Lee, Christine U.

Breast biopsy markers have evolved from simple metallic devices to sophisticated multimaterial tools that have become essential for breast cancer care, demonstrating their clinical benefits in surgical planning, radiation targeting, and cost reduction.

ABSTRACT Genital lymphedema presents significant challenges in surgical management, with limited effective interventions. This case report explores the use of contrast‐enhanced ultrasound (CEUS) with microbubble injection as an alternative adjunct technique for lymphatic mapping in lymphaticovenous anastomosis (LVA) surgery for genital lymphedema. A retrospective chart review approved by our institutional review board was performed for patients with genital lymphedema undergoing LVA surgery between 2020 and 2024. Intraoperative CEUS for lymphatic mapping was used with intradermal injection of microbubble suspension Lumason (Bracco Suisse, Monroe Township, NJ, USA). Data regarding demographics, comorbidities, clinical and operative characteristics, complications, and surgical outcomes were retrieved. Three patients with genital lymphedema who underwent LVA were identified. The first patient was a 34‐year‐old female with recurrent lymphangioma circumscriptum and vesicular drainage. She successfully underwent CEUS‐guided LVA followed by two debulking procedures. The second patient was a 16‐year‐old male with congenital scrotal and lower extremity lymphedema. He had two CEUS‐guided LVAs and subsequent debulking for anterior scrotal swelling, with long‐term reduction in edema. The third patient was a 31‐year‐old female with primary lymphedema of the right lower extremity and genital region. She underwent seven CEUS and indocyanine green lymphography (ICG) guided anastomoses targeting the mons and lower abdomen, resulting in substantial symptomatic and volumetric improvement. CEUS detected target lymphatic vessels in all cases, including cases where ICG imaging failed to identify candidate lymphatic vessels. CEUS with intradermal microbubble injection successfully identified target lymphatic vessels in the preoperative planning for LVA surgery in patients with genital lymphedema.

Background: Lymphaticovenous anastomosis (LVA) is an effective surgical treatment for extremity lymphedema. Indocyanine green (ICG) fluorescent lymphography, the traditional standard for imaging lymphatic vessels, has limitations, including difficulty depicting deeper or congested lymphatics and contraindication in iodine hypersensitivity. This study evaluated contrast-enhanced ultrasound (CEUS) with microbubbles for identifying lymphatic vessels for LVA and compared it with ICG lymphography. Methods: In this single-center retrospective review, intraoperative CEUS with intradermal injection of microbubble suspension (Lumason, Bracco Diagnostics, Inc.) was used in patients before LVA surgery between October 2019 and February 2023. Pre- or intraoperative ICG lymphography was also used to identify target lymphatic vessels. All patients diagnosed with primary or secondary extremity lymphedema who underwent LVA were included. Technical success rate was defined as lymphatic vessels identified by CEUS that led to successful LVAs. Descriptive statistics were used. Results: Thirty-two patients underwent LVA surgery, with a mean age of 58.5 ± 13.9 years. CEUS identified lymphatic vessels in all 32 patients, including 7 in whom ICG failed. Two patients with ICG allergy underwent CEUS only. CEUS identified more candidate lymphatics per patient (5.3 ± 4.2) compared with ICG (2.5 ± 2.7). Of the 182 anastomoses, 96 (52.8%) were identified by both CEUS and ICG, 75 (41.2%) by CEUS only, and 11 (6%) by ICG only. Conclusions: CEUS is a promising tool for identifying lymphatic vessels in patients with lymphedema undergoing LVA, particularly when ICG lymphography is inadequate or contraindicated.

The Doppler twinkling artifact (TA) plays a crucial role in detecting some biopsy markers including those made of polymethyl methacrylate (PMMA), facilitating precise lymph node localization in diagnostic and therapeutic procedures. This study presents comprehensive signal processing analysis methods to quantify and characterize the TA phenomenon using raw, per-channel radiofrequency (RF) data acquired from PMMA markers scanned with an L7-4 linear array transducer. We evaluated signals at different stages along the image reconstruction pipeline including (1) beamforming, (2) beamformed RF signal conversion into in-phase/quadrature (IQ) signals, and (3) Doppler velocity calculations and image reconstruction. We analyzed changes of pulses within an ensemble and between ensembles (i.e., frames). We also evaluated the impact of wall filters with various cutoff frequencies on color and power Doppler image reconstruction. Comparative analysis between PMMA markers and a non-twinkling control sample demonstrated distinct TA signatures or lack thereof in color and power Doppler images. The IQ data from PMMA marker locations exhibiting TA signatures showed substantially higher variability compared to non-twinkling samples, with standard deviations approximately 20 times higher between ensembles and 5 times higher within ensembles. This quantitative analysis framework provides valuable insight into the TA signal, potentially leading to more reliable and accurate diagnostic interpretations.

The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation has been reported for objects with rough surfaces like kidney stones, sandpaper, and polymethyl methacrylate (PMMA) bone cement. Passive cavitation detection (PCD) is a method for determining the presence of bubble oscillation from subharmonic, ultraharmonic, and inharmonic components in the Fourier domain. We evaluated multiple PMMA samples with varying twinkling amounts as well as a non-twinkling metal rod. Ultrasound scans were conducted using a Verasonics L11-4v probe on a V1 system from 3–9 MHz Doppler transmit frequency. A Sonic Concepts Y-107 PCD probe connected to a JSR DPR300 pulser/receiver collected data during Doppler ultrasound transmission. The Fourier spectra showed increased magnitude trends in the midband frequency range between the fundamental, f, and second harmonic, 2f, on the twinkling samples compared to non-twinkling metal rod. The midband increase was highest at frequencies that showed the most twinkling. This work indicates that the presence of color Doppler twinkling signal on PMMA gives rise to additional peaks in the Fourier domain, particularly in the midband range. Additionally, as there were no distinct subharmonic peaks, the increased midband magnitudes could be due to cavitation on the rough surfaces of the PMMA.

Summary: Prior studies on contrast-enhanced ultrasound (CEUS) lymphography for preoperative mapping before lymphaticovenous anastomosis surgery in patients with extremity lymphedema have been limited to using only Lumason and Sonazoid as microbubble contrast agents. The purpose of this study was to determine the feasibility of using two other Food & Drug Administration–approved microbubble agents, Optison and Definity, for imaging lymphatic vessels in the upper extremities. Nine female adults with unilateral upper extremity lymphedema anticipating lymphaticovenous anastomosis surgery underwent CEUS lymphography of the unaffected upper extremity randomized to either Lumason, Definity, or Optison. Lymphatic vessels were visualized in all but one case when undilated Definity was used. In the eight upper extremities where lymphatic vessels were visualized, an average of eight intradermal injections of microbubbles were performed in the extremity. Lymphatic vessels could be identified in 57% (36 of 63) of the injections. The effective dilution for each of the microbubble agents is provided. This was the first successful demonstration of lymphatic vessel visualization using either Definity or Optison. Broadening the range of available microbubble agents for CEUS lymphography could improve accessibility to the procedure and provide potentially safer alternatives.

Summary: Lymphedema following oncologic intervention can cause significant lifelong morbidity for patients in whom conservative management fails. The associated swelling, discomfort, pain, and recurrent cellulitis greatly diminish quality of life. Surgical procedures, including suction-assisted lipectomy, lymphovenous anastomosis (LVA), and vascularized lymph node transfers, show effectiveness in both volume reduction in affected extremities and symptom relief. However, the success of procedures like LVA is dependent on effective preoperative lymphatic mapping to identify suitable vessels for anastomosis. Traditional superficial lymphatic mapping uses near infrared fluorescence indocyanine green (ICG) imaging. Moreover, recent advances in contrast-enhanced ultrasound (CEUS) lymphography increased lymphovenous bypass target identification for LVA in the extremities.7 CEUS lymphography uses microbubbles as a contrast-enhancing agent injected intradermally into the affected extremity with subsequent identification of superficial collecting lymphatic vessels using ultrasound. Although a recent report noted an uptick in severe and critical adverse drug reactions to an ultrasound contrast agent injected intravenously in stress echocardiography, adverse drug reactions associated with ultrasound contrast-enhancing agents in body ultrasound are rare. The safety profile and potential complications from CEUS lymphography in the lymphedema population have yet to be fully characterized. In this case report, the authors present the first cutaneous adverse drug event following a secondary exposure to the contrast used for CEUS imaging. Mechanisms and justifications for an immune-mediated process are explored, and a review of similar manifestations in other related contrast applications is discussed.

AbstractA 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography.