RADIATION PROTECTION IN DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY

1
RADIATION PROTECTION INDIAGNOSTIC
ANDINTERVENTIONAL RADIOLOGY
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• L 3 Biological effects of ionizing radiation

2
Introduction

• Subject matter radiobiology
• The mechanisms of different types of biological
  effects following exposure to ionizing radiation
• Types of models used to derive risk coefficients
  for estimating the detriment

3
Topics

• Classification of radiation health effects
• Factors affecting radio sensitivity
• Dose-effect response curve
• Whole body response acute radiation syndrome
• Effects of antenatal exposure and delayed effects
  of radiation
• Epidemiology

4
Overview

• To become familiar with the mechanisms of
  different types of biological effects following
  exposure to ionizing radiation. To be aware of
  the models used to derive risk coefficients for
  estimating the detriment.

5
Part 3 Biological effect of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 1 Classification of radiation health
  effects

6
Radiation health effects
TYPE OF EFFECTS
CELL TRANSFORMATION
CELL DEATH
BOTH
ANTENATAL somatic and hereditary expressed in the
foetus, in the live born or descendants
STOCHASTIC somatic hereditary epidemiologically
attributable in large populations
DETERMINISTIC Somatic Clinically attributable in
the exposed individual
7
Biological effects of ionizing radiation

• Deterministic
• e.g. Lens opacities, skin injuries,
• infertility, epilation, etc
• Stochastic
• Cancer, genetic effects.

8
Deterministic effects

• Deterministic(Threshold/non-stochastic)
• Existence of a dose threshold value (below this
  dose, the effect is not observable)
• Severity of the effect increases with dose
• A large number of cells are involved

Radiation injury from an industrial source
9
Threshold Doses for Deterministic Effects

• Cataracts of the lens of the eye 2-10 Gy
• Permanent sterility
• males 3.5-6 Gy
  
• females 2.5-6 Gy
• Temporary sterility
• males 0.15 Gy
• females 0.6 Gy

Severity of effect
dose
threshold
10
Stochastic Effects

• Stochastic(Non-Threshold)
• No threshold
• Probability of the effect increases with dose
• Generally occurs with a single cell
• e.g. Cancer, genetic effects

11
No change
DNA mutation
radiation hit cell nucleus!
12
DIRECT ACTION
INDIRECT ACTION
13
(No Transcript)
14
(No Transcript)
15
Viable Cell
Mutation repaired
Unviable Cell
Cell death
Cancer ?
DNA Mutation
Cell survives but mutated
16
Outcomes after cell exposure
DAMAGE TO DNA
TRANSFORMED CELL
CELL DEATH (APOPTOSIS)
DAMAGE REPAIRED
17
Outcomes after cell exposure
DAMAGE TO DNA
DAMAGE REPAIRED
CELL NECROSIS OR APOPTOSIS
TRANSFORMED CELL
18
How DNA is repaired ?
19
Altered base
Enzyme Glycosylases recognizes lesion and
releases damaged base
AP-endunuclease makes incision and releases
remaining sugar
DNA-polymerase fills resulting gap but nick
remains
DNA ligase seals the nick Repair completed
DNA has been repaired with no loss of genetic
information
20
Repair of DNA damage

• RADIOBIOLOGISTS ASSUME THAT THE REPAIR SYSTEM IS
  NOT 100 EFFECTIVE.

21
Response
Conditioning dose
Response
Challenging dose
ADAPTIVE RESPONSE
Response
Conditioning dose
Challenging dose
22
Outcomes after cell exposure
DAMAGE TO DNA
CELL NECROSIS OR APOPTOSIS
DAMAGE REPAIRED
TRANSFORMED CELL
23
Normal human lymphocyte chromosomes uniformly
distributed
24
Apoptotic cell chromosomes and
nucleus fragmented and collapsed into
apoptotic bodies
25
Effects of cell death
Probability of cell death
100
Acute dose (in mSv)
5000
26
Outcomes after cell exposure
DAMAGE TO DNA
CELL NECROSIS OR APOPTOSIS
DAMAGE REPAIRED
TRANSFORMED CELL
27
Chromosomal deletions
28
Chromosomal translocations
29
(No Transcript)
30
CANCER INITIATION
TUMOR PROMOTION
MALIGNANT PROGRESSION
STEAM CELL
NECROSIS OR APOPTOSIS
MUTATION
METASTASIS
MALIGNANT TRANSFOMATION
DIVISION
31
NORMAL TISSUE
32
CELL INITIATION An initiating event creates a
mutation in one of the basal cells
33
DYSPLASIA More mutations occurred. The initiated
cell has gained proliferative advantages. Rapidly
dividing cells begin to accumulate within the
epithelium.
34
BENIGN TUMOR More changes within the
proliferative cell line lead to full tumor
development.
35
MALIGNANT TUMOR The tumor breaks trough the
basal lamina. The cells are irregularly shaped
and the cell line is immortal. They have an
increased mobility and invasiveness.
36
METASTASIS Cancer cells break through the wall
of a lymphatic vessel or blood capillary. They
can now migrate throughout the body
and potentially seed new tumors.
37
A simple generalized scheme for multistage
oncogenesis
Damage to chromosomal DNA
of a normal target cell
Failure to correct
DNA repair
Appearance of specific
neoplasia-initiating mutation
Promotional growth
of pre-neoplasm
Conversion to overtly
malignant phenotype
Malignant progression
and tumour spread
38
-15
Energy deposition
10
PHYSICAL INTERACTIONS
Excitation/ionization
-12
Initial particle tracks
10
Radical formation
-9
10
PHYSICO-CHEMICAL INTERACTIONS
Diffusion, chemical reactions
Initial DNA damage
-6
10
)
c
e
s
(

-3
DNA breaks / base damage
E
1 ms
10
M
I
T
0
1 second
10
Repair processes
Timing of events leading to radiation effects.
Damage fixation
BIOLOGICAL RESPONSE
3
10
Cell killing
1 hour
Mutations/transformations/aberrations
1 day
6
10
Proliferation of "damaged" cells
Promotion/completion
1 year
Teratogenesis
9
MEDICAL EFFECTS
10
Cancer
100 years
Hereditary defects
39
Part 3 Biological effect of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 2 Factors affecting the radiosensitivity

40
Radiosensitivity RS (1)

• RS Probability of a cell, tissue or organ of
  suffering an effect per unit of dose.
• Bergonie and Tribondeau (1906) RS LAWS RS
  will be greater if the cell
• Is highly mitotic.
• Is undifferentiated.
• Has a high cariocinetic future.

41
Radiosensitivity (2)
Low RS
Medium RS
High RS
Bone Marrow Spleen Thymus Lymphatic
nodes Gonads Eye lens Lymphocytes (exception to
the RS laws)
Muscle Bones Nervous system
Skin Mesoderm organs (liver, heart, lungs)
42
Factors affecting the radiosensitivity

• Physical
• LET (linear energy transfer) ? RS
• Dose rate ? RS
• Chemical
• Increase RS OXYGEN, cytotoxic drugs.
• Decrease RS SULFURE (cys, cysteamine)
• Biological
• Cycle status
• ? RS G2, M
• ? RS S
• Repair of damage (sub-lethal damage may be
  repaired e.g. fractionated dose)

survivor cells
? LET
? LET
G0
M
M
M
G1
G2
S
43
Part 3 Biological effect of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 3 Dose-effect response curve

44
Systemic effects

• Effects may be morphological and/or functional
• Factors
• Which Organ
• How much Dose
• Effects
• Immediate (usually reversible) lt 6 months e.g.
  inflammation, bleeding.
• Delayed (usually irreversible) gt 6 months e.g.
  atrophy, sclerosis, fibrosis.
• Categorization of dose
• lt 1 Gy LOW DOSE
• 1-10 Gy MODERATE DOSE
• gt 10 Gy HIGH DOSE
• Regeneration means replacement by the original
  tissue while Repair means replacement by
  connective tissue.

45
Skin effects

• Following the RS laws (Bergonie and Tribondeau),
  the most RS cells are those from the basal
  stratum of the epidermis.
• Effects are
• Erythema 1 to 24 hours after irradiation of
  about 3-5 Gy
• Alopecia() 5 Gy is reversible 20 Gy is
  irreversible.
• Pigmentation Reversible, appears 8 days after
  irradiation.
• Dry or moist desquamation traduces epidermal
  hypoplasia (dose ? 20 Gy).
• Delayed effects teleangiectasia (), fibrosis.

Histologic view of the skin
From Atlas de Histologia.... J. Boya
Basal stratum cells, highly mitotic, some of them
with melanin, responsible of pigmentation.
()alopecia loss or absence of hair ()
ectasia swelling of part of the body
46
Skin reactions
Threshold
Weeks to
Injury
Dose to
Onset
Skin (Sv)
Early transient erythema
2
ltlt1
Temporary epilation
3
3
Main erythema
6
1.5
Permanent epilation
7
3
Dry desquamation
10
4
Skin damage from prolonged fluoroscopic exposure
Invasive fibrosis
10
Dermal atrophy
11
gt14
Telangiectasis
12
gt52
Moist desquamation
15
4
Late erythema
15
6-10
Dermal necrosis
18
gt10
Secondary ulceration
20
gt6
47
Skin injuries
48
Skin injuries
49
Effects in eye

• Eye lens is highly RS.
• Coagulation of proteins occur with doses greater
  than 2 Gy.
• There are 2 basic effects

Histologic view of eye
Effect
Sv/year for many years
Sv single brief exposure
gt 0.1
0.5-2.0
Detectable opacities
From Atlas de Histologia.... J. Boya
Eye lens is highly RS, moreover, it is surrounded
by highly RS cuboid cells.
gt 0.15
5.0
Visual impairment (cataract)
50
Eye injuries
51
Part 3 Biological effect of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 4 Whole body response acute radiation
  syndrome

52
Whole body response adult

• Acute irradiation syndrome

Chronic irradiation syndrome
1-10 Gy

• Whole body clinic of a partial-body irradiation
• Mechanism Neurovegetative disorder
• Similar to a sick feeling
• Quite frequent in fractionated radiotherapy

10 - 50 Gy
gt 50 Gy
Survival time
BONE MARROW
GASTRO INTESTINAL
Lethal dose 50 / 30
CNS
(central nervous system)
Dose
53
Lethal dose 50 / 30

• Dose which would cause death to 50 of the
  population in 30 days.
• Its value is about 2-3 Gy for humans for whole
  body irradiation.

54
Part 3 Biological effect of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 5 Effects of antenatal exposure and
  delayed effect

55
Effects of antenatal exposure (1)

• As post-conception time increases RS decreases
• It is not easy to establish a cause-effect
  relation because there are a lot of teratogenic
  agents, effects are unspecific and not unique to
  radiation.
• There are 3 kinds of effects lethality,
  congenital anomalies and large delay effects
  (cancer and hereditary effects).

Congenital anomalies

Lethality
Time
Pre-implantation
Foetus
Organogenesis
56
Effects of antenatal exposure (2)

• Lethal effects can be induced by relatively small
  doses (such as 0.1 Gy) before or immediately
  after implantation of the embryo into the uterine
  wall. They may also be induced after higher doses
  during all the stages during intra-uterine
  development.

0.1 Gy

Lethality
Time
Pre-implantation
Organogenesis
Foetus
57
Effects of antenatal exposure (3)

• Mental retardation
• ICRP establishes that mental retardation can be
  induced by radiation (Intelligence Quotient score
  lt 100).
• It occurs during the most RS period 8-25 week of
  pregnancy.
• Risks of antenatal exposure related to mental
  retardation are

15-25 week
8-15 week
Severe mental retardation with a risk factor of
0.1/Sv
Severe mental retardation with a risk factor of
0.4/Sv
58
Delayed effects of radiation

• Classification
• SOMATIC they affect the health of the irradiated
  person. They are mainly different kinds of cancer
  (leukemia is the most common, with a delay period
  of 2-5 years, but also colon, lung, stomach
  cancer)
• GENETIC they affect the health of the offspring
  of the irradiated person. They are mutations that
  cause malformation of any kind (such as
  mongolism)

59
Part 3 Biological effects of ionizing radiation
IAEA Training Material on Radiation Protection in
Diagnostic and Interventional Radiology

• Topic 6 Epidemiology

60
Epidemiology I

• Irradiated populations can be studied by
• following cohorts of exposed and non-exposed
  people
• back-tracing patients suffering from the disease
  with regard to possible exposure (case controls)

61
Epidemiology II

• Irradiated populations are
• people exposed from the atomic bomb explosions
• people exposed during nuclear and other radiation
  accidents
• patients exposed for medical reasons
• people exposed to natural radiation
• workers in radiation industries

62
Epidemiology III

• Most valid data come from high dose / high dose
  rate exposure to low LET radiation, including
  some radionuclides iodine 131I, and from high
  LET internal exposure to a emitters in lung, bone
  and liver.

63
Epidemiology IV

• Information is scanty (not much,less than needed)
  on
• Consequences of low doses delivered at low dose
  rates
• To detect an increase from a 20 spontaneous
  cancer incidence to 25 (corresponding to an
  exposure to 1 Sv) gt 1300 persons must be studied
• Consequences of external high LET radiation
• (neutrons) and several radionuclides
• Presence and influence of confounding factors
• especially if different populations are to be
  compared

64
Epidemiology V

• Modifying influence of cancer background
  incidence
• does radiation-induced cancer increase at a fixed
  level or in proportion to existing cancer
  additive vs. multiplicative risk model ?
• Is, for example, the risk greater in
• European women which have a higher background
  breast tumor rate than Japanese women ?
• Smokers exposed to radon in homes or mines than
  in non-smokers ?

65
Detectability limits in Radioepidemiology
4
10
REGION OF DETECTABILITY
Theoretical limit of detectability due to
statistical causes (90 confidence
interval)
3
10
)
v
S
m
(

E
2
10
S
O
D

E
CHERNOBYL DOSES
V
I
1
10
T
C
E
F
F
E
0
10
REGION OF UNDETECTABILITY
-1
10
0
1
2
4
3
5
6
7
8
9
10
11
10
10
10
10
10
10
10
10
10
10
10
10
Number of people in study and control groups
66
High and Low Spontaneous Cancer Rates
Incidence/105
Tissue High
Low Male / Female Male /Female
Nasopharynx 23.3 9.5 0.2 0.1 Esophagus
20.1 8.3 0.5 0.2 Stomach
95.5 40.1 5.2 2.2 Colon 35.0 29.6 1.8
1.3 Liver 46.7 11.5 0.7 0.3 LungBronchus 110.8
29.6 10.3 2.4 Skin melanoma 33.1
29.8 0.2 0.2 Breast female 103.7
14.6 Cervix 53.5 3.0
from UNSCEAR 2000
67
Data on irradiated populations
Population Approximate Size Atomic bomb
survivors Japan 86 000 Atomic
testsSemipalatinsk/Altai 30 000
Marshallese islanders 2 800 Nuclear
accidents intervention teams Chernobyl (total) gt
200 000 population Chernobyl (gt185 kBq /m2
137Cs) 1 500 000 population Chelyabinsk
(total) 70 000 Medical procedures low LET
iodine treatment and therapy 70 000 chest
fluoroscopy 64 000 children hemangioma
treatment 14 000 high LET thorotrast
angiography 4 200 Ra-224 treatment 2
800 Prenatal exposure (fetal radiography, atomic
bombs) 6 000 Occupational exposure workers
nuclear industry (Japan, UK) 115 000 uranium
miners 21 000 radium dial painters 2
500 radiologists 10 000 Natural exposure
(Chinese, EC and US studies) several 100 000
68
Populations Studied for Specific Cancers (I)

• Leukemia atomic bomb survivors, radiotherapy for
  ankylosing spondylitis and cervix cancer,
  radiologists, people at the Majak plant,
  Chelyabinsk and the Techa river, prenatal
  radio-diagnostics (Oxford survey)
• Lung cancer atomic bomb survivors, U and other
  miners in CSSR, Canada, USA, Germany, Sweden

69
Populations Studied for Specific Cancers (II)

• Breast cancer atomic bomb survivors, fluoroscopy
  TB patients, radiotherapy mastitis
• Thyroid cancer radiotherapy thymus enlargement,
  tinea capitis skin hemangioma, fallout at
  Marshall islands, children near the Chernobyl
  accident
• Liver cancer Thorotrast angiography
• Osteosarcoma 224Ra (226Ra) treatment, 226Ra
  (watch) dial painters.

70
Excess Solid-Tumor Deaths amongAtomic-Bomb
Survivors
71
Relative Mortality Risks at Different Times After
Exposure
20
Leukaemia ( 10.7/y)
10
5
Estimated relative risk at 1 Gy
All cancers except
2
leukaemia ( 4.8/y)
1
0.5
1950-
1963-
1959-
1955-
1971-
1967-
1975-
1979-
1954
1966
1962
1958
1974
1970
1978
1982
Interval of follow-up Atomic bomb survivors
72
Relative Risks of Radon from Indoor Exposure and
from Mining
2
1.5

,

,
,



,

1
miner studies (cohorts)
indoor studies (case controls)
0.6
Relative risk
log-linear fit to indoor studies
estimated from correlation study in different
regions
0.5
0.4
0.3
0
100
200
300
400
500
Radon concentration Bq/m3
73
Breast Cancer in Women Exposed to Fluoroscopy
4
,
3
,
2
Observed/expected breast cancers
,
,
1
,
0
0
1
2
3
4
Mean absorbed dose (Gy)
74
Thyroid Tumors in Irradiated Children
10
8
,
Thyroid Cancer
6
,
Relative risk
,
4
,
,
Thyroid benign
2
tumors
,
,
,
0
0
0.05
0.1
0.15
0.2
0.25
Mean dose (Gy)
75
Thyroid Cancer Cases in Children after the
Chernobyl Accident
100
Children under 15 years of age at diagnosis

80


Belarus




60
"
No of Cases
"

"
"
"
"
40
Ukraine
"

"
"
20
Russian Fed.
"
"
"

"












0



86
87
88
89
90
91
92
93
94
95
96
97
98
76
Thyroid Cancer in Children in the Chernobyl Region
Region No of Cases before
the accident after the accident Belarus (1977
-1985) 7 (1986-1994) 390 Ukraine (1981-198
5) 24 (1986-1995) 220 Russia (Bryansk and
Kaluga region only) (1986-1995) 62 The data
represent incidences (not mortality) and are
preliminary results. Most excess cancers occurred
since 1993. Thyroid cancer has a high rate of
cure gt90, but many of the cancers found are of
the aggressive papillary type.
77
Risk Estimates from Occupational Exposure
Study Excess relative risk
per Sv All cancer Leukemia UK National
Registry Radiation Workers 0.47 (-0.12-1.20) 4.3
(0.4-13.6) 1,218,000 person years 34 mSv
average dose US Workers -1.0 (lt0-0.83 lt0
(lt0-3.4) 705,000 person years 32 mSv
average dose Atomic Bomb Survivors 0.33
(0.11-0.6) 6.2 (2.7-13.8) 2,185,000 person
years 251 mSv average dose
78
Doses and Risks for in Utero Radiodiagnostics
Exposure Mean foetal dose Hered. Disease
Fatal cancer
(mGy) to age
14 y X Ray Abdomen 2.6 6.2
10-5 7.7 10-5 Barium enema 16 3.9 10-4 4.8
10-4 Barium meal 2.8 6.7 10-5 8.4 10-5 IV
urography 3.2 7.7 10-5 9.6 10-5 Lumbar
spine 3.2 7.6 10-5 9.5 10-5 Pelvis 1.7 4.0
10-5 5.1 10-5 Computed tomography Abdomen 8.0 1.9
10-4 2.4 10-4 Lumbar spine 2.4 5.7 10-5 7.1
10-5 Pelvis 25 6.1 10-4 7.7 10-4 Nuclear
medicine Tc bone scan 3.3 7.9 10-4 1.0 10-4
Tc brain scan 4.3 1.0 10-5 1.3 10-4
79
Extrapolation by Additive and Multiplicative
Risks Models
Following exposure to 2 Gy at an age of 45 years

Spontaneous risks increase with age
45
Radiation risks become apparent after a lag
period (5) -10 years
35
Additive risk models imply constant risk
independent of background.
Annual Probability of death /1000 persons
Multiplicative risk models imply an increase
proportional to background risk
25
15
5
Age Years
80
Risk Probability Coefficients (ICRP)
Tissue Probability of fatal
Cancer (10-2/Sv)
Population Workers Bladder
0.30 0.24 Bone marrow 0.50 0.40 Bone surface
0.05 0.04 Breast 0.20 0.16 Colon
0.85 0.68 Liver 0.15 0.12 Lung
0.85 0.68 Esophagus 0.30 0.24 Ovary
0.10 0.08 Skin 0.02 0.02 Stomach
1.10 0.88 Thyroid 0.08 0.06 Remainder
0.50 0.40 Total all cancers 5.00 4.00 Genetic
effects weighted 1.00 0.50
81
Proportion of Fatal Cancers Attributable to
Different Agents
Agent or Class Percentage of all
Cancer Disease
Best estimate Range Smoking
31 29 - 33 Alcoholic beverages 5 3 - 7 Diet
35 20 - 60 Natural hormones 15 10 - 20 Infection
10 5 - 15 Occupation 3 2 - 6 Medicines, medical
practices 1 0.5 - 2 Electromagnetic radiation
8 5 -10 Ionizing (85 from natural radiation)
4.5 Ultraviolet
2.5 Lower frequency
lt1 Industrial products lt1 lt1 -
2 Pollution 2 lt1 - 4 Other ? ?
82
Tissue risk factor (1)

• RISK FACTOR The quotient of increase in
  probability of a stochastic effect and the
  received dose. It is measured in Sv-1 or mSv-1.

Effect
? probability
? probability
Risk factor

? dose
? dose
Dose
83
Tissue risk factor (2)

• EXAMPLE A risk factor of 0.005 Sv-1 for bone
  marrow (lifetime mortality in a population of all
  ages from specific fatal cancer after exposure to
  low doses) means that if 1,000 people would
  receive 1 Sv to the bone marrow, 5 will die from
  a cancer induced by radiation.

? probability
? probability
Risk factor

Effect
? dose
? dose
Dose
84
Indicators of relative organ tissue risk
TISSUE OR ORGAN
wT
0.20
Gonads
0.12
Bone marrow (red)
0.12
Colon
0.12
Lung
0.12
Stomach
0.05
Bladder
0.05
Breast
0.05
Liver
0.05
Oesophagus
0.05
Thyroid
0.01
Skin
0.01
Bone surface
0.05
Remainder
85
Summary

• Effects of ionizing radiation may be
  deterministic and stochastic, immediate or
  delayed, somatic or genetic
• Some tissues are highly radiosensitive
• Each tissue has its own risk factor
• Risk from exposure may be assessed through such
  factors

86
Where to Get More Information (1)

• 1990 Recommendations of the ICRP. ICRP
  Publication 60. Pergamon Press 1991
• Radiological protection of the worker in medicine
  and dentistry. ICRP Publication 57. Pergamon
  Press 1989
• Sources and Effects of Ionizing Radiation. United
  Nations Scientific Committee on the Effects of
  Atomic Radiation UNSCEAR 2000 Report to the
  General Assembly, with Scientific Annexes. New
  York, United Nations 2000.

87
Where to Get More Information (2)

• Avoidance of radiation injuries from medical
  interventional procedures. ICRP Publication 85.
  Ann ICRP 200030 (2). Pergamon
• Manual of clinical oncology 6th edition. UICC.
  Springer-Verlag. 1994
• Atlas de Histologia y organografia microscopica.
  J. Boya. Panamericana. 1998
• Tubiana M. et al. Introduction to Radiobiology.
  London Taylor Francis, 1990. 371 pp. ISBN
  0-85066-763-1.