Imaging Dynamic Expiration: Feasibility of MRI Spirometry Using Hyperpolarized Xenon Gas.

PURPOSE: To examine the feasibility of imaging-based spirometry using high-temporal-resolution projection MRI and hyperpolarized xenon 129 (129Xe) gas. MATERIALS AND METHODS: In this prospective exploratory study, five healthy participants (age range, 25-45 years; three men) underwent an MRI spirometry technique using inhaled hyperpolarized 129Xe and rapid two-dimensional projection MRI. Participants inhaled 129Xe, then performed a forced expiratory maneuver while in an MR imager. Images of the lungs during expiration were captured in time intervals as short as 250 msec. Volume-corrected images of the lungs at expiration commencement (0 second), 1 second after expiration, and 6 seconds after expiration were extracted to generate forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio pulmonary maps. For comparison, participants performed conventional spirometry in the sitting position using room air, in the supine position using room air, and in the supine position using a room air and 129Xe mixture. Paired t tests with Bonferroni corrections for multiple comparisons were used for statistical analyses. RESULTS: The mean MRI-derived FEV1/FVC value was lower in comparison with conventional spirometry (0.52 ± 0.03 vs 0.70 ± 0.05, P < .01), which may reflect selective 129Xe retention. A secondary finding of this study was that 1 L of inhaled 129Xe negatively impacted pulmonary function as measured by conventional spirometry (in supine position), which reduced measured FEV1 (2.70 ± 0.90 vs 3.04 ± 0.85, P < .01) and FEV1/FVC (0.70 ± 0.05 vs 0.79 ± 0.04, P < .01). CONCLUSION: A forced expiratory maneuver was successfully imaged with hyperpolarized 129Xe and high-temporal-resolution MRI. Derivation of regional lung spirometric maps was feasible.Keywords: MR-Imaging, MR-Dynamic Contrast Enhanced, MR-Functional Imaging, Pulmonary, Thorax, Diaphragm, Lung, Pleura, Physics Supplemental material is available for this article. © RSNA, 2021.

MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies.

A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γ+TNF-α+IL2+) and multi-(IFN-γ+TNF-α+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.

A case series of thoracic dynamic contrast-enhanced MR lymphangiography: technique and applications.

Dynamic contrast-enhanced magnetic resonance lymphangiography is a radiation-free, high spatial resolution technique which is increasingly used to evaluate thoracic lymphatic disorders and for pre-procedural planning. DCE has the added advantage of allowing dynamic real-time evaluation of lymphatic flow. It can be employed to investigate commonly encountered clinical situations such as recurrent pleural effusions following trauma, thoracic duct injury after thoracic surgery, and exclude diseases and congenital malformations of the thoracic lymphatic system. The imaging procedure and protocol are detailed in this case series to highlight the application of dynamic contrast-enhanced magnetic resonance lymphangiography in everyday practice and its importance to guide surgical planning.

Magnetic resonance imaging of the time course of hyperpolarized 129Xe gas exchange in the human lungs and heart.

PURPOSE: To perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma. MATERIALS AND METHODS: HPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test. RESULTS: The technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05). CONCLUSION: This time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs. KEY POINTS: • The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Ultra low dose aerosol challenge with Mycobacterium tuberculosis leads to divergent outcomes in rhesus and cynomolgus macaques.

Well characterised animal models that can accurately predict efficacy are critical to the development of an improved TB vaccine. The use of high dose challenge for measurement of efficacy in Non-human primate models brings the risk that vaccines with the potential to be efficacious against natural challenge could appear ineffective and thus disregarded. Therefore, there is a need to develop a challenge regimen that is more relevant to natural human infection. This study has established that ultra-low dose infection of macaques via the aerosol route can be reproducibly achieved and provides the first description of the development of TB disease in both rhesus and cynomolgus macaques following exposure to estimated retained doses in the lung of less than 10 CFU of Mycobacterium tuberculosis. CT scanning in vivo and histopathology revealed differences in the progression and burden of disease between the two species. Rhesus macaques exhibited a more progressive disease and cynomolgus macaques showed a reduced disease burden. The ability to deliver reproducible ultra-low dose aerosols to macaques will enable the development of refined models of M. tuberculosis infection for evaluation of the efficacy of novel tuberculosis vaccines that offers increased clinical relevance and improved animal welfare.

Route of delivery to the airway influences the distribution of pulmonary disease but not the outcome of Mycobacterium tuberculosis infection in rhesus macaques.

Non-human primates (NHP) provide a key component in the preclinical assessment pathway for new TB vaccines. In the established models, Mycobacterium tuberculosis challenge is typically delivered to airways of macaques either by aerosol or bronchoscopic instillation and therefore, an understanding of these delivery routes would facilitate the comparison of data generated from models using different challenge methods. This study compared the clinical effects, antigen-specific IFNγ response profiles and disease burden following delivery of comparable doses of M. tuberculosis to the lungs of rhesus macaques by either aerosol or bronchoscopic instillation. The outcome of infection in terms of clinical effects and overall disease burden was comparable between both routes of challenge. However, the pathology in the lungs differed as disease was localised to the site of inoculation following bronchoscopic instillation while aerosol exposure resulted in lesions being evenly distributed through the lung. Whilst the IFNγ response to PPD was similar, responses to CFP10 and ESAT6 peptide pools measured with an ex vivo ELISPOT differed with regards to responses to the N-terminal regions depending on the route of infection. Both challenge routes therefore provide valid and comparable models for evaluation of new TB vaccines, although subtle differences in host responses may occur.