Medulloblastoma is an undifferentiated, neuroepithelial tumor of the cerebellum and the most common malignant brain tumor in children. While the current medical practice has significantly improved survival rates for children with medulloblastoma, approximately one-third of these patients die, and 20% of survivors sustain severe neurological damage. The standard of care for medulloblastoma includes surgical resection followed by radiation therapy and chemotherapy. Although larger resections that effectively remove the tumor correlate with improved patient outcome, the surgeon must attempt to minimize damage to surrounding healthy brain tissue. To improve tumor visualization and localization, we aim to adapt a dual axis confocal (DAC) microscope to detect tumor margins and guide surgical resection, and to identify new reagents that can mark the margins with novel molecular probes for clear differention of tumor from normal tissue. The DAC microscope will be modified with a GRIN relay lens to reach into the cavity ofthe resected tumor and interrogate the margins for residual cancer. The imaging reagents that are being developed will include peptides and antibodies that we will refine for use as fluorescent probes that label mouse and human medulloblastoma. These reagents are selected based on data obtained by high throughput analyses including DNA microarays and phage display, and take advantage of commercially available reagents. Binding of these markers to tumor margins will be visualized using the refined confocal microscope that is based on a dual axis design and will be modified for optimal use for surgical resection. We will develop software to identify tumor margins using the microanatomic features of cancer and normal brain after staining with vital dyes. The modifications to the microscope include those that stabilize the system and enable multispectral analyses through a disposable tip. To test the microscope in the clinic we will first use a FDA-approved dye as a contrast agent. As we develop new reagents, we will also validate their utility in image-guided resections. We will also develop image-processing algorithms to aid in the discrimination of tumors from surrounding normal brain. The research proposed here will serve as a foundation for the use of molecular probes and advanced microscopy for precision image-guided resection of solid brain tumors in humans. Successful completion of the aims to this project will have a significant benfit for children suffering from medulloblastoma by prolonging disease-free survival and reducing the neurological deficits associated with tumor resection.
There is a clear correlation between effective tumor resection and disease-free survival in patients with medulloblastoma. However, there is a risk of severe neurological damage if normal tissue is removed. Image guidance with fine temporal and spatial resolution will improve resection and lead improved outcomes for children with medulloblastoma. The probes and instruments that we develop and refine will also have utiliity in resection of other tumor types and the approach can be extended to a greater number of patients.
|Lee, Alex G; Nechvatal, Jordan M; Shen, Bin et al. (2016) Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys. Neurobiol Stress 3:68-73|
|Carroll, V N; Truillet, C; Shen, B et al. (2016) [(11)C]Ascorbic and [(11)C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem Commun (Camb) 52:4888-90|
|Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren et al. (2016) Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction. Radiology 280:815-25|
|Zhou, Zijian; Song, Jibin; Nie, Liming et al. (2016) Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. Chem Soc Rev 45:6597-6626|
|Neumann, Kiel D; Qin, Linlin; VÄvere, Amy L et al. (2016) Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor. J Labelled Comp Radiopharm 59:30-4|
|Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan et al. (2016) Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol 11:986-994|
|Sun, Ziyan; Cheng, Kai; Wu, Fengyu et al. (2016) Robust surface coating for a fast, facile fluorine-18 labeling of iron oxide nanoparticles for PET/MR dual-modality imaging. Nanoscale 8:19644-19653|
|Zhang, Ruiping; Cheng, Kai; Antaris, Alexander L et al. (2016) Hybrid anisotropic nanostructures for dual-modal cancer imaging and image-guided chemo-thermo therapies. Biomaterials 103:265-77|
|Van de Sompel, Dominique; Sasportas, Laura S; Jokerst, Jesse V et al. (2016) Comparison of Deconvolution Filters for Photoacoustic Tomography. PLoS One 11:e0152597|
|Li, Yulin; Deutzmann, Anja; Choi, Peter S et al. (2016) BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia. Oncotarget 7:26926-34|
Showing the most recent 10 out of 404 publications