Ultrasound microflow imaging for the evaluation of inflammation associated with superficial vein thrombosis: a proof-of-concept case report

Abstract

Venous thrombosis is associated with an inflammatory process contributing to thrombus initiation, propagation, venous wall remodeling, and fibrous sequelae. Conventional ultrasound is the gold standard for diagnosing venous thrombosis, but primarily focuses on luminal obstruction and vein compressibility, providing limited information about vascular wall inflammation and microvascular perfusion. This proof-of-concept case study examines the potential of microvascular flow imaging (MVFI), specifically Samsung MV-Flow^®, to evaluate perithrombotic inflammation, quantified by measuring the vascularity index (VI). A 40-year-old male with Behçet’s disease and a history of thrombotic episodes presented with acute thigh pain. Conventional ultrasound confirmed an occlusive thrombus in a superficial tributary of the great saphenous vein. MV-Flow imaging with an LA4-18 MHz probe revealed pronounced perivascular hyperemia. Serial follow-ups at 1, 3, and 6 months under immunosuppressive and antithrombotic therapy demonstrated clinical improvement, thrombus regression, and a consistent decrease in the VI from 11.7% to 5.15%, mirroring normalization of C-reactive protein (CRP) levels. This case demonstrates the added diagnostic value of MVFI in detecting and quantifying perithrombotic microvascularization. Compared with conventional Doppler, MVFI offers improved sensitivity for low-velocity blood flow and enables objective monitoring of inflammatory activity via the VI. These findings suggest that MVFI may represent a useful adjunct to standard venous ultrasound for assessing inflammation associated with venous thrombosis and for monitoring disease evolution, supporting further investigation in larger clinical studies.

Introduction

Venous thrombosis is not only a disorder of coagulation but also a condition in which inflammation plays a central role in thrombus initiation, propagation, and resolution. In the early phase, the recruitment of neutrophils and monocytes, cytokine release, and endothelial activation predominate in the clot environment (1,2). Later, the thrombus becomes more fibrotic, with reduced inflammatory activity. Thus, inflammatory assessment may help differentiate between recent and chronic thrombosis, a distinction that has important therapeutic implications. Histopathological studies suggest that inflammation promotes venous wall fibrosis and valve destruction, thereby contributing to the development of chronic venous insufficiency (3,4). Moreover, excessive or dysregulated inflammation may impair clot lysis and venous recanalization, thereby predisposing patients to recurrent events or chronic venous obstruction (5-7). Prospective data show that elevated inflammatory markers measured at baseline are associated with a higher risk of developing post-thrombotic syndrome (PTS) (8).

Current imaging techniques, primarily ultrasound, are effective for detecting venous thrombosis but are limited in assessing vascular wall inflammation, microvascular flow abnormalities, and in situ thrombus organization as reported in histology in mice (9) and in vivo in humans with contrast-enhanced ultrasound (CEUS) (10). The development of new ultrasound imaging modes dedicated to microvascular flow, known as microvascular flow imaging (MVFI) techniques, is a significant advancement in non-invasive vascular diagnostics, offering high-resolution, real-time visualization of low-velocity blood flow. Unlike conventional color or power Doppler, MVFI employs advanced motion suppression and clutter filtering algorithms to isolate slow-flow signals from tissue motion artifacts, thereby enhancing sensitivity and specificity for detecting microvascular perfusion (11,12). This recent modality has already demonstrated utility across several clinical domains, such as the detection of low-grade synovial inflammation in inflammatory arthritis (13) and in assessing renal cortical perfusion and inflammatory activity in Crohn’s disease (14,15). However, it must be acknowledged that, to date, no standardized methodology exists for microvascular flow assessment.

Through this case report, we aim to demonstrate that measuring microvascularization around venous thrombosis with MVFI can serve as a surrogate for assessing inflammation associated with acute thrombosis.

Case presentation

A 40-year-old male with a history of Behçet’s disease and multiple unprovoked deep and superficial vein thromboses leading to a severe PTS, presented with an acute onset of localized pain in the medial side of the right thigh. The patient was prescribed vitamin K antagonist (VKA) therapy, colchicine 1 mg, and azathioprine 150 mg; however, azathioprine had not been taken for several weeks before this. Physical examination revealed rubor, calor, and tenderness along the right great saphenous vein at the level of the thigh. Laboratory tests showed a normal leukocyte count (4.2×10⁹/L) but an elevated C-reactive protein (CRP) level (19.3 mg/L). Given the patient’s history and current symptoms, a venous duplex ultrasound was performed. B-mode and color Doppler imaging identified a hypoechoic, occlusive thrombus of a superficial tributary of the great saphenous vein of the right lower limb. The vein was non-compressible, with an increased caliber, and without detectable color flow within the lumen.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Technical note on ultrasound examination

To further evaluate the venous thrombosis, MV-Flow acquisitions (Samsung Electronics^®) using a high-frequency linear probe (LA4-18, 4–18 MHz frequency range) were performed. MV-Flow is an MVFI mode developed by Samsung^®, designed to visualize microvascular structures within tissues better. This mode is a specific microflow analysis method with a higher frame rate. This technology then filters out tissue motion, providing a more sensitive detection of slow blood flows in small vessels. When applied to venous thrombosis, MV-Flow mode reveals perivenous hyperemia as an intense microvascular network, not present around non-thrombosed veins.

Nevertheless, the MV-Flow gain setting is crucial for ensuring sufficient sensitivity and avoiding background noise. In our case, the gain was preset at 50% and remained unchanged across successive examinations, allowing images obtained with the same settings to be compared (Figure 1).

Figure 1.

MV-Flow imaging findings and vascularity index quantification during follow-up of superficial vein thrombosis. Initial assessment (T0) reveals a significant microvascular network surrounding the hypoechoic thrombus (upper panel), which is also present during follow-up but progressively decreases in size at 1 month, 3 months, and 6 months. This reduction in hyperemia can be quantified using the vascularity index (bottom panel).

An assessment of perivenous microvascularization using MV-Flow was performed along the entire length of the thrombosed vein, with cross-sectional images recorded. The image visually exhibiting the most developed microvascular network was selected for analysis. From this image, the vascularity index (VI) was measured, defined as the percentage of microvascular signal detected (i.e., the number of pixels with Doppler signal) within a standardized region of interest (ROI) surrounding the thrombosed vein. VI has already been proposed in various circumstances and can be measured in different defined areas (16-18). ROI was manually defined here as being the cross-sectional area of a disc twice the diameter of the thrombosed vein on MV-Flow images (Figure 1). For this purpose, we used custom-developed software that enables post-acquisition analysis, performed by a single trained operator. The VI data obtained with our software were similar to the data obtained with the Samsung proprietary software. Post-processing was conducted here to standardize the measurements better.

Lastly, pulsed Doppler was acquired, sampling selected small perivenous vessels, with the area of interest positioned using guidance from the MV-Flow image. The resulting Doppler spectrum showed an arterial systolo-diastolic flow, indicative of hyperemia (Figure 2). This finding confirms that the observed MVFI signal represents true hyperemia rather than Doppler artifacts or a venous signal related to vein recanalization.

Figure 2.

Pulsed Doppler evaluation of perivenous hyperemia flows. The MV-Flow images (A,B) allow the pulsed Doppler sampling to be positioned (C,D). The pulsed flow shows that the vessels visualized perivenously are small arterioles. Noteworthy is a low initial resistivity index (systolic-diastolic flow) associated with inflammation, which becomes more resistive during follow-up.

Management and outcome

Following the diagnosis of superficial vein thrombosis, as the patient had an international normalized ratio (INR) of 2.69, anticoagulant therapy with a VKA was continued. But, given the context of Behçet’s disease, azathioprine was reintroduced and maintained in combination with colchicine to manage the underlying systemic inflammatory condition. The patient received motivational intervention to promote medication adherence.

Clinical follow-up was conducted at 1, 3, and 6 months after diagnosis. At each visit, the patient reported progressive improvement in symptoms, including resolution of erythema and tenderness. The favorable clinical course was attributed to both the typically self-limiting nature of superficial venous thrombosis and the reinstatement of immunosuppressive therapy, which likely contributed to the suppression of the underlying inflammatory activity.

At each follow-up visit, a venous duplex ultrasound was performed. B-mode imaging revealed a progressive reduction in the caliber of the thrombosed superficial vein, documenting the thrombus resolution and the vessel remodeling. The VI showed a progressive and consistent decline over time, decreasing from 11.7% to 5.2% at 6 months, in parallel with both symptom resolution and a reduction in CRP levels, decreasing from 19.3 to 5.2 mg/L at 6 months follow-up.

Discussion

In this case report, we demonstrate that using an MVFI mode enables imaging of the microvascularization surrounding venous thrombosis without the need for a contrast agent, with greater sensitivity than conventional modes. Pulsed Doppler was used to characterize the perivenous MV-Flow signal, demonstrating arterial flow with a systolic-diastolic pattern, consistent with inflammatory hyperemia. Hyperemia can be detected globally by color Doppler or power Doppler in inflammatory tissue (19). Yet, the signal strength and number of small vessels detected are significantly lower than those with MVFI. Additionally, using MV-Flow in this case, we can quantify microvascularization using the VI (18), which is more challenging and less relevant to conventional methods. Compared with CEUS, which helps assess perivenous inflammation, the VI offers a contrast-free alternative that is readily available in daily practice and can be easily combined with venous ultrasound for diagnosis. Superficial vein thrombosis lends itself well to MVFI use, thanks to the use of high-frequency probes and the absence of large nearby arteries that could generate artefacts. For use in deep vein thrombosis, an MVFI mode that is less sensitive to motion artifacts and is available with lower-frequency probes will be required. This seems an appealing challenge, as assessing inflammation in deep vein thrombosis could allow thrombus aging, provide insights into prognosis and recurrence risk, and help identify patients at risk of PTS, potentially guiding the development of adjunctive anti-inflammatory strategies in addition to standard anticoagulation.

A limitation of this case is that, at present, there is no consensus or standardized protocol for MVFI or for measuring the VI. Parameters such as ROI selection, acquisition settings, and computational methods remain largely operator-dependent, and no large-scale clinical validation studies have established reproducibility or reference values. Future studies involving larger cohorts and standardized acquisition protocols are required to assess the reliability, reproducibility, and clinical significance of MVFI-derived quantitative metrics.

Conclusions

Easily accessible by Doppler ultrasound, the microvascularization around a venous thrombosis can be detected with MVFI and measured using the VI. The assessment and follow-up of this marker can help monitor perivenous inflammation. This biomarker may be helpful as both a diagnostic and prognostic marker and requires further investigation in the management of venous thrombosis.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.