Establishing a hemoglobin adjustment for 129Xe gas exchange MRI and MRS
Aryil Bechtel
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorJunlan Lu
Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA
Search for more papers by this authorDavid Mummy
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorElianna Bier
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorSuphachart Leewiwatwong
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorJohn Mugler III
Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, USA
Search for more papers by this authorSakib Kabir
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorAlex Church
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorCorresponding Author
Bastiaan Driehuys
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Correspondence
Bastiaan Driehuys, Department of Radiology, Box 3302, Duke University Medical Center, Durham, NC 27710, USA.
Email: [email protected]
Search for more papers by this authorAryil Bechtel
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorJunlan Lu
Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA
Search for more papers by this authorDavid Mummy
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorElianna Bier
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorSuphachart Leewiwatwong
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorJohn Mugler III
Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, USA
Search for more papers by this authorSakib Kabir
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorAlex Church
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorCorresponding Author
Bastiaan Driehuys
Radiology, Duke University Medical Center, Durham, North Carolina, USA
Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA
Biomedical Engineering, Duke University, Durham, North Carolina, USA
Correspondence
Bastiaan Driehuys, Department of Radiology, Box 3302, Duke University Medical Center, Durham, NC 27710, USA.
Email: [email protected]
Search for more papers by this authorAbstract
Purpose
129Xe MRI and MRS signals from airspaces, membrane tissues (M), and red blood cells (RBCs) provide measurements of pulmonary gas exchange. However, 129Xe MRI/MRS studies have yet to account for hemoglobin concentration (Hb), which is expected to affect the uptake of 129Xe in the membrane and RBC compartments. We propose a framework to adjust the membrane and RBC signals for Hb and use this to assess sex-specific differences in RBC/M and establish a Hb-adjusted healthy reference range for the RBC/M ratio.
Methods
We combined the 1D model of xenon gas exchange (MOXE) with the principle of TR-flip angle equivalence to establish scaling factors that normalize the dissolved-phase signals with respect to a standard (14 g/dL). 129Xe MRI/MRS data from a healthy, young cohort (n = 18, age = 25.0 3.4 years) were used to validate this model and assess the impact of Hb adjustment on M/gas and RBC/gas images and RBC/M.
Results
Adjusting for Hb caused RBC/M to change by up to 20% in healthy individuals with normal Hb and had marked impacts on M/gas and RBC/gas distributions in 3D gas-exchange maps. RBC/M was higher in males than females both before and after Hb adjustment (p < 0.001). After Hb adjustment, the healthy reference value for RBC/M for a consortium-recommended acquisition of TR = 15 ms and flip = 20° was 0.589 0.083 (mean SD).
Conclusion
MOXE provides a useful framework for evaluating the Hb dependence of the membrane and RBC signals. This work indicates that adjusting for Hb is essential for accurately assessing 129Xe gas-exchange MRI/MRS metrics.
CONFLICT OF INTEREST STATEMENT
Bastiaan Driehuys is founder and chief technology officer for Polarean Imaging. David Mummy is a consultant for Polarean Imaging.
REFERENCES
- 1Marshall H, Stewart NJ, Chan HF, Rao M, Norquay G, Wild JM. In vivo methods and applications of xenon-129 magnetic resonance. Prog Nucl Magn Reson Spectrosc. 2021; 122: 42-62. doi:10.1016/J.PNMRS.2020.11.002
- 2Wang JM, Robertson SH, Wang Z, et al. Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis. Thorax. 2018; 73: 21-28. doi:10.1136/THORAXJNL-2017-210070
- 3Virgincar RS, Cleveland ZI, Sivaram Kaushik S, et al. Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease. NMR Biomed. 2013; 26: 424-435. doi:10.1002/NBM.2880
- 4Thomen RP, Walkup LL, Roach DJ, Cleveland ZI, Clancy JP, Woods JC. Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. J Cyst Fibros. 2017; 16: 275-282. doi:10.1016/J.JCF.2016.07.008
- 5Wang Z, Bier EA, Swaminathan A, et al. Diverse cardiopulmonary diseases are associated with distinct xenon magnetic resonance imaging signatures. Eur Respir J. 2019; 54:1900831. doi:10.1183/13993003.00831-2019
- 6Bier EA, Robertson SH, Schrank GM, et al. A protocol for quantifying cardiogenic oscillations in dynamic 129 Xe gas exchange spectroscopy: the effects of idiopathic pulmonary fibrosis. NMR Biomed. 2019; 32:e4029. doi:10.1002/NBM.4029
- 7Niedbalski PJ, Hall CS, Castro M, et al. Protocols for multi-site trials using hyperpolarized 129Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: a position paper from the 129Xe MRI clinical trials consortium. Magn Reson Med. 2021; 86: 2966-2986. doi:10.1002/mrm.28985
- 8Wang Z, Rankine L, Bier EA, et al. Using hyperpolarized 129Xe gas-exchange MRI to model the regional airspace, membrane, and capillary contributions to diffusing capacity. J Appl Physiol. 2021; 130: 1398-1409. doi:10.1152/japplphysiol.00702.2020
- 9Qing K, Mugler JP, Altes TA, et al. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR Biomed. 2014; 27: 1490-1501. doi:10.1002/nbm.3179
- 10Mummy DG, Bier EA, Wang Z, et al. Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in nonspecific interstitial pneumonia. Radiology. 2021; 301: 211-220. doi:10.1148/radiol.2021204149
- 11Weatherley ND, Stewart NJ, Chan HF, et al. Hyperpolarised xenon magnetic resonance spectroscopy for the longitudinal assessment of changes in gas diffusion in IPF. Thorax. 2019; 74: 500-502. doi:10.1136/thoraxjnl-2018-211851
- 12Hahn AD, Carey KJ, Barton GP, et al. Hyperpolarized 129 Xe MR spectroscopy in the lung shows 1-year reduced function in idiopathic pulmonary fibrosis. Radiology 2022; 305: 688-696. doi:10.1148/radiol.211433
- 13Kaushik SS, Freeman MS, Yoon SW, et al. Measuring diffusion limitation with a perfusion-limited gas-hyperpolarized Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis. J Appl Physiol. 2014; 117: 577-585. doi:10.1152/japplphysiol.00326.2014.-Al
- 14Stewart NJ, Leung G, Norquay G, et al. Experimental validation of the hyperpolarized 129 Xe chemical shift saturation recovery technique in healthy volunteers and subjects with interstitial lung disease. Magn Reson Med. 2015; 74: 196-207. doi:10.1002/mrm.25400
- 15Xie J, Li H, Zhang H, et al. Single breath-hold measurement of pulmonary gas exchange and diffusion in humans with hyperpolarized 129Xe MR. NMR Biomed. 2019; 32:e4068. doi:10.1002/NBM.4068
- 16Marrades RM, Diaz O, Roca J, et al. Adjustment of DL(CO) for hemoglobin concentration. Am J Respir Crit Care Med. 1997; 155: 236-241. doi:10.1164/ajrccm.155.1.9001318
- 17Bifone A, Song YQ, Seydoux R, et al. NMR of laser-polarized xenon in human blood. Proc Natl Acad Sci U S A. 1996; 93: 12932-12936. doi:10.1073/pnas.93.23.12932
- 18Munkholm M, Marott JL, Bjerre-Kristensen L, et al. Reference equations for pulmonary diffusing capacity of carbon monoxide and nitric oxide in adult Caucasians. Eur Respir J. 2018; 52:1500677. doi:10.1183/13993003.00677-2015
- 19Chang Y v. MOXE: a model of gas exchange for hyperpolarized 129Xe magnetic resonance of the lung. Magn Reson Med. 2013; 69: 884-890. doi:10.1002/MRM.24304
- 20Ruppert K, Amzajerdian F, Hamedani H, et al. Assessment of flip angle–TR equivalence for standardized dissolved-phase imaging of the lung with hyperpolarized 129Xe MRI. Magn Reson Med. 2019; 81: 1784-1794. doi:10.1002/MRM.27538
- 21Chang Y v, Quirk JD, Ruset IC, Atkinson JJ, William Hersman F, Woods JC. Quantification of human lung structure and physiology using hyperpolarized 129 Xe. Magn Reson Med. 2014; 71: 339-344. doi:10.1002/mrm.24992
- 22Nijboer JMM, van der Horst ICC, Hendriks HGD, ten Duis HJ, Nijsten MWN. Myth or reality: hematocrit and hemoglobin differ in trauma. J Trauma – Injury Infect Crit Care. 2007; 62: 1310-1312. doi:10.1097/TA.0B013E3180341F54
- 23Foster KE, Sahay RD, Zhang N, Hardie WD. Results of a prospective study evaluating a noninvasive method of hemoglobin adjustment for determining the diffusing capacity of the lung. Ann Am Thorac Soc. 2017; 14: 41-48. doi:10.1513/AnnalsATS.201603-197OC
- 24Brudin LH, Valind SO, Rhodes CG, Turton DR, Hughes JM. Regional lung hematocrit in humans using positron emission tomography. J Appl Physiol. 1986; 60: 1155-1163. doi:10.1152/JAPPL.1986.60.4.1155
- 25Overholser KA, Lomangino NA, Harris TR, Bradléy JD, Bosan S. Deduction of pulmonary microvascular hematocrit from indicator dilution curves. Bull Math Biol. 1994; 56: 225-247. doi:10.1007/BF02460641
- 26Reinhart WH, Piety NZ, Shevkoplyas SS. Influence of feeding hematocrit and perfusion pressure on hematocrit reduction (Fåhræus effect) in an artificial microvascular network. Microcirculation. 2017; 24. doi:10.1111/MICC.12396
- 27Vasilescu DM, Phillion AB, Kinose D, et al. Comprehensive stereological assessment of the human lung using multiresolution computed tomography. J Appl Physiol. 2020; 128: 1604-1616. doi:10.1152/japplphysiol.00803.2019
- 28Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol. 1978; 32: 121-140. doi:10.1016/0034-5687(78)90104-4
- 29Weibel ER, Knight BW. A morphometric study on the thickness of the pulmonary air-blood barrier. J Cell Biol. 1964; 21: 367-396. doi:10.1083/JCB.21.3.367
- 30Niedbalski PJ, Lu J, Hall CS, et al. Utilizing flip angle/TR equivalence to reduce breath hold duration in hyperpolarized 129Xe 1-point Dixon gas exchange imaging. Magn Reson Med. 2022; 87: 1490-1499. doi:10.1002/mrm.29040
- 31Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012; 40: 1324-1343. doi:10.1183/09031936.00080312
- 32Wang Z, He M, Bier E, et al. Hyperpolarized 129 Xe gas transfer MRI: the transition from 1.5T to 3T magnetic resonance in medicine. Magn Reson Med. 2018; 80: 2374-2383. doi:10.1002/mrm.27377
- 33Wang Z, Robertson SH, Wang J, et al. Quantitative analysis of hyperpolarized 129 Xe gas transfer MRI. Med Phys. 2017; 44: 2415-2428. doi:10.1002/mp.12264
- 34Wang Z, He M, Virgincar RS, Bier EA, Luo S, Driehuys B. Quantifying hyperpolarized 129Xe gas exchange MRI across platforms, field strength, and acquisition parameters. In Proceedings of the 27th Annual Meeting and Exhibition of ISMRM, Montréal, QC, Canada, 2019. #4139.
- 35Fischbach FT. A Manual of Laboratory and Diagnostic Tests. 7th ed. Lippincott Williams & Wilkins; 2003.
- 36Hahn AD, Kammerman J, Evans M, et al. Repeatability of regional pulmonary functional metrics of hyperpolarized 129Xe dissolved phase MRI. J Magn Reson Imaging. 2019; 50: 1182-1190. doi:10.1002/JMRI.26745
- 37Stewart NJ, Horn FC, Norquay G, et al. Reproducibility of quantitative indices of lung function and microstructure from 129Xe chemical shift saturation recovery (CSSR) MR spectroscopy. Magn Reson Med. 2017; 77: 2107-2113. doi:10.1002/mrm.26310
- 38Li H, Zhang Z, Zhao X, Sun X, Ye C, Zhou X. Quantitative evaluation of radiation-induced lung injury with hyperpolarized xenon magnetic resonance. Magn Reson Med. 2016; 76: 408-416. doi:10.1002/MRM.25894
- 39Zhong J, Zhang H, Ruan W, et al. Simultaneous assessment of both lung morphometry and gas exchange function within a single breath-hold by hyperpolarized 129Xe MRI. NMR Biomed. 2017; 30:e3730. doi:10.1002/NBM.3730
- 40Zhang Z, Guan Y, Li H, et al. Quantitative comparison of lung physiological parameters in single and multiple breathhold with hyperpolarized xenon magnetic resonance. Biomed Phys Eng Express. 2016; 2:055013. doi:10.1088/2057-1976/2/5/055013
10.1088/2057-1976/2/5/055013 Google Scholar
- 41Graham BL, Brusasco V, Burgos F, et al. ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 2017; 49. doi:10.1183/13993003.00016-2016
- 42Bellemare F, Jeanneret A, Couture J. Sex differences in thoracic dimensions and configuration. Am J Respir Crit Care Med. 2003; 168: 305-312. doi:10.1164/rccm.200208-876OC
- 43Qing K, Tustison N, Altes T, et al. Gas uptake measures on hyperpolarized Xenon-129 MRI are inversely proportional to lung inflation level. In Proceedings of the 23rd Annual Meeting and Exhibition of ISMRM, Toronto, ON, Canada, 2015. #1488.
- 44Collier GJ, Chan HF, Stewart NJ, et al. Age and lung volume dependence of dissolved xenon-129 imaging parameters. In Proceedings of the Joint Annual Meeting ISMRM-ESMRMB 2022 and ISMRT Annual Meeting, London, England, UK, 2022. #1174.
- 45Grist JT, Chen M, Collier GJ, et al. Hyperpolarized 129Xe MRI abnormalities in dyspneic patients 3 months after COVID-19 pneumonia. Radiology. 2021; 301: E353-E360. doi:10.1148/radiol.2021210033
- 46Ruppert K, Qian Y, Amzajerdian F, et al. Biases in apparent alveolar Septal Wall thickness measurements with hyperpolarized Xenon-129 MRI revealed by numerical simulations. American Thoracic Society International Conference Meetings Abstracts. American Thoracic Society; 2021:A4597. Accessed September 1, 2022. doi:10.1164/ajrccm-conference
10.1164/ajrccm?conference Google Scholar
- 47Reid JA, Heard BE. The capillary network of Normal and emphysematous human lungs studied by injections of Indian ink. Thorax. 1963; 18: 201-212. doi:10.1136/THX.18.3.201
- 48Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular Endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020; 383: 120-128. doi:10.1056/nejmoa2015432
- 49Zanen P, van der Lee I, van der Mark T, van den Bosch JMM. Reference values for alveolar membrane diffusion capacity and pulmonary capillary blood volume. Eur Respir J. 2001; 18: 764-769. doi:10.1183/09031936.01.00232101
- 50Crapo RO, Crapo JD, Morris AH. Lung tissue and capillary blood volumes by rebreathing and morphometric techniques. Respir Physiol. 1982; 49: 175-186. doi:10.1016/0034-5687(82)90072-X
- 51Stewart NJ, Parra-Robles J, Wild JM. Finite element modeling of (129)Xe diffusive gas exchange NMR in the human alveoli. J Magn Reson. 2016; 271: 21-33. doi:10.1016/J.JMR.2016.07.016
- 52Ziegler AK, Grand J, Stangerup I, et al. Time course for the recovery of physical performance, blood hemoglobin, and ferritin content after blood donation. Transfusion (Paris). 2015; 55: 898-905. doi:10.1111/TRF.12926
- 53Elzik ME, Dirschl DR, Dahners LE. Correlation of transfusion volume to change in hematocrit. Am J Hematol. 2006; 81: 145-146. doi:10.1002/AJH.20517
- 54Kim KH, Oh KY. Clinical applications of therapeutic phlebotomy. J Blood Med. 2016; 7: 139-144. doi:10.2147/JBM.S108479
- 55Mummy D, Swaminathan A, Bier E, et al. Hyperpolarized 129Xe MRI and spectroscopy in healthy control subjects reveals age-related changes in measurements of pulmonary gas exchange. In Proceedings of the Joint Annual Meeting ISMRM-ESMRMB 2022 and ISMRT Annual Meeting, London, England, UK, 2022. #1168.
- 56Ruppert K, Mata JF, Brookeman JR, Hagspiel KD, Mugler JP. Exploring lung function with hyperpolarized 129Xe nuclear magnetic resonance. Magn Reson Med. 2004; 51: 676-687. doi:10.1002/MRM.10736
- 57Ladefoged J, Andersen AM. Solubility of Xenon-133 at 37°C in water, saline, olive oil, liquid paraffin, solutions of albumin, and blood. Phys Med Biol. 1967; 12: 353-358. doi:10.1088/0031-9155/12/3/307
