Lecture 7: Radiation Effects and Safety Measures

Main-chain scission

Produces many smaller molecules; viscosity decreases.

Cross-linking

Side chains become sticky; viscosity increases.

Point lesions

Disruptions of single chemical bonds but no grossly apparent changes; primary mechanism of cellular damage from low doses of radiation over long periods of time.

DNA damage

Main chain scission, often quickly repaired; mis-repair possible via point mutation.

Frame shift

Can result from both side rail damage and is generally irreparable.

Rung breakage

Simple; 2 nitrogenous bases separated by an ionizing event; typically reparable.

Base separation/loss of base

Typically irreparable; results in a frame shift.

Point mutation

Change/loss of triplet code; single nucleotide is changed.

Silent mutation

Ends up coding for the same protein.

Nonsense mutation

Codes for a stop codon.

Missense mutation

Can be conservative or non-conservative.

Radiolysis of Water

Indirect effect of radiation; principle action is primarily a result of byproducts from the radiolysis of water.

Free radical

Formation from radiolysis; very unstable and can disrupt molecular bonds.

Hydrogen peroxide

Formation from radiolysis; very toxic.

Oxygen effect

Biologic tissue is more sensitive under aerobic conditions.

Oxygen Enhancement Ratio (OER)

Anoxic dose / aerobic dose; always positive.

LET (linear energy Transfer)

OER is dependent on LET; greatest for low-LET, max at 3.0.

Age risk

Highest risk is before birth; younger patients have more rapidly dividing cells and higher metabolic rates.

Law of Bergonie & Tribondeau

Greater maturity of cells increases resistance against radiation.

Radiosensitizers

Halogenated pyrimidines that increase sensitivity to radiation.

Radioprotectors

Contains -SH- group which competes with O2 for free radical binding; protects the patient.

Deterministic effects

Dose dependent; tend to be seen with higher doses characterized by a threshold dose greater than 0.5 Gy (50 rads).

Nondeterministic or Stochastic Effects

Dose independent effects where the severity of the dose is independent of the dose, with probability of response increasing with increased dose.

Acute Radiation Lethality

Mega-radiation levels, such as those from Hiroshima or Chernobyl, with LD 50/30 being the lethal dose to kill 50% of the population in about 30 days.

Humans LD

The lethal dose for humans is between 300 to 400 rads.

Hematologic death

Occurs with doses more than 100 rads.

Gastrointestinal death

Occurs with doses more than 1,000 rads.

Central nervous system death

Occurs with doses more than 10,000 rads.

Skin

Subject to a deterministic effect; epithelial cells have moderate sensitivity and replace themselves about 2% per day.

Epidermal basal (stem) cells

The earliest damage in skin radiation injury.

Nonlinear threshold

Skin response is nonlinear with a threshold at about 200 rads.

Moist desquamation

Indicates clinical tolerance level of the patient and takes about 1800 rads over 4 weeks.

Erythema

The earliest sign of skin radiation injury, with S.E.D50 for erythema being 600 rads.

Fluoroscopy

Boost mode gives up to a 15 fold increase in radiation per unit time, with standard fluoroscopy at 2 rads/min and boost mode at 30 rads/min.

Spermatogonia

Among the most radiosensitive cells in the body, more so than oocytes.

Testes radiation effects

As little as 10 rads can cause a decrease in spermatozoa; 200 rads can cause temporary sterility, and 500 rads can cause permanent sterility.

Ovaries radiation effects

Pre-puberty radiation can cause germ cell death and ovarian atrophy; post-puberty irradiation has similar effects as testes.

Cytogenic Phenomena

A hit usually disrupts molecular bonds and produces visible chromosomal damage, with every chromosomal aberration being inducible by radiation.

Cytogenic Damage

Damage is usually manifest during the next cellular mitosis, with significant radiation damage causing chromosomal aberrations in the next 1 to 2 cell divisions.

Single hit

A type of cytogenic damage that occurs at very low radiation doses.

Multi hit aberrations

The most significant latent human damage that occurs at high doses, where frequency increases when dosages increase.

Rings

Results from multi-damage on the same chromosome.

Dicentrics

Reciprocal translocations from adjacent hits.

Absolute risk

Estimates based on the slope of linear dose response.

Excess risk

Calculated as observed cases minus expected cases.

Relative risk

Calculated as observed cases divided by expected cases.

Cataract Formation

Lens radiosensitivity is age dependent.

Greater effect with older age

Older age results in a greater effect and shorter latent period for cataract formation.

Deterministic effect

A type of effect associated with cataract formation.

Acute threshold for cataract formation

Probably about 2 Gy.

Fractionated threshold for cataract formation

As high as 10 Gy, indicating that breaking up the dose over a set period of time is safer.

Latent period for cataracts

Average of 15 years, but reported from 5 to 30 years.

Life span Shortening

Since 1965, radiologic occupations are considered safe, with a potential loss of about 12 days due to radiation.

Radiation Induced Carcinogenesis

Typically follows a non-threshold dose response, with mortality generally linear below 4.0 Sv.

Radiation-induced Leukemia

The cancer that requires the least dose to develop and is the earliest to develop.

Thyroid Cancers

Highly sensitive for radiation cancer, arising almost exclusively from follicular epithelium.

Morality of thyroid cancer

Much less (only 5 to 10%) than medullary thyroid cancer.

Natural incidences of thyroid cancer

Statistics show 4/100,000 natural incidences, but only 5% are fatal.

Susceptibility to thyroid cancers

Females are 3x as susceptible to all types of thyroid cancers.

Increased risk for children

Children in their first five years have an increased risk for thyroid cancers.

Yellow bone marrow

Not as sensitive as red marrow.

Red marrow

Mostly found in the axial skeleton - spine, pelvis.

Yellow marrow

Mostly found in the appendicular skeleton - hand, foot.

High dose

Suppresses RBCs and lymphocytes.

Long term effects of high dose radiation

May increase leukocyte proliferation.

Risk of leukemia from x-ray exams

As high as 12%.

Radiation-induced Leukemia Data

Linear - quadratic, non-threshold, 4 to 7 year latency (at risk for about 20 years, after which you're probably fine), 3:1 relative risk.

Solid Tumors

3 times more common than Leukemia.

Solid Tumors latency

Average latency = 20 years or more.

Specific examples of Solid Tumors

Lung cancer - relative risk of up to 8:1; Breast cancer - relative risk from 2.5 to 10.

Overall Quantitative Radiation-Induced Cancer risks

A single exposure to a lot of radiation (10 rads) doesn't result in as much excess mortality as does continuous exposure to low doses (1 rad, or 100 mrads).

Overall lifetime cancer risk increase

About 1% for every 10 rad (33% natural incidence).

Females radiosensitivity

About 70% more radiosensitive to cancer than males.

Newborn radiosensitivity

Newborns are 3 times more radiosensitive for cancer than a 25 year old.

70 year old radiosensitivity

70 year old's are about 3 times less radiosensitive than a 25 year old.

Genetic Mutations Data from drosophila

Linear non-threshold curves, no 'dose rate' effect; genetic effects are cumulative.

Doubling dose from 5 to 150 rads

Natural mutation rate is doubled in as little as 5 rads.

Doubling dose in Mega-mouse experiments

Much higher in mice than fruit flies, more like 100 or 200 rads.

Substantial dose rate effect in Mega-mouse experiments

Same dose administered over time results in fewer mutations than acute exposure.

Dose rate effect in gonads

Chronic irradiation is considerably less effective in inducing mutations in spermatogonia and oocytes.

Frequency of radiation induced genetic mutations

Very low.

Pertinent conclusions from Mega-mouse experiments

Most mutations are harmful; any dose of radiation entails some genetic risk.

Number of mutations and dose relationship

Proportional to dose; linear extrapolation from high dose is a valid estimate of low-dose effects.

Increase in spontaneous mutation rate

A dose of 1.0 rem per generation increases the natural spontaneous mutation rate by approximately 1%.

Fetal Effects

1st trimester is the most sensitive.

High risk in 1st trimester

High risk of prenatal death, congenital deformities, and neonatal death; risk of leukemia extends to the 2nd trimester.

Fetal exposure

First two weeks: High dose (250 mG) results in resorption of embryo or spontaneous abortion & death.

Congenital abnormalities

1% increase in congenital abnormalities from the normal averages following a 100 mGy (10 rad) fetal dose. Normally, 5% of all live births exhibit congenital abnormality.

Fetal Risks

Below 50 mGy: Probably no risk of embryonic death or major malformation during organogenesis (2nd to 10th week).

Exposure reduction principles

Minimize time, Maximize distance, Employ shielding.

Exposure time

Exposure rate x time. Scatter exposure rate expressed in mR/hr.

Distance

Scatter is generally 0.1% of beam entrance skin intensity at 1.0 meter (about 3 feet).

Scatter radiation

Secondary: primary or secondary beam of radiation. Primary source of scatter radiation is the patient.

Factors affecting scatter

Thickness of body part, Field size = (irradiated voxel)², Kilovoltage and/or dose rate, Orientation of body part and tube, Use of grid.

Proper collimation

Beam restricting devices: Older devices include aperture diaphragm, cones and cylinders. Modern design: Variable aperture collimator.

Variable aperture collimator

Lead shutters to control the field size. Actual dimensions can be off by 2% of the source image distance.

kVp

Once above 70 kVp, you have to put lead in the walls.

Use of grid

Generally employed for kVp's that are greater than 70 kVp and/or for body parts that are thicker than 12 cm.

Grid ratio

Grid ratio = h/d; Greater the height, the better at stopping scatter radiation; Smaller the distance between the lead bars, the better at stopping radiation.

Type of radiation

Primary beam radiation - what the actual beam is being directed at; 1.6 mm lead barrier is typical (double that of secondary radiation). Secondary radiation; Scatter radiation - patient is the major source; Leakage radiation - from the tube head in all directions (usually limited because it gets checked every three years); Requires 0.8 mm (half of what the primary beam radiation requires).