Multimodal soft tissue markers for bridging high-resolution diagnostic imaging with therapeutic intervention

Abstract

Diagnostic imaging often outperforms the surgeon’s ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.

Biodegradable Fiducial Markers for Bimodal Near-Infrared Fluorescence- and X-ray-Based Imaging

“…The presented FMs in this study were designed to offer visualization during NIRF imaging-guided biopsy or tumor removal surgery. For this purpose, the contrasting property is needed for a relatively short time, perioperatively or by a few days from a biopsy to the resection surgery. , Moreover, the FMs were formulated to ensure contrast in the X-ray by at least several weeks or months supporting diagnostic or therapy techniques. , Thus, for these purposes, core–shell FMs were proposed with fluorescent shells and a radiopaque core.…”

“…Advanced navigation devices supporting oncological treatment, e.g., for real-time tumor surgery, augmented reality-supported surgery, and modern radiotherapy, are developed nowadays . The majority of them require a temporary application of fiducial markers (FMs) implanted close to or in the surgical field as a reference point to precisely label tumor localization or determine the tumor margin. , For X-ray-based real-time imaging, mainly metallic FMs are used. However, after fulfilling the function, e.g., within a few months of adjuvant therapy, the nondegradable FMs are often removed due to possible interference during future diagnostic imaging , or the patient’s discomfort or pain. , Therefore, the development of materials for FMs with a defined lifetime in vivo may improve the quality of convalescence and life of the patients.…”

Carbohydrate based biomarkers enable hybrid near infrared fluorescence and 64Cu based radio-guidance for improved surgical precision

“…The marker is intrinsically visible in ultrasonography (US) and magnetic resonance imaging (MRI), and has x-ray contrast due to the incorporation of the xSAIB construct 32 , 39 . xSAIB is a mixed isobutyrate, triiodophenoxyacetate sucrose ester derivative, which contains six aromatically bound iodine per molecule providing the high electron density required for CT imaging and 2D x-ray fluoroscopy 40 . These image features allow for preoperative localization via US/CT or 2D x-ray fluorescence guidance during injection of the marker.…”

“…The latter approach may be highly relevant in robotic surgery where NC-mark could serve as beacons or waypoints even for deeply situated lesions. Marker systems similar to NC-mark has previously been described where NIR fluorescence and radiolabeling was achieved through incorporation of a custom synthesized Cy7.5 fluorophore and 64 Cu radiolabeling via ionophores 33 . In that study, the use of ionophores yielded a less stable and less convenient radiolabeling procedure compared to radiolabeling of NC-mark.…”

“…6,6'-di-triidobenzene-isobuturic-sucrose (xSAIB) was custom synthesized 33 . The freeze dried, premixed stealth liposome mixture of hydrogenated soy phosphatidylcholine (HSPC), cholesterol (CHOL) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE- PEG2000) (565:382:53, molar ratio) was purchased from Lipoid.…”