Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial.

The aim of the present study was to apply hyperpolarised (HP) (3)He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and alpha(1)-antitrypsin deficiency (alpha(1)-ATD) from healthy volunteers and compare HP (3)He MRI findings with high-resolution computed tomography (HRCT) in a multicentre study. Quantitative measurements of HP (3)He MRI (apparent diffusion coefficient (ADC)) and HRCT (mean lung density (MLD)) were correlated with pulmonary function tests. A prospective three centre study enrolled 122 subjects with COPD (either acquired or genetic) and age-matched never-smokers. All diagnostic studies were completed in 94 subjects (52 with COPD; 13 with alpha(1)-ATD; 29 healthy subjects; 63 males; and 31 females; median age 62 yrs). The consensus assessment of radiologists, blinded for other test results, estimated nonventilated lung volume (HP (3)He MRI) and percentage diseased lung (HRCT). Quantitative evaluation of all data for each centre consisted of ADC (HP (3)He MRI) and MLD measurements (HRCT), and correlation with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) indicating airway obstruction, and the diffusing capacity of the lung for carbon monoxide (D(L,CO)) indicating alveolar destruction. Using lung function tests as a reference, regional analysis of HP (3)He MRI and HRCT correctly categorised normal volunteers in 100% and 97%, COPD in 42% and 69% and alpha(1)-ATD in 69% and 85% of cases, respectively. Direct comparison of HP (3)He MRI and CT revealed 23% of subjects with moderate/severe structural abnormalities had only mild ventilation defects. In comparison with lung function tests, ADC was more effective in separating COPD patients from healthy subjects than MLD (p<0.001 versus 0.038). ADC measurements showed better correlation with D(L,CO) than MLD (r = 0.59 versus 0.29). Hyperpolarised (3)He MRI correctly categorised patients with COPD and normal volunteers. It offers additional functional information, without the use of ionising radiation whereas HRCT gives better morphological information. We showed the feasibility of a multicentre study using different magnetic resonance systems.

(3) He Spin Filter for Neutrons.

The strongly spin-dependent absorption of neutrons in nuclear spin-polarized (3)He opens up the possibility of polarizing neutrons from reactors and spallation sources over the full kinematical range of cold, thermal and hot neutrons. This paper gives a report on the neutron spin filter (NSF) development program at Mainz. The polarization technique is based on direct optical pumping of metastable (3)He atoms combined with a polarization preserving mechanical compression of the gas up to a pressure of several bar, necessary to run a NSF. The concept of a remote type of operation using detachable NSF cells is presented which requires long nuclear spin relaxation times of order 100 hours. A short survey of their use under experimental conditions, e.g. large solid-angle polarization analysis, is given. In neutron particle physics NSFs are used in precision measurements to test fundamental symmetry concepts.

Quantification of regional intrapulmonary oxygen partial pressure evolution during apnea by (3)He MRI.

We present a new method to determine in vivo the temporal evolution of intrapulmonary oxygen concentrations by functional lung imaging with hyperpolarized (3)Helium ((3)He-->). Single-breath, single-bolus visualization of (3)He--> administered to the airspaces is used to analyze nuclear spin relaxation caused by the local oxygen partial pressure p(O(2))(t). We model the dynamics of hyperpolarization in the lung by rate equations. Based hereupon, a double acquisition technique is presented to separate depolarization by RF pulses and oxygen induced relaxation. It permits the determination of p(O(2)) with a high accuracy of up to 3% with simultaneous flip angle calibration using no additional input parameters. The time course of p(O(2)) during short periods of breathholding is found to be linear in a pig as well as in a human volunteer. We also measured the wall relaxation time in the lung and deduced a lower limit of 4.3 min.

MR imaging of the lungs with hyperpolarized helium-3 gas transported by air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Imaging of a mixture of hyperpolarized 3He and 129Xe.

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.

[A software program for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) with oxygen-sensitive (3)He-MRI]. / Ein Auswerteprogramm zur quantitativen Analyse von Messungen des alveolären Sauerstoffpartialdrucks (p(A)O(2)) mit der sauerstoffsensitiven (3)He-MR-Tomographie.

PURPOSE: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea. MATERIAL AND METHODS: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm. RESULTS: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients. CONCLUSION: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

[A software tool for analysis and quantification of regional pulmonary ventilation using dynamic hyperpolarised-(3)He-MRI]. / Ein Auswerteprogramm zur quantitativen Untersuchung der Lungenventilation mittels dynamischer MRT von hochpolarisiertem.

PURPOSE: (3)He-MRI is able to visualize the regional distribution of lung ventilation with a temporal and spatial resolution so far unmatched by any other technique. The aim of the study was the development of a new software tool for quantification of dynamic ventilation parameters in absolute physical units. MATERIALS AND METHODS: During continuous breathing, a bolus of hyperpolarized (3)He (300 ml) was applied at inspiration and a series of 168 coronal projection images simultaneously acquired using a 2D FLASH-sequence. Postprocessing software was developed to analyze the (3)He distribution in the lung. After correction for lung motion, several ventilation parameters (rise time, delay time, (3)He amount and (3)He peak flow) were calculated. Due to normalization of signal intensities, these parameters are presented in absolute physical units. The data sets were analyzed on a ROI basis as well as on a pixel-by-pixel basis. RESULTS: Using the developed software, the measurements were analyzed in 6 lung-healthy volunteers, in one patient after lung transplantation, and in one patient with lung emphysema. The volunteers' parameter maps of the pixel-based analysis showed an almost homogeneous distribution of the ventilation parameters within the lung. In the parameter maps of both patients, regions with poor ventilation were observed. CONCLUSION: The developed software permits an objective and quantitative analysis of regional lung ventilation in absolute physical units. The clinical significance of the parameters, however, has to be determined in larger clinical studies. The software may become valuable in grading and following pulmonary function as well as in monitoring any therapy.

[Reformation as proposed solution for the problem of sectioning different levels with 3He-MRT and HR-CT of the chest]. / Reformatierungen als Lösungsansatz für die Problematik der unterschiedlichen Schichtführung beim Vergleich von 3He-MRT und HR-CT der Lunge.

PURPOSE: 3He-MRI of the lung has been shown to be a sensitive method for functional imaging of the lung. A previous study compared 3He-MRI (coronal planes) with CT (transverse planes) by looking for ventilation defects and their pathomorphologic correlation. Anatomic structures, such as lobar fissures and hilar vessels, were used for orientation, but the reliable assignment of ventilation defects to lung segments is problematic. The present work compares multiplanar reformations of 3He-MRI and HR-CT, which were generated from planes determined by the respective method, and investigates their suitability as a solution of this problem. MATERIALS AND METHODS: A total of 16 data sets taken from 15 patients with unilateral lung transplantation and one patient with lung emphysema were retrospectively evaluated. Transverse planes of 3He-MRI and coronal planes of HR-CT were reformatted on an external workstation and images evaluated by two readers in consensus. The evaluation searched for ventilation defects on 3He-MRI and their corresponding defects on HR-CT. The defects were related to anatomic structures, with hilar vessels and tracheobronchial tree selected for 3He-MRI reformations and lobar fissures for HR-CT reformations. RESULTS: All cases were successfully reformatted and all ventilation defects were correctly assigned to anatomic structures. On HR-CT reformations, the lobar fissures were partially visible in 12 of 16 cases and completely visible in the remaining 4 cases. Since reformation compromises the spatial resolution, the reformatted images should be evaluated together with the source images. CONCLUSION: Looking at HR-CT and 3He-MRI images and their reformations enables the detection of ventilation defects and their assignment to lung segments, facilitating the correlation of ventilation defects with a pathomorphologic pattern on HR-CT.

Magnetized boxes for housing polarized spins in homogeneous fields.

We present novel types of permanently magnetized as well as current powered boxes built from soft-ferromagnetic materials. They provide shielded magnetic fields which are homogeneous within a large fraction of the enclosed volume, thus minimizing size, weight, and costs. For the permanently magnetized solutions, homogenization is achieved either by an optimized distribution of the permanent field sources or by jacketing the field with a soft-ferromagnetic cylindrical shell which is magnetized in parallel to the enclosed field. The latter principle may be applied up to fields of about 0.1T. With fields of about 1mT, such boxes are being used for shipping spin-polarized (3)He worldwide for MRI purposes. For current powered boxes, we present concepts and realizations of uniaxial and tri-axial shielded magnetic fields which are homogeneous on the level of 10(-4) within the entire shielded volume. This is achieved by inserting tightly fitting solenoids into a box from soft-magnetic material. The flexible tri-axial solution suits in particular laboratory applications, e.g. for establishing a spin quantization axis.

Magnetic resonance imaging of dissolved hyperpolarized 129Xe using a membrane-based continuous flow system.

A technique for continuous production of solutions containing hyperpolarized (129)Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized (129)Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of (129)Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized (129)Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.

Assessment of a single-acquisition imaging sequence for oxygen-sensitive (3)He-MRI.

MRI of the lungs using hyperpolarized helium-3 ((3)He) allows the determination of intrapulmonary oxygen partial pressures (p(O2)). The need to separate competing processes of signal loss has hitherto required two different imaging series during two different breathing maneuvers. In this work, a new imaging strategy to measure p(O2) by a single series of consecutive scans is presented. The feasibility of the method is demonstrated in three healthy human volunteers. Maps and histograms of intrapulmonary p(O2) are calculated. Changes in the oxygen concentration of the inhaled gas mixture are well reproduced in the histograms. Monte Carlo (MC) simulations of the temporal evolution of (3)He hyperpolarization within the lungs were performed to evaluate the accuracy of this measurement technique, and its limitations.

Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility.

The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs.