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

• Published in: Radiology Vol. 280; no. 1; pp. 137 - 150
• Main Authors: Neuschmelting, Volker, Lockau, Hannah, Ntziachristos, Vasilis, Grimm, Jan, Kircher, Moritz F
• Format: Journal Article
• Language: English
• Published: United States Radiological Society of North America 01.07.2016
• Subjects: Animals; Diagnostic Imaging - methods; Disease Models, Animal; Lymph Nodes - pathology; Lymphatic Metastasis; Melanoma - diagnostic imaging; Melanoma - pathology; Mice; Neoplasm Micrometastasis - diagnostic imaging; Neoplasm Micrometastasis - pathology; Original Research; Photoacoustic Techniques - methods; Sensitivity and Specificity
• ISSN: 0033-8419; 1527-1315
• DOI: 10.1148/radiol.2016160191

Purpose To study whether multispectral optoacoustic tomography (MSOT) can serve as a label-free imaging modality for the detection of lymph node micrometastases and in-transit metastases from melanoma on the basis of the intrinsic contrast of melanin in comparison to fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Materials and Methods The study was approved by the institutional animal care and use committee. Sequential MSOT was performed in a mouse B16F10 melanoma limb lymph node metastasis model (n = 13) to survey the development of macro-, micro- and in-transit metastases (metastases that are in transit from the primary tumor site to the local nodal basin) in vivo. The in vitro limit of detection was assessed in a B16F10 cell phantom. Signal specificity was determined on the basis of a simultaneous lymphadenitis (n = 4) and 4T1 breast cancer lymph metastasis (n = 2) model. MSOT was compared with intravenous FDG PET/CT. The diagnosis was assessed with histologic examination. Differences in the signal ratio (metastatic node to contralateral limb) between the two modalities were determined with the two-tailed paired t test. Results The mean signal ratios acquired with MSOT in micrometastases (2.5 ± 0.3, n = 6) and in-transit metastases (8.3 ± 5.8, n = 4) were higher than those obtained with FDG PET/CT (1.1 ± 0.5 [P < .01] and 1.3 ± 0.6 [P < .05], respectively). MSOT was able to help differentiate even small melanoma lymph node metastases from the other lymphadenopathies (P < .05 for both) in vivo, whereas FDG PET/CT could not (P > .1 for both). In vitro, the limit of detection was at an approximate cell density of five cells per microliter (P < .01). Conclusion MSOT enabled detection of melanoma lymph node micrometastases and in-transit metastases undetectable with FDG PET/CT and helped differentiate melanoma metastasis from other lymphadenopathies. (©) RSNA, 2016 Online supplemental material is available for this article.