Surface-Enhanced Raman Spectroscopy (SERS) for Intraoperative Brain Tumor Imaging and Photothermal Therapy
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1 Surface-Enhanced Raman Spectroscopy (SERS) for Intraoperative Brain Tumor Imaging and Photothermal Therapy Hamed Arami SCIT seminar, October 05, 2017
2 Background: Intraoperative Detection of Brain Tumors Intraoperatively it is difficult to distinguish the exact margin between brain tumors and the adjacent normal brain tissue. Residual cancer cells result in tumor recurrence. Resection that includes normal brain tissue can result in neurological deficits. Developing intraoperative methods to better delineate brain tumor margins
3 Background: Intraoperative Detection of Brain Tumors Intraoperatively it is difficult to distinguish the exact margin between brain tumors and the adjacent normal brain tissue. Residual cancer cells result in tumor recurrence. Resection that includes normal brain tissue can result in neurological deficits. Developing intraoperative methods to better delineate brain tumor margins
4 Background: Intraoperative Detection of Brain Tumors Intraoperatively it is difficult to distinguish the exact margin between brain tumors and the adjacent normal brain tissue. Residual cancer cells result in tumor recurrence. Resection that includes normal brain tissue can result in neurological deficits. Developing intraoperative methods to better delineate brain tumor margins
5 Background: Intraoperative Detection of Brain Tumors Intraoperatively it is difficult to distinguish the exact margin between brain tumors and the adjacent normal brain tissue. Residual cancer cells result in tumor recurrence. Resection that includes normal brain tissue can result in neurological deficits. Developing intraoperative methods to better delineate brain tumor margins
6 Background: Surface Enhanced Raman Spectroscopy (SERS) SERS ( x) SERS SERS Raman Guerrini et al. Chemical Society Reviews (2012).
7 Background: Intraoperative Raman Spectroscopy in Humans Raman Probe Brain Tumor M. Jermyn et al. Science Translational Medicine, 2015.
8 Background: Intraoperative Raman Spectroscopy in Humans SERS ( x) Raman M. Jermyn et al. Science Translational Medicine, 2015.
9 Background: In Vivo Evaluation of Multiplexing Different NPs - High sensitivity - Multiplexing C. L. Zavaleta et al. PNAS, 2009.
10 Background: Intraoperative Surface Enhanced Raman Spectroscopy M. Kircher et al. Nature Medicine, 2012.
11 Aims, Significance & Study Design
12 Aims, Significance & Study Design
13 Aims, Significance & Study Design
14 Methods: Tumor Implantation and Bioluminescent Imaging (U87 Brain Tumor Cells) (a) SYRINGE EXPOSED SKULL 4 weeks after implantation (b) Tumor Fluorescent (c) Raman
15 Methods: Preparation of the Nanoparticles (a) (b) Gold Raman active layer Silica Nanoparticles PEG-maleimide PEG coated Raman Nanoparticles (c) PEG NP SH ph PEG NP PEG-maleimide Thiolated nanoparticles (NP) Stabilized PEG coated nanoparticles (NP)
16 Results: Nanoparticles Characterizations Intensity (a.u.) Hydrodynamic size: 149.5nm Polydispersity index: Hydrodynamic size (nm) Counts (a.u.) Zeta potential: -27.2mV Zeta potential (mv) Raman signal intensity (a.u.) Raman spectrum Raman shift (cm -1 )
17 Results: Mouse brain MRI (T2-weighted, U87 tumor)
18 Results: Intratumoral Diffusion of the Raman Nanoparticles (NPs volume and concentration ~ 2 µl & 1 nm) Tumor Fluorescent (c) Raman Max 5mm Radiant Efficacy Min (n=3) Raman Signal Intensity (a.u.) (b)
19
20 Summary: Case No. Tumor Dog s weight (kg) Nanoparticles concentration (nm) Nanoparticles volume (ml) 1 Oligodendroglioma Psammomatous Meningioma 3 Fibrolastic Meningioma
21 Dog Frontal Lobe Meningioma post-contrast T1 MRI and histology: Pre-Operative Post-Operative Anterior (ventral) tissue Posterior (dorsal) tissue Histology of the tumor tissue (H&E) Whorls and Psammoma bodies (center) and dura mater (left, right, bottom)
22 SEM at a tissue section, showing nanoparticles embedded in tumor tissue: Tumor Nanoparticles embedded in tumor
23 Elemental Analyses Using Electronic Microscopy: Tumor tissue surface Electron beam on the nanoparticles Si peak Gold peak Nanoparticles delivered to tumor
24 Conclusions & Future Directions Surface enhanced Raman spectroscopy shows potential for simultaneous detection and ablation of brain tumors Nanoparticles systematic design appears to help their uniform intratumoral diffusion in brain microenvironment These are proof of concept data that require further investigation for clinical translation
25 Conclusions & Future Directions Surface enhanced Raman spectroscopy shows potential for simultaneous detection and ablation of brain tumors Nanoparticles systematic design appears to help their uniform intratumoral diffusion in brain microenvironment These are proof of concept data that require further investigation for clinical translation
26 Conclusions & Future Directions Surface enhanced Raman spectroscopy shows potential for simultaneous detection and ablation of brain tumors Nanoparticles systematic design appears to help their uniform intratumoral diffusion in brain microenvironment These are proof of concept data that require further investigation for clinical translation
27 Acknowledgements Image: Raman nanoparticles diffused into the brain tumor Prof. Sanjiv1RO1EB /NIBIB Gambhir (Stanford, Radiology) Prof. Bob Sinclair (Stanford, Materials Science) Edwin Chang, Chirag Patel Steven Madsen, Ryan Miller, Demir Akin UC Davis Veterinary School Gambhir s lab Stanford Cancer Imaging Training Molecular Imaging Program at Stanford (MIPS)
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