Vascular perfusion kinetics by contrast-enhanced ultrasound are related to synovial microvascularity in the joints of psoriatic arthritis

Abstract

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA.

Role of Contrast-enhanced Ultrasound in the Evaluation of Inflammatory Arthritis

“…The agents were injected with the dosage of 4.8 ml[20212223] or 2.4 ml,[24] reconstituted by a 10 ml saline solution. And, a linear transducer, ranging from 4 to 12 MHz, was required for contrast imaging.…”

“…Relatively lower acoustic pressure was also selected for optimizing the detection of flow perfusion, set at about 45 kPa. [22] In recent studies, contrast-tuned imaging technology (CnTI) was emerged in evaluating the results of CEUS imaging. CnTI permitted the transmission of the frequencies of microbubbles and filtered out irrelevant signals caused by surrounding tissues.…”

“…[22243435] Another study conducted by Klauser et al . applied SI ration to assess the procedure of the enhancement.…”

Noninvasive Evaluation of Microcirculation under Normal and Pathological Conditions Using Contrast-Enhanced Ultrasonography (CEUS)

“…However, low MI CEUS is superior to Doppler CEUS in detecting intra-articular microvascularity [44]. Also, the method provides valuable quantitative data through TIC, as revealed by some studies that observed positive correlations between the peak signal intensity and microvascular density (CD105+) in the case of psoriatic arthritis [45].…”

Psoriatic disease treatment nowadays: unmet needs among the “jungle of biologic drugs and small molecules”

“…Indubitably, the evolution in psoriatic arthritis (PsA) knowledge represents an emblematic example [2]. Indeed, fundamental advances in understanding PsA pathogenesis and natural history have deeply changed its perception by both patients and physicians [3]. In the past, psoriasis was considered just a mere esthetic concern due to a primary defect in keratinocytes, leading to their hyper-proliferation.…”