Noninvasive in vivo imaging of Tissue Pathology by Stavros G. Demos, Ph.D., LLNL Physicist

• 1. LLNL-PRES-573032This work was performed under the auspices of theU.S. Department of Energy by Lawrence LivermoreNational Laboratory under contract DE-AC52-07NA27344.Lawrence Livermore National Security, LLCStavros G. Demos, Ph.D.Physicist, LLNL

2. Normal Esophagus Barretts EsophagusAutofluorescence Capturing UV Microscope In vivo imaging of tissues microstructure Instantaneous diagnostic decision-making Non-invasive Reduces overall time spent in surgery Eliminates anxiety in waiting for diagnosis Reduces overall costs Greatly improves healthcareLawrence Livermore National Laboratory LLNL-PRES-573032 2 3. Tissue sample is removed from the patient, sent to the lab, sliced intosections, mounted on slides, stained, and examined undermicroscope1. Invasive2. Results in multiple and repetitive surgeries3. Imprecise4. Random sampling error often misses pre-cancerous cells5. Feedback takes extended amounts of time, (typically days)6. Costs are extremely highLawrence Livermore National Laboratory LLNL-PRES-5730323Source: murrasaca.com 4. Endomicroscope systems Instantaneous/real-time diagnostic info. for surgeon Early, instant, accurate detection of disease (cancer, etc.) Imaging helps guide surgical intervention1. Noninvasive2. Reduces repetitive surgeries3. Precise cellular level images4. Random sampling error is not a factor5. Feedback is instantaneous6. Drastically reduces overall costsLawrence Livermore National Laboratory LLNL-PRES-5730324Source: www.gastroarkansas.com 5. Current Market Solutions:1) Optical sectioning trade-off: poor light collection efficiency2) Contrast agents trade-offs: long preparation time and expenseLawrence Livermore National Laboratory LLNL-PRES-5730325Source: maunakeatech.comMauna Keas Confocal Laser Endomicroscopy product:*optical sectioning*fluorescein 6. eliminates need for Optical Sectioning:a) Limits photon penetration depthb) Allows high throughput designs w/ optimal signal collectioneliminates need for Contrast Agents/Staining:(Intrinsic UV excited fluorophores)a) Act as natural stainsyields resolution suitable for tissue diagnosis:a) Provides diffraction limited spatial resolutionb) Eliminates motion artifacts in vivoLawrence Livermore National Laboratory LLNL-PRES-5730326 7. Visualization at the cellular level Details of epithelial microstructure Visualization of the margins Targeted biopsies High resolution images (spatial resolution ~ 1 m)Lawrence Livermore National Laboratory LLNL-PRES-5730327Epithelium of StomachAF capturing UV Microscope: Real TimeGold Standard: Tissue biopsyH&E StainFeatures seen are comparable to Gold Standard,BUTAF capturing UV microscope provides greaterspeed, ease, & cost efficiency 8. Heeryae.comIn vivo pathology markets Microscopy of the lumens of several organs Laparoscopic microscopy & Hand-held microscopyEx vivo market Similar to frozen section biopsy without tissue processing, (all done in OR)Pharmaceutical Industry Visualization of cellular biochemistry & molecular function Cellular level view of drug delivery, targeting, cellular response,metabolism, and drug removalLaboratory Animal Research In vivo study of tumors, tissue abnormalities, etc.University and Secondary Bio/Anatomy Edu. In vivo lessons/study of the GI tract, organs, tissues, and cellular levelfeaturesLawrence Livermore National Laboratory LLNL-PRES-573032 8 9. Available tabletop prototype Tested microendoscope concept and design parameters (ex vivo) Diagnostic studies: human esophageal tissues and animal tissues (ex vivo) Animal imaging and stem cell localization/targetingFuture Development: Proof of Principle in Humans (in vivo)Lawrence Livermore National Laboratory LLNL-PRES-5730329Source: businessinsider.com1 Construct pre-product microendoscope2 Validation using human subjects3 Commercialization 10. Genaro [email protected] Livermore National Laboratory LLNL-PRES-57303210