Professional Documents
Culture Documents
ON
PRESENTED BY
AMEER BASHA SANJEEVIAH
04391A0561 (3/4CSE) 05395A0508(3/4CSE)
ameerbasha2u@yahoo.co.in sanjeev_guru486@yahoo.co.in
• Introduction
1. Hand bone density
2. Hand radiographic absorptiometry
• IMAGE ACQUISITION
• EXPERIMENTAL RESULTS
• REFERENCES
1. INTRODUCTION
Conventional examination of the hand radiographs is well established as a
diagnostic as well as an outcome measuree in Rheumatoid Arthritis (RA). It is readily
available and has been correlated with measures of disease activity and function. X-
ray changes are, however, historical rather than predictive, and there is significant
observer variation in quantifying erosive changes. The earliest radiographic changes
seen in the hand are soft-tissue swelling symmetrically around the joints involved,
juxta-articular osteoporosis and erosion of the ‘bare’ areas of bone (i.e. areas lacking
articular cartilage).These changes help to confirm the presence of an inflammatory
process.
The presence of early soft-tissue swelling is easily recognized on plain
radiographs but not readily quantified. Although the presence of early osteoporosis is
recognized in the affected hand, a mild osteoporosis may be extremely subtle to the
eyes. The recognition of the changes in soft-tissue and bone density is subjective and
is known to vary from assessor to assessor. Therefore, attention has been focused on
the more objective erosion and joint narrowing assessment. Use of magnetic
resonance (MR) technique has been shown to sensitively detect early local edema and
inflammation prior to a positive finding on plain film radiographs. However, MR is an
expensive examination and may not be used as a routine technique.
Presently, radiographs of the hands and wrists are employed to assess disease
progression. The parameters used to determine progression are the changes in
erosions and joint-space narrowing observed on the radiographs. There are some
problems with both of these parameters. First, both erosion and joint narrowing are
not the earliest changes in RA and further they may be substantially irreversible.
Second, these two changes may occur independently of each other. Third, there is a
tremendous variability in erosive disease: some patients never develop erosions; some
go into spontaneous remission of their erosive disease; and for some, the progression
is relentless. Fourth, joint-space or cartilage loss may be caused by either the disease
itself or by mechanical stress. Present scoring methods require that any degree of
joint-space loss be recorded as a progressive change due to RA.
Quantitative techniques currently available may provide a new approach in
monitoring disease progression in patients with RA. Adoption of these techniques
may have implications for the management of patients with RA and for possible
detection of the disease at an early stage.
1.1. Hand bone densitometry
Considerable advances have been made over the past two decades in developing
radiological techniques for assessing bone density. However; all of these techniques
have been utilized on aging-related osteoporosis, a pathological change involving
general bone mineral reduction. Owing to the wide availability of DXA, recently
published research describes the use of Bone Mineral Density (BMD) measurements
in the hands of patients with chronic RA. Most published observations on RA have
examined BMD changes, focusing on only the general bone loss around the joints.
Quantification of the difference of bone loss between the juxta-articular bone and the
shaft of tubular bones in the hands could be a sensitive index for quantitative analysis
of RA patients. Hand BMD measurements offer an observer independent and
reproducible means of quantifying the cumulative effects of local and systemic
inflammation. The technique could be of use in the assessment of patients with early
RA, in whom conventional measures of disease are not helpful until disease is
(irreversibly) more advanced.
1.2. Hand radiographic absorptiometry
In conventional Radiographic Absorptiometry, radiographs of the hand are
acquired with reference wedges placed on the films. The films are and subsequently
analyzed using an optical densitometer. The resulting density values computed by the
densitometer are calibrated relative to that of the reference wedge and are expressed
in arbitrary units.
Recent improvements in hardware and software available for digital image
processing have led to the quantitative assessment of radiological abnormalities in
diagnostic radiology. Such improvements have also enabled introduction of several
radiographic absorptiometry techniques. One such technique uses centralized analysis
of hand radiographs and averages the BMD of the second to fourth middle phalanges.
Another technique developed in Japan uses the diaphysis of the second metacarpal to
determine BMD. A third technique developed in Europe measures the diaphysis and
proximal metaphysics of the second middle phalanx. Based on published short-term
precision errors, computer-assisted Radiographic Absorptiometry appears to be
suitable for the measurements of the BMD of phalanges and metacarpals, and is used
in several hundred centers worldwide.
In this work we present preliminary results of an ongoing research work
aimed at developing an automated radiographic absorptiometry system for the
assessment and monitoring of both BMD and soft tissue swelling in early stage RA.
This paper focuses on the reproducibility and accuracy of the methodology being
developed. The paper is organized as follows: the next section provides an overview
of the image acquisition procedure. In section 3 the image analysis algorithms used in
this work are presented. In section 4 we present results obtained by analyzing the data
collected in a small reproducibility study involving 10 normal subjects.
2. IMAGE ACQUISITION
One key factor influencing the outcome of any radiographic absorptiometry technique
is the standardization of the image acquisition technique. Variability in acquisition
parameters can significantly affect the measured values. In order to carry out this
work, a standard image acquisition protocol was defined. This protocol has been
successfully used in earlier large scale multinational phase 3 clinical trials for
Rheuatoid Arthrtis related drugs. Radiographs of the left and right hands are taken one
at a time. Templates were developed to guide the positioning of the hand with respect
to the center of the x-ray beam. The X-ray beam was centered between the 2nd and
3rd metacarpo-phalangeal joints and angled at 90° to the film surface. This results in a
tangential image of the joints. Improper beam centering generally results in
overlapping joint margins. The X-ray exposure parameters were maintained constant
for all subjects. All normal subjects were imaged at the same clinic at UCSF. In
addition to providing a template for hand positioning, two sets of calibration wedges
were also provided to the clinic. Each set of wedges consisted of one Acrylic wedge,
for soft tissue and one Aluminum wedge for bone tissue. These wedges were custom
designed for the purposes of this research work.
Figure1.Template used to position the left hand according to the standardized
protocol.
An image with poor contrast, such as the one at the left of Figure 2, can be improved
by adjusting the image histogram to produce the image shown at the right of Figure 2.
Figure 2. Adjusting the image histogram to improve image contrast
3.IMAGEANALYSIS
One of the major difficulties in analyzing hand radiograph images is the high
level of noise present in the images. Additionally the trabecular texture of the hand in
the vicinity of the joints increases the noise in edge maps of this regions. Use of non-
standard acquisition protocol can add additional challenges at it can result in further
degradation of image quality. This last challenge is minimized in this work, as a
standard image acquisition protocol is followed. Given a particular application
varying degrees of accuracy in anatomy segmentation can be considered acceptable.
For instance in detecting joint-space narrowing there is a need for accurate and
reliable determination of the joint-space of any finger and the bone edges in this
region. However, accurate delineation of the bone edges in the vicinity of the joint is
not as relevant. Depending upon the application there can be additional constraints on
performance issues as well. In an application for which off-line processing of the data
is acceptable, more sophisticated algorithms can be employed. This particular
application requires that the overall process be fast, accurate and reproducible enough
for on-line processing. Accurate estimation of the bone edges in the middle shaft and
in the joint vicinity of high relevance in this work. This is primarily because the
disease progression follows different patterns in the joint area as compared to the
middle phalange area. Also, the manifestations of the disease symptoms in its early
stage have different effects on soft-tissue and bone as well, which require reliable
segmentation of these two types of tissue at different time points. The algorithm for
hand segmentation can be outlined into the following main stages:
• Hand outline delineation
• Joint identification
• Bone outline delineation
• Segmentation of soft tissue and bone
The first stage of the algorithm has been well studied in the literature and is
not described here. The second stage can be more challenging, especially when
dealing with hands of patients in advanced stage of disease progression. As this
system will be applied to a patient population that is in their early disease stage it is
expected that the joints will be well defined. The system provided to the radiologists
allows them to adjust the location of the automatically identified joints. Results
presented in this work were obtained by having the radiologists place control points to
identify the joints, rather than having them automatically computed by the system.
3.1. Control point placement
A simple user interface was provided to enable placement of control points on
the joints. This was primarily done to investigate the sensitivity of the system to the
initial control point positioning, which in an automated system would invariably be
the same for the same image. The user placed 16 control points on each image. These
joints are show in Figure 4. In addition to placing the control points for the joints, the
control points for the two wedges are also placed by the radiologists. For each wedge,
six control points are placed with four at the corners and two in the middle. Once all
the control points are placed, the remaining steps of the generalized algorithm stated
above are carried out autonomously. The middle phalange or cortex control points are
computed automatically and are located at the middle of straight line connecting the
two joints, one above and one below the middle phalange. The diameters of the
circular regions of interest placed around each joint are computed proportionally to
the length of the fingers.
Let ji be the control points placed at the joints and mi be the control points placed at
the cortex of the phalanges. The distance di between joint ji and ji+4 is given by:
(1)
In the equation above jix and jiy are the x and y coordinates of the control point
i
j respectively. Also i and i+4 are indexes for two joints on the same finger, as only
the joints on the fingers are used in this work and not the thumb. Using the distance
computations above the radius rij for the Region of Interest (ROI) placed at the joint ji
and rim for the ROI placed around the cortex mi is given by:
(2)
and
(3)
The resulting ROIs are larger around the joints and are smaller around in the middle
phalange, yet they all cover bone and soft-tissue evenly.
Figure 3. Various stages of the bone delineation step. From left to right: original
image, two joint and one middle phalange control points, histogram equalized image,
Sobel gradient edge map, edges computed along with 7th order Bezier curve fit,
segmented bone and soft tissue regions.
4. EXPERIMENTAL RESULTS
A small study, involving 10 normal subjects, was conducted at UCSF to
determine the reproducibility and accuracy of the technique being developed. The
average age of the patients was 47.1 years. The youngest and oldest subjects were 32
and 58 years old respectively. Left and right hands of each subject were imaged twice.
For one of the subjects during the first acquisition one set of wedges was employed,
and during the second acquisition a different set of wedges was required. This was
done to observe any variability introduced by changing the wedges. Two distinct
users, one radiologist and one technician analyzed the set of 40 images. While the
radiologist was a trained expert, the technician was trained only on the use of the
system. In Figure 6a and 6b the final bone ridge outlines and segmentation results for
a left hand are shown.
As the results for left and right hands were similar, only results for the left
hand are presented. The coefficient of variance (CV) was computed as follows23:
(5)
The system used in this work was developed using the NIH-Image/J software.
A set of “plugin” modules were written for the Image/J package, and some
customization of that source code was done to accommodate multiple region-of-
interests. The equalization and edge detection routines described in section 3 are all
part of the standard ImageJ package.
Intra-reader variability was accessed by comparing the results of each reader
for reading each ROI and also per patient. Figure 4a and 4b show the CV for each
ROI and each patient respectively for the expert reader. Inter-reader variability was
accessed by comparing the results of one reader against that of the other. Figure 5a
and 5b, show the inter-reader CVs for each ROI and for each patient respectively. In
each of these charts, CV-Softav and CV_Boneav represent the CVs computed on
average gray-scale measurements on soft tissue and bone regions in the segmented
ROIs. Meanwhile, the CV_Soft_d and CV_Bone_d represent the corrected values of
CV_Softav and CV_Boneav using the Acrylic and Alumynium wedge profiles
respectively.
As an overall estimate for any given patient, the average CV for an individual
reader is 3.0% and the average CV for interreader accuracy is about 4.0 %.
Figure 5b. Left hand inter-reader CVs per patient. Each set of bars in both of the
charts above is grouped from left to right as CV_Softav, CV_Bone_av, CV_Soft_d,
CV_bone_d.
Figure 6a. A sample left hand with all the bone ridges outlined by the system and the two
wedges outlined by the radiologist.
Figure 6b. Segmentation result of the hand in Figure 6a.
4. Code for enhancing the image size: The code we have generated will take the
values of pixels from a file of pixels and uses them to generate the binary image.
Here we have followed the threshold method and the threshold value is identified
accordingly.
The code useful in c language is …
//This is the module for converting the grey level image to a binary image by
threshold method.
#include<stdio.h>
#include<conio.h>
#include<graphics.h>
main()
{
int i,j,th,gd,gm,bin;
int image[64][64];
long int sum=0;
char ch;
float avg;
FILE *fp;
gd=DETECT;
initgraph(&gd,&gm,””);
fp=fopen(“d:\lin.txt”,”r”);
if(fp==NULL)
printf(“File Not Open”)
for(i=0;i<64;i++_
for(j=0;j<64;j++)
{
ch=getc(fp);
image[i][j]=ch;
sum=sum+ch; //Sum of grey levels
}
avg=(ing\t)(sum/(64*64.0));//Threshold generation
for(j=0;j<64;j++)
{
if(image[i][j]>avg)
bin=0;
else
bin=15;
putpixel(i+20,j+20,bin);
}
getch();
closegraph();
fclose(fp);
}
REFERENCES
1. Fries J.F., Block D.A., Sharp J.T. et al. Assesment of radiologic progression in
rheumatoid arthritis. A randomized, controlled trial. Arthritis Rheum 1986;29;1-9
2. Sharp J.T., Wolfe F., Mitchell D.M., Bloch D.A., The progression of erosion and
joint space narrowing scores in rheumatoid arthritis during the first twenty-five years
of disease. Arthritis-Rheum. 1991; 34; 660-8
3. Van Leeuwen M.A, van Rijswijk M.H, vander Heijde D.M, et al. The acute-phase
response in relation to radiographic progression in early rheumatoid arthritis: a
prospective study during the first three years of the disease. Br J. Rheumatol 1993;
32(suppl. 3); 9-13
4. Eberhardt K.B, Truedsson L, Pettersson H., et. al. Disease activity and joint
damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM
rheumatoid factor. Ann Rheum Dis 1990; 49; 906-9
5. Van Leeuwen M.A, vander Heijde D.M, van Rijswijk M.H. et al. Interrelationship
outcome measures and process variables in early rheumatoid arthritis. A comparison
of radiologic damage, physcial disability, joint counts, and acute phase reactants. J.
Rheumatol 1994; 21; 425-9
6. Makisara G.L., Makisara P., Prognosis of functional capacity and work capacity in
rheumatoid arthritis. Clin. Rheum. 1982;1:117-25
7. Nørgaard, F., Earliest roentgenological changes in polyarthritis of the rheumatoid
type: rheumatoid arthritis. Radiology, 1965;85: p. 325-29.
8. Martel, W., J.T. Hayes, and I.F. Duff, The pattern of bone erosion in the hand and
wrist in rheumatoid arthritis Radiology., 1965;84: p. 204-14.