[Multicenter analysis of tolerance and clinical safety of the extracellular MR contrast agent gadobenate dimeglumine (MultiHance)]. / Multizentrische Analyse der Verträglichkeit und klinischen Sicherheit des extrazellulären MR-Kontrastmittels Gadobenat-Dimeglumin (MultiHance).

PURPOSE: Retrospective analysis of the occurrence of adverse events and the diagnostic efficacy of a paramagnetic contrast agent with weak intermittent protein binding and high relaxivity. MATERIALS AND METHODS: Postmarketing surveillance studies for gadobenate dimeglumine (MultiHance, BRACCO Altana Pharma, Constance) were conducted in Germany between 1998 and 2006 and then retrospectively analyzed. Demographic data, relevant comorbidities, and allergies were recorded. The safety and tolerability of MultiHance were logged on a standardized data sheet. RESULTS: A total of 38,568 patients were included in the study. 829 patients (2.1%) had a known intolerance against contrast media. The examined regions included the central nervous system, the liver, and the vascular bed. The injection rate with automated injectors (n = 10456) varied between 1.0 und 3.0 ml/sec in 86.5% of patients. Adverse events totaled 1.2%. 11 patients (0.03%) experienced serious adverse events. The most frequent findings were nausea, vomiting and a feeling of warmth. CONCLUSION: MultiHance is a safe and very well tolerated contrast agent for magnetic resonance imaging (MRI) with a profile and frequency of adverse events similar to other extracellular MR contrast materials.

MR-based semi-automated quantification of renal functional parameters with a two-compartment model--an interobserver analysis.

PURPOSE: To assess the interobserver agreement in a semi-automated quantification approach of MR-renal perfusion and filtration parameters with a two-compartment model analysis. MATERIALS AND METHODS: Twelve consecutive patients underwent renal perfusion measurements after intravenous injection of 7 ml Gd-BOPTA at 4 ml/s at 3.0 T. Two independent observers placed two regions of interest (ROI) manually on the axial slice, one in the abdominal aorta to determine the arterial input function (AIF), and one at the tissue-air interface for retrospective triggering. The data were fitted on a pixel-by-pixel basis to the two-compartment model, producing maps of the perfusion parameters FP (plasma flow), TP (plasma mean transit time) and of the tubular filtration parameters FT (tubular flow) and TT (tubular mean transit time). A cortical ROI was segmented by selecting those pixels with plasma volume VP>10 ml/100 ml, and the model fit was repeated on a ROI basis to produce the cortical averages. RESULTS: The average values (observer 1/observer 2) were FP (226.2/187.3 ml/100 ml/min), TP (9.0/9.1s), FT (23.5/20.8 ml/100 ml/min), TT (142.1/140.0 s). The correlation coefficients between both observers were 0.90 (FP), 0.80 (TP), 0.80 (FT), 0.78 (TT). Correlations of all values were significant (p<0.05). A paired t-test yielded significant differences for FP (p=0.004). DISCUSSION/CONCLUSION: The data demonstrate a significant systematic difference for the parameter FP, while TP seems to be most stable. Further decrease of the residual variability of all parameters seems desirable to improve the robustness of the method for clinical routine.

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.

[Comparison of MultiHance and Gadovist for cerebral MR perfusion imaging in healthy volunteers]. / Vergleich von MultiHance((R)) und Gadovist((R)) zur zerebralen MR-Perfusionsmessung bei gesunden Probanden.

To evaluate the weakly protein interacting MR contrast agent MultiHance((R)) and the one-molar agent Gadovist((R)) for cerebral perfusion MR imaging, a randomized intraindividual study was conducted in 12 healthy male volunteers. Perfusion-MRI was performed with single and double dose of each contrast agent on a 1.5T MR system using a gradient-echo EPI sequence. The imaging parameters, slice positioning and contrast media application were standardized. For the quantitative assessment rCBV and rCBF measurements of gray and white matter were performed. Additionally, the percentage of signal drop and the full width half maximum (FWHM) of ROI signal time curves were quantified. In a qualitative analysis the image quality of the rCBV and rCBF maps were assessed. Single dosage of the used new contrast agents was sufficient to achieve high quality perfusion maps. The susceptibility effect, described by percentage of signal loss (Gadovist((R)): 29.4% vs. MultiHance((R)): 28.3%) and the FWHM (Gadovist((R)): 6.4 s vs. Multihance((R)): 7.0 s) were not different between the agents for single dose. The one molar MR contrast agent Gadovist((R)) has no advantages over MultiHance((R)), a MR contrast agent with a higher relaxivity in perfusion MRI. Both agents allow the calculation of high quality perfusion maps at a dosage of 0.1 mmol/kg bw with physiologic absolute values for regional CBV and CBF. The susceptibility effect is comparable for both agents and stronger than with conventional MR contrast media.

MR imaging of the wrist in rheumatoid arthritis using gadobenate dimeglumine.

OBJECTIVE: To determine the dosage of gadobenate dimeglumine (Gd-BOPTA) necessary for MRI of rheumatoid arthritis of the wrist. DESIGN AND PATIENTS: Seven wrists inflamed with rheumatoid arthritis were imaged using a dedicated 0.2-T MR unit. Four cumulative dosages of 0.0125, 0.025, 0.05 and 0.1 mmol/kg body weight (BW) Gd-BOPTA were tested. Three-dimensional T1-weighted gradient-recalled echo sequences (GRE; TR: 100 ms, TE: 18 ms, flip angle 90 degrees , 4:55 min) were acquired prior to an intravenous injection and after each additional dosage of Gd-BOPTA. Relative enhancement, signal-difference-to-noise ratios (SDNRs) and the size of the inflamed tissue were quantified. Three radiologists independently evaluated the image quality, the size and the contrast of the enhancing tissue. RESULTS: The readers agreed on a dose of 0.05 mmol/kg BW as satisfactory for the evaluation of the size of the inflammatory tissue and for determination of bone involvement (kappa = 0.9, P < 0.001). Highly inflammatory pannus was depicted with adequate image contrast using 0.025 mmol/kg BW Gd-BOPTA. According to the SDNR and relative enhancement findings, a dose of 0.05 mmol/kg BW suffices for both off-center and centered regions of tissue inflammation (t-test, P < 0.05). CONCLUSION: Gadolinium-BOPTA is an alternative contrast agent for MRI of rheumatoid disease. This study shows that a dose of 0.05 mmol/kg BW suffices at low field strength.

Off-site evaluation of liver lesion detection by Gd-BOPTA-enhanced MR imaging.

The aim of this study was to determine the efficacy of Gd-BOPTA-enhanced MRI in liver lesion detection in comparison with unenhanced MRI and dynamic CT. The image sets of 148 of 151 patients enrolled in a multicenter German phase-III trial were evaluated by two independent radiologists unaffiliated with the investigating centers. Patients underwent a routine MRI protocol comprising T2- and T1-weighted spin-echo and T1-weighted gradient-echo (GE) sequences pre and 1 h post 0.1 mmol/kg Gd-BOPTA (Bracco-Byk Gulden, Konstanz, Germany). Additionally, a serial T1-weighted GE scan was performed after administration of the first half of the dose. All patients underwent dynamic contrast-enhanced CT. The evaluation was performed with regard to the number and size of lesions detected per patient by each modality or sequence. Furthermore, all pre CM and pre + post CM image sets were analyzed for number of lesions per patient. Both readers detected significantly more lesions in the contrast-enhanced image set compared with the unenhanced image set (32 and 39 %, respectively; p < 0.0001). While contrast-enhanced CT detected a similar number of lesions to unenhanced MRI, it was clearly inferior to contrast-enhanced MRI (reader 1: p = 0.0117; reader 2: p = 0.0225). Of the T1-weighted scans performed, the dynamic and late T1-weighted GE exams contributed most to the increased lesion detection rate (reader 1: p = 0.0007; reader 2: p = 0.0037). The size of the smallest lesion detected by means of MRI was significantly larger in the pre-CM image sets than in the pre + post CM image sets (reader 1: p = 0.001; reader 2: p < 0.0001). Gd-BOPTA-enhanced MRI detected significantly smaller lesions than contrast-enhanced CT (reader 1: p = 0.0117; reader 2: p = 0.0925). Gd-BOPTA-enhanced MR imaging improves liver lesion detection significantly over unenhanced MRI and dynamic CT.

[Comparison of contrast behavior of gadobenate-dimeglumine and Gd-DTPA in intra-axial brain tumors. A double-blind randomized intraindividual cross-over study]. / Vergleich des Kontrastverhaltens von Gadobenat-Dimeglumine und Gd-DTPA bei intraaxialen Hirntumoren. Eine doppelblinde randomisierte intraindividuelle Cross-over-Studie.

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.

[Ultra-small superparamagnetic iron oxide particles: the signal behavior and relaxation times of the bone marrow after repeated i.v. application in the pig model at 1.5 tesla]. / Ultrakleine superparamagnetische Eisenoxidpartikel: Signalverhalten und Relaxationszeiten des Knochenmarks nach wiederholter i.v. Applikation im Schweinemodell bei 1,5 Tesla.

PURPOSE: Evaluation of the influence of an iron-containing MR contrast agent on the signal behaviour and the relaxation time of the bone marrow at 1.5 tesla after repeated doses. ANIMALS AND METHODS: 14 pigs received i.v. on days 1, 9, and 15 ultra-small (core diameter 6-8 nm) superparamagnetic iron oxide particles at doses of 20 (low dose = LD) or 200 mumol/kg body weight (high dose = HD). RESULTS: Following the first administration a dose-independent reduction in the bone-marrow signal intensity in the T2-weighted gradient-echo sequence (FFE) was observed together with a reduction in the T1 and T2 relaxation times. Following the second application there were no further signal-reductions in the HD-group; in contrast, there was a signal reduction in the LD-group, made possible by a signal recovery in the meantime. On the other hand, the relaxation times T1 and T2 were shortened after each administration of contrast medium. CONCLUSION: Nano-SIPS result at both doses in a signal reduction in the bone marrow. Only in the LD-group may repeated examinations with new contrast agent offer diagnostically sufficient images. Relaxometry shows a shortening of T1 as well as T2. This effect could be summed up after repeated doses. Almost no iron remained in the medullary space three weeks after i.v. administration of the contrast agent, which suggests mobilization and metabolization.

Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen. Safety and diagnostic efficacy.

PURPOSE: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. MATERIAL AND METHODS: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. RESULTS: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. CONCLUSION: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore the 1200 mg dose can be recommended in view of the risk-to-benefit ratio.

Extra- and intracellular accumulation of ultrasmall superparamagnetic iron oxides (USPIO) in experimentally induced abscesses of the peripheral soft tissues and their effects on magnetic resonance imaging.

UNLABELLED: The effects of ultrasmall superparamagnetic iron oxide (USPIO) particles on magnetic resonance imaging (MRI) were studied in an animal abscess model and the findings compared with microscopic sections of the abscesses. Staphylogenic abscesses of the right hind leg were induced in six Sprague-Dawley rats. The USPIO particles consisted of polyethylene-glycol-coated Fe3O4 with a mean size of 26 nm and were injected intravenously (i.v.), with three animals receiving a dose of 50 micromol/kg and three animals a dose of 150 micromol/kg. Before and immediately after i.v. administration of the particles, MR data were acquired with fast gradient-echo technique FLASH sequences applied over a period of 60 min. The Fe3O4-induced signal changes were registered in regions of interest (ROIs) placed over the margin and center of the abscess, over the perifocal granulation tissue and over corresponding sites of the contralateral healthy muscle. Microscopic sections were prepared using the conventional paraffin technique and, in part, a kryohistologic method before staining of the specimen with hematoxylin and Berlin-blue reaction. In addition to the mostly perfusion dependent loss of signal intensity within 8 s after injection, a signal reduction, which could be rather pronounced, was observed in the abscess margin and perifocal granulation tissue, with the underlying mechanism mainly attributed to extravasation and predominantly extracellular deposition of Fe3O4. CONCLUSION: The USPIO particles used in this study lead to a prolonged demarcation of abscesses in the peripheral soft tissues due to particle extravasation and accumulation in the periphery of the abscesses. Besides the known accumulation of already characterized USPIO in the RES of liver, spleen and lymph nodes the study could demonstrate ultrasmall iron oxide deposition (BY 818) in abscesses of the peripheral soft tissue.

Mechanisms of accumulation of small particles of iron oxide in experimentally induced osteosarcomas of rats: a correlation of magnetic resonance imaging and histology. Preliminary results.

RATIONALE AND OBJECTIVES: This study was conducted to investigate the distribution and kinetics of small particles of iron oxide in osteosarcoma-like tumors. METHODS: Magnetic resonance (MR) imaging was performed in eight athymic nude rats with an experimentally induced osteosarcoma of the right hind leg immediately after intravenous injection of a superparamagnetic iron oxide preparation. Five animals received 150 mumol iron oxide/ kg and three received 50 mumol iron oxide/kg. The iron oxide preparation consisted of polythylenglycol-coated particles with a core diameter of 6 to 8 nm. The MR images were correlated with histologic slices of the tumors. RESULTS: The tumors accumulated iron oxide rapidly. A marked decrease in signal intensity, preferentially along the periphery of the tumor, was followed by a partial return of the signal intensity within the first minute. The maximum signal decrement throughout the entire tumor exceeded 41% and 21% with one dose each of 150 mumol iron/kg and 50 mumol iron/kg, respectively. The rate of return depended on the injected dose and tumor area, with the signal intensity approaching the initial value before the injection of iron oxide after 45 minutes. Histologic correlation only showed deposition of contrast medium in the proliferative areas of the tumors, mainly confined to the tumor margin. In addition to a predominantly extracellular deposition, intracellular storage could be detected. CONCLUSIONS: The findings help to advance the understanding of the distribution and kinetics of intravenous-injected small particles of iron oxide in osteosarcoma-like tumors. A first-pass accumulation of iron oxide could be documented by MR imaging in the periphery of osteosarcomas. Due to sieving of iron oxide particles by liver, spleen, and bone marrow, the signal intensity at 45 minutes after the injection of iron oxide returned to 89% (150 mumol iron oxide/kg) and 95% (50 mumol iron oxide/kg) of the preinjection intensity.

Hepatocellular carcinoma: evaluation with dynamic and static gadobenate dimeglumine-enhanced MR imaging and histopathologic correlation.

PURPOSE: To analyze the potential of gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging for the characterization and diagnosis of hepatocellular carcinoma (HCC) by using static and dynamic sequences. MATERIALS AND METHODS: Twenty-eight patients with histopathologically proved HCC were evaluated with T1- and T2-weighted spin-echo and static and dynamic gradient-echo sequences before, during, and after intravenous administration of 0.1 mmol/kg gadobenate dimeglumine (0.5 mol/L). RESULTS: During the perfusion phase of the dynamic sequence, all 16 nodular well-differentiated HCC lesions showed a rapid increase in signal intensity 10-30 seconds after injection followed by a progressive decrease in signal intensity. The nine poorly differentiated HCC lesions showed no rapid increase in signal intensity. All eight large (> 3 cm), nodular, well-differentiated HCC lesions showed a hypointense rim before injection and both hypo- and hyperintense rims (double-ring sign) immediately after injection, compared with normal liver parenchyma. About 55 seconds after injection, substantial single-rim enhancement was detected in 21 of the 28 HCC lesions. CONCLUSION: Dynamic gadobenate dimeglumine-enhanced MR imaging allows improved characterization of HCC lesions, which show rapid increase in signal intensity during the early, arterial phase in well-differentiated HCC lesions and a double-ring sign in large well-differentiated nodular HCC lesions.

Pancreatic contrast enhancement with Mn-bis pyridoxal ethylene diamine diacetic acid and the influence of a hormonal stimulation of the pancreas in pigs.

RATIONALE AND OBJECTIVES: Pancreatic and hepatic contrast enhancement after different modes of administration of Mn-bis pyridoxal ethylene diamine diacetic acid (Mn-DPDP) and the influence of the hormones secretin and cholecystokinin on the uptake of this new contrast agent were studied by using magnetic resonance (MR) imaging and atomic absorption spectroscopy (AAS) examinations carried out on 13 young domestic pigs. METHODS: Mn-DPDP was administered either as bolus injection or 30-min infusion. The course of contrast enhancement was noted. MR imaging was carried out with or without pancreatic stimulation. The Mn content in pancreatic and hepatic tissue was analyzed by using AAS. RESULTS: Mn-DPDP caused a significant increase (66 +/- 40.1%) in pancreatic signal intensity, an increase in hepatic signal intensity (78 +/- 23.0%), and a significantly higher Mn content on tissue samples of both organs. The results showed a wide individual range. With infusion of Mn-DPDP, pancreatic enhancement was slower, with a peak at 82 +/- 34 min compared with 54 +/- 51 min following bolus injection. The Mn content of both hepatic and pancreatic tissue determined by AAS seemed to be higher after infusion. An incomplete washout of Mn after 24 hr was demonstrated. Hormonal stimulation of the pancreas further increased pancreatic signal intensity but did not influence hepatic contrast enhancement. CONCLUSION: Infusion is the method of choice for administering Mn-DPDP because it causes an increase in hepatic signal intensity but does not change pancreatic enhancement. Although pancreatic hormonal stimulation intensifies enhancement, the increase is not statistically significant, and this practice will not contribute to day-to-day clinical practice.

Experimental liver cancers: Mn-DPDP-enhanced rims in MR-microangiographic-histologic correlation study.

During both animal and clinical studies with manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP), enhanced rims around liver tumors on magnetic resonance (MR) images have been observed. To elucidate the origins of these rims and to assess their potential value in the differential diagnosis of liver masses, the authors studied 15 rats with induced hepatocellular carcinoma (HCC), 10 rats with implanted Novikoff hepatomas, and 11 rabbits with implanted VX2 carcinomas. A total of 69 primary and secondary liver cancers from these three animal models were studied. Mn-DPDP- and gadolinium tetraazacyclododecantetra acetic acid (DOTA)-enhanced MR images were compared. On the Mn-DPDP-enhanced images, 34 peritumoral rims of various patterns were displayed, all of which were exclusively related to the presence of highly malignant primary and secondary liver tumors. Peritumoral zones of malignant infiltration, surrounding parenchymal compression, and bile duct proliferation were seen to be the origin of these rims after comparison of MR images with the corresponding microangiograms and histologic specimens.

The uptake of manganese dipyridoxal-diphosphate by chemically induced hepatocellular carcinoma in rats. A correlation between contrast-media-enhanced magnetic resonance imaging, tumor differentiation, and vascularization.

OBJECTIVES AND RATIONALE: Negative enhancement of implanted liver tumors has been achieved in preclinical studies on manganese dipyridoxal-diphosphate (Mn-DPDP), a new hepatobiliary specific contrast agent for magnetic resonance imaging (MRI). The authors investigated the effects of Mn-DPDP on primary liver cancer and its possible mechanisms. METHODS: Magnetic resonance imaging was performed in 15 rats with chemically induced hepatocellular carcinoma (HCC) before and after Mn-DPDP injection. Both tumor-liver contrast-to-noise ratio and absolute tumor enhancement were evaluated and compared with the MRI results of a nonspecific contrast agent, gadolinium-DOTA, and correlated with corresponding microangiographic and histologic findings. RESULTS: Mn-DPDP injection led to a persistent positive enhancement in differentiated solid HCCs (22/23) with maximal conspicuity at 24 hours. Undifferentiated HCCs were all delineated by a prompt negative enhancement (20/20) with maximal conspicuity within 30 minutes.

Mn-DPDP enhanced MRI in experimental bile duct obstruction.

To assess both the effect of Mn-DPDP as a hepatobiliary-specific contrast agent in bile duct obstruction and the relative role of liver and kidney in the elimination of this agent from the body, an animal experiment was set up. Twelve rats were used and divided into three groups. In group 1 the common bile duct was ligated, in group 2 bile duct ligation was limited to one lobe, and group 3 served as control. Magnetic resonance T1-weighted SE images were obtained before and after the injection of 25 mumol/kg of Mn-DPDP during the first 2 h and at day 1, 2, 3, 4, and, in some animals, up to 21 days. In normal rats the absolute enhancement signal-to-noise ratio (S/N) versus time plots obtained from the liver after Mn-DPDP injection returned to precontrast values within 24 h. In the group with common bile duct ligation, important liver enhancement persisted up to 21 days. In the group with selective obstruction, liver intensity normalized after 3 days. The S/N plots from spleen, renal cortex, and obstructed liver lobe showed similarities in time course. The present data indicate that Mn elimination is strongly impaired in the presence of bile duct obstruction. Renal glomerular filtration is ineffective in eliminating Mn from the body. The persisting splenic and renal cortical enhancement suggests that free Mn or some Mn-DPDP metabolite either is strongly bound to plasma proteins and acts as a blood pooling agent and/or is uptaken by the splenic or renal parenchyma.

Mn-DPDP in MR imaging of pancreatic adenocarcinoma: initial clinical experience.

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP) was tested as a contrast agent for magnetic resonance imaging of pancreatic adenocarcinoma in 15 patients. At enhanced T1-weighted spin-echo (SE) and enhanced T1-weighted gradient-echo (GRE) imaging, statistically significant increases in signal-to-noise ratio (S/N) for the pancreas (21% and 92%, respectively) and contrast-to-noise ratio (C/N) (91% and 209%, respectively) were found. The C/N at enhanced T1-weighted SE imaging was superior to that at unenhanced imaging, including T2-weighted SE imaging (P = .001). Subjective image analysis showed that delineation of the pancreas and pancreatic tumors was clearly improved (P = .05) on enhanced T1-weighted SE and GRE images compared with on unenhanced T1- and T2-weighted images. The liver enhanced 19% at T1-weighted SE imaging and 90% at T1-weighted GRE imaging. There was a significantly higher S/N increase in hepatic parenchyma than in pancreatic tissue at enhanced T1-weighted GRE imaging (P = .0026) but not at enhanced T1-weighted SE imaging.