Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model

The aim of this study was to validate an experimental model designed to distinguish four categories of contrast agents, non specific agents (NDA, Gd-DOTA) characterized by rapid and total extravasation; low diffusion agents (LDA, P760) characterized by delayed extravasation; and rapid (P792) and slow clearance (P717) blood pool agents (BPA) characterized by limited extravasation. Plasma and peritoneal gadolinium concentrations were simultaneously measured after intravenous injection of various contrast agents in mice. Products of each category were compared in this model. The plasma pharmacokinetic profiles were similar for Gd-DOTA and P760 (t1/2 = 13.3 and 13.8 min. respectively), whereas the half-lives were 22 and 1212 min for P792 and P717, respectively. The plasma clearance was inversely related to the size of the contrast agent. The intraperitoneal diffusion patterns of the various products were related to the molecular volume; C_max per dose decreased progressively (78.7, 51.2, 44.2, 33.5 1/1) and t_max increased (7, 15, 40, and 120 min) for Gd-DOTA, P760, P792 and P717, respectively. Nevertheless, the same quantities of Gd-DOTA and P760 (AUC ratio of 78.4 and 76.8, respectively) diffused into the peritoneum, whereas only 44.5% of P792 and 21.5% of P717 extravasated. The data obtained in this peritoneal permeability model with the various categories of contrast agents provide an estimation of the quantities of contrast agents diffusing into a permeable interstitium and may be used to predict the corresponding signal intensity, which can be measured locally.     

Functional and metabolic evaluation of the hypertrophied heart using MRI and31P-MRS

4. Conclusions Diastolic LV function and myocardial HEP metabolism are impaired only when LVH is caused by permanent pressure or volume overload, and not by a temporary increase in cardiac workload during part of the day as in elite athletes. Therefore, training-induced and pressure/volume-overload-induced LVH seem to represent different phenotypes of LVH, possibly related to genetic reprogramming which only occurs during permanent cardiac overload [17]. Moreover, there is an association between impaired LV diastolic function and altered myocardial HEP metabolism in patients with hypertension and in patients with aortic valve disease. Finally we did not find a correlation between myocardial HEP metabolism and LV mass in any of the groups studied. The latter indicates that LVH should be regarded as an epiphenomenon to cardiac overload, and not as a primary factor causing abnormal HEP metabolism.     

Monitoring kidney and renal cyst volumes applying MR approaches on a rapamycin treated mouse model of ADPKD

Object  The aim of our study was to determine total cystic volume in a mouse model of PKD using MR imaging to monitor therapeutic effects in vivo. Materials and methods  We imaged eight female pcy-mice in two groups: four belonged to an untreated control group and four were treated with the anticystic agent rapamycin, which has proven to be effective in reducing cystogenesis in animal models. The mice were imaged using a 9.4 Tesla animal scanner. MRI measurements were taken at six time points during the therapy. Total renal volumes and total cyst volumes were calculated using a thresholding approach. Results  During the course of the treatment, the total cyst volume increased significantly faster than the total renal volume in the untreated group, indicating that growth of the total renal volume in the untreated group was primarily due to the growth of the cysts, rather than the parenchyma. The measured total renal volume in the control (placebo) group was significantly higher than the volume in the treated group. Conclusion  Using MRI, we were able to monitor the cystic volume in a mouse model of PKD to assess the therapeutic effect of anticystic treatment.     

Effects of functional electrical stimulation in denervated thigh muscles of paraplegic patients mapped with T 2 imaging

OBJECT: Functional electrical stimulation (FES) for paraplegic patients, with the long-term goal of ultimately restoring muscle function, is associated with several positive effects: improvement of blood circulation, skin condition, peripheral trophism and metabolism, prophylaxis against decubitus ulcer and better physical fitness. Since fibres of denervated muscles (lacking a supplying nerve) need to be activated directly, the fraction of elicited muscle tissue follows the geometric distribution of the electrical field, which can be simulated using electrophysiological computer models. Experimental validation of these results, however, has not yet been established. MATERIALS AND METHODS: We acquired T (2) parameter images using a multislice multi-spin-echo MR sequence before and immediately after FES in nine denervated paraplegic patients and three healthy subjects in order to visualise the geometric distribution of activation by electrically induced muscle stimulation in denervated versus innervated (healthy) thigh muscle. RESULTS AND CONCLUSION: After realigning and normalisation, maps of relative T (2) increase were calculated. The results demonstrate that the spatial distribution of short-term effects of FES of denervated muscle tissue of paraplegic patients who regularly perform FES can be visualised by T (2) parameter images. This may be used to refine models of the electrical field of FES in muscle and fibre activation in the future.     

Versatile coil design and positioning of transverse-field RF surface coils for clinical 1.5-T MRI applications

Clinical MRI/MRS applications require radio frequency (RF) surface coils positioned at an arbitrary angle with respect to B₀. In these experimental conditions the standard circular loop (CL) coil, producing an axial RF field, shows a large signal loss in the central region of interest (ROI). We demonstrate that transverse-field figure-of-eight (FO8) RF surface coils design are not subject to the same amount of signal loss in the central ROI as loop coils when their orientations are changed. The 1.5-T CL and FO8 prototypes (diameter = 10 cm) were built on Plexiglas using copper strips (width = 4 mm, thickness = 100 m). The two linear elements of the FO8 coil were 1 cm apart. Axial spoiled gradient echo (SPGR) images of a phantom containing doped water were acquired with the coil plane at =0°, 45°, and 90°. As increases, the CL images show, in the central ROI, a signal that decreases from a maximum value to zero. Whereas the FO8 images show, in the same ROI, a signal that varies little from the maximum value (20%). Optimized FO8 coils can be oriented with the coil plane positioned along any direction with respect to B₀ without significant signal loss. Transverse RF coil design should be useful for clinical MRS studies and also for parallel imaging techniques where versatile RF coils disposed along arbitrary directions are required.     

Comparative analysis of high field MRI and histology for ex vivo whole organ imaging: assessment of placental functional morphology in a murine model

Magnetic Resonance Materials in Physics, Biology and Medicine - The purpose of our study was to evaluate MRI as a tool to examine placental morphology in a murine model in comparison to classical...     

Tissue oxygen tension measurements in the Shionogi model of prostate cancer using 19 F MRS and MRI

Objectives: To investigate changes in tumour tissue oxygenation throughout the tumour growth–regression–relapse cycle in an androgen-dependent animal tumour model. Materials and methods: ¹⁹F T₁ relaxometry of Perfluoro-15-Crown-5-Ether was used to measure in vivo partial oxygen pressure (pO₂) of Shionogi tumours on a 2.35-T MR scanner. Perfluoro-15-Crown-5-Ether was administered as an emulsion injected intravenously or as a neat compound injected directly into the tumour. Non-localized, tumour ¹⁹F T₁ measurements, made at multiple time points throughout the tumour cycle, were translated into pO₂ levels. Results: No correlation between tumour size and pO₂ values was found. Values of pO₂ for growing tumours (50 ± 30 torr) were significantly lower than for regressing and relapsing tumours after 9 days post-castration (70 ± 10 torr, p<0.05). Maximum pO₂ values (90 ± 30 torr) were reached between fifth and eighth day post-castration, when tumour pO₂ was significantly higher than both pre-castration (p<0.001) and after 9 days post-castration (p<0.05). Conclusion: We demonstrate that longitudinal pO₂ measurements in vivo are feasible. Values of pO₂ for growing androgen-dependent tumours were significantly lower than for regressing and relapsing androgen-independent tumours. These results have potential clinical importance in optimizing the timing of chemotherapy and/or radiotherapy of hormone dependent tumours.     

Study of performance and leakage currents in nanometer-scale bulk,SOI and double-gate MOSFETs

We consider the performance and leakage issues in 80-to-20 nm Ge, Si, and InGaAs bulk, SOI and Double-gate (DG) devices. The performance is studied with DAMOCLES, band-to-band tunneling processes with a nonlocal band-to-band model as a post-processor in DAMOCLES, and gate tunneling by a Green’s function method accounting also for image force effects, so far ignored at ‘internal’ interfaces. The performance is affected by the bottleneck effect in III–Vs, especially for thin channels, but InGaAs and Ge still may be optimized to outperform Si. Zener leakage is high for Ge and tolerable for InGaAs. The effect of image forces led to an order of magnitude increase in gate tunneling currents.     

Effect of new manganese contrast agent on tissue intensities in human volunteers: comparison of 0.23, 0.6 and 1.5 T MRI,a part of a phase I trial

To evaluate the effect of a new oral manganese contrast agent (CMC-001) on magnetic resonance imaging (MRI) intensities at different magnetic field strengths. Twelve healthy volunteers underwent abdominal MRI 1 week before and within 2.5–4.5 h after CMC-001 (MnCl₂ and absorption promoters dissolved in water) intake at three different MR scanners of 0.23, 0.6 and 1.5 T. Image contrast and intensity enhancement of liver and pancreas were analysed relatively to muscle and fat intensities. Manganese blood levels were followed for 24 h. Whole-blood manganese concentration levels stayed within the normal range. The liver intensities on T2w images decreased about 10% for the 1/2 contrast dose and about 20% for the full contrast dose independent of the field strength. The liver intensities on T1w images increased more than 30% for 1/2 contrast dose and over 40% for full contrast dose. The maximum T1 enhancement was achieved at the highest field. Pancreas intensities were not affected. Contrast between liver, muscle and fat intensities increased with magnetic field, as well as standard errors of the volunteer-averaged intensities. Oral intake of CMC-001 influences liver intensities and does not affect pancreas intensities at different magnetic field strengths.