title: Lymph Node Micrometastases and In-Transit Metastases from Melanoma: In Vivo Detection with Multispectral Optoacoustic Imaging in a Mouse Model.
abstract: 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.
authors.affiliation: From the Department of Radiology (V. Neuschmelting, H.L., J.G., M.F.K.), Molecular Pharmacology Program (H.L., J.G.), and Center for Molecular Imaging and Nanotechnology (CMINT) (J.G., M.F.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Institute for Biological and Medical Imaging, Helmholtz Zentrum, Munich, Germany (V. Ntziachristos); Department of Biological Imaging, Technische Universität München, Munich, Germany (V. Ntziachristos); and Departments of Radiology (J.G., M.F.K.) and Pharmacology (J.G.), Weill Cornell Medical College, New York, NY.
authors.forename: Volker
authors.initials: V
authors.lastname: Neuschmelting
authors.affiliation: From the Department of Radiology (V. Neuschmelting, H.L., J.G., M.F.K.), Molecular Pharmacology Program (H.L., J.G.), and Center for Molecular Imaging and Nanotechnology (CMINT) (J.G., M.F.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Institute for Biological and Medical Imaging, Helmholtz Zentrum, Munich, Germany (V. Ntziachristos); Department of Biological Imaging, Technische Universität München, Munich, Germany (V. Ntziachristos); and Departments of Radiology (J.G., M.F.K.) and Pharmacology (J.G.), Weill Cornell Medical College, New York, NY.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lockau
authors.affiliation: From the Department of Radiology (V. Neuschmelting, H.L., J.G., M.F.K.), Molecular Pharmacology Program (H.L., J.G.), and Center for Molecular Imaging and Nanotechnology (CMINT) (J.G., M.F.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Institute for Biological and Medical Imaging, Helmholtz Zentrum, Munich, Germany (V. Ntziachristos); Department of Biological Imaging, Technische Universität München, Munich, Germany (V. Ntziachristos); and Departments of Radiology (J.G., M.F.K.) and Pharmacology (J.G.), Weill Cornell Medical College, New York, NY.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: From the Department of Radiology (V. Neuschmelting, H.L., J.G., M.F.K.), Molecular Pharmacology Program (H.L., J.G.), and Center for Molecular Imaging and Nanotechnology (CMINT) (J.G., M.F.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Institute for Biological and Medical Imaging, Helmholtz Zentrum, Munich, Germany (V. Ntziachristos); Department of Biological Imaging, Technische Universität München, Munich, Germany (V. Ntziachristos); and Departments of Radiology (J.G., M.F.K.) and Pharmacology (J.G.), Weill Cornell Medical College, New York, NY.
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
authors.affiliation: From the Department of Radiology (V. Neuschmelting, H.L., J.G., M.F.K.), Molecular Pharmacology Program (H.L., J.G.), and Center for Molecular Imaging and Nanotechnology (CMINT) (J.G., M.F.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Institute for Biological and Medical Imaging, Helmholtz Zentrum, Munich, Germany (V. Ntziachristos); Department of Biological Imaging, Technische Universität München, Munich, Germany (V. Ntziachristos); and Departments of Radiology (J.G., M.F.K.) and Pharmacology (J.G.), Weill Cornell Medical College, New York, NY.
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000473:pathology*; D051379:Mice; D061206:Neoplasm Micrometastasis / Q000000981:diagnostic imaging* / Q000473:pathology; D061088:Photoacoustic Techniques / Q000379:methods*; D012680:Sensitivity and Specificity