Helen Marshall¹, Laurie J Smith¹, Alberto Biancardi¹, Guilhem J Collier¹, Ho-Fung Chan¹, Paul JC Hughes¹, Martin L Brook¹, Joshua Astley¹, Ryan Munro¹, Smitha Rajaram¹, Andrew J Swift¹, David Capener¹, Jody Bray¹, Ayla K Hussain¹, James Ball¹, Olly Rodgers¹, Demi Jakymelen¹, Ian Smith¹, Bilal A Tahir¹, Madhwesha Rao¹, Graham Norquay¹, Nick D Weatherley¹, Leanne Armstrong¹, Latife Hardaker², Titti Fihn-Wikander³, François-Xavier Blé⁴, Rod Hughes⁵, and Jim M Wild^1
1Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom, ²Priory Medical Group, York, United Kingdom, ³Evidence Delivery, BioPharmaceuticals Medical, Biopharmaceuticals Business Unit, AstraZeneca, Gothenburg, Sweden, ⁴Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, Biopharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, ⁵Clinical Development, Research and Early Development, Respiratory & Immunology, AstraZeneca, Cambridge, United Kingdom

There is a need for biomarkers to guide appropriate treatment in patients with clinical features of both asthma and COPD.  A broadly-defined population of 164 patients with asthma and/or COPD taking part in the NOVELTY study were recruited from primary care and scanned with ¹²⁹Xe MRI (ventilation, acinar microstructure and gas exchange measurements).  ¹²⁹Xe MRI global and regional metrics showed significant differences between patients with asthma, asthma+COPD and COPD.  ¹²⁹Xe MRI metrics remained sensitive to diagnosis sub-groups when only patients with normal pulmonary function tests were considered.

David Mummy¹, Aparna Swaminathan², Elianna Bier³, Kevin Yarnall⁴, Aryil Bechtel⁵, Junlan Lu⁶, Suphachart Leewiwatwong⁶, Sakib Kabir¹, Jennifer Korzekwinski¹, and Bastiaan Driehuys^1,3,6
1Radiology, Duke University, Durham, NC, United States, ²Medicine, Duke University, Durham, NC, United States, ³Biomedical Engineering, Duke University, Durham, NC, United States, ⁴Mechanical Engineering, Duke University, Durham, NC, United States, ⁵Physics, Duke University, Durham, NC, United States, ⁶Medical Physics, Duke University, Durham, NC, United States

Age-related changes in ¹²⁹Xe gas exchange MRI and spectroscopy are not well understood. We assessed a suite of common ¹²⁹Xe-derived measures of gas exchange function in a population of healthy control subjects age 19-87. Increased age was associated with reduced red blood cell (RBC) to barrier ratio and with greater levels of ventilation defects and RBC transfer defects. These effects must be accounted for when evaluating ¹²⁹Xe-derived metrics as markers of disease in individual patients. Notably, high barrier uptake remained largely minimal across age groups, and does not appear to be a feature of healthy aging.

Ho-Fung Chan¹, Guilhem J Collier¹, Laurie J Smith¹, Alberto M Biancardi¹, Jody Bray¹, Helen Marshall¹, Paul J.C Hughes¹, Madhwesha Rao¹, Graham Norquay¹, Andrew J Swift¹, Kylie Hart^2,3, Michael Cousins^2,3, Sailesh Kotecha^2,3, and Jim M Wild^1
1Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom, ²Child Health, Cardiff University School of Medicine, Cardiff, United Kingdom, ³Neonatal Unit, Cardiff and Vale University Health Board, Cardiff, United Kingdom

Ventilation defects and increased alveolar heterogeneity have been observed previously with ¹²⁹Xe MRI in preterm-born children. We hypothesised that reduced gas exchange in preterm-born children could be measured with dissolved ¹²⁹Xe whole lung spectroscopy. The ratio of red blood cells (RBC) to tissue/plasma (TP) signals (RBC/TP) was significantly elevated in the lungs of 34 preterm-born children compared with 16 term-born children. This trend was unexpected and we hypothesise that in preterm-born children a reduced number of alveolar septa due to birth at an early stage of lung development can lead to decreased TP signal and thus increased RBC/TP ratio.

Matthew Willmering¹, Joseph Plummer^1,2, Laura Walkup^1,2,3,4, Zackary Cleveland^1,2,3,4, and Jason Woods^1,3,4,5
1Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Pediatrics, University of Cincinnati Medical Center, Cincinnati, OH, United States, ⁵Physics, University of Cincinnati, Cincinnati, OH, United States

Previous ¹²⁹Xe-MRI binning analysis techniques assumed normal distributions or relied on a Box-Cox transformation. Adapting these binning methods to account for known covariates of lung function and structure, such as age and height, was not straightforward. To account for these limitations, a new binning method is proposed here that uses the same modeling techniques used to increase sensitivity and specificity in spirometry and diffusing capacity for carbon monoxide (DLCO). By accounting for MRI image distribution shapes and covariates, healthy representative data distributions are better modelled and can permit increased sensitivity and specificity, particularly for early cardiopulmonary disease progression.

Joseph W Plummer^1,2, Abdullah S Bdaiwi^1,2, Mariah L Costa^1,2, Matthew M Willmering¹, Zackary I Cleveland^1,2,3, and Laura L Walkup^1,2,3,4
1Center for Pulmonary Imaging Research, Department of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Hyperpolarized ¹²⁹Xe-MRI is prone to B₁-inhomogeneity-induced signal artifacts, that often obscure pulmonary abnormalities. B₁-inhomeogeneity can be corrected by calculating a flip-angle map and rescaling the images. Current methods to acquire a flip-angle map in 2D-spiral sequences require two-successive images to be collected in a single breath-hold, doubling scan duration. We demonstrate that flip-angle maps can be calculated from a single image acquisition using keyhole reconstruction. Furthermore, analytical methods can be used to minimize the amount of required oversampling. This approach enables accurate B₁-artifact correction, with minimal impact to scan-duration, making it especially useful for short breath-hold studies.

Joseph Plummer^1,2, Matthew Willmering¹, Laura Walkup^1,2,3,4, Zackary Cleveland^1,2,3,4, and Jason Woods^1,3,4,5
1Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Pediatrics, University of Cincinnati Medical Center, Cincinnati, OH, United States, ⁵Physics, University of Cincinnati, Cincinnati, OH, United States

¹²⁹Xe-MRI can quantify abnormal gas-exchange by defining thresholds derived from voxel-level gas-exchange distributions in healthy subjects. Previous studies assumed a constant healthy distribution independent of age. By fitting to Box-Cox Power Exponential distributions, normal distributions cannot be assumed, and the distributions vary significantly with age. The effect size of age (5-69 years) on healthy ventilation, barrier-uptake, and red-blood cell to barrier (ratio) signal distributions were 14 to 57%. Thus, age and distribution shape should be considered when defining reference distributions for gas-exchange metrics. By accounting for age-dependent variations, the reference distributions abnormal thresholds could be narrowed.

Dustin J. Basler¹, Abdullah S. Bdaiwi^1,2, Matthew M. Willmering¹, Laura L. Walkup^1,2,3,4, Zackary I. Cleveland^1,2,3,4, and Jason C. Woods^1,3,4
1Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States

MRI of hyperpolarized ¹²⁹Xe has been shown to be a robust, non-invasive biomarker to assess pulmonary disease pathophysiology. Static spin-density maps (ventilation images) are commonly analyzed using the ventilation defect percentage (VDP) to quantify the degree of airway obstruction in diseases including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. However, VDP reduces the intrinsic 3D-spatial richness of ventilation images to a global measure, suppressing underlying spatial correlations. In this work, a gray-level run-length matrix (GLRLM) analysis is assessed as an adjunct to VDP analysis for quantifying obstruction in Cystic Fibrosis (CF) lung disease, relative to a healthy control cohort.     

Guilhem J. Collier¹, Ho-Fung Chan¹, Neil J. Stewart¹, Graham Norquay¹, Laurie J. Smith¹, Madhwesha Rao¹, Helen Marshall¹, Rolf F. Schulte², and Jim M. Wild^1
1POLARIS, University of Sheffield, Sheffield, United Kingdom, ²GE Healthcare, Munich, Germany

This work investigates the correlation between age and pulmonary gas transfer measurements assessed with dissolved xenon-129 MRI in 26 healthy volunteers with an age range of 23 to 68yrs. Dependence on lung inflation is also investigated by performing imaging at total lung capacity. Results show significant negative correlations of xenon tissue uptake and blood transfer and suggest that an age-correction should be performed when reporting results. Imaging at total lung capacity also confirms a significant decrease in xenon gas transfer when compared to imaging during standard inspiratory breath-hold.

Faraz Amzajerdian¹, Hooman Hamedani¹, Ryan Baron¹, Yi Xin¹, Tahmina Achekzai¹, Luis Loza¹, Mostafa Ismail¹, Ian Duncan¹, Stephen Kadlecek¹, Kai Ruppert¹, and Rahim Rizi^1
1University of Pennsylvania, Philadelphia, PA, United States

Hyperpolarized xenon-129 (HXe) imaging is capable of quantifying lung function through measurements of ventilation and gas exchange. However, traditional HXe approaches rely on long breath-holds for imaging, which may not be representative of steady-state behavior and are limited by the volume of gas that can be delivered. In this work, we imaged gas- and dissolved-phase xenon continuously over approximately 50 breaths and retrospectively binned the images, generating dynamic maps encompassing the entire respiratory cycle.

Mariah L. Costa^1,2, Brice J. Albert¹, Abdullah S. Bdaiwi^1,2, Harshavardhana H. Ediga^3,4, Satish K. Madala^3,5, Peter J. Niedbalski^1,6, and Zackary I. Cleveland^1,2,3,5,7
1Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Biochemistry, National Institute of Nutrition, Telangana, India, ⁵Pediatrics, University of Cincinnati, Cincinnati, OH, United States, ⁶Pulmonary and Critical Care, University of Kansas Medical Center, Kansas City, KS, United States, ⁷Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Hyperpolarized (HP) ¹²⁹Xe diffusion imaging, including the apparent diffusion coefficient (ADC) and more sophisticated diffusion morphometry, can assess microstructural dimensions of the acinar airspace. In diseases characterized by alveolar destruction (eg, emphysema), these parameters strongly indicate disease severity. Here, a time-efficient, 2D-spiral diffusion sequence was developed and compared to a conventional GRE-based sequence in a free-diffusion phantom, wild-type mice, a and a transgenic mouse model of lung fibrosis that develops emphysema as a comorbidity. Both sequences provided comparable SNR, ADC values, and morphometry metrics, indicating spiral sequences can assess airspace size in mice, while making efficient use of HP magnetization.

Faiyza Shoaib Alam^1,2, Brandon Zanette², Sharon Braganza², Daniel Li², Felix Ratjen^2,3, and Giles Santyr^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada, ³Division of Respirology, Hospital for Sick Children, Toronto, ON, Canada

Hyperpolarized ¹²⁹Xe MRI (Xe-MRI) yielding VDP has shown advantages over conventional PFT’s for assessing paediatric CF lung disease but is only a static “snapshot” of a dynamic process. Xe-MRI can be conducted in a MBW fashion to yield temporal/spatial heterogeneity of the gas during respiration, resulting in regional maps of fractional ventilation (r), a measure of percent gas clearance per breath. This work assessed the within-visit and inter-visit repeatability of MBW Xe-MRI between baseline and one-month follow-up in paediatric subjects with stable CF and found strong intra- and inter-visit repeatability. Significant correlations between MBW Xe-MRI and LCI were also found.

Suphachart Leewiwatwong¹, Junlan Lu², Jesse Zhang³, David Mummy⁴, Isabelle Dummer^4,5, Kevin Yarnall⁶, Ziyi Wang¹, and Bastiaan Driehuys^1,2,4
1Biomedical Engineering, Duke University, Durham, NC, United States, ²Medical Physics, Duke University, Durham, NC, United States, ³Mathematics, Duke University, Durham, NC, United States, ⁴Radiology, Duke University, Durham, NC, United States, ⁵Bioengineering, McGill University, Montréal, QC, Canada, ⁶Mechanical Engineering and Materials Science, Duke University, Durham, NC, United States

Quantification of ¹²⁹Xe MRI relies on accurate segmentation of the thoracic cavity. This segmentation could potentially be performed directly on the ¹²⁹Xe ventilation image using an automated convolutional neural network, but this task is challenging, especially in cases where peripheral ventilation defects obscure the lung boundary. Currently, overcoming this obstacle requires large, diverse training datasets created by time-consuming manual segmentation. Here, we demonstrate the use of a generative Pix2Pix model to synthesize both ¹²⁹Xe images with defects, and corresponding segmentation masks. We then test the effects of this additional training data on the performance of an existing U-net segmentation algorithm.