Super-Resolution Ultrasound Localization Microscopy of Microvascular Structure and Flow for Distinguishing Metastatic Lymph Nodes – An Initial Human Study

Abstract

Purpose Detecting and distinguishing metastatic lymph nodes (LNs) from those with benign lymphadenopathy are crucial for cancer diagnosis and prognosis but remain a clinical challenge. A recent advance in super-resolution ultrasound (SRUS) through localizing individual microbubbles has broken the diffraction limit and tracking enabled in vivo noninvasive imaging of vascular morphology and flow dynamics at a microscopic level. In this study we hypothesize that SRUS enables quantitative markers to distinguish metastatic LNs from benign ones in patients with lymphadenopathy.

Materials and Methods Clinical contrast-enhanced ultrasound image sequences of LNs from 6 patients with lymph node metastasis and 4 with benign lymphadenopathy were acquired and motion-corrected. These were then used to generate super-resolution microvascular images and super-resolved velocity maps. From these SRUS images, morphological and functional measures were obtained including micro-vessel density, fractal dimension, mean flow speed, and Local Flow Direction Irregularity (LFDI) measuring the variance in local flow direction. These measures were compared between pathologically proven reactive and metastasis LNs.

Results Our initial results indicate that the difference in the indicator of flow irregularity (LFDI) derived from the SRUS images is statistically significant between the two groups. The LFDI is 60% higher in metastatic LNs compared with reactive nodes.

Conclusion This pilot study demonstrates the feasibility of super-resolution ultrasound for clinical imaging of lymph nodes and the potential of using the irregularity of local blood flow directions afforded by SRUS for the characterization of LNs.

Zusammenfassung

Ziel Der Nachweis und die Differenzierung metastatischer Lymphknoten (LK) von den LK einer benignen Lymphadenopathie sind entscheidend für die Krebsdiagnose und -prognose, stellen jedoch eine klinische Herausforderung dar. Ein neuer Fortschritt der Superresolution-Ultraschall-Bildgebung (SRUS) durch Lokalisierung einzelner Mikrobläschen hat die Beugungsgrenze durchbrochen und eine nicht invasive In-vivo-Bildgebung der Gefäßmorphologie und Flussdynamik auf mikroskopischer Ebene ermöglicht. In dieser Studie stellen wir die Hypothese auf, dass SRUS quantitativen Markern ermöglicht, metastatische von benignen LK bei Patienten mit Lymphadenopathie zu unterscheiden.

Material und Methoden Klinische kontrastverstärkte Ultraschall-Bildsequenzen der LK von 6 Patienten mit Lymphknoten-Metastasen und von 4 mit gutartiger Lymphadenopathie wurden aufgenommen und bewegungskorrigiert. Diese wurden dann verwendet, um hochaufgelöste mikrovaskuläre Bilder und hochaufgelöste Geschwindigkeitskarten zu erstellen. Aus diesen SRUS-Bildern wurden morphologische und funktionelle Messwerte gewonnen, darunter die Dichte der Mikrogefäße, die fraktale Dimension, die mittlere Flussgeschwindigkeit und die Unregelmäßigkeit der lokalen Flussrichtung („Local Flow Direction Irregularity“, LFDI), die die Abweichung der lokalen Flussrichtung misst. Diese Messungen wurden zwischen pathologisch nachgewiesenen reaktiven und metastatischen LK verglichen.

Ergebnisse Unsere ersten Ergebnisse deuten darauf hin, dass der Unterschied beim Indikator Fluss-Unregelmäßigkeit (LFDI), der aus den SRUS-Bildern abgeleitet wird, zwischen den beiden Gruppen statistisch signifikant ist. Die LFDI ist bei metastatischen LK um 60% höher als bei reaktiven Knoten.

Schlussfolgerung Diese Pilotstudie zeigt die Durchführbarkeit der klinischen Superresolution-Ultraschall-Bildgebung bei Lymphknoten und das Potenzial der Nutzung der Unregelmäßigkeit lokaler Blutflussrichtungen, wie sie der SRUS für die Charakterisierung von LK bietet.

Keywords

blood flow - localization microscopy - microbubble contrast agents - super-resolution ultrasound - lymph node micro-vessel

Publication History

Received: 08 September 2021

Accepted after revision: 20 June 2022

Article published online:
07 October 2022

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