Multislice fractional ventilation imaging in large animals with hyperpolarized gas MRI.
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ABSTRACT: The noninvasive assessment of regional lung ventilation is of critical importance in the quantification of the severity of disease and evaluation of response to therapy in many pulmonary diseases. This work presents, for the first time, the implementation of a hyperpolarized (HP) gas MRI technique to measure whole-lung regional fractional ventilation (r) in Yorkshire pigs (n = 5) through the use of a gas mixing and delivery device in the supine position. The proposed technique utilizes a series of back-to-back HP gas breaths with images acquired during short end-inspiratory breath-holds. In order to decouple the radiofrequency pulse decay effect from the ventilatory signal build-up in the airways, the regional distribution of the flip angle (α) was estimated in the imaged slices by acquiring a series of back-to-back images with no interscan time delay during a breath-hold at the tail end of the ventilation sequence. Analysis was performed to assess the sensitivity of the multislice ventilation model to noise, oxygen and the number of flip angle images. The optimal α value was determined on the basis of the minimization of the error in r estimation: α(opt) = 5-6º for the set of acquisition parameters in pigs. The mean r values for the group of pigs were 0.27 ± 0.09, 0.35 ± 0.06 and 0.40 ± 0.04 for the ventral, middle and dorsal slices, respectively (excluding conductive airways r 0.9). A positive gravitational (ventral-dorsal) ventilation gradient effect was present in all animals. The trachea and major conductive airways showed a uniform near-unity r value, with progressively smaller values corresponding to smaller diameter airways, and ultimately leading to lung parenchyma. The results demonstrate the feasibility of the measurement of the fractional ventilation in large species, and provide a platform to address the technical challenges associated with long breathing time scales through the optimization of acquisition parameters in species with a pulmonary physiology very similar to that of humans.
Project description:NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized 129Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases. However, production and utilization of hyperpolarized 129Xe gas faces a number of translational challenges including the high cost and complexity of contrast agent production and imaging using proton-only (i.e., conventional) clinical MRI scanners, which are typically not suited to scan 129Xe nuclei. As a solution to circumvent the translational challenges of hyperpolarized 129Xe, we have recently demonstrated the feasibility of a simple and cheap process for production of proton-hyperpolarized propane gas contrast agent using ultralow-cost disposable production equipment and demonstrated the feasibility of lung ventilation imaging using hyperpolarized propane gas in excised pig lungs. However, previous pilot studies have concluded that the hyperpolarized state of propane gas decays very fast with an exponential decay T 1 constant of ∼0.8 s at 1 bar (physiologically relevant pressure); moreover, the previously reported production rates were too slow for potential clinical utilization. Here, we investigate the feasibility of high-capacity production of hyperpolarized butane gas via heterogeneous parahydrogen-induced polarization using Rh nanoparticle-based catalyst utilizing butene gas as a precursor for parahydrogen pairwise addition. We demonstrate a remarkable result: the lifetime of the hyperpolarized state can be nearly doubled compared to that of propane (T 1 of ∼1.6 s and long-lived spin-state T S of ∼3.8 s at clinically relevant 1 bar pressure). Moreover, we demonstrate a production speed of up to 0.7 standard liters of hyperpolarized gas per second. These two synergistic developments pave the way to biomedical utilization of proton-hyperpolarized gas media for ventilation imaging. Indeed, here we demonstrate the feasibility of phantom imaging of hyperpolarized butane gas in Tedlar bags and also the feasibility of subsecond 2D ventilation gas imaging in excised rabbit lungs with 1.6 × 1.6 mm2 in-plane resolution using a clinical MRI scanner. The demonstrated results have the potential to revolutionize functional pulmonary imaging with a simple and inexpensive on-demand production of proton-hyperpolarized gas contrast media, followed by visualization on virtually any MRI scanner, including emerging bedside low-field MRI scanner technology.
Project description:Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood-gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of (129)Xe, the magnetic resonance signal of which has been enhanced by 10(5) with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring (129)Xe alveolar-capillary transfer is sensitive to changes in blood-gas barrier thickness of approximately 5 microm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where (129)Xe replenishment of the RBCs is severely impaired in regions of lung injury.
Project description:Functional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping.
Project description:Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-1H) and hyperpolarized 3He (HP-3He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for 1H configured with the 3He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3?×?3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-1H: 0.28 (0.08) and HP-3He: 0.32 (0.14)], SVwidths [OE-1H: 0.28 (0.08) and HP-3He: 0.27 (0.10)], and SVslopes [OE-1H: -0.016 (0.006) cm-1 and HP-3He: -0.013 (0.007) cm-1]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized 3He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.
Project description:Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung-gas delivery to the airspaces and gas uptake by the lung parenchyma and blood-in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease.
Project description:Respiratory diseases are leading causes of mortality and morbidity worldwide. Pulmonary imaging is an essential component of the diagnosis, treatment planning, monitoring, and treatment assessment of respiratory diseases. Insights into numerous pulmonary pathologies can be gleaned from functional lung MRI techniques. These include hyperpolarized gas ventilation MRI, which enables visualization and quantification of regional lung ventilation with high spatial resolution. Segmentation of the ventilated lung is required to calculate clinically relevant biomarkers. Recent research in deep learning (DL) has shown promising results for numerous segmentation problems. Here, we evaluate several 3D convolutional neural networks to segment ventilated lung regions on hyperpolarized gas MRI scans. The dataset consists of 759 helium-3 (3He) or xenon-129 (129Xe) volumetric scans and corresponding expert segmentations from 341 healthy subjects and patients with a wide range of pathologies. We evaluated segmentation performance for several DL experimental methods via overlap, distance and error metrics and compared them to conventional segmentation methods, namely, spatial fuzzy c-means (SFCM) and K-means clustering. We observed that training on combined 3He and 129Xe MRI scans using a 3D nn-UNet outperformed other DL methods, achieving a mean ± SD Dice coefficient of 0.963 ± 0.018, average boundary Hausdorff distance of 1.505 ± 0.969 mm, Hausdorff 95th percentile of 5.754 ± 6.621 mm and relative error of 0.075 ± 0.039. Moreover, limited differences in performance were observed between 129Xe and 3He scans in the testing set. Combined training on 129Xe and 3He yielded statistically significant improvements over the conventional methods (p < 0.0001). In addition, we observed very strong correlation and agreement between DL and expert segmentations, with Pearson correlation of 0.99 (p < 0.0001) and Bland-Altman bias of - 0.8%. The DL approach evaluated provides accurate, robust and rapid segmentations of ventilated lung regions and successfully excludes non-lung regions such as the airways and artefacts. This approach is expected to eliminate the need for, or significantly reduce, subsequent time-consuming manual editing.
Project description:PurposeChemical exchange saturation transfer MRI can provide accurate pH images, but the slow scan time (due to long saturation periods and multiple offsets sampling) reduce both the volume coverage and spatial resolution capability, hence the possibility to interrogate the heterogeneity in tumors and organs. To overcome these limitations, we propose a fast multislice CEST-MRI sequence with high pH accuracy and spatial resolution.MethodsThe sequence first uses a long saturation pulse to induce the steady-state CEST contrast and a second short saturation pulse repeated after each image acquisition to compensate for signal losses based on an uneven irradiation scheme combined with a single-shot rapid acquisition with refocusing echoes readout. Sequence sensitivity and accuracy in measuring pH was optimized by simulation and assessed by in vitro studies in pH-varying phantoms. In vivo validation was performed in two applications by acquiring multislice pH images covering the whole tumors and kidneys after iopamidol injection.ResultsSimulated and in vivo data showed comparable contrast efficiency and pH responsiveness by reducing saturation time. The experimental data from a homogeneous, pH-varying, iopamidol-containing phantom show that the sequence produced a uniform CEST contrast across slices and accurate values across slices in less than 10 minutes. In vivo measurements allowed us to quantify the 3D pH gradients of tumors and kidneys, with pH ranges comparable with the literature.ConclusionThe proposed fast multislice CEST-MRI sequence allows volumetric acquisitions with good pH sensitivity, accuracy, and spatial resolution for several in vivo pH imaging applications.
Project description:PurposeTo develop a real-time imaging technique that allows for simultaneous visualization of vocal tract shaping in multiple scan planes, and provides dynamic visualization of complex articulatory features.Materials and methodsSimultaneous imaging of multiple slices was implemented using a custom real-time imaging platform. Midsagittal, coronal, and axial scan planes of the human upper airway were prescribed and imaged in real-time using a fast spiral gradient-echo pulse sequence. Two native speakers of English produced voiceless and voiced fricatives /f/-/v/, /θ/-/ð/, /s/-/z/, /∫/- in symmetrical maximally contrastive vocalic contexts /a_a/, /i_i/, and /u_u/. Vocal tract videos were synchronized with noise-cancelled audio recordings, facilitating the selection of frames associated with production of English fricatives.ResultsCoronal slices intersecting the postalveolar region of the vocal tract revealed tongue grooving to be most pronounced during fricative production in back vowel contexts, and more pronounced for sibilants /s/-/z/ than for /∫/-. The axial slice best revealed differences in dorsal and pharyngeal articulation; voiced fricatives were observed to be produced with a larger cross-sectional area in the pharyngeal airway. Partial saturation of spins provided accurate location of imaging planes with respect to each other.ConclusionReal-time MRI of multiple intersecting slices can provide valuable spatial and temporal information about vocal tract shaping, including details not observable from a single slice.