European Journal of Radiology 86 (2017) 335–342

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Management of COPD: Is there a role for quantitative imaging?

Miranda Kirby (PhD) a,b , Edwin J.R. van Beek (MD PhD) c , Joon Beom Seo (MD PhD) d ,
Juergen Biederer (MD) e,f,g , Yasutaka Nakano (MD PhD) h , Harvey O. Coxson (PhD) a,b ,
Grace Parraga (PhD) i,j,∗
a
Department of Radiology, University of British Columbia, Vancouver, Canada
b
UBC James Hogg Research Center & The Institute of Heart and Lung Health, St. Paul’s Hospital, Vancouver, Canada
c
Clinical Research Imaging Centre, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
d
Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Republic of Korea
e
Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Germany
f
Translational Lung Research Center Heidelberg (TLRC), Member of the German Lung Research Center (DZL), Germany
g
Radiologie Darmstadt, Gross-Gerau County Hospital, Germany
h
Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan
i
Robarts Research Institute, The University of Western Ontario, London, Canada
j
Department of Medical Biophysics, The University of Western Ontario, London, Canada

a r t i c l e i n f o a b s t r a c t

Article history: While the recent development of quantitative imaging methods have led to their increased use in the
Received 7 August 2016 diagnosis and management of many chronic diseases, medical imaging still plays a limited role in the
Accepted 26 August 2016 management of chronic obstructive pulmonary disease (COPD). In this review we highlight three pul-
monary imaging modalities: computed tomography (CT), magnetic resonance imaging (MRI) and optical
Keywords: coherence tomography (OCT) imaging and the COPD biomarkers that may be helpful for managing COPD
COPD
patients. We discussed the current role imaging plays in COPD management as well as the potential
Imaging
role quantitative imaging will play by identifying imaging phenotypes to enable more effective COPD
Computed tomography
Magnetic resonance imaging
management and improved outcomes.
Optical coherence tomography © 2016 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
International clinical guidelines reinforce the overwhelming
opinion that chronic obstructive pulmonary disease (COPD) is a
manageable and treatable disease for patients with all grades of
disease severity [1]. This is a very hopeful and optimistic notion
given that smoking cessation is the most effective intervention
for managing COPD to-date, and the only intervention yet shown
to slow the rate of lung function decline [2,3]. While it has been
reported that pharmacological therapy can improve lung func-
tion and reduce COPD symptoms [4], COPD exacerbations and
hospitalizations [5,6], the effects are not strong and therapeutic
developments still lag behind other major chronic illnesses. Pal-
liative treatments such as oxygen therapy [7] and lung volume
reduction either surgically [8] or using interventional broncho-
scopic valve placement [9] also independently offer a survival
∗ Corresponding author at: Robarts Research Institute, 1151 Richmond St N, Lon-
don, N6A 5B7, Canada.
E-mail address: gparraga@robarts.ca (G. Parraga).
advantage for some patients with very severe disease. Despite
the modest efficacy reported using existing management strate-
gies, COPD hospitalization and mortality rates continue to rise,
most strikingly in women [10], and health economists warn that
this upward trend will continue and very soon overwhelm our
healthcare systems [11]. In light of this dire situation, new COPD
management strategies are being actively pursued and investigated
to combat this growing public health emergency.
With precision medicine methods on the horizon for all patients
with chronic disease, there is a renewed optimism for the possibil-
ity of finding new ways to reduce the burden of COPD. Precision
medicine depends on a deeper understanding of the individual
patient’s genetic background and the gene-environment interac-
tions that lead to specific underlying biological processes – the
disease “endotype” (i.e. inflammation). By understanding how
these distinct underlying biological processes manifest in the indi-
vidual patient – the disease “phenotype” (i.e. emphysema) – it
is thought that precision medicine will enable the “right” treat-
ment to be provided to the right patient at the right time. A better
understanding of underlying disease endotypes will not only allow
for better patient management, but will also open doors for the

http://dx.doi.org/10.1016/j.ejrad.2016.08.022
0720-048X/© 2016 Elsevier Ireland Ltd. All rights reserved.
336 M. Kirby et al. / European Journal of Radiology 86 (2017) 335–342
discovery of new drugs/interventions and clinical trials that tar-
get the underlying pathologies embodied by chronic lung disease.
Furthermore, linking the endotype to the phenotype will enable
the identification and stratification of patients with certain dis-
ease features for clinical trials of targeted treatments, as well as
evaluation of treatment efficacy. In light of this, there is renewed
interest in the development and evaluation of the COPD phenotype
measurements. In patients with COPD, such phenotype measure-
ments currently include clinical and functional biomarkers as well
as recently discovered pulmonary imaging biomarkers.
The technical development, clinical and commercial translation
of medical imaging technologies and the more recent development
of quantitative imaging methods, have led to their increased use in
the diagnosis and management of many chronic diseases. Until very
recently however, for patients with COPD, medical imaging has not
played a major role outside the setting of acute complications or
lung cancer diagnosis. Therefore, in this review we highlight three
pulmonary imaging modalities: computed tomography (CT), mag-
netic resonance imaging (MRI) and optical coherence tomography
(OCT) imaging and the COPD biomarkers that may be helpful for
managing COPD patients. By summarizing how imaging is currently
used in COPD patient management and its potential to play a larger
role in COPD phenotyping and treatment decisions, we endeavour
to answer the question: Is there a role for quantitative imaging in
patients with COPD?
2. X-ray computed tomography measurements and
biomarkers of COPD
For over a decade, the clinical standard for COPD patient imag-
ing has been high resolution x-ray computed tomography (CT).
Pulmonary CT enables the direct and regional quantification of a
number of COPD pathologic features and biomarkers that are rele-
vant to the evaluation and management of COPD patients.
2.1. Parenchyma microstructure: emphysema
Regional tissue destruction or emphysema is very common in
COPD patients and appear as regions of low attenuation on CT
images acquired at suspended full-inspiration. To quantify low
attenuating regions, the most commonly used approaches make
use of the histogram of all CT densitometry values in the lung and
a CT density threshold cut-off or a percentile of the CT density his-
togram to generate “CT density masks.” Although various threshold
values and percentile points have been investigated, the −950 HU
threshold [12–14] and the 15th percentile on the frequency distri-
bution curve [15] are the most widely accepted.
A limitation of CT histogram measurement approaches for quan-
tifying the extent of emphysema is that these do not take into
account the size of the low attenuation areas in the lung or how
they cluster together, which may be an important consideration
in COPD patient management. One approach that does account for
clusters of values is the analysis of low attenuation clusters (LAC)
[16,17] which quantifies low attenuation regions as “emphysema-
tous holes.” Studies show that the LAC measurement is correlated
with mathematical models of emphysematous cluster formation
and agrees with radiologist emphysema scores [18–20].
Fig. 1A shows a centre slice, coronal CT image with all lung
voxels less than the −950 HU threshold highlighted in red. The
three-dimensional reconstruction of the CT airway tree and the low
attenuation clusters (colour-coded for the different lung lobes) are
shown below in Fig. 1B. Although it is clear in the CT density mask
for the subject with moderate and severe COPD that emphysema
is located predominantly in the upper and middle lobes, the LAC
analysis provides both a visual representation of the localized dis-
ease, depicted as large spheres in regions corresponding to greater
spatial clustering of the emphysematous lesions, as well as a quan-
titative measurement.
2.2. Large airways
Airways disease is another important pathological feature in
patients with COPD, and the proximal airways can be directly
visualized and quantified using low dose thoracic CT methods.
Several approaches have been used to segment the airway tree
and then quantify the airway wall dimensions, such as threshold-
based analysis [21] and full-width at half maximum algorithm
[22], subsequent to three-dimension reconstruction of the airway
tree [23–25]. While many of these algorithms are still experimen-
tal, several have been incorporated into commercially-available
software including VIDA Diagnostics, Inc. (Coralville, IA, USA), FLU-
IDDA (North Brunswick, NU, USA), Pulmo3D Software (Fraunhofer
MEVIS, Bremen, Germany), and Airway Inspector (Harvard Medical
School, Boston, MA).
There is a wealth of quantitative airway dimension mea-
surements that can be obtained from CT images. One of the
measurements used in clinical research is the mean airway wall
area (WA), or airway wall area expressed as a percentage (WA%),
which was shown to be significantly correlated with histologi-
cal measures of the small airways [26]. However, the anatomical
locations within the airway tree where WA measurements are
obtained vary across studies, from a single airway location (e.g. RB1
[27]) to an average of all airways of a particular generation (e.g.
5th generation airways [28]), and therefore it is difficult to com-
pare measurements between studies. Furthermore, it is difficult to
compare this measurement between patients because there are dif-
ferent distributions of airway sizes in different patients. Another
common CT airway measurement was introduced to avoid the
potential bias that occurs due to the different distribution of air-
way sizes is a standardized measure for airway wall thickness [29].
This measure, called the Pi10, is derived by plotting the square root
of the airway wall area versus the internal perimeter of each mea-
sured airway and using the regression line to calculate the square
root of the airway wall area for a representative airway with an
internal perimeter of 10 mm. More recently, Smith and colleagues
[30] proposed another way to overcome this potential measure-
ment bias by only including measurements from airway segments
that were anatomically matched for all subjects.
Most commercially available lung analysis software, such as is
shown in Fig. 1C (Apollo, VIDA Diagnostics Inc. Coralville, IA, USA),
allows the three-dimensional reconstruction and labeling of the
airway branching structure. This approach allows investigators to
select an individual airway (e.g. RB1 ) and obtain specific regional
airway measurements.
2.3. Functional small airways disease
It has long been known that small airway obstruction may
be identified using evidence of CT lucency, or gas trapping,
on CT expiratory images in the absence of emphysema [31].
Although numerous approaches have been evaluated, including the
inspiratory-to-expiratory volume change of voxels with attenua-
tion values from −860 to −950 HU (RVC−860to−950 ) [32] and the
expiratory-to-inspiratory ratio of mean lung density in HU (E/I
ratio) [33,34], a more regionally quantitative approach was recently
introduced. This approach provides a way to quantify regional gas
trapping, or “functional small airways disease,” on a voxel-by-voxel
basis by registration of the full-inspiration and full-expiration tho-
racic CT images [35,36]. While measurements generated using this
approach have not yet been histologically validated, such measure-
ments were shown to be reproducible over short periods of time
 M. Kirby et al. / European Journal of Radiology 86 (2017) 335–342 337

Fig. 1. CT density mask generated using the −950 HU threshold cut-off of the CT densitometry histogram (A) with the low attenuation cluster analysis (B) and three-
dimensional reconstruction of the airway tree generated (C) using VIDA Diagnostics, Inc. (Coralville, IA, USA) for an at risk, GOLD I, GOLD II and GOLD III+ COPD subject.
At risk subject is a 66 year old male ex-smoker with a 25 pack-year smoking history (FEV1 = 103%pred , FEV1 /FVC = 0.94); GOLD I subject is a 79 year old female ex-smoker
with a 8 pack-year smoking history (FEV1 = 88%pred , FEV1 /FVC = 0.71); GOLD II subject is a 66 year old male ex-smoker with a 50 pack-year smoking history (FEV1 = 59%pred ,
FEV1 /FVC = 0.46); GOLD III+ subject is a 78 year old male ex-smoker with a 20 pack-year smoking history (FEV1 = 38%pred , FEV1 /FVC = 0.28).

[37], they correlated with pulmonary function [31,32], showed spa- information may also be derived using physiologic signal alter-
tial agreement with functional abnormalities identified with other ations such as pulsatile blood flow or ventilation stemming from
imaging modalities [38], and were associated with longitudinal the 1 H MRI signal itself or using intravenous or inhaled contrast
changes in FEV1 [39]. agents.

2.4. Functional information: dual-energy CT 3.1. Non-contrast enhanced 1 H MRI

Conventional anatomical CT cannot provide direct informa-
tion regarding which parts of the lung receive ventilation or
perfusion – functional information. Therefore, other approaches
such as dual-energy CT (DECT) [40–42] are being developed
and evaluated. A recent study investigating DECT with combined
xenon-enhanced ventilation and iodine contrast enhanced perfu-
sion imaging demonstrated the feasibility of obtaining regional and
quantitative ventilation and perfusion measurements and, impor-
tantly, the measurements of the ventilation-perfusion relationship
on a voxel-by-voxel basis [43]. In patients with COPD, these DECT
ventilation-perfusion measurements were shown to be signifi-
cantly associated with measures of pulmonary function [43].
3. Magnetic resonance imaging measurements of COPD
There is growing interest in the use of pulmonary MRI for
research, not only because of the relative speed in which images can
be generated, and excellent safety and tolerability profile [44,45],
but also because of the unique combination of morphological
and functional information MRI provides. Morpho-functional pul-
monary measurements can be achieved using conventional 1 H MRI
using the inherent signal of the parenchyma. In addition, functional
Clinical non-contrast enhanced 1 H MRI is used to visualize and
detect tissue abnormalities in the body. However, direct visual-
ization of lung tissue is difficult due to the low proton density
and rapid signal decay due to the very short transverse mag-
netization relaxation time (T2*) of aerated lung tissue [46]. This
results in multiple susceptibility artifacts at air-tissue interfaces
of the alveoli. Therefore, clinical MRI for pulmonary applications
necessarily focuses on abnormalities with high signal intensity
against the dark background of the lung tissue [47]. For example,
fluid accumulation or solid pathology and atelectasis are visualized
with excellent signal-to-background ratio. Lung tissue abnormali-
ties in COPD patients such as focal emphysema, bronchiectasis and
consolidation may be detected and quantified/scored using MRI
despite a slightly lower spatial resolution compared to CT [48].
Already in clinical use, steady state gradient echo and T2-weighted
fast spin echo techniques help to differentiate healthy lung tissue
from focal emphysema, bullae and pneumothorax [47,48]. Beyond
such “clinical” scans, experimental pulmonary MRI offers tremen-
dous flexibility in the type of images and information that can be
obtained.
One approach used to generate images with greater signal from
the lung parenchyma involves pulse sequences that incorporate
338 M. Kirby et al. / European Journal of Radiology 86 (2017) 335–342
ultra-short echo times or UTE MRI [49]. Short echo times (TE) or
zero-echo times (where echo time is typically defined as the time
between the end of radiofrequency excitation and the beginning
of data acquisition), effectively reduce 1 H signal loss from the lung
parenchyma. As a result, UTE MR images may be used to identify
many of the same pulmonary pathological features as CT [50,51].
Measurements generated using this approach often quantify the
1 H signal intensity directly [52] or T2* [53]. Longitudinal relax-
ation times (T1) themselves may be used for direct quantitative
imaging of lung parenchyma alterations in COPD [54]. Studies have
determined that in COPD patients there are significantly shorter
T1-relaxation times and intra-individual regional differences of T1
correspond to lung parenchyma differences on CT at the lobar or
segmental level [55,56].
Regarding functional information, fast-time-resolved imaging
(obtained with gradient echo or steady state gradient echo based
sequences) can be used to detect impaired respiratory mechanics
[56,57]. Regional ventilation maps can also be generated using vol-
umetric analysis of inspiratory and expiratory 4D data sets [57].
Moreover, the inherent signal alterations from blood flow may be
used to generate lung perfusion maps. Arterial spin labeling (ASL)
uses the intrinsic contrast of magnetized, inflowing blood into the
imaging plane or volume. Since ASL does not rely on exogenous con-
trast, it may be used for serial or longitudinal studies with virtually
unlimited repetition of measurements [58]. However, pulmonary
ASL imaging has not yet made its way into clinical applications, and
successful implementation in COPD patients has not been reported
[59].
Fourier Decomposition MRI [60,61] is another recently intro-
duced 1 H-based MRI approach. This technique acquires images
during free breathing and then co-registers the images such
that the changes in MR signal intensity over time in each voxel
due to the breathing and cardiac cycle can be decomposed to
yield ventilation-weighted and perfusion-weighted MR images. In
ventilation-weighted images, measurements of the “ventilation
defects” have been shown to agree well with dynamic contrast
enhanced MRI in patients with cystic fibrosis [62] and with hyper-
polarized 3 He MRI and CT emphysema measurements in patients
with COPD [63].
3.2. Oxygen-enhanced 1 H MRI
Oxygen-enhanced MRI exploits the signal inherent to T1 sig-
nal alterations stemming from the presence of O2 in tissue and air.
Pulmonary 1 H images obtained during inhalation of different con-
centrations of O2 (i.e., room air and 100% of O2 ) can be subtracted
to depict signal changes in the ventilated lung related to a com-
bination of ventilation, membrane function, and perfusion effects
[59,64]. In COPD patients, Ohno and colleagues [65] demonstrated
that measurements of the mean relative enhancement ratio (the
difference in signal intensity between images acquired during 100%
oxygen and room-air breathing, normalized to the signal intensity
of room air breathing) showed greater heterogeneity in subjects
with emphysema compared to healthy volunteers.
3.3. 1H MRI with application of intravenous contrast material
First pass perfusion contrast-enhanced imaging uses an intra-
venous bolus injection of a clinically approved contrast medium
based on gadolinium chelates. The bolus is injected during con-
tinuous acquisition of time-resolved T1-weighted ultrashort TR
and TE gradient-echo (GRE) imaging. When incorporated with
parallel imaging and view-sharing technology, dynamic volume
studies (one full lung volume/second) can be employed. The visual
evaluation of the image sets is facilitated by subtraction of the
non-enhanced from the contrast-enhanced image signal, which
results in a bright display of the contrast-enhanced lung vessels
and parenchyma [66]. Lung perfusion deficits due to hypoxic vaso-
constriction are used for the indirect visualization of ventilation
defects in obstructive lung disease. Furthermore, visualizing per-
fusion dynamically during image acquisition not only allows for
perfusion abnormalities to be detected at peak enhancement, but
also for other conditions such as delayed perfusion to be detected
[67]. Semi-quantitative analysis of contrast-enhanced studies is
based on the calculation of signal-time curves, signal-to-noise
ratios, and contrast-to-noise ratios with region-of-interest analysis
of lung tissue signal. Absolute quantification remains difficult due
to the non-linear relationship of contrast material concentration
and T1-shortening effects; hence the injected amount of contrast
material has to be chosen carefully [68,69]. Because perfusion MRI
relies on contrast material that is approved for clinical use and stan-
dard MRI scanner hardware, it is one of the most straightforward
and robust functional pulmonary MRI approaches [47]. A nearly
finalized multi-centre trial of 600 COPD patients that evaluates first
pass perfusion MRI and CT will certainly provide insights into the
clinical value and feasibility of first pass perfusion MRI [56,70].
Another method for assessing pulmonary ventilation uses
gadolinium-DTPA that is typically administered intravenously but
can also be aerosolized and inhaled. Using this approach, pul-
monary ventilation appears as bright T1-signal in lung regions
where contrast is retained. This approach has been used for exper-
imental imaging in large animals and human volunteers, but use in
COPD has not yet been documented [71].
3.4. Multinuclear MRI with inhaled gas-contrast
MRI with inhaled hyperpolarized 3 He or 129 Xe gas provides
another way of obtaining pulmonary structural and functional mea-
surements [72]. Parenchyma microstructural information can be
obtained using a variety of diffusion-weighted MR pulse sequences.
During inspiration breath-hold, the gas diffuses within the lung
micro-structure and the “apparent” diffusion coefficient (ADC) is
derived such that it reflects the level of restriction of the gas to dif-
fusion. Studies have shown that 3 He and 129 Xe diffusion-weighted
measurements are significantly correlated with histology in ex-
vivo lungs [73,74]. In addition to lung microstructural information,
ventilation images that show the regional distribution of inhaled
gas may be acquired. Static ventilation images have been quanti-
fied in a number of ways, including ventilation defect counting or
scoring [75,76], as well as more automated measurements using
manual segmentation [75], thresholding [77] or more complex
algorithms [78–80]. Finally, unlike hyperpolarized 3 He gas, hyper-
polarized 129 Xe gas is soluble in blood and tissues making it possible
to measure regional perfusion [81] and alveolar transport kinet-
ics [82]. While there is still limited clinical experience using this
approach in COPD patients, measurements have been shown to
be strongly associated with the diffusing capacity of the lung for
carbon monoxide (DLCO ) in patients with idiopathic pulmonary
fibrosis [83], and therefore there is strong potential to phenotype
COPD patients using hyperpolarized 129 Xe MRI.
3 He and 129 Xe static ventilation images and diffusion-weighted
images are shown in Fig. 2 for a single healthy volunteer and
three COPD patients in whom 3 He and 129 Xe ventilation defects are
readily visualized. The 3 He and 129 Xe ADC maps are also brighter
reflecting larger ADC numbers for the COPD subjects indicative of
airspace enlargement and/or emphysematous tissue destruction.
Other approaches, such as MRI with inhaled fluorinated gases
have also been investigated in patients with COPD. Although 19 F
MRI has reduced image quality in comparison to hyperpolarized
noble gas MRI, 19 F MRI has the advantage that it does not require
specialized and expensive polarization equipment, and therefore
has potential for more widespread use. 19 F MRI is still very early
 M. Kirby et al. / European Journal of Radiology 86 (2017) 335–342 339

Fig. 2. Hyperpolarized 3 He and 129 Xe static ventilation images and ADC maps for a healthy volunteer and three COPD subjects.
Subject in column 1 is a 79 year old female never-smoker (FEV1 93%pred , FEV1 /FVC = 0.70); Subject in column 2 is a 77 year old female ex-smoker with a 40 pack-year smoking
history (FEV1 50%pred , FEV1 /FVC = 0.50); Subject in column 3 is a 68 year old female ex-smoker with a 52 pack-year smoking history (FEV1 59%pred , FEV1 /FVC = 0.53); Subject
in column 4 is a 76 year old male ex-smoker with a 70 pack-year smoking history (FEV1 35%pred , FEV1 /FVC = 0.31).

in development and although quantitative measurements have yet
to be developed, 19 F MRI images show more heterogeneous signal
intensity with observable ventilation defects in COPD compared to
healthy volunteers [84].
4. Optical coherence tomography imaging measurements
of COPD
Optical coherence tomography (OCT) is most commonly used for
coronary artery and retinal imaging. Recently, investigators have
begun to explore the use of OCT for airway diseases because of
the very high resolution (approximately 15 ␮m axial resolution)
images that may be acquired. OCT imaging can be performed dur-
ing bronchoscopic procedures and are limited only by the diameter
of airway that can be accessed using the OCT probe. Typical OCT
probes are 1.5 mm in diameter, and therefore the small airways that
are the site of airflow limitation in COPD [85] can be evaluated. Fig. 3
shows OCT images obtained in a proximal airway (approximately
3 mm in diameter) and a peripheral airway along the same airway
path with the same diameter as the 1.5 mm diameter OCT probe for
four ex-smokers with and without airflow limitation. In compari-
son to the ex-smokers without COPD, who have notably thickened
airway walls, the ex-smokers with COPD have larger alveoli and
greater destruction of the airway wall.
While OCT airway imaging has been used more extensively to
evaluate cancer [86,87], in COPD patients airway wall OCT measure-
ments are highly reproducible [88] and are significantly associated
with pulmonary function measurements and CT airway wall mea-
surements [28]. Although measuring treatment changes have not
yet been demonstrated in COPD patients, OCT has been shown
to identify changes in the airway wall following bronchial ther-
moplasty in asthma [89]. It is also possible to obtain information
related to the elastic properties of the airway using OCT by measur-
ing the airway diameter at various airway pressures and deriving
airway compliance measurements [90].
5. Pulmonary imaging to improve COPD patient
management
5.1. How is imaging currently used in COPD patient
management?
In current clinical practice, imaging is not routinely acquired
for COPD patients. Moreover, chest imaging was not included in
recommendations for COPD patient management from the Cana-
dian Thoracic Society [91] or in European reports [92], and imaging
was only noted as valuable in excluding alternative diagnoses and
establishing the presence of comorbidities in the GOLD Execu-
tive Summary [1]. In fact, one of the only instances where CT has
been mentioned as useful in COPD management decisions was for
lung volume reduction therapies [93]. The National Emphysema
Treatment Trial (NETT) [8] demonstrated that patients with severe
COPD with a predominance of CT emphysema in the upper lobes
and reduced exercise capacity may experience improved outcomes
and survival following lung volume reduction surgery compared
to standard medical therapy. Thoracic imaging is also used in
COPD patient management when planning endobronchial valve
placement. Significant improvements in pulmonary function have
340 M. Kirby et al. / European Journal of Radiology 86 (2017) 335–342

Fig. 3. OCT image acquired in a proximal and peripheral airway along the same airway path for four ex-smokers with and at risk of COPD.
Subject A is a 61 year old male ex-smoker, with 44 pack-years smoking history (FEV1 = 96%pred , FEV1 /FVC = 0.81; Subject B is a 67 year old female ex-smoker with 51 pack-year
smoking history (FEV1 = 102%pred , FEV1 /FVC = 0.82); Subject C is a 65 year old female ex-smoker with a 85 pack-year smoking history (FEV1 = 41%pred , FEV1 /FVC = 0.57); Subject
D is a 63 year old male ex-smoker with a 100 pack-year smoking history (FEV1 28%pred , FEV1 /FVC = 0.29).

been shown in COPD patients with heterogeneous emphysema and 6. Conclusions

intact interlobar fissures [9,94].
5.2. Potential role of quantitative imaging?
The quantitative imaging field is rapidly developing, and in con-
cert with emerging imaging informatics tools, large quantities of
imaging information can be mined to determine image features
that predict outcomes following interventions. For example, the
NETT study demonstrated that the regional distribution of emphy-
sema is a clinically important feature to help select patients who
better respond to lung volume reduction surgery [8], however
there have been numerous others, particularly from the large, mul-
ticentre cohort studies, including COPDGene [95], ECLIPSE [96]
and SPIROMICS [97]. For instance, the presence of CT emphysema
predicts lung function decline [94]; CT emphysema extent pre-
dicts response to certain COPD treatments [98]; CT emphysema
extent and airway dimension measurements predict mortality
[99]; CT emphysema extent and airway dimension measurements
[100], as well as MRI ventilation defect measurements [101], may
predict COPD exacerbations that require hospitalizations. Other
quantitative imaging measurements, namely pulmonary artery
enlargement (PA:A ratio measured on CT >1) were also shown to be
associated with severe exacerbations of COPD [102]. Importantly,
the genetic determinants of these quantitative imaging phenotypes
are also being investigated [103,104], and large multi-centre cohort
studies incorporating multi-modality imaging, such as the German
ASCONET study, will certainly help provide more insight into the
clinical value and feasibility of thoracic imaging in COPD patients
[70].
More research is required to investigate whether quantitative
imaging may help identify phenotypes that will enable effective
COPD management to improve outcomes. Furthermore, linking
information from multiple scales, from disease endotype to imag-
ing phenotype, may improve how COPD patients are managed at
all levels from drug discovery, such that there are more treatment
options for patients with COPD, to real-time incorporation of quan-
titative imaging into patient management decisions.
The challenges inherent to managing patients with COPD and
reducing the overall disease burden demands more and better
treatment options, and new approaches that can help to individual-
ize patient management strategies. Towards this goal, new imaging
methods and measurements have been developed over the last
several decades. The development of low dose CT and the commer-
cialization of CT analysis tools have led to the incorporation of CT
in large-scale, multi-center studies, enabling new discoveries and
a better understanding of COPD pathogenesis and phenotypes at
the population level. Furthermore, the number of MRI techniques
for pulmonary evaluation has experienced a large growth over the
last two decades, and continues to grow, as evidence is mounting
that pulmonary MRI measurements provide very sensitive COPD
biomarkers. Finally, OCT provides unique information and remains
the only imaging modality that can directly visualize and quan-
tify the small airways – an important therapeutic target in COPD
patients. Despite the advances in imaging methods and measure-
ments, the road towards precision medicine in COPD is still long and
will require the standardization of imaging protocols and methods,
development and validation of imaging biomarkers, and demon-
strating efficacy in clinical trials. Initiatives such as the Quantitative
Imaging Biomarkers Alliance (QIBA) and the Xenon Clinical Trials
Consortium are an important step forward, and will be critical in
achieving this goal. Furthermore, it is unlikely there is a “one size
fits all” imaging modality, and future studies must investigate how
we can incorporate multi-modality imaging information for indi-
vidual patients. These challenges, once surmounted can cement the
role of quantitative imaging in guiding the management of patients
with COPD.
Conflicts of interest
None.
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