James H. Holmes

Functional lung imaging using hyperpolarized gas MRI

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe‐129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology. J. Magn. Reson. Imaging 2007.

Generalized k-space decomposition with chemical shift correction for non-Cartesian water-fat imaging.

Chemical‐shift artifacts associated with non‐Cartesian imaging are more complex to model and less clinically acceptable than the bulk fat shift that occurs with conventional spin‐warp Cartesian imaging. A novel k‐space based iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL) approach is introduced that decomposes multiple species while simultaneously correcting distortion of off‐resonant species. The new signal model accounts for the additional phase accumulated by off‐resonant spins at each point in the k‐space acquisition trajectory. This phase can then be corrected by adjusting the decomposition matrix for each k‐space point during the final IDEAL processing step with little increase in reconstruction time. The technique is demonstrated with water‐fat decomposition using projection reconstruction (PR)/radial, spiral, and Cartesian spin‐warp imaging of phantoms and human subjects, in each case achieving substantial correction of chemical‐shift artifacts. Simulations of the point‐spread‐function (PSF) for off‐resonant spins are examined to show the nature of the chemical‐shift distortion for each acquisition. Also introduced is an approach to improve the signal model for species which have multiple resonant peaks. Many chemical species, including fat, have multiple resonant peaks, although such species are often approximated as a single peak. The improved multipeak decomposition is demonstrated with water‐fat imaging, showing a substantial improvement in water‐fat separation. Magn Reson Med 59:1151–1164, 2008.

Iterative projection reconstruction of time-resolved images using highly-constrained back-projection (HYPR).

Highly‐constrained back‐projection (HYPR) is a technique for the reconstruction of sparse, highly‐undersampled time‐resolved image data. A novel iterative HYPR (I‐HYPR) algorithm is presented and validated in computer simulations. The reconstruction method is then applied to cerebral perfusion MRI simulated as a radial acquisition and contrast‐enhanced angiography of the head to assess feasibility in accelerating acquisitions requiring high temporal resolution and accurate representation of contrast kinetics. The I‐HYPR algorithm is shown to be more robust than standard HYPR in these applications in which the sparsity condition is not met or in which quantitative information is required. Specifically, iterative reconstruction of undersampled perfusion and contrast‐enhanced angiography data improved accuracy of the representation of contrast kinetics and increased the temporal separation of arterial and venous contrast kinetics. The I‐HYPR reconstruction may have important diagnostic applications in settings requiring high temporal resolution and quantitative signal dynamics. Because I‐HYPR allows relaxation of the sparsity requirements for the composite frame, the iterative reconstruction can enable novel acquisition strategies that independently optimize the quality of the composite and temporal resolution of the dynamic frames. Magn Reson Med, 2007.

The RPN5 Subunit of the 26s Proteasome Is Essential for Gametogenesis, Sporophyte Development, and Complex Assembly in Arabidopsis

The 26S proteasome is an essential multicatalytic protease complex that degrades a wide range of intracellular proteins, especially those modified with ubiquitin. Arabidopsis thaliana and other plants use pairs of genes to encode most of the core subunits, with both of the isoforms often incorporated into the mature complex. Here, we show that the gene pair encoding the regulatory particle non-ATPase subunit (RPN5) has a unique role in proteasome function and Arabidopsis development. Homozygous rpn5a rpn5b mutants could not be generated due to a defect in male gametogenesis. While single rpn5b mutants appear wild-type, single rpn5a mutants display a host of morphogenic defects, including abnormal embryogenesis, partially deetiolated development in the dark, a severely dwarfed phenotype when grown in the light, and infertility. Proteasome complexes missing RPN5a are less stable in vitro, suggesting that some of the rpn5a defects are caused by altered complex integrity. The rpn5a phenotype could be rescued by expression of either RPN5a or RPN5b, indicating functional redundancy. However, abnormal phenotypes generated by overexpression implied that paralog-specific functions also exist. Collectively, the data point to a specific role for RPN5 in the plant 26S proteasome and suggest that its two paralogous genes in Arabidopsis have both redundant and unique roles in development.

3D hyperpolarized He-3 MRI of ventilation using a multi-echo projection acquisition

A method is presented for high‐resolution 3D imaging of the whole lung using inhaled hyperpolarized (HP) He‐3 MR with multiple half‐echo radial trajectories that can accelerate imaging through undersampling. A multiple half‐echo radial trajectory can be used to reduce the level of artifact for undersampled 3D projection reconstruction (PR) imaging by increasing the amount of data acquired per unit time for HP He‐3 lung imaging. The point spread functions (PSFs) for breath‐held He‐3 MRI using multiple half‐echo trajectories were evaluated using simulations to predict the effects of T2* and gas diffusion on image quality. Results from PSF simulations were consistent with imaging results in volunteer studies showing improved image quality with increasing number of echoes using up to 8 half‐echoes. The 8‐half‐echo acquisition is shown to accommodate lost breath‐holds as short as 6 sec using a retrospective reconstruction at reduced resolution and also to allow reduced breath‐hold time compared with an equivalent Cartesian trajectory. Furthermore, preliminary results from a 3D dynamic inhalation‐exhalation maneuver are demonstrated using the 8‐half‐echo trajectory. Results demonstrate the first high‐resolution 3D PR imaging of ventilation and respiratory dynamics in humans using HP He‐3 MR. Magn Reson Med 59:1062–1071, 2008.

Imaging of lung ventilation and respiratory dynamics in a single ventilation cycle using hyperpolarized He‐3 MRI

To image respiratory dynamics and three‐dimensional (3D) ventilation during inhalation, breath‐hold, and exhalation for evaluation of obstructive lung disease using a single dose of hyperpolarized (HP) He‐3 during MRI.

Three-dimensional imaging of ventilation dynamics in asthmatics using multiecho projection acquisition with constrained reconstruction.

The purpose of this work is to detect dynamic gas trapping in three dimensions during forced exhalation at isotropic high spatial resolution and high temporal resolution using hyperpolarized helium‐3 MRI. Ten subjects underwent hyperpolarized helium‐3 MRI and multidetector CT. MRI was performed throughout inspiration, breath‐hold, and forced expiration. A multiecho three‐dimensional projection acquisition was used to improve data collection efficiency and an iterative constrained reconstruction was implemented to improve signal to noise ratio (SNR) and increase robustness to motion. Two radiologists evaluated the dynamic MRI and breath‐held multidetector CT data for gas and air trapping, respectively. Phantom studies showed the proposed technique significantly improved depiction of moving objects compared to view‐sharing methods. Gas trapping was detected using MRI in five of the six asthmatic subjects who displayed air trapping with multidetector CT. Locations in disagreement were found to represent small to moderate regions of air trapping. The proposed technique provides whole‐lung three‐dimensional imaging of respiration dynamics at high spatial and temporal resolution and compares well to the current standard, multidetector CT. While multidetector CT can provide information about static regional air trapping, it is unable to depict dynamics in a setting more comparable to a spirometry maneuver and explore the longitudinal time evolution of the trapped regions. Magn Reson Med, 2009.

Interleaved variable density sampling with a constrained parallel imaging reconstruction for dynamic contrast-enhanced MR angiography.

For MR applications such as contrast‐enhanced MR angiography, it is desirable to achieve simultaneously high spatial and temporal resolution. The current clinical standard uses view‐sharing methods combined with parallel imaging; however, this approach still provides limited spatial and temporal resolution. To improve on the clinical standard, we present an interleaved variable density (IVD) sampling method that pseudorandomly undersamples each individual frame of a 3D Cartesian ky–kz plane combined with parallel imaging acceleration. From this dataset, time‐resolved images are reconstructed with a method that combines parallel imaging with a multiplicative constraint. Total acceleration factors on the order of 20 are achieved for contrast‐enhanced MR angiography of the lower extremities, and improvements in temporal fidelity of the depiction of the contrast bolus passage are demonstrated relative to the clinical standard. Magn Reson Med, 2011.

Helium-3 MR q-space Imaging with Radial Acquisition and Iterative Highly Constrained Back-Projection

An undersampled diffusion‐weighted stack‐of‐stars acquisition is combined with iterative highly constrained back‐projection to perform hyperpolarized helium‐3 MR q‐space imaging with combined regional correction of radiofrequency‐ and T1‐related signal loss in a single breath‐held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole‐lung coverage in a 13‐sec breath‐hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two‐dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500‐mL volume to the 1000‐mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium‐3 q‐space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions. Magn Reson Med, 2010.

Measurement of lung airways in three dimensions using hyperpolarized helium-3 MRI

Large airway measurement is clinically important in cases of airway disease and trauma. The gold standard is computed tomography (CT), which allows for airway measurement. However, the ionizing radiation dose associated with CT is a major limitation in longitudinal studies and trauma. To avoid ionizing radiation from CT, we present a method for measuring the large airway diameter in humans using hyperpolarized helium-3 (HPHe) MRI in conjunction with a dynamic 3D radial acquisition. An algorithm is introduced which utilizes the significant airway contrast for semi-automated segmentation and skeletonization which is used to derive the airway lumen diameter. The HPHe MRI method was validated with quantitative CT in an excised and desiccated porcine lung (linear regression R(2) = 0.974 and slope = 0.966 over 32 airway segments). The airway lumen diameters were then compared in 24 human subjects (22 asthmatics and 2 normals; linear regression R(2) value of 0.799 and slope = 0.768 over 309 airway segments). The feasibility for airway path analysis to areas of ventilation defect is also demonstrated.