Detection and Prediction of Osteoarthritis in Knee
Detection and Prediction of Osteoarthritis in Knee
Detection and Prediction of Osteoarthritis in Knee
PII: S2405-4518(16)30039-3
DOI: http://dx.doi.org/10.1016/j.bsbt.2016.11.004
Reference: BSBT44
To appear in: Biosurface and Biotribology
Received date: 7 October 2016
Revised date: 16 November 2016
Accepted date: 22 November 2016
Cite this article as: Gwidon W. Stachowiak, Marcin Wolski, Tomasz
Woloszynski and Pawel Podsiadlo, Detection and Prediction of Osteoarthritis in
Knee and Hand Joints Based on the X-ray Image Analysis, Biosurface and
Biotribology, http://dx.doi.org/10.1016/j.bsbt.2016.11.004
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Detection and Prediction of Osteoarthritis in Knee and Hand Joints Based on the X-ray
Image Analysis
Tribology Laboratory, School of Mechanical and Civil Engineering Curtin University, Bentley,
Corresponding author:
Marcin Wolski
Email | marcin.wolski@curtin.edu.au
1
Abstract
Current assessment of osteoarthritis (OA) is primary based on visual grading of joint space
not sensitive enough for the detection of the early stages of OA and time consuming. A
radiographs. The goal is to develop an automated decision support system for the
detection and prediction of OA based on TB texture regions selected on knee and hand
radiographs. In this review, we describe our progress towards this development which
was conducted in five stages, i.e., (i) development of automated methods for the selection
of TB texture regions on knee and hand radiographs (ii), development of fractal signature
methods for TB texture analysis, (iii) applications of the methods in the analysis of x-ray
images of knees and hands, (iv) development of TB texture classification system, and (v)
development of ReadMyXray website for knee x-ray analysis. The results achieved so far
are encouraging and it is hoped, that once the system is fully developed and evaluated, it
2
Introduction
Osteoarthritis (OA) is a debilitating and costly disease to all societies across the
globe [1]. As people live longer and the populations rapidly age, this cost is continuously
increasing and OA becomes an important issue that cannot be ignored. One way of
mitigating this cost is through early detection and, more importantly, prediction of OA. To
achieve this, new automated diagnosis and prognosis techniques designed to assist the
could be initiated in a timely manner, thus reducing impact of OA on quality of their lives
and slowing down its progression [2]. The patients would also benefit from inclusion in
ranelate and bisphosphonates [3, 4]. The two DMOADs showed promising results in
animal models of OA. Strontium ranelate was found to reduce cartilage and bone
pathology, while bisphosphonates could prevent bone remodeling and preserve its
structural integrity.
computed tomography (CT) are routinely used in medical examinations. Classical x-ray
technique, even though more than 100 years old, is cheap, fast, easy to use and still
provides valuable information about changes occurring in human bones [5]. Current OA
3
assessment is based primarily on visual grading of joint space narrowing (JSN) and
osteophytes using atlases, e.g., the Osteoarthritis Research Society International (OARSI)
atlas [6] or Kellgren-Lawrence (K-L) grading scheme [7]. The individual grading is time
consuming, prone to high intra- and inter-rater variability, and is not sensitive enough to
detect changes occurring in joints at the early stages of OA [8-10]. For example, it was
shown that about 11% to 13% of cartilage volume can be lost before JSN of grade one is
observed on radiographs [8], and cartilage defect occur before radiographic OA or knee
the trabecular bone (TB) texture radiographic images. The reasons are following: (i) TB
changes at the early stages of OA [12, 13], (ii) TB exhibits fractal properties, i.e., it is self-
similar over a range of scales [14, 15], (iii) TB texture images selected on 2D radiographs
are directly related to the underlying 3D bone structure [16], and (iv) OA changes have
been detected on TB texture images using fractal methods [17, 18]. In this work we focus
on OA in knee and hand joints, since these joints are most commonly affected by the
disease.
In this paper, the progress towards the development of the detection and
been divided into five stages, i.e.: (i) development of automated methods for the selection
of TB texture regions on knee and hand radiographs (ii), development of fractal signature
methods for the bone texture analysis in knees and hands, (iii) applications of the methods
developed to the analysis of x-ray images of knees and hands, (iv) development of bone
4
texture classification system, and (v) development of dedicated website for the automated
In the first stage, an automated methods for the selection of TB texture regions of
interest (ROI) on knee [19] and hand [20] x-ray images were developed. Currently, the
bone regions are usually selected manually by a trained observer which is time-consuming
and observer-dependent.
Knee radiographs
The method developed selects two square ROIs on an x-ray image on the TB
immediately under the medial and lateral cortical plates of the tibia without the need for a
human operator (Fig. 1(a)). The method has three major components: image
preprocessing, delineation of cortical bone plates and location of the ROIs. In the first
component, image is resized to 512 × 512 pixels, its contrast is adjusted, edges are
enhanced, and knee borders together with the joint space line are found. In the second
component, active shape models (ASMs) are used to delineate superior borders of the
medial and lateral cortical tibia plates. The final component consists of placing the ROIs
under the cortical borders and performing horizontal and vertical adjustments of their
positions so that they do not overlap periarticular osteopenia, subchondral bone sclerosis
and fibula head (only lateral ROI). The accuracy of the method in the selection of the
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regions was compared against gold standard ROIs selected manually by an experienced
radiologist on 132 knee x-ray images. The agreement with the gold standard was
evaluated by means of similarity index (SI). SI is an overlap measure between the region
selected by the automated method and the corresponding gold standard region. It takes
values between 0 (no overlap) and 1 (entire overlap). In general, values of SI ≥ 0.70 indicate
excellent agreement [21]. The results obtained showed that the method developed is
accurate and reliable (SI ≥ 0.81). However, errors in ROI selection can occur. These errors
could be due to low contrast between knee and background and the deformation of knee
bones. For such cases, a special user interface was developed to enable manual adjustment
of ROIs.
Hand radiographs
For hand radiographs, automated selection of bone regions is far more difficult
than for knee joints. Compared to tibia, finger bones and subsequently ROIs are much
smaller, e.g., 20 × 20 pixels as opposed to 256 × 256 pixels for knee ROIs. Also, there are
more bones in hand, i.e. regions to be selected (16 in hands as opposed to 2 in knees). In
addition finger bones have varying orientations with respect to the image horizontal axis.
There is no such problem with knees. The method developed selects square ROIs above
and below cortical plates of the 2nd-5th distal interphalangeal (DIP) and proximal
interphalangeal (PIP) joints as these joints are often affected by OA. For one hand, all
together 16 ROIs (2 regions per joint) are selected (Fig. 1(b)). The ROIs selection is executed
in four stages: (i) x-ray image segmentation into hand and background, (ii) identification
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of the 2nd-5th finger regions, (iii) localization of centre points of distal phalanges heads
and DIP, PIP and metacarpophalangeal (MCP) joints, (iv) location of the ROIs under and
above the DIP and PIP joints. The accuracy of the method developed was evaluated using
gold standard ROIs selected manually by a trained observer on 40 hand x-ray images.
Effects of hand translation, rotation, finger separation and flexion were tested. It was
found that the selection of the ROIs on hand radiographs using the new method is
accurate and reliable (SI ≥ 0.7). Nevertheless, in some isolated cases the selection of ROIs
structures present (e.g., rings). Thus, a mouse pointer tool was developed to adjust the
Development of directional fractal signature methods for bone texture analysis in knees
and hands
In the second stage, methods for the analysis of the ROIs selected on knee and
hand radiographs were developed. The methods would have to be not only sensitive
enough to differentiate between healthy and osteoarthritic joints, but also be able to detect
minute changes occurring in TB due to OA, i.e., to detect an early development of OA.
As bone texture images exhibit anisotropic and multiscale nature (i.e., their
characteristics change with direction and scale) we decided to use fractal signature (FS)
based techniques, principles of which were originally developed by Peleg [22]. FS is a set
of fractal dimensions (FDs) calculated at individual scales (i.e., trabecular image sizes)
7
while FD is the most popular fractal measure of texture roughness. High (low) FD values
Knee radiographs
For the analysis of x-ray images of knee joints, we developed the variance
orientation transform (VOT) method [23]. The method calculates FS in all possible
directions (i.e., directional FS (DFS)) allowing for detailed analysis of multiscale bone
texture roughness. Briefly, in the VOT method, absolute differences of grayscale level
values are calculated for pairs of pixels within a circular search region of a fixed size,
which moves across the bone texture image (Fig. 2(a)). The differences between the pixels’
grey-scale level values along with the corresponding directions and distances between the
pixels are stored. The direction is defined as an angle between a line running through the
pair of pixels and the x-ray horizontal axis. For each direction, the variances of the
differences stored are plotted in log–log coordinates against distances (Fig. 2(b)). The log–
log data points are then divided into overlapping sub-sets of points, a line is fitted to each
sub-set, and its slope is used to calculate the Hurst coefficient (H) at an individual scale. H
with the central log–log data point in the corresponding sub-set. At each scale, the Hurst
coefficients obtained are plotted in polar coordinates against directions and an ellipse is
fitted to the resulting plot (Fig. 2(c)). Using the ellipses fitted, the following bone texture
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• Roughest part FS (FSSta). FSSta quantifies the texture roughness in the roughest
• Texture aspect ratio signature (StrS). The parameter measures a degree of bone
texture anisotropy at different scales. It takes values between 0 and 1, with lower
values representing higher anisotropy. It is calculated as the ratio of the minor to the
individual scales. It is defined as an angle between the major axis of the ellipse fitted
As an example, the VOT method was applied to two bone texture regions selected in
the medial compartment of tibia from subjects with and without knee OA (Figs. 3(a) and
3(b)). Corresponding rose plots obtained for these two regions are shown in Figs. 3(e) and
3(f), respectively. From the Fig. 3, it can be seen that the plot corresponding to the healthy
knee approximates an ellipse, while the plot corresponding to the OA knee exhibits
roughly circular shape. This indicates that bone texture roughness in the healthy joint, as
compared to the diseased bone, varies considerably with direction, i.e., OA texture is less
anisotropic than in the healthy knee [24]. The mean StrS values obtained were 0.72 (OA)
and 0.52 (non-OA). The plots also show that Hurst coefficients calculated for healthy bone
are, in general, lower (i.e., higher FDs) than those for OA bone. This means that the
healthy bone texture is generally rougher than the OA bone [24]. This agrees with the
9
mean FDSta values obtained for the non-OA and OA subjects, i.e., 2.87 and 2.83,
respectively. The means of StdS obtained were 105° (non-OA) and 60° (OA), showing the
dominating texture directions, i.e., directions in which bone texture is the smoothest.
The effects of radiographic conditions on the VOT method were evaluated, i.e.,
radiographic noise, blur, exposure, magnification, projection angle, translation of the ROIs,
and image resolution/size [25, 26]. The results obtained showed that the method is
considerably affected by image noise (greater than 5%), blur, magnification, projection
Hand radiographs
ROIs selected on hand radiographs are considerably smaller than those on knee
radiographs, e.g., 20 × 20 (hand) vs 256 × 256 (knee) pixels. We found that the VOT at
image sizes less than 48 × 48 pixels does not provide reliable results as there is not enough
data for the analysis [27]. To address this problem, we developed an augmented VOT
The AVOT method’s operating principles are similar to VOT, except that the size
of the search region is automatically adjusted to the size of a TB texture ROI, and FSs can
be calculated with respect to any reference direction. This was achieved through the
reduction of the marginal subsets of points in the log–log plot from five to three. Details of
the algorithm and the reduction procedure are given in [27]. As a result, the AVOT
method can reliably calculate FSs of small bone texture regions selected on arbitrary
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oriented finger bones.
Applications of the methods developed to the analysis of x-ray images of knees and
hands
In the third stage, the potential of the VOT and AVOT methods for the detection
Detection of differences in TB texture between subjects with and without knee OA,
OA (K-L grade < 2), but with and without cartilage defects,
Association of baseline bone texture with knee joint replacement (KJR) at 6-year
follow-up,
Association of baseline bone texture with incident of knee OA at 30-, 60- and 84-
Detection of differences in TB texture between subjects with and without hand OA.
Initially a pilot study was conducted to evaluate the VOT method abilities to
For this study 26 cases and 26 controls were used. Controls were the subjects with
(K-L grade ≥ 2) and without (K-L grade < 2) knee OA, respectively. The subjects were
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individually matched by sex, age and body mass index (BMI). Tibial bone texture ROIs
(two per knee joint) were selected on cases and controls knee x-rays, and analysed by the
VOT method. Examples of the ROIs selected on a knee x-ray are shown in Fig. 1(a). Bone
texture parameters obtained for cases and controls were compared using paired t-test. The
results showed that OA textures were smoother and less anisotropic than textures in
healthy joints, i.e., that trabeculae in OA joins are thicker and less structured than in non-
OA joints. For this study, a database from Lund University (Sweden) was used [32].
Detection of differences in TB texture between subjects with and without cartilage defects
bone changes in joints with and without cartilage defects was investigated [29]. Cases (n =
28) were subjects with cartilage defects (grade ≥ 2), whereas controls (n = 28) exhibited
normal cartilage (grade < 2). The subjects were individually matched by sex, age, BMI,
whether arthroscopic partial meniscectomy (APM) was performed or not, and APM’s
location (i.e., medial or lateral compartment). All subjects were without radiographic knee
OA (K-L grade < 2). Cartilage defects were identified and graded based on MRI scans [29].
An example of a MRI scan of a knee joint with cartilage defects is shown Fig. 4 [33].
Databases from the University of Western Australia and Monash University (Australia)
were used [34]. On each x-ray image, bone regions in the medial and lateral compartment
were selected and analysed using the VOT method. Paired t-tests were used to evaluate
differences in fractal parameters between cases and controls. The results showed that TB
texture was rougher for cases than for controls, suggesting that thinning and fenestration
12
of trabeculae occur in knee joints with early OA (i.e., with cartilage defects). This finding
seems to contradict our previous results [28] which showed that OA knees exhibit lower
roughness than healthy joints. However, a possible explanation is that TB changes occur in
two stages due to OA. In the early OA stage, trabecular structures undergo thinning and
fenestration, whereas in the late OA, TB thickens. This explanation is consistent with other
studies in which it was shown that early knee OA exhibits bone resorption, while later
The results from this study show that the VOT method is sensitive enough to
In another study, a potential of the VOT method in predicting KJR in patients with
OA was assessed [37]. Medial and lateral bone ROIs were selected on knee radiographs of
114 subjects with symptomatic knee OA. A database from Monash University (Australia)
was used [30]. 28 subjects (25%) underwent KJR over 6-years. The associations between
tertiles of bone texture parameters obtained at baseline and the incidence of KJR were
studied using logistic regression. The statistical analyses were performed with adjustment
for baseline age, sex, BMI, Western Ontario and McMaster Universities Osteoarthritis
Index (WOMAC) score, and osteophyte and JSN grades. It was found that in knees
exhibiting higher baseline bone texture roughness, the risk of KJR is reduced. This could
[38].
These results showed that the VOT method could identify subjects with knee OA
Association of baseline bone texture with incident of knee OA at 30-, 60- and 84-month follow-ups
Recently, a much wider study, involving 3026 subjects (6052 knees) from the
conducted [31]. In the study, 894 subjects (626 knees) recruited by University of Alabama
(UAB), and 807 subjects (1158 knees) from University of Iowa (UIowa) were used.
up periods (30, 60 and 84 months) were investigated. At the baseline, subjects were
without radiographic knee OA (i.e., K-L grade 0 or 1). There were 195 (22%, UAB) and 303
VOT method with incident OA were evaluated using logistic regression adjusted for age,
sex, race, BMI, leg alignment and baseline K-L grade (0 or 1). The analyses were stratified
by two radiographic modalities used, i.e., digitized film in the UAB and computer
radiography in the UIowa. Results obtained showed that baseline bone texture parameters
are associated with the OA incident at follow-up. Specifically, for subjects from UAB, it
14
was found that the baseline higher medial bone roughness was associated with increased
odds of OA incidence at a follow-up. For subjects from UIowa, lower anisotropy of bone
textures at baseline was associated with increased odds of OA. The higher roughness of
bone texture at baseline in subjects who had incident of OA, as compared to those who did
not, could be a result of fenestration and breakage of TB structures due to early OA. The
results agree with our previous findings [29] that in knee joints with pre-radiographic OA,
These results are promising, showing that the VOT method can be used in the
Hand x-ray images from 40 subjects from the Osteoarthritis Initiative (OAI)
database [University of California, San Francisco] were analyzed using AVOT method.
The subjects were individually matched by sex, age, BMI and race [27]. Half of the subjects
(i.e., cases) had radiographic OA (approximate K-L grade ≥ 2) in the 5th DIP joint. Controls
did not have OA (approximate K-L grade < 2) in the joint. On each hand radiograph, two
ROIs were selected, i.e., the first in the base of the 5th distal phalanx and the second in the
head of the 5th middle phalanx (Fig. 5). The regions were analyzed with the AVOT
method and the differences in the parameters obtained between cases and controls were
evaluated using paired t-tests. We found that TB texture was smoother for cases than for
controls in the horizontal directions, rougher in the vertical direction, and less anisotropic.
The results obtained were encouraging, showing that the AVOT method could be
used for OA detection in hands. A study with larger number of subjects will be conducted
in the future.
the classification of knee x-ray images based on bone textures. To simplify the
which calculates only three parameters (i.e., overall roughness, anisotropy and direction)
[39]. The parameters quantify texture features sensitive to OA changes in trabecular bone.
The VOT method calculates a relatively large number of parameters (i.e., 27) which
description of the SDM method is given in [39]. Briefly, the method is executed in several
convoluting the image data with Gaussian kernels at different scales. Second, the gradient
and Laplacian operators are applied over all scales and their extremum values are found.
Next, histograms of the differences of the extremum values in different directions are
constructed. Using the histograms, the three, mentioned above, parameters are then
obtained.
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OA progression and achieved high prediction scores in the sample of patients tested [40].
In the study, we analyzed the radiographs from 105 subjects (90 men and 15 women with
a mean age of 54 years) [40]. Altogether, radiographs from 203 knees, 68 with and 135
without radiographic tibiofemoral OA (i.e., K-L grade < 2), were analyzed. Two sets of
knee radiographs (baseline and follow-up) were obtained 4 years apart. ROIs of medial
compartment tibial TB texture were selected using an automated region selection method.
TB texture was then analyzed using the SDM method and three parameters were
produced for each ROI: roughness, degree of anisotropy and direction of anisotropy. A
logistic regression model based on the parameters was evaluated in the prediction of
baseline and follow-up. The model was adjusted for age, sex, and BMI. For knees with and
parameters calculated on medial TB texture had the prediction accuracy of 0.77 and 0.75
(DMC) system for the classification of knee x-ray images [41]. The schematic illustration of
the DMC is shown in Fig. 6. The DMC consisted of a heterogeneous ensemble of classifiers
(linear, quadratic, tree, k nearest neighbors, Parzen and support vector machine). To
produce a class for TB texture (e.g., healthy or OA), classifiers in the ensemble were
combined using a specially developed probabilistic model [42]. The model selectively
combined only those classifiers which performed well on similar TB texture images during
system training. We assessed the DMC in the detection of radiographic OA and prediction
17
of radiographic OA progression, and the results were encouraging.
For the detection, in a pilot study [41], knee radiographs from 51 subjects were
initially analyzed. Healthy and OA classes were defined as K-L grade 0 in both
tibiofemoral compartments in both knees and K-L grades 2 or 3 in at least one tibiofemoral
on two sets of knee radiographs taken from 50 subjects 4 years apart. The definition of
non-progressive and progressive classes was based on the increase in the sum of
tibiofemoral JSN and osteophytes grades between baseline and follow-up. The DMC
achieved classification accuracies of 90.51% and 80% (averages over 5 repetitions of two-
fold cross validation) for the detection of radiographic OA and prediction of radiographic
OA progression, respectively.
using the classification system developed is possible. Thus, our future research will
calculated by the VOT method on knee radiographs. Also, the system will be extended to
provides, free of charge, fractal-based assessment of bone texture of knee x-rays. Medical
18
practitioners, researchers and members of a general public can upload knee radiographs
for analysis, which are then analysed using the VOT method. A bone roughness report is
Currently, a work is undertaken to extend the website usability for analysis of hand
radiographs using the AVOT method and also to enable x-ray image classification by the
Summary
The current research efforts directed towards the development of methods for
Radiographs of knee joints were analyzed using the VOT method. A number of
studies were conducted. We found that the method could not only differentiate between
OA and healthy knee joints and identify pre-radiographic OA bone changes, but it also
For the analysis of very small images, like those found in hand radiographs, the
VOT method was augmented (i.e., AVOT), and successfully applied to hand radiographs.
We showed that the method is sensitive enough to show the differences between healthy
Classification system of knee bone textures was developed. Initially, for the
19
classification, the bone textures selected were analyzed by means the SDM method. The
SDM calculates much lower number of bone texture parameters than the VOT method,
thus reducing the complexity of the classification system developed. As the system was
planning to extend it by including support for the VOT method, and also to extend it to
The results obtained show that automated OA detection and prediction based on x-
ray images of knee and hand joints is possible. To assist the medical practitioners in knee
It should be noted that as the imaging technologies advance rapidly, the techniques
developed can be adapted to be used in the analysis and classification of MRI images, CT
Our future work will include development of regression models for prediction of
OA in knee and hand joints and evaluation of the models developed in longitudinal and
prospective studies. It is also planned to modify and test the methods developed for
analysis of other joint disorders than OA, such as rheumatoid arthritis and osteoporosis.
classification of TB textures of not only knees, but also hands and other joints.
Acknowledgements
The authors wish to thank the Curtin University, Department of Mechanical Engineering
20
and the School of Civil and Mechanical Engineering for their support during preparation
of the manuscript.
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24
(a)
(b)
Fig. 1. X-ray images of (a) knee and (b) hand
25
Fig. 2. A schematic illustration of the VOT method: (a) a search region that moves across the
image, (b) a log–log plot, (c) a rose plot of Hurst coefficients and (d) texture parameters
calculated from the plot.
26
(a) (b)
(c) (d)
(e) (f)
Fig. 3. X-ray images of (a) normal and (b) osteoarthritic knee joints
images, and (e, f) rose plots of Hurst coefficients, along with ellipses
27
Fig. 4. Example of grade 2 and grade 3 cartilage defects
visible on a MRI scan. Image adapted from [33].
28
(a) (b)
Fig. 5. X-ray images of (a) normal and (b) osteoarthritic DIP
29
Selected TB bone texture ROIs
Classified ROIs
Fig. 6. A schematic illustration of the DMC system for classification of TB bone textures.
30
Fig. 7. Example of a bone roughness report from ReadMyXray website.
31