Chronic kidney disease (CKD) is characterized by inflammation and fibrosis in the kidney. Renal biopsies and estimated glomerular filtration rate (eGFR) remain the standard of care, but these endpoints have limitations in detecting the stage, progression, and spatial distribution of fibrotic pathology in the kidney. MRI diffusion tensor imaging (DTI) has emerged as a promising noninvasive technology to evaluate renal fibrosis in vivo both in clinical and preclinical studies.
View Article and Find Full Text PDFAlthough critical for development of novel therapies, understanding altered lung function in disease models is challenging because the transport and diffusion of gases over short distances, on which proper function relies, is not readily visualized. In this review we summarize progress introducing hyperpolarized Xe imaging as a method to follow these processes in vivo. The work is organized in sections highlighting methods to observe the gas replacement effects of breathing (Gas Dynamics during the Breathing Cycle) and gas diffusion throughout the parenchymal airspaces (3).
View Article and Find Full Text PDFHyperpolarized Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology.
View Article and Find Full Text PDFJ Med Imaging (Bellingham)
April 2019
Three-dimensional (3D) printing has significantly impacted the quality, efficiency, and reproducibility of preclinical magnetic resonance imaging. It has vastly expanded the ability to produce MR-compatible parts that readily permit customization of animal handling, achieve consistent positioning of anatomy and RF coils promptly, and accelerate throughput. It permits the rapid and cost-effective creation of parts customized to a specific imaging study, animal species, animal weight, or even one unique animal, not routinely used in preclinical research.
View Article and Find Full Text PDFObjective: The objective of our study was to identify the magnitude and distribution of ventilation defect scores (VDSs) derived from hyperpolarized (HP) Xe-MRI associated with clinically relevant airway obstruction.
Materials And Methods: From 2012 to 2015, 76 subjects underwent HP Xe-MRI (48 healthy volunteers [mean age ± SD, 54 ± 17 years]; 20 patients with asthma [mean age, 44 ± 20 years]; eight patients with chronic obstructive pulmonary disease [mean age, 67 ± 5 years]). All subjects underwent spirometry 1 day before MRI to establish the presence of airway obstruction (forced expiratory volume in 1 second-to-forced vital capacity ratio [FEV/FVC] < 70%).
Hyperpolarized (HP) Xe MRI is emerging as a powerful, non-invasive method to image lung function and is beginning to find clinical application across a range of conditions. As clinical implementation progresses, it becomes important to translate back to well-defined animal models, where novel disease signatures can be characterized longitudinally and validated against histology. To date, preclinical Xe MRI has been limited to only a few sites worldwide with 2D imaging that is not generally sufficient to fully capture the heterogeneity of lung disease.
View Article and Find Full Text PDFPurpose: The purpose of this work was to accurately characterize the spectral properties of hyperpolarized Xe in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy volunteers.
Methods: Subjects underwent hyperpolarized Xe breath-hold spectroscopy, during which 38 dissolved-phase free induction decays (FIDs) were acquired after reaching steady state (echo time/repetition time = 0.875/50 ms; bandwidth = 8.
Purpose: Hyperpolarized Xe magnetic resonance imaging (MRI) using Dixon-based decomposition enables single-breath imaging of Xe in the airspaces, interstitial barrier tissues, and red blood cells (RBCs). However, methods to quantitatively visualize information from these images of pulmonary gas transfer are lacking. Here, we introduce a novel method to transform these data into quantitative maps of pulmonary ventilation, and Xe gas transfer to barrier and RBC compartments.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
April 2017
Human genome-wide association studies have identified over 50 loci associated with pulmonary function and related phenotypes, yet follow-up studies to determine causal genes or variants are rare. Single nucleotide polymorphisms in serotonin receptor 4 () are associated with human pulmonary function in genome-wide association studies and follow-up animal work has demonstrated that is causally associated with pulmonary function in mice, although the precise mechanisms were not identified. We sought to elucidate the role of neural innervation and pulmonary architecture in the lung phenotype of animals.
View Article and Find Full Text PDFObjectives: The aim of this study was to investigate ventilation in mild to moderate asthmatic patients and age-matched controls using hyperpolarized (HP) Xenon magnetic resonance imaging (MRI) and correlate findings with pulmonary function tests (PFTs).
Materials And Methods: This single-center, Health Insurance Portability and Accountability Act-compliant prospective study was approved by our institutional review board. Thirty subjects (10 young asthmatic patients, 26 ± 6 years; 3 males, 7 females; 10 older asthmatic patients, 64 ± 6 years; 3 males, 7 females; 10 healthy controls) were enrolled.
Purpose: Xe interacts with biological media to exhibit chemical shifts exceeding 200 ppm that report on physiology and pathology. Extracting this functional information requires shifts to be measured precisely. Historically, shifts have been reported relative to the gas-phase resonance originating from pulmonary airspaces.
View Article and Find Full Text PDFPurpose: The aim of this study was to evaluate the effect of hyperpolarized (129)Xe dose on image signal-to-noise ratio (SNR) and ventilation defect conspicuity on both multi-slice gradient echo and isotropic 3D-radially acquired ventilation MRI.
Materials And Methods: Ten non-smoking older subjects (ages 60.8±7.
Rationale And Objectives: Clinical deployment of hyperpolarized (129)Xe magnetic resonance imaging requires accurate quantification and visualization of the ventilation defect percentage (VDP). Here, we improve the robustness of our previous semiautomated analysis method to reduce operator dependence, correct for B1 inhomogeneity and vascular structures, and extend the analysis to display multiple intensity clusters.
Materials And Methods: Two segmentation methods were compared-a seeded region-growing method, previously validated by expert reader scoring, and a new linear-binning method that corrects the effects of bias field and vascular structures.
A variety of pulmonary pathologies, in particular interstitial lung diseases, are characterized by thickening of the pulmonary blood-gas barrier, and this thickening results in reduced gas exchange. Such diffusive impairment is challenging to quantify spatially, because the distributions of the metabolically relevant gases (CO2 and O2) cannot be detected directly within the lungs. Hyperpolarized (HP) (129)Xe is a promising surrogate for these metabolic gases, because MR spectroscopy and imaging allow gaseous alveolar (129)Xe to be detected separately from (129)Xe dissolved in the red blood cells (RBCs) and the adjacent tissues, which comprise blood plasma and lung interstitium.
View Article and Find Full Text PDFAlthough some central aspects of pulmonary function (ventilation and perfusion) are known to be heterogeneous, the distribution of diffusive gas exchange remains poorly characterized. A solution is offered by hyperpolarized 129Xe magnetic resonance (MR) imaging, because this gas can be separately detected in the lung's air spaces and dissolved in its tissues. Early dissolved-phase 129Xe images exhibited intensity gradients that favored the dependent lung.
View Article and Find Full Text PDFIn this study, hyperpolarized (129) Xe MR ventilation and (1) H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age-matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader-based ventilation defect score percentage (VDS%) and a semi-automated segmentation-based ventilation defect percentage (VDP). Reader-based values were assigned by two experienced radiologists and resolved by consensus.
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