School of Engineering Department of Biomedical Engineering Fall 2014-2015 EENG624 – Biomedical Optics Instructor: Jad AYOUB Chapters 1. Introduction to biomedical optics 2. Single scattering: Rayleigh theory and Mie theory 3. Monte Carlo modeling of photon transport 4. Convolution for broad-beam responses 5. Radiative transfer equation and diffusion theory 6. Hybrid model of Monte Carlo method and diffusion theory 7. Sensing of optical properties and spectroscopy 8. Ballistic imaging and microscopy 9. Optical coherence tomography 10.Mueller optical coherence tomography 11.Diffuse optical tomography 12.Photoacoustic tomography 13.Ultrasound-modulated optical tomography Chapter 1 - Introduction • Motivation for Optical Imaging • General Behavior of Light in Biological Tissue • Basic Physics of Light-Matter Interaction Motivation for Optical Imaging 1. Optical photons provide nonionizing and safe radiation for medical applications. 2. Optical spectra -based on absorption, fluorescence, or Raman scattering- provide biochemical information because they are related to molecular conformation. 3. Optical absorption, in particular, reveals angiogenesis and hypermetabolism, both of which are hallmarks of cancer; the former is related to the concentration of hemoglobin and the latter to the oxygen saturation of hemoglobin. Therefore, optical absorption provides contrast for functional imaging. 4. Optical scattering spectra provide information about the size distribution of optical scatterers, such as cell nuclei. 5. Optical polarization provides information about structurally anisotropic tissue components, such as collagen and muscle fiber. Motivation for Optical Imaging (cont’d) 6. Optical frequency shifts due to the optical Doppler effect provide information about blood flow. 7. Optical properties of targeted contrast agents provide contrast for the molecular imaging of biomarkers. 8. Optical properties or bioluminescence of products from gene expression provide contrast for the molecular imaging of gene activities. 9. Optical spectroscopy permits simultaneous detection of multiple contrast agents. 10. Optical transparency in the eye provides a unique opportunity for high-resolution imaging of the retina. Behavior of light in Biological Tissue Optical properties of biological tissue Basic properties • n [–]: index of refraction; e.g., 1.37 • μa [cm–1]: absorption coefficient; e.g., 0.1 • μs [cm–1]: scattering coefficient; e.g., 100 • g [–]: scattering anisotropy, <cosθ>; e.g., 0.9 Derived properties • μt [cm–1]: total interaction (extinction) coefficient, μa + μs • lt [cm]: mean free path, 1/ μt; e.g., 0.1 mm • μs’ [cm–1]: reduced scattering coefficient, μs(1 – g) • μt’ [cm–1]: transport interaction coefficient, μa + μs’ • lt’ [cm]: transport mean free path, 1/ μt’; e.g., 1 mm • μeff [cm–1]: effective attenuation coefficient, (3μa μt’)1/2 • δ [cm]: penetration depth, 1/(3μa μt’)1/2; e.g., 5 mm Light- Matter Interaction Beer’s Law • ππΌ/πΌ − ππ₯ = ππ‘ • πΌ π₯ = πΌ 0 π −ππ‘ π₯ = πΌ(0)π −π₯/ππ‘ I : Ballistic intensity x: Pathlength ππ‘ : Total interaction (extinction) coefficient Spectra of major Biological Absorbers Absorption and its biological origins • Absorption cross section: ππ • Number of density: Na • Absorption coefficient: total cross-sectional area for absorption per unit volume: ππ = ππ ππ • Light attenuates as it propagates in an absorbing medium: ππΌ = −ππ ππ₯ πΌ πΌ π₯ = πΌ0 π −πππ₯ : Beer’s law • Transmittance: π = πΌ(π₯) : πΌ0 Probability of survival after propagation over π₯. Absorption and its biological origins • Origin of absorption: o Hemoglobin (Oxygenated & de-Oxygenated) o Melanin o Water Melanin absorbs (UV) light strongly water can be highly absorbing in some spectral regions Scattering and its biological origins • Scattering cross section: ππ • Number of density: Ns • Scattering coefficient: total cross-sectional area for scattering per unit volume: ππ = ππ ππ • Light attenuates as it propagates in an Scattering medium: ππΌ = −ππ ππ₯ πΌ πΌ π₯ = πΌ0 π −ππ π₯ : Beer’s law πΌ(s) • Transmittance: π = = π −ππ π₯ : Probability of survival after propagation πΌ0 over π₯. Scattering and its biological origins • extinction coefficient : ππ‘ = ππ +ππ (Total interaction coefficient) • The reciprocal of ππ‘ is the mean free path between interaction events Biological structures of various sizes for photon scattering Exercise 1 • In a purely absorbing (non-scattering) medium with absorption coefficient ππ , what percentage of light is left after a lightbeam propagates a length of L? Exercise 1 • In a purely absorbing (non-scattering) medium with absorption coefficient ππ , what percentage of light is left after a lightbeam propagates a length of L? Exercise 2 • In a purely absorbing (non-scattering) medium with absorption coefficient ππ , Derive the average length of survival of a photon? Exercise 2 • In a purely absorbing (non-scattering) medium with absorption coefficient ππ , Derive the average length of survival of a photon? Exercise 3 • In a purely scattering (non-absorbing) medium with scattering coefficient ππ , what percentage of light has not been scattered after the original lightbeam propagates a length of L? Exercise 3 • In a purely scattering (non-absorbing) medium with scattering coefficient ππ , what percentage of light has not been scattered after the original lightbeam propagates a length of L? Exercise 4 • In a purely scattering (non-absorbing) medium with scattering coefficient ππ , Derive the average length of survival of a photon. Exercise 4 • In a purely scattering (non-absorbing) medium with scattering coefficient ππ , Derive the average length of survival of a photon. Exercise 5 • In a scattering medium with absorption coefficient ππ and scattering coefficient ππ , what percentage of light has survived scattering and absorption after the original lightbeam propagates a length of L? Of the percentage that has been absorbed and scattered, what is the percentage that has been absorbed? Oxygen Saturation and Concentration • Estimating concentration by absorption coefficients (@ π1 ≠ π2 ): • π1 , π2 : the two wavelengths • πππ₯ , πππ : Molar extinction coefficients of oxy- and deoxyhemoglobin • πΆππ₯ , πΆππ : Molar concentrations of oxy- and deoxyhemoglobin. Oxygen Saturation and Concentration • Once πΆππ₯ and πΆππ are obtained, the oxygen saturation (ππ2 ) and the total concentration (πΆπ»π΅ ) of hemoglobin can be computed as follows: • This principle provides the basis for pulse oximetry and functional imaging. Angiogenesis can increase πΆπ»π΅ , whereas tumor hypermetabolism can decrease ππ2 . Application: NIRS (Near IR spectroscopy)