Two- and three-dimensional Doppler sonographic evaluation of the effect of local cryotherapy on synovial perfusion in wrist arthritis

Sir, Physical treatment including local cold and heat application has been used since antiquity in patients with arthritis. Both methods are known to relieve pain and improve disability in different stages of various rheumatic diseases. An analgesic effect can be readily accomplished after 3 min of local cryotherapy by destimulating pain receptors, which are located in the subcutis. Antiphlogistic effects are obtained after cold application for 20 min and longer by vasoconstriction, by inhibiting the cellular metabolism in the inflammatory cells and by repressing the release of lysosomal enzymes [1, 2]. Whereas the effects of local cold treatment inside the cutis and subcutis have been investigated extensively, not much is known about the influence of cryotherapy inside the affected and inflamed joints themselves. In a study by Oosterveld and Rasker [3] in which a temperature probe was positioned inside the knee joint cavity of patients with rheumatoid arthritis (RA), a decrease in temperature not only in the skin and superficial tissues but also inside the joint cavity could be verified. Imaging procedures such as high resolution grey-scale ultrasound and power Doppler ultrasonography (PDUS) including three-dimensional (3D) mode have enlarged the diagnostic spectrum by direct visualization of pathomorphologic synovial changes in rheumatic diseases [4, 5]. PDUS had already been used to assess a decrease of synovial vascularization during anti-inflammatory therapy with TNF-α inhibitors or after intra-articular steroid injection [6, 7]. In a small pilot study, we analysed the possibility to visualize changes in synovial perfusion due to local cryotherapy in acute wrist arthritis by means of 2D and 3D PDUS. Wrists of 13 patients with RA, with clinically active arthritis as determined by soft-tissue swelling and tenderness, were examined by ultrasound (Table 1). Ultrasonography was carried out by a linear array transducer with variable frequency from 5 to 12 MHz (L12-5/38, HDI 5000 ATL/Philips, Bothell, WA, USA). Vascularity adjacent to, and inside, the joint capsule was visualized by PDUS. Doppler settings were standardized with a pulse repetition frequency (PRF) of 700–1000 Hz and the gain was set as suggested by Rubin et al. [8]. In a region with high-power Doppler signal intensity (region of interest, ROI), a 3D volume was acquired by a free-hand sweep. The online 3D power Doppler software (3D CPAR) provided by the HDI 5000 was used to generate a 3D image of a peri- and intra-articular blood vessel tree, in which the grey-scale information of the surrounding tissue had already been subtracted. After the first sonographic examination, a cold pack (TMP Tüshaus Type 12 × 29 cm) was put for 20 min on the inflamed wrist. Temperature of the cutis decreased from 33°C to 5.5°C after 20 min cold application. Immediately after removal of the cold pack, sonographic re-examination was performed by the same investigator. One of the two experienced ultrasound investigators (J.S. or K.S.) performed sonographic examination under supervision of the other. One representative 2D and 3D image of each patient, before and after local cryotherapy, were additionally reviewed by two blinded readers (P.K. and A.S.). The two investigators and the two blinded readers analysed the degree of vascularity by means of 2D and 3D power Doppler images before and after the application of local cold, using a semiquantitative grading system from 0 to 3 (0 = no flow, 1 = mild flow, 2 = moderate flow, 3 = intense flow). Informed consent was obtained from each patient. Demographic and clinical data as well as power Doppler sonographic findings of the examined patients The median grading level, before and after local cryotherapy, resulted from all the scores of the two ultrasound investigators and the two blinded readers (0 = no flow, 1 = mild flow, 2 = moderate flow, 3 = intense flow). RF, rheumatoid factor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; CryoTh, cryotherapy (local application of a cold pack on an inflamed wrist for 20 min); Pred, prednisolone; NSAID, non-steroidal anti-inflammatory drug; MTX, methotrexate; Lef, leflunomide. Demographic and clinical data as well as power Doppler sonographic findings of the examined patients The median grading level, before and after local cryotherapy, resulted from all the scores of the two ultrasound investigators and the two blinded readers (0 = no flow, 1 = mild flow, 2 = moderate flow, 3 = intense flow). RF, rheumatoid factor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; CryoTh, cryotherapy (local application of a cold pack on an inflamed wrist for 20 min); Pred, prednisolone; NSAID, non-steroidal anti-inflammatory drug; MTX, methotrexate; Lef, leflunomide. 2D and 3D power Doppler sonographic images of three patients before and after local cryotherapy of the wrist (Patient 8, Patient 3 and Patient 11). A reduction of synovial blood vessels in size and number in Patients 8 and 3 is more obvious in a 3D mode compared with 2D PDUS, because 3D imaging visualizes the whole blood vessel tree in the region of interest. An increased peri- and intra-articular microvascular power Doppler flow indicating arthritic activity could be found in all the examined joints (Fig. 1). In all patients, the ROI was identified at the second examination after 20 min of cryotherapy, so that the blinded readers could match the respective images. The rate of exact agreement in scoring between the two ultrasound investigators was 0.67 for all assessments before and after cryotherapy, compared with a rate of 0.65 between the two blinded readers. Median grading scores were calculated, which were based on the 2D and 3D scores of the four different assessors. A significant reduction of vascular signal, which was determined as a decrease of at least one grading level, was found in seven out of 13 patients (54%) after the application of local cold pack (Table 1). Five out of these seven patients (71%), who showed a temporary decrease of synovial blood flow, mentioned clinical symptoms of wrist arthritis for a period of no longer than 8 weeks. The discrimination between patients who showed a temporary reduction of synovial perfusion after local cold application and those who did not show a reaction of synovial blood vessels may reflect an underlying disturbance of normal vasoregulatory function, which possibly depends at least partially on the amount of the newly formed blood vessels (angiogenesis) [9, 10]. The 2D and 3D PDUS are able to detect and visualize changes in synovial perfusion, indicating that these methods are useful tools in the assessment of disease activity and response to different treatments in arthritis patients. We are grateful for the help of Andrea Schlichting (A.S.) who read the ultrasound images under blinded conditions.