Regional variations in hyperpolarized 129Xe lung MRI: Insights from CSI-CSSR and CSSR in healthy and irradiated rat models.

Purpose: To compare pulmonary function metrics obtained with hyperpolarized xenon-129 (HXe) MRS, using chemical shift saturation recovery (CSSR) and CSI-CSSR, in healthy rats and a rat model of radiation-induced lung injury.

Methods: HXe-MR data were acquired in two healthy rats and one rat with radiation-induced lung injury using whole-lung spectroscopy and CSI-CSSR techniques. The CSI-CSSR acquisitions were performed with both fixed TE and variable TE.

Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy.

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas diffusion, Xenon uptake by lung parenchyma, and other lung function metrics. However, by trading spatial for temporal resolution, it also enables tracing of pulmonary Xenon gas exchange on a ms timescale. This article describes one such technique, chemical shift saturation recovery (CSSR) MR spectroscopy.

Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

Purpose: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters.

Methods: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances.

Preclinical MRI Using Hyperpolarized Xe.

Although 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).

Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

Purpose: To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment.

Methods: Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration.

Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats.

Hyperpolarized Xe MRI of the rat brain with chemical shift saturation recovery and spiral-IDEAL readout.

Purpose: To demonstrate the feasibility of Xe chemical shift saturation recovery (CSSR) combined with spiral-IDEAL imaging for simultaneous measurement of the time-course of red blood cell (RBC) and brain tissue signals in the rat brain.

Methods: Images of both the RBC and brain tissue Xe signals from the brains of five rats were obtained using interleaved spiral-IDEAL imaging following chemical shift saturation pulses applied at multiple CSSR delay times, τ. A linear fit of the signals to τ was used to calculate the slope of the signal for both RBC and brain tissue compartments on a voxel-by-voxel basis.

Radial Flow Perfusion Enables Real-Time Profiling of Cellular Metabolism at Low Oxygen Levels with Hyperpolarized C NMR Spectroscopy.

In this study, we describe new methods for studying cancer cell metabolism with hyperpolarized C magnetic resonance spectroscopy (HP C MRS) that will enable quantitative studies at low oxygen concentrations. Cultured hepatocellular carcinoma cells were grown on the surfaces of non-porous microcarriers inside an NMR spectrometer. They were perfused radially from a central distributer in a modified NMR tube (bioreactor).

Deriving Regionally Specific Biomarkers of Emphysema and Small Airways Disease Using Variable Threshold Parametric Response Mapping on Volumetric Lung CT Images.

Purpose: This study aims to develop and validate a parametric response mapping (PRM) methodology to accurately identify diseased regions of the lung by using variable thresholds to account for alterations in regional lung function between the gravitationally-independent (anterior) and gravitationally-dependent (posterior) lung in CT images acquired in the supine position.

Methods: 34 male Sprague-Dawley rats (260-540 g) were imaged, 4 of which received elastase injection (100 units/kg) as a model for emphysema (EMPH). Gated volumetric CT was performed at end-inspiration (EI) and end-expiration (EE) on separate groups of free-breathing (n = 20) and ventilated (n = 10) rats in the supine position.

Ventilation heterogeneity imaged by multibreath wash-ins of hyperpolarized He and Xe in healthy rabbits.

Key Points: Multibreath imaging to estimate regional gas mixing efficiency is superior to intensity-based single-breath ventilation markers, as it is capable of revealing minute but essential measures of ventilation heterogeneity which may be sensitive to subclinical alterations in the early stages of both obstructive and restrictive respiratory disorders. Large-scale convective stratification of ventilation in central-to-peripheral directions is the dominant feature of observed ventilation heterogeneity when imaging a heavy/less diffusive xenon gas mixture; smaller-scale patchiness, probably originating from asymmetric lung function at bronchial airway branching due to the interaction of convective and diffusive flows, is the dominant feature when imaging a lighter/more diffusive helium gas mixture. Since detecting low regional ventilation is crucial for characterizing diseased lungs, our results suggest that dilution with natural abundance helium and imaging at higher lung volumes seem advisable when imaging with hyperpolarized Xe; this will allow the imaging gas to reach slow-filling and/or non-dependent lung regions, which might otherwise be impossible to distinguish from total ventilation shunt regions.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

Objectives: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury.

Design: Prospective, longitudinal imaging study.

Measuring pulmonary gas exchange using compartment-selective xenon-polarization transfer contrast (XTC) MRI.

Purpose: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)-specific gas-phase (GP) depolarization maps using xenon-polarization transfer contrast (XTC) MR imaging.

Methods: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single-breath XTC data were acquired through a series of three GP images using a 2D multi-slice GRE during a 12 s breath-hold.

Metabolic Imaging and Biological Assessment: Platforms to Evaluate Acute Lung Injury and Inflammation.

Pulmonary inflammation is a hallmark of several pulmonary disorders including acute lung injury and acute respiratory distress syndrome. Moreover, it has been shown that patients with hyperinflammatory phenotype have a significantly higher mortality rate. Despite this, current therapeutic approaches focus on managing the injury rather than subsiding the inflammatory burden of the lung.

Positional Therapy and Regional Pulmonary Ventilation.

Background: Prone ventilation redistributes lung inflation along the gravitational axis; however, localized, nongravitational effects of body position are less well characterized. The authors hypothesize that positional inflation improvements follow both gravitational and nongravitational distributions. This study is a nonoverlapping reanalysis of previously published large animal data.

Pulmonary pyruvate metabolism as an index of inflammation and injury in a rat model of acute respiratory distress syndrome.

Increased pulmonary lactate production is correlated with severity of lung injury and outcome in acute respiratory distress syndrome (ARDS) patients. This study was conducted to investigate the relative contributions of inflammation and hypoxia to the lung's metabolic shift to glycolysis in an experimental animal model of ARDS using hyperpolarized (HP) C MRI. Fifty-three intubated and mechanically ventilated male rats were imaged using HP C MRI before, and 1, 2.

Investigating biases in the measurement of apparent alveolar septal wall thickness with hyperpolarized 129Xe MRI.

Purpose: To investigate biases in the measurement of apparent alveolar septal wall thickness (SWT) with hyperpolarized xenon-129 (HXe) as a function of acquisition parameters.

Methods: The HXe MRI scans with simultaneous gas-phase and dissolved-phase excitation were performed using 1-dimensional projection scans in mechanically ventilated rabbits. The dissolved-phase magnetization was periodically saturated, and the dissolved-phase xenon uptake dynamics were measured at end inspiration and end expiration with temporal resolutions up to 10 ms using a Look-Locker-type acquisition.

Computational pipeline for estimation of small-molecule T1 relaxation times.

Molecular imaging of biologic molecules and cellular processes is increasingly accessible through hyperpolarization of chemically-equivalent stable isotopes, most commonly C. However, many molecules are poor candidates for imaging due to their biophysical properties, particularly short spin-lattice relaxation times (T). The inability to consistently predict the T from molecular structure, lack of experimental data for many biologically-relevant molecules and the high cost of developing probes can limit the development of hyperpolarized probes.

Hyperpolarized Metabolic Imaging Detects Latent Hepatocellular Carcinoma Domains Surviving Locoregional Therapy.

Background And Aims: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon.

Detection of lung transplant rejection in a rat model using hyperpolarized [1- C] pyruvate-based metabolic imaging.

The current standard for noninvasive imaging of acute rejection consists of X-ray/CT, which derive their contrast from changes in ventilation, inflammation and edema, as well as remodeling during rejection. We propose the use of hyperpolarized [1- C] pyruvate MRI-which provides real-time metabolic assessment of tissue-as an early biomarker for tissue rejection. In this preliminary study, we used μCT-derived parameters and HP C MR-derived biomarkers to predict rejection in an orthotopic left lung transplant model in both allogeneic and syngeneic rats.

Quantification of Ventilation and Gas Uptake in Free-Breathing Mice With Hyperpolarized Xe MRI.

Hyperpolarized Xe magnetic resonance imaging is a powerful modality capable of assessing lung structure and function. While it has shown promise as a clinical tool for the longitudinal assessment of lung function, its utility as an investigative tool for animal models of pulmonary diseases is limited by the necessity of invasive intubation and mechanical ventilation procedures. In this paper, we overcame this limitation by developing a gas delivery system and implementing a set of imaging schemes to acquire high-resolution gas- and dissolved-phase images in free-breathing mice.

Measurement of Regional 2D Gas Transport Efficiency in Rabbit Lung Using Hyperpolarized 129Xe MRI.

While hyperpolarized xenon-129 (HXe) MRI offers a wide array of tools for assessing functional aspects of the lung, existing techniques provide only limited quantitative information about the impact of an observed pathology on overall lung function. By selectively destroying the alveolar HXe gas phase magnetization in a volume of interest and monitoring the subsequent decrease in the signal from xenon dissolved in the blood inside the left ventricle of the heart, it is possible to directly measure the contribution of that saturated lung volume to the gas transport capacity of the entire lung. In mechanically ventilated rabbits, we found that both xenon gas transport and transport efficiency exhibited a gravitation-induced anterior-to-posterior gradient that disappeared or reversed direction, respectively, when the animal was turned from supine to prone position.

Multibreath Hyperpolarized He Imaging Scheme to Measure Alveolar Oxygen Tension and Apparent Diffusion Coefficient.

Rationale And Objectives: In this study, we compared a newly developed multibreath simultaneous alveolar oxygen tension and apparent diffusion coefficient (PO-ADC) imaging sequence to a single-breath acquisition, with the aim of mitigating the compromising effects of intervoxel flow and slow-filling regions on single-breath measurements, especially in chronic obstructive pulmonary disease (COPD) subjects.

Materials And Methods: Both single-breath and multibreath simultaneous PO-ADC imaging schemes were performed on a total of 10 human subjects (five asymptomatic smokers and five COPD subjects). Estimated PO and ADC values derived from the different sequences were compared both globally and regionally.

Assessment of flip angle-TR equivalence for standardized dissolved-phase imaging of the lung with hyperpolarized 129Xe MRI.

Purpose: To investigate the feasibility of describing the impact of any flip angle-TR combination on the resulting distribution of the hyperpolarized xenon-129 (HXe) dissolved-phase magnetization in the chest using a single virtual parameter, TR .

Methods: HXe MRI scans with simultaneous gas- (GP) and dissolved-phase (DP) excitation were performed using 2D projection scans in mechanically ventilated rabbits. Measurements with DP flip angles ranging from 6-90° and TRs ranging from 8.

A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized He Magnetic Resonance Imaging.

Rationale And Objectives: The purpose of this study was to assess the effectiveness of hyperpolarized helium-3 magnetic resonance (MR)-based imaging markers in predicting future forced expiratory volume in one second decline/chronic obstructive pulmonary disorder progression in smokers compared to current diagnostic techniques.

Materials And Methods: Total 60 subjects (15 nonsmokers and 45 smokers) participated in both baseline and follow-up visits (∼1.4 years apart).