Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging

Abstract

Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with (99m)Tc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.

Lymph Node Micrometastases and In-Transit Metastases from Melanoma: In Vivo Detection with Multispectral Optoacoustic Imaging in a Mouse Model

“…Ex vivo, the MSOT signal of melanin obtained from excised SLN has already been shown to have excellent correlation with the histologic analyses of melanoma cell infiltration in animals (17) and improve the pathologic diagnosis in humans (18). In vivo, MSOT has recently been shown to be able to depict …”

“…The specificity issue of FDG PET/ CT is widely acknowledged in this regard (12). Recently, more specific 18 Fbased tracers targeted to melanin are subject to preclinical development, with the intention to potentially overcome this issue (27,28).…”

“…In the recent first clinical feasibility study in 20 patients, MSOT was not only able to reliably depict SLN with use of indocyanine green and help guide SLN excision, but also could provide specific information about the node status with high sensitivity (18). However, because there is yet limited knowledge about the potential capabilities and limits of the technique for detecting melanoma metastasis in vivo, we conducted this study on the basis of an experimental lymph node melanoma metastasis model under controlled conditions.…”

Visual Quality Enhancement in Optoacoustic Tomography Using Active Contour Segmentation Priors

“…The performance of active contour models was outlined herein for whole-body segmentation of mice using three representative anatomical regions. Considering that the recently developed hand-held probes for optoacoustic clinical translation employ the same acquisition geometry, the methods presented in this work can further be applied in the development of diagnostic tools for translational imaging in human subjects [50]. The optimum values of the parameters used in the segmentation procedure such as the weighting factors to estimate the image forces or the number and location of the initial contour points were determined heuristically.…”

Multiplexed imaging for diagnosis and therapy

“…The added value of anatomical CT or MR to multi-tracer PET/SPECT/OI investigations is rather evident, but fewer investigations have highlighted the utility of adding a functional modality to a multi-signal methodology. PAI and US signals, for example, are detectable using the same equipment, making this pair attractive, as illustrated by a handheld hybrid US-MSOT probe for the visualisation of sentinel lymph nodes and the determination of their metastatic status in melanoma; in a 20-patient clinical trial 149 , indocyanine green (ICG) and melanin contrast were detected up to 5 cm in depth, and delivered 100% sensitivity and 48.6% specificity for metastatic status, as verified by histology. A similar US-MSOT system demonstrated simultaneous imaging of haemoglobin oxygen saturation and flow (Doppler US) in the vasculature of healthy human volunteers 150 , and frequency splitting in ultra-broadband optoacoustics identified inflammation parameters for the staging of psoriasis 151 .…”