Using hyperpolarized 3He MRI to evaluate treatment efficacy in cystic fibrosis patients.

PURPOSE: To use hyperpolarized (HP) (3)He MR imaging to assess functional lung ventilation in subjects with cystic fibrosis (CF) before and after treatment. MATERIALS AND METHODS: We performed HP (3)He static ventilation MRI scans on three subjects, using a Philips 3.0 Tesla (T) Achieva MRI scanner, before and after 11 days of in-patient treatment with combined intravenous and inhaled therapies for pulmonary exacerbations of CF. We also collected spirometry data. We quantified pulmonary ventilation volume measured with HP (3)He MRI using an advanced semi-automated analysis technique. RESULTS: Following 11 days of treatment with intravenous antibiotics, hypertonic saline, and rhDNase, HP (3)He MR images in one subject displayed a 25% increase in total ventilation volume. Total ventilation volume in the other two subjects slightly decreased. All three subjects showed increases in FEV(1) and FVC following treatment. CONCLUSION: In all subjects, the HP (3)He MR images provided detailed information on precisely where in the lungs gas was reaching. These data provide additional support for the conclusion that HP noble gas MRI can be a powerful tool for evaluating lung ventilation in patients with cystic fibrosis, but also raise important questions about the correlation between spirometry and HP gas MRI measurements.

Distribution of hyperpolarized xenon in the brain following sensory stimulation: preliminary MRI findings.

In hyperpolarized xenon magnetic resonance imaging (HP (129)Xe MRI), the inhaled spin-1/2 isotope of xenon gas is used to generate the MR signal. Because hyperpolarized xenon is an MR signal source with properties very different from those generated from water-protons, HP (129)Xe MRI may yield structural and functional information not detectable by conventional proton-based MRI methods. Here we demonstrate the differential distribution of HP (129)Xe in the cerebral cortex of the rat following a pain stimulus evoked in the animal's forepaw. Areas of higher HP (129)Xe signal corresponded to those areas previously demonstrated by conventional functional MRI (fMRI) methods as being activated by a forepaw pain stimulus. The percent increase in HP (129)Xe signal over baseline was 13-28%, and was detectable with a single set of pre and post stimulus images. Recent innovations in the production of highly polarized (129)Xe should make feasible the emergence of HP (129)Xe MRI as a viable adjunct method to conventional MRI for the study of brain function and disease.

MRI of stroke using hyperpolarized 129Xe.

Because there is no background signal from xenon in biological tissue, and because inhaled xenon is delivered to the brain by blood flow, we would expect a perfusion deficit, such as is seen in stroke, to reduce the xenon concentration in the region of the deficit. Thermal polarization yields negligible xenon signal relative to hyperpolarized xenon; therefore, hyperpolarized xenon can be used as a tracer of cerebral blood flow. Using a rat permanent right middle cerebral artery occlusion model, we demonstrated that hyperpolarized (129)Xe MRI is able to detect, in vivo, the hypoperfused area of focal cerebral ischemia, that is the ischemic core area of stroke. To the best of our knowledge, this is the first time that hyperpolarized (129)Xe MRI has been used to explore normal and abnormal cerebral perfusion. Our study shows a novel application of hyperpolarized (129)Xe MRI for imaging stroke, and further demonstrates its capacity to serve as a complementary tool to proton MRI for the study of the pathophysiology during brain hypoperfusion.

Investigation of hyperpolarized 3He magnetic resonance imaging utility in examining human airway diameter behavior in asthma through comparison with high-resolution computed tomography.

RATIONALE AND OBJECTIVES: Application of a previously developed model-based algorithm on hyperpolarized (HP) (3)He magnetic resonance (MR) dynamic projection images of phantoms was extended to investigate the utility of HP (3)He MR imaging (MRI) in quantifying airway caliber changes associated with asthma. MATERIALS AND METHODS: Airways of seven volunteers were imaged and measured using HP (3)He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data were obtained at functional residual capacity and 1 L above functional residual capacity. RESULTS: Comparison of the resultant data showed that HP (3)He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37% to 43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did yield the observation that 49% to 69% of these airways displayed bronchodilation following MCh challenge. CONCLUSION: The current implementation of HP (3)He MRI did not match the MCh-induced postchallenge-to-prechallenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation.

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.

Measurement of the internal diameter of plastic tubes from projection MR images using a model-based least-squares fit approach.

Hyperpolarized (HP) 3He MRI is an emerging tool in the diagnosis and evaluation of pulmonary diseases involving bronchoconstriction, such as asthma. Previously, airway diameters from dynamic HP 3He MR images of the lung were assessed manually and subjectively, and were thus prone to uncertainties associated with human error and partial volume effects. A model-based algorithm capable of fully utilizing pixel intensity profile information and attaining subpixel resolution has been developed to measure surrogate airway diameters from HP 3He MR static projection images of plastic tubes. This goal was achieved by fitting ideal pixel intensity profiles for various diameter (6.4 to 19.1 mm) circular tubes to actual pixel intensity data. A phantom was constructed from plastic tubes of various diameters connected in series and filled with water mixed with contrast agent. Projection MR images were then taken of the phantom. The favorable performance of the model-based algorithm compared to manual assessment demonstrates the viability of our approach. The manual and algorithm approaches yielded diameter measurements that generally stayed within 1 x the pixel dimension. However, inconsistency of the manual approach can be observed from the larger standard deviations of its measured values. The method was then extended to HP 3He MRI, producing encouraging results at tube diameters characteristic of airways beyond the second generation, thereby justifying their application to lung airway imaging and measurement. Potential obstacles when measuring airway diameters using this method are discussed.

Quantification of airway diameters and 3D airway tree rendering from dynamic hyperpolarized 3He magnetic resonance imaging.

As another step toward extracting quantitative information from hyperpolarized 3He MRI, airway diameters in humans were measured from projection images and multislice images of the lungs. Values obtained were in good agreement with the Weibel lung morphometry model. The measurement of airway caliber can now be achieved without the use of ionizing radiation. Furthermore, it was demonstrated that 3D airway tree renderings could be constructed from the multislice data. Both the measurement of airway diameters and the rendering of 3D airway information hold promise for the clinical assessment of bronchoconstrictive diseases such as asthma and the associated evaluation of treatment effectiveness. Work is being done to address the uncertainties of the manually intensive methods we have developed.

MRI of the lung gas-space at very low-field using hyperpolarized noble gases.

In hyperpolarized (HP) noble-gas magnetic resonance imaging, large nuclear spin polarizations, about 100,000 times that ordinarily obtainable at thermal equilibrium, are created in 3He and 129Xe. The enhanced signal that results can be employed in high-resolution MRI studies of void spaces such as in the lungs. In HP gas MRI the signal-to-noise ratio (SNR) depends only weakly on the static magnetic field (B(0)), making very low-field (VLF) MRI possible; indeed, it is possible to contemplate portable MRI using light-weight solenoids or permanent magnets. This article reports the first in vivo VLF MR images of the lungs in humans and in rats, obtained at a field of only 15 millitesla (150 Gauss).