Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging

Abstract

The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of our study was to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma at a very early stage and in aiding tumor resection by intraoperative guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a mouse model of B16 melanoma metastatic to the liver (n 5 10) was established to study the development of micrometastases in vivo. Next, the mice were imaged by a scalable PAI instrument, ultrasound, 9.4-T highresolution MRI, PET/CT, and bioluminescence imaging. PAI scans acquired with optical wavelengths of 680-850 nm were kept spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in signal-to-background ratios among different modalities were determined with the 2-tailed paired t test. The diagnostic results were assessed with histologic examination. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify the tumor boundaries. Surgical removal of metastatic melanoma was precisely guided in vivo by the portable PAI system. Results: PAI was able to detect metastases as small as approximately 400 μm at a depth of up to 7 mm in vivo-a size that is smaller than can be detected with ultrasound and MRI. The tumor-to-liver ratio for PAI at 8 d (4.2 ± 0.2, n 5 6) and 14 d (9.2 ± 0.4, n 5 5) was significantly higher than for PET/CT (1.8 ± 0.1, n 5 5, and 4.5 ± 0.2, n 5 5, respectively; P , 0.001 for both). Functional PAI revealed dynamic oxygen saturation changes during tumor growth. The limit of detection was approximately 219 cells/μL in vitro. We successfully performed intraoperative PAI-guided surgery in vivo using the portable PAI system. Conclusion: Our findings offer a rapid and effective complementary clinical imaging application to noninvasively detect micrometastases and guide intraoperative resection.

RGD-Functionalized Melanin Nanoparticles for Intraoperative Photoacoustic Imaging-Guided Breast Cancer Surgery

“…In addition, we found that the tumour, when artificially located in deep tissue, could be clearly imaged and discriminated with a depth of up to 5 mm. A previous study reported the application of PAI with endogenous melanin as contrast for the resection of B16 melanoma liver metastasis [30]. Hepatic melanoma in vivo as small as 400 µm could be detected at a depth of up to 7 mm and precisely resected using PAI guidance, demonstrating the advantages of PA (i.e., high resolution, high sensitivity, deep penetration and early detection of hepatic micrometastasis).…”

Small Subcutaneous Soft Tissue Tumors (<5 cm) Can Be Sarcomas and Contrast-Enhanced Ultrasound (CEUS) Is Useful to Identify Potentially Malignant Masses

“…Further studies are needed in order to confirm our data in a larger sample and to assess the influence of any technical problem. New imaging tools and techniques will probably make easier in the future the diagnosis of malignancy in case of subcutaneous masses [35,36].…”

Research on Local Sound Field Control Technology Based on Acoustic Metamaterial Triode Structure

“…Lv et al studied the application of in vivo photoacoustic imaging in the dynamic monitoring of the early stages of ischemic stroke and proposed a highly sensitive in vivo photoacoustic imaging model [4]. Qian et al proposed a guided surgery method based on photoacoustic imaging to achieve tumor resection [5]. Lu et al proposed a photoacoustic contrast agent based on functional peptide-modified gold nanoparticles for the problems of the photoacoustic imaging of bacterial infections [6].…”