REVIEWS AND COMMENTARY • STATEMENTS AND GUIDELINES

Imaging of Pulmonary Hypertension in Adults: A Position
Paper from the Fleischner Society
Martine Remy-Jardin, MD, PhD* • Christopher J. Ryerson, MD • Mark L. Schiebler, MD •Ann N. C. Leung, MD, PhD • James M. Wild, PhD • Marius M. Hoeper, MD • Philip O. Alderson, MD •Lawrence R. Goodman, MD • John Mayo, MD • Linda B. Haramati, MS, MD • Yoshiharu Ohno, MD •Patricia Thistlethwaite, MD, PhD • Edwin J. R. van Beek, MD, PhD • Shandra Lee Knight, MS •David A. Lynch, MB, BCh • Geoffrey D. Rubin, MD • Marc Humbert, MD, PhD**
From the Department of Thoracic Imaging, Hôpital Calmette, Boulevard Jules Leclercq, 59037 Lille, France (M.R.J.); Department of Medicine, University of British
Columbia and Centre for Heart Lung Innovation, St Paul’s Hospital, Vancouver, Canada (C.J.R.); Department of Radiology, UW-Madison School of Medicine andPublic Health, Madison, Wis (M.L.S.); Department of Radiology, Stanford University Medical Center, Stanford, Calif (A.N.C.L.); Division of Imaging, Department of
Infection Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, England (J.M.W.); Department of Respiratory Medicine, Hannover Medical School andGerman Centre of Lung Research (DZL), Hannover, Germany (M.M.H.); Department of Radiology, Saint Louis University School of Medicine, St Louis, Mo (P.O.A.);
Department of Radiology, Medical College of Wisconsin, Milwaukee, Wis (L.R.G.); Department of Radiology, Vancouver General Hospital, Vancouver, Canada (J.M.);
Department of Radiology and Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (L.B.H.); Department of Radiology, Fujita
Health University School of Medicine, Toyoake, Japan (Y.O.); Division of Cardiothoracic Surgery, University of California, San Diego, La Jolla, Calif (P.T.); Edinburgh
Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland (E.J.R.v.B.); Department of Library and Knowledge Services (S.L.K.) and
Department of Radiology (D.A.L.), National Jewish Health, Denver, Colo; Department of Radiology, Duke University School of Medicine, Durham, NC (G.D.R.); andUniversité Paris Saclay, Inserm UMR S999, Department of Pneumology, AP-HP, Pulmonary Hypertension Reference Center, Hôpital de Bicêtre, Le Kremlin Bicêtre,France (M.H.). Received July 15, 2020; revision requested August 7; final revision received October 22; accepted October 28. Address correspondence to M.R.J. (e-mail:martine.remy@chru-lille.fr).
*Chair and **Co-Chair of the Fleischner Society writing committee of the position paper for Imaging of Pulmonary Hypertension.
M.H. supported by the Investissement d’Avenir program managed by the French National Research Agency under the grant contract ANR-18-RHUS-0006(DESTINATION 2024).
Conflicts of interest are listed at the end of this article.
Radiology 2021; 00:1–19﻿ • https://doi.org/10.1148/radiol.2020203108• Content code:

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into fivedifferent groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management.
Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed fromwithin the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience
with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, andnuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging
in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH?
This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning,
and follow-up of PH.
This article is a simultaneous joint publication in Radiology and European Respiratory Journal. The articles are identical except forstylistic changes in keeping with each journal’s style. Either version may be used in citing this article.
© 2021 RSNA and the European Respiratory Society.
Online supplemental material is available for this article.

Pulmonary hypertension (PH) is a hemodynamic condition defined by a mean pulmonary artery (PA) pressure(PAP) greater than 20 mm Hg and classified into different
groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management(1–6) (Table 1). The diagnostic process starts after theclinical suspicion of PH and echocardiography compatible
with PH and continues with the identification of the morecommon clinical groups of PH (such as group 2 due tochronic left heart disease and group 3 due to chronic lungdiseases), then distinguishes group 4 due to chronic thromboembolic PH (CTEPH), and finally makes the diagnosisof group 1 pulmonary arterial hypertension (PAH), which
is a diagnosis of exclusion.
This overview of PH categorization highlights thenecessity of an optimized approach for each stage ofpatient management. This requires integrating imaging

modalities and incorporating the latest technologic advances. The radiologic community faces new challenges
regarding PH evaluation. One important objective of
this position paper is to share current imaging options
with PH clinicians for an optimal use of available resources. Whereas diagnosis and treatment are optimallyapproached in specialized centers, all radiologists canplay a more active role in the early recognition of thisdisease, helping to reduce the delay in diagnosis. To reachthese objectives, this position paper focuses on a seriesof questions relevant for both nonexpert and expert centers, emphasizing noninvasive imaging (eg, CT, MRI,and nuclear medicine) approaches in a target populationof adult patients with PH (Table 2). Specific attention
is directed toward imaging of chronic precapillary PH(groups 1, 3, 4, and 5). An expert center can be defined
as a center fulfilling the criteria of a PH referral center asThis copy is for personal use only. To order printed copies, contact reprints@rsna.org

Imaging of Pulmonary Hypertension in Adults

Abbreviations

Table 1: Updated Clinical Classification of PH

BPA = balloon pulmonary angioplasty, CTEPH = chronic thromboembolic PH, ILD = interstitial lung disease, PA = pulmonary artery, PAH= pulmonary arterial hypertension, PAP = pulmonary artery pressure,
PCH = pulmonary capillary hemangiomatosis, PEA = pulmonary endarterectomy, PH = pulmonary hypertension, PVOD = pulmonary venoocclusive disease, RV = right ventricle, V/Q = ventilation-perfusion

Classification

SummaryThis systematic review and position paper highlights the key roleof imaging in the recognition, work-up, treatment planning, andfollow-up of pulmonary hypertension.

Key Results
A mean pulmonary artery pressure of greater than 20 mm Hg defines pulmonary hypertension (PH).
n Pulmonary artery diameter is insufficient as a standalone criterion
for PH.
n Per current guidelines, ventilation-perfusion lung scan is the recommended investigation in patients with PH to rule out chronic
thromboembolic PH.
n Single-energy CT can provide diagnostic information on PH
etiology and should play a more important role in the diagnostic
strategy.
n Dual-energy CT combines morphologic information with lungperfusion (ie, iodine maps), which has the potential of increasing
CT diagnostic capabilities.
n Besides lifelong anticoagulation, pulmonary endarterectomy is thetreatment of choice in patients with proximal obstructing lesions;for inoperable cases, medical therapy with or without balloon pulmonary angioplasty is recommended.
n Cardiac MRI has become the reference standard to determine
right ventricular function in patients with PH of various etiologies; several MRI-derived variables, such as right ventricular ejection fraction, provide independent prognostic information.
n

per European Society of Cardiology and European Respiratory
Society guidelines (Table E1 in Appendix E1 [online]) (7).

Materials and Methods
A working group was formed from within the FleischnerSociety based on expertise in the imaging (M.R.J., M.L.S.,
A.N.C.L., J.M.W., M.M.H., P.O.A., L.R.G., J.M., L.B.H.,
Y.O., E.J.R.v.B., D.A.L., G.D.R.) and/or management of patients with PH (M.M.H., M.H., P.T.) as well as experience
with methodologies of systematic reviews (C.J.R.). A librarianalso was included (S.L.K.). The working group identified five
key questions that focused on the utility of CT, MRI, and nuclear medicine in the evaluation of PH (Appendix E2 [online]).
Overview of Modalities for Imaging PH
Noninvasive imaging modalities used in the assessment of patients with suspected or established PH are transthoracic Doppler echocardiography, chest radiography, CT, radionuclide ventilation-perfusion (V/Q) lung scintigraphy, and MRI. Table 2,
modified from Ascha et al (8), summarizes their relative strengths
and weaknesses. Transthoracic Doppler echocardiography—the
most widely used noninvasive screening tool in PH—will not
be reviewed in this position paper because it has been covered
in recent international guidelines and proceedings of the World
Symposium on PH (7,9).
2Group 1: PAH
1.1 Idiopathic PAH
1.2 Heritable PAH
1.3 Drug and toxin–induced PAH
1.4 PAH associated with:   1.4.1 Connective tissue disease   1.4.2 HIV infection   1.4.3 Portal hypertension   1.4.4 Congenital heart disease  1.4.5 Schistosomiasis
1.5 PAH long-term responders to calcium channel blockers
1.6 PAH with overt features of venous and capillary (PVOD/
PCH) involvement
1.7 Persistent PH of newborn syndrome
Group 2: PH due to left heart disease
2.1 PH due to heart failure with preserved LVEF
2.2 PH due to heart failure with reduced LVEF
2.3 Valvular heart disease
2.4 Congenital/acquired cardiovascular conditions leading topostcapillary PH
Group 3: PH due to lung diseases and/or hypoxia
3.1 Obstructive lung disease
3.2 Restrictive lung disease
3.3 Other lung disease with mixed restrictive/obstructive pattern
3.4 Hypoxia without lung disease
3.5 Developmental lung disorders
Group 4: PH due to pulmonary artery obstructions
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions
Group 5: PH with unclear and/or multifactorial mechanisms
5.1 Hematologic disorders
5.2 Systemic and metabolic disorders
5.3 Others
5.4 Complex congenital heart diseaseNote.—HIV = human immunodeficiency virus, LVEF = left
ventricular ejection fraction, PAH = pulmonary arterial hypertension, PCH = pulmonary capillary hemangiomatosis, PH =pulmonary hypertension, PVOD = pulmonary veno-occlusive
disease. Source.—Reference 1.

Whereas chest radiography is not specifically reviewed inthis article, its role in advanced PH deserves specific mention. In a majority of patients with idiopathic PAH, chest
radiography is abnormal at the time of diagnosis, showing
central pulmonary arterial dilatation that contrasts withpruning of peripheral blood vessels (7). Right atrium andright ventricle (RV) enlargement may be seen in more advanced cases (7). Chest radiography may assist in differential diagnosis of PH by showing signs suggesting lungdisease or pulmonary venous congestion due to left heartdisease. It may also help in distinguishing between arterial
and venous PH by respectively demonstrating increased anddecreased artery-to-vein ratio (7). Overall, the degree of PH
in any given patient does not correlate with the extent ofradiology.rsna.org n Radiology: Volume 00: Number 0— 2021

Remy-Jardin et al
Table 2: Relative Strengths and Weaknesses of Imaging Modalities in the Context of PH

Variable

SPECT/CT
V/Q

Single-energy
CT
Angiography*

Dual-energy CT
Angiography
MRI

Pulmonary
Angiography

2

2

1

1

1

2

2
2

1
2

111
11

111
11

2
111

2
2

1

1

111

1111

11

11

2
11

2
11

111
111

111
1111

111
11

2
11

Chest
Radiography V/Q Scan

PH detection
1
Evaluation of
anatomic
compartments
Lung
1
Cardiac1
chambers
Pulmonary
1vessels
Mediastinum 2
Assessment of
11
PH etiology
General strengths Readily
available

Planning ofNo radiation;
Assessment
Excellent
Screening for chronic Combined
endovascular
excellentof anatomy
evaluation
evaluation
thromboembolic
treatment
evaluation ofand lungof etiologies
of lung
PH; SPECT
cardiac function (PEA, BPA)
perfusionof PH
parenchyma(tomographic(iodine maps) and pulmonary
with lungV/Q) currently
flow in one
in a single
perfusion
replacing planar
examination
test
V/Q
Absence ofNeeds validation Limited in
LimitedLung
Weaknesses
Limited role Need further
perivascularevaluation
hemodynamic for all dualassessment
imaging toin thestructureof lungenergy CT
assessment;
limited;assessment assess the cause ofevaluation;
parenchyma;
technologies
limitedneeds moreof etiology PH; interpretiveinvasive test
not widely
evaluation
validation;
limitations inavailable; moreradiation dose of distal
patients withtechnical
pulmonary
added withcomorbid
expertisearteries
use of CT
conditions
needed(beyondsubsegmental
level)
2.2
2.6–3.5
2–5
3–5
None
10–30
Average effective 0.05
radiation
exposure(mSv)
Note.—Modified from reference 8. BPA = balloon pulmonary angioplasty, PEA = pulmonary endarterectomy, PH = pulmonary hypertension,
V/Q scan = ventilation-perfusion scintigraphy. 2 = no utility, 1 = limited utility, 11 = moderately useful, 111 = useful, 1111 = very
useful.
* Non–electrocardiogram-gated CT.

radiographic abnormalities. As for electrocardiography, anormal chest radiograph does not exclude PH (7).

Question No. 1: Is Noninvasive Imaging Capableof Identifying PH?
In patients with PH, increased PAP results in structural,functional, and hemodynamic changes assessable with imaging. Numerous CT (10–14) and MRI studies (15–18)
have shown that absolute or relative size of the PA can bedirectly correlated with PAP as measured with right heart
catheterization. However, the diagnostic performance ofstatic PA dimensions on routine chest CT studies to identify PH has yielded inconsistent results, with areas under
the receiver operating characteristic curve, or AUCs, ranging from 0.55–0.93 for PA diameter and 0.73–0.95 for PA
Radiology: Volume 00: Number 0— 2021 n radiology.rsna.org

diameter–to-aorta ratio (hereafter, PA ratio), respectively(10–13,19–22).
This variability likely reflects heterogeneity arising fromdifferences in diagnostic criteria and reference standards used
to establish the presence of PH, lack of standardization in
vascular measurement techniques and applied cutoff values,
and nonuniform patient selection practices resulting in study
populations that differed in chronicity and severity of PH.
Optimized selection of PA size cutoffs to discriminate between the presence or absence of PH would ideally incorporate knowledge of the distribution of values in the healthy
population. Older age, male sex, and higher body surface
area are each correlated with larger PA size and PA ratio decreases with increasing age (23,24). Moreover, the PA ratio
is not applicable in the case of aortic dilatation. Based on
3

Imaging of Pulmonary Hypertension in Adults
Table 3: Proposed Thresholds of PA Diameter for Suggesting Underlying PH according to the Clinical Context

Incidental Finding
CT Criteria

Populations with Low
Risk of PH*

Populations with Intermediate
Risk of PH†

Populations with High
Risk of PH‡

Suspected PH

PA diameter (mm)PA diameter–to-aorta ratio

.34
.1.1

.32
.1.0

.30
.0.9

Any size
Any value

Note.—Pulmonary artery (PA) measurements for diagnosis of pulmonary hypertension (PH) are unreliable in patients with congenital
heart disease including aortic or pulmonic valvular stenosis, arteriovenous malformations, connective tissue disorders such as Marfan
syndrome and Ehlers-Danlos syndrome, vasculitides such as Behçet disease and Takayasu arteritis, and idiopathic/mycotic/traumaticaneurysms or pseudoaneurysms.
* No known risk factors. Estimated risk of PH less than 1%.
†
Estimated risk of PH 1%–10%. Predisposing conditions include connective tissue disease (apart from systemic sclerosis), portal hypertension, prior pulmonary embolism, human immunodeficiency virus infection, thalassemia, schistosomiasis.
‡
Estimated risk of PH greater than 10%. Predisposing conditions include left heart disease, chronic obstructive pulmonary disease, interstitiallung disease, obstructive sleep apnea, systemic sclerosis, chronic kidney disease requiring dialysis, congenital heart disease, sickle cell disease.

measurements obtained from electrocardiogram-gated chest
CT scans in 706 healthy Americans, the 90th percentile cutoffs for normal PA diameter were 28.9 mm for men and 26.9mm for women; corresponding 90th percentile cutoff for PA
ratio was 0.91 for both sexes (23). Similarly derived 90th
percentile PA diameter and PA ratio cutoffs observed in 813
healthy Koreans were 31.3 mm and 1.05 for men and 29.6mm and 1.03 for women, respectively (24).
Both duration and severity of elevated PAP likely affect thedegree of associated PA dilatation (15). PA diameter is unreliable for detection of PH in diseases such as acute respiratory
distress syndrome in which the duration of PAP elevation isrelatively short (19). Chronic mild elevation of PAP, as typically occurs in PH due to lung diseases such as interstitial lungdisease (ILD) and chronic obstructive pulmonary disease, mayalso be difficult to accurately diagnose due to overlap in PA
size measurements between normal and these diseased populations (25–29). In a prospective study of 134 patients suspectedof having PH (30), PA diameter and PA ratio showed poor
(AUCs of 0.65 and 0.64) and fair (AUCs of 0.73 and 0.78)
performance in detection of PH in patients with and without
advanced ILD, respectively. Discriminatory performance ofvascular measurements in this prospective study of patientswith mild to moderate PH (mean PAP, 32.3 mm Hg in ILD
and 37.9 mm Hg in non-ILD PH groups) was notably inferior
to performance observed in a retrospective study of 489 patients with higher mean PAP (mean PAP of the whole cohort,
41 mm Hg; mean PAP of patients with ILD, 41 mm Hg; mean
PAP of non-ILD patients, 43 mm Hg) referred to a PH center(16). In this latter study, AUCs for PA diameter and PA ratio
were 0.87 and 0.80 in ILD group and 0.83 and 0.79 in nonILD group, respectively. Applied cutoffs of PA diameter greaterthan 29 mm and greater than 30 mm in ILD and non-ILD
groups yielded corresponding sensitivities of 75% and 76%
and specificities of 89% and 73%, respectively. The additionof ventricular measurements such as right and left ventricular diameter greater than or equal to 1.2 on contrast-enhanced
chest CT examinations may improve diagnostic performance,
particularly in patients with moderate to severe PH (21).
4

Truong et al (31) derived and validated a CT-based four-tierseverity classification system of PA diameter and PA ratio (eachmeasurement subdivided as normal, mild, moderate, and severe)for the diagnosis of PH, designed to maximize test sensitivity
and specificity at low and high cutoff values, respectively. Using sex-specific normal cutoffs for PA diameter in men (29mm) and women (27 mm) and a sex-neutral PA ratio (0.9),
sensitivities for the normal tier in the derivation cohort were99% and 93% with corresponding specificities of 57% and 65%
and negative predictive values of 96% and 86%, respectively. In
the most severe tier, PA diameter and PA ratio cutoff values ofgreater than 34 mm and greater than 1.1 yielded specificitiesof 98% and 100% with corresponding sensitivities of 65% and
50% and positive predictive values of 98% and 100%, respectively. It is important to recognize that these results, using cutoff
values from the four-tier classification system, were found in ahigh-risk, retrospectively enrolled population of 228 patients
who underwent evaluation for suspected PH at a tertiary care
medical center and were eventually found to have a high prevalence of disease (60%); those with PH had clearly elevated mean
PAP (45 mm Hg). Diagnostic accuracy of these PA size measurements at chest CT to diagnose PH in practice settings where
the prevalence and severity of disease is likely to be lower would
benefit from further validation in prospective studies. Table 3
shows an empirical guide to the potential relevance of a dilated
PA when found as an incidental finding with differing thresholds
according to the risk of PH. Figures E1 and E2 (online) illustrate
the need to integrate the clinical context in the interpretation of
PA diameter in clinical practice.
At MRI, dynamic PA size measurements (PA diameter, PA
ratio, PA area, and PA relative area change) show comparable
performance to CT-based measurements in diagnosis of PH with
AUCs ranging from 0.71–0.93 (15–18,32). Overall, diagnostic
performance of MRI is superior to that of non–electrocardiogram-gated CT due to its ability to assess and quantify additional
structural and functional cardiovascular metrics indicative of increased PAP and pulmonary vascular resistance. These include
interventricular septal angle, RV ejection fraction, ventricularmass index, and PA pulsatility, each of which has been reported
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Remy-Jardin et al

to show good to excellent discrimination (AUCs, 0.87–0.99)
between patients with and patients without PH (32–37). All ofthese measurements are also attainable with electrocardiogramgated CT, but their use for the assessment of PH has not beenstudied except in small cohorts (38). Quantitation of pulmonary
blood flow dynamics at MRI has also been reported to have diagnostic value (39–42); in a study of 233 patients suspected ofhaving PH (mean PAP, 45 mm Hg in PH subgroup), a simple
visual score of artifacts arising from abnormally slow pulmonary
blood flow imaged by using an electrocardiogram-gated spinecho double inversion-recovery “black blood” sequence outperformed PA diameter and PA ratio (AUC of 0.86 vs 0.81 and0.75) in diagnosis of PH (35). By using regression analysis, Johns
and colleagues (43) have developed and validated two multiparametric cardiac MRI models of similar performance (AUCs of
0.95 and 0.93) that included interventricular septal angle, ventricular mass index, and either extent of black blood slow flow(model 1) or diastolic PA area (model 2). Sensitivity, specificity,
positive predictive value, and negative predictive value of model
1 for diagnosis of PH in their validation cohort of 303 patientssuspected of having PH (disease prevalence, 85%; mean PAP, 42mm Hg) were 93%, 79%, 96%, and 67%, respectively. Practicalconsiderations for assessing PH in the clinic are detailed in Appendix E3 (online).

Question No. 2: What Is the Role of Imaging in
Establishing the Cause of PH?
In the stratification of potential causes of PH, V/Q lung scintigraphy plays a key role to screen for CTEPH while CT is a major
imaging tool, traditionally indicated for further evaluation of theunderlying cause of PH (7,9). This section provides an updated
approach to the technologic developments and current clinicalapproach to PH management in routine clinical practice.
V/Q Scintigraphy
Current guidelines state that a V/Q lung scan should be performed in patients with PH to rule out CTEPH (7,44). Other
than this one indication, V/Q lung scanning is rarely usefulin elucidating a cause of PH. The recognition of CTEPH isbased on approaches similar to those used for the detection of
acute pulmonary embolism, utilizing chest radiography withcombined V/Q lung scanning techniques. The identificationof lung segments and/or subsegments without perfusion but
preserved ventilation (ie, mismatch) is highly suggestive ofPE (45). In patients with PH and a clear chest radiograph, anormal-near normal V/Q lung scan virtually excludes CTEPH
with a sensitivity of 90%–100% and a specificity of 94%–
100% (46,47). The presence of mismatched perfusion defects
is compatible with CTEPH and requires further work-up in anexpert center (6,7,44) (Fig 1).
This importance of a definitive end point in PH requires
unequivocal lung scan interpretations. Recently, Stein et al (48)and Metter et al (49) studied lung scintigraphy for suspected
acute pulmonary embolism in general patient populations andadvocated for the replacement of probability-based V/Q lungscan interpretations with a more definitive approach, that is,normal, nondiagnostic or abnormal for PE. The same strategy
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is recommended in the diagnostic work-up of patients with PH.
Increased sensitivity for detecting acute pulmonary embolism
is provided by using SPECT perfusion lung scintigraphy compared with planar lung scintigraphy (50–52). The increased sensitivity for PE at SPECT is primarily related to the detection ofsmaller perfusion defects such as those caused by subsegmental
acute emboli. Indeterminate results are less frequent than withplanar scanning. A recent study (53) found SPECT perfusionscans to be more sensitive than planar V/Q scans in identifying
obstructed vascular segments in CTEPH. Mismatched perfusion defects similar to those seen in CTEPH have been reported
on V/Q SPECT scans in 10% of PAH and 7.1% of patientswith pulmonary venous and capillary hypertension (pulmonaryveno-occlusive disease [PVOD]/pulmonary capillary hemangiomatosis [PCH]) (54). In the majority of patients with PAH,
V/Q scintigraphy is normal or without significant abnormalities
and cannot help discriminating PVOD/PCH from idiopathic
PAH (55). When abnormal, the most frequent pattern in patients with PVOD/PCH is that of patchy perfusion defects withsimilar perfusion characteristics depicted on dual-energy CTlung perfusion images (56). SPECT lung scintigraphy was compared with contrast-enhanced perfusion MRI in a series of 74
patients with PH—30 of the patients had CTEPH and 10 had
chronic thromboembolic disease without PH (57). SPECT and
MRI showed virtually identical sensitivity (97% SPECT, 100%
MRI) for PE. The only patient missed with SPECT perfusion
scintigraphy had distal CTEPH. SPECT/CT has been widely
evaluated in the scintigraphic evaluation of PE but not extensively in the diagnostic approach of CTEPH.
It is worth noting that, if the perfusion agent (ie, technetiumlabeled particles of macroaggregates of human albumin, or Tc99m MAA) is detected beneath the diaphragm, this may signal
the presence of a right-to-left cardiac shunt. Plainly, intracardiac
shunts are an important cause of PAH. If cardiac defects have acomponent of right-to-left flow, some Tc-99m MAA particles
will bypass the lung and localize in other organs (eg, liver, kidneys, brain). More definitive diagnosis of such shunts is provided
by obtaining a lateral view of the cranium, which will show Tc99m intracerebral activity. Subdiaphragmatic Tc-99m MAA
activity also has been seen in patients with hepatic failure whohave macroscopic intrapulmonary shunts (hepatopulmonary
syndrome), in patients with congenital pulmonary arteriovenous
malformations (Osler-Weber-Rendu disease), and in patients
who have undergone cavopulmonary anastomotic surgery.
Role of Single-Energy CT
Fast scanning, excellent spatial and temporal resolution, andability to comprehensively evaluate the cardiopulmonary structures are some of the distinct features of CT. Depending on theclinical context, both noncontrast and contrast-enhanced CT
examinations can be considered. Noncontrast chest CT is a
powerful noninvasive test for all situations in which lung disease(eg, chronic obstructive pulmonary disease, ILD) is responsible
for the hemodynamic syndrome (ie, group 3 PH). Several systemic and metabolic disorders described in the subgroup of
PH with unclear and/or multifactorial mechanism (group 5)
can also benefit from a noncontrast chest CT examination,
5

Imaging of Pulmonary Hypertension in Adults

Figure 1: Ventilation-perfusion scintigraphy in a 78-year-old woman with normal chest radiograph referred for clinical suspicion of chronic thromboembolic pulmonary
hypertension (CTEPH). (a) Planar ventilation (81m krypton) and perfusion (99m Tc macroaggregate albumin) imaging shows multiple segmental and subsegmental defects innormally ventilated lungs, highly suggestive of CTEPH. (b) SPECT perfusion images provide detailed analysis of perfusion defects in coronal plane. ANT = anterior, LAO =left anterior oblique, LPO = left posterior oblique, POST = posterior, RAO = right anterior oblique, RPO = right posterior oblique.

such as sarcoidosis, pulmonary Langerhans cell histiocytosis,
and neurofibromatosis. Noncontrast CT examinations can also
show features depictable in group 1 PH. In PAH, pulmonary
microvasculopathy can lead to subtle changes at CT, including centrilobular micronodules, peripheral neovascularization,and lobular areas of ground-glass attenuation. The presence of
nodular ground-glass opacities, septal lines, and adenopathy is
6highly suggestive of PAH with overt features of venous andcapillary (PVOD/PCH) involvement (58,59) (Fig 2).
Contrast-enhanced chest CT is the second CT-based approach that can be used to elucidate the etiology of PH. Whilemorphologic changes depictable in PH etiologies previously
quoted can be similarly identified, the principal benefit ofcontrast-enhanced CT is for the detection of CTEPH (groupradiology.rsna.org n Radiology: Volume 00: Number 0— 2021

Remy-Jardin et al

Figure 2: Images show CT findings in patients with pulmonary hypertension due to presence of pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH). (a) Transverse CT section at level of right and left main bronchi from noncontrast examination in a 45-year-old woman shows centrilobular lung nodules
in both lungs with enlarged left hilum due to underlying lymphadenopathy. (b) Same examination as that shown in a. Transverse CT section obtained at level of lower lobes
shows bilateral centrilobular nodules seen and thin septal lines in right lower lobe. (c) Transverse CT section at level of lower lobes from noncontrast examination obtainedin a 51-year-old woman shows profuse nodular ground-glass opacities. (d) Transverse CT section at level of carina from chest CT angiographic study obtained in a
35-year-old woman shows mediastinal lymphadenopathy. (e) Transverse CT section at level of lower lobes from noncontrast examination in a 61-year-old woman before
treatment. Note presence of centrilobular nodules in both lungs. (f) Transverse CT section at same level as that shown in e (same patient); noncontrast chest CT examination
obtained 6 weeks after initiation of endothelin receptor antagonist shows CT features of pulmonary edema.

4), the diagnosis of which relies not only on the depictionof vascular signs of chronic obstruction of the PAs (Fig 3),
but also for diagnosing less common entities such as fibrosing mediastinitis (group 5) (Fig 4) and intracardiac shunts,
patent ductus arteriosus, and abnormal pulmonary venous
return that may be missed with echocardiography (group 1).
The absence of morphologic abnormalities at the level of cardiovascular structures and assessable PAs raises the possibilityof PAH (group 1 PH).
In the current guidelines (7), there is a distinction between CT
angiography and high-resolution CT (ie, noncontrast CT), theformer being indicated in the work-up of patients with CTEPH
and the latter recommended in all patients with PH. The guidelines acknowledge the important role for CT in patient management once the cause of PH has been recognized, but not in
the triage of patients between CTEPH and non-CTEPH. Thissituation reflects the long-standing influence of a study from Tunariu et al (46) in which the accuracy of an early multidetector
CT technology was compared with that of V/Q scanning. In
what is now considered suboptimal and outdated CT technology, CT angiography demonstrated high specificity (99.3%) but
low sensitivity (ie, 51.3%) for CTEPH. A recent meta-analysis (60) evaluated the diagnostic accuracy of CT for CTEPH,
which documented the limited diagnostic value of four- andeight-row multidetector CT technology compared with scanners ranging from 64-row multidetector CT to recent developments such as 320-row CT or dual-source CT (47,61,62). In theRadiology: Volume 00: Number 0— 2021 n radiology.rsna.org

latter category of equipment, the pooled sensitivity was 99% andthe specificity was 97%, leading the authors to conclude that
CT could become the standard for CTEPH screening. Besides
technologic considerations, a current limitation of CT angiography in the diagnostic approach to PH is based on the variable
expertise among radiologists in identifying the CT features ofchronic thromboembolic disease and accordingly, education andtraining are clearly needed in this area. As proposed in Table 4,
a structured examination for specific imaging findings can help
in the recognition of CTEPH. In a recent study investigating
the diagnosis of underlying CTEPH in association with acutepulmonary embolism, Ende-Verhaar et al (63) emphasized theimportance of decreased arterial diameter, intravascular webs,
and mosaic perfusion as well as dilated bronchial arteries.
Role of Dual-Energy CT Angiography
Dual-energy CT angiography offers additional diagnostic capabilities when compared with single-energy CT through thecreation of iodine maps, which have been considered surrogate markers of lung perfusion. In the clinical context of PH,
dual-energy CT lung perfusion has mainly been investigatedin CTEPH, showing good agreement with scintigraphy for thedetection of perfusion defects (64). Dual-energy CT–depicted
perfusion defects have also shown good correlation with hemodynamic estimates of PH severity (65,66). Recently, the diagnostic value of dual-energy CT perfusion has been comparedwith that of V/Q scintigraphy, with sensitivities and specifici7

Imaging of Pulmonary Hypertension in Adults

Figure 3: Images show chest CT angiography in a 25-year-old man with persistent dyspnea 1 year after bilateral acute pulmonary embolism (PE), suggestive of interim
development of chronic thromboembolic pulmonary hypertension. (a–c) Transverse CT sections and (d, e) maximum intensity projections in coronal oblique and (f) transversal views show numerous vascular features of chronic PE including partial filling defects (single white arrows and single black arrows), endoluminal band and web (whitearrowheads), and severely stenosed pulmonary arteries (black arrowheads). Presence of systemic collateral supply from enlarged bronchial arteries (double black arrowsin e) and inferior phrenic arteries (double white arrows in f). Reperfusion of left interlobar pulmonary artery beyond its obstruction (black arrowhead in e) by ipsilateral enlarged bronchial arteries.

Figure 4: Images show chest CT angiography in a 69-year-old woman with previous history of silicosis, responsible for fibrosing mediastinitis and subsequent development of pulmonary hypertension (PH) (group 5 PH). (a, b) Transverse CT sections and (c) coronal oblique reformation show severe stenosis of right and left interlobar pulmonary arteries (arrowheads) by silicotic hilar adenopathy. Diameter of both arterial sections does not exceed 5 mm, responsible for pulmonary hypertension with marked
dilatation of mediastinal pulmonary arteries.

ties ranging from 97% to 100% and 86%–92%, respectively(61,62) (Fig 5). Whereas excellent agreement between the two
imaging modalities has been reported at a patient level, intermodality agreement at the segmental level varies from modest
to moderate (61,62,64,67), owing to differences in their depiction of the distal pulmonary circulation. Perfusion scintigraphydemonstrates the distribution of labeled microspheres at thearteriolar level, while dual-energy CT perfusion captures a systemic phase of lung parenchymal enhancement as systemic-topulmonary shunts contribute to perfuse the arterial bed distal
8

to the occluded pulmonary arterial segment (68,69). Whenan analysis of iodine maps is combined with standard CT images of pulmonary arterial morphology, dual-energy CT has asensitivity and specificity of 100% for a diagnosis of CTEPH(61,62,70). These promising results require validation on alarger scale but reinforce the growing importance of modern
CT techniques in the diagnosis of CTEPH (71,72). Moreover,the patterns of lung perfusion demonstrated with dual-energy
CT can differentiate PAH from peripheral forms of CTEPH,
concordant with V/Q scintigraphy (56). Considerations on theradiology.rsna.org n Radiology: Volume 00: Number 0— 2021

Remy-Jardin et al
Table 4: CT Features of Acute and Chronic Obstruction of Pulmonary Arteries

CT Features
Mediastinal images
Partial filling defects
Complete filling defects
Arterial retraction
Reperfusion channels
Webs, bands
Focal stenosis
Enlarged bronchial arteries
Enlarged nonbronchial systemic arteries
Pleural abnormalities
Lung images
Lung infarction/sequelae
Bronchial dilatation
Mosaic perfusion

Acute PE

Chronic PE

Yes
Yes
…
…
…
…
…
…
Yes (effusion)

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

Yes (subpleural, wedge-shaped consolidation)…
…

Yes (nonspecific fibrotic infiltration/cysts)
Yes (adjacent to severely stenosed arteries)
Yes

Note.—PE = pulmonary embolism.

Figure 5: Images show dual-source dual-energy CT lung perfusion imaging in a 51-year-old woman with chronic thromboembolic pulmonary hypertension (CTEPH).
(a–d) Transverse CT sections and (e, f) coronal reformations of dual-energy CT lung perfusion images (window settings: 400 HU/40 HU) show multiple triangular perfusion defects of variable extent in both lungs, highly suggestive of pulmonary thromboembolic disease.

evolving role of CT in the diagnosis approach of PH etiology
are summarized in Appendix E4 (online).
Practical Considerations for Acquiring CT Angiograms in
Patients with PH
Chest CT angiography is routinely performed without electrocardiogram synchronization and consists of thin-section volumetric CT acquisitions. Short breath-hold (1–4 sec) acquisiRadiology: Volume 00: Number 0— 2021 n radiology.rsna.org

tion with the highest temporal resolution (ie, shortest rotationtime) avoids respiratory motion artifacts while minimizing cardiac motion artifacts. The entire thorax should be scanned witha single volumetric acquisition and reconstructed as contiguous thin sections (1 mm). Both lung and mediastinal images
should be reviewed.
The injection protocol is based on bolus tracking with
two options: (a) the traditional CT pulmonary angiographic
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Imaging of Pulmonary Hypertension in Adults

examination, with a region of interest positioned in the pulmonary trunk (threshold for triggering data acquisition, 120 HU);or (b) concurrent opacification of pulmonary and systemic circulations, with a region of interest positioned in the ascending
aorta (threshold, 100 HU). The volume and flow rate are similar to those selected for a standard chest CT angiographic examination (ie, 60 mL–80 mL at 4 mL/sec). When pulmonary
vascular resistance is known to be high, a decrease in flow rate(ie, 2 mL/sec instead of 4 mL/sec) is recommended owing to
the slow progression of the contrast material through the PAs.
In patients with high cardiac output, low-kilovoltage-peak scanning and high flow rate (ie, 4 mL/sec–6 mL/sec depending on
the patient venous access) are recommended to ensure adequate
vascular opacification.
The iodine concentration of the contrast material used usually ranges between 300 mg I/mL and 350 mg I/mL; it may be
increased to 370 mg I/mL–400 mg I/mL when scanning withdual-energy CT to ensure adequate opacification of lung microcirculation on the postprocessed iodine maps. Scan acquisition
during a systemic arterial phase (ie, region of interest within theascending aorta) may mask perfusion defects due to enhancement
via bronchial and/or nonbronchial systemic collaterals (68). Thisscanning condition may influence the pretherapeutic evaluationof perfusion defects, but it does not preclude adequate recognitionof pulmonary embolism–type defects on iodine maps (61,62,70).

Question No. 3: How Does Imaging Determine theSeverity and Complications of PH?
Assessment of RV Consequences of PH
During the development of PH, there are important changes
to the volume of the RV and the end-systolic and end-diastolicpressures. In the progressive march to cor pulmonale, the end
stage of this disease, the RV has a larger end-diastolic volume,the filling pressures increase, the wall thickness increases, thewall stiffness increases, there is more diastolic dysfunction, thepressures needed to open the pulmonary valve eventually become suprasystemic, and the interventricular septum becomesflattened and then bowed toward the left ventricular cavity;
this further limits filling of the left ventricle. Over time, theability of the RV to cope with both volume and pressure overload is exceeded. Cor pulmonale is a very difficult disorder that
results in rapid demise without aggressive management. Even
with maximal intravenous pulmonary arteriolar dilation therapies using phosphodiesterase inhibitors (eg, sildenafil), thedeadly nature of cor pulmonale is only temporarily improved.
The severity of PH in patients with PAH should be evaluated with a combination of clinical data, including exercise tests,
biochemical markers, imaging (echocardiography or MRI), andhemodynamic evaluations (7). Cardiac MRI is more accurate
than echocardiography for the assessment of RV morphology
and function and also allows measurement of stroke volume andcarbon monoxide. The following cardiac MRI–derived measures
are predictive of life expectancy after treatment for PH: RV endsystolic volume, RV end-diastolic volume index (pooled hazard
ratio, 1.06; 95% CI: 1.00, 1.12; P = .049), RV ejection fraction(pooled hazard ratio, 1.23; 95% CI: 1.07, 1.41; P = .003), stroke
10

volume index, RV end-systolic volume index (pooled hazard ratio, 1.05; 95% CI: 1.01, 1.09; P = .013), global longitudinalstrain rate, global circumferential strain rate, and left ventricular
end-diastolic index (pooled hazard ratio, 1.16; 95% CI: 1.00,
1.34; P = .045) (Table E2 in Appendix E1 [online]) (73–80).
There is variability in these measures partly due to the wide range
of individuals studied and a lack of grouping by disease severity.
Obviously, individuals with PH with very mild disease foundincidentally will differ markedly from those with severe longstanding PH.
Disease severity (mild, moderate, or severe) is linked withvarying levels of derangement in imaging biomarkers. T1 mapping of the myocardium may be uniquely characteristic in PH.
In a study of 490 consecutive patients, the T1 at the RV insertion point discriminated patients with PH from healthy individuals and was strongly correlated with the interventricularseptal angle (81).
Assessment of Small-Vessel Disease
Small-vessel disease or pulmonary microvasculopathy refers to
distal alterations in the pulmonary circulation in the presence ofPH. While idiopathic or heritable PAH is characterized by major
remodeling of precapillary PAs (,500 mm) with plexiform lesions, PVOD/PCH preferentially affects the pulmonary venules
and may be associated with pulmonary capillary dilatation andproliferation (2). In CTEPH, there is growing evidence that, in
addition to mechanical obstruction of proximal arteries, some patients develop a pulmonary microvasculopathy affecting the wallof distal muscular PAs out to arterioles and venules (82,83). Their
depiction in the pretherapeutic evaluation of CTEPH will be discussed in the following section entitled “Question No. 4: How
Should Imaging Be Used to Assess CTEPH before Treatment?”
In PAH, pulmonary microvasculopathy can lead to subtle
changes on CT images as previously described. V/Q scintigraphy will not demonstrate significant abnormalities and may benormal in the majority of patients with PAH. It cannot discriminate PVOD from idiopathic PAH (54). When abnormal, themost frequent pattern is patchy perfusion defects as also seen on
dual-energy CT lung perfusion images (56). Postprocessing of
the pulmonary arterial tree from digital angiograms, CT angiography, and MR angiography can be used to determine fractal geometry. As PH progresses, the pulmonary arterial tree simplifies,
and this simplification can be enumerated by using three-dimensional fractal geometry. When fractal dimension was computed
using three-dimensional box counting the distance metric (eg,the readout of vessel tortuosity), it was found to be correlatedwith mean PAP (Spearman r = 0.60) (84). Loss of distal small PA
sizes relative to the main PAs is a sign of vessel pruning.
What Are the Complications of Marked PA Enlargement inPatients with PH?
Enlargement of the PA in patients with PAH may compress theleft main or left anterior descending coronary arteries resulting indecreased coronary blood flow (Fig 6). In a study of 765 patientswith PAH (85), 121 had angina or anginalike symptoms and 94
patients had abnormal CT angiography based on the relationship between the PA and the left main coronary artery. Left mainradiology.rsna.org n Radiology: Volume 00: Number 0— 2021

Remy-Jardin et al

coronary artery stenosis greaterthan or equal to 50% was detected in 48 of 94 patients. The
best predictor of left main coronary artery stenosis greater thanor equal to 50% was a PA diameter greater than or equal to 40
mm. When it occurs, left main
coronary artery compression isa very serious issue for patientswith PAH. The treatment planused will vary depending on
the local expertise. The options
include the following: stentplacement, cardiac surgery withbypass grafting, medical management to significantly lower
the PAPs, and occasionally lungtransplantation. Any surgery
must be carefully considered
due to the increased operative
Figure 6: Images show long-standing pulmonary arterial hypertension from connective tissue disease (scleroderma) withmortality in patients with PH.
compression of left main coronary artery. (a) Multiplanar reformation of left main coronary artery origin from left sinus of
There is no single treatment opValsalva shows compression (arrow) by massive pulmonary artery (PA). (b) Volume-rendered coronary CT angiographyshows enlarged pulmonary trunk (PA) and very small left main coronary artery (arrow). Ao = aorta.
tion that always works for thiscritical issue.
Dissection of the main PA is rare but associated with highmortality. In a recent systematic review (86) of 150 cases reported since 1842, the average age at diagnosis was 45 years witha slight male predominance (1.1:1). The most common clinicalpresentation of PA dissection was dyspnea with chest pain. The
reported causes were PH, congenital heart disease (overcirculation lesions such as a patent ductus arteriosus), and acquired
heart diseases. The pulmonary trunk was the site of dissection in
73% of cases. The most severe complication of PA dissection was
cardiac tamponade from hemopericardium and was observed at
autopsy in 84.2% of cases (86).

Question No. 4: How Should Imaging Be Used toAssess CTEPH before Treatment?
Context
In 0.6% to 4.4% of acute pulmonary embolism, abnormal
persistent obstruction of PAs by residual organized thrombi,
combined with a variable degree of microscopic vasculopathy, may lead to CTEPH (6,44,63,82). If left untreated, then
CTEPH leads to right-heart failure and premature death (6,7).
The CTEPH medical arsenal has progressed markedly in recent
years. As stated in the proceedings of the 6th World Symposium on PH, CTEPH management is a fast-growing field of
pulmonary vascular medicine where multimodal, individualized approach to treatment at expert centers with multidisciplinary teams is mandatory (6,7).
Current CTEPH Management
The CTEPH treatment algorithm has been recently proposedby a task force of the 6th World Symposium on PH (6) (Fig 7).
CTEPH treatment decisions in an expert center involve multiRadiology: Volume 00: Number 0— 2021 n radiology.rsna.org

Figure 7: Flowchart shows revised treatment algorithm for management ofpatients with chronic thromboembolic pulmonary hypertension (CTEPH). # =multidisciplinary (pulmonary endarterectomy surgeon, pulmonary hypertension
expert, balloon pulmonary angioplasty [BPA] interventionist, and radiologist), ¶ =treatment assessment may differ depending on level of expertise, ‡ = BPA without
medical therapy can be considered in selected cases. (Reprinted, with permission,from reference 6).

disciplinary teams including experienced surgeons for pulmonary endarterectomy (PEA), interventional radiologists/cardiologists for balloon pulmonary angioplasty (BPA), radiologists
experienced in pulmonary vascular imaging, and pulmonologists/cardiologists with expertise in PH (6). Besides indefinite
anticoagulation, PEA is the treatment of choice in patients
who are deemed operative candidates by having obstructing
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Imaging of Pulmonary Hypertension in Adults

Figure 8: Images show updated University of California San Diego chronic thromboembolic pulmonary hypertension (CTEPH) surgical classifications. This figure illustrates location of organized thromboembolic material within pulmonary arteries conditioning their surgical accessibility: levels 1–3
are accessible lesions and level 4 disease is nonoperable. A, Level 1 disease involves one or both main pulmonary arteries. B, Level 2 disease begins
at lobar branches or past the takeoff of upper lobe artery. C, Level 3 disease starts at segmental vessels. D, Level 4 disease begins at subsegmental
vessels.

lesions in the main, lobar, segmental, and subsegmental arteries (6,7). However, around half of patients with CTEPH withpulmonary vascular resistance out of proportion to degree ofvascular obstruction at imaging may manifest severe distal microvasculopathy and are deemed ineligible for operation (6).
For technically inoperable cases, PH medical therapy is recommended with or without BPA (6). Oral riociguat (a guanylate
cyclase stimulator) and subcutaneous treprostinil are currently
the only drugs approved for inoperable CTEPH (6,7).
PEA Operability Assessment
Defining the anatomic distribution of CTEPH lesions is essential in this therapeutic approach and certain features are more
likely to predict a good surgical outcome (6). The most important surgical advance has been in redefining the distal limitsof endarterectomy (87,88). However, it is important to stressthat there is inevitable variation between surgical centers withregard to the suitability of PEA operability (89). Criteria forinoperability usually include distal PA obstructions, imbalance
between increased pulmonary vascular resistance and the number of accessible occlusions suggesting microvascular disease, apulmonary vascular resistance greater than 1500 dyn∙sec∙cm–5,
12

and comorbidity (6). CTEPH lesion type and location can beclassified according to the updated University of California San
Diego CTEPH surgical classification, which includes the following four levels (Fig 8): level 0 (no evidence of thromboembolic disease in either lung), level I (lesions starting in the main
PAs with level IC corresponding to complete occlusion of one
main PA), level II (lesions starting at the level of lobar arteries
or in the main descending PAs), level III (lesions starting at thelevel of the segmental arteries), and level IV (lesions starting at
the level of the subsegmental arteries) (87).
Once the diagnosis of CTEPH is confirmed, CT angiography
can be used for assessment of operability (6) (Figs 9, 10). CT canprovide a vascular roadmap for surgical planning and is the bestmodality for delineation of the proximal extent of the organizedthromboembolic material, with good PEA plane correlation (87).
However, it must be emphasized that the use of CT for estimationof surgical suitability requires considerable imaging expertise andis usually best performed by high-volume and experienced institutions (6,7,90). There is a large knowledge gap within the imaging
community in the interpretation of CT in CTEPH due to the relative rarity of disease in the general population (6). The scanning
protocol follows the recommendations for chest CT angiography.
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Remy-Jardin et al

Figure 9: (a–f) Images show CT angiography and pulmonary angiographic evaluation prior to pulmonary endarterectomy in a 57-year-old patient with central andperipheral chronic thromboembolic pulmonary hypertension (CTEPH). Sagittal views of right (a, b) and left (c, d) pulmonary arteries on CT images and corresponding pulmonary angiograms show numerous vascular features of CTEPH on central and peripheral arteries. In right lung, arrows point to stenosis and poststenosis dilatation, webs,
and vessel pruning; in left lung, arrowheads point to a large mural defect and endoluminal webs below. Maximum intensity projections (coronal plane) illustrate bilateral
CTEPH vascular lesions at pulmonary arterial phase (e; arrows point to stenosis and poststenosis dilatation, webs and endoluminal defect) and dilated right-sided bronchialarteries at later phase of data acquisition (arrows, f).

Analysis of PAs requires combined use of cross-sectional imaging
and multiplanar reformations to improve detection of thin webs
and bands, focal stenoses, and the display of subsegmental vessels. Digital subtraction angiography, previously considered as thereference standard, has been largely replaced with noninvasive
modalities. With advances in distal PEA, the advent of BPA, anda general focus on more distal vascular assessment, conventional
digital subtraction angiography may not always be suitable for fineanatomic analysis. For such purposes, selective segmental angiography, cone-beam CT, and electrocardiogram-gated CT may also
be considered for precise delineation of distal pulmonary vessels(90,91).
There is often no clear correlation between the degree of mechanical obstruction found at imaging and the severity of hemodynamic compromise measured with right heart catheterization(6). This discrepancy is due to the degree of remodeling affecting
Radiology: Volume 00: Number 0— 2021 n radiology.rsna.org

small pulmonary vessels (82). Identifying small pulmonary vascular disease prior to intervention is of major importance because it translates into more severe disease and worse outcomes.
Patients with inoperable CTEPH with marked small pulmonary
vascular disease are candidates for medical therapy with or without BPA (6).
The development of hypertrophied bronchial arteries
is a well-known feature of CTEPH, reflecting collaterals
between the systemic and pulmonary arterial circulation(6,82,83,92). Anastomoses exist between bronchial arteries
and precapillary pulmonary arterioles but also between postcapillary venules and small veins (82). Collateral anastomoses from the systemic circulation have an important role inmaintaining perfusion and viability of the ischemic pulmonary parenchyma downstream of proximal PA obstructions.
Some authors have proposed that distal thrombosis can be
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Imaging of Pulmonary Hypertension in Adults

Figure 10: (a–c) Images show CT angiography and pulmonary angiographic evaluation in a 28-year-old patient with peripheral chronic thromboembolic pulmonary
hypertension. Maximum intensity projection (coronal plane) (a) and corresponding right (b) and left (c) anteroposterior views of digital pulmonary angiographic study.
Presence of vessel pruning and poor distal perfusion (dotted circles) on peripheral pulmonary arteries on CT angiographic reformat and corresponding perfusion defects(dotted circles) on angiographic views.

of CTEPH was significantly greater than in the distal type.
Poor subpleural perfusion in the capillary phase of digital
subtraction angiography predicts worse outcomes following
PEA in operable CTEPH (93). Poor subpleural perfusion
is defined as less than or equal to 1.5 cm (approximately
one rib width) from the lateral pleura in the capillary phaseof digital subtraction angiography on the posterior-anterior
views and by lateral views of the dorsal area (Fig 11). In
such cases, V/Q lung scanning also shows reduced subpleural perfusion with a preserved ventilation (94).

Figure 11: Image shows digital subtraction pulmonary angiography (right-sided injection) performed in a 55-year-old woman
with inoperable chronic thromboembolic pulmonary hypertension.
On this anteroposterior view obtained at capillary phase of angiographic study, note poor subpleural perfusion (arrows).

diffuse when bronchial arteries and anastomoses fail to develop, jeopardizing patency of the small pulmonary arterioles (83). Shimizu and colleagues (92) have reported thatthe cross-sectional area of bronchial arteries correlated withthe central extent of the thromboembolic material fromanalysis of the CT angiography in patients with CTEPH. In
that study, bronchial artery total area in the proximal type14

BPA Assessment
BPA is an alternative therapy for patients with inoperable
CTEPH (95,96). Kawakami and colleagues (91) have recently
reviewed 500 consecutive procedures (1936 lesions) of BPA in
97 patients with CTEPH. The lesion distribution and characteristics evaluated were as follows: type A, ringlike stenosis
lesion; type B, web lesion; type C, subtotal lesion; type D,
total occlusion lesion; and type E, tortuous lesion. The success rate was higher, and the complication rate was lower, in
ringlike stenosis and web lesions. The total occlusion lesions
had the lowest success rate. Tortuous lesions were associatedwith a high complication rate. Optical coherence tomography
may be helpful to better characterize endovascular lesions incases where the diagnosis is unclear. However, experts in BPA
rarely use this technique because of the need for high contrast
agent volume and the concern for renal toxicity, as well as therequirement for forceful injection that may increase perfusionpressure in the peripheral pulmonary vasculature and cause
pulmonary injury (97).
Poor subpleural perfusion in the capillary phase of pulmonary angiography, suggesting the presence of small vessel disease
with diffuse distal thrombosis, is a predictor of BPA failure (94).
Taniguchi et al (94) showed that in patients with inoperable
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Remy-Jardin et al

CTEPH, bronchial artery total area in the normally perfusedgroup was larger than that of the poorly perfused group. Poorly
developed bronchial arteries might be involved in the development of diffuse distal thrombosis in patients with CTEPH (83).

Question No. 5: Should Imaging Be Performed after Treatment of PH?
CTEPH after PEA or BPA
The main goals of all treatment modalities for CTEPH, especially PEA and BPA, are to improve symptoms (ideally toa stage where the patient has recovered from CTEPH-related
physical limitations) and to improve pulmonary hemodynamics with the ambition to normalize or near-normalize pulmonary hemodynamics at rest. Hence, the initial focus of the
postprocedural assessment in patients who underwent PEA or
BPA is their exercise capacity (eg, 6-minute walk test), hemodynamics at rest, and RV function. After PEA surgery, a reduction of the PA pressure to less than or equal to 25 mm Hg atrest is achieved in about 50% of patients; another 30% achievenearly normalized pulmonary hemodynamics with mean PA
pressures between 25 mm Hg and 30 mm Hg (98). For BPA,
large-scale long-term data are not yet available, but the proportion of patients attaining normal or near-normal pulmonary
hemodynamics at rest is lower than with PEA surgery (95,
99–101). However, BPA results improve after an initial learning curve (96). Moreover, recent data indicate that the different
treatment options are likely to be complementary; combining
treatment options leads to marked pulmonary vascular resistance reduction, as recently demonstrated in the Riociguat versus Balloon Pulmonary Angioplasty in Nonoperable Chronic
Thromboembolic Pulmonary Hypertension, or RACE, study
showing added benefit of BPA on top of initial riociguat therapy and vice versa (102).
Normalization or near-normalization of pulmonary hemodynamics after PEA or BPA is usually accompanied by substantial
symptomatic improvement. In patients for whom these treatment goals have been met, there is usually no clinical need forfollow-up imaging, except for echocardiography. For patients
who remain symptomatic or have residual PH or both after
PEA, imaging is required to determine further treatment options, such as BPA in those patients with residual peripheral
CTEPH after PEA (103). Conventional digital subtraction angiography remains the most widely used imaging tool to triage
patients to a repeat PEA or BPA after their first intervention for
CTEPH. However, novel imaging tools such as cone-beam CT
may provide more detailed information on vessel structure andobstructive lesions (104–106). Two-dimensional digital subtraction angiography allows quantification of regional lung iodine
concentrations before and after BPA (107).
Besides these clinical considerations, there is an abundant literature on the CT and MRI evaluation of pulmonary perfusion,
blood flow, and magnitude of residual pulmonary vascular disease
after PEA or BPA.
Phase-contrast MRI has been used to demonstrate changes
in blood flow in the PA before and after BPA (108). Perfusion
scintigraphy can be used to detect residual perfusion defects
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after PEA or BPA but is insufficient to guide further treatment.
SPECT lung scintigraphy has been described to assess regionallung perfusion changes after BPA (108). Dual-energy CT may
give more detailed information and a higher spatial resolution
than does SPECT, providing information on vessel morphology
at the same time. In preliminary studies from Japan, assessmentof regional lung blood volume before and after BPA with dualenergy CT was found to be more reliable than SPECT imaging (109,110). Automated quantification of regional lung blood
volume determined with dual-energy CT may also be an option
to evaluate changes in regional blood flow and show any new orresidual defects in the blood volume (iodine) maps (111). Dynamic contrast-enhanced MRI perfusion imaging can provide
qualitative and semiquantitative assessment of pulmonary perfusion and shows promise for quantitative mapping of pulmonary perfusion in CTEPH (112). Dynamic contrast-enhanced
perfusion methods have been used to demonstrate improvement
in regional perfusion parameters, regional blood flow, regional
blood volume, and mean pulmonary transit time in patientswith CTEPH undergoing BPA (113). When coupled with gas
ventilation MRI, delayed contrast enhancement perfusion MRI
has also been used to assess improvement in lung V/Q matching
before and after PEA in CTEPH (114).
After successful PEA, cine MRI can demonstrate normalization of right and left ventricular end-systolic and end-diastolicvolumes, re-establishment of interventricular synchrony, a returnof the “leftward” ventricular septal bowing, and a decrease in the
RV mass (115–117). Serial MRI studies have shown that reverse
cardiac remodeling occurs within the first 4 weeks after PEA withfew changes at 3 months and 6 months after surgery (118). Morerecently, Maschke et al (119) demonstrated with MRI that global
RV function and right and left ventricle synchronization improved
after PEA, but that there were regional differences in the recoveryof circumferential and radial function. The clinical implications ofthese findings remain unknown.
By using serial MRI after BPA, Sato et al (120) have shown
improvement of right and left ventricular ejection fraction. In another study by Fukui et al (117), MRI-derived RV function wasmarkedly improved after BPA whereas left ventricular function
was largely unchanged. The decline in RV end-systolic and enddiastolic volume was tightly correlated with the decline in pulmonary vascular resistance measured by using right heart catheterization (r = 0.74 and r = 0.72, respectively; P , .001 for both), again
showing that improved RV function follows afterload reduction.
Cardiac MRI has also been used to demonstrate improved ventricular synchrony and an increase in the interventricular septal
myocardial T1 values (a return to native myocardial T1 values)
after BPA (121,122).
After BPA, MRI studies combining regional pulmonary parenchymal perfusion measurements and cardiac MRI showed
improved pulmonary blood flow in the treated lobes and to alesser degree in the nontreated lobes, correlating with changes
in hemodynamics as well as in the ventricular mass index (113).
Cardiac MRI studies have also been used to predict which patients will recover exercise capacity after PEA in CTEPH. Exercise is limited in those patients with an impaired stroke volume
response at MRI (123).
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Imaging of Pulmonary Hypertension in Adults

Patients with PAH and CTEPH Undergoing Medical
Treatments
Imaging as part of the follow-up assessment of patients with
PAH or CTEPH receiving medical therapy currently focuseslargely on the heart. Transthoracic echocardiography is themost widely used imaging tool in clinical practice, but is not
the focus of this article. MRI is often considered the reference
standard for cardiac imaging because it provides high-resolution three-dimensional imaging and allows reliable quantification of chamber volumes, muscle mass, and blood flows as well
as functional assessment of the heart (124). Neither scintigraphy nor CT has a currently established role in the routine
follow-up assessment of patients undergoing medical therapy
for PAH or CTEPH. Hence, this section will focus on the useof MRI as follow-up tool in patients with PAH or CTEPH
undergoing medical therapy. This section was not supported bya dedicated systematic review of the literature.
Several MRI measurements can be used to determine RV
function. Serial cardiac-gated contiguous breath-hold short-axis
balanced steady-state free precession cine images are postprocessed to calculate end-diastolic and end-systolic chamber volumes (125). Of note, the RV stroke volume is the sum of bloodejected into the pulmonary circulation and the amount of tricuspid valve regurgitation. Effective pulmonary blood flow (andthereby, effective stroke volume) can be determined after postprocessing of two-dimensional phase contrast images obtainedat the level of the pulmonary valve and/or four-dimensional flow
images.
MRI has been used to determine cardiac function in patients undergoing treatment for PAH (126). At baseline, MRI
volumetry–derived RV stroke volume indexed to body surface
area, RV ejection fraction, and RV end-diastolic volume index
are independent predictors of survival in patients with PAH(74,75,127). The same was found for the RV end-diastolic volume index when corrected for age, sex, and body surface area,and for PA stiffness (80,128). During follow-up, a decline in
RV stroke volume index as well as increases in RV volumes
and decreased left ventricular filling were associated with a highmortality risk (74). Notably, changes in RV ejection fraction
were more predictive of outcome than were changes in pulmonary vascular resistance assessed with right heart catheterization (75). Serial MRI has shown that during the initial periodof RV failure, there is a parallel decline in longitudinal andcircumferential RV strain; over time, the deterioration in longitudinal strain eventually stopped while circumferential strain
continued to decline. This was worsened by the progressive leftward displacement of the interventricular septum (116). MRI
has also been used to demonstrate increased PA stiffness andreduced RV and PA coupling in patients with PH, measurements that may be useful during follow-up assessments as well(129–131). According to a meta-analysis of articles publishedin April 2015 (78), the strongest MRI-derived predictors ofoutcome were RV ejection fraction (pooled hazard ratio, 1.23;
95% CI: 1.07, 1.41; P = .003), RV end-diastolic volume index(pooled hazard ratio, 1.06; 95% CI: 1.00, 1.12; P = .049),
RV end-systolic volume index (pooled hazard ratio, 1.05; 95%
CI: 1.01, 1.09; P = .013), and left ventricular end-diastolic
16

volume index (pooled hazard ratio, 1.16; 95% CI: 1.00, 1.34;
P = .045). RV and left ventricle mass were not associated withoutcome (78).
Although some studies have attempted to estimate mean PAP
and pulmonary vascular resistance with MRI (132,133), MRIderived pressure estimates are still not sufficiently reliable for thefollow-up assessment of patients treated for PH. Smaller clinical
trials have used MRI-derived end points such as RV mass and RVejection fraction (134–136) but MRI has not yet been used inlarge multicenter studies, mainly for logistical reasons and for thesimple fact that regulatory agencies have not yet approved drugs
based on MRI-derived variables. Patients with PVOD/PCH usually have a poor response to PAH therapy and the use of PAH
drugs can be associated with a potential risk of life-threatening
pulmonary edema (137,138) (Figs 2e and 2f).

Conclusion
The last decade has shown the importance of noninvasive imaging
in the diagnostic approach of pulmonary hypertension (PH), theprognostic classification, and treatment monitoring. Besides thisimportant role acknowledged by current guidelines and practiceacross centers, imaging modalities continue to evolve, and artificial
intelligence has entered the field of medical imaging. Appendix E5(online) provides an overview of emerging techniques and/or approaches that could push back some current limitations of imaging and open new areas of applications in PH management. Several clinically relevant areas are highlighted. Appendix E6 (online)
summarizes the key messages of each section of this article. The
working group followed the search strategy detailed in Appendix
E7 (Tables E3–E15) and in Figure E3 (all online).
Author contributions: Guarantors of integrity of entire study, M.R.J., Y.O., M.H.;
study concepts/study design or data acquisition or data analysis/interpretation, allauthors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors;agrees to ensure any questions related to the work are appropriately resolved, allauthors; literature research, all authors; clinical studies, L.R.G., G.D.R.; statisticalanalysis, C.J.R., P.O.A., L.R.G., P.T.; and manuscript editing, all authors
Disclosures of Conflicts of Interest: M.R.J. Activities related to the present article:

disclosed no relevant relationships. Activities not related to the present article: received
payment for lectures including service on speakers bureaus from Siemens Healthineers,
Boehringer Ingelheim, Roche, and MSD. Other relationships: disclosed no relevant
relationships. C.J.R. disclosed no relevant relationships. M.L.S. disclosed no relevant
relationships. A.N.C.L. disclosed no relevant relationships. J.M.W. disclosed no relevant
relationships. M.M.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is board member and consultant
for Acceleron, Actelion, Bayer, Janssen, MSD, and Pfizer; received payment for lectures
including service on speakers bureaus from Acceleron, Actelion, Bayer, Janssen, MSD,
and Pfizer. Other relationships: disclosed no relevant relationships. P.O.A. disclosed no
relevant relationships. L.R.G. disclosed no relevant relationships. J.M. Activities related
to the present article: disclosed no relevant relationships. Activities not related to thepresent article: received payment for lectures including service on speakers bureaus from
Siemens Healthineers Canada. Other relationships: disclosed no relevant relationships.
L.B.H. disclosed no relevant relationships. Y.O. Activities related to the present article:
received research grant from Canon Medical Systems. Activities not related to the present article: has grants/grants pending with Bayer Pharma. Other relationships: received
Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; received research grant from Smoking Research
Foundation; received research grant from Daiichi Sankyo. P.T. 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: is board member of Aidence,
Imbio, and QCTIS; is a consultant for InHealth and Mentholatum. Other relationships: is owner and founder of QCTIS; author and spouse are directors. S.L.K. disclosed no relevant relationships. D.A.L. Activities related to the present article: disclosed
no relevant relationships. Activities not related to the present article: is a consultant forradiology.rsna.org n Radiology: Volume 00: Number 0— 2021

Remy-Jardin et al
Parexel Imaging, Boehringer Ingelheim, Veracyte, Daiichi Sankyo, and Astra-Zeneca;
received payment for lectures including service on speakers bureaus from Boehringer
Ingelheim. Other relationships: disclosed no relevant relationships. G.D.R. disclosed
no relevant relationships. M.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a board member andconsultant for Acceleron, Actelion, Bayer, GSK, and Merck; has grants/grants pending
with Acceleron, Actelion, and Bayer; received payment for lectures including service on
speakers bureaus from Actelion, Bayer, GSK, and Merck. Other relationships: disclosed
no relevant relationships.

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