Improving Lung Lesion Detection in Low Dose
Positron Emission Tomography Images Using
Machine Learning
Yinghwey Nai, Joshua D. Schaefferkoetter, Daniel Fakhry-Darian, Maurizio Conti, Xinmei Shi, David
W. Townsend, Arvind K. Sinha, Ivan Tham, Daniel C. Alexander, and Anthonin Reilhac
 screening of lung cancer using computed tomography (CT) has
Abstract—Lung cancer suffers from poor prognosis, leading to
high death rates. Combined PET/CT improves lung lesion
detection but requires low dose protocols for frequent disease
screening and monitoring. In this study, we investigate the
feasibility of using machine learning to improve low dose PET
images to standard dose, high-quality images for better lesion
detection at low dose PET scans. We employ image quality
transfer (IQT), which is a machine learning algorithm that uses
patch-regression to map parameters from low to high-quality
images e.g. enhancing resolution or information content. We
acquired 20 standard dose PET images and simulated low dose
PET images with 9 different count levels from the standard dose
PET images. For each count levels, 10 pairs of standard dose PET
images with one simulated low dose PET images were used to train
linear, single non-linear regression tree, and random regression-
forest models for IQT. The models were then used to estimate
standard dose images from low dose images for each count levels
for 10 different subjects. Improvement in image quality and lesion
detection could be observed in the images estimated from the low
dose images using IQT. Among the models employed, the
regression tree model produced the best estimates of standard dose
PET images. An average bias of less than 20% in SUVmean of 25
lesions in the estimated images from the standard dose PET images
can be obtained down to 7.5 × 106 counts. Overall, despite the
increase in bias, the improvement in image quality shows the
potential of IQT in improving the accuracy in lesion detection.
Image Quality Transfer, Lesion Detection, Lung Cancer, Machine
Learning, Positron Emission Tomography
I. INTRODUCTION
L UNG cancer is one of the top three leading cause of
cancer death in Singapore and worldwide. However, the
general prognosis of lung cancer is poor as the lesions are
asymptomatic until the disease is at an advanced stage [1]. The
This study was funded by the National University Cancer Institute,
Singapore Centre Grant Seed Funding Program. No other potential conflict of
interest relevant to this article was reported. This study was approved by the
Domain Specific Review Board (DSRB) of the National University Hospital
Singapore, and all the subjects signed an informed consent to participate.
Yinghwey Nai, is with A*STAR-NUS, Clinical Imaging Research Centre,
Singapore (e-mail: nai_ying_hwey@circ.a-star.edu.sg)
Joshua D. Schaefferkoetter was with A*STAR-NUS, Clinical Imaging
Research Centre, Singapore (e-mail: jschaefferkoetter@gmail.com)
Anthonin Reilhac works at A*STAR-NUS, Clinical Imaging Research
Centre, Singapore (e-mail: Anthonin_Reilhac@circ.a-star.edu.sg)
Daniel Fakhry-Darian works at A*STAR-NUS, Clinical Imaging Research
Centre, Singapore (e-mail: medv1598@nus.edu.sg )
Maurizio Conti is with Siemens Medical Solutions USA, Inc., Molecular
Imaging (e-mail: maurizioconti@siemens-healthineers.com)
978-1-5386-8494-8/18/$31.00 ©2018 IEEE
improved the sensitivity of detecting small cancerous lesions
but results in high false positives. Combined PET/CT scanner
helps to increase the accuracy of lesion detection by providing
metabolic information with [18F]fluorodeoxyglucose (FDG) on
top of CT information. PET/CT can thus improve lung cancer
screening.
Machine learning has the ability to learn and transfer the rich
information in high-quality images to low-quality images.
Image quality transfer (IQT) is a newly-developed machine
learning algorithm that relies on simple patch-regression to
estimate high-quality versions of low-quality images. For
example, the algorithm has been shown to improve the
detection of brain-pathways that were identifiable only in high-
quality diffusion-weighted imaging data [2]. We have
previously investigated the diagnostic image quality of low-
dose PET images in terms of lung lesion detectability by
simulating and comparing low-dose PET images to standard
dose PET images [3]. In this study, we investigate the feasibility
to extrapolate IQT to improve lung lesion detection in low-dose
PET data.
II. METHODS
In our previous study, we have acquired PET/CT images of
twenty subjects with biopsy-proven lung cancer [1]. The
subjects were injected with standard doses of 219.3 + 4.96 MBq
of [18F]FDG and scanned after an hour uptake, with 2 bed-
positions of 10 min each. The PET images were acquired on the
Biograph mCT (Siemens Medical Solutions, USA) in list-mode
format. Low dose PET images were simulated by randomly
discarding events in the list-mode to obtain 9 different true
count levels with 0.25 × 106, 0.5 × 106, 1.0 × 106, 2.0 × 106,
Xinmei Shi is with Department of Radiation Oncology, National University
Cancer Institute and A*STAR-NUS, Clinical Imaging Research Centre in
Singapore (e-mail: xin_mei_shi@nuhs.edu.sg)
David W. Townsend is with the Department of Diagnostic Radiology,
National University Hospital, Singapore and A*STAR-NUS, Clinical Imaging
Research Centre, Singapore (e-mail: dnrdwt@nus.edu.sg)
Arvind K. Sinha is with the 4Department of Diagnostic Imaging, National
University Hospital, Singapore (e-mail: arvind_kumar_sinha@nuhs.edu.sg)
Ivan Tham is with the Department of Radiation Oncology, National
University Cancer Institute and A*STAR-NUS, Clinical Imaging Research
Centre in Singapore (e-mail: mdcitwk@nus.edu.sg)
Daniel C. Alexander works at the Centre for Medical Image Computing and
Department of Computer Science, University College of London, UK and
National University of Singapore, Clinical Imaging Research Centre, Singapore
(e-mail: d.alexander@ucl.ac.uk)
5.0 × 106, 7.5 × 106, 10 × 106, 15 × 106 and 20 × 106 counts.
The standard dose (SD) and simulated actual low dose PET
images (ASLD) were reconstructed with ordinary Poisson
ordered-subset expectation maximization (OP-OSEM)
algorithm, with time-of-flight information and system
resolution modeling to obtain matrices of 400 × 400 × 171
(2.04 mm × 2.04 mm × 2.03 mm). All PET images are
corrected for scattering and attenuation.
A training set consisting of 10 subjects with a SD PET image
and one simulated low dose PET images for each of the 9
different count levels was employed. For validation, we used 10
different subjects with ASLD images for prediction at each
count level and one SD image each for evaluation. Regions of
interest (ROI) were seeded at the voxel with the highest activity
near the center of each suspected lesion on the SD PET images
with a 40% threshold. 3 cubic (1 cm3) ROIs were delineated
within the healthy lung air spaces on the SD image of each
subject. Smoothed ASLD (sASLD) were generated by
smoothing ASLD images with 5 mm FWHM using SPM8.
Masks were generated for all 20 subjects covering all the lung
space and body on the SD PET images.
IQT training was carried out at each count level with a
matched pair of SD and ASLD PET images, using only voxels
within the mask. Cubic patch sizes of 3 and 5 voxels were
employed for patch regression. Global linear regression, single
non-linear regression-tree, and random-forest regression
models were implemented in the training to determine the
corresponding standard dose estimate from the low dose image.
The root-median-square error (RMSE) of the masked IQT-
estimated images from the original SD images was calculated.
The bias in mean standardized uptake values (SUVmean) between
the estimated and standard dose images were determined for all
ROIs drawn on the SD PET images.
III. RESULTS
In this study, 10 sets of subject data were used as training
data for the linear, single regression-tree and random-forest
regression models in IQT, and the trained models were then
used to estimate standard dose images from low dose PET
images of 10 subjects at 9 different count levels.
Fig. 1 shows the average root-median-square error (RMSE)
of the masked ASLD and IQT-estimated images from SD
images of 10 subjects. RMSE was generally smaller in non-
1400
Masked Image
Root-Median-Square Error
1200
1000
(RMSE)
800
600
400
200
0
0.25 0.5 1 2 5 7.5
X 106 Count Levels
Fig. 1. Average root-median-square error (RMSE) of the masked ASLD and
IQT-estimated images from the SD images of 10 subjects.
linear regression IQT-estimated images across the different
count levels. RMSE also increased with decreasing counts for
both ASLD and IQT-estimated images. However, the linear
regression model did not improve the image quality as observed
by the greater RMSE in the estimated images than the ASLD
images at count levels below 0.5 × 106 counts.
In general, the bias of IQT-estimated images was smaller
than that of sASLD images down to 7.5 × 106 count levels with
a bias of less than 20% (Fig. 2). The bias was also generally
X 106 Counts Levels
0.25 0.5 1 2 5 7.5 10 15 20
-5
-15
-25
Bias (%)
-35
-45 sASLD Linear 3x3 Linear 5x5
-55 Tree 3x3 Tree 5x5 Forest 3x3
Forest 5x5
-65
Fig. 2. Average bias in mean SUV between the IQT-estimated and SD images
for all lesion ROIs drawn on the SD images.
smaller in IQT-estimated images generated using 3×3 patch
size than 5 × 5 patch size, especially in the non-linear
regression models up to 2 × 106 counts below which, the
opposite trend was observed (Fig. 2).
Fig. 3 shows the coronal views of the ASLD and IQT-
estimated PET images at the 9 different count levels, as well as
the corresponding SD PET images and the mask generated for
one subject. All the images are viewed at the same image
intensity range at the same slices. There was only one large
lesion in this subject and the lesion could be observed with
reasonable confidence up to 5 × 106 counts level in both ASLD
and IQT-estimated images. The ASLD image appeared fuzzy
with more “empty spaces” within the tissue regions at 0.25 ×
106 counts level. The visual distinction of the lung air space
from the normal and lesion tissues became more difficult below
7.5 × 106 counts level in ASLD images. As a result, lesions
may appear as normal tissues due to increase noise in low dose
PET images (Fig. 3). On the other hand, the IQT-estimated
image was able to distinguish the lesion and normal tissues
better. Visually, the estimated image showed better body and
lesions contours but appeared more pixelated below 1 × 106
count levels probably due to “spaces” within ASLD images.
ASLD In general, the random-forest regression model yielded
Linear 3x3
Linear 5x5
closer estimates to the standard dose PET image, followed by
Tree 3x3 the single regression tree then linear models, as supported by
Tree 5x5 the smaller RMSE in masked images of the IQT-estimated
Forest 3x3
images from the original SD images. The patch sizes of 3 and 5
Forest 5x5
voxels showed no clear distinction in better estimation of
standard dose image across the subjects and different count
levels. However, non-linear regression models with 3 × 3 patch
10 15 20
size showed better body contours, but yielded high noise in the
background of estimated images using ASLD below 1 × 106
counts. Thus, 3 × 3 patch size may not be suitable below this
Fig. 3. The above SD image and body mask for one subject were used to simulate ASLD PET images at 9 different count levels. These ASLD images were then
used as inputs into the learned IQT to estimate the corresponding high-quality PET images with linear, non-linear regression tree and non-linear regression forest
algorithms, with 3 × 3 and 5 × 5 patch sizes. The images shown were the threshold to the same image intensity range. Increase background noise was observed in
images estimated using 3 × 3 patch sized, non-linear algorithms below 1 × 106 count levels.
limit. current results were limited by the small sample size but
In this study, low dose PET images were simulated from SD showed the potential of using IQT machine learning algorithm
images. Simulated low-dose images have different random to improve lung lesion detection in low-dose PET data.
fraction and dead-time counts, and thus may not represent
actual low-dose PET images. IQT algorithm may work better REFERENCES
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for training and validation in this study. IQT algorithm may [2] D. C. Alexander et al., “Image quality transfer and
improve with larger sample size. applications in diffusion MRI,” NeuroImage, vol. 152, pp.
283–298, May 2017
IV. CONCLUSION AND FUTURE WORKS [3] J. D. Schaefferkoetter et al., “Quantitative Accuracy and
Lesion Detectability of Low-Dose 18 F-FDG PET for
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images. Regression forest algorithm yielded the lowest root-
median-square error for masked images and showed a
consistent trend in bias across count levels. Thus, it is the most
suitable for estimating high-quality images among the 3
algorithms employed. Bias in SUV of less than 20% was
obtained with ASLD and IQT-estimated images above 7.5 × 106
count levels. The estimation of high-quality images using IQT
is limited with ASLD images above 7.5 × 106 counts. Our