The NCIBT will pursue seven collaborative research projects involving highly qualified investigators who are well-renowned in their respective fields. Each project has been chosen for its ability to use NCIBT technology and challenge its investigators to advance the technology further.
These collaborative projects are geographically broadly distributed to ensure a significant national impact. These collaborative projects will serve as technology drivers and test-beds in five areas of clinical applications including: surgical oncology, stroke management, interventional cardiology, ophthalmology, and fetal health.
Each of these collaborative projects relates to at least one TRD, some are synergistically related to multiple TRDs, often to multiple aims in a TRD.
CP1: Optical Imaging to Improve Surgery & Targeted Therapy in Brain Tumors
This grant supports development and validation of an antibody-based imaging strategy to improve extent of brain tumor resection and to develop new methods to quantify and increase the efficiency of antibody delivery to tumor.
Simultaneous evaluation of endogenous and exogenous tissue fluorescence using the iFLIM technology will improve the sensitivity and specificity of antibody-based imaging and its utility in defining tumor margins.
- Zhou Q, van den Berg NS, Rosenthal EL, Iv M, Zhang M, Vega Leonel JCM, Walters S, Nishio N, Granucci M, Raymundo R, Yi G, Vogel H, Cayrol R, Lee YJ, Lu G, Hom M, Kang W, Hayden Gephart M, Recht L, Nagpal S, Thomas R, Patel C, Grant GA, Li G. EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics. 2021 May 21;11(15):7130-7143. doi: 10.7150/thno.60582. eCollection 2021. PMID: 34158840 Free PMC article. Clinical Trial.
- Pei J, Juniper G, van den Berg NS, Nisho N, Broadt T, Welch AR, Yi GS, Raymundo RC, Chirita SU, Lu G, Krishnan G, Lee YJ, Kapoor S, Zhou Q, Colevas AD, Lui NS, Poultsides GA, Li G, Zinn KR, Rosenthal EL. Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Mol Imaging Biol. 2021 Feb;23(1):109-116. doi: 10.1007/s11307-020-01536-2. Epub 2020 Sep 3. PMID: 32880818 Clinical Trial.
CP2: Diffuse Optics for Pediatric Hydrocephalus Management
This proposal aims to develop a novel diffuse optical biomarker of intracranial pressure based on the pulsatile blood flow index measured by diffuse correlation spectroscopy (DCS)9,10. The research will validate this biomarker against invasive measurements during shunt placement in infants with hydrocephalus. This biomarker will then be translated for diagnosis of shunt failure in older children with shunts.
This collaboration will help translate biomarkers and measurements from infants to older children more effectively, leading to a non-invasive biomarker of elevated ICP to aid in planning shunt surgery timing. This promises to reduce brain injury in hydrocephalus caused by intracranial hypertension. As a non-invasive, non-threatening, and reliable tool for diagnosing shunt failure in older children, diffuse optics could revolutionize care by limiting exposure to ionizing radiation (head CT) and invasive procedures posing risk of infection (shunt taps).
CP3: Full field OCT for cellular level structural and functional retinal imaging
This grant supports development and implementation of novel in vivo retinal imaging techniques to improve the diagnosis of retinal diseases and monitoring of novel therapies in experimental animals and humans.
Advances in iFLIM and AI-ML-DL will result in customized devices suitable for multimodal studies of retinal disease, improve detection of retinal fluorophores underlying retinal disease, and permit the acquisition, processing, integration and cross validation of structural and functional data, thus expanding theutility of multimodal retinal imaging platforms.
CP4: Perioperative diffuse optical imaging of tissue blood flow and oxygenation for optimization of mastectomy skin flap viability
This grant supports extension of an innovative speckle contrast diffuse correlation tomography (scDCT) prototype to a next generation multi-wavelength scDCT (MW-scDCT) device for perioperative imaging of blood flow and oxygenation distributions in mastectomy skin flaps.
The interferometric approach developed under this collaborative project will likely outperform the conventional speckle contrast approach in achieving higher signal-to-noise ratios with less illumination and cheaper camera technology, but motion artifacts may be worse, and compensation strategies will need to be developed15. Most importantly, this approach should offer deeper penetration depth, which is critical for assessing thick (cm-scale) skin flaps.
- S. Mazdeyasna, C. Huang, A. Bonaroti, M. Mohtasebi, Q. Cheng, L. Wong, G. Yu. Noncontact optical imaging of blood flow distributions in mastectomy skin flaps: a comparison study with fluorescence angiography. Plastic and Reconstructive Surgery, In press (2021)
- M. Zhao, C. Huang, S. Mazdeyasna, G. Yu. Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements. Biomedical Optics Express, 12 (9): 5894-5908 (2021)
- X. Liu, Y. Gu, C. Huang, Y. Cheng, E. G. Abu Jawdeh, H. S. Bada, L. Chen, G. Yu. Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor. Journal of Biomedical Optics, 26 (1): 012705 (2021)
- C. Huang, S. Mazdeyasna, M. Mohtasebi, K. Saatman, Q. Cheng, G. Yu, L. Chen. Speckle contrast diffuse correlation tomography of cerebral blood flow in perinatal disease model of neonatal piglets. Journal of Biophotonics, 14 (4): e202000366 (2021)
CP5: Intravascular NIRF-IVUS imaging of inflammation-guided arterial therapy
The main goal of this project is to engineer a next-generation intravascular near-infrared fluorescence-intravascular ultrasound (NIRF-IVUS) imaging system to assess human coronary artery disease (CAD). The iFLIM technology will advance iNIRF-IVUS molecular imaging by incorporating iFLIM for characterizing atheroma.
The advancement of the iFLIM devices in TRD 1 aided by the intelligent design in TRD 3 and an adaptation to rotational scanning will provide the first comprehensive intravascular anatomical-substructural-molecular imaging system for coronary artery disease and thus enable personalized management.
CP6: In utero Repair of Fetal Myelomeningocele
These multi-PI grants support development of fetal tissue engineering methods of in utero repair of Myelomeningocele (MMC), the most severe form of Spina bifida, seeking to preserve neurologic function.
The integration of iFLIM and iNIRS in the experimental workflow of in utero repair of MMC will help refine the precision of surgical dissection, application of therapeutic agents, and closure of the defect and thus promote improvement in the outcome of fetal MMC. This novel multi-disciplinary approach integrates the principles and technologies from fetal surgery, imaging, biomaterials, developmental biology and stem cell biology and could significantly alter the standard-of-care for MMC.
- Kaeli Yamashiro, Laura Galganski, Jamie Peyton, Kalie Haynes, Victoria Vicuna, Priyadarsini Kumar, Benjamin Keller, James Becker, Christopher Pivetti, Sarah Stokes, Christina Theodorou, Jordan Jackson, Aijun Wang, Diana Farmer. Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study. Fetal Diagn Ther. 2020;47(12):912-917.PMID: 33166951. PMCID: PMC7746588. DOI: 10.1159/000510813
- Sarah Stokes, Jordan Jackson, Christina Theodorou, Christopher Pivetti, Priyadarsini Kumar, Kaeli Yamashiro, Aijun Wang, Diana Farmer. A Novel Model of Fetal Spinal Cord Exposure Allowing for Long-Term Postnatal Survival. Fetal Diagn Ther. 2021 Jun 10;1-7.
- PMID: 34111873. DOI: 10.1159/000516542
- Christina Theodorou, Sarah Stokes, Jordan Jackson, Christopher Pivetti, Priyadarsini Kumar, Kaeli Yamashiro, Zachary J Paxton, Lizette Reynaga, Alicia A Hyllen, Aijun Wang, Diana Farmer. Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair. J Pediatr Surg. 2021 Jun 5; S0022-3468(21)00435-8. PMID: 34217509. DOI: 10.1016/j.jpedsurg.2021.05.025
- Jordan Jackson, Christopher Pivetti, Sarah Stokes, Christina Theodorou, Priyadarsini Kumar, Zachary J Paxton, Alicia A Hyllen, Lizette Reynaga, Aijun Wang, Diana Farmer. Placental mesenchymal stromal cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair. 2021 Jul 14; 267:660-668. PMID: 34273796. DOI: 10.1016/j.jss.2021.06.011
- Sarah Stokes, Kaeli Yamashiro, Melissa A. Vanover, Laura A. Galganski, Jordan E. Jackson, Christina M. Theodorou, Christopher D. Pivetti, Diana Lee Farmer, Aijun Wang. Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model. BioMed Research International. 2021 Aug 13; 2021:2180883. PMID: 34423032. PMCID: PMC8378975. DOI: 10.1155/2021/2180883
CP7: Bimodal Intraoral imaging device for detection of oral epithelial neoplasia
Principal Investigators: Gracie Vargas, Xingde Li, and Rongguang Liang
Institutions: University of Texas Med Br Galveston, JHU, University of Arizona, respectively
Associated with: TRD 1 (Aim 2) and TRD 3 (Aim 2)
This multi-PI, multi-institutional project is developing a new bimodal intraoral imaging integrating rapid large area surveillance by widefield fluorescence (WF) imaging with histopathological-scale optical biopsy by nonlinear optical microscopy (NLOM) to aid in oral and oropharynx epithelial neoplasia detection through biopsy guidance.
Adaptation of the new iFLIM and analytical/visualization tools will enable multimodal studies of clinically relevant markers of neoplasia (oral carcinoma) and lead to refined detection of malignant transformation.
- A. Li, H. Guan, H. C. Park, Y. Yue, D. Chen, W. Liang, M.-J. Li, H. Lu, and X. D. Li. Twist-free ultralight two-photon fiberscope enabling neuroimaging on freely rotating/walking mice. Optica 8(6), 870-879, (2021).
- D. Chen, D. W. Nauen, H. C. Park, D. Li, W. Yuan, A. Li, H. Guan, C. Kut, K. L. Chaichana, C. Bettegowda, A. Quiñones-Hinojosa, and X. D. Li. Label-free imaging of human brain tissue at subcellular resolution for potential rapid intra-operative assessment of glioma surgery. Theranostics 11(15), 7222-7234, (2021).
- W. Yuan, D. Chen, R. Sarabia-Estrada, H. Guerrero-Cázares, D. W. Li, A. Quiñones-Hinojosa, and X. D. Li. Theranostic OCT microneedle for fast ultrahigh-resolution deep-brain imaging and efficient laser ablation in vivo. Science Advances 6(15), eaaz9664, (2020).