Bio-Economics Supply and Demand According to Chance

1) Oxygen and Mitochondria 2) In Vitro to In Vivo Measurements 3) MRI to Optical Imaging Grand Unified Theory of Britt Supply Demand

Balance and Feedback

Increased Demand: higher cost… Unless Supply reacts to meet demand Demand Quantity Price Economics: Supply and Demand Balance and Feedback

Supply: “G(BC)P” Pubs/year Results: 1478 Times cited: 68,155 Ave. citations per: h-index: 122  pulse ~60 yrs Impact: ~3   ~200 yrs

Demand 1500 Citations/year 1000 Results: 1478 Times cited: 68,155 Ave. citations per: h-index: 122  pulse ~60 yrs Impact: ~3   ~200 yrs

Increased Demand: higher Metabolic cost… Unless Supply reacts to meet demand Supply Demand Quantity Price Bio-Economics: Supply and Demand

Cell-Vascular Coupling Diseases Coronary Artery Disease, Peripheral Vascular Disease, Cancer, Neurological Disease, Diabetes… Consequences (causes) Restricted blood flow to tissue Cellular O 2 demand cannot be met Ischemia, hypoxia, necrosis… ROS generation Impaired cellular function, mitochondrial disease Causes (consequences) Decreased vessel compliance, remodeling endothelial/eNOS damage, impaired reactivity,

Cell-Vascular Coupling Diseases Quantify tissue oxygen consumption, perfusion Perturbations: Occlusion, breathing, exercise... Individual Physiology: detection, diagnosis, therapy response… BC Pioneered Optical Measurements

Intrinsic Signal Optical Imaging 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. Grinvald, Lieke, Frostig, Gilbert, and Wiesel, Nature, Whisker Stimulator Lens Ron Frostig, UCI

Hemodynamic Response stimulation Initial Dip Overshoot (BOLD)Undershoot 1 mm 630 nm light (deoxy Hb) t ~ 1 st ~ 4 st ~ 7 s

Spatial Frequency Domain Imaging (SFDI) Rd (fx)Rd (fx) Spatial Frequency, f x (mm -1 ) µ a, µ s ' Cuccia et. al., Opt Lett, (2005) Cuccia et. al., JBO (2009) 1 0 photon density depth Tissue Structured light SFDI Implications: 1)Optical Property Mapping 1)Depth-Resolved Imaging Tissue: a low-pass spatial filter

Hyperspectral SFDI L. Gao, R. T. Kester, and T. S. Tkaczyk, Opt. Express 17, (2009). Full images (350 x 350 pixels) of 46 Wavelengths at 5 Hz. Close up Photo of Mapper Soren Konecky Tomasz Tkaczyk

Intrinsic Signal Tomograpy depth Black & White: Baseline Color: Functional Change increase decrease

Biomedical Optics Before Chance (B.C.) Light Source Detector cuvette pre-1987

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 Supply Demand

New Unit of Measure: 1 BCU = 100 mW/cm 2 ~Max exposure intensity for biotissue damage BCU: Max intensity At the limit

Photons are Cheaper $10 6 /Tesla $ /photon