Wayne L. Davis

Intracranial MRA: Single volume vs. multiple thin slab 3D time-of-flight acquisition

Single volume three-dimensional (3D) time-of-flight (TOF) MR angiography is the most commonly used noninvasive method for evaluating the intracranial vasculature. The sensitivity of this technique to signal loss from flow saturation limits its utility. A recently developed multislab 3D TOF technique, MOTSA, is less affected by flow saturation and would therefore be expected to yield improved vessel visualization. To study this hypothesis, intracranial MR angiograms were obtained on 10 volunteers using three techniques: MOTSA, single volume 3D TOF using a standard 4.9 ms TE (3D TOFA), and single volume 3D TOF using a 6.8 ms TE (3D TOFB). All three sets of axial source images and maximum intensity projection (MIP) images were reviewed. Each exam was evaluated for the number of intracranial vessels visualized. A total of 502 vessel segments were studied with each technique. With use of the MIP images, 86% of selected vessels were visualized with MOTSA, 64% with 3D TOFA (TE = 4.9 ms), and 67% with TOFB (TE = 6.8 ms). Similarly, with the axial source images, 91% of selected vessels were visualized with MOTSA, 77% with 3D TOFA (TE = 4.9 ms), and 82% with 3D TOFB (TE = 6.8 ms). There is improved visualization of selected intracranial vessels in normal volunteers with MOTSA as compared with single volume 3D TOF. These improvements are believed to be primarily a result of decreased sensitivity to flow saturation seen with the MOTSA technique. No difference in overall vessel visualization was noted for the two single volume 3D TOF techniques.

Contrast-to-noise-ratio measurements in three-dimensional magnetic resonance angiography

RATIONALE AND OBJECTIVES.The authors report on the development and preliminary validation of a technique for measuring contrast-to-noise ratio (CNR) at all points along selected vessel segments in the original three-dimensional magnetic resonance angiography (MRA) dataset. METHODS.Contrast-to-noise ratio dependencies on flow rate, field of view, and flip angle were measured on images from a conventional time-of-flight MRA pulse sequence using constant flow in a branching vascular phantom. An estimate of the inherent variability of the technique was obtained from multiple scans of a flow phantom and a human volunteer. RESULTS.The overall standard deviation (SD) of the CNR was found to be approximately 6.1 % of the average CNR value for the flow phantom study and 7.3% for the human study. Vessel CNR was found to increase with field of view and was found to become nonuniform for low flow rate and/or high flip angles. CONCLUSION.In general, such CNR measurements allow the investigation of the mechanism of signal loss and general technique optimization in MRA.

The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1

The nematode Caenorhabditis elegans is an excellent model system in which to study in vivo organization and function of the intermediate filament (IF) system for epithelial development and function. Using a transgenic ifb-2::cfp reporter strain, a mutagenesis screen was performed to identify mutants with aberrant expression patterns of the IF protein IFB-2, which is expressed in a dense network at the subapical endotube just below the microvillar brush border of intestinal cells. Two of the isolated alleles (kc2 and kc3) were mapped to the same gene, which we refer to as ifo-1 (intestinal filament organizer). The encoded polypeptide colocalizes with IF proteins and F-actin in the intestine. The apical localization of IFO-1 does not rely on IFB-2 but is dependent on LET-413, a basolateral protein involved in apical junction assembly and maintenance of cell polarity. In mutant worms, IFB-2 and IFC-2 are mislocalized in cytoplasmic granules and accumulate in large aggregates at the C. elegans apical junction (CeAJ) in a DLG-1-dependent fashion. Electron microscopy reveals loss of the prominent endotube and disordered but still intact microvilli. Semiquantitative fluorescence microscopy revealed a significant decrease of F-actin, suggesting a general role of IFO-1 in cytoskeletal organization. Furthermore, downregulation of the cytoskeletal organizer ERM-1 and the adherens junction component DLG-1, each of which leads to F-actin reduction on its own, induces a novel synthetic phenotype in ifo-1 mutants resulting in disruption of the lumen. We conclude that IFO-1 is a multipurpose linker between different cytoskeletal components of the C. elegans intestinal terminal web and contributes to proper epithelial tube formation.

Effects of contrast media on cultured myocardial cells.

To quantify and characterize mechanisms of negative inotropic effects of ionic and nonionic angiographic contrast media, spontaneously contracting monolayers of cultured chick ventricular cells were studied using the Renografin-76 and iohexol as characteristic ionic and nonionic contrast agents. Utilizing microscopic video-motion detector techniques the effect of each contrast agent on contraction amplitude was measured. Also, the effect of changes in the ionized calcium concentration and osmolality induced by the contrast agents was evaluated. The study demonstrated a linear depression of contractility by increasing contrast concentrations. The negative inotropic effect of Renografin-76 was significantly greater than that of iohexol. Renografin-76 demonstrated significant calcium binding, whereas iohexol had none. Correction for calcium binding by Renografin-76 partially reversed the negative inotropic effect of this agent. Hypertonic sugar solutions of equivalent osmolality to the contrast agents demonstrated dose-related negative inotropic effects such that, in this preparation, calcium binding by Renografin-76 and its high osmolality accounted for all its negative inotropic effect. In contrast, iohexol demonstrated an intrinsic negative inotropic effect not completely explained by its osmolality.

Effects of contrast media on calcium transients and motion in cultured ventricular cells.

To investigate the mechanisms of the negative inotropic effects of contrast media, we superfused spontaneously contracting cultured chick embryo ventricular cells with Renografin-76 and iohexol (12% solutions), and hypertonic sucrose during simultaneous measurement of [Ca2+]i transients (indo-1) and motion (video-motion detector system). Exposure to contrast agents caused a significant reduction of contractility, with Renografin-76 having a much greater effect on amplitude of motion than iohexol. Renografin-76 significantly depressed [Ca2+]i transient amplitude, whereas iohexol had no effect. Addition of Ca2+ to correct for calcium binding by Renografin-76 completely reversed its depression of [Ca2+]i transients but only partially reversed the negative inotropic effects. Hypertonic sucrose caused a significant decrease in contraction amplitude, with no significant effects on [Ca2+]i transient amplitude. We conclude that the marked negative inotropic effect of Renografin-76 is caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by iohexol likely is a result of hypertonicity and not caused by alteration of [Ca2+]i.

A novel function for the MAP kinase SMA-5 in intestinal tube stability.

In vivo evidence links SMA-5 to the maintenance of the apical domain in the Caenorhabditis elegans intestine. sma-5 mutations induce morphological and biochemical changes of the intermediate filament system, demonstrating the close relationship between posttranslational modification and structural integrity of the evolutionarily conserved intestinal cytoskeleton.