ORIGINAL RESEARCH • STATEMENTS AND GUIDELINES

Expanding Applications of Pulmonary MRI in the Clinical
Evaluation of Lung Disorders: Fleischner Society Position Paper
Hiroto Hatabu, MD, PhD* • Yoshiharu Ohno, MD, PhD** • Warren B. Gefter, MD • Grace Parraga, PhD •Bruno Madore, PhD • Kyung Soo Lee, MD, PhD • Talissa A. Altes, MD • David A. Lynch, MB, BCh • John R. Mayo,
MD • Joon Beom Seo, MD, PhD • Jim M. Wild, PhD • Edwin J. R. van Beek, MD, PhD • Mark L. Schiebler, MD** •Hans-Ulrich Kauczor, MD** • For the Fleischner Society
From the Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis St, Boston, MA
02115 (H.H.); Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Department of Medical Biophysics, Western University, London, Canada (G.P.); Department of Radiology, Brigham and
Women’s Hospital and Harvard Medical School, Boston, Mass (B.M.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine(SKKU-SOM), Seoul, Korea (K.S.L.); Department of Radiology, University of Missouri, Columbia, Mo (T.A.A.); Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.); Department of Radiology, Vancouver General Hospital and University of British Colombia, Vancouver, Canada (J.R.M.); Department of Radiology,
Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Section of Academic Radiology, University of
Sheffield, Sheffield, England, United Kingdom (J.M.W.); Edinburgh Imaging, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, United
Kingdom (E.J.R.v.B.); Department of Radiology, UW Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); and Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.).
Received March 27, 2020; revision requested May 20; revision received July 2; accepted July 15. Address correspondence to H.H. (e-mail: hhatabu@partners.org).
*Chair and **Vice Chair of the Fleischner Society writing committee of the position paper for Pulmonary MRI.
Conflicts of interest are listed at the end of this article.
Radiology 2020; 00:1–16﻿ • https://doi.org/10.1148/radiol.2020201138• Content codes:

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI
techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With theuse of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lungparenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists
and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinicaluse of pulmonary MRI into three categories: (a) suggested for current clinical use, (b) promising but requiring further validation or
regulatory approval, and (c) appropriate for research investigations. This position paper also provides recommendations for vendors
and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods.
© RSNA, 2020
Online supplemental material is available for this article.

Pulmonary MRI has had limited clinical use for patientswith lung disease, especially when compared with radiography, CT, and PET/CT. However, MRI has become
practical in many countries due to advances in MRI pulse
sequences, multicoil parallel imaging, and acceleration
methods, along with the increased (but not universal)
availability of postprocessing software. Recently, ultrashortecho time (UTE) and zero echo time proton MRI haveextended the use of conventional or anatomic proton MRI
for clinical examinations, and inhaled-gas methods haveopened up avenues for functional lung imaging. The transition to MRI from radiography-based methods has been
driven by the fact that MRI does not impart ionizing radiation, which is particularly important in younger patientswith chronic illness (eg, cystic fibrosis [CF]), for young andpregnant women, or for those patients requiring extensive
longitudinal follow-up (eg, severe asthma).
The purpose of this Fleischner Society position paper
is to familiarize our community with recent advances inpulmonary MRI and to provide a consensus expert opinion regarding appropriate clinical indications for this modality. These opinions were initially endorsed in consensus
among the writing committee members, following which
the manuscript was endorsed by the Society members atlarge and was approved by the Fleischner Society Publication Development and Oversight Committee and the
Fleischner Executive Committee before submission toRadiology.
Common clinical indications for pulmonary MRI werereviewed by members of the writing committee and havebeen divided into three groups: (a) group 1 indications
are suggested for current clinical use of pulmonary MRI(four or more publications from multiple institutions withclinical studies of more than 100 patients); (b) group 2 indications are promising but require further validation or
regulatory approval (two to three publications with fewer
than 100 patients, those that use methods requiring further confirmation or regulatory approval, such as hyperpolarized gases); and (c) group 3 indications are appropriate
for research investigations (clinical studies not meeting theabove criteria or limited to preclinical research) (Table 1).

Background, Brief History of MRI of Lung, andEmergence of UTE and Zero Echo Time MRI
Pulse Sequences
In the 1970s, Paul Lauterbur developed the first MRI
scanner, for which he jointly received the 2003 Nobel Prize in Medicine or Physiology with Peter Mansfield.

This copy is for personal use only. To order printed copies, contact reprints@rsna.org

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

Abbreviations
CF = cystic fibrosis, CI = confidence interval, COPD = chronic obstructive pulmonary disease, DW = diffusion weighted, FDG = fluorine 18
fluorodeoxyglucose, GRE = gradient echo, NSCLC = non–small celllung cancer, SE = spin echo, UTE = ultrashort echo time

Summary
Due to technical advances in pulmonary MRI, the Fleischner Society
offers its consensus recommendations for the clinical use of MRI in
evaluating patients with common lung disorders.

Key Results
Ultrashort echo time and zero echo time pulse sequences have improved pulmonary MRI, thus allowing expanded clinical applications, such as the serial imaging of children with cystic fibrosis.
n Current recommendations for the clinical use of pulmonary MRI
are offered as three categories: (a) for current clinical use, (b)promising but require further validation or regulatory approval,and (c) appropriate for research investigations.
n Opportunities for prospective, randomized multicenter trials toinvestigate pulmonary MRI methods are suggested.
nMuch later, in 1996, Cutillo remarked that “lung imaging isa latecomer in magnetic resonance imaging” (1). The conceptual framework of the lung’s air and soft-tissue interfaces andits three-dimensional structure were investigated in the 1980s(2). The large difference in magnetic susceptibility between airand lung parenchyma results in broad frequency distributions
and phase dispersion within voxels, causing an incoherent proton spectrum, noise after image reconstruction, and short T2*(3–6). Moreover, the gap in susceptibility between lung parenchyma and the chest wall manifests as a dark line perpendicular
to the frequency-encoding direction. In 1991, the phenomenon of susceptibility effects was described in detail, and potential solutions were proposed using projection reconstruction
MRI with UTE (7–9). But this solution required more than
2 decades of hardware and software improvements before successful clinical implementation was possible (10–12). Clinical
MRI of the lung has since been pursued using spin-echo (SE)and gradient-echo (GRE) sequences with short echo time andhalf-Fourier single-shot fast SE sequences (13–15). MRI of thepulmonary vasculature is possible using electrocardiographic
gating, surface coils, and cine GRE MRI (16,17).
In 1994, ventilation MRI using hyperpolarized xenon 129(129Xe) was first reported in small animals (18). In 1996, hyperpolarized helium 3 (3He) MRI was pioneered in healthy
volunteers and participants with lung disease (19,20), and contrast material–enhanced perfusion MRI emerged (21). This wasfollowed by reports using perfusion parametric mapping withthree-dimensional imaging and breath holding (22–24). Dynamic oxygen-enhanced proton ventilation MRI was also introduced and shown to be highly correlated with measurements ofthe diffusing capacity of the lung for carbon monoxide (25–27).
In 2009, unenhanced perfusion and ventilation proton MRI using Fourier decomposition were pioneered (28).
Despite these advancements in the field of pulmonary functional imaging, there has been limited clinical utilization of
pulmonary MRI, primarily due to the benefits provided by highresolution CT, which include speed, availability, familiarity, ease2of access, and superb natural contrast and spatial resolution of
the lung parenchyma. In contradistinction to CT, pulmonary
MRI has a longer acquisition time with sensitivity to respiratory motion and is affected by the lung’s lower proton density
and aforementioned susceptibility effects from air and soft-tissue
interfaces.
Nevertheless, pulmonary MRI is poised to become a primaryclinical imaging modality due to the development of UTE andzero echo time sequences, which have been “game changers” forpulmonary MRI. These sequences provide a higher signal-tonoise ratio from the lung’s relatively short T2*. Their evolution,from longer to shorter echo times, is described in Figure 1 andexplained in detail in Appendix E1 (online).

Clinical Indications for Pulmonary MRI
Data Support Current Clinical Application (Suggested for
Current Clinical Use)
Evaluation of CF.—CF manifests with pulmonary pathologic
findings from birth. Pulmonary MRI can demonstrate thepresence of bronchiectasis and mucus plugging in CF, but imaging is challenging because of the great range in patient age aswell as disease severity in this population, due to the different
classes of CF transmembrane conductance regulator mutations
and exogenous factors such as bacterial colonization. Thesevariations in CF result in different degrees of disease severity,
but therapeutic agents, including modulators and potentiators,
may extend life expectancy for individuals with CF.
To our knowledge, only in Germany has proton MRI been
introduced into the routine clinical management and long-termmonitoring of patients with CF as the standard of care. Similar
to CT, proton MRI provides morphologic information withrespect to mucus distribution, bronchiectasis, inflammatory
airway wall thickening, consolidation, and atelectasis, and it
depicts disease activity from birth (29–31) (Fig 2). Inspiratory
and expiratory three-dimensional GRE MRI reveals air trapping (32) as a low spatial resolution radiation-free alternative toinspiratory and expiratory CT, although steady-state free precession methods can be used to distinguish mucus from airway
wall thickening (33). An MRI scoring system, similar to CT
scoring systems, may help grade disease severity (34). MRI canalso reveal perfusion abnormalities caused by hypoxic pulmonary vasoconstriction with high sensitivity that reflects ventilation impairment due to airway obstruction (Euler-Liljestrand
reflex) (35). MRI perfusion defects can reveal even a small airway (,1 mm in diameter) obstruction, which is difficult if not
impossible to detect using CT. For example, CT demonstrated
only 20% of potentially detectable perfusion abnormalities inyoung patients with CF (30). In addition, MRI perfusion defects correlated with the multiple breath wash-out lung clearance index measurement in young children and adolescents(36). Also, two single-center studies showed that mucus plugging, consolidation, and perfusion abnormalities were increasedin pulmonary exacerbations of CF and reversed after antibiotic therapy (30,36,37). A multicenter MRI study in young
children with CF also showed that lung clearance index values
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Hatabu et al

had a moderate
Table 1: Summary of Clinical Indications for Pulmonary MRI
to strong corData Support Current Clinical
Data Promising: Further Validation
relationwithApplication
or Regulatory Approval Required
Investigational
the MRI scores(38).
Cystic fibrosis
Pulmonary embolism
Chronic obstructive pulmonary disease
HyperpolarLung cancer staging
Pulmonary parenchymal abnormalities
ized gas MRILung nodule characterization
Asthmawith 3He reveals
Pulmonary hypertension
Lung nodule detection
Interstitial lung diseaseventilation abnormalities witha high sensitivity
in patients with
Lung Imaging Reporting and Data System category. All eight
CF (39,40) who have normal spirometry and normal CT (41).
cancers were accurately depicted with MRI. The Lung ImQuantification of ventilation defects is feasible and may be useaging Reporting and Data System score was overestimatedful for monitoring therapy effectiveness (42). This, in combiwith MRI in one patient for category 4A, two patients fornation with the fact that hyperpolarized 3He is more sensitive
category 3, and five patients for category 2 nodules. The authors
to lung function decline than pulmonary function tests(43),concluded that MRI was comparable to low-dose CT in a lunghighlights its value in helping detect very early lung disease.
cancer screening program (56). The use of UTE pulse sequences
Preliminary therapy studies using hyperpolarized 3He ventilahas improved the detection of small lung nodules at MRI (57).
tion as an end point showed response to a CF transmembraneThis free-breathing method allows for the better delineation of
conductance regulator gene potentiator in parallel with changes
lung parenchymal structure than routine breath-hold GRE techin forced expiratory volume in 1 second (39), but very few studniques (57).
ies support MRI use in very young children, to our knowledge
After detection, characterizing the potential for malignancy is(44). MRI with hyperpolarized 129Xe is less costly than hyperpopivotal. Numerous MRI sequences have been evaluated for pulmolarized 3He and shows promise for clinical use in specialist CF
nary nodule characterization (58). Currently, diffusion-weighted
centers (37,45–48), including evaluation of treatment responses(DW) MRI is considered the most useful, with a meta-analysis
and correlation with pulmonary function measurements such aspooled sensitivity and specificity of 83% and 80%, respectively,lung clearance index. Unenhanced MRI methods for perfusionin the differentiation between malignant and benign lesions (59).
and/or ventilation imaging (eg, arterial spin labeling, echo time–
Some studies have shown that dynamic contrast-enhanced MRI
dependent mapping of T1 relaxation times, and Fourier decomhas greater specificity and accuracy than PET/CT (60,61) (Fig
position MRI) also provide alternatives for CF lung ventilation
3). When DW MRI and fluorine 18 fluorodeoxyglucose (FDG)
and perfusion measurements (49–51). The next area of research
PET/CT were compared in a meta-analysis for diagnosis of thewill need to focus on how MRI results change patient outcomessame nodule, DW MRI yielded an area under the receiver(eg, life expectancy, hospitalization length of stay, cost of care)
operating characteristic curve of 0.93 (95% confidence interval
compared with CT and its cost effectiveness.
[CI]: 0.90, 0.95) versus 0.86 (95% CI: 0.83, 0.89) for FDG PET/
In conclusion, proton-based pulmonary MRI for longitudiCT (P = .001). This meta-analysis also showed a diagnostic odds
nal assessment of patients with CF is the current clinical stanratio of 50 (95% CI: 19, 132) for DW MRI, which was superior
dard in Germany, and data support its more widespread use into that of PET/CT (odds ratio = 15; 95% CI: 7, 32; P = .006)
patients with CF. The use of hyperpolarized gas remains an im(62). Thus, current data show that DW MRI outperforms FDG
portant research tool, awaiting regulatory approval for clinical
PET/CT in the characterization of solitary pulmonary nodules.
use beyond the United Kingdom.
Currently, CT and FDG PET/CT are used for lung cancer
staging (tumor, node, metastasis or TNM system), and MRI is
Lung cancer and lung nodule characterization.—Early lungrarely employed, and typically only for selected problem solvcancer detection and pulmonary nodule characterization are
ing. Although MRI had originally been proposed as superior
important challenges for radiology. Although CT serves as theto CT for T factor evaluations (63–66), short inversion timeclinical workhorse, MRI plays a role in specific clinical scenarinversion-recovery turbo SE MRI and/or DW MRI are as helpios. Various MRI techniques, such as SE sequences, including
ful as PET/CT for N factor evaluation in non–small cell lungshort inversion time inversion recovery, turbo SE sequence, andcancer (NSCLC) (67–79). Short inversion time inversion-recovGRE sequences, yield detection rates ranging from 26% to 96%
ery turbo SE MRI is also more sensitive and accurate than DW(52–55). Recently, three-dimensional GRE sequences with UTE
MRI and PET/CT (75). When both MRI and PET/CT data
(echo time, less than 200 msec) enabled a detection rate of greater
are available, inclusive criteria (positive for nodal metastasis eithan 90% for nonsolid, part-solid, and solid nodules ranging
ther at MRI or at PET/CT) improve the sensitivity for detectingfrom 4 to 29 mm in diameter, thus challenging thin-section
nodal metastasis compared with PET/CT alone, and they may
CT in nodule detection (54). In a recent study, the potential
decrease unnecessary open thoracotomy, mediastinoscopy, orof MRI as a screening tool for lung cancer was compared withendobronchial US (80). Another meta-analysis identified better
low-dose CT (56) for 224 lung cancer screening participants
diagnostic performance for MRI compared with FDG PET/CT
with nodules of 4 mm or greater; patients were then assigned aRadiology: Volume 00: Number 0— 2020 n radiology.rsna.org

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Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

brain and hepatic metastases,
PET/CT is more useful forthe detection of lymph nodeand soft-tissue metastases (81).
Currently, lung cancer staging
may use both brain MRI andwhole-body PET/CT. Withavailable whole-body MRI data,
the coregistered PET/MRI may
serve as a staging tool. NSCLC
was correctly upstaged in 37 of
143 patients (26%) in the PET/MRI group compared with 26of 120 patients (22%) in the
PET/CT plus brain MRI group(95% CI: –6%, 15%; P = .43),
which was an insignificant difference (82). Integrated (simultaneous, rather than registered)
PET/MRI can also be used as apossible adjunct to FDG PET/
CT for clinical NSCLC staging
with comparable staging performance (83,84).
In conclusion, studies support the utility of MRI for thecharacterization of known lungnodules and lung cancer staging
as potential alternatives to PET/
CT. Although UTE results arepromising for lung nodule detection, confirmatory studies are
required.
Pulmonary hypertension.—The
European Society of Cardiology and European Respiratory
Society issued a recent consensus statement on the diagnosis
and treatment of pulmonary
Figure 1: Diagram illustrates the race toward shorter echo time (TE) values. The evolution of echo times has involved
hypertension (85,86). Dynamic
regular MRI pulse sequences with, A–C, short TE setting, followed by, D, E, specially designed ultrashort echo time and,contrast-enhanced lung perfuF, zero echo time sequences. Echo time is defined as time between excitation of magnetization and sampling of central
sion MRI has similar sensitivity
k-space region. With typical MRI hardware, a minimum amount of time is required to switch between radiofrequency (RF)and specificity to both planartransmission (radiofrequency pulses) and radiofrequency reception (readout window), called D here and depicted greatly
exaggerated in C–F. D can be a limiting factor in how small echo times can get, and a D of 5 msec might be consideredscintigraphy (87) and SPECT
typical. Due to finite width of radiofrequency pulse and of D, a central region in k-space cannot be sampled by zero echo(88) in its ability to screen fortime pulse sequences; this is depicted in F using a small silvery sphere at origin of radial pattern. GRE = gradient echo, PF =chronic thromboembolic pulpartial Fourier, PR = projection reconstruction, 3D = three-dimensional.
monary hypertension. The rightventricle is not well designed for
acute pressure overload and decompensates into cor pulmonale
on a per-node and per-patient basis (79). Thus, the current eviafter exposure to chronic pressure (and/or volume) overload (89).
dence supports the broader clinical use of MRI for TNM staging
The findings of septal flattening, delayed contrast enhancementin patients with NSCLC (Fig 4). Tables 2 and 3 show reportedof the septal insertions, and an elevation in the right ventriculardiagnostic performances of dedicated MRI for T and N factor
end diastolic volume index have prognostic value in pulmonary
assessments in patients with NSCLC.
hypertension (90–93). Quantitative contrast-enhanced MR anWhole-body MRI also provides acceptable accuracy and efgiography is useful for the assessment of the severity of pulmoficacy for NSCLC staging compared with whole-body PET/
nary hypertension and the longitudinal assessment of therapy efCT. Although whole-body MRI is more useful for depicting
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Hatabu et alof the smaller pulmonary arterial branches. Bright-blood,
steady-state free precession
imaging can also be used to delineate thrombus in the major
pulmonary vessels in patientswith chronic thromboembolic
pulmonary hypertension (97)
and to reveal decreased flow inthe pulmonary artery due topulmonary hypertension (98).
The distensibility (relative areachange) in the pulmonary artery is predictive of outcomes inpatients with pulmonary hypertension (97,99), while the rightventricular end diastolic volume
index and pulmonary arteryarea predict survival (100), as
confirmed with meta-analysis(101).
In conclusion, strong evidence supports the current
clinical use of cardiopulmonary
MRI in patients with pulmonary hypertension.
Data Promising but Requiring
Further Validation orRegulatory Approval
Pulmonary embolism.—Since
2004, pulmonary contrastenhanced MR angiography has
revealed both the direct signsof pulmonary embolism within
pulmonary arteries and lungperfusion using parallel imaging techniques, time-resolved,
or four-dimensional contrastenhanced MR angiography (Fig
E2 [online]) (102,103). This
technique can be considered as
an alternative to CT angiography for patients presenting withsigns and symptoms of pulmoFigure 2: Typical constellation of imaging findings in an adolescent female patient with cystic fibrosis. A, Contrastnary embolism. In the clinicalenhanced T1-weighted image shows mucus-filled bronchoceles (arrow) dominant in upper lobes and superior segments
setting of suspected pulmonaryof lower lobes. B, Fat-saturated T2-weighted image best depicts mucus plugging (arrow). C, Maximum intensity projection
embolism, single-center resultsof contrast-enhanced T1-weighted imaging shows tree-in-bud pattern of small airways disease (circles). D, Contrastenhanced T1-weighted imaging may help differentiate airway wall inflammation (anterior black arrowhead) from mucus
for the primary use of MR an(posterior black arrowhead) by different signal intensities. E, Subtraction map from dynamic contrast-enhanced MR perfugiography for the diagnosis ofsion reveals perfusion abnormalities (arrowheads). F, Contrast-enhanced MR angiography shows dilated bronchial arteries
pulmonary embolism in 675(arrowhead).
patients at low to intermediaterisk showed patient outcomes using MR angiography as the prifect (24,94–96) (Fig 5) (Table E1 [online]). Contrast-enhanced
mary diagnostic test were similar to CT angiography at 6 months
MR angiography has been used in the setting of chronic thromof follow-up (104). Important technical developments since theboembolic pulmonary hypertension for the diagnosis of proximal
Prospective Investigation of Pulmonary Embolism Diagnosis III
arterial enlargement, webs of chronic thrombi, and amputation
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Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

Figure 3: Images in 82-year-old man with invasive adenocarcinoma in right upper lobe. A, Thin-section CT scan with 1-mm-thick sections (left), pulmonary MRI scanwith ultrashort echo time at 110 msec and 1-mm-thick sections (middle), and fluorine 18 fluorodeoxyglucose (FDG) PET/CT scan with 2.5-mm-thick sections (right). CT
and MRI scans show solid nodule with notch. This nodule demonstrates high FDG uptake on PET/CT scan. CT and MRI scans also show bullae and emphysematous lungsurrounding tumor. B, Dynamic first-pass contrast material–enhanced perfusion gradient-echo MRI scans obtained with a 3-T system demonstrate well-enhanced nodule(arrows) in right upper lobe. This nodule shows enhancement from lung parenchymal phase and is well enhanced at systemic circulation phase. t is the time after injection ofgadolinium-based contrast agent followed by saline chaser.

Figure 4: Images in 74-year-old man with lung cancer and right hilar and subcarinal lymph node metastases. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT scan(left), short inversion time inversion-recovery turbo fast spin-echo image obtained with a 3-T system (middle), and diffusion-weighted (DW) image obtained with a fast spinecho sequence from same system (right). PET/CT scan shows high uptake of FDG at right hilar (thin arrow) and subcarinal (thick arrow) lymph nodes. Short inversion timeinversion-recovery fast spin-echo image demonstrates right hilar (thin arrow) and subcarinal (thick arrow) lymph nodes as areas of high signal intensity, although DW image
shows only subcarinal lymph node (thick arrow) as high signal intensity and cannot visualize right hilar lymph node as high signal intensity (thin arrow). All methods could enable accurate diagnosis of N stage in this patient. In addition, PET/CT and short inversion time inversion-recovery fast spin-echo imaging could enable accurate diagnosisof lymph node metastases on a per-node basis. DW imaging could accurately depict subcarinal lymph node metastasis, but right hilar lymph node was determined to be afalse-negative finding.

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Hatabu et al
Table 2: Reported Diagnostic Performances of T Factor at MRI as Compared with CT

Study

Year

Field Strength(T)
Sequence

Webb et al (63) 1991 0.3 + 1.5
Sakai et al (64) 1997 1.5
Ohno et al (65) 2001 1.5
Tang et al (66)2015 3.0

MRI Accuracy CT Accuracy(%)(%)

Image Analysis

ECG-gated T1-and T2-weighted

Distinction between stage T0– 73
T2 and T3–T4
Free-breathing cine-GRASSChest wall invasion76
Dynamic ECG-triggered 3D GRE Tumor invasion of pulmonary 75–88
vessels
Breath-hold dynamic CE 2D GRE T stage
82.2

78
68
68–71
84.4

Note.—CE = contrast enhanced, ECG = electrocardiogram, GRASS = gradient-recalled acquisition in the steady state, GRE = gradientrecalled echo, 3D = three-dimensional, 2D = two-dimensional.

Table 3: Diagnostic Performance of N Factor of the TNM Staging System for MRI, CT, and FDG PET/CT

Study

Field
Year Strength (T) Sequence

Takenaka et al 2002 1.5(67)

Reference
Standard

MRI Accuracy (%)

2004 1.5

ECG-triggered
Histologic findings 83 (T1WI),
T1-weighted TSE,
96 (STIR)
STIR
STIR
Histologic findings 89

2007 1.5

STIR

Hasegawa et al 2008 1.5(70)Nomori et al 2008 1.5(71)
Morikawa et al 2009 1.5(72)
Nakayama et 2010 1.5
al (73)Usuda et al2011 1.5(74)

DWI

Ohno et al(68)
Ohno et al(69)

Ohno et al(75)

2011 1.5

Ohno et al(76)

2015 3Usuda (77)2015 1.5

Nomori (78) 2016 1.5Peerlings et al 2016 Mainly 1.5
(79)

DWI
STIR
DWI

PET/CT
CT Accuracy (%) Accuracy (%)
83

NA

72

NA

Histologic findings 87.8 (qualitative),82.6 (qualitative), NA
and/or follow-up 92.2 (quantitative)
83.5(quantitative)
Histologic findings 95
NA
NA
Histologic findings 98
NA
and/or follow-up
Histologic findings 84.7 (qualitative),NA
84.7 (quantitative)
Histologic findings 94
NA

T1-weighted SE,
Histologic findings 81
NA
T2-weighted FSE,
SS EPI SPAIR
NA
STIR, DWI
Histologic findings 84.4 (qualitative
STIR), 82.8
(qualitative
DWI),86.8(quantitative STIR),
84.4 (quantitative
DWI)
STIR FASE, EPI
Histologic findings 84.2 (STIR FASE),
NA
DWI, FASE
76.8 (EPI DWI),
DWI
83.2 (FASE DWI)SE T1-weighted,
Histologic findings 91
NA
FSE T2-weighted,
and/or follow-up
DWI
DWI
Histologic findings 75
NA
DWI and STIR
Meta-analysis
NA
NA

96
80.3
NA
71
83.6 (qualitative),
85.6(quantitative)

73.7
48
67
NA

Note.—DWI = diffusion weighted imaging, ECG = electrocardiogram, EPI = echo-planar imaging, FASE = fast-advantage spin echo, FDG= fluorine 18 fluorodeoxyglucose, FSE = fast spin echo, NA = not applicable, SE = spin echo, SS = single shot, SPAIR = spectral attenuatedinversion recovery, STIR = short inversion time inversion recovery.

study have improved the resolution and image quality of the MRI
examinations (105). Advances in scanner hardware have resulted
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in improved interpolated resolution (0.7 3 0.7 3 1.0 mm vs 0.5
3 0.7 3 1.5 mm in Prospective Investigation of Pulmonary Em7

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

Figure 5: Images in 42-year-old woman with chronic pulmonary arterial hypertension from an atrial septal defect with pulmonary insufficiency. A, Coronal MR angiogram shows an enlarged pulmonary artery (arrow). B, Four-dimensional flow systolic phase pathlines from emitter plane at pulmonary valve shows rapid flow in red at thepulmonary trunk and turbulent (helical) flows in right and left (arrow) pulmonary arteries. C, Four-dimensional flow in diastolic phase shows lower velocity pulmonary insufficiency path lines in blue (arrow) from same emitter plane at pulmonary valve, with calculated regurgitant fraction of 28%.

Figure 6: Images in 82-year-old man with solid nodules in lung apices. Pulmonary MRI scan with ultrashort echo time at 192 msec (left) and thin-section CT scans with
1-mm-thick sections (center and right) show solid nodules (arrows) in the apices. Nodule diameters were 19 mm and 25 mm on MRI scan and 19 mm and 26 mm on thinsection CT scan. These nodules were diagnosed as invasive adenocarcinoma in right apex and squamous cell carcinoma in left apex.

bolism Diagnosis III), increased number of slices (140–160 vs 44[101]), and a lower repetition time (2.9 msec vs 6.6 msec). The
software changes also include the use of an auto calibrating k-space
two-dimensional scheme for three-dimensional acquisition (106).
In conclusion, single-center data (n = 675) have shown that
pulmonary MR angiography is similar to CT angiography forthe primary evaluation of suspected pulmonary embolism. Confirmatory prospective, multicenter, outcomes-based trials comparing pulmonary MR angiography and CT angiography areneeded.
Pulmonary parenchymal abnormalities.—Since 2000, advancements in MRI gradient systems and pulse sequences
enabled the evaluation of lung parenchyma by using single-shot fast or turbo spin echo with and without halfFourier acquisition, balanced steady-state free precession,and three-dimensional GRE with UTE less than 200 msec
(12,15,107–109). These techniques can increase the signalto-noise ratio within the lung parenchyma (15). Steadystate free precession and three-dimensional GRE with UTE
emerged for visualization of lung parenchymal structures in
the 2010s (12,107–109). When compared with CT, threedimensional GRE with UTE showed almost perfect agreement for imaging lung nodules or masses, ground-glass
opacity, patchy opacity and consolidation, honeycombing
and traction bronchiectasis, and substantial agreement in
8visualizing reticular opacity, emphysema, and bullae (109).
Three-dimensional GRE with UTE is equally useful compared with thin-section CT for lung nodule detection andcharacterization (Figs 6–8) (54,110). Another applicationof this technique is the quantitative regional T2* measurement of the lung by direct T2* decay at three-dimensional
GRE with UTEs for the assessment of lung microstructureand emphysema (111).
In conclusion, several studies suggest MRI may be comparable to CT in the detection of lung nodules, ground-glass
opacity, consolidation, honeycombing, traction bronchiectasis,and reticular changes. However, the limited availability andinvestigational status of UTE proton pulse sequences have curtailed clinical adoption. Evidence from multicenter clinical trials is required for validation.
Investigational (Appropriate for Research Investigations andMechanistic and Hypothesis-driven Research in Patients or
Preclinical Studies)
Chronic obstructive pulmonary disease.—Chronic obstructive pulmonary disease (COPD) is the most common chronic
respiratory illness in the world, and it is increasing in prevalence with decidedly poor prognosis and outcomes. Pulmonary
function tests and CT currently serve as the established clinicaltools for COPD evaluations and large-scale multicenter studradiology.rsna.org n Radiology: Volume 00: Number 0— 2020

Hatabu et al

Figure 7: Images in 74-year-old man with solid lung nodule. Pulmonary MRI scan obtained with ultrashort echo time at 110 msec (left) andthin-section CT scan obtained with 1-mm-thick sections (right) show solid nodule in left lower lobe (arrows). The nodule measures 14 mm on MRI scan and
15 mm on thin-section CT scan. This nodule was diagnosed as invasive adenocarcinoma.

Figure 8: Images in 72-year-old man with usual interstitial pneumonia. Pulmonary MRI with ultra-short echo time at 192 msec at end of tidal expiration by respiratory
triggering (left) and thin-section CT at end full inspiration with 1 mm section thickness (right) shows honeycombing in the right lower lobe (black arrow) and reticulation in theleft lower lobe (white arrow). Although honeycombing was demonstrated with good agreement, reticulation was demonstrated with difference due to different respiratory
volumes.

ies (112). Several smaller COPD studies have employed MRI
methods.
The first large-scale multi-institutional study involved a collaboration with the United Kingdom, Germany, and Denmark,the Polarized Helium Imaging of the Lung study (113). This prospective study compared hyperpolarized helium MRI and CT innearly 200 patients with COPD and never-smokers. Using pulmonary function tests as a reference, regional analysis of hyperpolarized helium MRI and thin-section CT correctly categorized
healthy volunteers in 100% and 97% and COPD in 42% and69%, respectively. The apparent diffusion coefficients of hyperpolarized helium MRI better correlate with diffusing capacity of
the lung for carbon monoxide than CT lung density (r = 0.59
vs r = 0.29) (113). The first evidence of hyperpolarized helium
MRI utility in COPD was provided much earlier (114,115),
and these findings opened the door to larger studies in patientsand in those exposed to secondhand smoke (116). In one pilot
hyperpolarized helium MRI study, increased ventilation defects
and apparent diffusion coefficients were detected during a 2-year
period in patients with COPD in whom forced expiratory volume in 1 second remained unchanged (117), underscoring theRadiology: Volume 00: Number 0— 2020 n radiology.rsna.org

sensitivity of MRI to COPD abnormalities. In a larger COPD
cohort study, hyperpolarized helium MRI apparent diffusion coefficient values were used to explain ventilation improvements
after bronchodilator treatment (118). Moreover, in a comparison of CT, pulmonary function tests, and hyperpolarized helium
MRI in a larger COPD cohort, only hyperpolarized helium
MRI enabled the prediction of exacerbations in patients withmild to moderate COPD without previous exacerbations (119).
Time-resolved hyperpolarized helium MRI was also exploited todirectly visualize collateral ventilation in a small group (four of10) of patients with COPD (120). DW hyperpolarized helium
MRI has also helped detect subclinical emphysema in healthy
smokers (121,122) with high sensitivity, although hyperpolarized xenon MRI b value acquisition methods can quantify mean
alveolar dimensions in COPD (123) (Fig 9).
Quantitative perfusion MRI has also been employed in patients with COPD with correlation to CT and pulmonary function tests (124–128). In 144 participants, pulmonary microvascular blood flow was reduced in mild COPD compared with
control participants who were smokers, independent of small
airway disease at CT and gas trapping at pulmonary function
9

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

Figure 9: Images in 61-year-old man with mild to moderate chronic obstructive pulmonary disease (COPD) (top) and 61-yearold woman with severe COPD (bottom). Images on left are MRI ventilation scans coregistered to CT scans, and images on right are
corresponding center slice MRI apparent diffusion coefficient maps. MRI ventilation (cyan) was volume rendered in three dimensions
and coregistered to center-slice thoracic CT scan (gray scale) and three-dimensional rendered airway tree (yellow). The patient withmild to moderate COPD had forced expiratory volume in 1 second of 55% percentage predicted, ventilation defect percentage of
29%, and apparent diffusion coefficient of 0.36 cm2/sec. The patient with severe COPD had forced expiratory volume in 1 secondof 30% percentage predicted, ventilation defect percentage of 36%, and apparent diffusion coefficient of 0.54 cm2/sec.

tests (126). Pulmonary microvascular blood flow at MRI was
associated with signs of endothelial injury, including elevatedendothelial microparticles and reduced circulating endothelial
cells (127,128). In 79 participants, perfusion MRI was moresensitive to abnormalities among smokers with normal pulmonary function (129), and it helped distinguish patients among
three phenotypes (130). In 15 patients with COPD, perfusion
MRI helped evaluate acute exacerbations and postexacerbation improvements, showing that perfusion defects resolved after therapy (131). In a multicenter study of 160 patients with
COPD, oxygen-enhanced pulmonary MRI showed functional
derangements that distinguished patients similar to clinical severity staging (132). UTE MRI also showed reproducible signal
intensity changes in the lung parenchyma, which were related topulmonary function tests and CT measurements such as relative
area of the density histogram less than or equal to –950 HU andforced expiratory volume in 1 second/forced vital capacity (133).
Fluorine 19 MRI in patients with COPD has also been piloted
with promising results (134,135). A noncontrast method for the10assessment of ventilation and perfusion in patients with COPD
has also been employed (Appendix E1 [online]) (136).
Only three relatively large-scale MRI studies of COPD
have been reported: two multicenter trials in Europe, Japan,
and South Korea (113,132) and a single-center Canadianstudy (137). Comparative studies between 3He and 129Xe indicate similar sensitivity to lung obstruction and emphysema(138–140). Clinical trials with multiple institutions using hyperpolarized xenon are under way.
Asthma.—Asthma is the most common chronic disease in children (141), and it is a leading cause of workplace absence in adults(142). Until recently, MRI has played a very limited role in theclinical assessment of asthma. However, CT has been used to measure functional air trapping (143), and the National Institutes of
Health–funded Severe Asthma Research Program study also highlighted the utility of CT in understanding asthma severity (144).
Pulmonary MRI without exogenous contrast material, suchas Fourier decomposition MRI (28), provides a method toradiology.rsna.org n Radiology: Volume 00: Number 0— 2020

Hatabu et al

and honeycombing havedifferent T2 relaxation
times in nonspecific interstitial pneumonia orusual interstitial pneumonia (165). MR elastography has revealed
increased lung stiffnessin 15 patients with interstitial lung disease (166).
Oxygen-enhanced
proton MRI of interstitial lung disease has
shown
enhancementchanges in patients
versus healthy controls(167–170). Hyperpolarized xenon MRI spectroscopy revealed re­duced
signal from red blood
Figure 10: MRI ventilation image coregistered to CT scan in 41-year-old woman with asthma. MRI ventilation (cyan) was
volume rendered in three dimensions and coregistered to center-slice thoracic CT scan (gray scale) and three-dimensional renderedcells compared with tissue
airway tree (yellow). Zooming in on left lower lobe MRI ventilation defect with three-dimensional rendered pulmonary vasculature
in idiopathic pulmonary(red) reveals vascular pruning within ventilation defects. In this patient, the forced expiratory volume in 1 second was 60% percentfibrosis versus healthy
age predicted, and ventilation defect percentage was 15%.
volunteers (171). Hyperpolarized
xenon
generate ventilation and perfusion maps in patients with asthma
MRI showed good correlations with pulmonary function tests(145). In a similar manner, multivolume acquisitions (146), fol(172). In patients with idiopathic pulmonary fibrosis, the ratio
lowed by quantification of signal intensities related to inhalation,of hyperpolarized xenon MRI red blood cells–to–tissue barrier isprovide ventilation heterogeneity maps in asthma.
more sensitive to change than forced vital capacity and diffusAlthough MRI with intravenous gadolinium-based contrast
ing capacity of the lung for carbon monoxide (173), althoughagents has been used to generate quantitative lung perfusion inhyperpolarized xenon and hyperpolarized helium apparent diffuformation for direct comparison with pulmonary function testsion coefficients are more sensitive to acinar microstructural
measurements, the vast majority of asthma MRI studies involve
changes that correlate with the Likert fibrosis score derived
inhaled gas contrast hyperpolarized helium and hyperpolarizedfrom CT (138,174). Early and late T1 contrast enhancement
xenon methods that were pioneered by the team at the University
features may help differentiate inflammation from fibrotic-preof Virginia. These investigators provided the initial evidence ofdominant pathology, as shown in a biopsy study that classified
the utility of hyperpolarized helium ventilation MRI in patients
26 patients with usual interstitial pneumonia as inflammation
with asthma (147–150). They were also the first to describe theor fibrosis predominant (175).
spatial persistence of hyperpolarized helium MRI ventilation
Cost-effectiveness and Timeliness of Lung MRI
abnormalities in asthma (151,152) and the clinical relevance of
these hyperpolarized helium MRI measures (153,154). Others
MRI is associated with cost, complexity, and difficulty in readhave evaluated hyperpolarized helium MRI response to methaing. Few publications are available regarding (a) cost-effectivecholine challenge and other triggers such as exercise (155) andness data to support clinical use, to our knowledge, and (b) MRI
treatment (148,156, 157). These studies focused on ventilation
timeliness (ie, time to complete the examination after ordering)
quantification, which can be automated by coregistration ofcompared with CT. More studies on the cost-effectiveness ofventilation volume and the thoracic cavity volume (158). Morepulmonary MRI and its timeliness are needed, particularly forrecently, the relationships of hyperpolarized MRI ventilation abchildren with chronic disease in need of longitudinal follow-up
normalities with asthma control (159), eosinophilic inflammaimaging (eg, patients with CF and adults in lung cancer screention (160), and mucus plugs (161) were ascertained, all of which
ing programs) (176). Recently, Allen et al (177) reported thatare relevant for the clinical management of asthma (Fig 10).
MRI has a near equivalent life expectancy benefit and superior
cost-effectiveness compared with low-dose CT in a Markov
Interstitial lung disease.—Recent developments in UTE hymodel of lung cancer screening. To our knowledge, no publicadrogen 1 MRI (12) have shown comparable diagnostic accutions show data of the timeliness of lung MRI examinations.
racy to CT (109,162,163) in interstitial lung disease (Fig 8).
Summary and Future Directions
T1 values of fibrotic lung parenchyma are longer than thoseof emphysematous lung parenchyma and are influenced by
Until recently, the clinical use of pulmonary MRI has beenlung volume (164), while ground-glass opacity, reticulation,
limited. However, advanced methods are expanding opporRadiology: Volume 00: Number 0— 2020 n radiology.rsna.org

11

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders

tunities to exploit the advantages of MRI for the evaluationof several common lung disorders. MRI helps visualize lungstructural and functional abnormalities without ionizing radiation, making state-of-the-art MRI techniques an alternative toCT, particularly for pediatric patients, women of childbearing
age, pregnant women, and patients requiring serial follow-up
imaging where radiation burden is an issue. A clinically relevant example is the use of proton MRI in the serial imagingof children with CF. However, proton MRI pulse sequences
are not universally accessible beyond specialist or research centers, so they remain underused for lung imaging. To maximize
the potential of MRI to improve patient care, vendors and developers must ensure that more effective pulse sequences andmeasurements are more widely and easily available. The current roadblocks that stymie widespread adoption need to beaddressed.
Although CT will remain the principal imaging tool for routine pulmonary imaging examinations, including in the pediatricpopulation, MRI has either emerged as the clinical standard or
has shown enormous potential to change clinical care for certain
patients and indications. In addition, the unique informationthese MRI tools provide can be used for mechanistic, hypothesisdriven research in patients and preclinical models. Prospective andrandomized multicenter trials should be conducted to directlycompare MRI with conventional clinical approaches and imaging
for the most promising or most burdensome pulmonary diseases.
The results of such trials, along with continued improvements inpulmonary MRI methods, will likely necessitate future updated
modifications in the recommendations proposed here.
Acknowledgments: We thank the librarians Myung Ah Shim, BA, and Jaero Park,MS, for their dedicated support in manuscript formatting. Both librarians work at
the Samsung Medical Information and Media Services of Samsung Medical Centerin Seoul, South Korea.
Author contributions: Guarantors of integrity of entire study, H.H., Y.O.; study
concepts/study design or data acquisition or data analysis/interpretation, all authors;
manuscript drafting or manuscript revision for important intellectual content, allauthors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, H.H., Y.O., W.B.G., G.P., B.M., K.S.L., J.R.M., J.M.W., E.J.R.v.B.,
M.L.S., H.U.K.; clinical studies, H.H., J.R.M., H.U.K.; experimental studies,
J.R.M.; statistical analysis, XXX; and manuscript editing, H.H., Y.O., W.B.G., G.P.,
B.M., K.S.L., T.A.A., J.R.M., J.B.S., J.M.W., E.J.R.v.B., M.L.S., H.U.K.
K.S.L. developed and implemented the systemic search strategy. D.A.L. advisedon the systemic search. All authors participated in the literature search. H.H., Y.O.,
W.B.G., G.P., B.M., K.S.L., D.A.L., J.M.W., E.J.R.v.B., M.L.S., and H.U.K. created the first draft of the Review. All authors critically reviewed the manuscript andapproved the final version, taking accountability for the work. The Document Development and Oversight Committee and Executive Committee of the FleischnerSociety approved the manuscript before submission to Radiology.
Disclosures of Conflicts of Interest: H.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article:
is a consultant for Mitsubishi Chemical; has grants/grants pending with Canon
Medical and Konica Minolta; receives payment from Canon Medical for serving
on medical advisory board. Other relationships: disclosed no relevant relationships.
Y.O. Activities related to the present article: institution received research grant from
Canon Medical Systems. Activities not related to the present article: has grants/
grants pending with Daiichi Sankyo. Other relationships: disclosed no relevant relationships. W.B.G. Activities related to the present article: disclosed no relevant
relationships. Activities not related to the present article: is a consultant for Imbio;
has grants/grants pending with Siemens Medical Solutions USA. Other relationships: disclosed no relevant relationships. G.P. disclosed no relevant relationships.
B.M. Activities related to the present article: disclosed no relevant relationships.

12

Activities not related to the present article: has a consultancy agreement with MilliKelvin Technologies; has grants/grants pending; has patents (planned, pending, orissued); receives royalties. Other relationships: disclosed no relevant relationships.
K.S.L. disclosed no relevant relationships. T.A.A. Activities related to the present
article: institution received grant from National Institutes of Health. Activities not
related to the present article: is a consultant for Vertex; receives payment for lectures, including service on speakers bureaus, from Philips; receives payment from
Philips for development of educational presentations. Other relationships: disclosed
no relevant relationships. D.A.L. disclosed no relevant relationships. J.R.M. Activities related to the present article: disclosed no relevant relationships. Activities
not related to the present article: receives payment for lectures, including service
on speakers bureaus, from Siemens Healthineers. Other relationships: disclosed no
relevant relationships. J.B.S. disclosed no relevant relationships. J.M.W. disclosed
no relevant relationships. E.J.R.v.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: receives
payment for board membership from Aidence, Imbio, and QCTIS; is a consultant
for InHealth and Mentholatum. Other relationships: disclosed no relevant relationships. M.L.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships.
Other relationships: is a shareholder in HealthMyne, Stemina Biomarker Discovery,
and X-Vac. H.U.K. Activities related to the present article: disclosed no relevant
relationships. Activities not related to the present article: has grants/grants pending
with Siemens, Philips, and Bayer; receives payment for lectures, including service
on speakers bureaus, from Philips, Boehringer Ingelheim, MSD, and Astra Zeneca.
Other relationships: disclosed no relevant relationships.

References

1. Cutillo AG. Application of magnetic resonance to the study of lung.
Armonk, NY: Futura, 1996.
2. Morris AH, Blatter DD, Case TA, et al. A new nuclear magnetic resonanceproperty of lung. J Appl Physiol (1985) 1985;58(3):759–762.
3. Case TA, Durney CH, Ailion DC, Cutillo AG, Morris AH. A mathematicalmodel of diamagnetic line broadening in lung tissue and similar heterogeneous systems: Calculations and measurements. J Magn Reason (1969)
1987;73(2):304–314.
4. Durney CH, Bertolina J, Ailion DC, et al. Calculation and interpretation of
inhomogenous line broadening in models of lungs and other heterogenous
structures. J Magn Reason (1969) 1989;85(3):554–570.
5. Bertolina JA, Durney CH, Ailion DC, Cutillo AG, Morris AH, Goodrich
KC. Experimental verification of inhomogenous line-broadening calculations
in lung models and other inhomogenous structures. J Magn Reson (1969)
1992;99(1):161–169.
6. Cutillo AG, Ganesan K, Ailion DC, et al. Alveolar air-tissue interface
and nuclear magnetic resonance behavior of lung. J Appl Physiol (1985)
1991;70(5):2145–2154.
7. Bergin CJ, Pauly JM, Macovski A. Lung parenchyma: projection reconstruction MR imaging. Radiology 1991;179(3):777–781.
8. Bergin CJ, Glover GH, Pauly JM. Lung parenchyma: magnetic susceptibility
in MR imaging. Radiology 1991;180(3):845–848.
9. Bergin CJ, Noll DC, Pauly JM, Glover GH, Macovski A. MR imaging of lungparenchyma: a solution to susceptibility. Radiology 1992;183(3):673–676.
10. Pauly JM, Conolly SM, Nishimura DG, Macovski A. Slice-selective excitationfor very short T2 species [abstr]. In: Book of abstracts: Society of Magnetic
Resonance in Medicine 1989. Berkeley, Calif: Society of Magnetic Resonancein Medicine, 1989; 28.
11. Glover GH, Pauly JM, Bradshaw KM. Boron-11 imaging with a threedimensional reconstruction method. J Magn Reson Imaging 1992;2(1):47–52.
12. Johnson KM, Fain SB, Schiebler ML, Nagle S. Optimized 3D ultrashortecho time pulmonary MRI. Magn Reson Med 2013;70(5):1241–1250.
13. Mayo JR, MacKay A, Müller NL. MR imaging of the lungs: value of short
TE spin-echo pulse sequences. AJR Am J Roentgenol 1992;159(5):951–956.
14. Alsop DC, Hatabu H, Bonnet M, Listerud J, Gefter W. Multi-slice, breathhold imaging of the lung with submillisecond echo times. Magn Reson Med
1995;33(5):678–682.
15. Hatabu H, Gaa J, Tadamura E, et al. MR imaging of pulmonary parenchyma
with a half-Fourier single-shot turbo spin-echo (HASTE) sequence. Eur JRadiol 1999;29(2):152–159.
16. Hatabu H, Gefter WB, Kressel HY, Axel L, Lenkinski RE. Pulmonary
vasculature: high-resolution MR imaging. Work in progress. Radiology
1989;171(2):391–395.
17. Gefter WB, Hatabu H, Dinsmore BJ, et al. Pulmonary vascular cine MR
imaging: a noninvasive approach to dynamic imaging of the pulmonary
circulation. Radiology 1990;176(3):761–770.
18. Albert MS, Cates GD, Driehuys B, et al. Biological magnetic resonanceimaging using laser-polarized 129Xe. Nature 1994;370(6486):199–201.

radiology.rsna.org n Radiology: Volume 00: Number 0— 2020

Hatabu et al
19. Kauczor HU, Hofmann D, Kreitner KF, et al. Normal and abnormal
pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging.
Radiology 1996;201(2):564–568.
20. MacFall JR, Charles HC, Black RD, et al. Human lung air spaces: potential
for MR imaging with hyperpolarized He-3. Radiology 1996;200(2):553–558.
21. Hatabu H, Gaa J, Kim D, Li W, Prasad PV, Edelman RR. Pulmonary
perfusion: qualitative assessment with dynamic contrast-enhanced MRI using ultra-short TE and inversion recovery turbo FLASH. Magn Reson Med
1996;36(4):503–508.
22. Hatabu H, Tadamura E, Levin DL, et al. Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI. Magn Reson Med
1999;42(6):1033–1038.
23. Levin DL, Chen Q, Zhang M, Edelman RR, Hatabu H. Evaluation ofregional pulmonary perfusion using ultrafast magnetic resonance imaging.
Magn Reson Med 2001;46(1):166–171.
24. Ohno Y, Hatabu H, Murase K, et al. Quantitative assessment of regionalpulmonary perfusion in the entire lung using three-dimensional ultrafast
dynamic contrast-enhanced magnetic resonance imaging: Preliminary experience in 40 subjects. J Magn Reson Imaging 2004;20(3):353–365.
25. Edelman RR, Hatabu H, Tadamura E, Li W, Prasad PV. Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced
magnetic resonance imaging. Nat Med 1996;2(11):1236–1239.
26. Hatabu H, Tadamura E, Chen Q, et al. Pulmonary ventilation: dynamic
MRI with inhalation of molecular oxygen. Eur J Radiol 2001;37(3):172–178.
27. Ohno Y, Hatabu H, Takenaka D, Van Cauteren M, Fujii M, Sugimura
K. Dynamic oxygen-enhanced MRI reflects diffusing capacity of the lung.
Magn Reson Med 2002;47(6):1139–1144.
28. Bauman G, Puderbach M, Deimling M, et al. Non-contrast-enhanced
perfusion and ventilation assessment of the human lung by means of fourier
decomposition in proton MRI. Magn Reson Med 2009;62(3):656–664.
29. Puderbach M, Eichinger M, Haeselbarth J, et al. Assessment of morphological
MRI for pulmonary changes in cystic fibrosis (CF) patients: comparison tothin-section CT and chest x-ray. Invest Radiol 2007;42(10):715–725.
30. Wielpütz MO, Puderbach M, Kopp-Schneider A, et al. Magnetic resonance imaging detects changes in structure and perfusion, and responseto therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med
2014;189(8):956–965.
31. Roach DJ, Crémillieux Y, Fleck RJ, et al. Ultrashort Echo-Time Magnetic
Resonance Imaging Is a Sensitive Method for the Evaluation of Early
Cystic Fibrosis Lung Disease. Ann Am Thorac Soc 2016;13(11):1923–
1931.
32. Ciet P, Tiddens HA, Wielopolski PA, et al. Magnetic resonance imaging
in children: common problems and possible solutions for lung and airways
imaging. Pediatr Radiol 2015;45(13):1901–1915.
33. Failo R, Wielopolski PA, Tiddens HA, Hop WC, Mucelli RP, Lequin MH.
Lung morphology assessment using MRI: a robust ultra-short TR/TE 2D
steady state free precession sequence used in cystic fibrosis patients. Magn
Reson Med 2009;61(2):299–306.
34. Eichinger M, Optazaite DE, Kopp-Schneider A, et al. Morphologic andfunctional scoring of cystic fibrosis lung disease using MRI. Eur J Radiol
2012;81(6):1321–1329.
35. Hopkins SR, Wielpütz MO, Kauczor H-U. Imaging lung perfusion. J Appl
Physiol (1985) 2012;113(2):328–339.
36. Stahl M, Wielpütz MO, Graeber SY, et al. Comparison of Lung Clearance Index
and Magnetic Resonance Imaging for Assessment of Lung Disease in Children
with Cystic Fibrosis. Am J Respir Crit Care Med 2017;195(3):349–359.
37. Santyr G, Kanhere N, Morgado F, Rayment JH, Ratjen F, Couch MJ. Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis
Lung Disease. Acad Radiol 2019;26(3):344–354.
38. Wielpütz MO, von Stackelberg O, Stahl M, et al. Multicentre standardisationof chest MRI as radiation-free outcome measure of lung disease in young
children with cystic fibrosis. J Cyst Fibros 2018;17(4):518–527.
39. Altes TA, Johnson M, Fidler M, et al. Use of hyperpolarized helium-3 MRI
to assess response to ivacaftor treatment in patients with cystic fibrosis. J Cyst
Fibros 2017;16(2):267–274.
40. van Beek EJ, Hill C, Woodhouse N, et al. Assessment of lung disease inchildren with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison
with Shwachman score, Chrispin-Norman score and spirometry. Eur Radiol
2007;17(4):1018–1024.
41. Marshall H, Horsley A, Taylor CJ, et al. Detection of early subclinical lungdisease in children with cystic fibrosis by lung ventilation imaging withhyperpolarised gas MRI. Thorax 2017;72(8):760–762.
42. Woodhouse N, Wild JM, van Beek EJ, Hoggard N, Barker N, Taylor CJ.
Assessment of hyperpolarized 3He lung MRI for regional evaluation of interventional therapy: a pilot study in pediatric cystic fibrosis. J Magn Reson
Imaging 2009;30(5):981–988.
Radiology: Volume 00: Number 0— 2020 n radiology.rsna.org

43. Smith L, Marshall H, Aldag I, et al. Longitudinal Assessment of Children
with Mild Cystic Fibrosis Using Hyperpolarized Gas Lung Magnetic
Resonance Imaging and Lung Clearance Index. Am J Respir Crit Care Med
2018;197(3):397–400.
44. Altes TA, Meyer CH, Mata JF, et al. Hyperpolarized helium-3 magnetic
resonance lung imaging of non-sedated infants and young children: a proofof-concept study. Clin Imaging 2017;45:105–110.
45. Thomen RP, Walkup LL, Roach DJ, Cleveland ZI, Clancy JP, Woods JC.
Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease inpediatric patients. J Cyst Fibros 2017;16(2):275–282.
46. Kanhere N, Couch MJ, Kowalik K, et al. Correlation of Lung Clearance Index
with Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Subjects
with Cystic Fibrosis. Am J Respir Crit Care Med 2017;196(8):1073–1075.
47. Couch MJ, Thomen R, Kanhere N, et al. A two-center analysis of hyperpolarized 129Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker
for multi-site trials. J Cyst Fibros 2019;18(5):728–733.
48. Rayment JH, Couch MJ, McDonald N, et al. Hyperpolarised 129Xe magnetic
resonance imaging to monitor treatment response in children with cystic
fibrosis. Eur Respir J 2019;53(5):1802188.
49. Bauman G, Puderbach M, Heimann T, et al. Validation of Fourier decomposition MRI with dynamic contrast-enhanced MRI using visual andautomated scoring of pulmonary perfusion in young cystic fibrosis patients.
Eur J Radiol 2013;82(12):2371–2377.
50. Triphan SM, Jobst BJ, Breuer FA, et al. Echo time dependence of observed
T1 in the human lung. J Magn Reson Imaging 2015;42(3):610–616.
51. Veldhoen S, Weng AM, Knapp J, et al. Self-gated Non-Contrast-enhanced
Functional Lung MR Imaging for Quantitative Ventilation Assessment inPatients with Cystic Fibrosis. Radiology 2017;283(1):242–251.
52. Koyama H, Ohno Y, Kono A, et al. Quantitative and qualitative assessmentof non-contrast-enhanced pulmonary MR imaging for management of
pulmonary nodules in 161 subjects. Eur Radiol 2008;18(10):2120–2131.
53. Cieszanowski A, Lisowska A, Dabrowska M, et al. MR Imaging of Pulmonary
Nodules: Detection Rate and Accuracy of Size Estimation in Comparison
to Computed Tomography. PLoS One 2016;11(6):e0156272.
54. Ohno Y, Koyama H, Yoshikawa T, et al. Standard-, Reduced-, and No-DoseThin-Section Radiologic Examinations: Comparison of Capability for Nodule
Detection and Nodule Type Assessment in Patients Suspected of Having
Pulmonary Nodules. Radiology 2017;284(2):562–573.
55. Yi CA, Jeon TY, Lee KS, et al. 3-T MRI: usefulness for evaluating primarylung cancer and small nodules in lobes not containing primary tumors. AJR
Am J Roentgenol 2007;189(2):386–392.
56. Meier-Schroers M, Homsi R, Gieseke J, Schild HH, Thomas D. Lungcancer screening with MRI: Evaluation of MRI for lung cancer screening
by comparison of LDCT- and MRI-derived Lung-RADS categories in thefirst two screening rounds. Eur Radiol 2019;29(2):898–905.
57. Jiang W, Ong F, Johnson KM, et al. Motion robust high resolution 3D
free-breathing pulmonary MRI using dynamic 3D image self-navigator.
Magn Reson Med 2018;79(6):2954–2967.
58. Ohno Y, Nishio M, Koyama H, et al. Dynamic contrast-enhanced CT
and MRI for pulmonary nodule assessment. AJR Am J Roentgenol
2014;202(3):515–529.
59. Li B, Li Q, Chen C, Guan Y, Liu S. A systematic review and meta-analysisof the accuracy of diffusion-weighted MRI in the detection of malignant
pulmonary nodules and masses. Acad Radiol 2014;21(1):21–29.
60. Ohno Y, Koyama H, Takenaka D, et al. Dynamic MRI, dynamic multidetector-row computed tomography (MDCT), and coregistered 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/CT:
comparative study of capability for management of pulmonary nodules. J
Magn Reson Imaging 2008;27(6):1284–1295.
61. Ohno Y, Nishio M, Koyama H, et al. Solitary pulmonary nodules: Comparisonof dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic
first-pass contrast-enhanced MR imaging, and FDG PET/CT. Radiology
2015;274(2):563–575.
62. Basso Dias A, Zanon M, Altmayer S, et al. Fluorine 18-FDG PET/CT and
Diffusion-weighted MRI for Malignant versus Benign Pulmonary Lesions:
A Meta-Analysis. Radiology 2019;290(2):525–534.
63. Webb WR, Gatsonis C, Zerhouni EA, et al. CT and MR imaging in staging
non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic
Oncology Group. Radiology 1991;178(3):705–713.
64. Sakai S, Murayama S, Murakami J, Hashiguchi N, Masuda K. Bronchogenic
carcinoma invasion of the chest wall: evaluation with dynamic cine MRI
during breathing. J Comput Assist Tomogr. 1997; 21(4):595-600.
65. Ohno Y, Adachi S, Motoyama A, et al. Multiphase ECG-triggered 3D
contrast-enhanced MR angiography: utility for evaluation of hilar andmediastinal invasion of bronchogenic carcinoma. J Magn Reson Imaging
2001;13(2):215–224.
13

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders
66. Tang W, Wu N, OuYang H, Huang Y, Liu L, Li M. The presurgical T staging
of non-small cell lung cancer: efficacy comparison of 64-MDCT and 3.0 T
MRI. Cancer Imaging. 2015;15(1):14.
67. Takenaka D, Ohno Y, Hatabu H, et al. Differentiation of metastatic versus
non-metastatic mediastinal lymph nodes in patients with non-small cell lungcancer using respiratory-triggered short inversion time inversion recovery(STIR) turbo spin-echo MR imaging. Eur J Radiol. 2002 Dec;44(3):216-24.
68. Ohno Y, Hatabu H, Takenaka D, et al. Metastases in mediastinal and hilar
lymph nodes in patients with non-small cell lung cancer: quantitative andqualitative assessment with STIR turbo spin-echo MR imaging. Radiology.
2004; 231(3):872-879.
69. Ohno Y, Koyama H, Nogami M, et al. STIR turbo SE MR imaging vs.
coregistered FDG-PET/CT: quantitative and qualitative assessment of Nstage in non-small-cell lung cancer patients. J Magn Reson Imaging. 2007;
26(4):1071-1080.
70. Hasegawa I, Boiselle PM, Kuwabara K, Sawafuji M, Sugiura H. Mediastinal
lymph nodes in patients with non-small cell lung cancer: preliminary experience with diffusion-weighted MR imaging. J Thorac Imaging. 2008; 23(3):157-161.
71. Nomori H, Mori T, Ikeda K, et al. Diffusion-weighted magnetic resonanceimaging can be used in place of positron emission tomography for N
staging of non-small cell lung cancer with fewer false-positive results.
J Thorac Cardiovasc Surg. 2008; 135(4): 816-822.
72. Morikawa M, Demura Y, Ishizaki T, et al. The effectiveness of 18F-FDG
PET/CT combined with STIR MRI for diagnosing nodal involvementin the thorax. J Nucl Med. 2009 Jan;50(1):81-7.
73. Nakayama J, Miyasaka K, Omatsu T, et al. Metastases in mediastinal
and hilar lymph nodes in patients with non-small cell lung cancer:
quantitative assessment with diffusion-weighted magnetic resonanceimaging and apparent diffusion coefficient. J Comput Assist Tomogr.
2010; 34(1): 1-8.
74. Usuda K, Zhao XT, Sagawa M, et al. Diffusion-weighted imaging is
superior to positron emission tomography in the detection and nodal
assessment of lung cancers. Ann Thorac Surg. 2011; 91(6): 1689-1695.
75. Ohno Y, Koyama H, Yoshikawa T, et al. N stage disease in patients with
non-small cell lung cancer: efficacy of quantitative and qualitative assessmentwith STIR turbo spin-echo imaging, diffusion-weighted MR imaging, andfluorodeoxyglucose PET/CT. Radiology 2011;261(2):605–615.
76. Ohno Y, Koyama H, Yoshikawa T, et al. Diffusion-weighted MR imaging using FASE sequence for 3T MR system: Preliminary comparisonof capability for N-stage assessment by means of diffusion-weighted
MR imaging using EPI sequence, STIR FASE imaging and FDG
PET/CT for non-small cell lung cancer patients. Eur J Radiol. 2015;84(11):2321-31.
77. Usuda K, Maeda S, Motono N, et al. Diagnostic Performance of DiffusionWeighted Imaging for Multiple Hilar and Mediastinal Lymph Nodeswith FDG Accumulation. Asian Pac J Cancer Prev. 2015; 16(15):6401-6406.
78. Nomori H, Cong Y, Sugimura H, Kato Y. Diffusion-weighted imaging
can correctly identify false-positive lymph nodes on positron emission
tomography in non-small cell lung cancer. Surg Today. 2016; 46(10):1146-1151.
79. Peerlings J, Troost EG, Nelemans PJ, et al. The Diagnostic Value of
MR Imaging in Determining the Lymph Node Status of Patients with
Non-Small Cell Lung Cancer: A Meta-Analysis. Radiology 2016;281(1):86–98.
80. Kim YN, Yi CA, Lee KS, et al. A proposal for combined MRI and PET/CT
interpretation criteria for preoperative nodal staging in non-small-cell lungcancer. Eur Radiol 2012;22(7):1537–1546.
81. Yi CA, Shin KM, Lee KS, et al. Non-small cell lung cancer staging: efficacy
comparison of integrated PET/CT versus 3.0-T whole-body MR imaging.
Radiology 2008;248(2):632–642.
82. Yi CA, Lee KS, Lee HY, et al. Coregistered whole body magnetic resonanceimaging-positron emission tomography (MRI-PET) versus PET-computed
tomography plus brain MRI in staging resectable lung cancer: comparisonsof clinical effectiveness in a randomized trial. Cancer 2013;119(10):1784–
1791.
83. Schaarschmidt BM, Grueneisen J, Metzenmacher M, et al. Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer : does it change
therapeutic decisions in comparison to 18F-FDG PET/CT? Eur Radiol
2017;27(2):681–688.
84. Lee SM, Goo JM, Park CM, et al. Preoperative staging of non-small celllung cancer: prospective comparison of PET/MR and PET/CT. Eur Radiol
2016;26(11):3850–3857.
85. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the
diagnosis and treatment of pulmonary hypertension: The Joint Task Force for14

the Diagnosis and Treatment of Pulmonary Hypertension of the European
Society of Cardiology (ESC) and the European Respiratory Society (ERS):
Endorsed by: Association for European Paediatric and Congenital Cardiology(AEPC), International Society for Heart and Lung Transplantation (ISHLT).
Eur Heart J 2016;37(1):67–119.
86. Kiely DG, Levin D, Hassoun P, et al. EXPRESS: Statement on imaging andpulmonary hypertension from the Pulmonary Vascular Research Institute(PVRI). Pulm Circ 2019. 10.1177/2045894019841990. Published online
March 18, 2019.
87. Rajaram S, Swift AJ, Telfer A, et al. 3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic
pulmonary hypertension: results from the ASPIRE Registry. Thorax
2013;68(7):677–678.
88. Johns CS, Swift AJ, Rajaram S, et al. Lung perfusion: MRI vs. SPECT for
screening in suspected chronic thromboembolic pulmonary hypertension. J
Magn Reson Imaging 2017;46(6):1693–1697.
89. Swift AJ, Wild JM, Nagle SK, et al. Quantitative magnetic resonance imaging
of pulmonary hypertension: a practical approach to the current state of theart. J Thorac Imaging 2014;29(2):68–79.
90. van de Veerdonk MC, Kind T, Marcus JT, et al. Progressive right ventricular
dysfunction in patients with pulmonary arterial hypertension responding totherapy. J Am Coll Cardiol 2011;58(24):2511–2519.
91. Peacock AJ, Crawley S, McLure L, et al. Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving
pulmonary arterial hypertension-targeted therapy: the EURO-MR study.
Circ Cardiovasc Imaging 2014;7(1):107–114.
92. van Wolferen SA, van de Veerdonk MC, Mauritz GJ, et al. Clinicallysignificant change in stroke volume in pulmonary hypertension. Chest
2011;139(5):1003–1009.
93. van Wolferen SA, Marcus JT, Boonstra A, et al. Prognostic value of rightventricular mass, volume, and function in idiopathic pulmonary arterial
hypertension. Eur Heart J 2007;28(10):1250–1257.
94. Ohno Y, Hatabu H, Murase K, et al. Primary pulmonary hypertension:
3D dynamic perfusion MRI for quantitative analysis of regional pulmonary
perfusion. AJR Am J Roentgenol 2007;188(1):48–56.
95. Ohno Y, Koyama H, Nogami M, et al. Dynamic perfusion MRI: capability
for evaluation of disease severity and progression of pulmonary arterial hypertension in patients with connective tissue disease. J Magn Reson Imaging
2008;28(4):887–899.
96. Ohno Y, Koyama H, Yoshikawa T, et al. Contrast-enhanced multidetector-row
computed tomography vs. Time-resolved magnetic resonance angiography
vs. contrast-enhanced perfusion MRI: assessment of treatment response by
patients with inoperable chronic thromboembolic pulmonary hypertension.
J Magn Reson Imaging 2012;36(3):612–623.
97. Rajaram S, Swift AJ, Capener D, et al. Diagnostic accuracy of contrastenhanced MR angiography and unenhanced proton MR imaging comparedwith CT pulmonary angiography in chronic thromboembolic pulmonary
hypertension. Eur Radiol 2012;22(2):310–317.
98. Swift AJ, Rajaram S, Condliffe R, et al. Pulmonary artery relative area change
detects mild elevations in pulmonary vascular resistance and predicts adverse
outcome in pulmonary hypertension. Invest Radiol 2012;47(10):571–577.
99. Gan CT, Lankhaar JW, Westerhof N, et al. Noninvasively assessed pulmonary
artery stiffness predicts mortality in pulmonary arterial hypertension. Chest
2007;132(6):1906–1912.
100. Swift AJ, Capener D, Johns C, et al. Magnetic Resonance Imaging in the
Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension.
Am J Respir Crit Care Med 2017;196(2):228–239.
101. Baggen VJ, Leiner T, Post MC, et al. Cardiac magnetic resonancefindings predicting mortality in patients with pulmonary arterial
hypertension: a systematic review and meta-analysis. Eur Radiol
2016;26(11):3771–3780.
102. Ohno Y, Higashino T, Takenaka D, et al. MR angiography with sensitivity
encoding (SENSE) for suspected pulmonary embolism: comparison with
MDCT and ventilation-perfusion scintigraphy. AJR Am J Roentgenol
2004;183(1):91–98.
103. Kluge A, Luboldt W, Bachmann G. Acute pulmonary embolism to thesubsegmental level: diagnostic accuracy of three MRI techniques comparedwith 16-MDCT. AJR Am J Roentgenol 2006;187(1):W7–W14.
104. Repplinger MD, Nagle SK, Harringa JB, et al. Clinical outcomes aftermagnetic resonance angiography (MRA) versus computed tomographic
angiography (CTA) for pulmonary embolism evaluation. Emerg Radiol
2018;25(5):469–477.
105. Sostman HD, Jablonski KA, Woodard PK, et al. Factors in the technical quality of gadolinium enhanced magnetic resonance angiography
for pulmonary embolism in PIOPED III. Int J Cardiovasc Imaging
2012;28(2):303–312.
radiology.rsna.org n Radiology: Volume 00: Number 0— 2020

Hatabu et al106. Brau AC, Beatty PJ, Skare S, Bammer R. Comparison of reconstruction
accuracy and efficiency among autocalibrating data-driven parallel imaging
methods. Magn Reson Med 2008;59(2):382–395.
107. Rajaram S, Swift AJ, Capener D, et al. Lung morphology assessment withbalanced steady-state free precession MR imaging compared with CT.
Radiology 2012;263(2):569–577.
108. Dournes G, Grodzki D, Macey J, et al. Quiet Submillimeter MR Imaging of the Lung Is Feasible with a PETRA Sequence at 1.5 T. Radiology
2015;276(1):258–265.
109. Ohno Y, Koyama H, Yoshikawa T, et al. Pulmonary high-resolution ultrashort
TE MR imaging: Comparison with thin-section standard- and low-dosecomputed tomography for the assessment of pulmonary parenchyma diseases.
J Magn Reson Imaging 2016;43(2):512–532.
110. Wielpütz MO, Lee HY, Koyama H, et al. Morphologic Characterization of
Pulmonary Nodules With Ultrashort TE MRI at 3T. AJR Am J Roentgenol
2018;210(6):1216–1225.
111. Ohno Y, Koyama H, Yoshikawa T, et al. T2* measurements of 3-T MRI withultrashort TEs: capabilities of pulmonary function assessment and clinical stage
classification in smokers. AJR Am J Roentgenol 2011;197(2):W279–W285.
112. Sørensen L, Nielsen M, Petersen J, Pedersen JH, Dirksen A, de Bruijne M.
Chronic Obstructive Pulmonary Disease Quantification Using CT Texture
Analysis and Densitometry: Results From the Danish Lung Cancer Screening
Trial. AJR Am J Roentgenol 2020;214(6):1269–1279.
113. van Beek EJ, Dahmen AM, Stavngaard T, et al. Hyperpolarised 3He MRI
versus HRCT in COPD and normal volunteers: PHIL trial. Eur Respir J
2009;34(6):1311–1321.
114. Salerno M, de Lange EE, Altes TA, Truwit JD, Brookeman JR, Mugler JP
3rd. Emphysema: hyperpolarized helium 3 diffusion MR imaging of thelungs compared with spirometric indexes--initial experience. Radiology
2002;222(1):252–260.
115. Salerno M, Altes TA, Brookeman JR, de Lange EE, Mugler JP 3rd. Rapid
hyperpolarized 3He diffusion MRI of healthy and emphysematous humanlungs using an optimized interleaved-spiral pulse sequence. J Magn Reson
Imaging 2003;17(5):581–588.
116. Wang C, Mugler JP 3rd, de Lange EE, Patrie JT, Mata JF, Altes TA. Lung
injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR. J Magn Reson Imaging 2014;39(1):77–84.
117. Kirby M, Mathew L, Wheatley A, Santyr GE, McCormack DG, Parraga G.
Chronic obstructive pulmonary disease: longitudinal hyperpolarized (3)HeMR imaging. Radiology 2010;256(1):280–289.
118. Kirby M, Mathew L, Heydarian M, Etemad-Rezai R, McCormack DG,
Parraga G. Chronic obstructive pulmonary disease: quantification of bronchodilator effects by using hyperpolarized ³He MR imaging. Radiology
2011;261(1):283–292.
119. Kirby M, Pike D, Coxson HO, McCormack DG, Parraga G. Hyperpolarized (3)He ventilation defects used to predict pulmonary exacerbations
in mild to moderate chronic obstructive pulmonary disease. Radiology
2014;273(3):887–896.
120. Marshall H, Deppe MH, Parra-Robles J, et al. Direct visualisation ofcollateral ventilation in COPD with hyperpolarised gas MRI. Thorax
2012;67(7):613–617.
121. Swift AJ, Wild JM, Fichele S, et al. Emphysematous changes and normal
variation in smokers and COPD patients using diffusion 3He MRI. Eur JRadiol 2005;54(3):352–358.
122. Fain SB, Panth SR, Evans MD, et al. Early emphysematous changes inasymptomatic smokers: detection with 3He MR imaging. Radiology
2006;239(3):875–883.
123. Chan HF, Stewart NJ, Norquay G, Collier GJ, Wild JM. 3D diffusionweighted 129 Xe MRI for whole lung morphometry. Magn Reson Med
2018;79(6):2986–2995.
124. Jang YM, Oh YM, Seo JB, et al. Quantitatively assessed dynamic contrastenhanced magnetic resonance imaging in patients with chronic obstructive
pulmonary disease: correlation of perfusion parameters with pulmonary
function test and quantitative computed tomography. Invest Radiol
2008;43(6):403–410.
125. Hueper K, Parikh MA, Prince MR, et al. Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic
resonance imaging and their relationships to global lung perfusion and lung
diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive
pulmonary disease study. Invest Radiol 2013;48(4):223–230.
126. Hueper K, Vogel-Claussen J, Parikh MA, et al. Pulmonary MicrovascularBlood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study. Am J Respir Crit Care Med 2015;192(5):570–580.
127. Thomashow MA, Shimbo D, Parikh MA, et al. Endothelial microparticles
in mild chronic obstructive pulmonary disease and emphysema. The MultiRadiology: Volume 00: Number 0— 2020 n radiology.rsna.org

Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease
study. Am J Respir Crit Care Med 2013;188(1):60–68.
128. Doyle MF, Tracy RP, Parikh MA, et al. Endothelial progenitor cells
in chronic obstructive pulmonary disease and emphysema. PLoS One
2017;12(3):e0173446.
129. Fan L, Xia Y, Guan Y, et al. Capability of differentiating smokers with normal
pulmonary function from COPD patients: a comparison of CT pulmonary
volume analysis and MR perfusion imaging. Eur Radiol 2013;23(5):1234–1241.
130. Fan L, Xia Y, Guan Y, Zhang TF, Liu SY. Characteristic features of pulmonary function test, CT volume analysis and MR perfusion imaging in
COPD patients with different HRCT phenotypes. Clin Respir J 2014;8(1):45–54.
131. Sergiacomi G, Taglieri A, Chiaravalloti A, et al. Acute COPD exacerbation: 3
T MRI evaluation of pulmonary regional perfusion--preliminary experience.
Respir Med 2014;108(6):875–882.
132. Ohno Y, Iwasawa T, Seo JB, et al. Oxygen-enhanced magnetic resonanceimaging versus computed tomography: multicenter study for clinical stage
classification of smoking-related chronic obstructive pulmonary disease. Am
J Respir Crit Care Med 2008;177(10):1095–1102.
133. Ma W, Sheikh K, Svenningsen S, et al. Ultra-short echo-time pulmonary
MRI: evaluation and reproducibility in COPD subjects with and without
bronchiectasis. J Magn Reson Imaging 2015;41(5):1465–1474.
134. Gutberlet M, Kaireit TF, Voskrebenzev A, et al. Free-breathing Dynamic
19
F Gas MR Imaging for Mapping of Regional Lung Ventilation in Patientswith COPD. Radiology 2018;286(3):1040–1051.
135. Halaweish AF, Moon RE, Foster WM, et al. Perfluoropropane gas asa magnetic resonance lung imaging contrast agent in humans. Chest
2013;144(4):1300–1310.
136. Voskrebenzev A, Gutberlet M, Klimeš F, et al. Feasibility of quantitative
regional ventilation and perfusion mapping with phase-resolved functionallung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF
patients. Magn Reson Med 2018;79(4):2306–2314.
137. Kirby M, Pike D, McCormack DG, Lam S, Coxson HO, Parraga G. Longitudinal Computed Tomography and Magnetic Resonance Imaging of
COPD: Thoracic Imaging Network of Canada (TINCan) Study Objectives.
Chronic Obstr Pulm Dis (Miami) 2014;1(2):200–211.
138. Chan HF, Collier GJ, Weatherley ND, Wild JM. Comparison of in vivo lungmorphometry models from 3D multiple b-value 3 He and 129 Xe diffusionweighted MRI. Magn Reson Med 2019;81(5):2959–2971.
139. Stewart NJ, Chan HF, Hughes PJC, et al. Comparison of 3 He and 129 Xe
MRI for evaluation of lung microstructure and ventilation at 1.5T. J Magn
Reson Imaging 2018;48(3):632–642.
140. Kirby M, Svenningsen S, Owrangi A, et al. Hyperpolarized 3He and 129Xe
MR imaging in healthy volunteers and patients with chronic obstructive
pulmonary disease. Radiology 2012;265(2):600–610.
141. Woolcock AJ. Epidemiology of chronic airways disease. Chest
1989;96(3,Suppl):302S–306S.
142. To T, Stanojevic S, Moores G, et al. Global asthma prevalence in adults:
findings from the cross-sectional world health survey. BMC Public Health2012;12(1):204.
143. Bhatt SP, Soler X, Wang X, et al. Association between Functional Small
Airway Disease and FEV1 Decline in Chronic Obstructive Pulmonary
Disease. Am J Respir Crit Care Med 2016;194(2):178–184.
144. Aysola RS, Hoffman EA, Gierada D, et al. Airway remodeling measured bymultidetector CT is increased in severe asthma and correlates with pathology.
Chest 2008;134(6):1183–1191.
145. Capaldi DPI, Sheikh K, Eddy RL, et al. Free-breathing Functional Pulmonary MRI: Response to Bronchodilator and Bronchoprovocation in Severe
Asthma. Acad Radiol 2017;24(10):1268–1276.
146. Pennati F, Quirk JD, Yablonskiy DA, Castro M, Aliverti A, Woods JC. Assessment of regional lung function with multivolume (1)H MR imaging in
health and obstructive lung disease: comparison with (3)He MR imaging.
Radiology 2014;273(2):580–590.
147. Altes TA, Powers PL, Knight-Scott J, et al. Hyperpolarized 3He MR lungventilation imaging in asthmatics: preliminary findings. J Magn Reson Imaging 2001;13(3):378–384.
148. Samee S, Altes T, Powers P, et al. Imaging the lungs in asthmatic patientsby using hyperpolarized helium-3 magnetic resonance: assessment ofresponse to methacholine and exercise challenge. J Allergy Clin Immunol
2003;111(6):1205–1211.
149. Svenningsen S, Kirby M, Starr D, et al. Hyperpolarized (3) He and (129) Xe
MRI: differences in asthma before bronchodilation. J Magn Reson Imaging
2013;38(6):1521–1530.
150. Ebner L, He M, Virgincar RS, et al. Hyperpolarized 129Xenon Magnetic
Resonance Imaging to Quantify Regional Ventilation Differences in Mild
to Moderate Asthma: A Prospective Comparison Between Semiautomated15

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders
Ventilation Defect Percentage Calculation and Pulmonary Function Tests.
Invest Radiol 2017;52(2):120–127.
151. de Lange EE, Altes TA, Patrie JT, et al. Evaluation of asthma with hyperpolarized helium-3 MRI: correlation with clinical severity and spirometry.
Chest 2006;130(4):1055–1062.
152. de Lange EE, Altes TA, Patrie JT, et al. The variability of regional airflow
obstruction within the lungs of patients with asthma: assessment with hyperpolarized helium-3 magnetic resonance imaging. J Allergy Clin Immunol
2007;119(5):1072–1078.
153. Aysola R, de Lange EE, Castro M, Altes TA. Demonstration of the heterogeneous distribution of asthma in the lungs using CT and hyperpolarized
helium-3 MRI. J Magn Reson Imaging 2010;32(6):1379–1387.
154. Altes TA, Mugler JP 3rd, Ruppert K, et al. Clinical correlates of lung ventilation
defects in asthmatic children. J Allergy Clin Immunol 2016;137(3):789–96.
e7, e787.
155. Kruger SJ, Niles DJ, Dardzinski B, et al. Hyperpolarized Helium-3 MRI of
exercise-induced bronchoconstriction during challenge and therapy. J Magn
Reson Imaging 2014;39(5):1230–1237.
156. Horn FC, Marshall H, Collier GJ, et al. Regional Ventilation Changes inthe Lung: Treatment Response Mapping by Using Hyperpolarized Gas MR
Imaging as a Quantitative Biomarker. Radiology 2017;284(3):854–861.
157. Mummy DG, Carey KJ, Evans MD, et al. Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency.
J Allergy Clin Immunol 2020. 10.1016/j.jaci.2020.02.029. Published online
March 13, 2020.
158. Woodhouse N, Wild JM, Paley MN, et al. Combined helium-3/proton magnetic resonance imaging measurement of ventilated lung volumes in smokers
compared to never-smokers. J Magn Reson Imaging 2005;21(4):365–369.
159. Svenningsen S, Nair P, Guo F, McCormack DG, Parraga G. Is ventilation
heterogeneity related to asthma control? Eur Respir J 2016;48(2):370–379.
160. Svenningsen S, Eddy RL, Lim HF, Cox PG, Nair P, Parraga G. Sputum
Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity
in Severe Asthma. Am J Respir Crit Care Med 2018;197(7):876–884.
161. Svenningsen S, Haider E, Boylan C, et al. CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma. Chest 2019;155(6):1178–1189.
162. Ohno Y, Nishio M, Koyama H, et al. Pulmonary MR imaging with ultrashort TEs: utility for disease severity assessment of connective tissue disease
patients. Eur J Radiol 2013;82(8):1359–1365.
163. Pinal-Fernandez I, Pineda-Sanchez V, Pallisa-Nuñez E, et al. Fast 1.5 T
chest MRI for the assessment of interstitial lung disease extent secondary tosystemic sclerosis. Clin Rheumatol 2016;35(9):2339–2345.
164. Stadler A, Jakob PM, Griswold M, Stiebellehner L, Barth M, Bankier AA.
T1 mapping of the entire lung parenchyma: Influence of respiratory phaseand correlation to lung function test results in patients with diffuse lungdisease. Magn Reson Med 2008;59(1):96–101.

16

165. Buzan MT, Eichinger M, Kreuter M, et al. T2 mapping of CT remodelling
patterns in interstitial lung disease. Eur Radiol 2015;25(11):3167–3174.
166. Marinelli JP, Levin DL, Vassallo R, et al. Quantitative assessment of lung
stiffness in patients with interstitial lung disease using MR elastography. J
Magn Reson Imaging 2017;46(2):365–374.
167. Müller CJ, Schwaiblmair M, Scheidler J, et al. Pulmonary diffusing capacity:
assessment with oxygen-enhanced lung MR imaging preliminary findings.
Radiology 2002;222(2):499–506.
168. Ohno Y, Nishio M, Koyama H, et al. Oxygen-enhanced MRI for patientswith connective tissue diseases: comparison with thin-section CT of capability for pulmonary functional and disease severity assessment. Eur J Radiol
2014;83(2):391–397.
169. Molinari F, Eichinger M, Risse F, et al. Navigator-triggered oxygen-enhanced
MRI with simultaneous cardiac and respiratory synchronization for the assessment of interstitial lung disease. J Magn Reson Imaging 2007;26(6):1523–
1529.
170. Takenaka D, Puderbach M, Ohno Y, et al. Oxygen-enhanced lung magnetic
resonance imaging: influence of inversion pulse slice selectivity on inversion recovery half-Fourier single-shot turbo spin-echo signal. Jpn J Radiol
2011;29(4):244–250.
171. Kaushik SS, Freeman MS, Yoon SW, et al. Measuring diffusion limitation
with a perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis. J Appl Physiol (1985)
2014;117(6):577–585.
172. Wang JM, Robertson SH, Wang Z, et al. Using hyperpolarized 129Xe MRI
to quantify regional gas transfer in idiopathic pulmonary fibrosis. Thorax
2018;73(1):21–28.
173. Weatherley 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(5):500–502.
174. Rankine LJ, Wang Z, Wang JM, et al. 129Xenon Gas Exchange Magnetic
Resonance Imaging as a Potential Prognostic Marker for Progression of
Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc 2020;17(1):121–
125.
175. Yi CA, Lee KS, Han J, Chung MP, Chung MJ, Shin KM. 3-T MRI
for differentiating inflammation- and fibrosis-predominant lesionsof usual and nonspecific interstitial pneumonia: comparison study
with pathologic correlation. AJR Am J Roentgenol 2008;190(4):878–
885.
176. Biederer J, Ohno Y, Hatabu H, et al. Screening for lung cancer: Does MRI
have a role? Eur J Radiol 2017;86:353–360.
177. Allen BD, Schiebler ML, Sommer G, et al. Cost-effectiveness of lung MRI
in lung cancer screening. Eur Radiol 2020;30(3):1738–1746.

radiology.rsna.org n Radiology: Volume 00: Number 0— 2020