Assessment of lung disease in children with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison with Shwachman score, Chrispin-Norman score and spirometry.

This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years), with different severity of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a 21-second breath-hold and scored according to previously defined criteria. Spearman's non-parametric correlations test was performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted (r=-0.41; p=0.047) and FVC% predicted (r=-0.42; p=0.04), while there were trends of correlations between Shwachman score and MRI score (r=-0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring lung disease and assessing therapy in this patient population.

Measurements and modeling of long range 3He diffusion in the lung using a "slice-washout" method.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Combined helium-3/proton magnetic resonance imaging measurement of ventilated lung volumes in smokers compared to never-smokers.

PURPOSE: To use a combination of helium-3 (3-He) magnetic resonance imaging (MRI) and proton single-shot fast spin echo (SSFSE) to compare ventilated lung volumes in groups of "healthy" smokers, smokers diagnosed with moderate chronic obstructive pulmonary disease (COPD), and never-smokers. MATERIALS AND METHODS: All study participants were assessed with spirometry prior to imaging. 3-He images were collected during an arrested breath hold, after inhaling a mixture of 200 mL of hyperpolarized 3-He/800 mL of N2. Proton SSFSE images were acquired after inhaling 1 liter of room air. The ventilated volume for each study participant was calculated from the 3-He images, and a ratio was calculated to give a percentage ventilated lung volume. RESULTS: Never-smokers exhibited a 90% mean ventilated volume. The mean ventilated lung volumes for healthy smokers and smokers diagnosed with COPD were 75.2% and 67.6%, respectively. No correlation with spirometry was demonstrated for either of the smoking groups. CONCLUSION: Combined 3-He/Proton SSFSE MRI of the lungs is a noninvasive method, using nonionizing radiation, which demonstrates ventilated airspaces and enables the calculation of ventilated lung volumes. This method appears to be sensitive to early obstructive changes in the lungs of smokers.

Finite-difference simulations of 3He diffusion in 3D alveolar ducts: comparison with the "cylinder model".

Time-dependent measurements of 3He diffusion in the lung could provide an accurate method to quantify alveolar length scales and the progression of diseases such as emphysema. However, the apparent diffusion coefficient (ADC) presents a complex problem to model and solve analytically. Here, finite-difference methods were used to simulate diffusion in 3D alveolar ducts. The results were compared to the only available analytical model--the "cylinder model"--from which it is possible to estimate the average radii of the alveolar ducts from in vivo data. The trend in data observed from simulations was found to agree well with the cylinder model. However, the cylinder model always overestimated the average radii of the simulated alveolar ducts. The simulations also demonstrated that the measurement of the longitudinal ADC (along the alveolar ducts) should be sensitive to early emphysematous changes, whereas the measured radii should be far less sensitive.

MRI of helium-3 gas in healthy lungs: posture related variations of alveolar size.

PURPOSE: To probe the variation of alveolar size in healthy lung tissue as a function of posture using diffusion-weighted helium-3 hyperpolarized gas imaging. MATERIALS AND METHODS: Measurements of the helium-3 apparent diffusion coefficient (ADC) were made on six healthy subjects. These were used to show the variation of alveolar size between the lowermost dependent regions of the lung compared to the uppermost regions of the lung in four postures: supine, prone, left-lateral decubitus, and right-lateral decubitus. RESULTS: The distribution of acinar size in the lungs was found to be heterogeneous, and influenced by lung orientation. In nearly all postures, the ADC was significantly higher in the non-dependent uppermost regions of the lung compared to the dependent lowermost regions of the lung; the greatest variation was found in the left-lateral decubitus position. The difference in ADC between uppermost and lowermost regions was on average 0.012 cm(2)second(-1), which represents 20% of the average ADC value for the whole lung. A systematic decrease in ADC from the apex of the lung to the base was also found, which corresponds to an inherent gradient in alveolar size. CONCLUSION: The posture dependent variations in ADC were attributed to compression of the parenchyma under its own weight and the mass of the heart.

Investigating 3He diffusion NMR in the lungs using finite difference simulations and in vivo PGSE experiments.

Finite difference simulations have been used to model (3)He gas diffusion in simulated lung tissue. The technique has the advantage that a wide range of structural models and diffusion-sensitizing gradient waveforms can be investigated, for which analytical methods would otherwise be virtually impossible. Results from simulations and in vivo pulsed-gradient-spin-echo (PGSE) experiments show that the apparent diffusion coefficient (ADC) is a function of diffusion time and gradient strength, and suggests diffusion is locally anisotropic. The simulations have been compared to recent work on an analytical model that characterizes lung tissue as a series of independent cylinders. The results presented may have clinical implications for (3)He ADC measurements in assessing lung diseases such as chronic-obstructive-pulmonary-disease.

B1AC-MAMBA: B1 array combined with multiple-acquisition micro B0 array parallel magnetic resonance imaging.

The combination of an in-plane B(1) sensitivity encoding (SENSE) technique with a simultaneous multiple-slice B(0) field step technique (multiple-acquisition micro B(0) array (MAMBA)) has produced high scan time reduction factors (R < or = 8). In this study, two slices were acquired simultaneously in combination with x2 and x4 SENSE in-plane encoding using a MAMBA stepped B(0) field coil inside a four-channel phased-array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal-to-noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. The B(1) array combined with MAMBA (B(1)AC-MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole-body screening for disease.

MR tagging of human lungs using hyperpolarized 3He gas.

PURPOSE: To evaluate the use of spin-tagging in conjunction with hyperpolarized gas imaging for monitoring lung ventilation and gas diffusion. METHODS AND MATERIALS: Images were taken at 0.15 T using single shot RARE, with hyperpolarized (3)He gas prepared by the metastability exchange technique. Sinusoidal modulation of the longitudinal magnetization (tag) was produced by two 90-degree rf pulses separated by a gradient pulse. The diffusion of (3)He gas in the lungs was measured by monitoring the decay of the tags. This study was conducted on a 25-year-old, male, healthy volunteer. RESULTS: Clear tags in hyperpolarized (3)He gas both in vivo and in vitro were generated. The relative movement of the lung compared to a static, partial breath-hold was measured following inspiration or expiration. The diffusion coefficient of (3)He in the lungs was found to be 0.02 +/- 0.005 cm(2)seconds(-1). CONCLUSION: The spin-tagging of hyperpolarized (3)He in the lungs is possible, and allows regional lung movements to be measured following inspiration and expiration. It also allows quantification of the diffusion of the (3)He gas.