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.

Principal Investigator: Jeff Vitt, (Frank Sharp - retired)
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.

Principal Investigator: Theo Ruers
Institution: Netherland Cancer Institute
Associate with: TRD 2 (Aims 1,2,4) and TRD 3 (Aim 3)

In this project we are studying Phaser Theory, FLIM, and Prostate Cancer. We will use iFLIM to assess properties of tumor vs control tissue.

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
• 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).

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.

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.

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.

Principal Investigators: Herman Hedriana, Weijian Yang
Institution: UC Davis
Associate with: TRD 2 (Aim 1,2) and TRD 3 (Aim 3)

Grants: 2233238 (NSF), R21HD114014 (NIH-NIHCD)

The NSF Small Business Technology Transfer (STTR) Phase II project will build on an innovative technology for non-invasive, transabdominal measurement of fetal arterial blood oxygen saturation (fSpO2) developed at the University of California, Davis (UC Davis). The instrument shines light at two specific near infrared wavelengths, followed by precision sensing of the small amount of diffusely-scattered re-emitted light to capture spatio-temporal distribution of light intensity at multiple sites on the maternal abdomen. The relative concentration of oxygenated and deoxygenated hemoglobin in the pulsating fetal blood regulates light absorption by the fetal tissue, resulting in a faint pattern in the sensed light signals. The sensed signals are analyzed using signal processing and machine-learning algorithms to detect such patterns, and to infer fSpO2. The project activities include further revisions of the device prototype and fSpO2 inference algorithm, as well as collaboration with a team of clinical researchers at UC Davis medical center to demonstrate safe and accurate transabdominal fSpO2 measurement in a pilot patient study. The NIH R21 project will build on the iNIRS and TOF-filtered iDWS techniques of TRD2 and further develop these techniques for transabdominal fetal oximetry. The interferometric techniques offer depth resolution and significantly increase the measurement sensitivity of signals from deep tissues (i.e. fetus). The information obtained via iNIRS and TOF-filtered iDWS measurements has the potential to either supplant or supplement the existing approach used in the NSF project. Overall, both the NSF and NIH projects provide the foundation and support for impacting patient care in the longer term.

Use of Center’s technology (Push): The iNIRS techniques of TRD2 offer depth-resolved measurement and could facilitate the measurement of SpO2 from both maternal and fetal tissue from a single-site measurement. The TOF-filtered iDWS technologies of TRD2 could further increase the optical throughput, and thus significantly reduce light power while increasing the signal-to-noise ratio of fetal signal. These techniques are the foundation of the NIH R21 project, and the information obtained via the interferometric techniques may supplant or supplement those approaches used in the NSF project.

Effect on the SP: Center technologies are expected to yield improvements in non-invasive fetal oxygen saturation measurement in a more diverse patient population and/or improved measurement accuracy. Clinically, the technological innovation is expected to provide support for a new method of intrapartum fetal monitoring, potentially leading to reduction in the rate of unnecessary interventions, such as emergency cesarean section surgeries, and improved childbirth outcomes for mothers and neonates.

Selected Publications:

• Yang, W., Liu, S.J. and Ghiasi, S., The Regents of the University of California, 2024. TRANSABDOMINAL FETAL OXIMETRY BASED ON FREQUENCY-MODULATED CONTINUOUS-WAVE NEAR-INFRARED SPECTROSCOPY. U.S. Patent Application 18/249,714.
• Liu, S.J., Lee, S.Y., Pivetti, C., Kulubya, E., Wang, A., Farmer, D.L., Ghiasi, S. and Yang, W., 2023. Recovering fetal signals transabdominally through interferometric near-infrared spectroscopy (iNIRS). Biomedical Optics Express, 14(11), pp.6031-6047.
• Kasap, B., Vali, K., Qian, W., Mo, L., Chithiwala, Z.H., Curtin, A.C., Ghiasi, S. and Hedriana, H.L., 2024. Transcutaneous Discrimination of Fetal Heart Rate from Maternal Heart Rate: A Fetal Oximetry Proof-of-Concept. Reproductive Sciences, pp.1-11.