Multi-function Photoacoustic Imaging In Early Detection Of Melanoma Hepatic Metastasis And Intraoperative Guidance For Tumor Resection

Cancer metastasis is a primary feature of malignancy,which is often the main reason for the failure of cancer treatment.The liver is a highly metastasis-permissive organ,mainly resulting from the characteristic liver blood flow and composition.Moreover,liver metastasis is much more common than primary liver cancer.Colorectal cancers,breast cancer,ovarian cancer and melanoma are among the most common sources for metastatic disease to the liver.Melanoma is a malignant tumor of melanocytes,which are the cells that the pigment melanin and are derived from the neural crest.The liver is the most common(and often,the only)site of systemic metastasis of uveal melanoma.Early detection of liver metastasis was crucial for making appropriate treatment schedule and improving survival rates.Imaging of cancer metastasis plays an important role in the early diagnosis and treatment by providing three-dimensional high-resolution imaging arnd rapid physiopathological characterization.Yet,most conventional imaging techniques such as ultrasound(US),magnetic resonance imaging(MRI),or positron emission tomography(PET)are difficult to detect miniature cancerous lesions at very early stage.In this study,we longitudinally imaged in situ tumor hepatic invasion and distant metastasis models using photoacoustic(PA)imaging(PAI)in vivo and compared PAI with the common imaging modalities.Our proposed methods enabled whole liver morphology delineation and achieved as small as--400μm metastasis detection at a depth up to 7 mm in vivo.PAI also provided oxygen saturation changes during tumor growth,which showed significant difference between tumor and ambient normal tissue verified by immunohistochemistry.Besides,PAI also noninvasively measured metabolic kinetics of liver and tumor in primary liver cancer mice.We subsequently performed tumor resection by intraoperative image-guided surgery in vivo using a rapid portable PAI system,suggesting feasibility of PA navigation.PAI,possessing structural and functional features as a complementary clinical imaging technique,allowed early stage localization and characterization of melanoma hepatic micrometastasis.This method holds great potential for clinical translation to complement existing imaging techniques in the early diagnosis of tumor and guiding intraoperative resection.