Orthotopic DA (RT1a) into Lewis (RT1l) rat kidney allografts and control Lewis-into-Lewis grafts were assessed by magnetic resonance imaging (MRI) and perfusion measurement after intravenous injection of a superparamagnetic contrast agent. MRI anatomical scores (range 1-6) and perfusion rates were compared with graft histology (rank of rejection score 1-6). Not only acute rejection, but also chronic events were monitored after acute rejection was prevented by daily cyclosporine (Sandimmune) treatment during the first 2 weeks after transplantation. In acute allograft rejection (n = 11), MRI scores reached the maximum value of 6 and perfusion rates were severely reduced within 5 days after transplantation; histology showed severe acute rejection (histologic score 5-6). In the chronic phase (100-130 days after transplantation), allografts (n = 5) manifested rejection (in histology cellular rejection and vessel changes), accompanied by MRI scores of around 2-3 and reduced perfusion rates. Both in the acute and chronic phases, the MRI anatomical score correlated significantly with the histological score (Spearman rank correlation coefficient rs 0.89, n = 30, P < 0.01), and perfusion rates correlated significantly with the MRI score or histological score (rs values between -0.60 and -0.87, n = 23, P < 0.01). It is concluded that MRI represents an interesting tool for assessing the anatomical and hemodynamical status of a kidney allograft in the acute and chronic phases after transplantation.
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 l 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 isof lurane-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.Activation of specific brain areas following a stimulation paradigm leads to a local change in the physiological parameters of the nervous tissue which may be detected by using functional magnetic resonance imaging (fMRI) techniques (1, 2). Two mechanisms responsible for changes of the fMRI signal intensity in the activated areas have been postulated: (i) Stimulation of a brain area increases local perfusion. Depending on the MRI measurement technique, this change in local cerebral blood flow may lead to either an increase or a decrease in signal. (ii) Brain activation causes alteration in the degree of blood oxygenation. Venous blood contains a higher concentration of oxygenated hemoglobin during neuronal activation, which can be measured as a signal increase in susceptibility-weighted (gradient-recalled echo) experiments yielding blood oxygenation level-dependent (BOLD) contrast images (3). The signal increase is due to a prolongation of the T* 2 relaxation time caused by a decreased concentration of paramagnetic deoxyhemoglobin. Taking all these facts together, fMRI provides sensitive measures for the characterization of functional changes in the central nervous system without the need of exogenous contrast material.Although the main focus of fMRI studies is human brain mapping, they are also of great interest in experimental animal re...
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.
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