Background/Purpose: Chronic synovial inflammation is characterized by accumulation of inflammatory cells and increased vascularity.  Synovial histology remains the most definitive way to delineate the severity of inflammation. Herein we hypothesize that Diffusion tensor imaging (DTI) derived metrics may delineate the aggregation of the inflammatory cells. Dynamic contrast enhanced (DCE) imaging may provide information regarding vascularity in the inflamed synovium. Combination of these may provide information about the ongoing inflammation.

Methods:

Patients with chronic knee arthritis underwent conventional, DTI and DCE MRI (3T ) followed by arthroscopic synovial biopsy.  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 and DTI metrics. Synovium was subjected to histopathology, immunohistochemistry (IHC), culture and PCR. 

Results: There were 65 patients (45 male) with mean age 39 years [range 18-76] and mean disease duration 29 months [range 4-192]. Fifteen patients had tuberculosis and rest had; undifferentiated spondyloarthropathy (n=14), chronic monoarthritis (n=11), chronic undifferentiated monoarthritis (n=10), rheumatoid arthritis (n=6), osteoarthritis (n=3), ankylosing spondylitis (n=2), reactive arthritis (n=2) and juvenile idiopathic arthritis and leprosy one each.

The mean values of various DTI and DCE and IHC parameters are presented in (Table-1). Amongst the DTI parameters, FA significantly correlated with all the inflammatory cells infiltrating into the synovium (Table-2) and various proinflammatory cytokines.  FA was the best predictor of infiltrating T cells, B cells, plasma cells, macrophages, adhesion molecule and proinflammatory cytokines. DCE parameters significantly correlated with CD34 and blood volume was the best predictor of CD34.

Table 1: Mean values of DTI, DCE, IHC markers 

DTI indices	Mean ±SD
FA	0.22±0.031
MD (×10-3 mm2sec-1)	1.63 ±0.51
CL	0.06 ±0.027
CP	0.15 ±0.054
CS	0.75±0.023
DCE indices
BF(ml/100gm/min)	109.9±42.8
BV(ml/100gm)	9.5±4.2
k ep(min-1)	2.5 ±1.0
PCI	1820.4±211.6
Immune cells in synovium
CD3	154.94 ±48.65
CD4	63.42 ±32.85
CD8	53.58±17.63
CD20	39.34 ±13.96
CD34	52.94 ± 17.28
CD54	36.35±13.14
CD68	163.2±34.62
CD138	36.06±14.49
TOTALCELLS	489.66±106.39
IL-1β	31.09±18.15
TNF-α	24.71 ±11.52

FA: Fractional Anisotropy, MD: Mean Diffusivity, CL:Linear anisotropy, CP:Planar anisotropy, CS:Spherical isotropy, BV: Blood Volume, BF: Blood Flow, ktrans: Volume transfer constant, PCI: post-contrast signal intensity.

Table.2, Correlation between the values of DTI & DCE –MRI indices with various inflammatory cells, adhesion molecule and proinflammatory cytokines and angiogenesis marker in the synovium (n=65)

DTI-MRI Indices

Infiltrating Immune cells in synovium

DCE -MRI Indices

Angiogenesis Marker in the synovium

CD3

CD 4

CD 8

CD 20

CD68

CD 138

CD 54

TNF-α

IL-1β

Total Inflammatory cells

CD 34

FA

0.800#

0.773#

0.859#

0.276*

0.681#

0.308*

0.513#

0.418*

0.604#

0.913#

BF

0.814#

ADC

-0.396#

-0.391#

-0.468#

-0.087

-0.283*

-0.079

-0.203

-0.019

0.305*

0.431#

BV

0.848#

CL

0.452#

0.325#

0.410#

0.258*

0.141

0.257*

0.172

0.237

0.510#

0.464#

CP

0.044

0.054

0.127

0.025

0.106

0.019

0.083

0.087

0.067

0.072

kep

0.308*

CS

-0.307*

-0.376*

-0.354#

0.069

-0.351#

0.078

-0.159

-0.151

-0.346*

-0.322#

PCI

-0.070

0.111

0.102

0.067

-0.036

0.177

-0.156

0.15

0.107

0.069

PCI

0.156

 

# p<0.01 level

  * P<0.05

Conclusion: DTI and DCE metrics capture cellular and molecular events and correlated with the degree of synovial inflammation. They may replace synovial histology in future.

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