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Biomedical subjects

N Beckmann

Publications and source records attributed to N Beckmann.

At least 19 recordsLinked to original sources

MRI and ultrasonographic detection of morphologic and hemodynamic changes in chronic renal allograft rejection in the rat.

PURPOSE: The purpose of this study is to describe the sonographic, MRI, and histopathologic findings in a rat model of chronic renal allograft rejection. MATERIALS AND METHODS: Allogeneic renal grafts (male DA kidney into male Lewis rat with unilateral nephrectomy, N = 27) and syngeneic renal grafts (male Lewis kidney into male Lewis rat, N = 19) were examined serially with ultrasound, MRI, and histology. RESULTS: Nonparametric Spearman rank correlation showed significance between the histologic score and the following parameters: the MRI score (r(s) = 0.91, P < 0.01, N = 46), the ultrasound score (r(s) = 0.9, P < 0.01, N = 46), the power Doppler score (r(s) = 0.86, P < 0.01, N = 46), and the MRI perfusion (r(s) = -0.80, P < 0.01, N = 45). Positive correlations were also found between the MRI volume estimations (graft r(s) = 0.49, P < 0.01, N = 46; native r(s) = 0.59, P < 0.01, N = 46), and the ultrasound volume estimations (graft r(s) = 0.39, P < 0.01, N = 45; native r(s) = 0.64, P < 0.01, N = 46) as well as with actual graft weight. CONCLUSIONS: This study shows that both MRI and ultrasound can provide complementary, accurate information compared to histology in regard to the alterations in anatomy and hemodynamic changes associated with chronic allograft nephropathy.

Animals↗

Pulmonary edema induced by allergen challenge in the rat: noninvasive assessment by magnetic resonance imaging.

The course of pulmonary edema formation after an intratracheal (i.t.) instillation of ovalbumin was followed noninvasively by magnetic resonance imaging (MRI) in actively sensitized Brown Norway (BN) rats. Changes in edema volume assessed by MRI mimicked the results from the analysis of the number and activation of inflammatory cells recovered from the broncho-alveolar lavage (BAL) fluid. Rats treated with budesonide did not develop edema following challenge with ovalbumin, and these animals showed a significant decrease in BAL fluid inflammatory cell numbers and eosinophil peroxidase and myeloperoxidase activities. Thus, following lung edema formation by MRI provides a reliable means of assessing pulmonary inflammation after allergen challenge. Unlike BAL fluid analysis, which requires killing animals at each time point, this method is noninvasive. MRI could be of importance for the noninvasive profiling of anti-inflammatory drugs in animal models of asthma and in the clinic. Magn Reson Med 45:88-95, 2001.

Allergens↗

From anatomy to the target: contributions of magnetic resonance imaging to preclinical pharmaceutical research.

In recent years, in vivo magnetic resonance (MR) methods have become established tools in the drug discovery and development process. In this article, the role of MR imaging (MRI) in the preclinical evaluation of drugs in animal models of diseases is illustrated on the basis of selected examples. The individual sections are devoted to applications of anatomic, physiologic, and "molecular" imaging providing, respectively, structural-morphological, functional, and target-specific information. The impact of these developments upon clinical drug evaluation is also briefly addressed. The main advantages of MRI are versatility, allowing a comprehensive characterization of a disease state and of the corresponding drug intervention; high spatial resolution; and noninvasiveness, enabling repeated measurements. Successful applications in drug discovery exploit one or several of these aspects. Additionally, MRI is contributing to strengthen the link between preclinical and clinical drug research.

Animal Diseases↗

Current awareness.

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books, Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5 Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver, Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

Magnetic Resonance Spectroscopy↗

Non-invasive, quantitative assessment of the anatomical phenotype of corticotropin-releasing factor-overexpressing mice by MRI.

High resolution magnetic resonance imaging (MRI) was applied to quantify alterations in thymus and adrenal volumes, as well as body fat in genetically engineered corticotropin-releasing factor (CRF)-overexpressing mice. When compared to the organs in age-matched wild-type animals, the adrenals in CRF-overexpressing male mice were significantly enlarged and the thymus volume in females was significantly smaller. The fat content was significantly larger in CRF-overexpressing mice. The anatomical alterations observed in the MRI studies were in perfect line with post-mortem data (weights of organs). Furthermore, the observed interstrain differences are in agreement with recently published data on (i) the effect of continuous, intraventricular infusion of CRF in rats and (ii) the presence of atrophic adrenals in CRF-knockout mice. The present studies demonstrate that MRI can provide reliable measures of relatively small structures such as the adrenal glands and the thymus in mice. This makes MRI an attractive, non-terminal tool to monitor in laboratory animals, including transgenic mice, the consequence of continuous stress on relevant organs.

Adipose Tissue↗

MRI of lung parenchyma in rats and mice using a gradient-echo sequence.

Signal of lung parenchymal tissue from the living rat and mouse lung was detected at 4.7 T with a good signal-to-noise ratio and motion-suppressed artifacts using a short TE gradient-echo sequence. Neither cardiac nor respiratory gating were applied, and animals respired freely during data collection. Mean T(2)* relaxation times of parenchyma in the anterior, middle and posterior regions of both lungs ranged between 403 and 657 micros and 397 and 751 micros, respectively for the rat and mouse. For the rat in the prone position, there was a gradient in T(2)* values, from the posterior to the anterior regions of both lungs. In the supine position, however, T(2)* values were larger in the posterior and in the anterior portions. For the mouse in both prone and supine positions, there was a tendential gradient in T(2)* from the anterior to the posterior portions. The robustness of the approach renders it well suited for routine applications, e.g. in pharmacological studies concerning asthma models in small rodents. The method was applied to lung inflammation models involving challenge with ovalbumin or lipopolysaccharide.

Animals↗

The role of magnetic resonance imaging and spectroscopy in transplantation: from animal models to man.

Critical success factors in solid organ and vascular transplantation are the assessment of graft status/viability as well as stringent monitoring of transplant recipients, preferentially using noninvasive techniques. This review addresses the application of magnetic resonance imaging (MRI) and spectroscopy (MRS) in the field of transplantation. The first section is devoted to the description of the main MR techniques used for monitoring the status of the graft noninvasively. Subsequently, the role of MRI/MRS in the analysis of the viability of organs for transplantation is discussed. Since chronic rejection remains a major difficulty, development of new therapies is still ongoing. Thus, the third part is devoted to the use of MRI/MRS for monitoring graft rejection in animal models of transplantation. This is followed by a discussion of clinical studies of transplantation involving MRI/MRS. Finally, a general appraisal is made on available imaging techniques for the non-invasive characterization of grafts in situ, highlighting the role of MR methods in the field of transplantation.

Animals↗

High resolution magnetic resonance angiography non-invasively reveals mouse strain differences in the cerebrovascular anatomy in vivo.

High resolution magnetic resonance angiography (MRA) revealed highly variable arterial cerebrovascular structures in mice from different strains and within the same strain. C57Black/6 mice presented small unilateral anastomoses between the posterior cerebral and the superior cerebellar arteries. Well developed, either unilateral or bilateral, posterior communicating arteries (PcomA) were detected on CBA mice. The arterial structure of CD1 mice ranged from no detectable anastomoses to well developed, unilateral PcomAs. SV-129 mice showed significantly shorter middle cerebral arteries compared to the other strains, and clear bilateral anastomoses between the posterior cerebral and the superior cerebellar arteries. Because of its non-invasiveness, MRA may be of importance in murine stroke studies by enabling the selection of animals and/or the side for performing the surgical intervention, and the verification of its success. Magn Reson Med 44:252-258, 2000.

Animals↗

In vivo magnetic resonance methods in pharmaceutical research: current status and perspectives.

In the last decade, in vivo MR methods have become established tools in the drug discovery and development process. In this review, several successful and potential applications of MRI and MRS in stroke, rheumatoid and osteo-arthritis, oncology and cardiovascular disorders are dealt with in detail. The versatility of the MR approach, allowing the study of various pathophysiological aspects in these disorders, is emphasized. New indication areas, for the characterization of which MR methods have hardly been used up to now, such as respiratory, gastro-intestinal and skin diseases, are outlined in a subsequent section. A strength of MRI, being a non-invasive imaging modality, is the ability to provide functional, i.e. physiological, readouts. Functional MRI examples discussed are the analysis of heart wall motion, perfusion MRI, tracer uptake and clearance studies, and neuronal activation studies. Functional information may also be derived from experiments using target-specific contrast agents, which will become important tools in future MRI applications. Finally the role of MRI and MRS for characterization of transgenic and knock-out animals, which have become a key technology in modern pharmaceutical research, is discussed. The advantages of MRI and MRS are versatility, allowing a comprehensive characterization of a diseased state and of the drug intervention, and non-invasiveness, which is of relevance from a statistical, economical and animal welfare point of view. Successful applications in drug discovery exploit one or several of these aspects. In addition, the link between preclinical and clinical studies makes in vivo MR methods highly attractive methods for pharmaceutical research.

Animals↗

Magnetic resonance angiography of the rat cerebrovascular system without the use of contrast agents.

We describe and discuss the application of three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) to visualize non-invasively the cerebral vasculature of the rat. MR angiograms of healthy spontaneously hypertensive rats were obtained without the use of contrast agents. Total imaging time ranged from 1 to 50 min for a 3D data set. The influences of the data matrix and the inflow delay on the image quality and the total imaging time are assessed and discussed. Varying the inflow delay yielded in addition semiquantitative information on hemodynamics. The method was applied to obtain angiograms in rat models of permanent and temporal middle cerebral artery occlusion. Occlusion and reopening of the vessel could easily be verified by MRA. However, after reperfusion a slight reduction in blood flow was observed.

Animals↗

High-resolution three-dimensional magnetic resonance imaging for the investigation of knee joint damage during the time course of antigen-induced arthritis in rabbits.

OBJECTIVE: To investigate the efficacy of high-resolution 3-dimensional magnetic resonance imaging (3-D MRI) with gadolinium contrast agent enhancement in monitoring soft tissue and hard tissue changes during the course of antigen-induced arthritis in rabbits, comparing the images with the final histologic outcome. METHODS: Arthritis was induced by intraarticular injection of methylated bovine serum albumin into rabbits that had been presensitized to the same antigen. MRI was carried out before and on predetermined days after the onset of inflammatory arthritis, up to day 60. At each time point, 3-D gradient-echo images were acquired. At the end of the study, the knee joints were processed for histologic study. RESULTS: Time-related inflammatory changes, such as soft tissue swelling, were seen initially, followed by a reduction in the acute swelling and a progression to hard tissue damage at later time points. The final 3-D data sets were then used to compare MR images with the histologic sections. The knee joints were sectioned in the sagittal, coronal, or transverse direction. Comparison of final images and histologic features at day 60 enabled a more complete interpretation of the MR images, allowing direct correlation of joint damage observed using the MRI technique with that seen in the final histologic analysis. CONCLUSION: Qualitative information derived from MR images correlated extremely well with histologic findings. These results indicate the great potential of MRI for noninvasive investigation of drug effects in this model of arthritis.

Animals↗

High-resolution magnetic resonance angiography of the mouse brain: application to murine focal cerebral ischemia models.

Three-dimensional time-of-flight high-resolution magnetic resonance angiography was applied to visualize the cerebral vasculature of the mouse brain. In normal mice, angiograms of good quality, showing the essential details of the arterial cerebrovascular anatomy, could be obtained in only 2.5 min without the use of contrast agents. Signals from slowly flowing blood, e.g., in veins, could also be detected after administration of a blood pool contrast agent. The technique was applied to mouse models of permanent and transient brain ischemia, involving the occlusion of the middle cerebral artery. High-resolution magnetic resonance angiography proved to be a very useful tool for verifying the success of the occlusion in these models.

Animals↗

Effects of Sandimmune neoral on collagen-induced arthritis in DA rats: characterization by high resolution three-dimensional magnetic resonance imaging and by histology.

In the present work the time course of collagen-induced arthritis and the effect of Sandimmune Neoral in this model of arthritis were followed in the rat over an extended period of time (70 days) using high resolution three-dimensional (3D) magnetic resonance imaging (MRI). High resolution 3D gradient-echo (TR = 100 ms; TE = 3.8 ms) images with a voxel size of 94 x 81 x 60 micron3 were acquired from the hind paw of DA rats (n = 21) at various time points after injection of type II bovine collagen into the tail. Eleven rats were treated with Neoral (15 mg/kg/day p.o. together with vehicle) for 42 days starting at day 14 after collagen injection. The remaining controls received vehicle. Pathomorphological changes associated with the collagen-induced arthritic process, e.g., increase of joint space and cartilage and bone erosion, could be observed in vivo in the control group. In contrast, no changes in the joint architecture were detected in Neoral-treated animals. Indeed, Neoral showed strong anti-inflammatory effects and marked protection against cartilage and bone destruction in this model. Qualitative information derived from the MR images correlated significantly with histological findings.

Administration, Oral↗

Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging.

Changes in metabolism and local circulation occur in the spinal cord during peripheral noxious stimulation. Evidence is presented that this stimulation also causes signal intensity alterations in functional magnetic resonance images of the spinal cord during formalin-induced pain. These results indicate the potential of functional magnetic resonance imaging in assessing noninvasively the extent and intensity of spinal cord excitation in this well characterized pain model. Therefore, the aim of this study was to establish functional magnetic resonance imaging as a noninvasive method to characterize temporal changes in the spinal cord after a single injection of 50 microl of formalin subcutaneously into the hindpaw of the anesthetized rat. This challenge produced a biphasic licking activity in the freely moving conscious animal. Images of the spinal cord were acquired within 2 min, enabling monitoring of the site and the temporal evolution of the signal changes during the development of formalin-induced hyperalgesia without the need of any surgical procedure. The time course of changes in the spinal cord functional image in the isoflurane-anesthetized animal was similar to that obtained from behavioral experiments. Also, comparable physiological data, control experiments, and the inhibition of a response through application of the local anesthetic agent lidocaine indicate that the signal changes observed after formalin injection were specifically related to excitability changes in the relevant segments of the lumbar spinal cord. This approach could be useful to characterize different models of pain and hyperalgesia and, more importantly, to evaluate effects of analgesic drugs.

Animals↗