

Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison.

RATIONALE: Superparamagnetic iron-oxide particles are used frequently for cellular magnetic resonance imaging and in vivo cell tracking. The purpose of this study was to compare the labeling characteristics and efficiency as well as toxicity of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) for 3 cell lines. METHODS: Using human fibroblasts, immortalized rat progenitor cells and HEP-G2-hepatoma cells, dose- and time-dependence of SPIO and USPIO uptake were evaluated. The amount of intracellular (U)SPIO was monitored over 2 weeks after incubation by T2-magnetic resonance relaxometry, ICP-mass-spectrometry, and histology. Transmission-electronmicroscopy was used to specify the intracellular localization of the endocytosed iron particles. Cell death-rate and proliferation-index were assessed as indicators of cell-toxicity. RESULT: For all cell lines, SPIO showed better uptake than USPIO, which was highest in HEP-G2 cells (110 +/- 2 pg Fe/cell). Cellular iron concentrations in progenitor cells and fibroblasts were 13 +/- 1pg Fe/cell and 7.2 +/- 0.3pg Fe/cell, respectively. For all cell lines T2-relaxation times in cell pellets were below detection threshold (<3 milliseconds) after 5 hours of incubation with SPIO (3.0 micromol Fe/mL growth medium) and continued to be near the detection for the next 6 days. For both particle types and all cell lines cellular iron oxide contents decreased after recultivation and surprisingly were found lower than in unlabeled control cells after 15 days. Viability and proliferation of (U)SPIO-labeled and unlabeled cells were not significantly different. CONCLUSIONS: The hematopoetic progenitor, mesenchymal fibroblast and epithelial HEP-G2 cell lines accumulated SPIO more efficiently than USPIO indicating SPIO to be better suited for cell labeling. However, the results indicate that there may be an induction of forced cellular iron elimination after incubation with (U)SPIO.

Animals↗
PubMed2004

Lipid-rich atherosclerotic plaques detected by gadofluorine-enhanced in vivo magnetic resonance imaging.

BACKGROUND: MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non-lipid-rich plaques. METHODS AND RESULTS: Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 micromol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (P<0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 hour: 164% [P<0.005]; 24 hours: 207% [P<0.001]). At 1 hour and 24 hours after injection, the contrast-to-noise ratio was higher with the use of IR-DIFF-TFL than with IR-TFL (1 hour: 13.0+/-7.7 versus -19.8+/-10.3 [P<0.001]; 24 hours: 15.2+/-5.9 versus 11.4+/-8.9, respectively [P=0.052]). There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (r2=0.87; P<0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques. CONCLUSIONS: Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.

Animals↗
PubMed2004

Early MR lymphography with gadofluorine M in rabbits.

PURPOSE: To investigate the dose and time dependency of gadofluorine M for lymph node imaging and the detection of lymph node metastases in an animal model and to compare gadofluorine M with Gadomer (both, Schering, Berlin, Germany) for lymph node enhancement. MATERIALS AND METHODS: Enhancement of popliteal and iliac lymph nodes was studied in VX2 tumor-bearing rabbits before injection and at 5-120 minutes and 24 hours after intravenous bolus injection of 0.025, 0.05, and 0.1 mmol gadolinium per kilogram of body weight gadofluorine M (six rabbits) or 0.5 mmol/kg Gadomer (eight rabbits). Effects of treatment and time point at enhancement were evaluated with repeated measures analysis of variance. Means were separated with all-pairs comparison with Tukey-Kramer adjustment. After 1.5-T magnetic resonance (MR) imaging, lymph nodes were removed, and prepared sections were stained with hematoxylin-eosin for microscopic examination. RESULTS: MR images in VX2 tumor-bearing rabbits revealed rapid and strong signal intensity increase in the functional lymph node tissue by 15 minutes after intravenous injection of gadofluorine M. Maximum enhancement of 165%-309% was observed 60-90 minutes after injection (enhancement with 0.05 and 0.1 mmol/kg significantly different from that with 0.025 mmol/kg, P < or =.05). Metastatic tissue showed only slight enhancement at early time points, resulting in high-contrast differentiation between functional and metastatic tissue. Intravenous injection of the blood-pool agent Gadomer induced only short and inhomogeneous lymph node enhancement (enhancement significantly lower [P < or =.05] than that with gadofluorine M). CONCLUSION: Findings in the study showed that gadofluorine M produces rapid lymph node accumulation. Diagnosis of lymph node metastases was shown with intravenous injection of gadofluorine M with a minimum effective diagnostic dose of 0.025 mmol/kg.

Animals↗
PubMed2003

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↗
PubMed2003

Tissue-specific MR contrast agents.

The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.

Animals↗
PubMed2002

Interstitial magnetic resonance lymphography using a polymeric t1 contrast agent: initial experience with Gadomer-17.

RATIONALE AND OBJECTIVES: The detection of lymph node metastases is an important step in tumor staging and is significant for therapy planning. Lymph node-specific contrast agents can raise the sensitivity and specificity of modern diagnostic methods. This study investigated the suitability of the dendritic contrast agent Gadomer-17 in magnetic resonance (MR) lymph node imaging and compared three different dosages in such an application. METHODS: Doses of 1.0, 2.5, and 10.0 micromol Gd/kg body weight were interstitially injected into the hind legs of dogs; the signal intensities of two successive lymph node groups (inguinal and iliacal) were then recorded up to 120 minutes after injection. RESULTS: Gadomer-17 induced a strong increase in signal intensity of the examined lymph node groups. At 15 minutes postinjection, the enhancement increased by 120% to 680%, depending on the dose. The maximum enhancement was 450% to 960% at 60 to 90 minutes postinjection. Doses of 2.5 and 10.0 micromol Gd/kg showed comparable results; even the lowest dose (1.0 micromol Gd/kg) enhanced the contrast of the inguinal lymph nodes in 4 of 5 animals and the iliacal lymph nodes in three of five animals. Therefore, the minimum effective dose of Gadomer-17 in this study was approximately 2.5 micromol Gd/kg. CONCLUSION: This study revealed the excellent suitability of the dendritic contrast agent Gadomer-17 for MR imaging of the lymphatic system (lymph nodes and lymph vessels).

Animals↗
PubMed2002

Combined MR lymphangiography and MR imaging-guided needle localization of sentinel lymph nodes using Gadomer-17.

OBJECTIVE: The goals of our study were to determine the technical feasibility of dynamic MR lymphangiography for detecting sentinel lymph nodes using Gadomer-17 contrast material to compare these results to the clinically standardized blue dye contrast agent, and to show MR imaging-guided needle localization marking of the sentinel nodes. MATERIALS AND METHODS: Six anesthetized swine underwent MR imaging before and for 1 hr after interstitial injection of Gadomer-17 in the posterior tongue and intradermally in the stifle (knee). Using MR imaging guidance, we percutaneously placed a histology needle into the sentinel node or nodes. A standardized intraoperative sentinel node detection procedure was then performed using isosulfan blue contrast agent. Sentinel nodes identified on the MR images were compared with and matched to those identified by biopsy needle localization and the isosulfan blue contrast agent. RESULTS. Interstitial and intradermal injection of Gadomer-17 resulted in a lasting, increased MR signal in the regional lymph nodes. Seven sentinel nodes were identified in both the neck and the groin, with one pig showing two sentinel nodes in the neck and another showing two sentinel nodes in the groin. In all cases, the isosulfan blue contrast agent agreed with the location of the sentinel node determined by Gadomer-17 and marked with the needle. CONCLUSION: In this large animal model, dynamic MR angiography of sentinel lymph nodes is technically feasible using a contrast agent (Gadomer-17) and can be easily combined with MR imaging-guided needle localization.

Animals↗
PubMedDate not supplied

A new type of susceptibility-artefact-based magnetic resonance angiography: intra-arterial injection of superparamagnetic iron oxide particles (SPIO) A Resovist in combination with TrueFisp imaging: a feasibility study.

The goal of this study was to evaluate the use of super paramagnetic particles of iron oxide (SPIO) as a dark blood contrast agent, in combination with a bright blood steady-state free precession sequence for magnetic resonance angiography (MRA), in an animal model. The original concentration of the SPIO of 500 mmol Fe/l and dilutions to 250, 125, 60, 30, 10 and 5 mmol Fe/l were intra-arterially injected into the aorta of a pig. Then the dilution of 10 mmol Fe/l was chosen for repeated intra-arterial injections into two pigs. During these intra-arterial SPIO injections MR images were acquired with a 1.5 T scanner. Signal intensity measurements were performed in the aorta. The signal-to-noise ratio during SPIO bolus passage was significantly less than during baseline conditions (Fisher's F-ratio 159.8, p < 0.005) or the recovery signal-to-noise ratio (Fisher's F-ratio 144.6, p < 0.005). Also, confirmation of flow distal to the catheter-tip position was possible. The use of SPIO as a dark blood agent in combination with a bright blood MR imaging sequence is feasible. Temporary loss of intraluminal signal occurs due to local decrease of the signal because of induction of local inhomogeneities after mixture the present blood and SPIO solution. It provides immediate information about blood flow distal to the catheter and is a potentially useful to guide intravascular MR-interventional procedures.

Animals↗
PubMedDate not supplied

MRI tumor characterization using Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine M), a protein-avid contrast agent.

The rationale and objectives were to define the MRI tumor-characterizing potential of a new protein-avid contrast agent, Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine M; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd kg(-1), was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N-ethyl-N-nitrosourea (ENU), 45-250 mg kg(-1). These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two-compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (K(PS)) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff-Bloom-Richardson score) and location of necrosis. Eighteen tumor-bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. K(PS) and fEV*, but not fPV obtained from tumors correlated significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56, respectively. Estimates for K(PS) and fEV* but not fPV were significantly lower in a group consisting of benign and low-grade malignant tumors compared with the group of less-differentiated high-grade tumors (1.61 +/- 0.64 vs 3.37 +/- 1.49, p < 0.01; 0.45 +/- 0.17 vs 0.78 +/- 0.24, p < 0.01; and 0.076 +/- 0.048 vs 0.121 +/- 0.088, p = 0.24, respectively). It is concluded that the protein-avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low-grade malignant lesions from high-grade cancers.

Adenocarcinoma↗