Excised Whole Lymph Node Imaging for Cancer Staging with Angular Restriction Dual Fluorescent Optical Projection Tomography

Conventional pathology in sentinel lymph node biopsy fails to sufficiently evaluate the entire tissue volume, resulting in high rates of false negatives. To address this, a novel imaging system is proposed to augment the current protocol by providing high-resolution molecular imaging of the lymph node prior to sectioning, with the goal of guiding pathology. Optical projection tomography (OPT) offers a potential solution but spatial resolution of conventional OPT is generally quite poor in lymph node sized tissue samples. Here, we demonstrate the ability to use angular-restriction with filtered-backprojection to provide sensitive and accurate localization of clinically relevant sized micrometastases in lymph nodes (through Monte Carlo simulations and porcine lymph node metastases models).

[1]  L Wang,et al.  MCML--Monte Carlo modeling of light transport in multi-layered tissues. , 1995, Computer methods and programs in biomedicine.

[2]  Zhifang Li,et al.  High-dynamic-range fluorescence laminar optical tomography (HDR-FLOT). , 2017, Biomedical optics express.

[3]  James Sharpe,et al.  Optical projection tomography as a new tool for studying embryo anatomy , 2003, Journal of anatomy.

[4]  Tayyaba Hasan,et al.  Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging , 2014, Nature Medicine.

[5]  T. Hasan,et al.  Accounting for pharmacokinetic differences in dual-tracer receptor density imaging , 2014, Physics in medicine and biology.

[6]  Vasilis Ntziachristos,et al.  Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo , 2008, Proceedings of the National Academy of Sciences.

[7]  R. Weinberg,et al.  A Perspective on Cancer Cell Metastasis , 2011, Science.

[8]  Tayyaba Hasan,et al.  Imaging targeted-agent binding in vivo with two probes. , 2010, Journal of biomedical optics.

[9]  Bozena Kaminska,et al.  Angular domain transillumination imaging optimization with an ultrafast gated camera. , 2010, Journal of biomedical optics.

[10]  Steven L. Jacques,et al.  Monte Carlo Modeling of Light Transport in Tissue (Steady State and Time of Flight) , 2010 .

[11]  Brian W. Pogue,et al.  High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas , 2011, Molecular Imaging and Biology.

[12]  K. Tichauer,et al.  Enhanced detection of early photons in time-domain optical imaging by running in the "dead-time" regime. , 2016, Optics letters.

[13]  L. Irwig,et al.  Meta‐analysis of sentinel node imprint cytology in breast cancer , 2005, The British journal of surgery.

[14]  Donald L Weaver,et al.  Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale , 2010, Modern Pathology.

[15]  Rinaldo Cubeddu,et al.  Time-Gated Optical Projection Tomography Allows Visualization of Adult Zebrafish Internal Structures , 2012, PloS one.

[16]  Jason R. Gunn,et al.  In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging , 2012, Molecular Imaging and Biology.

[17]  Tayyaba Hasan,et al.  Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging. , 2012, Journal of biomedical optics.

[18]  K. Tichauer,et al.  Noninvasive detection of cancer spread to lymph nodes: A review of molecular imaging principles and protocols , 2018, Journal of surgical oncology.

[19]  V Ntziachristos,et al.  Intraoperative near-infrared fluorescence imaging for sentinel lymph node detection in vulvar cancer: first clinical results. , 2011, Gynecologic oncology.

[20]  C. Lawton Association of Occult Metastases in Sentinel Lymph Nodes and Bone Marrow With Survival Among Women With Early-Stage Invasive Breast Cancer , 2012 .

[21]  Xavier Intes,et al.  Mesoscopic fluorescence tomography of a photosensitizer (HPPH) 3D biodistribution in skin cancer. , 2014, Academic radiology.

[22]  E. Ng Two dimensional angular domain optical imaging in biological tissues , 2013 .

[23]  M. Skobe,et al.  Lymphatic function, lymphangiogenesis, and cancer metastasis , 2001, Microscopy research and technique.