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Bio-Economics Supply and Demand According to Chance Grand Unified Theory of Britt Supply Demand 1) Oxygen and Mitochondria 2) In Vitro to In Vivo Measurements 3) MRI to Optical Imaging Balance and Feedback Economics: Supply and Demand Price Balance and Feedback Demand Increased Demand: higher cost… Unless Supply reacts to meet demand Quantity http://en.wikipedia.org/wiki/Supply_and_demand Supply: “G(BC)P” Results: 1478 Times cited: 68,155 Ave. citations per: 46.11 h-index: 122 70 50 30 10 Pubs/year d pulse ~60 yrs Impact: ~3d ~200 yrs Demand Results: 1478 Times cited: 68,155 Ave. citations per: 46.11 h-index: 122 d pulse ~60 yrs Impact: ~3d ~200 yrs Citations/year 1500 1000 Bio-Economics: Supply and Demand Price Supply Demand Increased Demand: higher Metabolic cost… Unless Supply reacts to meet demand Quantity http://en.wikipedia.org/wiki/Supply_and_demand Cell-Vascular Coupling Diseases Coronary Artery Disease, Peripheral Vascular Disease, Cancer, Neurological Disease, Diabetes… Causes (consequences) Decreased vessel compliance, remodeling endothelial/eNOS damage, impaired reactivity, Consequences (causes) Restricted blood flow to tissue Cellular O2 demand cannot be met Ischemia, hypoxia, necrosis… ROS generation Impaired cellular function, mitochondrial disease Cell-Vascular Coupling Diseases BC Pioneered Optical Measurements Quantify tissue oxygen consumption, perfusion Perturbations: Occlusion, breathing, exercise... Individual Physiology: detection, diagnosis, therapy response… Intrinsic Signal Optical Imaging Lens Whisker Stimulator • Remove skin/muscle, thin skull. • Mechanical Movement of C2 Whisker. • 5 deflections at 5 Hz. • Illuminate with 630 nm light. • Measure change in remitted light. Signal R (t ) R0 R0 Grinvald, Lieke, Frostig, Gilbert, and Wiesel, Nature, 1986. Ron Frostig, UCI Hemodynamic Response stimulation Initial Dip R(t ) R0 R0 630 nm light (deoxy Hb) Overshoot (BOLD) Undershoot t~4s t~7s 1 mm t~1s Rd (fx) Spatial Frequency Domain Imaging (SFDI) Cuccia et. al., Opt Lett, (2005) Cuccia et. al., JBO (2009) µa, µs' Structured light depth 1 Tissue Spatial Frequency, fx (mm-1) SFDI Implications: 0 photon density 1) Optical Property Mapping 1) Depth-Resolved Imaging Tissue Tissue: a low-pass spatial filter Hyperspectral SFDI Soren Konecky Photo of Mapper Close up Full images (350 x 350 pixels) of 46 Wavelengths at 5 Hz. L. Gao, R. T. Kester, and T. S. Tkaczyk, Opt. Express 17, 12293-12308 (2009). Tomasz Tkaczyk Intrinsic Signal Tomograpy depth Black & White: Baseline Color: Functional Change increase 0.5 1 decrease -1 -0.5 Biomedical Optics Before Chance (B.C.) pre-1987 Light Source Detector cuvette Biomedical Optics Chance Era (C.E.) • No Cuvette (too expensive) • Abundant supply of body parts • Time-shared laser sources (“off time” saves $$) • RF electronics = “Radio Shack” Grand Unified Theory of Britt Demand Supply New Unit of Measure: 1 BCU = 100 mW/cm2 ~Max exposure intensity for biotissue damage BCU: Max intensity At the limit Photons are Cheaper $106/Tesla $10-14/photon