Enabling Clinical Technologies for Hyperpolarized Xenon Magnetic Resonance Imaging and Spectroscopy.

Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4-8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin-exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as Xe.

Effect of inhaled oxygen concentration on Xe chemical shift of red blood cells in rat lungs.

Purpose: To investigate the dependence of dissolved Xe chemical shift on the fraction of inhaled oxygen, F O , in the lungs of healthy rats.

Methods: The chemical shifts of Xe dissolved in red blood cells, δ , and blood plasma and/or tissue, δ , were measured using MRS in 12 Sprague Dawley rats mechanically ventilated at F O values of 0.14, 0.

A semi-empirical model to optimize continuous-flow hyperpolarized Xe production under practical cryogenic-accumulation conditions.

Continuous-flow spin exchange optical pumping (SEOP) with cryogenic accumulation is a powerful technique to generate multiple, large volumes of hyperpolarized (HP) Xe in rapid succession. It enables a range of studies, from dark matter tracking to preclinical and clinical MRI. Multiple analytical models based on first principles atomic physics and device-specific design features have been proposed for individual processes within HP Xe production.

Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models.

During lung inflation, airspace dimensions are affected nonlinearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats ( = 7) and healthy controls ( = 7) were imaged with HP MRI.

Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Purpose To assess the feasibility and optimize the accuracy of the multibreath wash-in hyperpolarized helium 3 ((3)He) approach to ventilation measurement by using magnetic resonance (MR) imaging as well as to examine the physiologic differences that this approach reveals among nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Materials and Methods All experiments were approved by the local institutional review board and compliant with HIPAA. Informed consent was obtained from all subjects.

Alterations of regional alveolar oxygen tension in asymptomatic current smokers: assessment with hyperpolarized (3)He MR imaging.

Purpose: To assess the ability of helium 3 ((3)He) magnetic resonance (MR) imaging of regional alveolar partial pressure of oxygen (Pao2) to depict smoking-induced functional alterations and to compare its efficacy to that of current diagnostic techniques.

Materials And Methods: This study was approved by the local institutional review board and was compliant with HIPAA. All subjects provided informed consent.

Hyperpolarized (3)He diffusion MRI and histology of secreted frizzled related protein-1 (SFRP1) deficient lungs in a Murine model.

Secreted frizzled related protein-1 (SFRP1) plays a key role in many diverse processes, including embryogenesis, tissue repair, bone formation, and tumor genesis. Previous studies have shown the effects of the SFRP1 gene on lung development using the SFRP1 knockout mouse model via histological and physiological studies. In this study, the feasibility of ADC (acquired via HP (3)He) to detect altered lung structure in the SFRP1 knockout (SFRP1(-/-)) mice was investigated, and compared to analysis by histology.

Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

Rationale And Objectives: Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error.

Positive end-expiratory pressure increments during anesthesia in normal lung result in hysteresis and greater numbers of smaller aerated airspaces.

Background: Although it is recognized that pulmonary hysteresis can influence the effects of positive end-expiratory pressure (PEEP), the extent to which expansion of previously opened (vs. newly opening) peripheral airspaces contribute to increased lung volume is unknown.

Methods: Following a recruitment maneuver, rats were ventilated with constant tidal volumes and imaged during ascending and descending ramps of PEEP.

Accelerated fractional ventilation imaging with hyperpolarized Gas MRI.

Purpose: To investigate the utility of accelerated imaging to enhance multibreath fractional ventilation (r) measurement accuracy using hyperpolarized gas MRI. Undersampling shortens the breath-hold time, thereby reducing the O2 -induced signal decay and allows subjects to maintain a more physiologically relevant breathing pattern. Additionally, it may improve r estimation accuracy by reducing radiofrequency destruction of hyperpolarized gas.

A variability study of regional alveolar oxygen tension measurement in humans using hyperpolarized (3) He MRI.

Purpose: A systematic study of the short-term and long-term variability of regional alveolar partial pressure of oxygen tension (pA O2 ) measurements using (3) He magnetic resonance imaging was presented. Additionally, the repeatability of the average evaluated pA O2 was compared with that of the standard pulmonary function tests.

Methods: Pulmonary function test and pA O2 imaging were performed on 4 nonsmokers (1 M, 3 F, 56 ± 1.

Imaging the interaction of atelectasis and overdistension in surfactant-depleted lungs.

Objective: Atelectasis and surfactant depletion may contribute to greater distension-and thereby injury-of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes.

Multislice fractional ventilation imaging in large animals with hyperpolarized gas MRI.

The noninvasive assessment of regional lung ventilation is of critical importance in the quantification of the severity of disease and evaluation of response to therapy in many pulmonary diseases. This work presents, for the first time, the implementation of a hyperpolarized (HP) gas MRI technique to measure whole-lung regional fractional ventilation (r) in Yorkshire pigs (n = 5) through the use of a gas mixing and delivery device in the supine position. The proposed technique utilizes a series of back-to-back HP gas breaths with images acquired during short end-inspiratory breath-holds.

A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently.

Regional function-structure relationships in lungs of an elastase murine model of emphysema.

Changes in lung function and structure were studied using hyperpolarized (3)He MRI in an elastase-induced murine model of emphysema. The combined analysis of the apparent diffusion coefficient (ADC) and fractional ventilation (R) were used to distinguish emphysematous changes and also to develop a model for classifying sections of the lung into diseased and normal. Twelve healthy male BALB/c mice (26 ± 2 g) were randomized into healthy and elastase-induced mice and studied ∼8-11 wk after model induction.

A simple and low-cost device for generating hyperpolarized contrast agents using parahydrogen.

A detailed description of the construction and use of a device for hyperpolarization of select contrast agents is presented. The device is based on molecular incorporation of the spin-order inherent to parahydrogen, followed by order transfer to a metastable heteronuclear alignment. Design considerations and experimental results relating to catalyst/solvent choice and handling, solvent heating, efficient gas entrainment and spin-order transfer are described.

Regional determination of oxygen uptake in rodent lungs using hyperpolarized gas and an analytical treatment of intrapulmonary gas redistribution.

A method is presented which allows for the accurate extraction of regional functional metrics in rodent lungs using hyperpolarized gas. The technique is based on the combination of measured T(1) decay, an independent measure of specific ventilation and mass balance considerations to extract the regional oxygen levels and uptake. In phantom and animal experiments, it is demonstrated that the redistribution of gas during the measurement is a significant confounding factor, and this effect is addressed analytically.

Quantitative imaging of alveolar recruitment with hyperpolarized gas MRI during mechanical ventilation.

The aim of this study was to assess the utility of (3)He MRI to noninvasively probe the effects of positive end-expiratory pressure (PEEP) maneuvers on alveolar recruitment and atelectasis buildup in mechanically ventilated animals. Sprague-Dawley rats (n = 13) were anesthetized, intubated, and ventilated in the supine position ((4)He-to-O(2) ratio: 4:1; tidal volume: 10 ml/kg, 60 breaths/min, and inspiration-to-expiration ratio: 1:2). Recruitment maneuvers consisted of either a stepwise increase of PEEP to 9 cmH(2)O and back to zero end-expiratory pressure or alternating between these two PEEP levels.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

Rationale And Objectives: The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease.

Regional correlation of emphysematous changes in lung function and structure: a comparison between pulmonary function testing and hyperpolarized MRI metrics.

Regional and global relationships of lung function and structure were studied using hyperpolarized ³He MRI in a rat elastase-induced model of emphysema (n = 4) and healthy controls (n = 5). Fractional ventilation (r) and apparent diffusion coefficient (ADC) of ³He were measured at a submillimeter planar resolution in ventral, middle, and dorsal slices 6 mo after model induction. Pulmonary function testing (PFT) was performed before MRI to yield forced expiratory volume in 50 ms (FEV₅₀), airway resistance (R(I)), and dynamic compliance (C(dyn)).

Optimal transfer of spin-order between a singlet nuclear pair and a heteronucleus.

Intramolecular spin-order transfer is a useful technique for signal enhancement of insensitive and low-concentration molecular species. We present a closed-form, optimized pulse sequence which maximizes the efficiency of transfer between a singlet (para) nuclear pair and a vicinal heteronucleus. Neglecting the decay of coherences while the nuclei are in the transverse plane, the scheme is unity efficient for all combinations of internuclear scalar couplings.

Improved technique for measurement of regional fractional ventilation by hyperpolarized 3He MRI.

Quantitative measurement of regional lung ventilation is of great significance in assessment of lung function in many obstructive and restrictive pulmonary diseases. A new technique for regional measurement of fractional ventilation using hyperpolarized 3He MRI is proposed, addressing the shortcomings of an earlier approach that limited its use to small animals. The new approach allows for the acquisition of similar quantitative maps over a shortened period and requires substantially less 3He gas.

Quantitative assessment of lung using hyperpolarized magnetic resonance imaging.

Improvements in the quantitative assessment of structure, function, and metabolic activity in the lung, combined with improvements in the spatial resolution of those assessments, enhance the diagnosis and evaluation of pulmonary disorders. Radiologic methods are among the most attractive techniques for the comprehensive assessment of the lung, as they allow quantitative assessment of this organ through measurements of a number of structural, functional, and metabolic parameters. Hyperpolarized nuclei magnetic resonance imaging (MRI) has opened up new territories for the quantitative assessment of lung function and structure with an unprecedented spatial resolution and sensitivity.

Simultaneous measurement of pulmonary partial pressure of oxygen and apparent diffusion coefficient by hyperpolarized 3He MRI.

Hyperpolarized (3)He (HP (3)He) MRI shows promise to assess structural and functional pulmonary parameters in a sensitive, regional, and noninvasive way. Structural HP (3)He MRI has applied the apparent diffusion coefficient (ADC) for the detection of disease-induced lung microstructure changes at the alveolar level, and HP (3)He pulmonary partial pressure of oxygen (pO(2)) imaging measures the oxygen transfer efficiency between the lung and blood stream. Although both parameters are affected in chronic obstructive pulmonary disease (COPD), a quantitative assessment of the regional correlation of the two parameters has not been reported in the literature.