Probing lung microstructure with hyperpolarized noble gas diffusion MRI: theoretical models and experimental results

The introduction of hyperpolarized gases (³He and ¹²⁹Xe) has opened the door to applications for which gaseous agents are uniquely suited—lung MRI. One of the pulmonary applications, diffusion MRI, relies on measuring Brownian motion of inhaled hyperpolarized gas atoms diffusing in lung airspaces. In this article we provide an overview of the theoretical ideas behind hyperpolarized gas diffusion MRI and the results obtained over the decade‐long research. We describe a simple technique based on measuring gas apparent diffusion coefficient (ADC) and an advanced technique, in vivo lung morphometry, that quantifies lung microstructure both in terms of Weibel parameters (acinar airways radii and alveolar depth) and standard metrics (mean linear intercept, surface‐to‐volume ratio, and alveolar density) that are widely used by lung researchers but were previously available only from invasive lung biopsy. This technique has the ability to provide unique three‐dimensional tomographic information on lung microstructure from a less than 15 s MRI scan with results that are in good agreement with direct histological measurements. These safe and sensitive diffusion measurements improve our understanding of lung structure and functioning in health and disease, providing a platform for monitoring the efficacy of therapeutic interventions in clinical trials. Magn Reson Med 71:486–505, 2014. © 2013 Wiley Periodicals, Inc.     

Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI: initial results in animals and healthy volunteers

Hyperpolarized xenon-129 is a noninvasive contrast agent for lung MRI, which upon inhalation dissolves in parenchymal structures, thus mirroring the gas-exchange process for oxygen in the lung. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI is an implementation of the XTC MRI technique in four dimensions (three spatial dimensions plus exchange time). The aim of this study was to evaluate the sensitivity of MXTC MRI for the detection of microstructural deformations of the healthy lung in response to gravity-induced tissue compression and the degree of lung inflation. MXTC MRI was performed in four rabbits and in three healthy human volunteers. Two lung function parameters, one related to tissue- to alveolar-volume ratio and the other to average septal-wall thickness, were determined regionally. A significant gradient in MXTC MRI parameters, consistent with gravity-induced lung tissue deformation in the supine imaging position, was found at low lung volumes. At high lung volumes, parameters were generally lower and the gradient in parameter values was less pronounced. Results show that MXTC MRI permits the quantification of subtle changes in healthy lung microstructure. Further, only structures participating in gas exchange are represented in MXTC MRI data, which potentially makes the technique especially sensitive to pathological changes in lung microstructure affecting gas exchange.     

Whole-body MRI in children: current status and future applications

Whole-body MRI (WBMRI) is a novel technique that makes imaging of the whole patient in a manner similar to scintigraphy or positron emission tomography (PET) possible. Unlike the latter two methods, it is without exposure to radiation and thus gaining increasing importance and application in pediatrics. With the introduction of a moving tabletop, sequential movement of the patient through the magnet has become possible with automatic direct realignment of the images after acquisition. The common scan plane is coronal with additional planes being added depending on the indication. WBMRI is targeted for maximum coverage of the body within the shortest possible time using the minimum number of sequences. The evaluation of the bone marrow has been the primary indication thus inversion recovery sequences like STIR or TIRM are mostly used with the T1-weighted sequence being added variably. For correct evaluation of the bone marrow in the pediatric age group understanding normal pattern of marrow transformation is essential. The primary role of WBMRI has been in oncology for the detection of tumor spread and also for the follow-up and evaluation of complications. The initial comparative studies of WBMRI with scintigraphy and PET in children have shown the high diagnostic potential of WBMRI. Emerging potential applications of WBMRI include the evaluation for osteonecrosis, chronic multifocal recurrent osteomyelitis, myopathies, and generalized vascular malformations. Future use of WBMRI may incorporate non-accidental trauma, virtual autopsy, body fat mapping and diffusion-weighted imaging.     

Pulmonary ventilation and perfusion scanning using hyperpolarized helium-3 MRI and arterial spin tagging in healthy normal subjects and in pulmonary embolism and orthotopic lung transplant patients.

Conventional nuclear ventilation/perfusion (V/Q) scanning is limited in spatial resolution and requires exposure to radioactivity. The acquisition of pulmonary V/Q images using MRI overcomes these difficulties. When inhaled, hyperpolarized helium-3 ((3)He) permits MRI of gas distribution. Magnetic labeling of blood (arterial spin-tagging (AST)) provides images of pulmonary perfusion. Three normal subjects, two patients who had undergone single lung transplantation for emphysema, and one subject with pulmonary embolism (PE), were imaged. (3)He distribution and blood perfusion appeared uniform in the normal subjects and throughout the lung allografts. Gas distribution and perfusion in the emphysematous lungs were non-uniform and paralleled radiographic abnormalities. AST imaging alone revealed a lower-lobe wedge-shaped perfusion defect in the patient with PE that corresponded to computed tomography (CT) imaging. Hyperpolarized (3)He gas is demonstrated to provide ventilation images of the lung. Blood perfusion information may be obtained during the same examination using the AST technique. The sequential application of these imaging methods provides a novel tool for studying V/Q relationships.     

Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: Review of current and emerging translational methods and applications

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation-induced lung injury. The strengths and challenges of the application of (3)He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques.     

Hyperpolarized 13C MRI of the pulmonary vasculature and parenchyma.

The study of lung perfusion in normal and diseased subjects is of great interest to physiologists and physicians. In this work we demonstrate the application of a liquid-phase hyperpolarized (HP) carbon-13 ((13)C) tracer to magnetic resonance imaging (MRI) of the pulmonary vasculature and pulmonary perfusion in a porcine model. Our results show that high spatial and temporal resolution images of pulmonary perfusion can be obtained with this contrast technique. Traditionally, pulmonary perfusion measurement techniques have been challenging because of insufficient signal for quantitative functional assessments. The use of polarized (13)C in MRI overcomes this limitation and may lead to a viable clinical method for studying the pulmonary vasculature and perfusion.     

Assessment of the lung microstructure in patients with asthma using hyperpolarized 3He diffusion MRI at two time scales: comparison with healthy subjects and patients with COPD

PURPOSE: To investigate short- and long-time-scale (3)He diffusion in asthma. MATERIALS AND METHODS: A hybrid MRI sequence was developed to obtain co-registered short- and long-time-scale apparent diffusion coefficient (ADC) maps during a single breath-hold. The study groups were: asthma (n = 14); healthy (n = 14); chronic obstructive pulmonary disease (COPD) (n = 9). Correlations were made between mean-ADC and %ADC-abn (abnormal) (%pixels with ADC > mean +2 SD of healthy) at both time scales and spirometry. Sensitivities were determined using receiver operating characteristic (ROC) analysis. RESULTS: For asthmatics, the short- and long-time-scale group-mean ADCs were 0.254 +/- 0.032 cm(2)/s and 0.0237 +/- 0.0055 cm(2)/s, respectively, representing a 9% and 27% (P = 0.038 and P = 0.005) increase compared to the healthy group. The group-mean %ADC-abn were 6.4% +/- 3.7% and 17.5% +/- 14.2%, representing a 107% and 272% (P = 0.004 and P = 0.006) increase. For COPD much greater elevations were observed. %ADC-abn provided better discrimination than mean-ADC between asthmatic and healthy subjects. In asthmatics ADC did not correlate with spirometry. CONCLUSION: With long-time scale (3)He diffusion magnetic resonance imaging (MRI) changes in lung microstructure were detected in asthma that more conspicuous regionally than at the short time scale. The hybrid diffusion method is a novel means of identifying small airway disease.     

Perfusion abnormalities in pulmonary embolism studied with perfusion MRI and ventilation-perfusion scintigraphy: an intra-modality and inter-modality agreement study

PURPOSE: To compare perfusion magnetic resonance imaging (MRI) and ventilation-perfusion scintigraphy (V-P scan) in the study of perfusion abnormalities in pulmonary embolism (PE) and to compare the PE results to the findings previously reported for pneumonia and chronic obstructive pulmonary disease (COPD), in terms of perfusion abnormalities. MATERIALS AND METHODS: Dynamic contrast-enhanced MR images and V-P scans of 20 patients with PE, 11 patients with acute pneumonia, and 13 patients with exacerbation of COPD were studied. Five categories of perfusion abnormalities within each imaging modality were defined. Intra- and inter-modality agreement (kappa values) in the evaluation of perfusion abnormalities were calculated, based on the two observers of each imaging modality (all blinded to each other and true diagnosis). Finally, three categories of perfusion MRI diagnosis (PE, pneumonia, and COPD) were also defined and the inter-observer agreement (kappa value) was calculated. RESULTS: For PE, the intra-modality agreement (kappa value) in the evaluation of perfusion abnormalities was 0.77 for MRI and 0.65 for V-P scan. The inter-modality agreement varied from 0.52 to 0.57, respectively, and was observer-dependent. For the pooled group of PE, pneumonia, and COPD, the intra-modality agreement of perfusion abnormalities was 0.76 for MRI and 0.65 for V-P scan, and the inter-modality agreement varied from 0.51 to 0.56. The kappa value for inter-observer agreement for MRI diagnosis was 0.92. CONCLUSION: Evaluation of perfusion abnormalities in PE, pneumonia, and COPD using perfusion MRI and V-P scan showed a high intra-modality agreement that was higher than the inter-modality agreement. Further studies are now needed in patients presenting with possible PE to evaluate the sensitivity and specificity of the method.     

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.     

Computer based simulation in CT and MRI radiography education: Current role and future opportunities

ObjectiveThe use of Computer-based simulation (CBS), a form of simulation which utilises digital and web based platforms, is widely acknowledged in healthcare education. This literature review explores the current evidence relating to CBS activities in supporting radiographer education in CT and MRI.Key findingsJournal articles published between 2010 and 2020 were reviewed (n = 663). The content was evaluated and summarised with the following headings; current utility, overview of CBS types, knowledge acquisition and evaluation, and student perspective.CBS utility in CT and MRI radiography education is limited. Its current use is for pre-registration education, and the interfaces used vary in design but are predominantly used as a preclinical learning tool to support the training of geometric scan planning, image acquisition and reconstruction, and associated technical skills. CBS was positively acknowledged by student radiographers; based on its inherent flexibility, self-paced learning and the ability to practice in a safe environment. Nonetheless, the educational validation of CBS in CT and MRI education pertaining to knowledge and skill acquisition has not been fully assessed through rigorous academic assessments and metrics.ConclusionThe current use of CBS in CT and MRI education is limited. The development of software programmes with functionality and capability that correlates with current clinical practice is imperative; and to enable more research in CBS utility to be undertaken to establish the efficacy of this pedagogical approach.Implications for practiceDue to limited placement opportunities, the use of simulation is increasing and evolving; in line with the approach to design and deliver high quality Simulation Based Education (SBE) in Diagnostic Radiography education. The continued development, utility and evaluation of CBS interfaces to support student radiographers at pre and post registration level is therefore essential.     

MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: Current status and future needs

Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR‐guided HIFU system. The MR‐based evaluation of HIFU treatment is most often restricted to contrast‐enhanced T₁‐weighted imaging, while it has been shown that the non‐perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU‐induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been—or could be—used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI‐based evaluation of HIFU treatment. Magn Reson Med 75:302–317, 2016. © 2015 Wiley Periodicals, Inc.