Collaborative Projects

Principal Investigators: Gordon Li, Eben Rosenthal and Stephanie Goldschmidt

Institution: Stanford University and Vanderbilt University
Associated with: TRD 1 (Aims 1,2,3,4) and TRD 3 (Aims 1,2,3,4)

Grant: 5R01CA239257 

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.

Push: Apply iFLIM devices, fiber probes, and TRD3 analytics alongside panitumumab-IRDye800 imaging to provide quantitative time-resolved fluorescence measurements, assess molecular probe delivery, tissue metabolism, and distinguish endogenous versus exogenous tumor fluorescence.

Pull: Adapt iFLIM hardware and fiber interfaces for IRDye800 detection and develop real-time intraoperative analytics and visualization tools to integrate fluorescence features into surgical decision-making.  

Principal Investigators: Wesley Baker and Arjun Yodh 
Institution: Children’s Hospital of Philadelphia and University of Pennsylvania
Associated with: TRD 2 (Aims 2,3) and TRD 3 (Aims 2,3,4)

Grant: 5R01NS113945-02

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).

Push: Use iDWS technology to improve accuracy and brain specificity of pulsatile blood-flow measurements in older children; apply machine learning methods to reduce superficial signal contamination and generate ICP biomarkers. 

Pull: Extend optical biomarkers validated in infants to older children with thicker extracerebral tissue by creating age-independent, brain-specific monitoring approaches and optimizing sensor configurations.  

Principal Investigators: Nathan Doble and Robert J. Zawadzki
Institutions: Ohio State University and UC Davis, respectively
Associated with: TRD 1 (Aims 1,2,3,4) and TRD 3 (Aims 2,3,4)

Grant: 1R01EY031098-01A1

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.

Push: Implement iFLIM in both in vivo and ex vivo retinal imaging systems to improve fluorescence specificity; apply AI and multimodal data integration approaches from TRD3.  

Pull: Adapt iFLIM for identification of native retinal fluorophores and develop AI methods to integrate and analyze multimodal retinal datasets while optimizing instrument design.  

Principal Investigator: Guoqiang Yu 
Institution: University of Kentucky
Associated with: TRD 1 (Aim 1,2), TRD 2 (Aims 1,2), and TRD 3 (Aims 2,3)

Grant: 1R01EB028792

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.

Push: Apply iDWS and iNIRS technologies to improve signal detection and generate quantitative blood-flow maps; use iFLIM to assess tissue viability through metabolic autofluorescence markers. 

Pull: Adapt interferometric diffuse optical imaging for noncontact surgical environments and develop 3D blood-flow visualization and reconstruction approaches to compare interferometric and speckle-contrast methods. 

Principal Investigator: Farouc Jaffer, MD, PhD 
Institution: MGH, Harvard Medical School
Associated with: TRD 1 (Aims 1,3) and TRD 3 (Aim 3,4)

Grant: 1R01HL150538-01

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.

Push: Integrate iFLIM into NIRF-IVUS systems to characterize plaque composition and provide biochemical information in addition to structural and inflammatory data. 

Pull: Engineer a miniaturized integrated NIRF-IVUS-FLIM catheter and rotary optical system capable of simultaneous time-resolved fluorescence and NIRF acquisition in coronary arteries. 

Principal Investigators: Diana Farmer and Aijun Wang
Institution: UC Davis
Associated with: TRD 1 (Aims 1,2,3), TRD 2 (Aims 1,2,3) and TRD 3 (Aim 3)

Grants: 1R01NS115860-01A1, 5R01NS100761-04, CIRM Grant CLIN2-12129

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.

Push: Incorporate iFLIM and iNIRS into fetal surgical imaging systems to assess structural, metabolic, and vascular tissue characteristics and monitor biomaterial scaffolds and tissue-engineering constructs. 

Pull: Develop a dual-modality probe small enough for fetal microsurgery and create AI algorithms capable of differentiating viable neural placode tissue from surrounding scar tissue during surgery. 

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)

Grants: 5R01CA247595-02

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.

Push: Apply iFLIM to enhance metabolic imaging of oral mucosa and improve detection of precancerous lesions and early cancers, potentially adding FLIM as a new clinical contrast mechanism. 

Pull: Develop AI-based detection of oral neoplasia and adapt real-time visualization tools to improve lesion identification, biopsy guidance, and tumor margin assessment. 

Principal Investigators: Juergen Popp 
Institutions: University of Jena, Germany  
Associated with: TRD 1 (Aim 2) and TRD 3 (Aim 2)

The iFLIM technology of TRD1 (Aim x) will be integrated with Raman spectroscopy will in a multimodal imaging device. The multi-dimensional data generated by this new device will be analyzed with new methodologies under TRD3 (Aim 2), to allow intraprocedural assessment of biomolecular characteristics of surgically exposed tissue and surgical ex vivo specimens. FLIm and Raman have already been combined under previous collaborations (i.e., cardiovascular project (1–3), tissue engineering project (4, 5)).

Complementarity of FLIm and Raman can lead to more sensitive and specific imaging protocols to detect cancer in real time during surgical procedures. While FLIm is a fast-imaging technique that can be used for real time mapping large areas, it has decreased chemical specificity. Raman spectroscopy, on the other hand, is intrinsically a slower imaging technique, but it has excellent chemical specificity, enabling detail characterization of areas of interest highlight by FLIm. Integrating Raman and FLIm in head and neck tumors through the development of novel devices combining the two modalities and using TRD3 AI-algorithms will advance the field of intrasurgical guidance. 

Push: Integration of NCIBT's iFLIM technology with Raman spectroscopy will create a multimodal platform combining rapid fluorescence lifetime imaging with highly specific molecular characterization. TRD3 AI and data-fusion methods will enable comprehensive analysis of biomolecular tissue signatures to support intraoperative decision making.

Pull: The project drives development of new multimodal instrumentation, real-time AI-enabled data fusion, and advanced visualization approaches that leverage the complementary strengths of FLIm and Raman spectroscopy to improve cancer detection, margin assessment, and surgical guidance in head and neck oncology.

Principal Investigators: Summer Gibbs, Cliff Pereira, and Dattesh Dave 
Institutions: Oregon Health Sciences University and UC Davis 
Associated with: TRD 1 (Aim 2) and TRD 3 (Aim 2)

This proposal aims to develop molecular probes for peripheral nerves in surgery. The goal of the project is to assess iFLIm use of nerve probes. The approach will involve 1) FLIm of nerve probes and 2) study in humans. The project will use Nerve-Specific Fluorophores for Image-Guided Surgery devices.

Push: The iFLIM technology of TRD1 will be used to characterize and optimize nerve-specific fluorescent probes for image-guided surgery, providing quantitative fluorescence lifetime information that complements conventional intensity-based imaging and improves visualization of peripheral nerves during surgical procedures.

Pull: The Center will be challenged to adapt iFLIM for sensitive detection of nerve-targeted fluorophores and develop advanced analytical and visualization methods that integrate fluorescence lifetime and probe-based contrast information for real-time nerve identification, surgical guidance, and nerve preservation.

Principal Investigators: Oybek Kholiqov
Institution: UC Davis, Cornell University
Associated with: TRD 2 (Aims 1,2,4) 

Grant: 1R41NS137832-01

This grant aims to develop an MR-compatible 16-channel long-wavelength interferometric Near-Infrared Spectroscopy (iNIRS) system for continuous monitoring of adult cerebral blood flow index (BFI) non-invasively. The device will be co-registered with functional MRI (BOLD and ASL) to validate brain hemodynamics monitoring in healthy adults.

The collaborative project will involve 1) the design of a novel detection engine to push performance boundaries of interferometric diffuse optics by multiple orders of magnitude, and 2) new parametric modeling and recovery approaches to provide quantitative waveforms of human cortical blood flow perfusion in clinically relevant units of ml/100g/min.

If successful, this project will improve the interpretability of measurements coming from interferometric diffuse optical systems, aiding adoption into clinical workflows.

Push: NCIBT's iNIRS technology will provide a next-generation MR-compatible interferometric optical platform for continuous, depth-resolved monitoring of cerebral blood flow, enabling validation of brain hemodynamic measurements against gold-standard MRI techniques.

Pull: The project drives development of advanced interferometric detection hardware and quantitative modeling approaches that can transform optical measurements into clinically meaningful cerebral perfusion metrics, improving interpretability and accelerating adoption of interferometric diffuse optics in neuroscience research and patient care.

 Collaborative Project 1 (Rosenthal)

Publications: 

1. Goldschmidt S, Marcu L, Ehrlich K, Hassan MA, Rivas I, Birkeland A, et al. Label-free fluorescence lifetime imaging can distinguish cancer from healthy tissue in spontaneously occurring canine oral tumors. Sci Rep. 2026 Jan 23;16(1):6077. doi:10.1038/s41598-026-37001-3 PubMed PMID: 41578004.  

Grants:  

1. Combinatorial fluorescence image guidance based on EGFR expression to differentiate between cancer and healthy tissue in head and neck squamous cell carcinoma. NCI-funded Paul Calabresi K12 Clinical Oncology Career Development Award. $349,500. PI: Stephanie Goldschmidt  (Awarded) 
2. Clinical Evaluation of a Theragnostic (Diagnostic and Therapeutic) Anti- PDL-1 Fluorescence Imaging Probe in Canine Oral Cancer. Center for Companion Animal health. $100,000. PI: Stephanie Goldschmidt (Awarded)  

 Collaborative Project 2 (Yodh/Baker)

Publications:  

1. Majeski JB, M Forti R, Chong SH, Aparanji S, Zhao M, Abramson K, Ramachandran NR, Srinivasan VJ, Baker WB, Yodh AG. Comparison of diffuse correlation spectroscopy, interferometric diffusing wave spectroscopy, and speckle contrast optical spectroscopy for blood flow monitoring. Neurophotonics. 2025 Jul;12(3):035005. doi: 10.1117/1.NPh.12.3.035005. Epub 2025 Aug 12. PMID: 40799972; PMCID: PMC12340614. 
2. Majeski J, Forti R, Chong S, Ramachandran N, Abramson K, Aparanji S, et al. A Comparative Study of Blood Flow Monitoring Using Interferometric Diffusing Wave Spectroscopy, Speckle Contrast Optical Spectroscopy, and Diffuse Correlation Spectroscopy. Optical Tomography and Spectroscopy. 2024; Optica Publishing Group.  
3. Forti RM, Majeski JB, Mason M, Weeks MK, Ramachandran NV, Abramson K, et al. Performance assessment methodologies for diffuse optical flow technologies. Optica Biophotonics Congress: Biomedical Optics 2024 (Translational, Microscopy, OCT, OTS, BRAIN), Technical Digest Series (Optica Publishing Group, 2024), paper OS1D.6 

 Collaborative Project 4 (Yu)

Presentations:  

1. Samanta R, Zhou W, Srinivasan VJ. Free-Space Interferometric Diffusing Wave Spectroscopy With an 8-bit Camera. Optica Biophotonics Congress: Biomedical Optics 2026 (Translational, Microscopy, OCT, OTS, BRAIN), Technical Digest Series (Optica Publishing Group, 2026), paper OS1D.3  

 Collaborative Project 5 (Jaffer)

Publications: 

1. Zhou X. Label-free characterization of human coronary arteries plaques via high-resolution laser scanning multispectral fluorescence lifetime imaging. Presented at: SPIE Photonics West Conference; 2026 Jan 18; San Francisco, CA. Conference 13826.  

Collaborative Project 10 (PI: Kholiqov)

Publication  

1. Mazumder D, Kholiqov O, Srinivasan VJ. Interferometric near-infrared spectroscopy (iNIRS) reveals that blood flow index depends on wavelength. Biomed Opt Express. 2024 Apr;15(4):2152–74. doi:10.1364/BOE.507373. PubMed PMID: 38633063  
2. Mazumder D, Aparanji S, Kholiqov O, Hamilton D, Samanta R, Srinivasan VJ. 1060 nm interferometric near-infrared spectroscopy. Opt Lett. 2025 Apr 1;50(7):2382–5. doi:10.1364/OL.558899. PubMed PMID: 40167726  

Grant: 

1. Neurotech Blueprint Seedling Award (Awarded) 
2. New York State Innovation Matching Grant (Awarded)