Hyperpolarised ³He gas MRI has been shown to provide quantitative measures of regional lung ventilation [1] and lung microstructure [2,3]. In particular, the ³He apparent diffusion coefficient (ADC) [2], estimates of alveolar dimension (Lm_D) [3], and T₂* [4] are sensitive to changes in lung microstructure and function. Previously, single breath-hold acquisition of 2D ³He ventilation, ADC, T₂*, and B₁ maps were demonstrated at 3T using compressed sensing (CS) [5]. However, this 2D multi-slice acquisition did not provide whole-lung coverage or multiple b-value data for Lm_D calculation. In this work, a 3D multiple-interleaved sequence was implemented with CS [6] to acquire whole-lung coverage co-registered ³He ventilation images, parametric maps of ADC, Lm_D, and T₂* within a single breath-hold.

The 3D multiple-interleaved sequence is summarised in Figure 1. The first and second interleaves were used to compute ADC maps, while the first four interleaves were used to calculate Lm_D by fitting data with the stretched exponential model [3]. Finally, the first and fifth interleaves were used to compute T₂* maps.

In order to simulate the optimal k-space sampling pattern for CS, a fully-sampled three-interleaved dataset (interleaves 1, 2 and 5 in Figure 1) was acquired in a healthy volunteer (M, 25y) on a GE HDx 1.5T MR scanner using 400mL of ³He (~25% polarisation). Imaging parameters: 3D SPGR, b=0, 1.6 s/cm², 80x66x22 matrix, FOV=40x32.5x24.4 cm³, TE₁/TR₁=4.1/5.7 ms, TE₂/TR₂=14.8/16.4 ms, diffusion time Δ=1.6ms, flip angle=1.4°, bandwidth=±31.25 kHz. Optimal k-space undersampling patterns were determined for acceleration factors (AFs) of 2 to 5 by minimising the mean absolute error between undersampled and fully-sampled ventilation images (MAE), ADC maps (ADC MAE), and T₂* maps (T₂* MAE). By retrospectively undersampling the fully-sampled dataset, images were reconstructed from the optimal undersampling patterns [6], and mean ADC and T₂* values were compared between each AF.

The full five-interleaved sequence was implemented with CS in a prospective acquisition on the same healthy volunteer. Three-fold undersampling was introduced to reduce the breath-hold time to 18s. Imaging parameters were as above, except four b-values (0, 1.6, 4.2, 7.2 s/cm²) and flip angle=1.9° were used. Prospective CS-sampled ADC and T₂* maps were compared to corresponding fully-sampled maps. Lm_D maps were compared to those acquired previously using 2D fully-sampled multiple b-value diffusion MRI in the same volunteer.

Global mean ADC and T₂* values from the fully-sampled three-interleaved dataset were consistent with reported values for healthy lungs at b=1.6 s/cm² and 1.5T [2,7]. A summary of the simulated changes in MAE, global ADC, and T₂* values with AF is shown in Table 1. The MAE value between fully-sampled and reconstructed ventilation images (b=0, interleave 1 in Figure 1) increased for each AF, but images showed good preservation of main details and no additional artefacts at high AFs (Figure 2 top row). Reconstructed ADC maps exhibited a similar trend; the global mean ADC value was approximately constant with increasing ADC MAE and sample slice ADC maps appeared visually similar (Figure 2 middle row). The T₂* MAE also increased with AF, and corresponding global T₂* values decreased (maps shown in Figure 2 bottom row). This decrease in T₂* with increased undersampling was observed previously in 2D CS experiments at 3T [5] and was attributed to the smoothing properties of the CS reconstruction.

The prospective CS five-interleaved dataset allowed whole-lung coverage, 3D co-registered ³He ventilation images, parametric maps of ADC, Lm_D, and T₂* to be acquired in a single breath-hold (Figure 3). Prospective CS-derived global mean ADC (0.175±0.076 cm²/s) and Lm_D (209.0±30.0 μm) values agreed with corresponding 3D and 2D fully-sampled equivalent values (0.173±0.082 cm²/s and 207.2±24.6 μm, respectively). The small positive bias in CS-derived values is consistent with previous observations in CS-derived microstructure measurements, and is attributable to the CS reconstruction process [8]. The global mean T₂* value for the prospective dataset was 16.40±12.86 ms, smaller than the fully-sampled mean value (23.70±18.38 ms). This was consistent with the CS simulations results; the prospective CS T₂* value was in agreement with the simulated T₂* value for AF=3 (17.08±13.73 ms).

We have demonstrated that it is feasible to acquire whole-lung coverage, co-registered images of lung ventilation, ADC, Lm_D, and T₂* in a single breath-hold with a 3D multiple-interleaved sequence and CS. Good agreement of ADC and Lm_D values was obtained between prospective CS and fully-sampled datasets in a healthy volunteer. Prospective T₂* values were smaller than fully-sampled equivalents, a result of smoothing from the CS reconstruction. Further work will investigate the difference between CS-derived and fully-sampled T₂* values and evaluate the sequence in patients and with ¹²⁹Xe.