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This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI) – hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas – and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multi-detector computed tomography (CT). However, MRI also offers capabilities for fast multi-spectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultra-short echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. Relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF) in both adults and children.

Multiple-region MRI (mrMRI) represents a generalization of the Shannon sampling theorem to permit sparse k-space sampling whenever the scanned object or its high-contrast edges are confined to multiple known regions. Use of an optimal mrMRI sampling pattern produces an image with root-mean-squared (RMS) noise over the supporting regions equal to the RMS noise in a conventional Fourier image with the same total area of support. Analytical solutions for such sampling patterns have been described previously for all arrangements of two or three (noncollinear) supporting regions. This work describes a robust numerical method for creating a library of optimal and near-optimal mrMRI sampling patterns for more complicated geometries. The average noise amplification over all sampling patterns in the demonstration library was only 4%, with 30% of the sampling patterns resulting in no noise amplification whatsoever.

With conventional Fourier transform (FT) magnetic resonance imaging (MRI), it is difficult to perform contrast-enhanced three-dimensional (3D) MR angiography (MRA) with the temporal and spatial resolution necessary to depict the carotid arteries. However, locally focused (LF) MRI is a more efficient method that utilizes prior knowledge of the image content to reconstruct images from sparse k-space samples. In this paper, we show how LF MRI can be used to perform high-resolution gadolinium (Gd)-enhanced 3D carotid MRA in less than 10 seconds. First, the accuracy of the technique was demonstrated by comparing LF and conventional (FT) images of a vascular phantom. Then the method was used to perform Gd-enhanced 3D MRA of a patient's carotid arteries. Instead of using bolus timing, the arterial phase was retrospectively identified in a consecutive series of images, just as in X-ray angiography. J. Magn. Reson. Imaging 1999;9:663–669. © 1999 Wiley-Liss, Inc.

Traditional Fourier MR imaging (FT MRI) utilizes the Whittaker-Kotel'nikov-Shannon (WKS) sampling theorem. This theorem specifies the spatial frequency components which need to be measured to reconstruct an image with a known field of view (FOV). In this paper, we generalize this result in order to find the optimal k-space sampling for images that vanish except in multiple, possibly non-adjacent regions within the FOV. This provides the basis for "multiple region MRI" (mrMRI), a method of producing such images from a traction of the k-space samples required by the WKS theorem. Image reconstruction does not suffer from noise amplification and can be performed rapidly with fast Fourier transforms, just as in conventional FT MRI. The mrMRI method can also be used to reconstruct images that have low spatial-frequency components throughout the entire FOV and high spatial frequencies (i.e. edges) confined to multiple small regions. The greater efficiency of mrMRI sampling can be parlayed into increased temporal or spatial resolution whenever the imaged objects have signal or "edge" intensity confined to multiple small portions of the FOV. Possible areas of application include MR angiography (MRA), interventional MRI, functional MRI, and spectroscopic MRI. The technique is demonstrated by using it to acquire Gd-enhanced first-pass 3D MRA images of the carotid arteries without the use of bolus-timing techniques.

Certain interventional MR procedures would benefit from T2-weighted imaging because of the sensitivity of T2-weighted images to tissue damage and target lesion contrast. To acquire such images with reasonable temporal resolution, a single-shot acquisition should be used because of the inherently long TR needed for T2 weighting. Unfortunately, most scanners require long readout times (eg, greater than 150 msec) and high bandwidths (eg, greater than 120 kHz) to perform conventional single-shot imaging with high spatial resolution. The resulting images are thus degraded by unacceptable artifacts and noise levels. This study illustrates how to create locally focused MR images that have high spatial resolution in a region of interest and lower spatial resolution elsewhere in the image. Because these images can be created from sparse k-space data, a scanner with modest gradients (eg, 10 mT/m maximal amplitude, 500 microsec minimal rise time) can acquire them after a single excitation with relatively short readout time and low bandwidth. This technique may make it practical to monitor interventions with T2-weighted imaging. The method was illustrated by reconstructing dynamic changes, which were simulated experimentally by moving objects in the vicinity of a normal human head.

The purpose of this work was to use 3D radial ultrashort echo time (UTE) MRI to perform whole-lung oxygen-enhanced (OE) imaging in humans. Eight healthy human subjects underwent two 3D radial UTE MRI acquisitions (TE = 0.08 ms): one while breathing 21% O2 and the other while breathing 100% O2. Scans were each performed over 5 min of free breathing, using prospective respiratory gating. For comparison purposes, conventional echo time (TE = 2.1 ms) images were acquired simultaneously during each acquisition using a radial " outward-inward" k-space trajectory. 3D percent OE maps were generated from these images. 3D OE maps showing lung signal enhancement were generated successfully in seven subjects (technical failure in one subject). Mean percent signal enhancement was 6.6% ± 1.8%, near the value predicted by theory of 6.3%. No significant enhancement was seen using the conventional echo time data, confirming the importance of UTE for this acquisition strategy. 3D radial UTE MRI shows promise as a method for OE MRI that enables whole-lung coverage and isotropic spatial resolution, in comparison to existing 2D OE methods, which rely on a less time-efficient inversion recovery pulse sequence. These qualities may help OE MRI become a viable low-cost method for 3D imaging of lung function in human subjects.

Truncation artefact (Gibbs ringing) causes central signal drop within vessels in pulmonary magnetic resonance angiography (MRA) that can be mistaken for emboli, reducing diagnostic accuracy for pulmonary embolism (PE). We propose a quantitative approach to differentiate truncation artefact from PE.Twenty-eight patients who underwent pulmonary computed tomography angiography (CTA) for suspected PE were recruited for pulmonary MRA. Signal intensity drops within pulmonary arteries that persisted on both arterial-phase and delayed-phase MRA were identified. The percent signal loss between the vessel lumen and central drop was measured. CTA served as the reference standard for presence of pulmonary emboli.A total of 65 signal intensity drops were identified on MRA. Of these, 48 (74%) were artefacts and 17 (26%) were PE, as confirmed by CTA. Truncation artefacts had a significantly lower median signal drop than PE on both arterial-phase (26% [range 12-58%] vs. 85% [range 53-91%]) and delayed-phase MRA (26% [range 11-55%] vs. 77% [range 47-89%]), p 0.0001 for both. Receiver operating characteristic (ROC) analyses revealed a threshold value of 51% (arterial phase) and 47% signal drop (delayed phase) to differentiate between truncation artefact and PE with 100% sensitivity and greater than 90% specificity.Quantitative signal drop is an objective tool to help differentiate truncation artefact and pulmonary embolism in pulmonary MRA.• Inexperienced readers may mistake truncation artefacts for emboli on pulmonary MRA • Pulmonary emboli have non-uniform signal drop • 51% (arterial phase) and 47% (delayed phase) cut-off differentiates truncation artefact from PE • Quantitative signal drop measurement enables more accurate pulmonary embolism diagnosis with MRA.

To assess the feasibility of spatial-temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE).A combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE=0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion.The method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition.The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson

To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure.Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring.Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods.A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible.

To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications.Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale.The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B.For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique.

This article reviews the magnetic resonance imaging (MRI) and angiography (MRA) techniques, imaging findings, and evidence for evaluating patients with acute chest pain due to acute pulmonary embolus (PE), aortic dissection (AD), and myocardial infarction (MI). When computed tomographic angiography (CTA) is contraindicated, MRI and MRA are important alternative imaging modalities for diagnosis and management of patients with acute PE, AD, and MI. Familiarity with the techniques, imaging findings, and evidence is critical to safely and appropriately managing patients presenting with acute chest pain.

To investigate the utility of hyperpolarized He-3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects with exercise induced bronchoconstriction (EIB) were recruited. This condition is described by airway constriction following exercise leading to reduced forced expiratory volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He-3 MRI.Thirteen EIB subjects underwent spirometry and He-3 MRI at baseline, postexercise, and postrecovery at multiple visits. On one visit montelukast was given and on two visits placebo was given. Regional VV was calculated in the apical/basilar dimension, in the anterior/posterior dimension, and for the entire lung volume. The whole lung VV was used as an end-point and compared with spirometry.Postchallenge FEV1 dropped with placebo but not with treatment, while postchallenge VV dropped more with placebo than treatment. Sources of variability for VV included region (anterior/posterior), scan, and treatment. VV correlated with FEV1/ forced vital capacity (FVC) and forced expiratory flow between 25 and 75% of FVC and showed gravitational dependence after exercise challenge.A paradigm testing the response of ventilation to montelukast revealed both a whole-lung and regional response to exercise challenge and therapy in EIB subjects.

The advent of gadolinium-based "hepatobiliary" contrast agents offers new opportunities for diagnostic magnetic resonance imaging (MRI) and has triggered great interest for innovative imaging approaches to the liver and bile ducts. In this review article we discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the U.S., gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared toward optimizing workflow and imaging quality are also discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents and will stimulate the reader's pursuit of new applications for future benefit.

MscL is a channel that opens a large pore in the Escherichia coli cytoplasmic membrane in response to mechanical stress. Previously, we highly enriched the MscL protein by using patch clamp as a functional assay and cloned the corresponding gene. The predicted protein contains a largely hydrophobic core spanning two-thirds of the molecule and a more hydrophilic carboxyl terminal tail. Because MscL had no homology to characterized proteins, it was impossible to predict functional regions of the protein by simple inspection. Here, by mutagenesis, we have searched for functionally important regions of this molecule. We show that a short deletion from the amino terminus (3 amino acids), and a larger deletion of 27 amino acids from the carboxyl terminus of this protein, had little if any effect in channel properties. We have thus narrowed the search of the core mechanosensitive mechanism to 106 residues of this 136-amino acid protein. In contrast, single residue substitutions of a lysine in the putative first transmembrane domain or a glutamine in the periplasmic loop caused pronounced shifts in the mechano-sensitivity curves and/or large changes in the kinetics of channel gating, suggesting that the conformational structure in these regions is critical for normal mechanosensitive channel gating.