Radiation Biology Rad T 290 Objectives – Radiation Biology Radiosensitivity Somatic Effects Embryonic and Fetal Risks Genetic Effects Patient Interactions **Photoelectric** Classic Coherent Scatter **Compton Scattering** Pair Production Photodisintegration Interaction in the body begin at the atomic level Atoms Molecules Cells Tissues Organ structures X-ray photons can change cells Some radiations are energetic enough to rearrange atoms in materials through which they pass, and can therefore he hazardous to living tissue. 1913 Interactions of X-rays with matter • No interaction; X-ray passes completely through tissue and into the image recording device. • Complete absorption; X-ray energy is completely absorbed by the tissue. No imaging information results. • Partial absorption with scatter; Scattering involves a partial transfer of energy to tissue, with the resulting scattered X-ray having less energy and a different trajectory. Scattered radiation tends to degrade image quality and is the primary source of radiation exposure to operator and staff. Coherent Scattering Also called: Classical scattering or Thompson scattering Occurs with energies below 10 keV Incident x-ray interacts with an atom of matter, causing it to become excited. Immediately the atom releases this excess energy and the scattered x-ray. Coherent Scattering The wavelength is equal to the incident x-ray or equal energy. The only difference is the direction of travel Energy in = Energy out - Only changes is direction Coherent / Classical Scatter Classical (Coherent) Scattering Excitation of the total complement of atomic electrons occurs as a result of interaction with the incident photon No ionization takes place Electrons in shells “vibrate” Small heat is released The photon is scattered in different directions No loss of E Thompson scatter Occurs primarily with low energy x-rays. Classical will occur throughout the diagnostic range. Coherent contributes slightly to film fog and reduces image contrast. Compton Effect or Compton Scattering Occurs throughout the diagnostic imaging range The incident x-ray interacts with the outer electron shell on an atom of matter, removing it. It not only causes ionization but scatters the incident x-ray causing a reductions in energy and the change of direction. COMPTON SCATTERING – OUTER SHELL ELECTRON IN BODY – INTERACTS WITH X-RAY PHOTON FROM TUBE Compton scatter A fairly high energy (high kVp) x-ray photon ejects an outer shell electron. Though the x-ray photon is deflected with somewhat reduced energy (modified scatter), it retains most of its original energy and exits the body as an energetic scattered photon. A Compton e- is also released Since the scattered photon exits the body, it does not pose a radiation hazard to the patient. It can, however, contribute to film fog and pose a radiation hazard to personnel (as in fluoroscopic procedures). XXXXX Compton scatter Both the scattered x-ray and the Compton electron have enough energy to cause more ionization before loosing all their energy In the end the scattered photon is absorbed photoelectrically Compton Effect The Compton electron looses all of its kinetic energy by ionization and excitation and drops into a vacancy in an electron shell previously created by some other ionizing event The probability of Compton effect increases as photon energy increases, however the atomic number does not affect the chances of the Compton effect Compton Scatter Compton is just as likely to occur with soft tissue as bone. Compton can occur with any given photon in any tissue Compton is very important in Radiography, but not in a good way. Scattered photons provides no useful diagnostic information Compton Effect Scattered radiation produces a uniform optical density on the radiograph that reduces image contrast Scattered radiation from Compton contributes to the majority of technologists exposure, especially during fluoroscopy STAY AWAY FROM YOUR PATIENT ! Photoelectric Effect or Absorption Inner-shell ionization The photon is not scattered it is totally absorbed The e- removed from the atom of matter is called a photoelectron, with an energy level equal to the difference between the incident photon and the e- binding energy. Binding Energy is very important Photoelectric – Absorption PHOTOELECTRIC ABSORBTION IN THE PATIENT (CASCADE OF ELECTRONS) Photoelectric effect • A relatively low energy (low kVp) x-ray photon uses all its energy (true absorption) to eject an inner shell electron, • leaving an orbital vacancy. • An electron from the shell above drops down to fill the vacancy and, in doing so, gives up energy in the form of a characteristic ray. • The photoelectric effect is more likely to occur in absorbers of high atomic number (eg, bone, positive contrast media) • and contributes significantly to patient dose, • as all the photon energy is absorbed by the patient (and for the latter reason, is responsible for the production of short-scale contrast). Electron transitions Are accompanied by the emission of more x- rays – secondary radiation Secondary radiation behaves much like scatter radiation Secondary contributes nothing to the image The probability that any given photon will undergo a photoelectric interaction is dependent on the photon energy and the atomic number of the atom CASCADE Photodisintegration Important X-ray Interactions Of the five interactions only two are important to radiology Photoelectric effect or photoelectric absorption Compton scatter Compton scatter Contributes to no useful information Is independent of the atomic number of tissue. The probability of Compton is the same for bone atoms and for soft tissue atoms The probability for Compton is more dependent on kVp or x-ray energy Compton Scatter Results in image fog by optical densities not representing diagnostic information Photon are Photons IR is does not know the difference Photoelectric Absorption Provides information to the IR because photons do not reach the IR This represents anatomic structures with high x-ray absorption characteristics; radiopaque structures; tissue with high atomic number; or tissue with high mass density Attenuation – The total reduction in the # of photons remaining in an x-ray beam after penetration through tissue Absorption = x-ray disappears (Photoelectric, Pair production & Photodisintegration) Scattering = partially absorbed, x-ray emerges from the interaction traveling in a different direction (sometimes with less energy) Absorption + Scattering = Attenuation Attenuation 3 Types of x-rays are important for IMAGE FORMATION DIFFERENTIAL ABSORPTION = the difference between those x-rays absorbed and those transmitted to the IR Compton scatter (no useful information) Photoelectric absorption (produces the light areas on the image) Transmitted x-rays (produces the grey/dark areas on the image) Differential Absorption Increases as the kVp is reduced Approximately 1% of photons that interact with the patient (primary beam) reach the IR. Of that 1% approximately 0.5% interact to form the image Differential Absorption The difference in x-ray interactions Fundamental for image formation Occurs because of Compton Scattering, Photoelectric absorption, and X-ray transmission Differential Absorption Compton vs. Photoelectric Below 80 kVp Photoelectric absorption is predominant above 80 kVp Compton scatter begins to increase. Dependent on the tissue attenuation properties Differential absorption factors High atomic number = larger atoms Mass Density = how tightly the atoms of tissue are packed Z # for air and soft tissue are about the same the OD changes are due to mass density difference Human Biology X-rays are harmful, low energy photons can cause skin burns, cancer, leukemia It is not known for certain the degree of effect following diagnostic levels of x-radiation Technologists Responsibilities Technologists, Student Technologists, Radiologists & Medical Physicists have ethical & professional responsibilities to produce high-quality x-ray images with minimal radiation exposure What is the acronym for this? 47 CARDINAL RULES OF RADIATION PROTECTION •TIME •DISTANCE •SHIELDING 49 Natural radiation • Natural radiation accounts for approximately 300 millirem (mrem) • 3 sources of environmental radiation: cosmic rays, terrestrial radiation and internally deposited radionuclides. The largest source of natural radiation is radon. Biological Response to Ionizing Radiation X-ray interactions with matter (human tissue) can cause biological changes. Technologists must understand cellular biology and how radiation interacts with cells in order to protect oneself and the patient. RBE – Relative Biological Effectiveness THE EARLY YEARS Early measurement of Radiation Skin dryness & erythemia Ulcers formed Late Effects: Cataracts Cancers Radiobiology Radiobiology The study of the effects of ionizing radiation on biologic tissue Most radiobiology research is designed to develop dose-response relationships to determine the effect of planned doses or accidents Comparsion of Units REMS R - ROENTGENS RADS – PATIENT DOSE OCCUPATIONAL EXPOSURE RADS REMS RADS REMS GRAYS SIEVERTS PATIENT ABSORBED DOSE Employee (technologists) = Rad VS. Rem 1 RAD X QF = 1 REM 1 GRAY X QF = 1 SIEVERT QF FOR X-RAYS = 1 So…… Rads = Rems TYPES OF RADIATON (ALL CAUSE IONIZATION) PARTICULATE ALPHA BETA FAST NEUTRONS Unit of mesaure is the curie (Ci) or becquerel (Bq) More destructive ELECTROMAGNETIC XRAY GAMMA (damaged caused by indirect action = free radicals – can be repaired) QUALITY FACTOR Qualifies what the damage is from different types of radiation Example: QF for X-ray is 1 QF for alpha is 20 Alpha is 20 x more damaging to tissue Measurement (Rad + QF = Rem) RBEMeasures biologic tissue response to radiation 66 Patient dose Is reported in Entrance Skin Exposure (ESE) REGULATORY AGENCIES NCRP – National Council on Radiation Protection and Measurement ? NRC – Nuclear Regulatory Committee ? Other regulatory agencies? REGULATORY AGENCIES NCRP – National Council on Radiation Protection and Measurement Reviews recommendation for radiation protection & safety NRC – Nuclear Regulatory Committee Makes LAWS & enforces regulations California Department of Public Health, Radiologic Health Branch (CDPH) Title 17 Human Radiation Response The effects of x-rays on human is the result of interactions at the atomic level Ionization or excitation The result if a deposit if energy in tissue. The excess energy can result in a molecular change that can be measurable if the molecule involved is critical to metabolic function At each stage cell repair is possible Atom ionization Can cause chemical binding property change. If the atom is part of a large molecule the ionization may cause molecule break down or relocation of the atom within the molecule Abnormal molecules In time may function improperly or cease to function. This may cause serious impairment or death of the cell This process is reversible by the ionized atom attracting a free e- and become neutral again Cell and tissues can regenerate and recover from the radiation injury Cell bombarded with photons What damage will they cause? TARGET THEORY BIOLOGIC RESPONSE TO IONIZING RADIATION DEPENTS ON WHERE THE PHOTON INTERACTS CELL STRUCTURE NUCLEUS & CYTOPLASM The most at risk area of the cell……. CHROMOSOMES, WHICH ARE MADE UP OF GENES. Cellular Absorption Direct vs. Indirect Hit Direct Hit Theory: When radiation interacts with DNA. Ionization of a DNA molecule. Break in the bases or phosphate bonds Can injure or kill the cell Indirect Hit Theory: Occurs when water molecules are ionized Produces chemical changes – injury or cell death Vast majority of cellular damage is from indirect hit. Cells The most radiosensitive part of the cell is the deoxyribonucleic acid (DNA) Water is the most abundant molecule in the body. The body is 80% water. Humans are basically made of structure water. Basic Cell Structure Two parts: 1. Nucleus 2. Cytoplasm Nucleus contains chromosomes – genetic info (DNA) DNA is at risk when a cell is exposed to ionizing radiation Cytoplasm – 80% water Tissue response to radiation A precise knowledge of various organ radiosensitivities in unnecessary. However, it is important to have a general knowledge of effects of radiation exposure A few important general principals are important to understand Response of cells to radiation CELL SENSITIVITY TO RADIATION TYPE OF CELL AGE OF CELL TYPE OF DAMAGE RECEIVED KIND OF RADIATION EXPOSURE Human cell types Two general types: Somatic cells Genetic cells MOST CONCERNING EFFECTS OF RADIATION EXPOSURE LATE EFFECTS SOMATIC EFFECTS = INDIVIDUAL EXPOSED GENETIC EFFECTS = FUTURE GENERATIONS Target Theory = for a cell to die after radiation exposure, the target molecule must be inactivated TARGET THEORY Photons hit master molecule DNA = cell dies Or doesn’t hit nucleus – and just passes through No essential damage Hormoresis – repair that can occur when below 5 rads of exposure DNA is the target molecule of radiation damage Radiolysis poison water theory The human body is 80% water molecules and 1% DNA molecules Irradiation of water represents the principal radiation interaction in the body When water is irradiation, it dissociates into other molecular products – RADIOLYSIS OF WATER Formation if ions & free radicals The ion pair may rejoin into a stable water molecule In this case, no damage is done HOH+ recombine to H2O Radiolysis poison water theory H 2 O molecules Ejection of electron = free radical H2 02 = hydrogen peroxide Or H O2 = Hydroperoxyl are formed Radiosensitivity of Cells Bergonie & Tribondeau (1906) – method of classifying a cell’s response to radiation according to sensitivity. Cells are most sensitive during active division (primitive in structure & function). The Law of Bergonie & Tribondeaux Cells that are most sensitive to radiation Young – immature cells Stem Cells Highly dividing (mitotic) cells Highly metabolic Categorizing Radiation Exposure Early vs Late effects of Radiation Early Effect = response that occurs within minutes or days after exposure Late Effects = response that occurs within months or years **most human responses have been observed after LARGE doses. To be cautious we assume even small doses are harmful** Predicting Radiation Dose Responses Radiobiology Irradiated tissue response, besides the cell properties, is determined by the amount of energy deposited per unit mass Linear Energy Transfer (LET) = the rate at which energy is transferred from ionizing radiation to tissue LET The ability of ionizing radiation to produce biologic response increases as the LET of radiation increases When the LET of radiation increases ionizations increase. When LET is high, ionizations occur frequently, increasing the potential for biologic damage Relative Biologic Effectiveness As the LET of radiation increases, the chances of biologic damage also increases Relative Biologic Effectiveness (RBE) = standardizes biologic effects of radiation exposure RBE for diagnostic x-rays is 1 radiation with lower LET is less than 1, radiation with higher LET is greater than 1 QUALITY FACTOR Qualifies what the damage is from different types of radiation Example: QF for X-ray is 1 QF for alpha is 20 Alpha is 20 x more damaging to tissue TYPES OF RADIATON (ALL CAUSE IONIZATION) PARTICULATE (HIGH LET) ALPHA BETA FAST NEUTRONS More destructive ELECTROMAGNETIC (LOW LET) XRAY GAMMA (damaged caused by indirect action = free radicals – can be repaired) Why did the bunny die?? BUNNY A Received 200 rads BUNNY B Received 200 rads Why did the bunny die?? BUNNY A 200 rads x 1 for X-RAY = 200 RADS BUNNY B 200 rads x 20 for alpha = 4000 rads LET vs RBE Biologic Factors Affecting Radiosensitivity Oxygen Effect – tissue is more sensitive when the tissue is oxygenated Age – Humans are most sensitive before birth, sensitivity decreases until maturity, after maturity humans are mostly resistant to radiation effects Age Radiosensitivity LD 50/30 HIGH DOSES RECEIVED 50% OF THE POPULATION WOULD DIE IN 30 DAYS 110 Threshold vs Chance Deterministic (non stochastic) vs Stochastic Radiation Dose-Response Relationships Every radiation dose-response relationship has two characteristics Linear or Nonlinear Threshold or Stochastic (chance) Linear Dose-Response Relationships Linear dose-response – when radiation dose is doubled the response to radiation is likewise doubled Nonthreshold dose-response – any dose, regardless of it size is expected to produce a response – chance Threshold dose-response – a radiation doses below a certain level no response is expected Linear nonthreshold = A & B Linear threshold = C & D LINEAR RESPONSE TO RADIATION – ASSUMES NO PHOTON IS SAFE A. DIAGNOSTIC X-RAY - No Threshold – LOW DOSE – OVER LONG EXPOSURE B. Early Radiology Exposure Threshold amount needed to see affect FIG. 9–7 Graph indicates no-threshold versus threshold response to radiation. Elsevier items and derived items © 2007, 2003 by Saunders, an imprint of Elsevier Inc. SOMATIC & GENETIC STOCHASTIC VS NON STOCHASTIC A = STOCHASTIC “CHANCE” EFFECTS NONTHRESHOLD GENETIC, LEUKEMIA, CANCER DIAGNOSTIC RADIOLOGY B= NON-STOCHASTIC THRESHOLD EFFECTS DETERMINISTIC SOMATIC EFFECTS SKIN ERYTHEMA, CATARACTS, STERILITY RAD -MALIGNANCIES Linear vs Non linear • Linear – direct response to the dose and the effects seen (proportionally) • Non linear – effects are not proportional to the dose received • S curve – rad therapy, skin erythema, most somatic, deterministic radiation effects. 120 Organ Systems Are identified by their rate of cell proliferation and their stage of development. Each organ system have different rates Immature cells are called undifferentiated cells, precursor cells or stem cells. Stem cells are more sensitive to radiation than mature cells Tissue types Radiosensitivity of tissue is also dependent on structural or functional features Tissue types include: Epithelium, Connective (supporting tissues), Muscle and Nervous The various organs of the body exhibit a wide range of sensitivity to radiation. This is determined by the function of the organ, the rate at which cells mature in the organ, and the inherent radiosensitivity of the cell type Example of cell sensitivity Organ or Tissue Weighting Factor Effective Dose NCRP: report # 116 Total Body Response to Radiation Acute Radiation Syndrome – full body exposure given in a few minutes. 3 stages of response: 1. Prodromal Stage: NVD stage (nausea, vomiting, diarrhea) 2. Latent Period: Feels well while undergoing biological changes 3. Manifest Stage: Full effects felt, leads to recovery or death 3 Acute Radiation Syndromes Early Effects • • • Bone marrow syndrome: results in infection, hemorrhage & anemia Gastrointestinal syndrome: results in diarrhea, nausea & vomiting, fever Central nervous syndrome: results in convulsions, coma, & eventual death from increased intracranial pressure. CNS least sensitive in ADULTS – MOST sensitive in the FETUS Late Effects of Radiation Somatic Effects: develop in the individual who is exposed Most common: Cataract formation & Carcinogenesis Genetic Effects: develop in future generations as a result of damage to germ cells. SENSITIVITY TO RADIAITION Which (Male or Female) GONADs are external vs internal Which gender is born with all their reproductive cells? Which gender constantly produces new cells? Which GENDER is more sensitive to radiation at birth? Why? Response of cells to radiation CELL SENSITIVITY TO RADIATION TYPE OF CELL AGE OF CELL TYPE OF DAMAGE RECEIVED KIND OF RADIATION EXPOSURE • What is this called • What type classification (direct or indirect?) 133 Pg 619 Permissible Occupational Dose • Annual dose: • 5 Rem / year 50 mSv / year (NOT TO EXCEED 1.25 rem/quarter) • Cumulative Dose • 1rem x age 10mSv X age OCCUPATIONAL EXPOSURES • 5 REMS / YEAR BUT NOT TO EXCEED 1.25 REM/QUARTER • Technologist essentially receive all exposure during fluoroscopy exams Occupational Dose ANNUAL LIMITS • WHOLE BODY = 5 rems / 5000mrem • LENS OF THE EYE = 15 rems • EXTREMITIES = 50 rems PUBLIC EXPOSURE • 10 % OF OCCUPATIONAL • (MUST BE MONITORED IF ABOVE 10%) • NON MEDICAL EXPOSURE • .5 RAD OR 500 MRAD • UNDER AGE 18 AND STUDENT • 100 mrem 1 mSv GSD • GENETICALY SIGNIFICANT DOSE • Takes all of the population into account • Annual AVERAGE gonadal dose to population of childbearing age • 0. 20 mSv or 20 millirem • *Bushong • *30 mrem per NRC website 139 Fetus Exposure Radiation exposure is most harmful during the first trimester of pregnancy Embryo-Fetus Exposure limit (Monthly) 0.05 rem or 0.5 mSv Effects of radiation in utero are time and dose related Effects include: Prenatal death, neonatal death, congenital abnormalities, malignancy inductions, general impairments of growth, genetic effects, and mental retardation. Irradiation in Utero The first trimester is the most radiosensitive period. After the 2 weeks of fertilization The first 2 weeks of pregnancy may be of least concern because the response is all or nothing After 200 rads delivered at various times Declared Pregnant Worker • Must declare pregnancy – 2 badges provided • 1 worn at collar (Mother’s exposure) • 1 worn inside apron at waist level Under 5 rad – negligible risk Risk increases above 15 rad Recommend abortion (spontaneous) 25 rad (“Baby exposure” approx 1/1000 of ESE) Pregnancy & Embryo Mother – occupational worker (5 rem) • Baby – (500 mRem) • .5 rem/ year • .05 rem/month • 5 mSv .5 mSv / month Pregnant patient • ALWAYS ASK LMP before exposure made • “10-day Rule” No longer used • “Grace period” of implantation • What is the State Law for gonadal shielding? Pregnant Patients Should never knowingly expose a pregnant patient unless a documented decision to so has been made If you must expose; use precise collimation & protective shields. Use a high kVp technique and only the minimal projections Unsuspected pregnancy Always screen female patients for last LMP don’t assume ages (patient privacy) If unsure obtain a blood test or reschedule exam if possible PREGNANT PATIENTS • • • • • • • • • Ascertain LMP - if fetus is exposed Medical Physicist will need information: Which x-ray machine used (mR/mAs) # Of projections (including repeats) Technique for each exposure SID Patient measurement at C/R Fluoro time & technique used Physicist will calculate fetal dose 90 % of cell damage will repair. At each stage cell repair is possible Protraction & Fractionation cause less biological effect If radiation is delivered over a long period of time rather than quickly, the effect of that dose is lessened. Allows for intercellular repair and tissue recovery. Protraction Dose is delivered continuously but at a lower dose rate Fractionation Same dose rate in short doses over a longer period (occupational exposure) Biologic Factors Affecting Radiosensitivity Recovery – human cells can recover from radiation damage. If the radiation dose is not sufficient to kill the cell before its next division. Then given sufficient time, the cell will recover If a tissue or organ receives a sufficient radiation dose it responds by shrinking or atrophy. Cells disintegrate and are carried away as waste products Hormesis Pg. 518 repair that can occur when below 5 rads of exposure A growing body of radiobiologic evidence suggests that a little bit of radiation is good for you. It stimulates hormonal and immune responses to other toxic environmental agents We still practice ALARA Why cancer risks at low doses are uncertain It has been difficult to estimate cancer induction risks, because most of the radiation exposures that humans receive are very close to background levels. At low dose levels of millirems to tens of rems, the risk of radiation-induced cancers is so low, that if the risk exists, it is not readily distinguishable from normal levels of cancer occurrence. In addition, leukemia or solid tumors induced by radiation are indistinguishable from those that result from other causes. 156 Always remember…. IMAGE GENTLY, LIGHTLY & WISELY !! Objectives – Radiation Biology Radiosensitivity Somatic Effects Questions Embryonic and Fetal Risks Genetic Effects