Power Doppler Ultrasound Signal Research Articles

3D Single Vessel Fractional Moving Blood Volume (3D-svFMBV): Fully Automated Tissue Perfusion Estimation Using Ultrasound.

Power Doppler ultrasound (PD-US) is the ideal modality to assess tissue perfusion as it is cheap, patient-friendly and does not require ionizing radiation. However, meaningful inter-patient comparison only occurs if differences in tissue-attenuation are corrected for. This can be done by standardizing the PD-US signal to a blood vessel assumed to have 100% vascularity. The original method to do this is called fractional moving blood volume (FMBV). We describe a novel, fully-automated method combining image processing, numerical modelling, and deep learning to estimate three-dimensional single vessel fractional moving blood volume (3D-svFMBV). We map the PD signals to a characteristic intensity profile within a single large vessel to define the standardization value at the high shear vessel margins. This removes the need for mathematical correction for background signal which can introduce error. The 3D-svFMBV was first tested on synthetic images generated using the characteristics of uterine artery and physiological ultrasound noise levels, demonstrating prediction of standardization value close to the theoretical ideal. Clinical utility was explored using 143 first-trimester placental ultrasound volumes. More biologically plausible perfusion estimates were obtained, showing improved prediction of pre-eclampsia compared with those generated with the semi-automated original 3D-FMBV technique. The proposed 3D-svFMBV method overcomes the limitations of the original technique to provide accurate and robust placental perfusion estimation. This not only has the potential to provide an early pregnancy screening tool but may also be used to assess perfusion of different organs and tumors.

Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis

Active rheumatoid arthritis (RA) is associated with increased cardiovascular risk and impaired function of high-density lipoprotein (HDL). Previous work suggests that HDL may become dysfunctional through oxidative modifications within the RA joint. The current work evaluates an association of synovial power doppler ultrasound signal (PDUS) with HDL function and structure. Two open-label clinical therapeutic studies using PDUS as a disease outcome measure were included in this analysis, including a 12-month trial of subcutaneous abatacept in 24 RA patients and a 6-month trial of IV tocilizumab in 46 RA patients. Laboratory assays included assessments of HDL function and structure, HDL and total cholesterol levels, and a cytokine/chemokine panel. Patients with the highest baseline PDUS scores in both clinical studies, had worse HDL function, including suppression of paraoxonase 1 (PON1) activity as well as lower HDL-C levels. Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted but were generally of lesser magnitude and consistency than PDUS across the HDL profile. Treatment with tocilizumab for 6 months was associated with increases in cholesterol levels and improvements in the HDL function profile, which correlated with greater decreases in PDUS scores. Similar trends were noted following treatment with abatacept for 3 months. Higher baseline PDUS scores identified patients with worse HDL function. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function.

Clinical and Power-Doppler ultrasound features related with persistence of fistulous tracts under treatment with adalimumab in hidradenitis suppurativa: 4 years of follow-up.

Fistulous tracts are the hallmark lesions of hidradenitis suppurativa (HS) and respond poorly to the currently available medical treatments. To evaluate the clinical and ultrasound features related with both healing and persistence of fistulous tracts in patients under treatment with adalimumab, a retrospective analysis of power-Doppler ultrasound (PD-US) images with fistulas in HS patients was performed. The clinical and sonographic staging of HS, body areas involved, and anatomic characteristics of the fistulous tracts were registered and graded. Chi-square test, univariate/multivariate Cox-regression analysis with clustered error, and Kaplan-Meier analysis were computed to analyze data. In total, 151 fistulous tracts from 33 HS patients were included. Age, BMI, length, thickness, subcutaneous pattern, high intensity of PD-US signal, and a high grade of fibrosis/edema were all related to a lower possibility of healing and a high risk of longer persistence at binomial Cox-regressions. Whereas, multivariate regressions showed that high fibrosis, was the variable with the highest risk of poor response and longer survival. Survival-analysis showed that fistulas with high fibrosis or PD-US signal have longer survival time than those with absent/low fibrosis or signal. Limitations include the impossibility to detect with ultrasound lesions less than 0.1 mm and smaller sample size. In conclusion, an accurate assessment of fibrosis may be crucial to define better when a surgical approach-besides the medical treatment-could be required. PD-US may assess the decrease of vascularization in HS lesions and consequently the reduction of inflammation due to immunomodulatory therapies.

Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy.

Musculoskeletal ultrasound quantifies the total synovial inflammatory burden in rheumatoid arthritis (RA) but is time consuming when scanning numerous joints. This study evaluated a novel patient-centered method for constructing a longitudinal ultrasound score in RA patients. Fifty-four RA patients starting intravenous tocilizumab were evaluated with power Doppler ultrasound (PDUS) of 34 joints and DAS28-ESR was assessed at baseline and weeks 4, 12, 16, and 24. The sentinel joint score (SJS) was derived from the reduced subset of joints with PDUS ≥ 1 at baseline. Total PDUS (tPDUS) score and US7 were also calculated. Changes in tPDUS and SJS were correlated. Effect sizes were calculated for tPDUS, SJS, and US7. The proportion of "flipped" joints without baseline PDUS signal that later developed PDUS signal was estimated. At baseline, 1236/1829 joints scanned (67.5%) did not have PDUS signal. The proportion of "flipped" joints at 24 weeks was 5.6% for ≥ 1, 2.9% for ≥ 2, and 1.0% for = 3 PD. tPDUS and SJS scores were highly correlated (r = 0.91 to 0.97). Overall the effect sizes for tPDUS, SJS, and US7 increased over 24 weeks, where SJS was the highest (SJS 1.00 4-week, 1.07 12-week, 1.26 24-week) and tPDUS and US7 were comparable (tPDUS 0.32 4-week, 0.52 12-week, 0.84 24-week; US7 0.23 4-week, 0.52 12-week, 0.74 24-week). In RA patients starting a biologic, scanning only joints with baseline PDUS signal can substantially reduce the number of joints requiring follow-up scanning by 67.5% and improves feasibility. "Flipped" joints are infrequently seen after starting therapy. ClinicalTrials.gov NCT01717859 Key messages • Only a small percent of joints develop power Doppler signal after baseline scanning. • Changes in the SJS correlate well with changes in clinical activity measured by DAS28-ESR over time. • The SJS effect size is higher than total PDUS and US7 scores, and may improve examination feasibility.

SAT0376 DOES SUPPRESSION OF IL-4 AND IL-13 LEAD TO THE DEVELOPMENT OF NEW ONSET SPONDYLO-ARTHRITIS IN SUSCEPTIBLE PATIENTS?

Background:Enthesitis is a key feature of peripheral Spondyloarthritis (SpA). Several pro-inflammatory cytokines including Interleukin-17 and Interleukin-23 are found within the enthesis (1). Dupilumab is a recombinant human monoclonal antibody that inhibits signalling of Interleukin-4 and Interleukin-13, approved for use in patients with moderate- to –severe atopic eczema. Here we describe a cohort of patients with severe atopic eczema who have developed a new peripheral SpA/ enthesitis after receiving Dupilumab.Objectives:To describe the clinical and imaging details of this cohort.Methods:All patients in St John’s Institute of Dermatology who exhibited new arthralgias on Dupilumab therapy were referred for assessment in Guy’s Rheumatology Department. These patients had a focussed history, examination, ultrasound and/or MRI of affected joints and entheseal sites.Results:To date we have seen 12 patients with a history of new inflammatory peripheral SpA type symptoms following onset of Dupilumab therapy. There were 7 males and 5 females all of whom have longstanding severe atopic Eczema. All patients had raised baseline IgE levels of mainly >10000. All patients exhibited a positive response to Dupilumab with a marked improvement in eczema as measured by the EASI score. All patients had normal inflammatory markers and negative immunological screening bloods. Musculoskeletal symptom onset was between 2 and 20 weeks after starting treatment. Typically, these patients had inflammatory symptoms affecting both the small joints and the entheseal sites. 2/12 patients developed inflammatory sounding spinal pain. 2/12 patients had ultrasound evidence of arthritis. 11/12 patients had radiological findings of enthesitis as seen on MRI or ultrasound (power doppler ultrasound signal). 9/12 patients were treated with non-steroidal anti-inflammatories with variable improvement.1 patient required no treatment and 1 patient received low dose prednisolone.Conclusion:In our centre approximately 200 patients have received Dupilumab. These musculoskeletal findings have not been reported previously in clinical trials. We hypothesise that the profound inhibition of IL- 4/13 may allow an inflammatory response at the enthesis presenting with a peripheral SpA pattern. IL-4 has been shown to suppress delayed type hypersensitivity reactions (DTHRs) and psoriasis in both human and mice studies (2). These findings and the demonstratation that IL-23 transcription and secretion can be suppressed by IL-4 with resultant reduction in Th17 function (3) may be key factors as to why a SpA type response is seen in certain subjects.

Age-Related Vascularization and Ossification of Joints in Children: An International Pilot Study to Test Multiobserver Ultrasound Reliability.

To determine the intra- and interobserver reliability of ultrasound (US)-detected age-related joint vascularization and ossification grading in healthy children. Following standardized image acquisition and machine setting protocols, 10 international US experts examined 4 joints (wrist, second metacarpophalangeal joint, knee, and ankle) in 12 healthy children (divided into 4 age groups: 2-4, 5-8, 9-12, and 13-16 years). Gray-scale was used to detect the ossification grade, and power Doppler ultrasound (PDUS) was used to detect physiologic vascularization. Ossification was graded from 0 (no ossification) to 3 (complete ossification). A positive PDUS signal was defined as any PDUS signal inside the joint. Kappa statistics were applied for intra- and interobserver reliability. According to the specific joint and age, up to 4 solitary PDUS signals (mean 1.5) were detected within each joint area with predominant localization of the physiologic vascularization in specific anatomic positions: fat pad, epiphysis, physis, and short bone cartilage. The kappa values for ossification grading were 0.87 (range 0.85-0.91) and 0.58 for intra- and interobserver reliability, respectively. The bias-adjusted kappa values for intra- and interobserver reliability were 0.71 (range 0.44-1.00) and 0.69, respectively. Detection of normal findings (i.e., grading of physiologic ossification during skeletal maturation and identification of physiologic vessels) can be highly reliable by using clear definitions and a standardized acquisition protocol. These data will permit development of a reliable and standardized US approach for evaluating pediatric joint pathologies.

Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers

IntroductionThe aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis.MethodsWe selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody® Human Array.ResultsThis study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines.In the multivariate logistic regression model used to explore prognostic biomarkers for active synovitis, serum levels of bFGF, DAS28-ESR and not receiving glucocorticoids were the best predictors of active synovitis. The predictive indexes provided by the model were specificity 73.3%, sensitivity 72%, and area under the curve in receiver operating characteristic 81.5% (95% CI: 70.1% to 92.8%).ConclusionsNearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses.

SAT0491 Comparing the Power Doppler Modality of 5 Ultrasound Machines using a Microvessel Flow Phantom

BackgroundIn many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS).[1-3] However, in our experience, PDUS may be highly...

FRI0100 Treat to target: defining the optimum target to prevent radiographic erosion progression during the first year of treatment in an early rheumatoid arthritis cohort

BackgroundThe target for most treat to target (T2T) regimes in early rheumatoid arthritis (eRA) is DAS28 remission. However, power Doppler ultrasound (PDUS) activity in patients in DAS28 remission is associated...

Achilles tendon biomechanics in psoriatic arthritis patients with ultrasound proven enthesitis

Objective: To investigate Achilles tendon (AT) biomechanics in psoriatic arthritis (PsA) patients with ultrasound confirmed features of enthesitis.Method: PsA patients and healthy control subjects underwent three-dimensional (3D) gait analysis to measure walking speed, rotational joint motion and the moments, power, and AT force at the ankle–subtalar joint complex. The Glasgow Ultrasound Enthesitis Scoring System (GUESS) was used to score the presence of enthesophytes, erosions, retrocalcaneal bursitis, and tendon thickening. Power Doppler ultrasound signal (PDUS) was used to detect active disease. Peripheral joint arthritis, acute-phase reactants, global health, disability, and foot impairments were recorded. A core set of biomechanical variables that influence the insertion of the AT and indirect estimates of tendon loading were compared between PsA patients and control subjects with and without enthesitis.Results: Forty-two PsA patients with a mean disease duration of 10.6 (SD 9.4) years and 29 control subjects were studied. Seventeen (40%) PsA patients had clinically detectable AT entheseal pain. Twenty-eight (67%) PsA patients and nine (31%) control subjects had one or more GUESS enthesitis features, predominantly enthesophytes. PsA patients with enthesitis walked significantly more slowly than control subjects (p = 0.019) and generated lower peak ankle joint moments (p = 0.006), power (p = 0.001), and AT force (p = 0.003). Ankle–subtalar joint complex motion was comparable and no between-group differences were found for peak dorsiflexion (p = 0.59), eversion (p = 0.05), and internal rotation (p = 0.19).Conclusions: In this group of PsA patients, the AT insertional angle was not influenced by ankle–subtalar joint motion in those with and without enthesitis. Moreover, the PsA patients with enthesitis had significantly lower AT loading.

Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

IntroductionIn many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom.MethodsThe flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine.ResultsThe minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes.ConclusionsWe created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.

Linking Power Doppler Ultrasound to the Presence of Th17 Cells in the Rheumatoid Arthritis Joint

BackgroundPower Doppler ultrasound (PDUS) is increasingly used to assess synovitis in Rheumatoid Arthritis (RA). Prior studies have shown correlations between PDUS scores and vessel counts, but relationships with T cell immunopathology have not been described.Methodology/Principal FindingsPBMC were isolated from healthy controls (HC) or RA patients and stimulated ex vivo with PMA and ionomycin for 3 hours in the presence of Golgistop. Paired synovial fluid (SF) or synovial tissue (ST) were analysed where available. Intracellular expression of IL-17, IFNγ, and TNFα by CD4+ T cells was determined by flow cytometry. Synovial blood flow was evaluated by PDUS signal at the knees, wrists and metacarpophalangeal joints of RA patients. Serum, SF and fibroblast culture supernatant levels of vascular endothelial growth factor-A (VEGF-A) were measured by ELISA. The frequency of IL17+IFNγ-CD4+ T cells (Th17 cells) was significantly elevated in peripheral blood (PB) from RA patients vs. HC (median (IQR) 0.5 (0.28–1.59)% vs. 0.32 (0.21–0.54)%, p = 0.005). Th17 cells were further enriched (mean 6.6-fold increase) in RA SF relative to RA PB. Patients with active disease had a higher percentage of IL-17+ T cells in ST than patients in remission, suggesting a possible role for Th17 cells in active synovitis in RA. Indeed, the percentage of Th17 cells, but not Th1, in SF positively correlated with CRP (r = 0.51, p = 0.04) and local PDUS-defined synovitis (r = 0.61, p = 0.002). Furthermore, patients with high levels of IL-17+CD4+ T cells in SF had increased levels of the angiogenic factor VEGF-A in SF. Finally, IL-17, but not IFNγ, increased VEGF-A production by RA synovial fibroblasts in vitro.Conclusions/SignificanceOur data demonstrate a link between the presence of pro-inflammatory Th17 cells in SF and local PDUS scores, and offer a novel immunological explanation for the observation that rapid joint damage progression occurs in patients with persistent positive PDUS signal.