The NCIBT will initially pursue seven service projects involving five academic institutions and two companies. These projects have been chosen for their ability to use NCIBT tools in their studies and offer feedback. These service projects are geographically broadly distributed to ensure a significant national impact. These service projects will serve as technology users in four areas of clinical and monitoring applications including: surgical oncology, neurological diseases, cognition, and trauma (hemorrhagic shock). Each service project relates to at least one TRD, some are synergistically related to multiple TRDs, often to multiple aims in a TRD.
SP1: Imaging Goggles for Fluorescence-Guided Surgery
Principal Investigator: Samuel Achilefu
Institution: Washington University in St. Louis
Associate with: TRD 1 (Aims 2,3,4) and TRD 3 (Aims 2,3,4)
Grants: 1R01EB030987-01A1
This grant supports development of a wearable CancerVision Goggle (CVG) system for real-time intraoperative fluorescence-guided surgery (FGS).
The proposed iFLIM technology and analytical tools will facilitate integration with the CVG for FGS in the operating room and improve accuracy of tumor margin assessment.
Selected Publications:
- Shen, D., et al., Selective imaging of solid tumors via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated AnnexinA2.Nat. Biomed. Eng., 2020. 4(3): p. 298-313.
- Mondal, S.B., S.-W.D. Tsen, and S. Achilefu. Head-Mounted Devices for Noninvasive Cancer Imaging and Intraoperative Image-Guided Surgery. Advanced Functional Materials, 2020. 30(37): p. 2000185.
- Mondal, S.B., et al., Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery. Journal of Nuclear Medicine, 2020. 61(8): p. 1113-1122.
SP2: Biomarker Signatures for Delayed Cerebral Ischemia and Outcome Following Subarachnoid Hemorrhage
Principal Investigator: Frank Sharp
Institution: UC Davis
Associate with: TRD 2 (Aim 1) and TRD 3 (Aim 3)
Grants: 1R61NS119345-01
Subarachnoid hemorrhage (SAH) accounts for 5% of all strokes and has a high mortality and cost to society. Nearly 1/3 of SAH patients develop delayed cerebral ischemia (DCI), often with cerebral infarction. Gene expression in blood can predict which SAH patients will develop vasospasm1. This project uses support vector machine (SVM) learning to identify the fewest number of genes at 1, 2 or 3 days after SAH that best predict (1) SAH patients who develop DCI at 4-14 days (2) and outcomes at three months.
NCIBT will provide a non-invasive blood flow biomarker to complement genetic profiles and learning approaches to integrate these biomarkers in more accurate prediction of patient outcomes.
Selected Publications:
- Xu H, Stamova B, Ander BP, Waldau B, Jickling GC, Sharp FR, Ko NU. mRNA Expression Profiles from Whole Blood Associated with Vasospasm in Patients with Subarachnoid Hemorrhage. Neurocrit Care. 2020;33(1):82-9. Epub 2019/10/09. doi: 10.1007/s12028-019-00861-x. PubMed PMID: 31595394; PMCID: PMC7392923.
- Zhou W, Kholiqov O, Zhu J, Zhao M, Zimmermann LL, Martin RM, Lyeth BG, Srinivasan VJ. Functional interferometric diffusing wave spectroscopy of the human brain. Science Advances. 2021;7(20):eabe0150. doi: 10.1126/sciadv.abe0150.
SP3: Brian-based Metrics for Prolonged Field Care (PFC) Tasks
Principal Investigators: Suvranu De and Xavier Intes
Institution: Rensselaer Polytechnic Institute
Associate with: TRD 2 (Aims 1,2,4) and TRD 3 (Aim 3)
Grants: Army W912CG2120001
This grant supports the development of new AI-based tools for training army field medics to better understand skill acquisition and standardize the prolonged field care (PFC) certification process. This work aggregates neuroimaging, computer vision, and eye-tracking with dedicated artificial intelligence methodsto make PFC certification faster, more objective, and scalable for all soldiers.
The new iNIRS/iDWS technology will improve monitoring of cortical activation by quantifying changes in blood flow and thus brain energetics in real time and in a real-world environment.
Selected Publications:
- Y Gao, L Cavuoto, A Dutta, U Kruger, P Yan, A Nemani, J Norfleet, BA Makled, J Silvestri, S Schwaitzberg, X Intes, S De. Decreasing the Surgical Errors by Neurostimulation of Primary Motor Cortex and the Associated Brain Activation via Neuroimaging. Frontiers in Neuroscience 15:651192 (2021).
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L. Tian, B. Hunt, MAL. Bell, J. Yi, J. T. Smith, M. Ochoa, X. Intes, NJ. Durr. Deep learning in biomedical optics. Laser in Surgery and Medicine 53(6), 748-775 (2021).
- Y Gao, H Chao, L Cavuoto, P Yan, U Kruger, JE Norfleet, BA Makled, S Schwaitzberg, S De, and X Intes. Deep learning-based motion artifact removal in functional near-infrared spectroscopy (fNIRS). DOI: 10.13140/RG.2.2.33766.86089.
- A Nemani, A Kamat, Y Gao, M Yucel, D Gee, C Cooper, S Schwaitzberg, X Intes, A Dutta and S De. Functional Brain Connectivity Related to Surgical Skill Dexterity in Physical and Virtual Simulation Environments. Neurophotonics 8(1), 015008 (2021).
- Y Erim, X Intes, U Kruger, P Yan, B Van Voorst, B Makled, J Norfleet and S De. Deep Neural Networks for the assessment of surgical skills: A systematic review. Journal of Defense Modeling and Simulation, in press (2021).
SP4: iFILM-based In vivo Evaluation of Thermal Injury by Cautery during Robotic Surgery Procedures
Principal Investigator: Jonathan Sorger
Institution: Intuitive Surgical Inc. (California)
Associate with: TRD 1 (Aim 2,3,4) and TRD 3 (Aim 2,3)
Grants: Intramural funding from Intuitive Surgical Inc.
This project evaluates in vivo the effects of various levels of radiofrequency energy appliedin cauterizing tissue during the dissection, transection andefforts to achieve hemostasis of robotic surgical procedures.
The new iFLIM technologies will help optimize use of cautery during robotic surgery.
Selected Publications:
- K.J. Wikiel, T. N. Robinson, E.L. Jones. Energy in robotic surgery. Ann Laparosc Endosc Surg (2021); 6:9; http://dx.doi.org/10.21037/ales.2020.03.06
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L. Lagarto, J.E. Phipps, L. Faller, D. Ma, J. Unger, J. Bec, S. Griffey, J. Sorger, D.G. Farwell, and L. Marcu. Electrocautery effects on fluorescence lifetime measurements: An in vivo study in the oral cavity. Journal of Photochemistry and Photobiology B: Biology 185, 90–99 (2018).
SP5: UC Davis Alzheimer’s Disease Research Center
Principal Investigator: Charles DeCarli
Institution: UC Davis
Associate with: TRD 2 (Aim 1,2,4) and TRD 3 (Aim 3)
Grants: P30 AG072972
The UC Davis Alzheimer’s Disease Research Center (UCD ADRC) advances the science of healthy brain aging among diverse populations in a highly diverse research environment by investigating theheterogeneity of cognitive aging and transition to dementia.
Tools developed by the NCIBT, which identify changes in cerebral perfusion, will likely contribute to our understanding of the pathophysiology, and possibly thefuture treatment, of Alzheimer’s disease and associated dementias. A user-friendly technology with the potential for wide dissemination will permit much-needed large population-based studies with reduced cost compared to current blood flow measurement technologies such as perfusion MRI.
Selected Publications:
- Zhou W, Kholiqov O, Zhu J, Zhao M, Zimmermann LL, Martin RM, Lyeth BG, Srinivasan VJ. Functional interferometric diffusing wave spectroscopy of the human brain. Science Advances. 2021;7(20):eabe0150. doi: 10.1126/sciadv.abe0150.
- Barnes LL, Bennett DA. Alzheimer's disease in African Americans: risk factors and challenges for the future. Health Aff (Millwood). 2014;33(4):580-6. doi: 10.1377/hlthaff.2013.1353. PubMed PMID: 24711318.
- Filshtein TJ, Dugger BN, Jin L-W, Olichney JM, Farias ST, Carvajal-Carmona L, Lott P, Mungas D, Reed B, Beckett LA, DeCarli C. Neuropathological Diagnoses of Demented Hispanic, Black, and Non-Hispanic White Decedents Seen at an Alzheimer’s Disease Center. Journal of Alzheimer's Disease. 2019;68:145-58. doi: 10.3233/JAD-180992.
SP6: Navigated Neurosurgical Procedures via 3D Augmented iFLIM
Principal Investigator: Bogdan Valcu
Institution: BrainLab, USA Headquarters Westchester, IL
Associate with: TRD 1 (Aim 2,3,4) and TRD 3 (Aim 2,3)
Grants: Intramural funding from BrainLab
This project seeks to incorporate multiple imaging modalities, including iFLIM time-resolved detection of both tissue autofluorescence and 5-ALA induced PpIX fluorescence, into BrainLab’s surgical navigation system. It will leverage the BrainLab platform’s interfacing capabilities
Incorporation of information regarding tissue metabolism from label-free iFLIM and from improved sensitivity and specificity of detection of 5-ALA enhanced PpIX fluorescence should enhanceguidance of surgical procedures such as tumor resection.
SP7: OMX-CV, A Novel Oxygen Delivery Biotherapeutic for Hemorrhagic Shock in the Battlefield
Principal Investigators: Emin Maltepe and Jeffrey Fineman
Institution: UC San Francisco
Associate with: TRD 2 (Aim 1,2) and TRD 3 (Aim 3)
Grants: USAMRAA W81XWH2010929
Hemorrhage is the leading cause of potentially preventable death prior to arrival of a combat casualty at a medical treatment facility. This project tests the utility of a novel, non-Hb-based oxygen carrier (OMX-CV) from Omniox, Inc., as a therapy for hemorrhagic shock.
If biomarkers can be validated in large animal models as proposed in this project, they will provide surrogate endpoints for optimizing OMX-CV therapy for hemorrhagic shock in humans. Provided that the optical properties (i.e.,absorption) of the oxygen carrier can be characterized and accounted for, iDOS may also aid in assessing treatment efficacy and monitoring recovery.