Publications by authors named "Sean B Fain"

128 Publications

Pulmonary Functional Imaging: Part 1-State-of-the-Art Technical and Physiologic Underpinnings.

Radiology 2021 Apr 6:203711. Epub 2021 Apr 6.

From the Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Joint Research Laboratory of Advanced Medical Imaging, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan (Y.O.); Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Department of Medicine, Robarts Research Institute, and Department of Medical Biophysics, Western University, London, Canada (G.P.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea (K.S.L.); Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Departments of Medical Physics and Radiology (S.B.F., M.L.S.), UW-Madison School of Medicine and Public Health, Madison, Wis; and Center for Pulmonary Functional Imaging, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02215 (H.H.).

Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021203711DOI Listing
April 2021

QIBA guidance: Computed tomography imaging for COVID-19 quantitative imaging applications.

Clin Imaging 2021 Feb 25;77:151-157. Epub 2021 Feb 25.

Duke University, United States of America.

As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases.
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http://dx.doi.org/10.1016/j.clinimag.2021.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906537PMC
February 2021

Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts.

Radiology 2021 Apr 16;299(1):222-231. Epub 2021 Feb 16.

From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (S.Y.A., A.A.D., S.E.M., F.N.R., C.L.P., G.R.W.), Applied Chest Imaging Laboratory (S.Y.A., R.S.J.E., A.A.D., S.E.M., F.N.R., C.L.P., G.V.S.F., G.R.W.), and Department of Radiology (R.S.J.E., G.V.S.F.), Brigham and Women's Hospital, 75 Francis St, PBB, CA-3, Boston, MA 02130; Departments of Biomedical Engineering and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wis (S.B.F.); COPD Foundation, Washington, DC (R.T.S., D.M.); Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, England (R.A.S.); Respiratory and Inflammation Therapy Area, Clinical Development, AstraZeneca, Mölndal, Sweden (L.H.N.); Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Nebraska Medical Center, Omaha, Neb (S.R.); Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich (M.K.H.); Department of Radiology, National Jewish Health, Denver, Colo (S.M.H., D.A.L.); and Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Department of Medicine, University of Pittsburgh, Pittsburgh, Pa (F.C.S.).

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; , NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 See also the editorial by Lee and Park in this issue.
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http://dx.doi.org/10.1148/radiol.2021203531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997617PMC
April 2021

Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3.

J Allergy Clin Immunol 2021 Feb 9. Epub 2021 Feb 9.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Kansas School of Medicine, Kansas City, Kan. Electronic address:

Background: Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function.

Objectives: We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma.

Methods: We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity.

Results: Greater baseline wall area percent (β = -0.15 [95% CI = -0.26 to -0.05]; P < .01), hyperinflation percent (β = -0.25 [95% CI = -0.41 to -0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal β = 10.64 [95% CI = 3.79-17.49]; P < .01; posterior-anterior β = -9.14, [95% CI = -15.49 to -2.78]; P < .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio = 1.06 [95% CI = 1.01-1.10]; P = .02) and air trapping percent (rate ratio =1.01 [95% CI = 1.00-1.02]; P = .03), as well as lower decline in the Jacobian determinant mean (rate ratio = 0.58 [95% CI = 0.41-0.82]; P < .01) and Jacobian determinant standard deviation (rate ratio = 0.52 [95% CI = 0.32-0.85]; P = .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires.

Conclusions: Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, and less pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations.
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http://dx.doi.org/10.1016/j.jaci.2021.01.029DOI Listing
February 2021

Experimental Protocol for MRI Mapping of the Blood Oxygenation-Sensitive Parameters T* and T in the Kidney.

Methods Mol Biol 2021 ;2216:403-417

Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins, and has also been suggested to play a role in the development of chronic kidney disease. Here we describe a step-by-step experimental protocol for indirect monitoring of renal blood oxygenation in rodents via the deoxyhemoglobin sensitive MR parameters T* and T-a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect. Since an absolute quantification of renal oxygenation from T*/T remains challenging, the effects of controlled and standardized variations in the fraction of inspired oxygen are used for bench marking. This MRI method may be useful for investigating renal blood oxygenation of small rodents in vivo under various experimental (patho)physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.
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http://dx.doi.org/10.1007/978-1-0716-0978-1_23DOI Listing
March 2021

Effects of neonatal lung abnormalities on parenchymal R * estimates.

J Magn Reson Imaging 2021 Jan 6. Epub 2021 Jan 6.

Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA.

Infants admitted to the neonatal intensive care unit (NICU) often suffer from multifaceted pulmonary morbidities that are not well understood. Ultrashort echo time (UTE) magnetic resonance imaging (MRI) is a promising technique for pulmonary imaging in this population without requiring exposure to ionizing radiation. The aims of this study were to investigate the effect of neonatal pulmonary disease on R * and tissue density and to utilize numerical simulations to evaluate the effect of different alveolar structures on predicted R *.This was a prospective study, in which 17 neonatal human subjects (five control, seven with bronchopulmonary dysplasia [BPD], five with congenital diaphragmatic hernia [CDH]) were enrolled. Twelve subjects were male and five were female, with postmenstrual age (PMA) at MRI of 39.7 ± 4.7 weeks. A 1.5T/multiecho three-dimensional UTE MRI was used. Pulmonary R * and tissue density were compared across disease groups over the whole lung and regionally. A spherical shell alveolar model was used to predict the expected R * over a range of tissue densities and tissue susceptibilities. Tests for significantly different mean R * and tissue densities across disease groups were evaluated using analysis of variance, with subsequent pairwise group comparisons performed using t tests. Lung tissue density was lower in the ipsilateral lung in CDH compared to both controls and BPD patients (both p < 0.05), while only the contralateral lung in CDH (CDHc) had higher whole-lung R * than both controls and BPD (both p < 0.05). R * differences were significant between controls and CDHc within all tissue density ranges (all p < 0.05) with the exception of the 80%-90% range (p = 0.17). Simulations predicted an inverse relationship between alveolar tissue density and R * that matches empirical human data. Alveolar wall thickness had no effect on R * independent of density (p = 1). The inverse relationship between R * and tissue density is influenced by the presence of disease globally and regionally in neonates with BPD and CDH in the NICU. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27487DOI Listing
January 2021

Alveolar Airspace Size in Healthy and Diseased Infant Lungs Measured via Hyperpolarized 3He Gas Diffusion Magnetic Resonance Imaging.

Neonatology 2020 11;117(6):704-712. Epub 2020 Nov 11.

Division of Pulmonary Medicine and Department of Radiology, Center for Pulmonary Imaging Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.

Background: Alveolar development and lung parenchymal simplification are not well characterized in vivo in neonatal patients with respiratory morbidities, such as bronchopulmonary dysplasia (BPD). Hyperpolarized (HP) gas diffusion magnetic resonance imaging (MRI) is a sensitive, safe, nonionizing, and noninvasive biomarker for measuring airspace size in vivo but has not yet been implemented in young infants.

Objective: This work quantified alveolar airspace size via HP gas diffusion MRI in healthy and diseased explanted infant lung specimens, with comparison to histological morphometry.

Methods: Lung specimens from 8 infants were obtained: 7 healthy left upper lobes (0-16 months, post-autopsy) and 1 left lung with filamin-A mutation, closely representing BPD lung disease (11 months, post-transplantation). Specimens were imaged using HP 3He diffusion MRI to generate apparent diffusion coefficients (ADCs) as biomarkers of alveolar airspace size, with comparison to mean linear intercept (Lm) via quantitative histology.

Results: Mean ADC and Lm were significantly increased throughout the diseased specimen (ADC = 0.26 ± 0.06 cm2/s, Lm = 587 ± 212 µm) compared with healthy specimens (ADC = 0.14 ± 0.03 cm2/s, Lm = 133 ± 37 µm; p < 1 × 10-7); increased values reflect enlarged airspaces. Mean ADCs in healthy specimens were significantly correlated to Lm (r = 0.69, p = 0.041).

Conclusions: HP gas diffusion MRI is sensitive to healthy and diseased regional alveolar airspace size in infant lungs, with good comparison to quantitative histology in ex vivo specimens. This work demonstrates the translational potential of gas MRI techniques for in vivo assessment of normal and abnormal alveolar development in neonates with pulmonary disease.
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http://dx.doi.org/10.1159/000511084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878286PMC
November 2020

Hyperpolarized Gas MRI Technology Breaks Through: Advancing Our Understanding of Anti-Type 2 Inflammation Therapies in Severe Asthma.

Authors:
Sean B Fain

Chest 2020 Oct;158(4):1293-1295

Departments of Medical Physics and Radiology, University of Wisconsin-Madison, Madison, WI. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.07.019DOI Listing
October 2020

Increased Work of Breathing due to Tracheomalacia in Neonates.

Ann Am Thorac Soc 2020 10;17(10):1247-1256

Center for Pulmonary Imaging Research.

Dynamic collapse of the tracheal lumen (tracheomalacia) occurs frequently in premature neonates, particularly in those with common comorbidities such as bronchopulmonary dysplasia. The tracheal collapse increases the effort necessary to breathe (work of breathing [WOB]). However, quantifying the increased WOB related to tracheomalacia has previously not been possible. Therefore, it is also not currently possible to separate the impact of tracheomalacia on patient symptoms from parenchymal abnormalities. To measure the increase in WOB due to airway motion in individual subjects with and without tracheomalacia and with different types of respiratory support. Fourteen neonatal intensive care unit subjects not using invasive mechanical ventilation were recruited. In eight, tracheomalacia was diagnosed via clinical bronchoscopy, and six did not have tracheomalacia. Self-gated three-dimensional ultrashort-echo-time magnetic resonance imaging (MRI) was performed on each subject with clinically indicated respiratory support to obtain cine images of tracheal anatomy and motion during the respiratory cycle. The component of WOB due to resistance within the trachea was then calculated via computational fluid dynamics (CFD) simulations of airflow on the basis of the subject's anatomy, motion, and respiratory airflow rates. A second CFD simulation was performed for each subject with the airway held static at its largest (i.e., most open) position to determine the increase in WOB due to airway motion and collapse. The tracheal-resistive component of WOB was increased because of airway motion by an average of 337% ± 295% in subjects with tracheomalacia and 24% ± 14% in subjects without tracheomalacia ( < 0.02). In the tracheomalacia group, subjects who were treated with continuous positive airway pressure (CPAP) using a RAM cannula expended less energy for breathing compared with the subjects who were breathing room air or on a high-flow nasal cannula. Neonatal subjects with tracheomalacia have increased energy expenditure compared with neonates with normal airways, and CPAP may be able to attenuate the increase in respiratory work. Subjects with tracheomalacia expend more energy on the tracheal-resistive component of WOB alone than nontracheomalacia patients expend on the resistive WOB for the entire respiratory system, according to previously reported values. CFD may be able to provide an objective measure of treatment response for children with tracheomalacia.
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http://dx.doi.org/10.1513/AnnalsATS.202002-162OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640633PMC
October 2020

Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency.

J Allergy Clin Immunol 2020 10 13;146(4):831-839.e6. Epub 2020 Mar 13.

Department of Medical Physics, University of Wisconsin-Madison, Madison, Wis; Department of Radiology, University of Wisconsin-Madison, Madison, Wis; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis. Electronic address:

Background: There is an unmet need for an objective biomarker to predict asthma exacerbations.

Objective: Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging.

Methods: Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations.

Results: A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n = 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n = 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI = 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response.

Conclusion: VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations.
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http://dx.doi.org/10.1016/j.jaci.2020.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487001PMC
October 2020

Transverse relaxation rates of pulmonary dissolved-phase Hyperpolarized Xe as a biomarker of lung injury in idiopathic pulmonary fibrosis.

Magn Reson Med 2020 10 11;84(4):1857-1867. Epub 2020 Mar 11.

Department of Medical Physics, Univsersity of Wisconsin, Madison, Wisconsin.

Purpose: The MR properties (chemical shifts and decay rates) of dissolved-phase hyperpolarized (HP) Xe are confounded by the large magnetic field inhomogeneity present in the lung. This work improves measurements of these properties using a model-based image reconstruction to characterize the decay rates of dissolved-phase HP Xe in healthy subjects and patients with idiopathic pulmonary fibrosis (IPF).

Methods: Whole-lung MRS and 3D radial MRI with four gradient echoes were performed after inhalation of HP Xe in healthy subjects and patients with IPF. A model-based image reconstruction formulated as a regularized optimization problem was solved iteratively to measure regional signal intensity in the gas, barrier, and red blood cell (RBC) compartments, while simultaneously measuring their chemical shifts and decay rates.

Results: The estimation of spectral properties reduced artifacts in images of HP Xe in the gas, barrier, and RBC compartments and improved image SNR by over 20%. decay rates of the RBC and barrier compartments were lower in patients with IPF compared to healthy subjects (P < 0.001 and P = 0.005, respectively) and correlated to DL (R = 0.71 and 0.64, respectively). Chemical shift of the RBC component measured with whole-lung spectroscopy was significantly different between IPF and normal subjects (P = 0.022).

Conclusion: Estimates for in both barrier and RBC dissolved-phase HP Xe compartments using a regional signal model improved image quality for dissolved-phase images and provided additional biomarkers of lung injury in IPF.
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http://dx.doi.org/10.1002/mrm.28246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329592PMC
October 2020

Inter- and intra-software reproducibility of computed tomography lung density measurements.

Med Phys 2020 Jul 31;47(7):2962-2969. Epub 2020 Mar 31.

Deparment of Medical Physics, University of Wisconsin, Madison, WI, USA.

Purpose: Multiple commercial, open-source, and academic software tools exist for objective quantification of lung density in computed tomography (CT) images. The purpose of this study was to evaluate the intersoftware reproducibility of CT lung density measurements.

Methods: Computed tomography images from 50 participants from the COPDGene cohort study were randomly selected for analysis; n = 10 participants across each global initiative for chronic obstructive lung disease (GOLD) grade (GOLD 0-IV). Academic-based groups (n = 4) and commercial vendors (n = 4) participated anonymously to generate CT lung density measurements using their software tools. Computed tomography total lung volume (TLV), percentage of the low attenuation areas in the lung with Hounsfield unit (HU) values below -950HU (LAA ), and the HU value corresponding to the 15th percentile on the parenchymal density histogram (Perc15) were included in the analysis. The intersoftware bias and reproducibility coefficient (RDC) was generated with and without quality assurance (QA) for manual correction of the lung segmentation; intrasoftware bias and RDC was also generated by repeated measurements on the same images.

Results: Intersoftware mean bias was within ±0.22 mL, ±0.46%, and ±0.97 HU for TLV, LAA and Perc15, respectively. The RDC was 0.35 L, 1.2% and 1.8 HU for TLV, LAA and Perc15, respectively. Intersoftware RDC remained unchanged following QA: 0.35 L, 1.2% and 1.8 HU for TLV, LAA and Perc15, respectively. All software investigated had an intrasoftware RDC of 0. The RDC was comparable for TLV, LAA and Perc15 measurements, respectively, for academic-based groups/commercial vendor-based software tools: 0.39 L/0.32 L, 1.2%/1.2%, and 1.7 HU/1.6 HU. Multivariable regression analysis showed that academic-based software tools had greater within-subject standard deviation of TLV than commercial vendors, but no significant differences between academic and commercial groups were found for LAA or Perc15 measurements.

Conclusions: Computed tomography total lung volume and lung density measurement bias and reproducibility was reported across eight different software tools. Bias was negligible across vendors, reproducibility was comparable for software tools generated by academic-based groups and commercial vendors, and segmentation QA had negligible impact on measurement variability between software tools. In summary, results from this study report the amount of additional measurement variability that should be accounted for when using different software tools to measure lung density longitudinally with well-standardized image acquisition protocols. However, intrasoftware reproducibility was deterministic for all cases so use of the same software tool to reduce variability for serial studies is highly recommended.
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http://dx.doi.org/10.1002/mp.14130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944589PMC
July 2020

Invited Commentary on "Quantitative CT Analysis of Diffuse Lung Disease".

Radiographics 2020 Mar-Apr;40(2):E1-E3

From the Departments of Medical Physics and Radiology, School of Medicine and Public Health, and Department of Biomedical Engineering, School of Engineering, University of Wisconsin-Madison, 1111 Highland Ave, Rm 2488, Madison, WI 53705 (S.B.F); Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.); and Department of Radiology, University of Michigan, Ann Arbor, Michigan, and Imbio, Minneapolis, Minn (C.H.).

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http://dx.doi.org/10.1148/rg.2020200005DOI Listing
June 2020

Safety of repeated hyperpolarized helium 3 magnetic resonance imaging in pediatric asthma patients.

Pediatr Radiol 2020 05 24;50(5):646-655. Epub 2020 Jan 24.

Department of Radiology, University of Wisconsin-Madison, 111 Highland Ave., 2488 WIMR, Madison, WI, 53705, USA.

Background: Hyperpolarized helium 3 magnetic resonance imaging (He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children.

Objective: To evaluate the safety of He MRI in children and adolescents with asthma.

Materials And Methods: This was a retrospective observational study. He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8-18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8-12 years, 13-15 years, 16-18 years) using linear mixed-effects models.

Results: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO after He MRI. The youngest age group (8-12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after H inhalation, and an increased SpO post MRI.

Conclusion: The use of He MRI is safe in children and adolescents with asthma.
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http://dx.doi.org/10.1007/s00247-019-04604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153994PMC
May 2020

Measuring the link between cardiac mechanical function and metabolism during hyperpolarized C-pyruvate magnetic resonance experiments.

Magn Reson Imaging 2020 05 21;68:9-17. Epub 2020 Jan 21.

Medical Physics, University of Wisconsin, Madison, WI, USA; Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Radiology, University of Wisconsin, Madison, WI, USA. Electronic address:

Purpose: The goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1-C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP C compounds, HP C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function.

Methods: Eight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned H/C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1-C]pyruvate metabolism in the myocardium. This was coupled with H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1-C]pyruvate. For comparison to the [1-C]pyruvate experiments, three female Sprague Dawley rats were imaged with H cine MRI to determine myocardial function pre- and post-saline infusion.

Results: We demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1-C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1-C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response.

Conclusion: The infusion of [1-C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease.
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http://dx.doi.org/10.1016/j.mri.2020.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131884PMC
May 2020

Characterization of and tissue density in the human lung: Application to neonatal imaging in the intensive care unit.

Magn Reson Med 2020 08 19;84(2):920-927. Epub 2019 Dec 19.

Department of Medical Physics, University of Wisconsin, Madison, Wisconsin.

Purpose: Novel demonstration of and tissue density estimation in infant lungs using 3D ultrashort echo time MRI. Differences between adult and neonates with no clinical indication of lung pathology is explored, as well as relationships between parameter estimates and gravitationally dependent position and lung inflation state. This provides a tool for probing physiologic processes that may be relevant to pulmonary disease and progression in newborns.

Methods: and tissue density were estimated in a phantom consisting of standards allowing for ground truth comparisons and in human subjects (N = 5 infants, N = 4 adults, no clinical indication of lung dysfunction) using a 3D radial multiecho ultrashort echo time MRI sequence. Whole lung averages were compared between infants and adults. Dependence of the metrics on anterior-posterior position as well as between end-tidal inspiration and expiration were explored, in addition to the general relationship between and tissue density.

Results: Estimates in the phantom did not differ significantly from ground truth. Neonates had significantly lower mean (P = .006) and higher mean tissue density (P = 1.5e-5) than adults. Tissue density and were both significantly dependent on anterior-posterior position and lung inflation state (P < .005). An overall inverse relationship was found between and tissue density, which was similar in both neonates and adults.

Conclusion: Estimation of tissue density and in free breathing, nonsedated, neonatal patients is feasible using multiecho ultrashort echo time MRI. was no different between infants and adults when matched for tissue density, although density of lung parenchyma was, on average, lower in adults than neonates.
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http://dx.doi.org/10.1002/mrm.28137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180096PMC
August 2020

Consensus-based technical recommendations for clinical translation of renal ASL MRI.

MAGMA 2020 Feb 12;33(1):141-161. Epub 2019 Dec 12.

Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.

Objectives: This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies.

Methods: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting.

Results: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model.

Discussion: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.
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http://dx.doi.org/10.1007/s10334-019-00800-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021752PMC
February 2020

Improved reconstruction stability for chemical shift encoded hyperpolarized C magnetic resonance spectroscopic imaging using k-t spiral acquisitions.

Magn Reson Med 2020 07 9;84(1):25-38. Epub 2019 Dec 9.

Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.

Purpose: A multiecho, field of view (FOV)-oversampled k-t spiral acquisition and direct iterative decomposition of water and fat with echo asymmetry and least-squares estimation reconstruction is demonstrated to improve the stability of hyperpolarized C magnetic resonance spectroscopic imaging (MRSI) in the presence of signal ambiguities attributed to low-SNR (signal-to-noise-ratio) species, local uncertainties in metabolite peaks, and echo-to-echo signal inconsistencies.

Theory: k-t spiral acquisitions redistribute readout points to be more densely spaced radially in k-space by acquiring an FOV and matrix that are oversampled by η. These more densely spaced spiral turns constitute effective intraspiral echoes and can supplement conventional interspiral echoes to improve spectral separation and reduce spectral cross-talk to better resolve C-labeled species for spectroscopic imaging.

Methods: Digital simulations and imaging phantom experiments were performed for a range of interspiral echo spacings and η using multiecho, k-t spiral acquisitions. Image spectral cross-talk artifacts were evaluated both qualitatively and quantitatively as the percent error in measured metabolite ratios. In vivo murine experiments evaluated the feasibility of multiecho, k-t spiral [1- C]pyruvate MRSI to reduce spectral cross-talk for 3 scenarios of different expected reconstruction stability.

Results: Digital simulations and imaging phantom experiments both demonstrated reduced or comparable image spectral cross-talk and percent errors in measured metabolite ratios with increasing η and better choices of echo spacings. In vivo images displayed markedly reduced spectral cross-talk in lactate images acquired with η = 7 versus η = 1.

Conclusion: The precision of hyperpolarized C metabolic imaging and quantification in the presence of low-SNR species, local uncertainties in metabolite resonances, and echo-to-echo signal inconsistencies can be improved with the use of FOV-oversampled k-t spiral acquisitions.
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http://dx.doi.org/10.1002/mrm.28122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083691PMC
July 2020

Consensus-based technical recommendations for clinical translation of renal BOLD MRI.

MAGMA 2020 Feb 25;33(1):199-215. Epub 2019 Nov 25.

Department of Radiology, Center for Advanced Imaging, NorthShore University Health System, Evanston, IL, USA.

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.
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http://dx.doi.org/10.1007/s10334-019-00802-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021747PMC
February 2020

Quantitative ferumoxytol-enhanced MRI in pregnancy: A feasibility study in the nonhuman primate.

Magn Reson Imaging 2020 01 23;65:100-108. Epub 2019 Oct 23.

Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI, USA. Electronic address:

Objectives: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model.

Materials And Methods: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test.

Results: In fetuses, a slope of 0.3 s/day (P = 0.008), 0.00 ppm/day (P = 0.699) and - 0.2 s/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points.

Conclusions: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.
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http://dx.doi.org/10.1016/j.mri.2019.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956847PMC
January 2020

Machine Learning Reveals the Texture of Regional Lung Ventilation at CT.

Authors:
Sean B Fain

Radiology 2019 12 22;293(3):685-686. Epub 2019 Oct 22.

From the Departments of Medical Physics, Radiology, and Biomedical Engineering, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705.

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http://dx.doi.org/10.1148/radiol.2019192162DOI Listing
December 2019

Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort.

Chest 2020 02 12;157(2):258-267. Epub 2019 Sep 12.

Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.

Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size.

Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression.

Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations.

Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations.

Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2019.08.2185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005378PMC
February 2020

Patient-specific modeling of aerosol delivery in healthy and asthmatic adults.

J Appl Physiol (1985) 2019 12 12;127(6):1720-1732. Epub 2019 Sep 12.

Department of Bioengineering, Northeastern University, Boston, Massachusetts.

The magnitude and regional heterogeneity of airway obstructions in severe asthmatics is likely linked to insufficient drug delivery, as evidenced by the inability to mitigate exacerbations with inhaled aerosol medications. To understand the correlation between morphometric features, airflow distribution, and inhaled dosimetry, we perform dynamic computational simulations in two healthy and four asthmatic subjects. Models incorporate computed tomography-based and patient-specific central airway geometries and hyperpolarized He MRI-measured segmental ventilation defect percentages (SVDPs), implemented as resistance boundary conditions. Particles [diameters () = 1, 3, and 5 μm] are simulated throughout inhalation, and we record their initial conditions, both spatially and temporally, with their fate in the lung. Predictions highlight that total central airway deposition is the same between the healthy subjects (26.6%,  = 3 μm) but variable among the asthmatic subjects (ranging from 5.9% to 59.3%,  = 3 μm). We found that by preferentially releasing the particles during times of fast or slow inhalation rates we enhance either central airway deposition percentages or peripheral particle delivery, respectively. These predictions highlight the potential to identify with simulations patients who may not receive adequate therapeutic dosages with inhaled aerosol medication and therefore identify patients who may benefit from alternative treatment strategies. Furthermore, by improving regional dose levels, we may be able to preferentially deliver drugs to the airways in need, reducing associated adverse side effects. Although it is evident that exacerbation mitigation is unsuccessful in some asthmatics, it remains unclear whether or not these patients receive adequate dosages of inhaled therapeutics. By coupling MRI and computed tomography data with patient-specific computational models, our predictions highlight the large intersubject variability, specifically in severe asthma.
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http://dx.doi.org/10.1152/japplphysiol.00221.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962611PMC
December 2019

Evaluation of a motion-robust 2D chemical shift-encoded technique for R2* and field map quantification in ferumoxytol-enhanced MRI of the placenta in pregnant rhesus macaques.

J Magn Reson Imaging 2020 02 5;51(2):580-592. Epub 2019 Jul 5.

Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA.

Background: 3D chemical shift-encoded (CSE)-MRI techniques enable assessment of ferumoxytol concentration but are unreliable in the presence of motion.

Purpose: To evaluate a motion-robust 2D-sequential CSE-MRI for R2* and B0 mapping in ferumoxytol-enhanced MRI of the placenta.

Study Type: Prospective.

Animal Model: Pregnant rhesus macaques.

Field Strength/sequence: 3.0T/CSE-MRI.

Assessment: 2D-sequential CSE-MRI was compared with 3D respiratory-gated CSE-MRI in placental imaging of 11 anesthetized animals at multiple timepoints before and after ferumoxytol administration, and in ferumoxytol phantoms (0 μg/mL-440 μg/mL). Motion artifacts of CSE-MRI in 10 pregnant women without ferumoxytol administration were assessed retrospectively by three blinded readers (4-point Likert scale). The repeatability of CSE-MRI in seven pregnant women was also prospectively studied.

Statistical Tests: Placental R2* and boundary B0 field measurements (ΔB0) were compared between 2D-sequential and 3D respiratory-gated CSE-MRI using linear regression and Bland-Altman analysis.

Results: In phantoms, a slope of 0.94 (r = 0.99, concordance correlation coefficient ρ = 0.99), and bias of -4.8 s (limit of agreement [LOA], -41.4 s , +31.8 s ) in R2*, and a slope of 1.07 (r = 1.00, ρ = 0.99) and bias of 11.4 Hz (LOA -12.0 Hz, +34.8 Hz) in ΔB0 were obtained in 2D CSE-MRI compared with 3D CSE-MRI for reference R2* ≤390 s . In animals, a slope of 0.92 (r = 0.97, ρ = 0.98) and bias of -2.2 s (LOA -55.6 s , +51.3 s ) in R2*, and a slope of 1.05 (r = 0.95, ρ = 0.97) and bias of 0.4 Hz (LOA -9.0 Hz, +9.7 Hz) in ΔB0 were obtained. In humans, motion-impaired R2* maps in 3D CSE-MRI (Reader 1: 1.8 ± 0.6, Reader 2: 1.3 ± 0.7, Reader 3: 1.9 ± 0.6), while 2D CSE-MRI was motion-free (Reader 1: 2.9 ± 0.3, Reader 2: 3.0 ± 0, Reader 3: 3.0 ± 0). A mean difference of 0.66 s and coefficient of repeatability of 9.48 s for placental R2* were observed in the repeated 2D CSE-MRI.

Data Conclusion: 2D-sequential CSE-MRI provides accurate R2* and B0 measurements in ferumoxytol-enhanced placental MRI of animals in the presence of respiratory motion, and motion-robustness in human placental imaging.

Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:580-592.
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http://dx.doi.org/10.1002/jmri.26849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839098PMC
February 2020

Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers.

Korean J Radiol 2019 07;20(7):1236-1245

School of Mechanical Engineering, Kyungpook National University, Daegu, Korea.

Objective: Considering the different prevalence rates of diseases such as asthma and chronic obstructive pulmonary disease in Asians relative to other races, Koreans may have unique airway structure and lung function. This study aimed to investigate unique features of airway structure and lung function based on quantitative computed tomography (QCT)-imaging metrics in the Korean Asian population (Koreans) as compared with the White American population (Whites).

Materials And Methods: QCT data of healthy non-smokers (223 Koreans vs. 70 Whites) were collected, including QCT structural variables of wall thickness (WT) and hydraulic diameter (D) and functional variables of air volume, total air volume change in the lung (ΔV), percent emphysema-like lung (Emph%), and percent functional small airway disease-like lung (fSAD%). Mann-Whitney U tests were performed to compare the two groups.

Results: As compared with Whites, Koreans had smaller volume at inspiration, ΔV between inspiration and expiration ( < 0.001), and Emph% at inspiration ( < 0.001). Especially, Korean females had a decrease of ΔV in the lower lobes ( < 0.001), associated with fSAD% at the lower lobes ( < 0.05). In addition, Koreans had smaller D and WT of the trachea (both, < 0.05), correlated with the forced expiratory volume in 1 second (R = 0.49, 0.39; all < 0.001) and forced vital capacity (R = 0.55, 0.45; all < 0.001).

Conclusion: Koreans had unique features of airway structure and lung function as compared with Whites, and the difference was clearer in female individuals. Discriminating structural and functional features between Koreans and Whites enables exploration of inter-racial differences of pulmonary disease in terms of severity, distribution, and phenotype.
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http://dx.doi.org/10.3348/kjr.2019.0083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609438PMC
July 2019

Elevated lung volumes in neonates with bronchopulmonary dysplasia measured via MRI.

Pediatr Pulmonol 2019 08 27;54(8):1311-1318. Epub 2019 May 27.

Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity defined by requirement for respiratory support at 36 weeks postmenstrual age (PMA), but structural sequelae like lung hyperinflation are often not quantified. Quiet-breathing, nonsedated magnetic resonance imaging (MRI) allows tomographic quantification of lung volumes and densities. We hypothesized that functional residual capacity (FRC) and intrapleural volume (IV) are increased in BPD and correlate with qualitative radiological scoring of hyperinflation.

Methods: Ultrashort echo time (UTE) MRI of 17 neonates (acquired at ~39 weeks PMA) were reconstructed at end-expiration and end-inspiration via the time course of the k point in k-space. Images were segmented to determine total lung, tidal, parenchymal tissue, and vascular tissue volumes. FRC was calculated by subtracting parenchymal and vascular tissue volumes from IV. Respiratory rate (RR) was calculated via the UTE respiratory waveform, yielding estimates of minute ventilation when combined with tidal volumes (TVs). Two radiologists scored hyperinflation on the MR images.

Results: IV at FRC increased in BPD: for control, mild, and severe (patients the median volumes were 32.8, 33.5, and 50.9 mL/kg, respectively. TV (medians: 2.21, 3.64, and 4.84 mL/kg) and minute ventilation (medians: 493, 750, and 991 mL/min) increased with increasing severity of BPD (despite decreasing RR, medians: 75.6, 63.0, and 56.1 breaths/min). FRC increased with increasing severity of BPD (39.3, 38.3, and 56.0 mL, respectively). Findings were consistent with increased hyperinflation scored by radiologists.

Conclusions: This study demonstrates that UTE MRI can quantify hyperinflation in neonatal BPD and that lung volumes significantly increase with disease severity.
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http://dx.doi.org/10.1002/ppul.24378DOI Listing
August 2019

Repeatability of regional pulmonary functional metrics of Hyperpolarized Xe dissolved-phase MRI.

J Magn Reson Imaging 2019 10 10;50(4):1182-1190. Epub 2019 Apr 10.

Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA.

Background: MRI of hyperpolarized Xenon (HP Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.

Purpose: To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase Xe imaging and their dependence on intervisit changes in lung inflation volume.

Study Type: Prospective.

Population: Fourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9).

Field Strength: 1.5T.

Assessment: Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs).

Statistical Tests: Repeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression.

Results: Mean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DL (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found.

Data Conclusion: Three commonly used Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DL .

Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190.
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http://dx.doi.org/10.1002/jmri.26745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750965PMC
October 2019

Deep convolutional neural networks with multiplane consensus labeling for lung function quantification using UTE proton MRI.

J Magn Reson Imaging 2019 10 4;50(4):1169-1181. Epub 2019 Apr 4.

Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Background: Ultrashort echo time (UTE) proton MRI has gained popularity for assessing lung structure and function in pulmonary imaging; however, the development of rapid biomarker extraction and regional quantification has lagged behind due to labor-intensive lung segmentation.

Purpose: To evaluate a deep learning (DL) approach for automated lung segmentation to extract image-based biomarkers from functional lung imaging using 3D radial UTE oxygen-enhanced (OE) MRI.

Study Type: Retrospective study aimed to evaluate a technical development.

Population: Forty-five human subjects, including 16 healthy volunteers, 5 asthma, and 24 patients with cystic fibrosis.

Field Strength/sequence: 1.5T MRI, 3D radial UTE (TE = 0.08 msec) sequence.

Assessment: Two 3D radial UTE volumes were acquired sequentially under normoxic (21% O ) and hyperoxic (100% O ) conditions. Automated segmentation of the lungs using 2D convolutional encoder-decoder based DL method, and the subsequent functional quantification via adaptive K-means were compared with the results obtained from the reference method, supervised region growing.

Statistical Tests: Relative to the reference method, the performance of DL on volumetric quantification was assessed using Dice coefficient with 95% confidence interval (CI) for accuracy, two-sided Wilcoxon signed-rank test for computation time, and Bland-Altman analysis on the functional measure derived from the OE images.

Results: The DL method produced strong agreement with supervised region growing for the right (Dice: 0.97; 95% CI = [0.96, 0.97]; P < 0.001) and left lungs (Dice: 0.96; 95% CI = [0.96, 0.97]; P < 0.001). The DL method averaged 46 seconds to generate the automatic segmentations in contrast to 1.93 hours using the reference method (P < 0.001). Bland-Altman analysis showed nonsignificant intermethod differences of volumetric (P ≥ 0.12) and functional measurements (P ≥ 0.34) in the left and right lungs.

Data Conclusion: DL provides rapid, automated, and robust lung segmentation for quantification of regional lung function using UTE proton MRI.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1169-1181.
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http://dx.doi.org/10.1002/jmri.26734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039686PMC
October 2019