bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism and pharmacokinetics of MnDPDP in man
Authors: Toft K. G. , Hustvedt S. O. , Grant D. , Martinsen I. , Gordon P. B. , Friisk G. A. , Korsmo Å. J. , Skotland T. 
Published: January 2010

Purpose: To study the metabolism and pharmacokinetics of mangafodipir trisodium injection, 0.01 mmol/ml (Teslascan), in healthy male volunteers. Material and Methods: Eight volunteers received mangafodipir trisodium as an infusion over 20 min, and 5 received it as an injection (≤ min). Both groups received 5 and 10 μmol/kg b.w. with a wash-out period of 3 weeks between doses. Metabolites were measured in plasma, total manganese and zinc were measured in plasma and urine and total manganese was measured in faeces. Results: The parent compound MnDPDP (manganese dipyridoxyl diphosphate) and 5 metabolites; MnDPMP (manganese dipyridoxyl monophosphate), MnPLED (manganese dipyridoxyl ethylenediamine) and the corresponding zinc compounds ZnDPDP, ZnDPMP and ZnPLED, were detected in plasma. ZnPLED was the only detectable metabolite 8 h after dosing. The apparent volume of distribution of manganese exceeded the interstitial body fluids. The volume of distribution of the ligand indicated distribution to the extracellular fluid only, with the plasma clearance close to the glomerular filtration rate. The manganese was incompletely excreted during the 4 days after treatment with the major part in faeces and less than 20% of the dose in the urine. Conclusion: Dephosphorylation and simultaneous transmetallation with zinc are the main metabolic pathways of MnDPDP in man.
Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration
Authors: Hustvedt S. O. , Grant D. , Southon T. E. , Zech K. 
Published: January 2010

Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14C-MnDPDP or 54MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moiety is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moiety is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. Conclusion: The ligand does not appear to facilitate the transport of Mn into any organ except the kidney for subsequent excretion, and it reduces distribution to the heart. The Mn is taken up by those organs indicated for MR imaging, primarily liver and pan-creas.
Comparison of manganese biodistribution and MR contrast enhancement in rats after intravenous injection of MnDPDP and MnCl2
Authors: Ni Y. , Petré C. , Bosmans H. , Miao Y. , Grant D. , Baert A. L. , Marchal G. 
Published: January 2010

Purpose: To compare the time course of the MR enhancing properties and biodistri-bution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate (MnDPDP) or Mn chloride (MnCl2). Material and Methods: Twenty-four adult rats were injected i.v. with 5 μmol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline. High resolution T1-weighted MR imaging was performed during early (10 min), mid (2 h) and late (24 h) phases after injection. Mn concentrations in major organs were measured by using an ICP-AES technique, and correlated with MR findings. Results: Variable degrees of signal enhancement of major organs observed in MR images corresponded with the amount of Mn uptake after injection of MnDPDP or MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this was reflected in a difference in signal intensity (SI) in the MR images. At 2 h, the Mn content and SI in the major organs were similar with both MnDPDP and MnCl2. An overall Mn clearance was achieved at 24 h without any important organ retention, with kidney excretion of Mn seen only with MnDPDP. Conclusion: With both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared to MnCl2 may account for the favourable cardiovascular safety of the contrast agent. These data contribute to an understanding of SI enhancement by MnDPDP, and are consistent with other studies showing that at a dose of 5 μmol/kg, MnDPDP can be safely used as a potent MR organ-specific contrast agent.
Clinical implications of studies with MnDPDP in animal models of hepatic abnormalities
Authors: Ni Y. , Marchal G. 
Published: January 2010

Mangafodipir trisodium (manganese dipyridoxal diphosphate or MnDPDP) has been introduced as a hepatobiliary MR contrast agent (Teslascan). Its potential to assist in the characterisation of focal liver lesions, the diagnosis of local and global obstructive cholestasis and the evaluation of hepatic function in diffuse liver diseases has been explored in multiple pre-clinical experiments with appropriate animal models. The prompt negative contrast enhancement and delayed peritumoural rim-enhancement seen after i.v. injection of MnDPDP are 2 typical features of primary and secondary liver tumours with high malignancy, while the persistent positive enhancement is a sign of liver tumours of well preserved hepatocytic nature. Liver with local and total biliary obstruction can be visualized in MnDPDP-enhanced MR images as a region with prolonged signal enhancement. This agent could also be used to non-invasively evaluate diffuse liver diseases of different causes. In the present paper, we review the experimental data in the literature, provide some unpublished results and discuss the potential impact on the clinical use of MnDPDP in the liver. We conclude that MnDPDP is a promising MR liver contrast agent for the detection and characterisation of focal and diffuse liver diseases.
Cardiovascular safety of MnDPDP and MnCl2
Authors: Jynge P. , Brurok H. , Asplund A. , Towart R. , Refsum H. , Karlsson J. O. G. 
Published: January 2010

Purpose: To investigate the apparent discrepancy between expected basic physiological responses at the cellular level and the in vivo behaviour of both MnDPDP and MnCl2 adminstered i.v. prompted parallel investigations of these substances. Material and Methods: Studies were performed in isolated perfused rat hearts, isolated bovine mesenteric arteries, conscious dogs, and dogs with acute ischaemic heart failure. Results: These studies confirmed that Mn++ at high concentrations acted as a calcium antagonist inducing negative inotropy. Mn++ at low concentrations was an effective su-peroxide scavenger, conserving nitric oxide and facilitating vasodilation. Mn++ maintained or elevated heart rate (HR) and blood pressure (BP), and did not worsen existing cardiac failure. MnDPDP was about 10 times less potent than MnCl2 in eliciting these cardiovascular responses. Conclusion: The ex vivo properties of Mn++, inducing vasodilation and negative inotropy, are counter-balanced in vivo through the action of 2 mechanisms: extensive plasma protein binding reducing active M++, and the release of catecholamines which maintain or even raise HR and BP. Taken together with pharmacokinetic factors, including maximal plasma concentrations in humans given the recommended 5 μmol/kg dose, it is concluded that MnDPDP in normal clinical use represents no safety risk to the cardiovascular system.
Cardiovascular effects of MnDPDP and mncl2 in Dogs with Acute Ischaemic Heart Failured
Authors: Karlsson J. O.G. , Mortensen E. , Pedersen H. K. , Sager G. , Refsum H. 
Published: January 2010

Purpose: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2. Material and Methods: The study involved slow i.v. infusion of either 10,60 and 300 μmol/kg of MnDPDP, or 1, 6 and 30 μmol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 ± 10 μm) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac ouput; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines. Results: Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 μmol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 μmol/kg MnCl2. Conclusion: The present study suggests that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.
General toxicology of MnDPDP
Authors: Larsen L. E. , Grant D. 
Published: January 2010

Purpose: To investigate the general toxicology of mangafodipir trisodium (MnDPDP, Teslascan). Material and Methods: Studies were performed in accordance with standard methods and in compliance with regulations current at the time of conduct. Results: Single-dose studies in rodents and dogs showed that MnDPDP was tolerated at doses of approximately 2000 μmol/kg, approximately 400 times a single imaging dose of 5 μmol/kg. The single dose tolerance of MnDPDP was approximately 10 times greater than MnCl2. A good safety profile of MnDPDP was also shown in repeat-dose studies (3 weeks), in which the no-observed-adverse-effect level for the rat, monkey and dog was 116, 29 and 10 μmol/kg, respectively. The local tolerance studies indicated that no adverse local tissue reactions are likely to occur after i.v. injection. Other studies indicate that accidental spillage of MnDPDP onto the skin is not expected to lead to significant systemic exposure, or to local irritation or hypersensitivity. MnDPDP was not genotoxic in a battery of several different tests. Conclusion: MnDPDP was shown to have a good safety profile suitable as an hepatobiliary MR contrast agent for i.v. administration.
Physicochemical characterisation of mangafodipir trisodium
Authors: Tirkkonen B. , Aukrust A. , Couture E. , Grace D. , Haile Y. , Holm K. M. , Hope H. , Larsen Å. , Lunde H. Sivertsen , Sjøgren C. E. 
Published: January 2010

Purpose: To determine the structure and various physicochemical properties of man-gafodipir (MnDPDP) trisodium, the active ingredient of Teslascan, a new organ-specific contrast medium for MR imaging. Material and Methods: The structure of MnDPDP trisodium crystals was determined by X-ray crystallography. The possible existence of polymorphism in MnDPDP trisodium was evaluated by powder X-ray diffraction, optical microscopy, thermal analysis and IR spectroscopy. In addition, various spectroscopic techniques and physicochemical measurements were used for characterisation of MnDPDP trisodium. Results: The crystallographic data obtained for MnDPDP trisodium show that the general core structure of the MnDPDP anion is similar to that seen in related substances. The metal coordination geometry is a distorted octahedron defined by 2 phenolate oxygens, 2 carboxylate oxygens and 2 amine nitrogens. The unit cell contains 2 MnDPDP anions, 6 sodium ions and 50 water molecules. The various spectroscopic data are consistent with the structure determined by X-ray crystallography. The product (Teslascan) has low viscosity, is isotonic with blood and has a physiological pH. Conclusion: MnDPDP trisodium is a crystalline, hygroscopic solid which is readily soluble in water. No evidence of polymorphism was seen in the samples studied.
Cerebral CT angiography in the diagnosis of acute subarachnoid hemorrhage
Authors: Lenhart M. , Bretschneider T. , Gmeinwieser J. , Ullrich O.-W. , Schlaier J. , Feuerbach S. 
Published: January 2010

Purpose: To evaluate the usefulness of CT angiography (CTA) in the detection of intracranial aneurysms in patients with acute subarachnoid hemorrhage (SAH). Material and Methods: In 53 patients with nontraumatic SAH a helical contrast-enhanced CTA was performed. CTA data were reconstructed with maximum intensity projection (MIP). Each patient underwent selective arteriography of the cerebral vessels (as the gold standard). CTA (axial images and MIP reconstructions) and arteriography were evaluated separately and their diagnostic information was compared. Results: In 14 of the 53 patients neither CTA nor angiography showed a vascular malformation. In the remaining 39 patients, angiography demonstrated a total of 51 aneurysms ranging in size from 3 mm to 16 mm. CTA missed one of these aneurysms, which was located at the internal carotid artery. 3-D CT reconstruction was slightly superior to arteriography in the demonstration of the neck, shape and direction of the aneurysms. Partial thrombosis of 3 aneurysms was demonstrated only by CTA. Conclusion: Although CTA cannot replace cerebral arteriography in the diagnostic work-up of acute SAH, it proved to be helpful in demonstrating the topographic anatomy of cerebral aneurysms and surrounding structures.
MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes
Authors: Yucel T. , Saatci I. , Sennaroglu L. , Cekirge S. , Aydingoz U. , Kaya S. 
Published: January 2010

Purpose: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes (“N0 neck”) who have squamous cell carcinoma of the head and neck region. Material and Methods: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. Results:) MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of the 20 necks, the rate of clinically occult disease being 35%, and 4 of them had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. Conclusion: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of “N0 neck”).
Solid nonpalpable breast lesions
Authors: Ciatto S. , Del Turco M. Rosselli , Ambrogetti D. , Bravetti P. , Catarzi S. , Morrone D. , Cariaggi M. P. 
Published: January 2010

Purpose: To evaluate the contribution of guided fine-needle aspiration cytology in reducing unnecessary biopsies of benign solid nonpalpable breast lesions with low suspicion of malignancy at mammography. Material and Methods: An evaluation was made of a consecutive series of 2444 solid nonpalpable breast lesions detected by mammography and undergoing guided (sonography or stereotaxy) fine-needle aspiration cytology. Surgical biopsy was made in the presence of strong suspicion of malignancy at mammography and/or of abnormal cytology. Results: The sensitivity was 96.7% and the specificity 77.7% (average follow-up 2.77 years). False-negative/inadequate cytology associated with low suspicion of malignancy at mammography resulted in a diagnostic delay in 27 cancer cases (invasive 20, intraductal 7). On the other hand, cytology led to surgical biopsy in 53 cancer cases which might not otherwise have been biopsied because of low radiological suspicion of cancer. Surgical biopsy of all cases, to avoid diagnostic delays, would have increased the benign biopsy rate by a factor of 4.5, with a rise in the benign: malignant biopsy ratio from 0.44:1 to 1.93:1. Conclusion: Stereotaxy- or ultrasound-guided fine-needle aspiration cytology of nonpalpable mammographic abnormalities can achieve a sharp reduction in unnecessary benign biopsies in cases of low suspicion of malignancy at mammography.
Air enema used in the evaluation of acute colitis
Authors: Laveskog A. , Måre K. , Granqvist S. , Ståhlberg D. 
Published: January 2010

Purpose: The purpose of this study was to evaluate air enema as a method of assessing acute colitis. Material and Methods: Twenty-seven patients with symptoms of acute colitis underwent plain abdominal radiography, air enema, and colonoscopy within 48 h. The films were evaluated by 3 observers with different levels of experience, both independently and together, and the results were then compared to the findings at endoscopy. Results: Air enema visualized a greater part of the colon than plain abdominal radiography. When air enema was compared to endoscopy as the reference, it showed good correlation, with a positive predictive value of 92% (sensitivity 62%, specificity 85%). Evaluation of the rectum was less accurate, a finding that emphasized the importance of rigid sigmoidoscopy. Conclusion: Air enema is a useful diagnostic method in acute colitis, it is easily performed and tolerated well with no observed complications. It is also easy to interpret, as shown by a high level of agreement (k=0.67) among the 3 independent observers with very different levels of experience.
MR findings in cases of suspected impacted fracture of the femoral neck
Authors: Stiris M. G. , Lilleås F. G. 
Published: January 2010

Purpose: To evaluate MR imaging of the hip in patients with a clinically suspected impacted fracture of the femoral neck in cases where conventional plain films show negative or equivocal findings. Material and Methods: Twenty-seven such patients were prospectively examined by MR imaging with a 1.0 T unit, within 24 hours of admittance to hospital. A coronal T1-weighted turbo spin-echo sequence (n=27>), and a coronal STIR sequence (n=25) or a coronal T2-weighted turbo spin-echo fat saturation sequence (n=2) were used. The evaluations were made by 2 radiologists with experience in musculoskeletal radiology. Results: There were 6 patients with a pertrochanteric fracture, 2 without and 4 with slight displacement. Five patients had an impacted fracture of the femoral neck, and 3 had a fracture of the superior pubic bone. Of 2 patients with advanced arthrosis, I had an impacted femoral neck fracture and the other a nondisplaced intertrochanteric fracture. There was 1 patient who had sustained a nondisplaced acetabular fracture with increased joint fluid and muscle contusions. Three patients had muscle contusions only. Two patients had bone marrow contusions only, while 2 others with advanced cox-arthrosis had increased joint fluid only. Three patients showed normal findings. Our findings led to emergency surgery in 13 cases, and conservative measures directed to the specific MR findings in 14 patients. Conclusion: MR imaging should be the first modality of choice in examining patients with a clinically suspected impacted fracture of the femoral neck where conventional films show negative or equivocal findings.
Sonographic evaluation of hip effusion in children
Authors: Chan Y. L. , Cheng J. C. Y. , Metreweli C. 
Published: January 2010

Purpose: To assess the difference in the sonographic appearance of hip effusions when the hip was placed in the extended and abducted position as compared to a neutral position. Material and Methods: Twenty-one consecutive children (aged 2–14 years) with hip pain or limping were examined for hip effusions by means of ultrasound. The capsule-femoral-neck distance, the presence of joint fluid, and the shape of the anterior capsule were compared in hips in slight extension and abduction with those in hips in a neutral position. Results: Of the 11 positive hip effusions, the maximal distance between the capsule and femoral neck was significantly larger (p < 0.005) in the extended and abducted hip position than in the neutral hip position, with a mean difference of 1.6 mm. Convex bulging of the anterior capsule was more confidently diagnosed in 3 hip effusions in the extended and abducted hip, and better visualization of fluid between the capsule and femoral neck was achieved in 4 joints in this posture. Conclusion: The study demonstrated an improvement in the sonographic detection of hip effusion in the extended and abducted postition compared to the neutral position.
Grase: Ultra-fast turbo gradient spin-echo sequence
Authors: Trattnig S. , Breitenseher M. , Kontaxis G. , Helbich T. , Rand T. , Imhof H. 
Published: January 2010

Purpose: Ultra-fast gradient and spin-echo (GRASE) imaging is a hybrid of turbo spin-echo (TSE) and echo-planar imaging (EPI). One scan consists of several spinechoes (SEs) (turbo factor, TF), each of which consists of a number of gradient echoes (EPI factor, EF). The aim of our study was to evaluate different combinations of TF and EF in GRASE imaging and to test its usefulness in musculoskeletal imaging. Material and Methods: On a 1.0 T MR unit, 11 GRASE sequences with different combinations of TF and EF (TR/TE 2150/120 ms) were evaluated in phantom studies with respect to signal-to-noise (S/N) ratio, nonuniformity of images, and geometrical distortion. From this study, the optimal GRASE-sequence was applied to 25 patients with different joint pathologies and compared to a T2-weighted TSE sequence (TR/TE 2855/130 ms). Lesion visualization, conspicuity, overall image quality, and artifacts were qualitatively analyzed by two observers independently of each other. Results: With respect to S/N ratio, signal nonuniformity, and geometrical distortion, the GRASE sequence with TF/EF 7/3 (S/N 47; signal nonuniformity 11.7%; distortion 1 pixel) proved to be superior to the other GRASE sequences within a scanning time of less than 120s. In a clinical study, the GRASE sequence proved superior to T2-weighted TSE (without fat suppression) in the visualization of bone-marrow and soft-tissue lesions ( p < 0.001) and ligamentous injuries, although the image quality was inferior.