Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility
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- van Beek, E.J.R., Schmiedeskamp, J., Wild, J.M. et al. Eur Radiol (2003) 13: 2583. doi:10.1007/s00330-003-2094-2
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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.
KeywordsMR imagingVentilation studiesHyperpolarized 3-heliumChronic obstructive lung disease
Lung diseases are taking an increasing toll on both mortality and morbidity in western society . The physical conditions of the lungs, including low-proton-density and static field inhomogeneity in the chest, render proton MR imaging of the lungs difficult . Hyperpolarized 3-helium (HP 3-He) MR imaging has been established over the past decade, with increasing clinical studies being reported over the past few years [3, 4, 5, 6, 7, 8]; however, due to equipment and manpower requirements, the availability of HP 3-He has remained largely confined to dedicated research centers using gas polarized with equipment built in-house. Two methods are available at present: the spin exchange technique  or the direct optical pumping technique .
Applications of the first method have been aimed at the installation of individual units, which have been commercialized by Amersham Health. This commercial polarizer is capable of producing 1 l of HP 3-He per 24 h at approximately 30–40% polarization. This is sufficient to perform four MR sequences in one patient with doses currently recommended and based on previous studies . Initial estimates to acquire this equipment are Euro 200,000; however, “on-tap” HP 3-He gas has the advantage of convenience and greater flexibility.
The second method has been used in small-scale individual units for relatively small amounts of HP 3-He gas or in an upscale version for production of larger quantities, such as required in nuclear spin experiments . These units can produce up to 25 l of gas polarized to 50–80% in 24 h. This offers the option of centralized polarization and distribution with the potential advantage that a larger-scale dedicated apparatus could be used to produce gas in large volumes at reduced costs to the imaging department. This principle is similar to that employed in nuclear medicine for radio-isotope distribution.
The T1 relaxation time of HP 3-He gas in the absence of paramagnetic oxygen gas and in a homogeneous magnetic field is potentially very long (days); however, hyperpolarization loss occurs due to wall relaxation in a holding cell and due to field inhomogeneities surrounding the cell. Thus, provided these losses can be sufficiently contained, the possibility of transporting the gas in a hyperpolarized state from a polarization facility to an imaging site becomes a realistic prospect. This article details the initial experience of hyperpolarized gas transport from Mainz to Sheffield.
Materials and methods
Upon arrival, polarization was assessed by comparison of signal-to-noise ratios (SNR) of polarized 3-He and a thermally polarized 3-He phantom within the MR system. The gas was delivered to healthy normal subjects and to subjects with emphysema in the MRI system using an integrated ventilator/applicator device . Vital functions were monitored using an MRI-compatible device (Maglife, Bruker, Wissembourg, France). The study had been approved by the South Sheffield Research and Ethics Committee, and informed consent was obtained from all subjects.
Magnetic resonance imaging was conducted using a 1.5-T whole-body clinical research system (Eclipse, Philips, Cleveland, Ohio), which was tuned to the 3-He Larmor frequency (48 MHz). A quadrature radio-frequency transceiver with a flexible twin saddle coil design (Medical Advances, IGC, Milwaukee, Wis.) was used.
Static ventilation distribution was assessed using an 18-s breath-hold sequence (FOV 42 cm, 128×128 matrix, TE/TR/flip angle 2.5 ms/7 ms/9°, 19 slices with a slice thickness of 10 mm) and centric phase encoding to maximise SNR . Dynamic free breathing imaging was performed using 250 ml of gas and either a non-slice selected fast low-angle shot (FLASH) sequence in the coronal plane (FOV 40 cm, 65×128 matrix, TE/TR/flip angle 6.1 ms/15 ms/8°) with a frame rate of 3.8 images/s  or a radial non-slice selected sequence in the coronal plane (FOV 41 cm, TE/TR 2.6 ms/5.4 ms) with sliding window reconstruction, giving an effective frame refreshment rate of 5.4 ms .
After initial trials to test the robustness of the transport system and the upgraded MRI system in Sheffield, it was shown that overnight transportation was most practical for both organizations. Subsequently, the transport was arranged six times between August 2002 and March 2003. The mean transport duration from production to imaging site (door to door) was 10 h (range 8–12 h), with imaging taking place between 16 and 20 h post-polarization. Initially, polarization at shipment was 50%, whereas this was increased for the last three shipments to 60%. Loss during transportation initially resulted in approximately 20% polarization at time of administration. Improved glass cells yielded polarization levels in excess of 30% during the last three shipments.
We have demonstrated that it is possible to deliver hyperpolarized 3-He gas from a central production facility to an imaging site over long distance. The polarization improved over time, largely due to better glass cells, resulting in consistent signal-to-noise ratio and image quality. Furthermore, it was shown that we have met the strict safety rules for commercial airfreight companies to accept these shipments and that distribution is achieved reliably.
The current costs of shipment are of the order of 250 Euro per shipment, equating to a minimum of 50–60 Euro per subject. This would be on top of the costs of HP 3-He gas, which is sold in non-polarized state at approximately 150 Euro per liter. If it is assumed that 1 l is used per subject, the overall costs per study would be of the order of 250 Euro (similar to a double dose of intravenous gadolinium), with up to 5 subjects studied in succession. In comparison, a dedicated local system is commercially available at a price of approximately 200,000 Euro, with the additional costs for 3-He gas, housing and personnel to run the system. Furthermore, as the maximum output is only 1 l per 24 h, this may decrease the work-flow efficiency.
There was a considerable loss of polarization between the end of polarization and use within the MR imaging suite; however, we noticed significant improvement with the use of larger, virtually iron-free glass cells during the last three shipments. Despite the loss of polarization, levels of 30% polarization or more are routinely achievable with good image quality. This level is comparable to that of local, alkali metal metastable spin-exchange polarizer systems . Several clinical studies have shown that this level is sufficient to perform HP 3-He imaging with meaningful results [6, 7, 8].
We have demonstrated that a central production facility for hyperpolarized 3-He gas, with transportation possible by road–air cargo over a distance in excess of 1000 km (650 miles) and application in human studies, is feasible. This will enhance the availability of HP 3-He to new groups, without the need for start-up costs other than MR hardware.
Acknowledgements. The authors acknowledge support from the European Commission Framework 5 program (www.phil.ens.fr), The British Council Germany, and the DAAD. We also thank Lufthansa for their cooperation. The University of Copenhagen (T. Skavngaard, L. Vejby-Sogaard, and A. Dirksen) contributed to the discussions. This work was presented in part at ECR 2003.