knee osteoarthritis ( oa ) is a highly prevalent disease among the elderly and increases from 
 middle age1 , 2 .
medial knee oa with varus deformity is 10 times more common than 
 lateral knee oa3 , and females are more 
 predisposed to it than males1 , 2 .
the prevalence rate of knee oa among females increases from 
 around the age of 401 , and early diagnosis 
 allows for treatment to be initiated even before symptoms present .
vibroarthrography ( vag ) is a noninvasive method of assessing cartilage degeneration or knee 
 oa4,5,6,7,8 .
a previous study8 demonstrated that a high frequency area ( 200600  hz ) 
 obtained by fast fourier transform ( fft ) is a key feature of knee oa .
another study7 reported that a frequency of 50150  hz in 
 patients with knee oa using fft was higher than that in age - matched elderly .
fft does not 
 take time information into account , and therefore fft analysis can not be applied to 
 investigate the relationship between knee joint motion and vag signal frequency information . 
 from this point of view , wavelet transform analysis is assumed to be a more suitable 
 frequency analysis for vag during tasks requiring knee joint motion because time is taken 
 into account by this analytic method .
the accelerometer and microphone used to measure vag signals from the knee joint were 
 positioned around knee joint areas , such as the medial or lateral femoral condyles7 , 8 . 

the skin around the knee joint locations was expected to move during the tasks ( gait , 
 standing up , and walking up and down stairs ) .
the most suitable location for the assessment 
 of knee oa using vag has not yet been reported . only shen et al.9 reported positioning the accelerometer at the lateral and 
 medial epicondyles , mid - patella , and tibia to investigate the origin of knee joint cartilage 
 pathology using vag .
the optimal location for vag measurements to classify normal knee and 
 knee joint pathology , however , has not been evaluated .
the aims of the present study were to investigate the most suitable location for vag 
 measurements of the knee joint to distinguish a healthy knee from knee oa using wavelet 
 transform analysis .
we conducted the study 
 on extremely different populations , first in healthy young adults and then in patients with 
 severe knee oa .
participants were 16 healthy females ( control group ; age : 22  2  years , height : 157  5  cm , 
 weight : 55  5  kg ) and 17 females with knee oa ( oa group ; age : 68  7  years , height : 153  
 6  cm , weight : 61  10  kg ) .
subjects in the control group were recruited from a university , 
 and exclusion criteria were as follows : history of previous lower extremity surgery , and 
 previous injury that resulted in ligamentous laxity at the knee joint .
the oa group was 
 recruited from a local orthopedic clinic using a leaflet and poster on the bulletin board . 

knee oa was diagnosed by an orthopedic surgeon according to the criteria of the american 
 college of rheumatology10 , and all 
 patients with knee oa had medial knee oa ( kellgren - lawrence classification ; grade iii : 2 , 
 grade iv : 15 ) .
all subjects were provided information regarding the nature of the study , and 
 written informed consent was obtained , as required by the research ethics committee of 
 seijoh university .
subjects were seated in an armless chair 40  cm high and asked to stand up from the seated 
 position taking 2  s to complete the movement .
measurements were performed on a randomly selected leg in the control group , and 
 on the painful leg in the oa group .
the standing - up task was performed three times , and the 
 mean of each parameter ( mentioned below ) was used for the final analysis .
the knee joint 
 angle at three markers ( femoral trochlear , lateral epicondyle , and lateral malleolus , fig . 1fig .
general stethoscopes 
 were placed at the medial epicondyle , lateral epicondyle , patella , and tibia .
the 
 three color markers were set at femoral trochlear , lateral epicondyle , and lateral 
 malleolus to assess the knee joint angle . )
was measured using a two - dimensional ( 2d ) camera system ( total motion coordinator 
 lite , toso system ltd . ,
general stethoscopes 
 were placed at the medial epicondyle , lateral epicondyle , patella , and tibia .
the 
 three color markers were set at femoral trochlear , lateral epicondyle , and lateral 
 malleolus to assess the knee joint angle .
japan ) were placed at the medial epicondyle , lateral 
 epicondyle , patella , and tibia ( fig .
1 ) to obtain 
 the vag signals . one meter of rubber tube was connected to the head of the stethoscope and 
 microphone ( size : 20  mm   mm ; flat area : 50 to 16 khz , operational amplifier : opa344 
 microamplifier series , texas instruments , dallas , tx , usa ) .
the vag 
 measurement system was confirmed to fall in a flat area from 100 to 2 khz using an 
 electrodynamic shaker ( asahi seisakusho , ltd .
the analogue vag signals sampled at 
 50 khz were translated to digital data using an ad converter , and the signals were stored in 
 a personal computer .
the signals were then analyzed by matlab ( r2013a , the mathworks , inc . , 

a bandpass filter was used from 100 to 2 khz , because muscle sound 
 ( mechanomyogram ) interference is 0 to 100  hz11 . for analysis of the time - frequency properties of vag ,
the mother wavelet used was  morlet ,  and the analyzed 
 frequency range was from 100 to 2 khz .
contour maps of the wavelet - transformed data were 
 obtained , and included time , frequency , and wavelet coefficient axes . in this study ,
one was a frequency analysis in which only frequency and 
 wavelet coefficient values were used , and the other was a time - frequency analysis . to perform the frequency analysis ,
then , 2d graphs were obtained to show the relationship between the 
 frequency and wavelet coefficient . to quantify the vag signal frequency properties , wavelet 
 coefficients were normalized , and the number of subjects with normalized wavelet 
 coefficients over 0.8 and frequency coefficients over 0.8
a time - frequency analysis was used to investigate when and at what knee angle the vag 
 signals were emitted from knee joints , and the knee joint angle and frequency at the maximum 
 wavelet coefficient were used to compare the oa and control groups .
the peak wavelet coefficient and knee angles at the peak coefficient were compared in four 
 locations between groups using an unpaired t - test .
next , the area under the receiver 
 operating characteristic ( roc ) curve of the four assessment locations was obtained using the 
 sensitivity and specificity of the peak frequency at the maximum wavelet coefficient and 
 knee flexion angles , respectively .
table 1table 1.difference in vibroarthrography signal frequency at peak wavelet coefficient 
 value between control and oa groups ( hz)measurement locationcontroloamedial151.8 ( 64.0)218.4 ( 138.2)lateral**164.6 ( 82.4)250.6 ( 86.3)patella155.6 ( 43.1)180.5 ( 77.1)tibia*122.2 ( 53.6)176.9 ( 91.2)medial : medial epicondyle ; lateral : lateral epicondyle . * p<0.05 , * * p<0.01 . 

the peak wavelet 
 coefficient at the lateral condyle and tibia in patients with knee oa was significantly 
 higher than that in the control group .
table 
 2table 2.difference in knee joint angle at peak wavelet coefficient value between control 
 and oa groups ( degree)measurement locationcontroloamedial**50.8 ( 15.4)34.6 ( 17.0)lateral**59.8 ( 17.4)39.4 ( 19.0)patella55.9 ( 23.6)41.6 ( 16.4)tibia**62.3 ( 17.9)37.5 ( 15.1)medial : medial epicondyle ; lateral : lateral epicondyle . * * p<0.01 .
shows knee joint angles at the peak wavelet coefficient between the control 
 and oa groups .
angles in all locations of vag measurement were significantly greater in the 
 oa group than in the control group .
2.roc curve of frequency ( a ) and knee joint angle ( b ) at peak wavelet efficiency 
 assessed at the four locations ( medial , medial epicondyle ; lateral , lateral 
 epicondyle ; patella ; tibia ) and table 3table 3.difference in auc value between control and oa groupsmeasurement locationfrequencyangleauc95% clauc95% clmedial0.570.360.780.77**0.600.93lateral0.77**0.610.940.80**0.650.95patella0.570.370.780.680.500.87tibia0.86**0.721.000.86**0.720.99medial : medial epicondyle ; lateral : lateral epicondyle ; auc : area under the curve ; 
 ci : confidence interval .
* p<0.05 , * * p<0.01 show the roc curves and the values of the area under the curve ( auc ) at the 
 four assessment locations .
the auc values of the frequency and angle measurements were 
 higher at the tibia than at the other locations .
roc curve of frequency ( a ) and knee joint angle ( b ) at peak wavelet efficiency 
 assessed at the four locations ( medial , medial epicondyle ; lateral , lateral 
 epicondyle ; patella ; tibia ) medial : medial epicondyle ; lateral : lateral epicondyle ; auc : area under the curve ; 
 ci : confidence interval .
the peak vag signal frequencies assessed at the lateral condyle and tibia in patients with 
 oa were significantly higher than the those measured in the control group ( table 1 ) , indicating that the signal frequency was 
 higher in the oa group than in control .
extremely different joint conditions were compared 
 between healthy young adults and patients with severe knee oa to investigate the optimal 
 measurement location and angle of the knee joint , and to distinguish a healthy knee from a 
 knee with oa .
the knees of the patients in the oa group were considered to be in the final 
 stage of oa ( kellgren - lawrence classification ; grade iii : 2 , iv : 15 ) , and we assumed that 
 the vag signal frequencies resulted from the impact between the femur and tibia when 
 standing up .
angles correlating with the peak vag signal intensity at all measurement 
 locations were significantly smaller in the oa group ( less knee joint extension ) than in the 
 control group .
we considered that the vag signals related to joint friction were associated 
 with the location of the knee joint cartilage degeneration and knee joint kinematics with 
 the combination of sliding and rolling . because there were no such data in the present 
 study , however
the vag results on the lateral epicondyles were assumed to have resulted from friction 
 between the lateral epicondyle and iliotibial band , with running being the cause of 
 iliotibial band friction syndrome12 . 

mccoy et al . indicated that vag signals due to friction with the iliotibial band was 
 observed at knee flexion angles between 19 and 55. the angle at the peak wavelet 
 coefficient value averaged 39.4  19.0 degrees ( table 
 1 ) , and both ranges were similar .
therefore , we considered that vag signals 
 measured at the lateral epicondyle might include signals representing friction between the 
 lateral epicondyle and iliotibial band . two previous studies8 , 9 investigated three or four assessment locations to obtain the origin 
 of knee joint vag signals .
no studies to date have compared knee - joint location for vag 
 assessment during a weight - bearing task to investigate vag features of knee oa . based on the 
 auc analysis ( table 3 ) ,
the tibia is the most 
 suitable location to distinguish normal knee joints from knee joints with oa through 
 assessing the location of vag .
two anatomic reasons were assumed to underlie this finding : 
 the tibia attached to the accelerometer is the flattest bone and the tissue is thinner 
 compared to that on the medial epicondyle , lateral epicondyle , and patella .
therefore , the 
 noise on the tibia might be lower than that at the other locations .
previous studies described a difference in the frequency based on fft7 , 8 or signal 
 variations ( jitter and shimmer analysis)13 between normal knee and knees with oa .
so far , however , there are 
 no true vag data between the femur and tibia , because it is impossible to measure areas just 
 next to impact in vivo . therefore , one should first investigate the 
 conditions for obtaining significant differences between healthy knees and knees with oa . 
 based on our findings ,
the tibia is the most suitable location for distinguishing vag 
 signals of a healthy knee joint from those of knees joints with oa .
first , the origin of the vag , such as the 
 femoral tibia joint including the meniscus or the patellar femoral joint , could not be 
 distinguished in the present study because the vag included the whole vibration around the 
 knee joint during the standing task
. we did not compare validity data as in some previous 
 vag studies . in the future , a basic animal vag study using an oa model
second , the subjects were young healthy adults and patients at the 
 final stage of knee oa .
alternatively , a quantitative cartilage assessment like t2 mapping on magnetic 
 resonance images could be conducted to validate vag in knee oa . in conclusion ,
vag signals were assessed at four locations ( lateral and medial epicondyles , 
 mid - patella , and tibia ) to investigate the optimal place to assess healthy and 
 osteoarthritic knees .
the tibia was the most suitable location to distinguish the two 
 conditions , and the frequency and knee flexion angle at the peak wavelet efficiency assessed 
 on the tibia in patients with knee oa were higher and lower , respectively , than the values 
 in the healthy population .
 [ purpose ] the aims of the present study were to investigate the most suitable location 
 for vibroarthrography measurements of the knee joint to distinguish a healthy knee from 
 knee osteoarthritis using wavelet transform analysis . 
 [ subjects and methods ] participants 
 were 16 healthy females and 17 females with severe knee osteoarthritis . 
 vibroarthrography 
 signals were measured on the medial and lateral epicondyles , mid - patella , and tibia using 
 stethoscopes with a microphone while subjects stood up from a seated position . 
 frequency 
 and knee flexion angles at the peak wavelet coefficient were obtained . [ results ] 
 peak 
 wavelet coefficients at the lateral condyle and tibia were significantly higher in 
 patients with knee osteoarthritis than in the control group . 
 knee joint angles at the peak 
 wavelet coefficient were smaller ( more extension ) in the osteoarthritis group compared to 
 the control group . 
 the area under the receiver operating characteristic curve on tibia 
 assessment with the frequency and knee flexion angles was higher than at the other 
 measurement locations ( both area under the curve : 0.86 ) . 
 [ conclusion ] the tibia is the 
 most suitable location for classifying knee osteoarthritis based on vibroarthrography 
 signals . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION