Qian Yu1, Shanshan Huang1, Zhiyou Wu1, Jiadi Zheng2, Xiaoyuan Chen3, Liming Nie4. 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China. 2. Department of Neurosurgery, Xiamen Hospital, Beijing University of Chinese Medicine, Xiamen, China; and. 3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland. 4. State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China nielm@xmu.edu.cn.
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 = 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 high-resolution 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 = 6) and 14 d (9.2 ± 0.4, n = 5) was significantly higher than for PET/CT (1.8 ± 0.1, n = 5, and 4.5 ± 0.2, n = 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.
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 = 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 high-resolution 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 = 6) and 14 d (9.2 ± 0.4, n = 5) was significantly higher than for PET/CT (1.8 ± 0.1, n = 5, and 4.5 ± 0.2, n = 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.
Authors: C M Balch; S J Soong; J E Gershenwald; J F Thompson; D S Reintgen; N Cascinelli; M Urist; K M McMasters; M I Ross; J M Kirkwood; M B Atkins; J A Thompson; D G Coit; D Byrd; R Desmond; Y Zhang; P Y Liu; G H Lyman; A Morabito Journal: J Clin Oncol Date: 2001-08-15 Impact factor: 44.544
Authors: Timothy M Pawlik; Daria Zorzi; Eddie K Abdalla; Bryan M Clary; Jeffrey E Gershenwald; Merrick I Ross; Thomas A Aloia; Steven A Curley; Luis H Camacho; Lorenzo Capussotti; Dominique Elias; Jean-Nicolas Vauthey Journal: Ann Surg Oncol Date: 2006-03-14 Impact factor: 5.344
Authors: Sumith A Kularatne; Mini Thomas; Carrie H Myers; Pravin Gagare; Ananda K Kanduluru; Christa J Crian; Brandy N Cichocki Journal: Clin Cancer Res Date: 2018-09-10 Impact factor: 12.531
Authors: Adrian Taruttis; Stefan Morscher; Neal C Burton; Daniel Razansky; Vasilis Ntziachristos Journal: PLoS One Date: 2012-01-25 Impact factor: 3.240
Authors: Jeeun Kang; Xiuyun Liu; Suyi Cao; Steven R Zeiler; Ernest M Graham; Emad M Boctor; Raymond C Koehler Journal: J Neural Eng Date: 2022-01-05 Impact factor: 5.043
Authors: Armanda De Marchi; Simona Pozza; Lorena Charrier; Filadelfo Cannone; Franco Cavallo; Alessandra Linari; Raimondo Piana; Irene Geniò; Paolo Balocco; Alessandro Massè Journal: Int J Environ Res Public Health Date: 2020-11-28 Impact factor: 3.390
Authors: Kevan Bell; Saad Abbasi; Deepak Dinakaran; Muba Taher; Gilbert Bigras; Frank K H van Landeghem; John R Mackey; Parsin Haji Reza Journal: Sci Rep Date: 2020-11-05 Impact factor: 4.379