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Vikas Agarwal1, Rishi Awasthi2, Deepak Tripathi1, Vinita Agrawal3, RKS Rathore4, Kusum Sharma5, CM Pandey6 and, Rakesh Kumar Gupta2
1Department
of Clinical Immunology, 2Radiodiagnosis, 3Pathology, 6Biostatistics, SGPGIMS, Lucknow. 4Department of Mathematics, IIT, Kanpur. 5Department of Medical Microbiology, PGIMER, Chandigarh
Financial Disclosures
No conflicts of interest to disclose
Chronic Inflammation
Infiltration with chronic inflammatory cells
Expression of proinflammatory cytokines & chemokines.
H+
OHH+ OH-
H+
OH- + H H+ OHH+ H+ OHOH-
H+
OH-
H+
OH H+
Magnetic field
OHH+
H2O
H2O OH-
Diffusion Gradient
H+ OH-
OH-
DTI indices
FA =Fractional Anisotropy
MD = Mean diffusivity CL = Linear anisotropy CP = Planar anisotropy CS= Spherical isotropy
Diffusion anisotropy can be exploited to gain information about the tissue organization at a microscopic level.
(Denis Le Bihan at el. J Magn Reson Imagn 2001)
The DTI indices were measured in the inflamed synovial membrane whereas
inflammatory cytokines were measured in synovial fluid, But not in synovial membrane.
DTI could replace synovial histology or synovial fluid analysis for serial assessment of the synovial inflammation
Hypothesis
DTI derived metrics may reflect the aggregation of the inflammatory cells in the inflamed synovium. DCE imaging may provide information regarding neo-angiogenesis in the inflamed synovium. These together may provide information about the ongoing inflammation, and its molecular correlates in situation in vivo.
Objectives
1. To correlate DTI & DCE metrics values with the inflammatory parameters;
Types and numbers of various immune inflammatory cells (CD4, CD8, B cell, Macrophage, Plasma cells) infiltrating in the synovium Proinflammatory molecules [TNF- and IL-1], expressed on these cells Adhesion molecules ICAM-1 (cd54) expressed on these cells. Proinflammatory cytokines in the SF
2.
To establish DTI & DCE metrics values as the potential surrogate marker of active inflammation in-vivo.
Patients
Newly diagnosed subjects with a inflammatory arthritis involving the knee joints were enrolled in the study Age : >18 years Inclusion criteria:
Image Acquisition Conventional MRI including DTI and DCE-MRI was performed on a 3-Tesla MR scanner using a standard 8channel knee coil Image Quantification Masks of synovial regions that enhanced on post contrast T1-weighted imaging were created using an automated segmentation algorithm. Created masks were used to segment the inflamed synovium to extract various DCE (BV, BF, ktrans, ve) and DTI (FA, MD) metrics from the segmented regions
Synovial Tissue
Synovial Fluid
Serum
ROI
(Region of Interest)
Results
Demographical Data
No. of Patients 65
Descriptive Data
DTI indices FA MD (10-3
mm2sec-1)
39.6113.42(18-76)
45/20 29.236.6 (6-192 months) 6
CL CP CS BF(ml/100gm/
min)
DCE indices
BV(ml/100gm) 9.5444.20 2.491.00 k ep(min-1) 1820.44211.64 PCI Immune cells in synovium 154.9348.65 CD3 63.4132.85 CD4 53.5817.62 CD8 39.3313.96 CD20 52.9317.27 CD34 36.3513.14 CD54 163.2034.61 CD68 36.0614.49 CD138 TOTALCEL 489.66106.38 LS 31.0918.15 IL-1 24.7011.51 TNF-
Chronic Monoarthritis
OA TB USPA Undifferentiated Arthritis JIA AS Reactive Arthritis Leprosy
11
3 15 14 10
1
2 2 1
250
300
CD 3 CD 8 Linear (CD 4)
80
100
0
0 50 CD68 100 150 Linear (CD68) 200 250
400
600
800
DTIMRI
CD 8
0.85** -0.46** 0.41** 0.12
CD 20
0.27* -0.08 0.25* 0.02
CD68
0.68** -0.28* 0.14 0.10
CD 138
0.30*
-0.08 0.25* 0.02
CD 54
0.51** -0.20 0.17 0.08
TNF- IL-1
0.41* -0.01 0.23 0.08 0.60** 0.30* 0.51** 0.06
FA MD CL CP
CS
PCI
-0.30*
-0.07
-0.37*
0.11
-0.35**
0.10
0.07
0.06
-0.35**
-0.03
0.07
0.17
-0.16
-0.16
-0.15
0.15
-0.34*
0.107
-0.32**
0.069
20 15 10 5 0 0 20 40 CD34 60
80
100
Series1
Linear (Series1)
Series1
Linear (Series1)
BF BV
80 100
0.81** 0.84**
k ep
PCI
0.30*
0.15
Linear (Series1)
0
-126.66 -120.28 -56.01 11.50 3.79 -7.32 -12.44 -48.16 -10.08
1
1269.34 828.04 494.02 125.45 145.44 768.64 219.97 357.25 156.83 3168.58
R2
0.64 0.59 0.73 0.00 0.09 0.46 0.26 0.36 0.17 0.83
Sig.
<0.001 <0.001 <0.001 0.026 0.013 <0.001 <0.001 <0.001 0.001 <0.001
SE
(estimates)
FA
29.42 21.02 9.08 13.52 13.89 25.55 11.36 14.58 10.54 43.67
CD20
CD 138 CD68 CD54 IL-1 TNF-
CD 34
BF BV Kep PCI
Conclusions
A high FA on DTI correlated with inflammatory cell aggregation in the inflamed synovium. DCE parameters (BV, BF) correlated with the markers of angiogenesis i.e. CD34. Correlation of both DTI and DCE parameters varied with the intensity of inflammation. Thus, DTI and DCE metrics capture cellular and molecular events of inflammation and correlated with the degree of inflammation.
Acknowledgement
This study was financially supported by Indian Council of Medical Research (ICMR, Grant No. 5/4-5/4/Ortho/08/NCD1), New Delhi, India.