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Purpose: Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models., Materials and Methods: SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length., Results: US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07-7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09-2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02-1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%-79%), and a median thrombus weight and length of 1.02 (0.96-1.43) g and 2.25 (1.5-4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model., Conclusion: SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions., Clinical Impact: Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The in vitro study was supported by an unrestricted research grant from LamePro B.V. and Bracco International B.V. Both corporations had no role in the study design, collection, analysis, and interpretation of data, nor in writing of the report, submitting the report for publication, or ultimate authority on any of the previous mentioned.

Purpose: In Paget-Schroetter Syndrome (PSS), subclavian vein thrombosis is caused by external compression of the subclavian vein at the costoclavicular junction. Paget-Schroetter Syndrome can be treated nonoperatively, surgically, or with a combination of treatments. Nonoperative management consists, in most cases, of anticoagulation (AC) or catheter-directed thrombolysis (CDT). With surgical management, decompression of the subclavian vein is performed by resection of the first rib. No prospective randomized trials are available to determine whether nonoperative or surgical management is superior. We report our long-term outcomes of both nonoperative and surgically treated patients., Materials and Methods: We retrospectively analyzed all patients with PSS who were treated between January 1990 and December 2015. Patients were divided based on primary nonoperative or primary surgical therapy. Long-term outcomes regarding functional outcomes were assessed by questionnaires using the "Disability of the Arm, Shoulder, and Hand" (DASH) questionnaire, a modified Villalta score, and a disease-specific question regarding lifestyle changes., Results: In total, 91 patients (95 limbs) were included. Seventy patients (73 limbs) were treated nonoperatively and 21 patients (22 limbs) surgically. Questionnaires were returned by 67 patients (70 limbs). The mean follow-up was 184 months (range, 43-459 months). All functional outcomes were better in the surgical group compared with the nonoperatively treated group (DASH general 3.11 vs 9.86; DASH work 0.35 vs 11.47; DASH sport 5.85 vs 17.98, and modified Villalta score 1.11 vs 3.20 points). Surgically treated patients were more likely to be able to continue their original lifestyle and sports activities (84% vs 40%, p=0.005). Patients with recurrence of thrombosis or the need for surgical intervention after primary nonoperative management reported worse functional outcomes., Conclusion: Surgical management of PSS with immediate CDT followed by first rib resection leads to excellent functional outcomes with low risk of complications. The results of nonoperative management in our non-matched retrospective comparative series were satisfactory, but resulted in worse functional outcomes and more patients needing to adjust their lifestyle compared with surgically treated patients., Clinical Impact: Patients with Paget-Schroetter Syndrome and their attending physicians are burdened by the lack of evidence concerning the optimal treatment of this entity. Case series comparing the outcomes of non-operative treatment with surgical treatment are scarce and often not focussed on functional outcomes. Data from this series can aid in the shared decision making after diagnosis of Paget-Schroetter Syndrome. Functional outcomes of non-operative management can be satisfying although high demand patient who are not willing to alter their daily activities are probably better off with surgical management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.