Presentation on theme: "BME 560 Medical Imaging: X-ray, CT, and Nuclear Methods"— Presentation transcript:
1 BME 560 Medical Imaging: X-ray, CT, and Nuclear Methods Radiation Biology Part 1
2 TodayEnergy Transfer to TissuesCell EffectsUnits and Terms
3 Energy Transfer to Tissues The impact of ionizing radiation on tissue is all about energy transferRadiation EnergyIonization of moleculesChemical changeBiological changeInteraction of EM radiation with matterProduction of free radicalsChanges to DNA
4 Energy Transfer to Tissues Remember the four ways EM radiation interacts with matterRayleigh scatterPhotoelectric effect (frees energetic electron)Compton scatter (frees energetic electron)Pair production (consumes electron)Changes to electron state may result in ionized particles
5 Energy Transfer to Tissues Particulate radiation (proton, electron, alpha) also transfers energy to tissuesCollisional transfer: Frees electronsRadiative transfer: Produces X-rays, which may in turn free electronsChanges to electron state may result in ionized particles
6 Energy Transfer to Tissues Types of ionization actionDirect: Free electron directly impacts targetIndirect: Free electron produces chemical change in another molecule that reacts with target
7 Energy Transfer to Tissues Free radicals: Highly reactive ions, atoms, or moleculesReactive oxygen species (ROS) do a majority (2/3) of the damage produced by ionizing radiationHydroxyl radical OH0Hydrogen peroxide H2O2H2OH2O+ + e-H+ + OH0ionizationVery reactive!OH0 + OH0H2O2
8 Energy Transfer to Tissues Linear Energy Transfer (LET)Energy transferred to a medium per unit of path lengthRelated to linear attenuation coefficientUnits: keV / micrometerRadiationLET (keV/mm)Cobalt-60 x rays0.2250 kV x rays2.010 MeV protons4.7150 MeV protons0.52.5 MeV a particles1662 GeV Fe ions1000
9 Cell EffectsDNA is believed to be the main pathway for biological impact of radiationOther parts of a cell may be damaged by ionization, butCells can self-repair many forms of damage,Or, if necessary, self-kill (apoptosis)
10 Cell Effects Ionization products result in breakage of the DNA helix Most DNA breaks can be self-repaired
11 Types of DNA damageEstimation of number of changes resulting from 1Gy low LET radiationInitial Physical DamageNumber of EventsIonization in cell nucleus~1MIonization directly in DNA~2000Excitation directly in DNADamaged BasesDNA single-strand breaks1000Damaged sugars1200Double strand breaks40DNA-protein cross links150Chromosome aberrations~1Lethal events~
12 Cell EffectsIncorrect rejoining of breaks in chromosomes results in aberrations.Most aberrations are lethal to the daughter cell
13 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.
14 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.
15 Cell Effects To be dangerous, the cell must: Suffer an ionization eventSuffer DNA damageBe unable to repair DNA damageSuffer a nonlethal chromosomal aberrationDivide successfully (and maintain this ability)Suffer a functional change that does not trigger apoptosis or killing by neighbors
16 Cell Effects Cell survival curve Usually modeled as 𝑆=exp(−𝛼𝐷−β 𝐷 2 ) Sublethal rangeCell survival curveUsually modeled as“Shoulder”𝑆=exp(−𝛼𝐷−β 𝐷 2 )Fraction of cells survivingDoseA: high LET B: low LET
17 Cell Effects Cell damage may be lethal or sublethal Sublethal damage is repairedFractioning the dose (applying the same dose over multiple exposures or longer time) causes less damage because cells can repair: Dose-rate effectTake advantage of this in radiotherapy: Cancer cells take longer to repair than normal tissue
18 Cell EffectsCell survival is a function of cell type and radiation typeNon- 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?
19 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.
20 Units and Terms Relative Biologic Effectiveness (RBE) Unitless Expresses the relative effect as compared to X-rayRBE = 1 for gamma-ray and X-ray; >1 for particlesDose of X-ray for certain biological effect𝑅𝐵𝐸 𝑟 = 𝐷 𝑋𝑟𝑎𝑦 𝐷 𝑟Dose of radiation r for same effect
21 Units and Terms Radiation Exposure Amount of radiation producing a specified amount of ionized particles in airUnit: coulomb/kg (producing 1 C of charge in 1 KG of air)Old unit: Roentgen (1 C/kg = 3876 R)Only applies to EM radiationDoes not correlate with biological effects
22 Units and Terms Absorbed Dose Energy deposited per unit mass of medium Unit: Gray (Gy) = 1 joule per kilogramOld unit: Rad = .01 GyDepends on the radiation type and the absorbing medium
23 Units and Terms Relate Absorbed Dose to Exposure Exposure is defined in airAbsorbed dose can be any mediumIf medium is air, 1 R ≈ .87 rad; 1 Gy ≈ C/kgFor other materials,𝐷𝑜𝑠𝑒 𝐺𝑦 ≈ 𝜇 𝜌 𝑚𝑎𝑡𝑒𝑟𝑖𝑎𝑙 𝜇 𝜌 𝑎𝑖𝑟 ×𝐸𝑥𝑝𝑜𝑠𝑢𝑟𝑒( 𝐶 𝑘𝑔 )
24 Units and Terms Kerma Kinetic Energy Released in Material Unit: Gray (Gy) = 1 joule per kilogramAccounts for secondary effects of energetic electrons (interactions elsewhere or Bremsstrahlung) where absorbed dose does not
25 Units and Terms Radioactivity Disintegrations per unit time Unit: Becquerel (Bq) = 1 decays per secondUnit: Curie (Ci) = 3.7 x 1010 decays per secondApplies to radioisotopes
26 Units and Terms Equivalent Dose Dose accounting for biological effect Unit: Sievert (Sv) = 1 Gy (energy per unit mass)Old unit: RemApply a weighting factor for the type of radiationSingle type of radiation: 𝐻= 𝑊 𝑅 𝐷 𝑅Multiple types: 𝐻= 𝑅 𝑊 𝑅 𝐷 𝑅WR = weighting factor for type of radiationDR = absorbed dose in Gy
27 Units and TermsEquivalent Dose – weighting factors
28 Units and Terms Effective Dose Measure of whole-body cancer risk due to non-uniform exposureUnit: Sievert (Sv) = 1 Gy (energy per unit mass)Apply a weighting factor for each tissue type exposed𝐸= 𝑇 𝑊 𝑇 𝐻 𝑇 = 𝑇 𝑊 𝑇 𝑅 𝑊 𝑅 𝐷 𝑅𝑇WT = weighting factor for tissue type TWR = weighting factor for type of radiationDRT = absorbed dose in Gy for tissue T
29 Units and Terms Effective Dose – tissue weights Organs Tissue weighting factorsICRP30(I36) 1979ICRP60(I3) 1990ICRP103(I6) 2007Gonads0.250.200.08Red Bone Marrow0.12Colon-LungStomachBreasts0.150.05Bladder0.04LiverOesophagusThyroid0.03Skin0.01Bone surfaceSalivary glandsBrainRemainder of body0.30Total1.00
30 Units and Terms Contrived Units for Biological Effect Physical Units LETkeV/mmrelatedRBERadioactivityBq or CiEquivalent doseSvAbsorbed doseGyrelatedweight for radiation typeRadiation exposureC/kgweight for tissue typerelatedKermaGyEffective doseSv
31 Units and Terms Example problem A hand X-ray is taken at 20 keV. Let Wbone=Wmuscle= Find the effective dose for an exposure of 2.5 x 10-4 C/kg.
32 ReferenceHall, E. J., Center for Radiological Research, Columbia University, “Web-Rad-Train,”