medical radiations physics 2 oral assessment

do I need to wear a monitor?

a personal radiation monitoring device supplied by a Personal Radiation Monitoring Service, approved in accordance with the criteria specified in the National Directory for Radiation Protection, is provided to each occupationally exposed person who is likely to be exposed to ionising radiation in excess of 1mSv in any one year.

RMIT monitor policy

wear OSLs at all times during radiation laboratories and in clinical practice

what is the measurement of dose?

• measurement, calculation, estimation and assessment of absorbed dose

• use weighting factors to convert to equivalent and effective dose

external dosimetry

• dosimetry of the external exposure

  • dose outside the body

personal dosimetry

type of external dosimetry, determines individual dose

radiation worker dose limit

20mSv/year

general public dose limit

1mSv/year

carer dose limit

5mSv/year

passive personal dosimetry

• produces radiation induced signal

• stores signal in device

• signal is processed and output is analysed

• TLD, film badge, OSL

• ionising radiation changes atomic structure in dosimeter

  • traps electrons at higher state (excited)

  • remains until monitor is read

    • returns to ground state - emit light

      • more radiation - more light emitted

OSL

optically stimulated luminescence dosimeter

• OSL material is beryllium oxide ceramic

  • when radiation enters material, it traps electrons released by radiation exposure

    • excited state

  • electrons are released only when monitor is read by OSL reader

  • stimulation of light → stored energy is released in form of light

• light output measured by photomultipliers → converted into dose

  • light photon in → converted to electrons → multiplied into many electrons → gives electronic signal → digital signal → dose

TLD

thermoluminescent dosimeter

• material calcium fluoride or lithium fluoride

• passive radiation dosimeter

• when ionising radiation passes, detector chip absorbs and slight changes in structure occurs

  • excited electrons are trapped

• when read, chip is heated

  • trapped electrons return to ground state and emits photons of visible light

  • light is proportional to radiation absorbed

active personal dosimeter

• real time value of exposure

• produces radiation induced signal and displays a direct reading of the detected dose or dose rate in real time

• mainly alpha, beta, gamma

  • does not do neutron

electronic personal dosimeter

active personal dosimeter

• electronic personal dosimeter (EPD)

  • displays direct reading of detected dose or dose rate

  • programmable dose rate or dose alarm

  • battery powered

  • G-M counter tube, semiconductor or scintillation detectors

• converts energy into electrical signals

• performs direct measurements - depends on electronic properties

internal dosimetry

• not easy

• complicated pathways

• dose monitoring via bio assay or imaging techniques

  • ie. gamma camera

    • requires lots of calculations

personal dose equivalent Hp(0.07)

• less than 1mm under the skin

  • operational quantity for individual monitoring for the assessment of dose to the skin and hands and feet

personal dose equivalent Hp(10)

• 10mm under the skin

  • operational quantity of dose for individual monitoring for the assessment of effective dose

medical dosimetry

• larger scale

• calculation of absorbed dose, equivalent dose and effective dose of ionising radiations used for medical purposes

  • diagnostic or therapy

  • ie. radiation therapy

• often performed by professional medical physicist with special training

  • lots of factors to be considered

• use ionisation chamber and other complex detectors

risk from in utero exposure

• low dose irradiation of the foetus in utero, particularly in the last trimester causes an increased risk of childhood malignancies

• an obstetric x ray examination, even though the dose is only about 10mGy, increases the risk of childhood cancer by 40%

• the excess absolute risk is about 6% per gray

environmental dosimetry

• measured when environment generate a significant radiation dose

• radiation incidents, nuclear reactor sites, radioactive mines

• ie. radon monitoring

purpose of the Radiation Act

• to protect the health and safety of persons and the environment from harmful effects of radiation

  • persons: public, patient, radiation worker

what is the Radiation Protection Principle

the principle that persons and the environment should be protected from unnecessary exposure to radiation through the processes of justification, limitation, optimisation

justification

• radiation activities must be justified, is it necessary

  • will it do more good than harm

• involves assessing whether the benefits of a radiation practice or use of a radiation source outweigh the detriment

limitation

• limit the dose

  • ALARA - as low as reasonably achievable

  • do not use excess dose when not necessary

• involves setting radiation dose limits or imposing other measures

  • so that health risks to any person or the risk to the environment exposed to radiation are below levels considered unacceptable

  • public effective dose is <1mSv/year

    • beyond 1mSv is not acceptable

  • radiation worker is 20mSv/year

  • patient has no dose limit

    • ensure patient does not receive excessive radiation

    • use National Dose Reference Level NDRL

      • we know maximum dose required for a particular examination

    • do not give excess dose than necessary

optimisation

• when planning to give radiation, plan should be optimised

  • apply the most effective radiation, dose, pathway

• in relation to the conduct of a radiation practice, or the use of a radiation source that may expose a person or the environment to ionising radiation, means keeping

  1. the magnitude of individual doses of, or the number of people that may be exposed to, ionising radiation, or

  2. if the magnitude of individual doses, or the number of people that may be exposed, is uncertain, the likelihood of incurring exposures of ionising radiation

  3. as low as reasonably achievable taking into account economic, social and environmental factors

     • photon facility cost vs x ray facility cost

     • social requirements

     • maintaining environment

  4. in relation to the conduct of a radiation practice, or the use of a radiation source, that may expose a person or the environment to non ionising radiation, equates to cost-effectiveness

     • although older machinery may provide more radiation, purchasing newer machinery goes against cost-effectiveness

cell cycle

G1 → synthesis → G2 → mitosis (prophase, metaphase, anaphase, telophase, cytokinesis)

radiosensitivity in the cell cycle

• M and G2 are the most sensitive stages

• S is the most resistant (especially late S phase), G1 is resistant (especially early G1)

• G0 is resistant as the cells are ‘dormant’ and not cycling through the cell cycle

cells are most sensitive at or close to mitosis

• resistance is usually greatest in the latter part of S phase

  • increased resistance is thought to be caused by homologous recombination repair between sister chromatids that is more likely to occur after DNA has replicated

checkpoints in the cell cycle

• cell cycle progression controlled by molecular checkpoint genes

  • genes ensure correct order of cell cycle events

• initiation of later events is dependent on completion of later events

• checkpoint genes halt cells in G2 and take a stock of any damage so repair can be initiated

• significant impact of losing genes to mutation

• there are a number of checkpoints where cellular inventory takes place

• cells exposed to any DNA damaging agent including ionising radiation are arrested in G2 phase

• function of the pause in cell cycle progression is to allow a check of chromosome integrity before the complex task of mitosis is attempted

the R’s of radiobiology

repair, reassortment, repopulation, reoxygenation

repair - the R’s of radiobiology

• most DSBs are irreparable

• most SSB are repaired given enough time

• some SSB cannot be repaired before cell reaches mitosis

  • mitotic death

• cell death from SSB has a linear dose response

• a big dose will increase the number of single strand breaks

  • some by chance will result in DSBs

  • cell survival curve is reflective of this

reassortment - the R’s of radiobiology

• progression of cells through cell cycle during interval between split doses

• cells previously in less sensitive phase cycle into more sensitive portion

• when tissue is irradiated, sensitive cells die

  • leaving resistant cells to continue cycling

• survivors of 1st RT fraction are in resistant phase

  • with a 2-4 interval between fractions, cell survival improves

• if the time interval is 6 hours, cell have ‘reassorted’ to radiosensitive phase

  • cell kill is increased

  • 6 hours, the cells start to repopulate and cell survival is higher

• the following time sequence applies to rapidly growing cells

repopulation - the R’s of radiobiology

• proliferating cells may be resistant due to a higher number of cells in S phase

• after cells are killed, remaining cells continue in cell cycle and repopulate

• the longer time between radiation doses, the more cells will repopulate and survive

  • to kill tumour cells, a higher total dose is required for equivalent biological effect

reoxygenation - the R’s of radiobiology

• the presence of oxygen greatly enhances the radiosensitivity of tissue to low LET radiation

• clinically demonstrated by relative radioresistance of hypoxic tumours

• described by the Oxygen Enhancement Ratio (OER)

  • ~2.5-3 for high doses

  • ~2 for lower doses

• for oxygen effect to be observed, oxygen must be present during or within microseconds after radiation exposure

  • oxygen reacts with free radical R

    • O2+R → RO2

      • RO2 is organic peroxide that is non restorable

      • O2 fixes the damage → makes damage permanent

what is Bergonie’s law

• tissues appear to be more radiosensitive if their cells are less-well differentiated, have greater proliferative capacity and divide more rapidly

  • less-well differentiated → not particularly specific to a specific organ

haemopoietic system radiation effect

• 60% bone marrow in pelvis and vertebrae

• after partial body irradiation, liver and spleen may become active

• stem cells particularly radiosensitive

• ~1Gy results in ~37% survival

• at large doses, all blood cell numbers altered

GIT radiation effects

• oral mucosa

• similar response to skin but more rapid

• frequent limiting factor in RT head and neck tumours

• oesophagus is radiosensitive

  • acute response of oesophagitis

  • substernal burning and pain with swallowing at 10-12 days

• stomach

  • precursors to cells (acid and mucin) are radiosensitive

    • different time delay

  • nausea and vomiting, delayed gastric emptying

• intestine

  • early and late effects

  • early: stripping of epithelium

    • flora return within ~ 4 days

  • late effects are more serious

    • fibrosis and ischaemia

    • involve all tissue layers

    • caused by vascular injury, atrophy of mucosa, adhesion formation

    • can be permanent depending on radiation

lung radiation effects

• intermediate to late responder

• acute pneumonitis at 2-6 months

• fibrosis over months to years

• lung is most sensitive of late responding organs

renal radiation effects

• kidney

• sensitive late responder

• damage develops slowly and may not be evident for years

bladder radiation effects

• superficial cell → lasts several months

• proliferation doesn’t start for months → radiation very slow effect

• latent damage to basal layer revealed after time

• frequency urination increases and further cell loss

• urinary irritation

• late effects of fibrosis and reduced bladder capacity

nervous system radiation effects

• less sensitive

• brain and spinal cord - most important reactions are late

• <6 months may get transient demyelination

testis radiation effects

0.1Gy temporary reduction spermatozoa

2Gy temporary zoospermia for up to 2 years

6-8Gy permanent sterility

ovary radiation effects

• after birth, oocytes (eggs) no longer divide → fixed number

• very radiosensitive

  • cell kill at 0.1Gy

  • sterilisation is immediate

• little effect of fractionation

  • immature and mature follicles equally damaged by radiation

heart radiation effects

• mainly late effects

• ie. acute pericarditis, cardiomyopathy from fibrosis

  • large amount of elasticity required

• fractionation has substantial sparing effect

  • beneficial

bone and cartilage radiation effects

• bone surface not radiosensitive

• particularly important in children esp <2 years

• in adults, osteoporosis may be a complication

lethal radiation damage

irreversible, irreparable - cell death

potentially lethal radiation damage

component of radiation damage can be modified by postirradiation environmental conditions

sublethal radiation damage

can be repaired in hours unless additional sublethal damage is added

potentially lethal damage repair

• survival of density inhibited stationary phase sub cultured immediately after irradiation or after delay (6-12 hours)

• stationary phase time inhibits growth, thus allowing time for damage repair before attempting complex mitosis process

sublethal damage repair

sublethal damage repair is the operational term for the increase in cell survival that is observed when a given radiation dose is split into two fractions separated by a time interval

oxygen enhancement ratio

• the ratio of hypoxic to aerobic IR doses needed to achieve the same biological effects

• oxygen presence (aerated cells) increases radiation effectiveness for cell killing

• lack of oxygen (hypoxic cells) results in more radioresistant cells

• cell surviving fractions are lower in the presence of oxygen vs hypoxic conditions

mechanism of oxygen enhancement

• radiochemistry of radiation effect

  • radiation absorption → energetic (ie. fast) charged particle → ion pair created

  • T1/2 of ion pair is shorter (10^-10 sec)

  • ion pair produces free radical OH*

  • T1/2 of free radical is short (10^-5 sec)

  • ion pair → indirect effect → break bonds → chemical changes

chronic hypoxia

• limited diffusion distance of O2 through respiring tissues

• tumours may outgrow blood supply, have O2 starved regions

acute hypoxia

• blood vessels can be temporarily shut down

• rapidly re-open to supply tissues with O2

oxygen significance for radiotherapy

• the presence of O2 enhances cell killing

  • tumours (animal) include both aerated and hypoxic cells

• hypoxia confers protection from

  • x rays (low/moderate LET radiations) and certain chemotherapeutic agents

• ie. agents involving free radical mechanisms

• if human tumours reoxygenate quickly

  • multi fraction therapy could deal with ‘resistant’ subpopulations

  • dosing at later intervals would maximise killing

low LET sparsely ionising radiation

• x rays

• gamma

• betas (higher energy)

high LET densely ionising radiation

• alphas

• betas (lower energy)

• protons

• neutrons

Linear Energy Transfer LET

LET is the energy transferred per unit length of the track

LET is the average energy locally imparted (deposited) per unit track length (keV/micrometres)

Relative Biological Effectiveness RBE

• relate biological effect to a ‘standard’

• needed because equal energy deposition events (doses) from different radiations do not produce equal effects in biological systems

2 standards 250kVp xrays and 60Co gamma rays

How is RBE related to LET

• as LET increases, the survival curve slope increases and initial shoulder decreases

• RBE increases with LET up to around 100keV/micrometre

• best RBE at 100keV/micrometre → provides enough energy for double stranded break

• too low only produces single strand break → easily repaired

• too high is a waste of energy

Oxygen enhancement ratio and LET

the OER decreases as LET increases

• the OER has a value of 2-3 for low LET radiations

• decreases with increasing LET above ~30keV/micrometre

• reaches unity by an LET of ~160keV/micrometre

• as the OER declines, RBE increases until an LET of ~100keV/micrometre is reached

• demonstrates repair process is not significant at higher LET

acute radiation exposure

• significant dose of radiation over a short period of time

• radiation sickness or death shortly after exposure

• long term effects

  • possibly cancer years later

chronic radiation exposure

occurs when an individual is exposed to a large amount of radiation in a short period of time

• severity and course depends on

  • how much total dose is received

  • how much of the body is exposed

  • sensitivity of exposed individual to radiation

• may appear shortly after exposure, then disappear for a few days

  • only to reappear in a much more serious form in a week or more

    • related to amount of exposure

four stages of acute radiation syndrome

1. prodromal syndrome

2. latent period

3. manifest illness

4. recovery or death

prodromal syndrome symptoms

50% lethal dose: easy fatigability, anorexia, nausea, vomiting

supralethal doses: fever, hypotension, immediate diarrhoea

cerebrovascular syndrome

• a total body dose of about 100Gy of gamma rays or its equivalent of neutrons results in death in 24-48 hours

• development of severe nausea and vomiting, usually within a matter of minutes

• followed by manifestations of disorientation, loss of coordination of muscular movement, respiratory distress, diarrhoea, convulsive seizures, coma and death

• the exact and immediate cause of death is not fully understood

• although death is usually attributed to events taking place within the central nervous system, much higher doses are required to produce death if the head alone is irradiated rather than the entire body

• it has been suggested that the immediate cause of death is

  • damage to the microvasculature

  • results in an increase in the fluid content of the brain owing to leakage from small vessels

  • resulting in a build up of pressure within the bony confines of the skull

gastrointestinal syndrome

• a total body exposure of more than 10Gy of gamma rays or its equivalent of neutrons

• death usually between 3 and 10 days

• the normal lining of the intestine is self renewing tissue

  • the stem cell compartment contains dividing cells

  • of the new cells produced, some maintain the pool, and some go on to differentiate and produce mature functioning cells

  • stem cells in the crypts divide rapidly and provide cells that differentiate to form the lining of the villi

  • a single cell layer separates the blood supply within the villus from the contents of the gastrointestinal (GI tract)

• an exposure to radiation kills cells in the crypts, cutting off a supply of cells to cover villi

  • as a consequence, the villi shrink, and eventually the barrier between blood supply and contents of GI tract is compromised

    • leading to a loss of fluid and massive infections

hematopoietic syndrome

• at doses of 2.5-5Gy, death, if it occurs, is a result of radiation damage to the hematopoietic system

• mitotically active precursor cells are sterilised by the radiation

  • subsequent supply of mature red blood cells, white blood cells and platelets is diminished

• the time of potential crisis at which circulating cells in the blood reaches a minimum value is delayed for some weeks

• it is only when mature circulating cells begin to die off and the supply of new cells from the depleted precursor population is inadequate to replace them that the full effect of the radiation becomes apparent

deterministic effect of radiation

• have a threshold

• above threshold, severity increases with dose

• ie. cataracts

stochastic effect of radiation

• no (or very low) threshold

• probability of occurrence increases with dose

• severity unrelated to dose

• ie. cancer

early human experience radiation carcinogenesis

• skin cancer in early x ray workers

• lung cancer in underground uranium miners in Saxony and Colorado

• bone cancer in radium dial painters

• liver cancer in Thorotrast patients

later human experience radiation carcinogenesis

• Hiroshima/Nagasaki survivors

• elevated incidence of leukaemia in early radiologists (1922)

• thyroid cancer from treatment of enlarged thymus

• thyroid and other cancers for treatment of tinea capitis

• breast cancer in tuberculosis fluoroscopy patients

latent period

time period between irradiation and appearance of disease

absolute risk model

• radiation induces cancers at some fixed number above the natural incidence

• defined as the chance of a person developing a specific disease over a specified time period

relative risk model

• radiation increases the natural incidence at all ages proportional to spontaneous background rates

  • predicts a larger number of induced cancers in old age

• used to compare risk in two different groups of people

time dependent relative risk

function of dose, age at exposure, time since exposure, gender, etc.

standardised mortality ratio

a single summary ratio that allows a comparison of mortality rates among two different populations

SMR = 1.0

implies rates are the same for the population of interest and the standard population

SMR > 1.0

implies rate is greater for population of interest compared to standard population

SMR < 1.0

implies death rate is lower for population of interest compared to standard population 0

if a response to radiation is expected, no matter how small the dose, the dose-response is:

nonthreshold

plating efficiency calculation

(number of colonies counted / number of cells seeded) * 100

surviving fraction calculation

colonies counted / (cells seeded * (PE/100))

the D0 represents the __ for human cells

mean lethal

D0 is the dose required to reduce the fraction of cells surviving to:

37%

D10 is the dose required to kill __ of the cell population

90%

if a cell survival curve is steep and has no shoulder, is it radiosensitive or radioresistive?

radiosensitive

if a cell survival curve is shallow and has a large initial shoulder, is it radiosensitive or radioresistive?

radioresistive

is the oxygen effect more pronounced in low or high LET?

low LET

what happens to RBE as LET increases to 100keV/micrometre?

increases

what happens to RBE as LET exceeds 100keV/micrometre?

decreases

what is the LET of 80kVp diagnostic x rays

1.0 keV/micrometre

a biologic reaction is produced by x Gy of a test radiation. It takes y Gy of 250kVp x rays to produce the same biologic reaction. What is the RBE of the test radiation?

y/x RBE → test radiation as DENOMINATOR

what would be the most likely immediate response to a whole body dose of 3Gy?

diarrhoea, nausea, vomiting

the mean latent period of bone cancer caused by ionising radiation exposure is around

15 years

irradiation in utero by diagnostic x rays increases the spontaneous incidence of leukaemia and childhood cancers by

40% (1→1.4)

what is the importance of the OSL

checking radiation dose, ensure radiation dose is within limits, monitoring dose