FIGURE 1: POST GD-ENHANCED MRI SHOWING SYNOVITIS CHANGE
1
In knee O A,knee pain decreases afterintra-articularsteroid treatm entbutthe optim al w ay to assess an effectofthis treatm ent on synovium is unknow n. O n contrastenhanced M RI,static synovialvolum e can be quantified as can the dynam ic rate ofenhancem entofsynovium atdifferent tim es aftercontrastinjection. The bestw ay to evaluate synovium aftertreatm entw ould m aximize the correlation betw een synovial change and pain change. In persons undergoing intra-articularsteroid injections ofthe knee, do changes in dynam ic param eters ofsynovialenhancem ent correlate betterw ith reduction in knee pain than changes in static synovial volum es? S ubjects w ith sym ptom atic knee O A (A C R criteria) D esign: O pen Label C linical Trial (‘TA SK’)IS R C TN 07329370,in w hich subjects had 2 contrastenhanced M R I’s,one before intra- articularsteroid injection and one 5-15 days afterw ard. Intervention:Intra-articulardepom edrone 80m g P ain A ssessm ents: V AS score -pain on nom inated activity (VASNA): 0 (no pain)to 10 A ssessm ents atbaseline and 5-15 days postinjection M R IS can:3T Philips M RI,G adolinium -enhanced sequences (~7 m inutes,axial,18 im ages at~22-second intervals)TR 5.3 m s, TE 1.463 m s,FoV 14cm x14cm ,S lice thickness 3m m (used for dynam ic data) (sagittal),taken ~8 m inutes afterenhancem ent:TR 500m s,TE 17m s,FoV 15.9cm x 15.9cm ,Slice thickness 3m m (used forstatic volum es)(Figure 1) M anual segm entation ofthe synovialtissue layer(including fluid and possibly cartilage)w as perform ed on the postcontrastknee im age by a single observer(IC C =0.94). W e excluded cartilage w ithin the segm ented space by thresholding in a registered sagittal scan (3D W ATSc:TR 20m s,TE 7.7m s,FoV 15cm x15cm ,slice thickness 1.5m m ). W e calculated the proportion s ofsynovial tissue in every voxel using s=(S-m f )/(m s-m f )truncated to [0,1],w here S is the voxel intensity and m f ,m s are the m eans ofthe intensity distributions of fluid and synovialtissue volum e (Figure 2). W e used the extended Tofts m odel ሺ ሺ= ሺ ሺ+ ሺ ( ) − ( − ) 0 w hich is a solution ofthe pharm acokinetic equation,to calculate the param eters K trans (perm eability),v e (extra-cellularspace)and v p (plasm a space)atevery im age voxel (Figure 3). W e calculated param eters ateach voxel based upon the tim e series ofintensity Si(i=0,..,n)over the dynam ic sequence:(a)the m axim um gradientG m ax, (b)the m axim um relative enhancem entSr =Sm ax/S0, and (c)the late relative enhancem entSl =(Sn+… +Sn-3)/(4*S0) W e overlaid the m anually segm ented regions ofsynovial tissue onto these param eterim ages (via im age registration)and calculated the m edian value. Assessm entofthe change in static volum e V and dynam ic param eters from baseline to post-injection visitw as done by calculation ofa P earson coefficientcorrelation m atrix. Assessm entoflinearregression m easures betw een each ofthese param eters and each pain scale w as then perform ed. Forthe 72 patients (41.7% fem ale,m ean age 64.3),every dynam ic param etershow ed a reduction in response to treatm entbetw een baseline and follow -up (Table 1). Sl ,Sr and G m ax all correlated w ith K trans (Table 2). The param eterw ith the strongestcorrelation w ith change in VAS pain w as change in Sl(r=0.29,b=0.64;95% C I0.11 to 1.17; p=0.02),w hich is a strongercorrelation than change in volum e V*s (r=0.19,b=0.18;95% C I-0.05 to 0.41;p=0.13).O therparameters w ith strong correlations to change in VAS pain w ere change in Sr (r=0.29,b=0.56;95% C I0.09 to 1.03;p=0.02)and change in K trans (r=0.27,b=26.93;95% C I2.24 to 51.63;p=0.03). D ynam ic m easures ofsynovial enhancem entcorrelate m ore strongly w ith pain reduction afterintraarticularsteroid injection than static m easures ofchange in synovial volum e. In studies exam ining synovial response to treatm entin osteoarthritis, dynam ic param eters m ay optim ize the detection oftreatm enteffects. BACKGROUND In knee O A,knee pain decreases afterintra-articularsteroid treatm entbutthe optim al w ay to assess an effectofthis treatm ent on synovium is unknow n. O n contrastenhanced M RI,static synovialvolum e can be quantified as can the dynam ic rate ofenhancem entofsynovium atdifferent tim es aftercontrastinjection. The bestw ay to evaluate synovium aftertreatm entw ould m aximize the correlation betw een synovial change and pain change. AIM In persons undergoing intra-articularsteroid injections ofthe knee, do changes in dynam ic param eters ofsynovialenhancem ent correlate betterw ith reduction in knee pain than changes in static synovial volum es? METHODS S ubjects w ith sym ptom atic knee O A (A C R criteria) D esign: O pen Label C linical Trial (‘TA SK’)IS R C TN 07329370,in w hich subjects had 2 contrastenhanced M R I’s,one before intra- articularsteroid injection and one 5-15 days afterw ard. Intervention:Intra-articulardepom edrone 80m g P ain A ssessm ents: V AS score -pain on nom inated activity (VASNA): 0 (no pain)to 10 A ssessm ents atbaseline and 5-15 days postinjection IM AGING M R IS can:3T Philips M RI,G adolinium -enhanced sequences (~7 m inutes,axial,18 im ages at~22-second intervals)TR 5.3 m s, TE 1.463 m s,FoV 14cm x14cm ,S lice thickness 3m m (used for dynam ic data) (sagittal),taken ~8 m inutes afterenhancem ent:TR 500m s,TE 17m s,FoV 15.9cm x 15.9cm ,Slice thickness 3m m (used forstatic volum es)(Figure 1) IM AG E ANALYSIS:M ANUAL SEG M ENTATIO N M anual segm entation ofthe synovialtissue layer(including fluid and possibly cartilage)w as perform ed on the postcontrastknee im age by a single observer(IC C =0.94). W e excluded cartilage w ithin the segm ented space by thresholding in a registered sagittal scan (3D W ATSc:TR 20m s,TE 7.7m s,FoV 15cm x15cm ,slice thickness 1.5m m ). W e calculated the proportion s ofsynovial tissue in every voxel using s=(S-m f )/(m s-m f )truncated to [0,1],w here S is the voxel intensity and m f ,m s are the m eans ofthe intensity distributions of fluid and synovialtissue volum e (Figure 2). IM AG E ANALYSIS:DYNAM IC PA R A M ETERS W e used the extended Tofts m odel ሺ ሺ= ሺ ሺ+ ሺ ( ) − ( − ) 0 w hich is a solution ofthe pharm acokinetic equation,to calculate the param eters K trans (perm eability),v e (extra-cellularspace)and v p (plasm a space)atevery im age voxel (Figure 3). W e calculated param eters ateach voxel based upon the tim e series ofintensity Si(i=0,..,n)over the dynam ic sequence:(a)the m axim um gradientG m ax, (b)the m axim um relative enhancem entSr =Sm ax/S0, and (c)the late relative enhancem entSl =(Sn+… +Sn-3)/(4*S0) W e overlaid the m anually segm ented regions ofsynovial tissue onto these param eterim ages (via im age registration)and calculated the m edian value. STA TISTIC A L A N A LYSIS Assessm entofthe change in static volum e V and dynam ic param eters from baseline to post-injection visitw as done by calculation ofa P earson coefficientcorrelation m atrix. Assessm entoflinearregression m easures betw een each ofthese param eters and each pain scale w as then perform ed. RESULTS Forthe 72 patients (41.7% fem ale,m ean age 64.3),every dynam ic param etershow ed a reduction in response to treatm entbetw een baseline and follow -up (Table 1). Sl ,Sr and G m ax all correlated w ith K trans (Table 2). The param eterw ith the strongestcorrelation w ith change in VAS pain w as change in Sl(r=0.29,b=0.64;95% C I0.11 to 1.17; p=0.02),w hich is a strongercorrelation than change in volum e V*s (r=0.19,b=0.18;95% C I-0.05 to 0.41;p=0.13).O therparameters w ith strong correlations to change in VAS pain w ere change in Sr (r=0.29,b=0.56;95% C I0.09 to 1.03;p=0.02)and change in K trans (r=0.27,b=26.93;95% C I2.24 to 51.63;p=0.03). CONCLUSION D ynam ic m easures ofsynovial enhancem entcorrelate m ore strongly w ith pain reduction afterintraarticularsteroid injection than static m easures ofchange in synovial volum e. In studies exam ining synovial response to treatm entin osteoarthritis, dynam ic param eters m ay optim ize the detection oftreatm enteffects. Late synovial enhancement detects effects of intra-articular steroids on synovitis better than synovial volume A. D. Gait 1 , E. J. Marjanovic 1,2 , M. J. Parkes 2 ,R. Hodgson 1 , T. F. Cootes 1 , T. W. O'Neill 2,5 , C. E. Hutchinson 3 , D. T. Felson 2,4,5 1 Department of Imaging Science and Biomedical Engineering (ISBE), Univ. of Manchester, Manchester, UNITED KINGDOM. 2 Research in Osteoarthritis Manchester (ROAM), Arthritis Research UK Epidemiology Unit, Univ. of Manchester, Manchester, UNITED KINGDOM. 3 Warwick Medical School, Univ. of Warwick, Coventry, UNITED KINGDOM. 4 Clinical Epidemiology Unit, Boston Univ. School of Medicine, Boston, MA, USA. 5 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UNITED KINGDOM. FIGURE 1: POST GD-ENHANCED MRI SHOWING SYNOVITIS CHANGE Baseline visit Post-injection visit Baseline, TA009 Visit 2, TA009 Baseline, TA024 Visit 2, TA024 FIGURE 2: EXAMPLES OF RESULTS OF IMAGE ANALYSIS FOLLOWING MANUAL SEGMENTATION OF SYNOVIAL TISSUE LAYER (CARTILAGE: GREEN; SYNOVIAL FLUID: BLUE; SYNOVIAL TISSUE: RED) ACKNOWLEDGEMENTS Thanks to Ross Little and Sue Cheung of Imaging Sciences, University of Manchester, and to Gio Buccanorsi of Bioxydyn, for their insights into the DCE-MRI modelling used in this work, gained from their experiences in oncological studies over a number of years. Supported by Arthritis Research UK programme grant 18676; Manchester Academic Health Science Centre (MAHSC); Salford Royal NHS Foundation Trust; National Institute for Health Research (NIHR) TABLE 1: STANDARDISED RESPONSE MEANS FOR CHANGE IN EACH PARAMETER IN THE STUDY, FOLLOWING TREATMENT TABLE 2: PEARSON CORRELATION COEFFICIENT MATRIX Colour Scale: 1.00 0.75 0.50 0.25 0.00 -0.25 -0.50 -0.75 -1.00 FIGURE 3: DIAGRAM OF DYNAMIC PARAMETERS vi vi K trans ve vp ve Variable Variable description SRM (m ean change /SD (m ean change) ) K trans Permeabilityparameterin Toftsequation -0.62 v e Fractional volum e ofextra- cellularspace -0.46 v p Fractional volum e ofplasm a space -0.23 V (Static)volum e -0.41 V×s (Static)volum e *synovial fraction -0.37 Gm ax M axim um gradient -0.63 S l Late relative enhancem ent -0.76 S r M axim um relative enhancem ent -0.73 Pain on nom inated activityVAS Visual analogue scale for pain, com pleted bypatient -1.17 Correlations K trans ve vp V V×s Gm ax Sl Sr Pain on nominated activityVAS* K trans 1.00 ve 0.71 1.00 vp -0.13 -0.10 1.00 V 0.15 0.10 0.04 1.00 V×s 0.11 0.08 0.13 0.94 1.00 Gm ax 0.70 0.34 0.21 0.09 0.03 1.00 Sl 0.78 0.66 -0.04 0.23 0.18 0.71 1.00 Sr 0.74 0.61 -0.05 0.20 0.14 0.74 0.98 1.00 Pain on nom inated activityVAS* 0.27 0.23 0.02 0.19 0.19 0.07 0.29 0.29 1.00 *Observations are 64 due to 8 patients missing VAS observations (patients did not complete question)
-
Upload
alan-sampson -
Category
Documents
-
view
42 -
download
0
description
Late synovial enhancement detects effects of intra-articular steroids on synovitis better than synovial volume A. D. Gait 1 , E . J. Marjanovic 1,2 , M. J. Parkes 2 ,R. Hodgson 1 , T. F. Cootes 1 , T . W. O'Neill 2 ,5 , C . E. Hutchinson 3 , D. T. Felson 2 ,4,5 - PowerPoint PPT Presentation
Transcript of FIGURE 1: POST GD-ENHANCED MRI SHOWING SYNOVITIS CHANGE
BACKGROUND
In knee OA, knee pain decreases after intra-articular steroid treatment but the optimal way to assess an effect of this treatment on synovium is unknown.
On contrast enhanced MRI, static synovial volume can be quantified as can the dynamic rate of enhancement of synovium at different times after contrast injection.
The best way to evaluate synovium after treatment would maximize the correlation between synovial change and pain change.
AIM
In persons undergoing intra-articular steroid injections of the knee, do changes in dynamic parameters of synovial enhancement correlate better with reduction in knee pain than changes in static synovial volumes?
METHODS
Subjects with symptomatic knee OA (ACR criteria) Design: Open Label Clinical Trial (‘TASK’) ISRCTN07329370, in which subjects had 2 contrast enhanced MRI’s, one before intra-articular steroid injection and one 5-15 days afterward. Intervention: Intra-articular depomedrone 80mg Pain Assessments: VAS score - pain on nominated activity (VASNA): 0 (no pain) to 10 Assessments at baseline and 5-15 days post injection
IMAGING
MRI Scan: 3T Philips MRI, Gadolinium-enhanced sequences (~7 minutes, axial, 18 images at ~22-second intervals) TR 5.3 ms,
TE 1.463 ms, FoV 14cmx14cm, Slice thickness 3mm (used for dynamic data)
(sagittal), taken ~8 minutes after enhancement: TR 500ms, TE 17ms, FoV 15.9cm x 15.9cm, Slice thickness 3mm (used for static volumes) (Figure 1)
IMAGE ANALYSIS: MANUAL SEGMENTATION
Manual segmentation of the synovial tissue layer (including fluid and possibly cartilage) was performed on the post contrast knee image by a single observer (ICC=0.94).
We excluded cartilage within the segmented space by thresholding in a registered sagittal scan (3DWATSc: TR 20ms, TE 7.7ms, FoV 15cmx15cm, slice thickness 1.5mm). We calculated the proportion s of synovial tissue in every voxel using s=(S-mf)/(ms-mf) truncated to [0,1], where S is the voxel intensity and mf, ms are the means of the intensity distributions of fluid and synovial tissue volume (Figure 2).
IMAGE ANALYSIS: DYNAMIC PARAMETERS
We used the extended Tofts model 𝐶𝑡ሺ𝑡ሻ= 𝑣𝑝𝐶𝑝ሺ𝑡ሻ+𝐾𝑡𝑟𝑎𝑛𝑠 𝐶𝑝(𝜏)𝑒−𝐾𝑡𝑟𝑎𝑛𝑠𝑣𝑒 (𝑡−𝜏)𝑑𝜏𝑡0 which is a solution of the pharmacokinetic equation, to calculate the parameters Ktrans (permeability), ve (extra-cellular space) and vp (plasma space) at every image voxel (Figure 3).
We calculated parameters at each voxel based upon the time series of intensity Si (i=0,..,n) over the dynamic sequence: (a) the maximum gradient Gmax, (b) the maximum relative enhancement Sr=Smax/S0, and (c) the late relative enhancement Sl=(Sn+…+Sn-3)/(4*S0)
We overlaid the manually segmented regions of synovial tissue onto
these parameter images (via image registration) and calculated the median value.
STATISTICAL ANALYSIS
Assessment of the change in static volume V and dynamic parameters from baseline to post-injection visit was done by calculation of a Pearson coefficient correlation matrix.
Assessment of linear regression measures between each of these parameters and each pain scale was then performed.
RESULTS
For the 72 patients (41.7% female, mean age 64.3), every dynamic parameter showed a reduction in response to treatment between baseline and follow-up (Table 1).
Sl, Sr and Gmax all correlated with Ktrans (Table 2).
The parameter with the strongest correlation with change in VAS pain was change in Sl (r=0.29, b=0.64; 95% CI 0.11 to 1.17; p=0.02), which is a stronger correlation than change in volume V*s (r=0.19, b=0.18; 95% CI -0.05 to 0.41; p=0.13). Other parameters with strong correlations to change in VAS pain were change in Sr (r=0.29, b=0.56; 95% CI 0.09 to 1.03; p=0.02) and change in Ktrans (r=0.27, b=26.93; 95% CI 2.24 to 51.63; p=0.03).
CONCLUSION
Dynamic measures of synovial enhancement correlate more strongly with pain reduction after intraarticular steroid injection than static measures of change in synovial volume.
In studies examining synovial response to treatment in osteoarthritis, dynamic parameters may optimize the detection of treatment effects.
Late synovial enhancement detects effects of intra-articular steroids on synovitis better than synovial volume A. D. Gait1, E. J. Marjanovic1,2, M. J. Parkes2,R. Hodgson1, T. F. Cootes1, T. W. O'Neill2,5, C. E. Hutchinson3, D. T. Felson2,4,5 1Department of Imaging Science and Biomedical Engineering (ISBE), Univ. of Manchester, Manchester, UNITED KINGDOM. 2Research in Osteoarthritis Manchester (ROAM), Arthritis Research UK Epidemiology Unit, Univ. of Manchester, Manchester, UNITED KINGDOM. 3Warwick Medical School, Univ. of Warwick, Coventry, UNITED KINGDOM.4Clinical Epidemiology Unit, Boston Univ. School of Medicine, Boston, MA, USA.5NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UNITED KINGDOM.
FIGURE 1: POST GD-ENHANCED MRI SHOWING SYNOVITIS CHANGE
Baseline visit Post-injection visit
Baseline, TA009 Visit 2, TA009Baseline, TA024 Visit 2, TA024
FIGURE 2: EXAMPLES OF RESULTS OF IMAGE ANALYSIS FOLLOWING MANUAL SEGMENTATION OF SYNOVIAL TISSUE LAYER (CARTILAGE: GREEN;
SYNOVIAL FLUID: BLUE; SYNOVIAL TISSUE: RED)
ACKNOWLEDGEMENTS
Thanks to Ross Little and Sue Cheung of Imaging Sciences, University of Manchester, and to Gio Buccanorsi of Bioxydyn, for their insights into the DCE-MRI modelling used in this work, gained from their experiences in oncological studies over a number of years.Supported by Arthritis Research UK programme grant 18676; Manchester Academic Health Science Centre (MAHSC); Salford Royal NHS Foundation Trust; National Institute for Health Research (NIHR)
Variable Variable description SRM (mean change / SD(mean change))
Ktrans Permeability parameter in Tofts equation
-0.62
veFractional volume of extra-
cellular space-0.46
vpFractional volume of plasma
space-0.23
V (Static) volume -0.41
V×s(Static) volume * synovial
fraction-0.37
Gmax Maximum gradient -0.63
Sl Late relative enhancement -0.76
SrMaximum relative
enhancement-0.73
Pain on nominated activity VAS Visual analogue scale for pain, completed by patient
-1.17
TABLE 1: STANDARDISED RESPONSE MEANS FOR CHANGE IN EACH PARAMETER IN THE STUDY, FOLLOWING TREATMENT
TABLE 2: PEARSON CORRELATION COEFFICIENT MATRIX
ColourScale:1.000.750.500.250.00-0.25-0.50-0.75-1.00
Correlations Ktrans ve vp V V×s Gmax Sl SrPain on nominated
activity VAS*
Ktrans 1.00
ve 0.71 1.00
vp -0.13 -0.10 1.00
V 0.15 0.10 0.04 1.00
V×s 0.11 0.08 0.13 0.94 1.00
Gmax 0.70 0.34 0.21 0.09 0.03 1.00
Sl 0.78 0.66 -0.04 0.23 0.18 0.71 1.00
Sr 0.74 0.61 -0.05 0.20 0.14 0.74 0.98 1.00
Pain on nominated activity VAS*
0.27 0.23 0.02 0.19 0.19 0.07 0.29 0.29 1.00
*Observations are 64 due to 8 patients missing VAS observations (patients did not complete question)
FIGURE 3: DIAGRAM OF DYNAMIC
PARAMETERS
vivi
Ktransve
vp
ve
![Remitting seronegative symmetrical synovitis with … · Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) is a rare rheumatologic ... [7]. However, cases of](https://static.fdocuments.net/doc/165x107/5adb86477f8b9a4a268b69df/remitting-seronegative-symmetrical-synovitis-with-seronegative-symmetrical-synovitis.jpg)
