Research ArticleCancer Imaging

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

Science Translational Medicine  09 Dec 2015:
Vol. 7, Issue 317, pp. 317ra199
DOI: 10.1126/scitranslmed.aad1278

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Imaging melanoma metastasis

Avoiding invasive biopsy altogether, an imaging technique that relies on endogenous biomolecules to generate acoustic signals could be used to detect metastases in the body. Stoffels et al. devised a multispectral optoacoustic tomography (MSOT) approach that could image the pigment melanin in lymph nodes. Melanin would only be present in the lymph nodes if the primary cancer—melanoma—had spread to distant locations. The authors used handheld MSOT detectors and a near-infrared fluorophore (which pools in lymph nodes) to image metastases in patients, and complemented these optoacoustic images with ultrasound to gain a complete picture of each lymph node’s status. Such a noninvasive approach could reduce the number of patients subjected to sentinel lymph node surgical excision by “ruling out” metastasis.

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 99mTc-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.

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