Probing renal blood volume with magnetic resonance imaging

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T₂*) in vivo, and is non‐invasive and indicative of renal tissue oxygenation. However, the renal T₂* to tissue pO₂ relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI‐based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T₂* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol‐enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI‐based assessment of renal BVf.     

Evaluation of the performance of a gamma camera equipped with a 5/8" versus 1" thick NaI detector

The upgrade of a gamma camera from a 5/8" to a 1" thick crystal, the latter with StarBrite technology, prompted to the investigation of changes in performance parameters for planar scintigraphy and SPECT as well as for PET in coincidence mode. For planar and SPECT parameters, the performance was measured according to NEMA Standard Protocol NU1-2001. No changes were found in terms of intrinsic uniformity, intrinsic spatial resolution, linearity, energy resolution, system resolution, and tomographic system resolution. The only change was an increase of system sensitivity for higher energy gamma rays. For the PET scanner in coincidence mode, the image quality of the camera was determined according to NEMA NU2-2001. Visually and in terms of contrast values there was a significant improvement of image quality. Changes in image quality relevant for clinical use were tested by evaluation of planar patient scans acquired within a short time with two gamma cameras of the same type, different only in crystal thickness (5/8" and 1"). No statistically significant difference was found between corresponding scans. For planar and SPECT imaging, the gamma camera with 1" thick detector and StarBrite technology demonstrated the same performance of a camera with a 5/8" crystal. For PET in coincidence mode the new detector proved clearly superior.     

Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin

Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, exhibit numerous functions related to inflammation, such as MHC class II down-regulation, interference with T cell adhesion, and induction of apoptosis. Here we demonstrate that both subcutaneous and oral administration of atorvastatin inhibit the development of actively induced chronic experimental autoimmune encephalomyelitis in SJL/J mice and significantly reduce the inflammatory infiltration into the central nervous system (CNS). When treatment was started after disease onset, atorvastatin reduced the incidence of relapses and protected from the development of further disability. Both the reduced autoreactive T cell response measured by proliferation toward the encephalitogenic peptide PLP139-151 and the cytokine profile indicate a potent blockade of T helper cell type 1 immune response. In in vitro assays atorvastatin not only inhibited antigen-specific responses, but also decreased T cell proliferation mediated by direct TCR engagement independently of MHC class II and LFA-1. Inhibition of proliferation was not due to apoptosis induction, but linked to a negative regulation on cell cycle progression. However, early T cell activation was unaffected, as reflected by unaltered calcium fluxes. Thus, our results provide evidence for a beneficial role of statins in the treatment of autoimmune attack on the CNS.     

Evaluation of a miniature electromagnetic position tracker

The advent of miniaturized electromagnetic digitizers opens a variety of potential clinical applications for computer aided interventions using flexible instruments; endoscopes or catheters can easily be tracked within the body. With respect to the new applications, the systematic distortions induced by various materials such as closed metallic loops, wire guides, catheters, and ultrasound scan heads were systematically evaluated in this paper for a new commercial tracking system. We employed the electromagnetic tracking system Aurora (Mednetix/CH, NDI/Can); data were acquired using the serial port of a PC running SuSE Linux 7.1 (SuSE, Gmbh, Nürnberg). Objects introduced into the digitizer volume included wire loops of different diameters, wire guides, optical tracking tools, an ultrasonic (US) scan head, an endoscope with radial ultrasound scan head and various other objects used in operating rooms and interventional suites. Beyond this, we determined the influence of a C-arm fluoroscopy unit. To quantify the reliability of the system, the miniaturized sensor was mounted on a nonmetallic measurement rack while the transmitter was fixed at three different distances within the digitizer range. The tracker was shown to be more sensitive to distortions caused by materials close to the emitter (average distortion error 13.6 mm +/- 16.6 mm for wire loops positioned at a distance between 100 mm and 200 mm from the emitter). Distortions caused by materials near the sensor (distances smaller than 100 mm) are small (typical error 2.2 mm +/- 1.9 mm). The C-arm fluoroscopy unit caused considerable distortions and limits the reliability of the tracker (distortion error 18.6 mm +/- 24.9 mm). Distortions resulting from the US scan head are high at distances smaller than about 100 mm from the emitter. The distortions also increase when the scan head is positioned horizontally and close to the sensor (average error 4.1 mm +/- 1.5 mm when the scan head is positioned within a distance of 100 mm from the sensor). The distortions are slightly higher when the ultrasound machine is switched on. We also evaluated the influence of common medical instruments on distance measurements. For these measurements the average deviation from the known distance of 200 mm amounted to 3.0 mm +/- 1.5 mm (undistorted distance measurement 1.5 mm +/- 0.3 mm). The deviations also depend on the relative orientation between emitter and sensor. The results demonstrate that the miniature tracking system opens up new perspectives with regard to surgery applications where a flexible instrument is to be tracked within the body. Significant distortions caused by metallic objects only occur in the worst cases, for example, in the presence of a closed, unisiolated wire loop or a C-arm fluorescence unit close to the emitter and which can be avoided by suitable usage.     

An inter-laboratory comparison study of image quality of PET scanners using the NEMA NU 2-2001 procedure for assessment of image quality

An inter-laboratory comparison study was conducted to assess the image quality of PET scanners in Austria. The survey included both dedicated PET scanners (D-PET, n = 8) and coincidence cameras (GC-PET, n = 7). Measurement of image quality was based on the NEMA (National Electrical Manufacturers Association) NU 2-2001 protocol and the IEC (International Electrotechnical Commission) body phantom. The latter contains six fillable spheres ranging in diameter from 37 mm down to 10 mm and a 'lung' insert. The two largest lesions L1-2 simulate cold lesions, the four smaller ones (L3-6) are filled with 18F and activity concentration ratios relative to background of 8:1 and 4:1, respectively. Acquisition and reconstruction in the study employed the participating institutes' standard oncological processing protocol. Calculation of contrast of the spheres was performed with a fully automated procedure. Contrast quality indices (CQIs) reflecting global performance were obtained by summing individual contrast values. Other image quality parameters calculated according to the NEMA protocol were background variability and relative error for correction of attenuation and scatter. Contrast values obtained were 61 +/- 16 and 37 +/- 14 for L1 (per cent contrast +/- SD for D-PET and GC-PET, respectively), 57 +/- 16 and 29 +/- 16 for L2, 46 +/- 10 and 26 +/- 6.3 for L3, 37 +/- 10 and 15 +/- 4.3 for L4, 26 +/- 11.5 and 6.1 +/- 2.5 for L5, 14 +/- 7.1 and 2.6 +/- 2.6 for L6, with D-PET systems consistently being superior to GC-PET systems. CQIs permitted ranking of the scanners, also demonstrating a clear distinction between D-PET and GC-PET systems. Background variability was largest for GC-PET systems; the relative error of attenuation and scatter correction was significantly correlated with image quality for D-PET systems only. The study demonstrated considerable differences in image quality not only between GC-PET and D-PET systems but also between individual D-PET systems with possible consequences for clinical interpretation of images and measurement of quantitative indices such as the standardized uptake value. The study provided valuable feedback to the participants as well as baseline data for improving interchangeability of PET images and of quantitative indices between different laboratories.     

Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage

BACKGROUND: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. RESULTS: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). CONCLUSIONS: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.     

Morphological study of placental terminal villi in intrahepatic cholestasis of pregnancy: Histochemistry, light and electron microscopy

Histochemistry, light and electron microscopy were used to study the changes in the morphology of the terminal villi of four term placentae from anicteric ICP and two from icteric ICP as compared to three normal placentae. Alterations observed in ICP placentae were a reduction of the intervillous space, syncytial and cytotrophoblastic hyperplasia, decreased alkaline phosphatase reaction, absence of glycogen, dilatation of rough endoplasmic reticulum, basal folding, and an increase of lipoprotein-like bodies in the syncytium.     

Diffusion tensor imaging to assess axonal regeneration in peripheral nerves

Development of outcome measures to assess ongoing nerve regeneration in the living animal that can be translated to human can provide extremely useful tools for monitoring the effects of therapeutic interventions to promote nerve regeneration. Diffusion tensor imaging (DTI), a magnetic resonance based technique, provides image contrast for nerve tracts and can be applied serially on the same subject with potential to monitor nerve fiber content. In this study, we examined the use of ex vivo high-resolution DTI for imaging intact and regenerating peripheral nerves in mice and correlated the MRI findings with electrophysiology and histology. DTI was done on sciatic nerves with crush, without crush, and after complete transection in different mouse strains. DTI measures, including fractional anisotropy (FA), parallel diffusivity, and perpendicular diffusivity were acquired and compared in segments of uninjured and crushed/transected nerves and correlated with morphometry. A comparison of axon regeneration after sciatic nerve crush showed a comparable pattern of regeneration in different mice strains. FA values were significantly lower in completely denervated nerve segments compared to uninjured sciatic nerve and this signal was restored toward normal in regenerating nerve segments (crushed nerves). Histology data indicate that the FA values and the parallel diffusivity showed a positive correlation with the total number of regenerating axons. These studies suggest that DTI is a sensitive measure of axon regeneration in mouse models and provide basis for further development of imaging technology for application to living animals and humans.