Presentation on theme: "BME 560 Medical Imaging: X-ray, CT, and Nuclear Methods Radiation Biology Part 1."— Presentation transcript:
BME 560 Medical Imaging: X-ray, CT, and Nuclear Methods Radiation Biology Part 1
Today Energy Transfer to Tissues Cell Effects Units and Terms
Energy Transfer to Tissues The impact of ionizing radiation on tissue is all about energy transfer Radiation Energy Ionization of molecules Chemical change Biological change Interaction of EM radiation with matter Production of free radicals Changes to DNA
Energy Transfer to Tissues Remember the four ways EM radiation interacts with matter –Rayleigh scatter –Photoelectric effect (frees energetic electron) –Compton scatter (frees energetic electron) –Pair production (consumes electron) Changes to electron state may result in ionized particles
Energy Transfer to Tissues Particulate radiation (proton, electron, alpha) also transfers energy to tissues –Collisional transfer: Frees electrons –Radiative transfer: Produces X-rays, which may in turn free electrons Changes to electron state may result in ionized particles
Energy Transfer to Tissues Types of ionization action –Direct: Free electron directly impacts target –Indirect: Free electron produces chemical change in another molecule that reacts with target
Energy Transfer to Tissues Free radicals: Highly reactive ions, atoms, or molecules –Reactive oxygen species (ROS) do a majority (2/3) of the damage produced by ionizing radiation Hydroxyl radical OH 0 Hydrogen peroxide H 2 O 2 H2OH2O H 2 O + + e - H + + OH 0 OH 0 + OH 0 H2O2H2O2 ionization Very reactive!
Energy Transfer to Tissues Linear Energy Transfer (LET) –Energy transferred to a medium per unit of path length –Related to linear attenuation coefficient –Units: keV / micrometer Radiation LET (keV/ m) Cobalt-60 x rays0.2 250 kV x rays2.0 10 MeV protons4.7 150 MeV protons0.5 2.5 MeV particles 166 2 GeV Fe ions1000
Cell Effects DNA is believed to be the main pathway for biological impact of radiation Other parts of a cell may be damaged by ionization, but –Cells can self-repair many forms of damage, –Or, if necessary, self-kill (apoptosis)
Cell Effects Ionization products result in breakage of the DNA helix Most DNA breaks can be self-repaired
Types of DNA damage Initial Physical DamageNumber of Events Ionization in cell nucleus~1M Ionization directly in DNA~2000 Excitation directly in DNA~2000 Damaged Bases1000-2000 DNA single-strand breaks1000 Damaged sugars1200 Double strand breaks40 DNA-protein cross links150 Chromosome aberrations~1 Lethal events~0.2-0.8 Estimation of number of changes resulting from 1Gy low LET radiation
Cell Effects Incorrect rejoining of breaks in chromosomes results in aberrations. Most aberrations are lethal to the daughter cell
Cell Effects Surviving daughters have DNA mutations. Most mutations do not cause a significant functional change. Many mutations with functional change will result in the cell killing itself or being killed by its neighbors, But some will produce a survivable, reproducible cell with altered function. The mutated gene is an oncogene.
Cell Effects Surviving daughters have DNA mutations. Most mutations do not cause a significant functional change. Many mutations with functional change will result in the cell killing itself or being killed by its neighbors, But some will produce a survivable, reproducible cell with altered function. The mutated gene is an oncogene. A mutated cell mush retain its ability to divide indefinitely in order to produce a colony sufficient to maintain cancerous growth.
Cell Effects To be dangerous, the cell must: –Suffer an ionization event –Suffer DNA damage –Be unable to repair DNA damage –Suffer a nonlethal chromosomal aberration –Divide successfully (and maintain this ability) –Suffer a functional change that does not trigger apoptosis or killing by neighbors
Cell Effects Cell survival curve –Usually modeled as Fraction of cells surviving Dose A: high LETB: low LET Sublethal range “Shoulder”
Cell Effects Cell damage may be lethal or sublethal –Sublethal damage is repaired –Fractioning the dose (applying the same dose over multiple exposures or longer time) causes less damage because cells can repair: Dose-rate effect –Take advantage of this in radiotherapy: Cancer cells take longer to repair than normal tissue
Cell Effects Cell survival is a function of cell type and radiation type –Non- or slowly proliferating cells (nerve, muscle, secretory) are less susceptible to radiation damage. –Highly-proliferating cells (epithelial, stem cells) are more susceptible. This leads to the concept of radiation “quality” –How effective is the radiation type at causing biological damage?
Units and Terms Linear Energy Transfer (LET) –Unit: keV per micrometer (energy per length) –A function of radiation type, energy, medium (generally water or water-equivalent for tissues) –Survival curve depends on LET. –Equal doses of different types of radiation do not give equal biological effect – they have different LET.
Units and Terms Relative Biologic Effectiveness (RBE) –Unitless –Expresses the relative effect as compared to X-ray –RBE = 1 for gamma-ray and X-ray; >1 for particles Dose of X-ray for certain biological effect Dose of radiation r for same effect
Units and Terms Radiation Exposure –Amount of radiation producing a specified amount of ionized particles in air –Unit: coulomb/kg (producing 1 C of charge in 1 KG of air) –Old unit: Roentgen (1 C/kg = 3876 R) –Only applies to EM radiation –Does not correlate with biological effects
Units and Terms Absorbed Dose –Energy deposited per unit mass of medium –Unit: Gray (Gy) = 1 joule per kilogram –Old unit: Rad =.01 Gy –Depends on the radiation type and the absorbing medium
Units and Terms Relate Absorbed Dose to Exposure –Exposure is defined in air –Absorbed dose can be any medium –If medium is air, 1 R ≈.87 rad; 1 Gy ≈.0297 C/kg –For other materials,
Units and Terms Kerma –Kinetic Energy Released in Material –Unit: Gray (Gy) = 1 joule per kilogram –Accounts for secondary effects of energetic electrons (interactions elsewhere or Bremsstrahlung) where absorbed dose does not
Units and Terms Radioactivity –Disintegrations per unit time –Unit: Becquerel (Bq) = 1 decays per second –Unit: Curie (Ci) = 3.7 x 10 10 decays per second –Applies to radioisotopes
Effective Dose – tissue weights Organs Tissue weighting factors ICRP30(I36) 1979 ICRP60(I3) 1990 ICRP103(I6) 2007 Gonads0.250.200.08 Red Bone Marrow0.12 Colon-0.12 Lung0.12 Stomach-0.12 Breasts0.150.050.12 Bladder-0.050.04 Liver-0.050.04 Oesophagus-0.050.04 Thyroid0.030.050.04 Skin-0.01 Bone surface0.030.01 Salivary glands--0.01 Brain--0.01 Remainder of body0.300.050.12 Total1.00 http://en.wikipedia.org/wiki/Effective_dose_%28radiation%29
Units and Terms LET keV/ m RBE Radiation exposure C/kg Absorbed dose Gy Kerma Gy Radioactivity Bq or Ci Equivalent dose Sv Effective dose Sv Physical Units Contrived Units for Biological Effect related weight for radiation type weight for tissue type related
Units and Terms Example problem –A hand X-ray is taken at 20 keV. Let W bone =W muscle =.002. Find the effective dose for an exposure of 2.5 x 10-4 C/kg.
Reference Hall, E. J., Center for Radiological Research, Columbia University, “Web-Rad-Train,” http://www.columbia.edu/~ejh1/web-rad- train/index.html