A method for imaging and spectroscopy using γ-rays and magnetic resonance.

Magnetic resonance imaging (MRI) provides fine spatial resolution, spectral sensitivity and a rich variety of contrast mechanisms for diagnostic medical applications. Nuclear imaging using γ-ray cameras offers the benefits of using small quantities of radioactive tracers that seek specific targets of interest within the body. Here we describe an imaging and spectroscopic modality that combines favourable aspects of both approaches. Spatial information is encoded into the spin orientations of tiny amounts of a polarized radioactive tracer using pulses of both radio-frequency electromagnetic radiation and magnetic-field gradients, as in MRI. However, rather than detecting weak radio-frequency signals, imaging information is obtained through the detection of γ-rays. A single γ-ray detector can be used to acquire an image; no γ-ray camera is needed. We demonstrate the feasibility of our technique by producing images and spectra from a glass cell containing only about 4 × 10(13) atoms (about 1 millicurie) of the metastable isomer (131m)Xe that were polarized using the laser technique of spin-exchange optical pumping. If the cell had instead been filled with water and imaged using conventional MRI, then it would have contained more than 10(24) water molecules. The high sensitivity of our modality expands the breadth of applications of magnetic resonance, and could lead to a new class of radioactive tracers.

Signal-to-noise ratio, T2 , and T2* for hyperpolarized helium-3 MRI of the human lung at three magnetic field strengths.

PURPOSE: To evaluate T2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 (3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. METHODS: Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose. RESULTS: As expected, T2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. CONCLUSIONS: Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Rapid acquisition of helium-3 and proton three-dimensional image sets of the human lung in a single breath-hold using compressed sensing.

PURPOSE: To develop and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. METHODS: The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. RESULTS: Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9. CONCLUSION: By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold.

Regional anisotropy of airspace orientation in the lung as assessed with hyperpolarized helium-3 diffusion MRI.

PURPOSE: To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths. MATERIALS AND METHODS: Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions. RESULTS: ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P < 0.05). CONCLUSION: These findings indicate that diffusion-weighted hyperpolarized (3) He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces.

A short-breath-hold technique for lung pO2 mapping with 3He MRI.

A pulse-sequence strategy was developed for generating regional maps of alveolar oxygen partial pressure (pO2) in a single 6-sec breath hold, for use in human subjects with impaired lung function. Like previously described methods, pO2 values are obtained by measuring the oxygen-induced T1 relaxation of inhaled hyperpolarized 3He. Unlike other methods, only two 3He images are acquired: one with reverse-centric and the other with centric phase-encoding order. This phase-encoding arrangement minimizes the effects of regional flip-angle variations, so that an accurate map of instantaneous pO2 can be calculated from two images acquired a few seconds apart. By combining this phase-encoding strategy with variable flip angles, the vast majority of the hyperpolarized magnetization goes directly into the T1 measurement, minimizing noise in the resulting pO2 map. The short-breath-hold pulse sequence was tested in phantoms containing known O2 concentrations. The mean difference between measured and prepared pO2 values was 1 mm Hg. The method was also tested in four healthy volunteers and three lung-transplant patients. Maps of healthy subjects were largely uniform, whereas focal regions of abnormal pO2 were observed in diseased subjects. Mean pO2 values varied with inhaled O2 concentration. Mean pO2 was consistent with normal steady-state values in subjects who inhaled 3He diluted only with room air.

Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry.

The apparent diffusion coefficients (ADCs) of hyperpolarized (3)He and (129)Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm(2) and 0 and 4.0 s/cm(2) were used for (3)He, and b-value pairs of 0 and 5.0 s/cm(2) and 0 and 10.0 s/cm(2) were used for (129)Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly (P < 0.05) for all gas and b-value combinations except (129)Xe with the b-value pair of 0 and 5.0 s/cm(2). The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with (3)He and the b-value pair of 0 and 1.6 s/cm(2) for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated (r = 0.62-0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.

Measurement of hyperpolarized gas diffusion at very short time scales.

We present a new pulse sequence for measuring very-short-time-scale restricted diffusion of hyperpolarized noble gases. The pulse sequence is based on concatenating a large number of bipolar diffusion-sensitizing gradients to increase the diffusion attenuation of the MR signal while maintaining a fundamentally short diffusion time. However, it differs in several respects from existing methods that use oscillating diffusion gradients for this purpose. First, a wait time is inserted between neighboring pairs of gradient pulses; second, consecutive pulse pairs may be applied along orthogonal axes; and finally, the diffusion-attenuated signal is not simply read out at the end of the gradient train but is periodically sampled during the wait times between neighboring pulse pairs. The first two features minimize systematic differences between the measured (apparent) diffusion coefficient and the actual time-dependent diffusivity, while the third feature optimizes the use of the available MR signal to improve the precision of the diffusivity measurement in the face of noise. The benefits of this technique are demonstrated using theoretical calculations, Monte-Carlo simulations of gas diffusion in simple geometries, and experimental phantom measurements in a glass sphere containing hyperpolarized (3)He gas. The advantages over the conventional single-bipolar approach were found to increase with decreasing diffusion time, and thus represent a significant step toward making accurate surface-to-volume measurements in the lung airspaces.

Very-low-field MRI of laser polarized xenon-129.

We describe a homebuilt MRI system for imaging laser-polarized xenon-129 at a very low holding field of 2.2mT. A unique feature of this system was the use of Maxwell coils oriented at so-called "magic angles" to generate the transverse magnetic field gradients, which provided a simple alternative to Golay coils. We used this system to image a laser-polarized xenon-129 phantom with both a conventional gradient-echo and a fully phase-encoded pulse sequence. In other contexts, a fully phase-encoded acquisition, also known as single-point or constant-time imaging, has been used to enable distortion-free imaging of short-T2∗ species. Here we used this technique to overcome imperfections associated with our homebuilt MRI system while also taking full advantage of the long T2∗ available at very low field. Our results demonstrate that xenon-129 image quality can be dramatically improved at low field by combining a fully phase-encoded k-space acquisition with auxiliary measurements of system imperfections including B0 field drift and gradient infidelity.

XTC MRI: sensitivity improvement through parameter optimization.

Xenon polarization Transfer Contrast (XTC) MRI pulse sequences permit the gas exchange of hyperpolarized xenon-129 in the lung to be measured quantitatively. However, the pulse sequence parameter values employed in previously published work were determined empirically without considering the now-known gas exchange rates and the underlying lung physiology. By using a theoretical model for the consumption of magnetization during data acquisition, the noise intensity in the computed gas-phase depolarization maps was minimized as a function of the gas-phase depolarization rate. With such optimization the theoretical model predicted an up to threefold improvement in precision. Experiments in rabbits demonstrated that for typical imaging parameter values the optimized XTC pulse sequence yielded a median noise intensity of only about 3% in the depolarization maps. Consequently, the reliable detection of variations in the average alveolar wall thickness of as little as 300 nm can be expected. This improvement in the precision of the XTC MRI technique should lead to a substantial increase in its sensitivity for detecting pathological changes in lung function.