2009. "Optimization of nanoparticle core size for magnetic particle imaging." Journal of Magnetism and Magnetic Materials 321(10):1548-1551. Abstract Magnetic Particle Imaging (MPI) is a powerful new diagnostic visualization platform designed for measuring the amount and location of superparamagnetic nanoscale molecular probes (NMPs) in biological tissues. Promising initial results indicate that MPI can be extremely sensitive and fast, with good spatial resolution for imaging human patients or live animals. Here, we present modeling results that show how MPI sensitivity and spatial resolution both depend on NMP-core physical properties, and how MPI performance can be effectively optimized through rational core design. Monodisperse magnetite cores are attractive since they are readily produced with a biocompatible coating and controllable size that facilitates quantitative imaging.
2009. "Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models ." Inhalation Toxicology 21(5-7):512-518. Abstract The percentages of total airἀows over the nasal respiratory and olfactory epithelium of female rabbits were cal-culated from computational ἀuid dynamics (CFD) simulations of steady-state inhalation. These airἀow calcula-tions, along with nasal airway geometry determinations, are critical parameters for hybrid CFD/physiologically based pharmacokinetic models that describe the nasal dosimetry of water-soluble or reactive gases and vapors in rabbits. CFD simulations were based upon three-dimensional computational meshes derived from magnetic resonance images of three adult female New Zealand White (NZW) rabbits. In the anterior portion of the nose, the maxillary turbinates of rabbits are considerably more complex than comparable regions in rats, mice, mon-keys, or humans. This leads to a greater surface area to volume ratio in this region and thus the potential for increased extraction of water soluble or reactive gases and vapors in the anterior portion of the nose compared to many other species. Although there was considerable interanimal variability in the Ḁne structures of the nasal turbinates and airἀows in the anterior portions of the nose, there was remarkable consistency between rabbits in the percentage of total inspired airἀows that reached the ethmoid turbinate region (~50%) that is presumably lined with olfactory epithelium. These latter results (airἀows reaching the ethmoid turbinate region) were higher than previous published estimates for the male F344 rat (19%) and human (7%). These diᴀerences in regional airἀows can have signiḀcant implications in interspecies extrapolations of nasal dosimetry.
2008. "MR Imaging of Apparent 3He Gas Transport in Narrow Pipes and Rodent Airways ." Journal of Magnetic Resonance 194(2):182-191. doi:10.1016/j.jmr.2008.07.006 Abstract High sensitivity makes hyperpolarized 3He an attractive signal source for visualizing gas flow with magnetic resonance (MR) imaging. Its rapid Brownian motion, however, can blur observed flow lamina and alter measured diffusion rates when excited nuclei traverse shear-induced velocity gradients during data acquisition. Here, both effects are described analytically, and predicted values for measured transport during laminar flow through a straight, 3.2-mm-diameter pipe are validated using two-dimensional (2D) constant-time images of different binary gas mixtures. Results show explicitly how measured transport in narrow conduits is characterized by apparent values that depend on underlying gas dynamics and imaging time. In ventilated rats, this is found to obscure acquired airflow images. Flow splitting at airway branches is still evident, however, and use of 3D vector flow mapping is shown to provide a quantitative view of pulmonary gas supply that highlights the correlation of airflow dynamics with lung structure.
2008. "3D He-3 diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs." Journal of Applied Physiology 105:1291-1300. doi:10.1152/japplphysiol.90375.2008 Abstract In this work, we validate 3He magnetic resonance imaging as a non-invasive morphometric tool to assess emphysematous disease state on a local level. Emphysema was induced intratracheally in rats with 25U/100g body weight of porcine pancreatic elastase dissolved in 200 μL saline. Rats were then paired with saline-dosed controls. Nine three-dimensional 3He diffusion-weighted images were acquired at one-, two-, or three-weeks post-dose, after which the lungs were harvested and prepared for histological analysis. Recently introduced indices sensitive to the heterogeneity of the airspace size distribution were calculated. These indices, D1 and D2, were derived from the moments of the mean equivalent airway diameters. Averaged over the entire lung, it is shown that the 3He diffusivity (Dave) and anisotropy (Dan) both correlate with histology (R = 0.85, p < 0.0001 and R = 0.88, p < 0.0001, respectively). By matching small (0.046 cm2) regions in 3He images with corresponding regions in histological slices, Dave and Dan each correlate significantly with both D1 and D2 (R = 0.93, p < 0.0001). It is concluded that 3He MRI is a viable non-invasive morphometric tool for localized in vivo emphysema assessment.
2008. "Metabolomics in Lung Inflammation: A High Resolution ¹H NMR Study of Mice Exposed to Silica Dust ." Toxicology Mechanisms and Methods 18(5):385-398. doi:10.1080/15376510701611032 Abstract First ¹H NMR metabolomics studies on excised lungs and bronchoalveolar lavage fluids (BALF) from mice exposed to crystalline silica are reported. High resolution ¹H NMR metabolic profiling on intact excised lungs is carried out using slow magic angle sample spinning (slow-MAS) ¹H PASS (phase altered spinning sidebands) at a sample spinning rate of 80 Hz while metabolic profiling on BALF is carried out using fast magic angle spinning at 2kHz. Major findings are that the relative concentrations of choline, phosphocholine (PC) and glycerophosphocholine(GPC) are significantly increased in silica exposed mice versus sham controls, indicating an altered membrane choline phospholipids metabolism (MCPM) during lung inflammation. The relative concentrations of glycogen/glucose, lactate and creatine are also increased in mice exposed to silica dusts, suggesting that the cellular energy pathways are affected by silica dust exposure. Elevated levels of Glycine, lysine, glutamate and proline are also fund increased in exposed mice suggesting the activation of a collagen pathway. Overall, metabolic profiles in the lungs of mice exposed to silica dusts are found to be spatially heterogeneous consistent with regional inflammation revealed by in vivo magnetic resonance imaging (MRI).
2008. "An Automated Self-similarity Analysis of the Pulmonary Tree of the Sprague-Dawley Rat." The Anatomical Record 291(12):1628-1648. doi:10.1002/ar.20771 Abstract Abstract In this study, we present an automated method for tabulating geometric information of biological trees, based on magnetic resonance imaging data of silicone casts of the pulmonary airway trees of Sprague Dawley rats. From a segmentation of the airway tree, we construct a scale-invariant triangulated surface that is subsequently distilled into a connected graph, representing the airway centerline. Segment statistics are derived from this graph. To validate the method, these statistics are compared to manual measurements of a single lung cast. Subsequently, we analyze the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop a parameterization of these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character and can be described by a simple set of equations.
2007. "3D MRI of Non-Gaussian ³He Gas Diffusion in the Rat Lung." Journal of Magnetic Resonance 188(2):357-366. doi:10.1016/j.jmr.2007.08.014 Abstract In ³He magnetic resonance images of pulmonary air spaces, the confining architecture of the parenchymal tissue results in a non-Gaussian distribution of signal phase that non-exponentially attenuates image intensity as diffusion weighting is increased. Here, two approaches previously used for the analysis of non-Gaussian effects in the lung are compared and related using diffusion-weighted ³He MR images of mechanically ventilated rats. Total lung coverage is achieved using a hybrid 3D pulse sequence that combines conventional phase encoding with sparse radial sampling for efficient gas usage. This enables the acquisition of nine 3D images using a total of only ~ 1 L of hyperpolarized ³He gas. Diffusion weighting ranges from 0 s/cm² to 40 s/cm². Results show that the non-Gaussian effects of ³He gas diffusion in healthy rat lungs are directly attributed to the anisotropic geometry of lung microstructure, and that quantitative analysis over the entire lung can be reliably repeated in time-course studies of the same animal.
2007. "Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques." Toxicologic Pathology 35(1):27-40. Abstract ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.
2006. "Magnetic Resonance Imaging (MRI) of PEM Dehydration and Gas Manifold Flooding During Continuous Fuel Cell Operation." Journal of Power Sources 161(2):856-863. Abstract The methods, apparatus, and results are reported for in-situ, near real time, magnetic resonance imaging (MRI) of MEA dehydration and gas manifold flooding in an operating PEM fuel cell. To acquire high-resolution, artifact-free images for visualizing water distribution, acquisition parameters for a standard, two-dimensional (2D), spin-echo sequence were first optimized for the measured magnetic field heterogeneity induced by fuel cell components. 2D images of water inside the fuel cell were then acquired every 128 seconds during 11.4 hours of continuous operation under constant load. Collected images revealed that MEA dehydration proceeded non-uniformly across its plane, starting from gas inlets and ending at gas outlets, and that upon completion of this dehydration process manifold flooding began. To understand these observations, acquired images were correlated to the current output and operating characteristics of the fuel cell. Results demonstrate the power of MRI for in-situ, near real-time imaging of water distribution and non-uniformity in operating PEM fuel cells, and highlight its utility for understanding PEM fuel cell operation, the causes of cell failure, and for developing new strategies of water management.
2006. "Application of Magnetic Resonance (MR) Imaging for the Development and Validation of Computational Fluid Dynamic (CFD) Models of the Rat Respiratory System." Inhalation Toxicology 18(10):787-794. doi: 10.1080/08958370600748729 Abstract Computational fluid dynamic (CFD) models of the respiratory system provide a quantitative, biological basis for extrapolating the localized dosimetry of inhaled materials and improving human health risk assessments based upon inhalation studies conducted in animals. Nevertheless, model development and validation have historically been tedious and time-consuming tasks that have traditionally limited CFD’s wider utilization for inhalation research. In recognition of this we previously reported on the use of proton (1H) Magnetic Resonance (MR) imaging for visualizing nasal-sinus passages in the rat, and on the use of three-dimensional (3D) image data for speeding computational mesh generation. Here, detailed 3D 1H MR imaging of pulmonary casts is reported, mesh generation is described in more detail, simulated gas-flows in nasal-sinus airways are presented, and the feasibility of validating CFD predictions with MR is tested by imaging the dynamics of hyperpolarized 3He at physiological flow rates in a straight pipe with a diameter comparable to the rat trachea. Results show that measured laminar flow structure is significantly blurred by rapid 3He diffusion but that the degree of blurring is generally predictable from the diffusion equation. Findings therefore support the notion that MR imaging is not only useful for defining airway architecture but also rapid CFD validation, and in this context, progress towards applications involving live animals and airway models is described.
2005. "T2-Shortening of 3He Gas by Magnetic Microspheres." Journal of Magnetic Resonance 173(1):90-96. Abstract In the interconnected pores of a material like the lung the transverse relaxation time (T2) for 3He gas is shortened by the deposition of magnetic microspheres and rapid molecular diffusion through induced field distortions. Here, this unique relaxation process is described theoretically and predicted T2-shortening is validated using pressurized 3He gas in a foam model of lung tissue. Results demonstrate that – 1) significant T2-shortening is induced by microsphere deposition, 2) shortened T2’s are accurately predicted, and 3) measured relaxation times are exploitable for quantifying the local volume fraction of magnetic microspheres deposited in gas-filled spaces.
2005. "NMR methods for in-situ biofilm metabolism studies." Journal of Microbiological Methods 62(3):337-344. Abstract Novel procedures and instrumentation are described for nuclear magnetic resonance (NMR) spectroscopy and imaging studies of live, in situ microbial films. A perfused NMR/optical microscope sample chamber containing a planar biofilm support was integrated into a recirculation/dilution flow loop growth reactor system and used to grow in situ Shewanella oneidensis strain MR-1 biofilms. Localized NMR techniques were developed and used to non-invasively monitor time-resolved metabolite concentrations and to image the biomass volume and distribution. As a first illustration of the feasibility of the methodology an initial 13C-labeled lactate metabolic pathway study was performed, yielding results consistent with existing genomic data for MR-1. These results represent progress toward our ultimate goal of correlating time- and depth-resolved metabolism and mass transport with gene expression in live in situ biofilms using combined NMR/optical microscopy techniques.
2005. "Relaxation Nuclear Magnetic Resonance Imaging Investigation of Heterogeneous Aging in a Hydroxy-Terminated Polybutadiene-Based Elastomer ." Macromolecules 38(26):10694-10701. Abstract Relaxation nuclear magnetic resonance imaging (R-NMRI) was employed to investigate the effects of thermo-oxidative aging in a hydroxy-terminated polybutadiene (HTPB) based elastomer. A series of three-dimensional (3D) Hahn-echo weighted single point images (SPI) of the elastomer were utilized to generate a 3D parameter map of the aged material. NMR spin-spin relaxation times (T2) were measured for each voxel producing a 3D NMR parameter (T2) map of the aged polymer. These T2 maps reveal a dramatic reduction of local polymer mobility near the aging surface with the degree of T2 heterogeneity varying as a function of aging. Using correlations between NMR T2 and material modulus, the impact of this heterogeneous thermo-oxidative aging on the mateial properties is discussed.
2004. "Simultaneous 1H PFG-NMR and Confocal Microscopy of Monolayer Cell Cultures: Effects of Apoptosis and Necrosis on Water Diffusion and Compartmentalization." Magnetic Resonance in Medicine 52(3):495-505. Abstract Apoptosis and necrosis is induced in monolayer cultures of Chinese hamster ovary cells using okadaic acid and hydrogen peroxide (H2O2) respectively, and the effect on water diffusion and compartmentalization is examined using pulsed-field-gradient (PFG) 1H-NMR and simultaneous confocal microscopy. In PFG experiments characterized by a fixed diffusion time (< 4.7 msec) and variable b-values (0-27,000 s/mm2) 1H-NMR data collected with untreated cells exhibits multi-exponential behavior. Analysis using a slow-exchange model reveals two distinct cellular water compartments with different apparent diffusion coefficients (0.56, 0.06 x 10-3 mm2/sec) and volume fractions (0.96, 0.04). During the first 12 hours of either necrosis or apoptosis the amount of water in the smallest compartment increases two-fold prior to significant changes in cell density or plasma membrane integrity. Over the same period water content in the largest compartment decreases by over a factor of two in apoptotic cells, in accordance with observed cell shrinkage, and changes little in necrotic counterparts where only slight swelling is evident. PFG 1H-NMR therefore serves as a sensitive indicator of early cell death in monolayer cultures and can distinguish apoptosis from necrosis. Measurements of restricted diffusion and water exchange are also presented to elucidate compartment origins and justify model assumptions.
2002. "Combined Confocal and Magnetic Resonance Microscopy." Applied Magnetic Resonance 22(2):145-158. Abstract Confocal and magnetic resonance microscopy are both used to study live cells in a minimally invasive way. Both techniques provide complementary information. Therefore, by examining cells simultaneously with both methodologies, more detailed information is obtained than is possible with each of the microscopes individually. In this paper two configurations of a combined confocal and magnetic resonance microscope described. In both cases the sample compartment is part of a temperature regulated perfusion system. The first configuration is capable of studying large single cells or three-dimensional cell agglomerates, whereas with the second configuration monolayers of mammalian cells can be investigated . Combined images are shown of Xenopus laevis frog oocytes, model JB6 tumor spheroids, and a single layer of Chinese hamster ovary cells. Finally, potential applications of the combined microscope are discussed.
2002. "Picoliter H-1 NMR Spectroscopy." Journal of Magnetic Resonance 154(2):336-343. Abstract A RF probe that fits inside the bore of a small gradient coil package is described for routine 1H-NMR microscopy measurements on small samples. The probe operates at 500 MHz and houses a 267-um-diameter solenoid transceiver. When used in three dimensional chemical shift imaging (3D-CSI) experiments, the measured signal-to-noise ratio (SNR) is shown to be within 20-30 percent of theoretical limits formulated by only considering the solenoid's resistive losses. This is illustrated using a 100-um-diameter globule of triacylglycerols (~900mM) that may be an oocyte precursor in young Xenopus Laevis frogs, and water sample containing choline at a concentration often found in live cells (~33mM). In chemical shift images generated using a few thousand scans, the choline methyl line is found to have an acceptable SNR in resolved from just 5 picoliters in the Xenopus globule. It is concluded that the probe's sensitivity is sufficient for performing 1H-NMR on picoliter-scale volumes in biological cells and tissues.
2002. "A combined confocal and magnetic resonance microscope for biological studies." Review of Scientific Instruments 73(12):4329-4338. Abstract Complementary data acquired with different microscopy techniques provide a basis for establishing a more comprehensive understanding of cell function in health and diseas, particularly when results acquired with different methodologies can be correlated in time and space.
2001. "Potential Technology for Studying Dosimetry and Response to Airborne Chemical and Biological Pollutants." Toxicology and Industrial Health 17(5-10):270-6. Abstract Advances in computational, and imaging techniques have enabled the rapid development of 3-dimensional (3-D) models of biological systems in unprecedented detail. Using these advances, 3-D models of the lungs and nasal passages of the rat and human are being developed to ultimately improve predictions of airborne pollutant dosimetry. Techniques for imaging the respiratory tract by magnetic resonance (MR) imaging were developed to improve the speed and accuracy of geometric data collection for mesh reconstruction. The MR imaging resolution is comparable to that obtained by manual measurements but at much greater speed and accuracy. Newly developed software (NWGrid) was utilized to translate imaging data from MR into 3-D mesh structures. Together, these approaches significantly reduced the time to develop a 3-D model. This more robust airway structure will ultimately facilate modeling gas or vapor exchange between the respiratory tract and vasculature as well as enable linkages of dosimetry with cell response models. The 3-D, finite volume, visco-elastic mesh structures forms the geometric basis for computational fluid dynamics modeling of inhalation, exhalation and the delivery of individual particles (or concentrations of gas or vapors) to discrete regions of the respiratory tract. The ability of these 3-D models to resolve dosimetry at such a high level of detail will require new techniques to measure regional airflows and particulate deposition for model validation.
2001. "Solenoidal Microcoil Design. Part II: Optimizing Winding Parameters for Maximum Signal-to-Noise Performance." Concepts in Magenetic Resonance 13(3):190-210. Abstract In high-field proton NMR, the signal-to-noise ratio (SNR) achieved with a close-fitting solenoidal microcoil is adversely affected by radio frequency (RF) losses in the coil, its leads, the capacitor used to tune it, and finally, the sample. In Part II, a rigorous description of these various losses is presented, and their severity is related to the details of coil design. Results not only provide a rational basis for defining a microcoil's optimal wire diameter and the number of turns, but also for evaluating how the SNR varies with coil size and NMR frequency in high-field proton NMR studies involving either conducting or non-conducting samples.
2001. "Solenoidal Microcoil Design. Part I: Optimizing RF Homogeneity and Coil Dimensions." Concepts in Magenetic Resonance 13(2):128-142. Abstract In Part I of this two part series, the spatial uniformity of the NMR response inside a solenoid-shaped transceiver coil is related to its dimensions, the size of the sample, and the type of radio frequency (RF) pulse sequence employed. The results establish practical guidelines for maximizing NMR sensitivity by defining minimum coil dimensions necessary for sufficient RF field homogeneity in common NMR experiments. IN Part II, strategies for optimizing other coil parameters are developed by condisering how the signal-tonoise ration (SNR) is influenced by a solenoid's size, number of turns, wire diameter, and operating frequency, particularly when its minimum dimensions are fixed by RF homogeneity constraints.
2000. "An Integrated Confocal and Magnetic Resonance Microscope for Cellular Research." Journal of Magnetic Resonance 147(2):371-377. Abstract Complementary date acquired with different microscopy techniques provide a basis for establishing a more comprehensive understanding of health and disease at a cellular level, particularly when data acquired with different methodologies can be correlated in both time and space. In this communication, a brief description of a novel instrument capable of simultaneously performing confocal optical and magnetic resonance microscopy is presented, and the first combined images of live Xenopus laevis oocytes are shown. Also, the potential benefits of combined microscopy are discussed, and it is shown that the a priori knowledge of the high-resolution and contract of the MR images.
2000. "In vivo MRI Measurements of Tumor Growth Induced by Dichloroacetate: Implications for Mode of Action." Toxicology 145(2-3):115-125.
1998. "A Compact Respiratory -Triggering Device for Routine Microimaging of Laboratory Mice." Journal of Magnetic Resonance Imaging (Nov-Dec 1998):1343-1348. Abstract There is no abstract currently available for this item