Feasibility of image registration and intensity-modulated radiotherapy planning with hyperpolarized helium-3 magnetic resonance imaging for non-small-cell lung cancer.

PURPOSE: To demonstrate the feasibility of registering hyperpolarized helium-3 magnetic resonance images ((3)He-MRI) to X-ray computed tomography (CT) for functionally weighted intensity-modulated radiotherapy (IMRT) planning. METHODS AND MATERIALS: Six patients with non-small-cell lung cancer underwent (3)He ventilation MRI, which was fused with radiotherapy planning CT using rigid registration. Registration accuracy was assessed using an overlap coefficient, calculated as the proportion of the segmented (3)He-MR volume (V(MRI)) that intersects the segmented CT lung volume expressed as a percentage of V(MRI). For each patient, an IMRT plan that minimized the volume of total lung receiving a dose > or = 20 Gy (V(20)) was compared with a plan that minimized the V(20) to well-ventilated lung defined by the registered (3)He-MRI. RESULTS: The (3)He-MRI and CT were registered with sufficient accuracy to enable functionally guided IMRT planning (median overlap, 89%; range, 72-97%). In comparison with the total lung IMRT plans, IMRT constrained with (3)He-MRI reduced the V(20) not only for the well-ventilated lung (median reduction, 3.1%; range, 0.4-5.1%; p = 0.028) but also for the total lung volume (median reduction, 1.6%; range, 0.2-3.7%; p = 0.028). CONCLUSIONS: Statistically significant improvements to IMRT plans are possible using functional information provided by (3)He-MRI that has been registered to radiotherapy planning CT.

Rapid lung volumetry using ultrafast dynamic magnetic resonance imaging during forced vital capacity maneuver: correlation with spirometry.

INTRODUCTION: Dynamic magnetic resonance imaging (MRI) has the potential for rapid noninvasive evaluation of changes in lung volume. The aim of this study was to perform rapid lung volumetry using ultrafast dynamic MRI to capture a forced vital capacity (FVC) maneuver. MATERIALS AND METHODS: Nine healthy volunteers underwent 2-dimensional spoiled gradient echo imaging in coronal and sagittal planes during FVC maneuvers. An elliptical model of the axial cross section of the lungs was used to generate rapid volume-time curves. Spirometric indices were correlated with MR volumetry findings. RESULTS: Total lung volume calculated from static MRI correlated well with the dynamic MR scans (r = 0.83; P < 0.01). Spirometric indices (first second of forced expiration and FVC) calculated from our MR volumetry technique correlated well with conventional spirometry (P < 0.01). CONCLUSION: The technique provides a means of sampling lung volume change during the rapid subsecond movements that take place during a FVC maneuver.

Steady-state free precession with hyperpolarized 3He: experiments and theory.

The magnetization response of hyperpolarized 3He gas to a steady-state free precession (SSFP) sequence was simulated using matrix product operators. The simulations included the effects of flip angle (alpha), sequence timings, resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2. Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects, confirm the predicted theory, and indicate increased SNR with SSFP through use of higher flip angles when compared to optimized spoiled gradient echo (SPGR). Simulations and experiments show some compromise to the SNR and some point spread function broadening at high alpha due to the incomplete refocusing of transverse magnetization, caused by diffusion dephasing from the readout gradient. Mixing of gas polarization levels by diffusion between slices is also identified as a source of signal loss in SSFP at higher alpha through incomplete refocusing. Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth. Some of the gas sample experiments demonstrated a transient signal response that deviates from theory in the initial phase. This was identified as being caused by radiation damping interactions between the large initial transverse magnetization and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments, performed without imaging gradients, diffusion dephasing can be mitigated, and the effective T2 is relatively long (1 s). Under these circumstances the SSFP sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR. Experiments and simulations were also performed to characterize the off-resonance behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off-resonance harmonic beating were observed in some of the in vivo SSFP images, for instance in axial slices close to the diaphragm where B0 inhomogeneity is highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo when compared to the SPGR sequence. The trends predicted by theory of increasing SSFP SNR with increasing flip angle were observed in the range alpha=10-20 degrees without compromise to image quality through blurring caused by excessive k-space filtering.

Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI.

INTRODUCTION: This study aims to quantify global and regional changes of diffusive motion of 3He gas within the lung, as determined by hyperpolarized 3He MR apparent diffusion coefficient (ADC) measurement, in non-smokers, smokers and chronic obstructive pulmonary disease (COPD) patients. METHODS: Age-matched groups of six healthy non-smokers, five healthy smokers and five patients with COPD. The experiments were performed with approval from the local Research Ethics Committee. Diffusion imaging was performed following hyperpolarized 3He gas inhalation, producing ADC maps. Mean and standard deviation of the ADCs were used to compare the subject groups and assess regional variations within individuals. RESULTS: The intra-individual standard deviation of ADC in the healthy smokers was significantly larger than that of the non-smoking group (P < 0.02). Compared to the non-smoking group, COPD patients had significantly higher mean and standard deviation of ADC (P < 0.01). The mean ADC in the anterior half of the chest was systematically higher than in the posterior half in the healthy non-smoking subject group. DISCUSSION: This study suggests that there are regional trends in the ADC values of healthy volunteers that may have implications for the clinical interpretation of ADC values. Less homogeneous ADC values have been detected in asymptomatic smokers, indicative of damage to the distal air spaces.

Hyperpolarized 3helium magnetic resonance ventilation imaging of the lung in cystic fibrosis: comparison with high resolution CT and spirometry.

The purpose of this study was to compare hyperpolarized 3helium magnetic resonance imaging (3He MRI) of the lungs in adults with cystic fibrosis (CF) with high-resolution computed tomography (HRCT) and spirometry. Eight patients with stable CF prospectively underwent 3He MRI, HRCT, and spirometry within 1 week. Three-dimensional (3D) gradient-echo sequence was used during an 18-s breath-hold following inhalation of hyperpolarized 3He. Each lung was divided into six zones; 3He MRI was scored as percentage ventilation per lung zone. HRCT was scored using a modified Bhalla scoring system. Univariate (Spearman rank) and multivariate correlations were performed between 3He MRI, HRCT, and spirometry. Results are expressed as mean+/-SD (range). Spirometry is expressed as percent predicted. There were four men and four women, mean age = 31.9+/-9 (20-46). Mean forced expiratory volume in 1 s (FEV)1 = 52%+/-29 (27-93). Mean 3He MRI score = 74%+/-25 (55-100). Mean HRCT score = 48.8+/-24 (13.5-83). The correlation between 3He MRI and HRCT was strong (R = +/-0.89, p < 0.001). Bronchiectasis was the only independent predictor of 3He MRI; 3He MRI correlated better with FEV1 and forced vital capacity (FVC) (R = 0.86 and 0.93, p < 0.01, respectively) than HRCT (R = +/-0.72 and +/-0.81, p < 0.05, respectively). This study showed that 3He MRI correlates strongly with structural HRCT abnormalities and is a stronger correlate of spirometry than HRCT in CF.

3D volume-localized pO2 measurement in the human lung with 3He MRI.

A method for 3D volume-localized quantification of pO2 in the lungs is presented that uses repetitive frame 3D gradient-echo imaging of (3)He. The method was demonstrated by experiments on (3)He phantoms containing known concentrations of O(2) and in vivo on a group of three healthy human volunteers. The results were compared with those obtained by equivalent 2D thin-slice and 2D projection methodologies, and were found to be consistent with published results from the 2D projection methodologies (pO(2) = 0.09-0.18 bar). Studies performed on the same subject, on three separate occasions, demonstrated a repeatability of pO(2) measurement to within 14% using the 3D technique. Experimental differences between the 2D and 3D methods were substantiated with theoretical and numerical analyses of the signal decay, which took into account the effects of out-of-slice diffusion as a source of error in the thin-slice 2D experiments. It is shown that the 2D thin-slice technique systematically underestimates pO2 when there is significant gas diffusion (factor of 4 underestimate for D = 0.9 cm(2)s(-1) representative of free (3)He in air).

Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.

PURPOSE: To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. RESULTS: A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). CONCLUSION: These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique.

Comparison between 2D and 3D gradient-echo sequences for MRI of human lung ventilation with hyperpolarized 3He.

Images of hyperpolarized 3He were acquired during breath-hold in four healthy volunteers with the use of an optimized 3D gradient-echo sequence. The images were compared with existing 2D gradient-echo methods. The average SNR from a 13-mm-thick slice in the peripheral lung was 1.4 times greater with 3D. In the airways the average SNR was 1.7 times greater with 3D. The higher SNR of 3D was particularly evident when regions of unimpeded gas diffusion, such as the major airways, were imaged with thin slices. This is because diffusion dephasing due to the slice-encoding gradient is minimized with a 3D sequence. The in vivo experimental findings were substantiated with experiments on phantoms of free gas, which showed more than four times the SNR with 3D compared to 2D. Theoretical simulations of the 2D and 3D k-space filters were also performed to predict the SNR and spatial resolution observed in the experimental images.

Dynamic radial projection MRI of inhaled hyperpolarized 3He gas.

A radial projection sliding-window sequence has been developed for imaging the rapid flow of (3)He gas in human lungs. The short echo time (TE) of the radial sequence lends itself to fast repetition times, and thus allows a rapid update in the image when it is reconstructed with a sliding window. Oversampling in the radial direction combined with angular undersampling can further reduce the time needed to acquire a complete image data set, without significantly compromising spatial resolution. Controlled flow phantom experiments using hyperpolarized (3)He gas exemplify the temporal resolution of the method. In vivo studies on three healthy volunteers, one patient with chronic obstructive pulmonary disease (COPD), and one patient with hemiparalysis of the right diaphragm demonstrate that it is possible to accurately resolve the passage of gas down the trachea and bronchi and into the peripheral lung.

Assessment and compensation of susceptibility artifacts in gradient echo MRI of hyperpolarized 3He gas.

The effects of macroscopic background field gradients upon 2D gradient echo images of inhaled (3)He in the human lung were investigated at 1.5 T. Effective compensation of in-slice signal loss in (3)He gradient echo images was then demonstrated using a multiple acquisition interleaved single gradient echo sequence. This method restores signal dephasing through a combination of separate images acquired with different slice refocusing gradients. In vivo imaging of volunteers with the sequence shows substantial restoration of signal at the lung periphery and close to blood vessels. The technique presented may be useful when using (3)He MRI for volumetric measurements of lung ventilation and in studies using (3)He combined with intravenous contrast as a means of assessing lung ventilation/perfusion (V/Q).