[show abstract][hide abstract] ABSTRACT: The purpose of our study was to assess the chondrogenic potential and the MR signal effects of GadofluorineM-Cy labeled matrix associated stem cell implants (MASI) in pig knee specimen.
Human mesenchymal stem cells (hMSCs) were labeled with the micelle-based contrast agent GadofluorineM-Cy. Ferucarbotran-labeled hMSCs, non-labeled hMSCs and scaffold only served as controls. Chondrogenic differentiation was induced and gene expression and histologic evaluation were performed. The proportions of spindle-shaped vs. round cells of chondrogenic pellets were compared between experimental groups using the Fisher's exact test. Labeled and unlabeled hMSCs and chondrocytes in scaffolds were implanted into cartilage defects of porcine femoral condyles and underwent MR imaging with T1- and T2-weighted SE and GE sequences. Contrast-to-noise ratios (CNR) between implants and adjacent cartilage were determined and analyzed for significant differences between different experimental groups using the Kruskal-Wallis test. Significance was assigned for p<0.017, considering a Bonferroni correction for multiple comparisons.
Collagen type II gene expression levels were not significantly different between different groups (p>0.017). However, hMSC differentiation into chondrocytes was superior for unlabeled and GadofluorineM-Cy-labeled cells compared with Ferucarbotran-labeled cells, as evidenced by a significantly higher proportion of spindle cells in chondrogenic pellets (p<0.05). GadofluorineM-Cy-labeled hMSCs and chondrocytes showed a positive signal effect on T1-weighted images and a negative signal effect on T2-weighted images while Ferucarbotran-labeled cells provided a negative signal effect on all sequences. CNR data for both GadofluorineM-Cy-labeled and Ferucarbotran-labeled hMSCs were significantly different compared to unlabeled control cells on T1-weighted SE and T2*-weighted MR images (p<0.017).
hMSCs can be labeled by simple incubation with GadofluorineM-Cy. The labeled cells provide significant MR signal effects and less impaired chondrogenesis compared to Ferucarbotran-labeled hMSCs. Thus, GadoflurineM-Cy might represent an alternative MR cell marker to Ferucarbotran, which is not distributed any more in Europe or North America.
PLoS ONE 01/2012; 7(12):e49971. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the potential of Gadofluorine M for targeted lymph node imaging in a human size animal model and on a clinical MR scanner at 1.5 and 3 T.
Pelvic and cervical lymph nodes in a swine model were investigated prior to and 24 hours after intravenous administration of 50 micromol/kg body weight Gadofluorine M, an experimental contrast agent. MR imaging was carried out on clinical 1.5 T and 3 T whole-body MR systems using clinically available coils and T 1-weighted sequences. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) with respect to the surrounding tissue were assessed and compared using the Student's t-test. The Gd concentration in the lymph nodes (n = 43) was measured post mortem by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES).
Gadofluorine M allowed for high signal and high contrast visualization of lymph nodes in all stations on post-contrast images with a significantly increased SNR and CNR (SNR pelvic lymph nodes post vs. pre: 46 +/- 7 vs.14 +/- 3, SNR cervical lymph nodes post vs. pre: 105 +/- 64 vs. 32 +/- 21; CNR pelvic lymph node vs. muscle post vs. pre 28 +/- 5 vs. 0.2 +/- 0.5, CNR cervical lymph node vs. muscle post vs. pre 76 +/- 53 vs. 11 +/- 15, p < 0.05 for all comparisons). The SNR and CNR in the pelvis were further improved using 3 T compared to 1.5 T scanners (SNR lymph nodes 3 T vs. 1.5 T 84 +/- 6 vs. 46 +/- 7, CNR lymph node vs. muscle 3 T vs. 1.5 T 53 +/- 9 vs. 28 +/- 5 respectively, p < 0.05). A high concentration of Gd in the lymph nodes was found (149 +/- 25 mmol Gd/L).
Gadofluorine M accumulates in the lymph nodes and allows for selective targeted high contrast MR imaging of lymph node tissue in a large animal model using clinically available MR imaging techniques. 3 T further improves SNR and CNR compared to 1.5 T.
RöFo - Fortschritte auf dem Gebiet der R 04/2010; 182(8):698-705. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the potential of gadofosveset-enhanced MR imaging for the characterization of human carotid atherosclerotic plaques.
Sixteen (9 symptomatic, 7 asymptomatic) patients with 70% to 99% carotid stenosis (according to NASCET criteria) were included (13 men, 3 women, mean age 67.6 years). All patients underwent baseline precontrast MR imaging of the carotid plaque. Immediately after completion of the baseline examination, 0.03 mmol/kg gadofosveset was administered. At 24 hours postinjection, the acquisition was repeated. Twelve patients were scheduled for carotid endarterectomy. Carotid endarterectomy specimens were HE-, CD31-, CD68-, and albumin-stained to correlate signal enhancement with plaque composition, intraplaque microvessel density, and macrophage and albumin content. A random intercept model was used to compare signal enhancement between symptomatic and asymptomatic patients, adjusting for size of various plaque components. This study was approved by the institutional medical ethics committee. All participants gave written informed consent.
Signal enhancement (SE) of the plaque was significantly higher in symptomatic patients compared with asymptomatic patients (median log SE 0.182 vs. -0.109, respectively, P < 0.001). A positive association (as expressed by a regression coefficient beta = 0.0035) was found between signal enhancement on the log scale and intraplaque albumin content (P = 0.038). There was no association between signal enhancement and various other plaque components.
In this study, the potential of gadofosveset-enhanced human carotid plaque MR imaging for identification of high-risk plaques was demonstrated. Signal enhancement of the plaque after administration of gadofosveset was associated with differences in intraplaque albumin content. Although promising, we emphasize that these results are based on a small patient population. Larger prospective studies are warranted.
[show abstract][hide abstract] ABSTRACT: A new contrast agent was developed by linking Gd-DTPA chelate to recombinant human albumin in the laboratory. The molar relaxivity of the new agent was tested in aqueous solution at B(0) 1.5 T and temperature 20 degrees C. The soluble compound had a higher molar longitudinal relaxivity and molar transverse relaxivity in water (r(1) = 7.2 s(-1) mM(-1), r(2) = 18.4 s(-1) mM(-1)) than those measured for Gd-DTPA solution (r(1) = 3.5 s(-1) mM(-1), r(2) = 5.5 s(-1) mM(-1)). The performance of the compound as a blood pool agent was investigated with soluble and microparticulate forms of the compound and comparisons were made with Gd-DTPA and the polymeric blood-pool agent, Gadomer. T(1)-weighted imaging experiments show that the soluble compound acts as a highly effective blood pool agent with hyperintensity in the vasculature persisting beyond 2 h post administration, compared with free Gd-DTPA, which was cleared from the blood pool after approximately 10 min. The clearance kinetics of the new agents were examined, due to the incomplete elimination within 14 days post injection; both rHA labeled compounds are probably not suitable for development as routine blood pool contrast media. However, with free sites on the Gd-loaded rHA molecule, there are possibilities for binding the agent to antibodies in the laboratory, which was demonstrated, and thus there exist potential applications for in vivo molecular imaging with this agent.
[show abstract][hide abstract] ABSTRACT: Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA.
Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T(1)-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.
GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.
[show abstract][hide abstract] ABSTRACT: To investigate the potential of gadofosveset for contrast material-enhanced magnetic resonance (MR) imaging of plaque in a rabbit model of atherosclerosis.
All experiments were approved by the animal ethics committee. Thirty-one New Zealand White rabbits were included in one of four study groups: animals with atherosclerosis imaged with gadofosveset (n = 10) or gadopentetate dimeglumine (n = 7) and control animals imaged with gadofosveset (n = 7) or gadopentetate dimeglumine (n = 7). Aortic atherosclerosis was induced through endothelial denudation combined with a cholesterol-enriched diet. Control rabbits underwent a sham surgical procedure and received a regular diet. After 8 weeks, pre- and postcontrast T1-weighted MR images of the aortic vessel wall were acquired. Relative signal enhancement was determined with dedicated software. Statistical analysis was performed by using a generalized linear mixed model. Immunohistochemical staining with CD31 and albumin was used to assess microvessel density and the albumin content of the vascular wall. Group differences were analyzed by using a chi(2) test. Gadofosveset spatial distribution and content within the vessel wall were determined with proton-induced x-ray emission (PIXE) analysis.
Postcontrast signal enhancement was significantly greater for atherosclerotic than for control animals imaged with gadofosveset (P = .022). Gadopentetate dimeglumine could not enable discrimination between normal and atherosclerotic vessel walls (P = .428). PIXE analysis showed higher amounts of gadopentetate dimeglumine than gadofosveset in both atherosclerotic and normal rabbit aortas. Immunohistochemical staining revealed the presence of albumin and increased microvessel density in the vascular walls of atherosclerotic rabbits.
These results suggest that gadofosveset can be used to differentiate between atherosclerotic and normal rabbit vessel walls. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/250/3/682/DC1.
[show abstract][hide abstract] ABSTRACT: To evaluate the microstructural anatomy of inguinal lymph nodes in pigs after interstitial MR-lymphography with the dendritic contrast agent Gadomer-17.
High-resolution T1-weighted MR-lymphography was performed in inguinal lymph nodes of 10 domestic pigs (39 - 46 kg) after subcutaneous injection of 10 mumol/kg body weight Gadomer-17 in the hind legs of the animals. A 1.5T MR scanner and a ring-shaped surface coil were used. Two different high-resolution gradient-echo sequences with additionally reconstructed maximum-intensity projections were evaluated in a total of 20 lymph nodes. The high-resolution MR-findings were correlated with the histologic sections of the excised inguinal lymph nodes.
Coronal T1-weighted 3D gradient-echo images (TR = 20 msec, TE = 6.1 - 8.3 msec, FA = 20 degrees ) with a slice thickness of 1 mm, a field-of-view of 120 mm and a matrix size of 256 x 256 (reconstructed to 1024 x 1024 voxels) yielding a reconstructed in-plane resolution of 117 x 117 microm (2) were best suited for the high-resolution MR lymphography of inguinal lymph nodes and enabled the differentiation of the hyperintense lymph node sinuses and hypointense lymphoid parenchyma of each lymph node (100 %). Even dilated lymphatic vessels evident in the histologic specimen were best demonstrated on the MIP images.
High-resolution interstitial MR lymphography with Gadomer-17 allows the visualization of different tissue compartments of inguinal lymph nodes. This new technique is feasible on a routine 1.5T scanner and may offer potential for the detection of micrometastases in lymph nodes of cancer patients.
RöFo - Fortschritte auf dem Gebiet der R 08/2005; 177(7):968-74. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To visualize and localize fistulas of the thoracic duct with interstitial T 1 -weighted MR lymphography using Gadomer-17.
In 10 domestic pigs, leaks of the thoracic duct were created surgically or interventional-radiologically. The lymphatic leakage was located within the abdominal portion of the thoracic duct in 5 pigs, within the thoracic portion of the thoracic duct in 3 pigs, and in both, abdominal and thoracic portions of the thoracic duct, in 2 pigs. Subsequently, 10 micro mol/kg KG Gadomer-17 (1.5-1.8 ml) was administered interstitially in both hind legs of the animals. MR lymphography was performed with a 1.5 T MR unit using two different 3D gradient echo sequences before and 10 - 90 minutes after administration of contrast material.
Leaks within the abdominal portion of the thoracic duct were directly visible as opacified fistulas. Indirect signs of active lymphatic fistulas were increasing extravasations of contrast material and free abdominal fluid. The 3D gradient echo sequence with the highest planar resolution (TR = 8,7 - 8,8 ms, TE = 4,2 - 4,3 ms, FA = 40 degrees, matrix size = 327 x 512) was best suited for distinct delineation of the lymphatic system and detailed demonstration of the thoracic duct fistulas. Intrathoracic leaks could not be demonstrated by MR lymphography due to reduced lymphatic flow or extravasated contrast medium at the abdominal puncture site.
Interstitial MR lymphography with Gadomer-17 allows sensitive detection and localization of abdominally located leaks of the thoracic duct.
RöFo - Fortschritte auf dem Gebiet der R 03/2003; 175(2):275-81. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the enhancement of regional lymph nodes and lymphatic vessels after intramammary injection of Gadomer-17.
T1-weighted MR-lymphography was performed in 8 domestic pigs after intramammary injection of 5 - 10 micromol/kg bodyweight (bw) Gadomer-17 on a 1.5 T-MR scanner. T1-weighted 3D gradient-echo images were acquired 10 to 120 minutes after contrast material injection in coronal and sagittal planes. The contrast enhancement of the draining lymphatic system was qualitatively assessed by two radiologists applying a three grade scale.
T1-Weighted MR-lymphography after intramammary injection of Gadomer-17 was feasible in each pig. A dose of 5 micromol/kg body weight Gadomer-17 was best suited for MR-lymphography of the mammary line and the draining lymphatic system. Enhancement of regional lymph nodes and lymphatic vessels was classified as good in 5, and excellent in three cases.
Intramammary injection of Gadomer-17 allows for good quality T1-weighted MR-lymphography of mammary gland draining regional lymph nodes and lymphatic vessels. This new technique might offer potential for the evaluation of the sentinel lymph node in patients with breast cancer.
RöFo - Fortschritte auf dem Gebiet der R 02/2002; 174(1):29-32. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the enhancement of regional lymph nodes, lymph vessels and the thoracic duct after subcutaneous administration of the dendritic contrast agent Gadomer-17.
Interstitial T(1)-weighted MR lymphography was performed in 15 domestic pigs in a 1.5 T MR scanner using the body coil. The contrast agent was injected subcutaneously at a dose of 2.5, 10 and 20 micromol gadolinium/kg/bw (1.4 - 2.3 ml) in the hind legs of 5 pigs, respectively. T(1)-weighted coronal 3D-gradient-echo images were obtained 1 to 150 minutes and 24 hours after contrast material injection.
Inguinal lymph nodes, iliac lymph nodes and lymph vessels showed peak enhancement within 10 minutes after subcutaneous administration of the contrast agent. The enhancement of the lymphatic system decreased slowly until 150 minutes post injection. The time-response study, which was performed for inguinal and iliac lymph nodes, revealed the best lymphographic effect for Gadomer-17 at a dose of 10 micromol gadolinium/kg/bw. At this dose the paraaortic lymph nodes and the thoracic duct were also best visualized.
Interstitial administration of the evaluated dendritic contrast agent Gadomer-17 is highly efficient for the performance of T(1)-weighted MR lymphography in regional lymph nodes, lymph vessels and the thoracic duct.
RöFo - Fortschritte auf dem Gebiet der R 01/2002; 173(12):1131-6. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the enhancement of the regional lymph nodes, lymphatic vessels, and thoracic duct after interstitial administration of lymphotropic perfluorinated gadolinium chelates at magnetic resonance (MR) imaging.
Two perfluorinated gadolinium chelates, gadofluoramide and gadofluorine 8, were injected subcutaneously into the hind legs of 10 pigs, respectively. Both contrast media were studied at doses of 10 and 25 micromol per kilogram of body weight. T1-weighted three-dimensional gradient-echo and maximum intensity projection images were obtained at 1.5 T between 1 and 210 minutes and 24 hours after injection. The contrast agents were qualitatively compared regarding enhancement and depiction of the regional lymph nodes, lymphatic vessels, and thoracic duct.
The inguinal and iliac lymph nodes and lymphatic vasculature enhanced substantially within 10 minutes after subcutaneous administration of both lymphotropic contrast agents. Gadofluorine 8 showed a lymphographic effect superior to that of gadofluoramide. The paraaortic lymph nodes and thoracic duct were best visualized 10--50 minutes after injection of 25 micromol/kg of gadofluorine 8. Lymphatic system enhancement diminished after 2 hours, and the liver and bowel tract enhanced within 24 hours.
Interstitial administration of perfluorinated gadolinium chelates offers great potential for T1-weighted MR lymphography with positive enhancement of the lymph nodes and lymphatic vasculature.
[show abstract][hide abstract] ABSTRACT: Magnetic resonance assessment of lung ventilation with aerosolized Gd-DTPA.
Eleven experimental procedures were carried out in a domestic pig model. The intubated pigs were aerosolized for 30 minutes with an aqueous formulation of Gd-DTPA. The contrast agent aerosol was generated by a small particle aerosol generator. Imaging was performed on a 1.5 T MR imager using a T1-weighted turbo spin echo sequence with respiratory gating (TR 141 ms, TE 8.5 ms, 6 averages, slice thickness 10 mm). Pulmonary signal intensities before and after ventilation were measured in peripheral portions of both lungs.
Immediately after ventilation with aerosolized Gd-DTPA, the signal intensity in both lungs increased significantly in all animals with values up to 237% above baseline (mean 139% +/- 48%), but with in some cases considerable regional intra- and interindividual intensity differences. Distinctive parenchymal enhancement was readily visualized in all eleven cases with good spatial resolution.
The presented data indicate that Gd-DTPA in aerosolized form can be used to demonstrate pulmonary ventilation in large animals with lung volumes comparable to man. Further experimental trials are necessary to improve reproducibility and to define the scope of this method for depicting lung disease.
RöFo - Fortschritte auf dem Gebiet der R 05/2000; 172(4):323-8. · 2.76 Impact Factor