Magnetic resonance lung function – a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial

BACKGROUND: Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI) is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment. METHODS: We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed. RESULTS: The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p ≤ 0.001) was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized. CONCLUSION: With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment

Discovery of Radio Emission from the Brown Dwarf LP944-20

Brown dwarfs are classified as objects which are not massive enough to sustain nuclear fusion of hydrogen, and are distinguished from planets by their ability to burn deuterium. Old (>10 Myr) brown dwarfs are expected to possess short-lived magnetic fields and, since they no longer generate energy from collapse and accretion, weak radio and X-ray emitting coronae. Several efforts have been undertaken in the past to detect chromospheric activity from the brown dwarf LP944-20 at X-ray and optical wavelengths, but only recently an X-ray flare from this object was detected. Here we report on the discovery of quiescent and flaring radio emission from this source, which represents the first detection of persistent radio emission from a brown dwarf, with luminosities that are several orders of magnitude larger than predicted from an empirical relation between the X-ray and radio luminosities of many stellar types. We show in the context of synchrotron emission, that LP944-20 possesses an unusually weak magnetic field in comparison to active dwarf M stars, which might explain the null results from previous optical and X-ray observations of this source, and the deviation from the empirical relations.Comment: Accepted to Natur

Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles

We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of distinguishing the competing models of induced fit and conformational selection. For allostery we review the classic models and show how conformational ensembles can play a role in unravelling the intricate pathways of communication that enable allostery to occur. Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future

An alternate conformation of the hyperthermostable HU protein from Thermotoga maritima has unexpectedly high flexibility

The homodimeric HU protein from the hyperthermophile Thermotoga maritima (HUTmar) is a model system which can yield insights into the molecular determinants of thermostability in proteins. Unusually for a thermostable protein, HUTmar exists in a structurally heterogeneous state as evidenced by the assignment of two distinct and approximately equally populated forms in solution. Relaxation measurements combined with chemical shift, hydrogen exchange, and nuclear Overhauser enhancement data confirm the main structural features of both forms. In addition, these data support a two-state model for HUTmar in which the major form closely resembles the X-ray structure while the very flexible minor form is less structured. HUTmar may therefore be a new example of the small class of hyperthermostable proteins with unexpected flexibility. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Lung parenchymal signal intensity in MRI: A technical review with educational aspirations regarding reversible versus irreversible transverse relaxation effects in common pulse sequences

Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T(2)(*) values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T(2)(*) values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice