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.

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.

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.

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.

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.

Magnetic resonance imaging for the evaluation of rejection of a kidney allograft in the rat.

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.

Noninvasive 3D MR microscopy as a tool in pharmacological research: application to a model of rheumatoid arthritis.

Magnetic resonance microscopy (MRM) was applied to noninvasively image skeletal structures in the hindpaw of the live rat to characterize the progression of a heterologous type II collagen-induced arthritic process. Using a resonator, with optimized filling factor, three-dimensional (3D) gradient-echo images with voxel dimensions of 94 x 81 x 60 micron3 were acquired in 54.6 min. Three-dimensional MRM reduces the slice positioning problem, which is critical in longitudinal studies. Moreover, due to the much smaller slice thickness of images derived from 3D data sets, partial volume effects are less pronounced than in corresponding 2D images. Distinct pathomorphological changes associated with the collagen-induced arthritic process (e.g., increase of metatarsophalangeal joint space, and bone and cartilage erosion) could thus be analyzed under in vivo conditions.

Comparative effects of the two endothelin ETA receptor antagonists, BQ-123 and FR139317, on endothelin-1-induced contraction in guinea-pig iliac artery.

The effects of two recently introduced endothelin ETA receptor antagonists, BQ-123 and FR139317, were investigated and compared in guinea-pig isolated iliac artery. Endothelins and sarafotoxins induced contraction of guinea-pig iliac artery with a pharmacological profile characteristic of the ETA receptor. The rank order of agonist potency was (mean EC50 values, nM): endothelin-1 (11.7) > or = endothelin-2 (14.9) > or = vasoactive intestinal contractor (19.5) > sarafotoxin S6b (49.8) > or = [Ala3,11]endothelin-1 (55.0) > sarafotoxin S6a (> 100) > endothelin-3 (> or = 1000). The C-terminal hexapeptide, endothelin-(16-21), sarafotoxin S6c and sarafotoxin S6d were neither agonists nor antagonists at concentrations up to 10, 3 and 1 microM, respectively. Both FR139317 (1-10 microM) and BQ-123 (0.1-1 microM) surmountably antagonized the effects of endothelin-1. Schild analysis suggested competitive antagonism for FR139317 (Schild slope 1.32 +/- 0.21, pA2 5.82 +/- 0.16, n = 5), but not for BQ-123 (Schild slope 0.28 +/- 0.08, n = 5), which was however more potent (apparent pKB 6.6-7.2) than FR139317. The potency of FR139317 was particularly low with respect to the reported affinity for ETA receptors, suggesting heterogeneity among ETA receptors. Thus, the endothelin receptor present in guinea-pig iliac artery has the following features: (1) rank order of agonist potencies of the ETA type; (2) low potency of FR139317 and (3) non-competitive antagonism by BQ-123.