Lymph node micrometastases and in-transit metastases from melanoma: <em>In vivo</em> detection with multispectral optoacoustic imaging in a mouse model.

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 &plusmn; 0.3, n = 6) and in-transit metastases (8.3 &plusmn; 5.8, n = 4) were higher than those obtained with FDG PET/CT (1.1 &plusmn; 0.5 [P &lt; .01] and 1.3 &plusmn; 0.6 [P &lt; .05], respectively). MSOT was able to help differentiate even small melanoma lymph node metastases from the other lymphadenopathies (P &lt; .05 for both) in vivo, whereas FDG PET/CT could not (P &gt; .1 for both). In vitro, the limit of detection was at an approximate cell density of five cells per microliter (P &lt; .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

Performance of a Multispectral Optoacoustic Tomography (MSOT) system equipped with 2D vs. 3D handheld probes for potential clinical translation.

A handheld approach to optoacoustic imaging is essential for the clinical translation. The first 2- and 3-dimensional handheld multispectral optoacoustic tomography (MSOT) probes featuring real-time unmixing have recently been developed. Imaging performance of both probes was determined in vitro and in a brain melanoma metastasis mouse model in vivo. T1-weighted MR images were acquired for anatomical reference. The limit of detection of melanoma cells in vitro was significantly lower using the 2D than the 3D probe. The signal decrease was more profound in relation to depth with the 3D versus the 2D probe. Both approaches were capable of imaging the melanoma tumors qualitatively at all time points. Quantitatively, the 2D approach enabled closer anatomical resemblance of the tumor compared to the 3D probe, particularly at depths beyond 3 mm. The 3D probe was shown to be superior for rapid 3D imaging and, thus, holds promise for more superficial target structures