Disclosures. Ultrasonography. Conventional radiography (XR) Magnetic resonance imaging. Conventional CT 10/27/2013

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1 What I can see in my gout patient that I couldn t before: the role of advanced imaging in gout diagnosis and monitoring Disclosures ND is supported by the Health Research Council of New Zealand I have no other relevant disclosures Nicola Dalbeth Bone and Joint Research Group University of Auckland, New Zealand Conventional radiography (XR) Features: Bone erosion New bone formation Joint space narrowing Soft tissue densities (tophi) Only imaging method currently included in gout classification criteria Asymmetrical swelling within a joint Subcortical cyst without erosions Wallace Arthritis Rheum 1977 Characteristic features Double contour sign Tophus Ultrasonography Many other features described Synovial hypertrophy Intra-articular PD signal Erosion Snow storm appearance in joint fluid Grassi Semin Arthritis Rheum 2006 Thiele Rheumatology 2007 Naredo Ann Rheum Dis 2013 Magnetic resonance imaging Synovitis Tophus Erosions Joint space narrowing Bone marrow edema (mild) Tendon disease Tenosynovitis Tophus Tendinitis Rupture Visualisation of tophi (170 HU) Gold standard for measurement of bone changes Erosion Sclerosis Spur formation Conventional CT Popp Sem Arthritis Rheum 1996 Poh J Rheumatol 2011 Pre- and post-contrast sagittal T1w MRI scans of the ankle Gerster Arthritis Rheum 1996 Dalbeth Ann Rheum Dis

2 Dual energy computed tomography (DECT) Urate deposits in patients with tophaceous gout Able to detect chemical composition of urate Conventional CT features PLUS urate 3D volume rendered image: urate=red 2D sagittal image: urate=green Images courtesy of Siemens Glazebrook Radiology 2011 Imaging methods in gout MSU crystals Bone erosion Joint space narrowing Tophus Synovitis Bone marrow edema Conventional radiography /- - - Ultrasonography +/ MRI Conventional CT +/ Dual-energy CT Gout is a disease of MSU crystal 2

3 Ultrasonography for gout diagnosis DECT for gout diagnosis High inter-reader kappa values when assessing acquired images ( ) Compared with controls with other forms of arthritis US double contour sign, compared with MSU crystals Sensitivity: % Specificity: % US tophus, compared with MSU crystals Sensitivity: % Specificity: % Thiele Rheumatology 2007 Ottaviani Clin Exp Rheum 2012 Naredo Ann Rheum Dis 2013 Gruber Rheumatology 2013 Inter-reader kappa values for urate 0.87 Compared with controls with other forms of arthritis DECT urate, compared with MSU crystals Sensitivity: % Specificity: % Glazebrook Radiology 2011 Bongartz Arthritis Rheum 2011 Choi Ann Rheum Dis 2012 Gruber Rheumatology 2013 Thresholds in DECT Ratio 1.28 Ratio 1.55 McQueen Ann Rheum Dis 2012 US: cartilage, bone and tendon involvement Hyperechoic aggregates in patellar tendon Double contour sign in MTP1 DECT: bone and tendon involvement DECT detects more urate than is clinically apparent Similar frequency of urate in bone and tendons Preferential sites of involvement MTP1, midfoot, ankle Achilles tendon, peroneal tendons Naredo Ann Rheum Dis 2013 Dalbeth Ann Rheum Dis

4 MRI: assessing disease complications Conventional CT: assessing disease complications Osteomyelitis: presence of high grade bone edema in concomitant osteomyelitis Spinal involvement Carpal tunnel involvement Tendon involvement including rupture T1w image in coronal plane demonstrating a tophus within the 4 th finger flexor tendon sheath Spinal disease Common in patients with poorly controlled gout (35% patients had erosion or tophi) Most frequent in lumbar spine No relationship between spinal pain and involvement on imaging Chen AJR 2000 Hsu Clin Radiology 2002 Poh J Rheumatol 2011 Konatalapalli J Rheumatol 2012 USS: cartilage involvement Thiele Rheumatology 2007 MRI: understanding mechanisms of disease Patterns of tophus spread Along compartmental and fascial lines Tophus associated with erosion BME and synovitis not independently associated with erosion Conventional CT: understanding mechanisms of disease Close relationship between intra-osseous tophus and bone erosion Preferential sites of involvement of bone erosion New bone formation strongly associated with both erosion and tophus Axial CT images of the hands showing tophus closely associated with erosion Popp Sem Arthritis Rheum 1996 McQueen Rheumatology 2013 Dalbeth Ann Rheum Dis 2009 Dalbeth Rheumatology 2010 Dalbeth Arthritis Res Ther

5 DECT: gout as a chronic disease DECT: understanding mechanisms of disease Even at sites without clinically apparent disease, MSU crystals are frequently observed Assessment of tophus structure Variable urate within tophi Analysis of sites of urate Tendon involvement frequent Preferential sites of Dalbeth J Clin Rheum 2012 Dalbeth Ann Rheum Dis 2013 Ultrasonography: response to treatment Baseline >6 months of ULT Change in tophus diameter over 1 year Sclesinger Rheumatol Int 2010 Perez-Ruiz J Rheumatol 2007 MRI: monitoring tophus size Assessment of tophus size Manual outlining Contrast not required for tophus measurement Intra-reader ICC 1.00, interreader ICC 0.98 Conventional CT: monitoring tophus size Tophus measurement Manual outlining Intra-reader ICC 1.00, inter-reader ICC 0.99 High correlation with physical measurement (r=0.91) Volume: 29.36cm3 Dalbeth Arthritis Rheum 2007 Schumacher Int J Clin Prac 2006 Manual outlining technique for tophus volume assessment Manual outlining technique for tophus volume assessment 5

6 Conventional CT: monitoring erosion DECT: monitoring disease CT erosion score Feasible (7 bones/foot) High inter-observer reliability (ICC 0.96) Captures bones most frequently affected by gout Correlates well with other measures of gout severity Distinguishes between mild and severe chronic gout Using modification of RAMRIS erosion score Dalbeth Rheumatology 2010 Sites for scoring CT bone erosion Measurement of urate Rapid, automated software Excellent inter-reader reproducibility (ICC>0.95) Higher reproducibility than physical measurement of tophi Detects more urate than physical examination Potential role for clinical trials Dalbeth Ann Rheum Dis 2011 Dalbeth J Clin Rheum 2012 Choi Ann Rheum Dis 2012 DECT urate volume measurement Images courtesy of Siemens Ultrasonography: detection of presymptomatic gout? Individuals with hyperuricaemia but no clinical manifestations of gout may have double contour sign or tophus In those with serum urate 7mg/dL (0.42mmol/L), ultrasonography showed Double contour sign present in 25% Tophus present in 18% Not present in those with normouricaemic controls Pineda Arthritis Res Ther 2011 Howard Arthritis Care Res 2011 De Miguel Ann Rheum Dis 2012 What I can see in my gout patient that I couldn t before Gout is a chronic disease of MSU crystal USS and DECT may show features of MSU crystal when diagnosis of gout is uncertain Preferential sites affected including those not appreciated by clinical assessment: eg. midfoot, Achilles tendon Close relationship between structural joint disease and tophi Questions What is the diagnostic accuracy of US and DECT in early gout? Do advanced imaging methods provide additional diagnostic information above clinical assessment? What is the best imaging tool for outcome measurement in gout? What are the prognostic implications of double contour sign/tophus on US in the absence of clinical symptoms? MSU crystals in asymptomatic hyperuricaemia: concept of pre-symptomatic gout 6

7 Acknowledgements Auckland Rheumatology Imaging Group Fiona McQueen Anthony Doyle Quentin Reeves Lucinda Boyer Barnaby Clark Angela Gao Mark Roger Tim Sheehan Maria Lobo Barbara Curteis Megan Williams Auckland Bone and Joint Research Group Opetaia Aati Anne Horne Meaghan House Rama Kalluru Kate Gregory Greg Gamble Funders Health Research Council of New Zealand Auckland Medical Research Foundation Auckland Regional Rheumatology Trust 7