X. Josette Chen

MRI of the lungs using hyperpolarized noble gases

The nuclear spin polarization of the noble gas isotopes 3He and 129Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments. Magn Reson Med 47:1029–1051, 2002.

Multiple mouse biological loading and monitoring system for MRI

The use of mice to study models of human disease has resulted in a surge of interest in developing mouse MRI. The ability to take 3D, high‐resolution images of live mice allows significant insight into anatomy and function. However, with imaging times on the order of hours, high throughput of specimens has been problematic. To facilitate high throughput, concurrent imaging of multiple mice has been developed; however, this poses further complexities regarding the ease and rapidity of loading several animals. In this study, custom‐built equipment was developed to streamline the preparation process and to safely maintain seven mice during a multiple‐mouse imaging session. Total preparation time for seven mice was ∼24 min. ECG and temperature were monitored throughout the scan and maintained by regulating anesthetic and heating. Proof of principle was demonstrated in a 3‐h imaging session of seven mice. Magn Reson Med 52:709–715, 2004.

Functional MR microscopy of the lung using hyperpolarized 3He

A new strategy designed to provide functional magnetic resonance images of the lung in small animals at microscopic resolution using hyperpolarized 3He is described. The pulse sequence is based on a combination of radial acquisition (RA) and CINE techniques, referred to as RA‐CINE, and is designed for use with hyperpolarized 3He to explore lung ventilation with high temporal and spatial resolution in small animal models. Ventilation of the live guinea pig is demonstrated with effective temporal resolution of 50 msec and in‐plane spatial resolution of <100 μm using hyperpolarized 3He. The RA‐CINE sequence allows one to follow gas inflow and outflow in the airways as well as in the distal part of the lungs. Regional analysis of signal intensity variations can be performed and can help assess functional lung parameters such as residual gas volume and lung compliance to gas inflow. Magn Reson Med 41:787–792, 1999.

Measurements of hyperpolarized gas properties in the lung. Part III: 3He T1

Hyperpolarized 3He spin‐lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T1 was dominated by interactions with oxygen and was used to measure the alveolar O2 partial pressure. In animals ventilated with a mixture of 79% 3He and 21% O2, T1 dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 ± 11 mL min−1 kg−1 under normoxic conditions, and 9.0 ± 2.0 mL min−1 kg−1 under hypoxic conditions. Cardiac output was estimated to be 400 ± 160 mL min−1 kg−1. The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 ± 0.3 mL and 10.7 ± 1.1 mL. Magn Reson Med 45:421–430, 2001.

Ultrasound-guided left-ventricular catheterization: a novel method of whole mouse perfusion for microimaging

We describe a novel technique to perform whole-body perfusion fixation in mice with specific relevance to micro-imaging. With the guidance of high-frequency ultrasound imaging, we were able to perfuse fixative and contrast agents via a catheter inserted into the left ventricle, and therefore preserved the integrity of the chest and abdominal cavity. In this preliminary study, our success rate over 15 animals was 73%. We demonstrate applications of this technique for magnetic resonance imaging and micro-CT, but we expect that this method can be generally applied to whole-body perfusions of other small animals in which the intact body is necessary.

Fast spin-echo for multiple mouse magnetic resonance phenotyping

High‐resolution magnetic resonance imaging is emerging as a powerful tool for phenotyping mice in biologic studies of genetic expression, development, and disease progression. In several applications, notably random mutagenesis trials, large cohorts of mice must be examined for abnormalities that may occur in any part of the body. In the aim of establishing a protocol for imaging multiple mice simultaneously in a standardized high‐throughput fashion, this study investigates variations of a three‐dimensional fast spin‐echo sequence that implements driven equilibrium, modified refocusing, and partial excitation pulses. Sequence variations are compared by simulated and experimental measurements in phantoms and mice. Results indicate that when using a short repetition time (TR ≤ T1) a sequence employing a partial excitation tip angle provides both improved signal and good T2 contrast compared with standard fast spin‐echo imaging. This sequence is used to simultaneously acquire four live mouse head images at 100 μm isotropic resolution with a scan time under 3 h at 7 T. Magn Reson Med, 2005.

Hyperpolarized 3He microspheres as a novel vascular signal source for MRI.

Hyperpolarized (HP) 3He can be encapsulated within biologically compatible microspheres while retaining sufficient polarization to be used as a signal source for MRI. Two microsphere sizes were used, with mean diameters of 5.3 ± 1.3 μm and 10.9 ± 3.0 μm. These suspensions ranged in concentration from 0.9–7.0% gas by volume. Spectroscopic measurements in phantoms at 2 T yielded 3He relaxation times that varied with gas concentration. At the highest 3He concentration, the spin‐lattice relaxation time, T1, was 63.8 ± 9.4 sec, while the transverse magnetization decayed with a time constant of T*2 = 11.0 ± 0.4 msec. In vivo MR images of the pelvic veins in a rat were acquired during intravenous injection of 3He microspheres (SNR ≈ 15). Advantages such as intravascular confinement, lack of background signal, and limited recirculation indicate quantitative perfusion measurements may be improved using this novel signal source. Magn Reson Med 43:440–445, 2000.

Optimization of the SNR-resolution tradeoff for registration of magnetic resonance images.

Image registration serves many applications in medical imaging, including longitudinal studies, treatment verification, and more recently, morphometry. Registration processing is regularly applied in magnetic resonance (MR) images, where imaging is highly adaptable in capturing soft tissue contrast. To obtain the greatest registration accuracy in MR imaging, the inherent imaging tradeoff between SNR and resolution at a given scan time should be optimized for computational accuracy, rather than human viewing. We investigated this SNR‐resolution tradeoff to optimize registration for digital morphometry. Tradeoff images were simulated from acquired gold standard MR images to emulate a shorter, constant acquisition time, but at the expense of SNR, resolution, or both. The group of images from each tradeoff was nonlinearly registered toward an average atlas producing deformation fields, useful for identifying differences in morphology. The gold standard data were also registered. The deformation fields were used to evaluate registration performance of each tradeoff relative to the gold standard. For fixed scan times, the optimal SNR for registration with MR imaging was found to be ∼20. Image resolution should be adjusted to produce this target voxel SNR when registration is a central processing task. Hum Brain Mapp 2008.

Trading off SNR and resolution in MR images

With a fixed time to acquire a magnetic resonance (MR) image, time can be spent to acquire better spatial resolution with decrease in signal‐to‐noise ratio (SNR) or decreased resolution with increase in SNR. This resolution/SNR tradeoff at fixed time has been investigated by a visual rater study using images of ex vivo mouse brains. Simulated images with a tradeoff between SNR and resolution were produced from high‐quality, 3D isotropic mouse brain images to emulate shorter constant acquisition times. The tradeoff images spanned a range of SNRs (63–6) and isotropic resolutions (32–81 µm). Fourteen readers identified the image which best displayed neuroanatomy. Additional experiments tested for (i) intra‐observer consistency, (ii) the effect of emulated scan time, and (iii) specifically biased questions pertaining to the perception of neuroanatomy. Optimal anatomical viewing depended primarily on the SNR of the images. Specifically, for fixed imaging time, preference lay in the SNR range of ∼30–35 with strong consistency and there was minimal effect from overall imaging time. Copyright

Segmentation, Registration, and Deformation Analysis of 3D MR Images of Mice

We demonstrate our mouse MR image and shape analysis pipeline. The long term goal of our work is the description of structural shape variations in normal, genetically identical mice and the subsequent detection of pathological phenotypes in genetically modified mice. The pipeline begins with the acquisition and reconstruction of high resolution MR images of mice. Regions of the images containing organs under study are enhanced via edge-preserving smoothing and mouse organs are segmented using a deformable mesh model. Images are registered using a multi-resolution approach and displacement fields are used to calculate local volume changes. Detailed descriptions and results for each step of the pipeline are presented.