Radiation in PET, SPECT, and CT NM Resident Lectures, Nov 28, 2011depts.washington.edu/imreslab/2011 Lectures/Alessio_DOSE... · 2012. 12. 21. · Radiation in PET, SPECT, and CT

Radiation in PET, SPECT, and CT NM Resident Lectures, Nov 28, 2011

Adam Alessio, [email protected] 1

Alessio, 1

Adam Alessio, PhD [email protected]

(206) 543-2419 Department of Radiology University of Washington

http://faculty.washington.edu/aalessio/

Alessio, 2

I.  Ionizing Radiation Dose Metrics II.  Radiation dosimetry for PET, SPECT, and CT III. Medical radiation dose in USA IV. Connection between radiation dose and adverse

side effects V.  How does this influence clinical practice?

GOALS:   Understand uncertainties in effective dose and radiation induced cancer risk

  Recognize 3 recent major reports on radiation dosimetry

Alessio, 3

•  Deterministic –  Severity depends on dose –  There is a dose threshold above which an effect

occurs –  Effects: Hematologic toxicity, renal failure,

gastrointeninal tract toxicity, lung fibrosis, burns, tumor cell death, …

•  Stochastic –  severity is independent of dose –  risk of event occurring is dependent on dose –  there is “no threshold” –  Effects: cancer induction, genetic mutations,…

Alessio, 4

Deterministic (>1Gy) •  Blood-forming organ (Bone marrow) syndrome (>1Gy, >100 rad), Symptoms include

internal bleeding, fatigue, bacterial infections, and fever. •  Gastrointestinal tract syndrome (10Gy, >1000 rad) Symptoms include nausea, vomiting,

diarrhea, dehydration, electrolytic imbalance, …. •  Central nervous system syndrome (>50Gy, >5000 rad) Symptoms include loss of

coordination, confusion, coma, … •  Other effects from an acute dose include:

–  (1-2Gy, 125 to 200 rad) to the ovaries can result in prolonged or permanent suppression of menstruation in about fifty percent (50%) of women.

–  (6Gy, 600 rad) to the ovaries or testicles can result in permanent sterilization.

Alessio, 5

Exposure: Amount of ionization per mass of air, Coulomb/kg = 3876 roentgens Can be measured directly Does not account for biological effects

Absorbed Dose: Energy per mass, Joules/kg = gray (Gy) = 100 rad Amount of energy imparted by radiation per mass Usually calculated from exposure measurement Does not account for biological effects

STOCHASTIC RISK ESTIMATION: Equivalent Dose:

(Absorbed Dose) * radiation weighting factor (wR or Q factor) Units are sieverts (Sv) = 100 rem Relates absorbed dose to probability of stochastic health effects (depends on the type of radiation)

Effective Dose: Sum Over All Tissues[(Equivalent DoseT) * tissue weighting factor (wT)]

Also measured in Sv Relates stochastic risk of specific organs’ equivalent dose to the risk of a uniform whole body dose

Alessio, 6

To go from absorbed dose (Gy) to equivalent dose (Sv), need:

For CT and PET, 1Gy*1 = 1Sv

Recommendations of the International Commission on Radiological Protection, ICRP Publication 103; Ann. ICRP 37 (2–4)



Alessio, 7

DWB(P) = absorbed dose to the whole body that has probability P of causing cancer DT(P) = absorbed dose in a single organ, T, that has probability P of causing cancer in that organ

To go from Equivalent Dose (Sv) to Effective Dose (Sv), need:

Example:

Say stomach absorbs 4 mGy and colon absorbs 2mGy of photons

  Equivalent dose to stomach = 4mSv   Equivalent dose to colon = 2mSv

  Effective Dose = 4mSv * 0.12 + 2mSv*0.12 = 0.72mSv

  Cancer risk from the whole body receiving a uniform dose of 0.72mSv is same as stomach receiving 4mSv and colon receiving 2mSv.

Alessio, 8

Not a real physical quantity, it is a construct designed by ICRP

Effective dose can be used to compare relative radiation detriment when used for patient populations with comparable age and gender distributions.

Purposes: 1.  assessing the relative detriment from nonuniform, partial-body

irradiations, 2.  optimizing radiological procedures involving multiple body organs

or tissues, 3.  comparing against alternative procedures or background

radiation levels, or 4.  assessing the relative radiation detriment from multiple

procedures and modalities

Effective dose not intended to describe dose to an individual (not patient specific)

McCollough CH, Schueler BA. Calculation of effective dose. Med Phys. 2000; 27: 828-837. Shrimpton PC, Wall BF, Yoshizumi TT, Hurwitz LM, Goodman PC. Effective dose and dose-length product in CT. Radiology. 2009; 250: 604-605.

Alessio, 9

Exposure (roentgens)

Absorbed Dose (gray)

Radiation hits matter/tissue

Equivalent Dose (sieverts)

Effective Dose (sieverts)

Estimate Stochastic Risk of Cancer Incidence

Estimate Deterministic Effect on Tissue

Weight absorbed dose by type of radiation

Weight by stochastic radiosensitivity of

tissues

Applications: Therapy, Radiation Accidents Applications: Radiation Safety, Radiation Protection, Imaging

RBE-Weighted Dose (gray)

Equivalent Uniform Dose (EUD) (gray)

Equivalent Uniform Dose that would yield a bio-response similar to nonuniform dose distributions

Isoeffective Dose (gray)

(barendsen, Bd*) Equivalent absorbed dose of low-LET radiation that when

delivered in specified manner has same clinical effects as high-LET radiation

Weight absorbed dose by Relative Biologic Effectiveness

(RBE)

Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry--Standardization of Nomenclature. J Nucl Med. 2009; 50: 477-484. *Sgouros G, Howell RW, Bolch WE, Fisher DR. MIRD Commentary: Proposed Name for a Dosimetry Unit Applicable to Deterministic Biological Effects--The Barendsen (Bd). J Nucl Med. 2009; 50: 485-487. Alessio, 10

Basic Idea: 1.  Model the patient as an “average” size

–  Contains Source organs that contribute dose to Target organs

2.  Model the biokinetics of the radiotracer in source organs

3.  Use simulation data to know absorbed dose to a target organ from a source organ (S-factors: depend on type of radiation and size, shape, and separation of organs)

4.  Tissue weighting factors describe radiosensitivity of each organ

Several groups publish NM dosimetry information: •  Task Group on Radiopharmaceutical Dosimetry of the International Commission on Radiological Protection (ICRP) •  Radiation Internal Dose Information Center (RIDIC)"•  Medical Internal Radiation Dosimetry Committee of the Society of Nuclear Medicine (MIRD)

Alessio, 11

For a Source Organ (rh ) and a target organ (rk ) the Mean Dose (Drk

) to a particular organ is

sum over all sources

using notation from Bushberg

Drk= AhS(rk ← rh )

h∑

where Ah (µCi-hr) is the cumulated activity for each source organand S (rad/µCi-hr) is a factor describing absorbed dose in target for each unit of activity in the source organ

Alessio, 12

•  Cumulated Activity in Source Organ: Total number of disintegrations from radionuclide located in particular source organ. –  Depends on:

1) Portion of injected dose taken up by source organ 2) Rate of elimination from source organ

•  Assume fraction (f) of injected activity is localized in source organ

•  Assume exponential physical decay of radionuclide (Half Life: Tp)

•  Assume exponential biological excretion from source organ (Half Life:Tb) Total Effective Half Life (Te):

Activity in organ at time t: As = fA0e

−ln 2Te

t⎛⎝⎜

⎞⎠⎟

Te =Tp iTbTp +Tb



Alessio, 13

•  Cumulated Activity in Source Organ (cont’d.) –  Now that we have activity at time t, need cumulative activity

(Sum activity over all time)

Ah = f ⋅A0 ⋅e−ln 2Te

t⎛⎝⎜

⎞⎠⎟

0

∞

∫ dt = f ⋅A0 ⋅Teln2

(µCi-hr)•  S Factor : Dose to target organ per unit of cumulated

activity in a specific source organ –  Specific to each source/target combination and radiation type

•  Putting it back together:


h∑

Alessio, 14

•  Patient is injected with 5mCi of Tc-99m-sulfur colloid. What is the absorbed dose to the a) liver and b) kidneys?

•  Source Organ: Liver (assume all activity in liver, uptake in liver is instantaneous, and no biologic removal)

•  Step 1: Find Accumulated Activity:

Te =Tp iTbTp +Tb

= Tp = 6.02hr

Ah = A0 i f i1.44Te =5,000µCi×1×1.44×6.02hr = 4.3×104µCiihr

• Step 2: Find S factors and organ doses Lookup from Table:


h∑Dliver = 2.0 radDkidneys = 1.7 rad

Alessio, 15

Sources of Uncertainty: 1. Model the patient as an “average” size

–  Patient dimensions can vary > 3x 2. Model the biokinetics of the radiotracer in source organs

–  Biokinetics are highly patient specific 3. Tissue weighting factors describe radiosensitivity of each organ

–  Our understanding of these factors has changed 20-40% over the years and is likely to continue to evolve

  As a result, dose estimates vary and are not patient specific

The uncertainty of applying dose estimates from the “median” patient to a specific patient is at a minimum 2x

Alessio, 16 Stabin MG. Radiopharmaceuticals for nuclear cardiology: radiation dosimetry, uncertainties, and risk. J Nucl Med. 2008; 49: 1555-1563.

Summary of effective doses from nuclear cardiology procedures

 Message: Dose estimates vary

Alessio, 17 Values from: Mettler FAJ, Huda W, Yoshizumi TT, Mahesh M. Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology. 2008; 248: 254-263.

Adult effective doses

Alessio, 18

•  Background Equivalent Radiation Time –  Time in years to obtain the same effective dose from

natural background radiation –  Natural background radiation is 3mSv/year in USA*

•  Equivalent # of Chest X-rays –  0.02 mSv/Chest X-ray

* NCRP 160, published March 2, 2009 Mettler FAJ, Thomadsen BR, Bhargavan M et al. Medical radiation exposure in the U.S. in 2006: preliminary results. Health Phys. 2008; 95: 502-507.




Adult effective doses

Alessio, 20

♦ CTDI100 : CTDI for 100 mm axial scan n = slices/scan, T = slice thickness

Absorbed dose to a single slice of plastic phantom (mGy)

Average dose measured by pencil ionization chamber inserted in plastic phantom: 16cm (head/pediatric), 32cm (body)

Alessio, 21

Entrance surface receives larger dose

dose gradient

Superficial regions receive larger doses after rotation

‘Body’ phantom: 32 cm dia. PMMA

2:1 dose ratio

20 mGy

10 mGy

Adapted from: McNitt-Gray, “Radiation Dose in CT”, Radiographics, 2002, 22:1541-1553.

‘Head’ phantom: 16 cm dia. PMMA

uniform dose 40 mGy

Example 120 kVp, 280 mAs (1 sec.), 10-mm collim.

In Transaxial Plane

Alessio, 22

♦ CTDI100: CTDI for 100 mm axial scan n = slices/scan, T = slice thickness

♦ CTDIw: Weighted CTDI weighted average between center and periphery of object/patient Accounts for non-uniform distribution of dose in slice

Absorbed dose to a plastic phantom (mGy)

Alessio, 23

CT Detector-Source Geometry

In transaxial plane source and detector spin around patient

Axial view patient bed moves axially

x-ray detectors

axial collimator x-ray source

& filter

single-slice (detector) or

multi-slice (4, 16, 64, 128 detector rows axially)

Alessio, 24

Along Scanner Axis

Single axial slice dose distribution (one full rotation, one table position);

Dsingle(z)

Cumulative dose distribution from multiple slices (depends on scan parameters such as pitch): Dcumul.(z)

intended or desired dose delivery distribution

actual dose delivery distribution tails off in z (axial) directions

doses from individual slices

cumulative dose from multi-slice scan

When we have multiple slice scanners operating at different pitches, this dose is difficult to represent as CTDIw, so we need…



Alessio, 25

♦ CTDI100:CTDI for 100 mm axial scan n = slices/scan, T = slice thickness

♦ CTDIw: Weighted CTDI weighted average between center and periphery of object/patient

♦ CTDIvol Volume CTDI accounts for pitch parameters and multi-slice helical acquisitions; s = table travel/rot. or axial spacing helical pitch = (s) / (nT)

♦ DLP Dose-Length Product CTDI times length of scan

CTDIvol is industry standard for reporting dose to single slice DLP serve as an index of dose to plastic phantom - not effective dose for indiv. patients

Absorbed dose to a plastic phantom (mGy)

Alessio, 26

♦ X-ray beam energy (kVp)

♦ X-ray tube current (mA)

♦ Rotation or exposure time

♦ Slice thickness

♦ Object thickness

♦ Pitch or spacing

♦ Dose-reduction techniques

♦ X-ray source to isocenter distance

Direct Influence on Dose

Indirect Influence on Dose

♦ Reconstructed slice thickness image statistics require higher kVp and/or mAs in thinner slices to achieve equivalent level of noise as in thicker slices.

♦ Reconstructed image resolution algorithms enhancing spatial resolution also increase image noise- higher kVp and/or mAs may be used to compensate.

Alessio, 27 McNitt-Gray, “Radiation Dose in CT”, Radiographics, 2002, 22:1541-1553.

CTDIw measured in head & body phantoms Dose varies linearly with tube current

Dose reduces more than linearly with tube voltage

As you decrease dose, you increase noise (usually decrease image quality) – No Free Lunch

Alessio, 28

?

Photo from www.imagegently.org

Alessio, 29

Cristy, M, and KF Eckerman. “Specific Absorbed Fractions of Energy At Various Ages From Internal Photon Sources.” Oak Ridge National Laboratory ORNL/TM-8381/V1 (1987)

•  CTDI and DLP Defines CT Technique •  Simulate CT Acquisition with this CT Technique using reference phantoms.

Provides absorbed dose to different organs. •  Use conversion of absorbed dose to organs to get whole body effective

dose

Alessio, 30

The Measurement, Reporting, and Management of Radiation Dose in CT, Report of AAPM Task Group 23 of the Diagnostic Imaging Council CT Committee. AAPM Report No 96. 2008

Connection between DLP and Effective Dose •  Rough conversion factors based on Monte Carlo simulations of “average” patients

CAVEAT: These values are very rough estimates from simplistic pediatric models of tissue size, location, composition, etc. This is current “state-of-the-art”, but still flawed.

0.0085 0.0067



Alessio, 31

Example with GE Dose report:

Connection between DLP and Effective Dose

Adult scan of the chest:


Alessio, 33

In the future…

1.  Find patient morphology and organ size from CT procedure

2.  Perform patient-specific Monte Carlo simulation to get “accurate” dose estimation

Value of more accurate dose estimates: •  Find age appropriate (“child-sized”) dose

estimates to guide pediatric acquisition protocols

•  Provide dose metrics more representative of patient’s risk for inclusion in dose report and patient medical record

Li, X. et al. Patient-specific dose estimation for pediatric abdomen-pelvis CT. Medical Imaging 2009: Physics of Medical Imaging Medical Imaging 2009: Physics of Medical Imaging Proc. SPIE 7258(1), 725804-725810 (2009).

Alessio, 34

Estimate for 1980

NCRP 1987 Total 3.6mSv per person

Estimate for 2006

Total ~6mSv per person

NCRP 160, published March 2, 2009 Mettler FAJ, Thomadsen BR, Bhargavan M et al. Medical radiation exposure in the U.S. in 2006: preliminary results. Health Phys. 2008; 95: 502-507.

  In past 25 years, the per capita dose from medical exposure (not including dental or radiotherapy) had increased almost 600% to about 3.0 mSv.

Alessio, 35 Mettler FAJ, Thomadsen BR, Bhargavan M et al. Medical radiation exposure in the U.S. in 2006: preliminary results. Health Phys. 2008; 95: 502-507. Alessio, 36

Mettler FAJ, Thomadsen BR, Bhargavan M et al. Medical radiation exposure in the U.S. in 2006: preliminary results. Health Phys. 2008; 95: 502-507.

•  CT accounts for 17% of the procedures and 49% of the collective dose

•  Nuclear Medicine accounts for 5% of procedures and 26% of the collective dose

 Final report from NCRP (SC 6-2) 160 - Published March 3, 2009

Estimated number and collective doses from various categories of radiographic and nuclear medicine procedures utilizing ionizing radiation (2006)



Alessio, 37

Mettler FAJ, Bhargavan M, Thomadsen BR et al. Nuclear medicine exposure in the United States, 2005-2007: preliminary results. Semin Nucl Med. 2008; 38: 384-391. Alessio, 38

???? Linear no-threshold model

Solid cancer incidence

Hormesis

Alessio, 39

Pierce and Preston, “Radiation-Related Cancer Risks at Low Doses among Atomic Bomb Survivors”, RADIATION RESEARCH 154, 178-186 (2000).

Estimated low-dose relative risks. Age-specific cancer rates over the 1958–1994 follow-up period relative to those for an unexposed person, averaged over the follow-up and over sex, and for age at exposure 30. The dashed curves represent +-1 standard error for the smoothed curve. The straight line is the linear risk estimate computed from the range 0–2 Sv. Because of an apparent distinction between distal and proximal zero-dose cancer rates, the unity baseline corresponds to zero-dose survivors within 3 km of the bombs. The horizontal dotted line represents the alternative baseline if the distal survivors were not omitted."

Alessio, 40

Hormesis: The assumption that any stimulatory hormetic effects from low doses of ionizing radiation will have a significant health benefit to humans that exceeds potential detrimental effects from the radiation exposure is unwarranted

US National Research Council, Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2 Stance is also supported by NCRP, and UNSCEAR

Support for Linear No-Threshold (LNT) Model: Until the [...] uncertainties on low-dose response are resolved, the Committee believes that an increase in the risk of tumour induction proportionate to the radiation dose is consistent with developing knowledge and that it remains, accordingly, the most scientifically defensible approximation of low-dose response. However, a strictly linear dose response should not be expected in all circumstances.

UNSCEAR 2000 REPORT Vol. II Also supported by ICRP, NCRP

????

Alessio, 41

Conclusions from this work:

We need to reduce the overall radiation dose from CT in the population by:

1.  Reduce the radiation from a given exam (reduce mA, automatic exposure control, lower kVp)

2.  replace CT use, when practical, with other options, such as ultrasonography and MRI

3.  decrease the number of CT studies that are prescribed.

An “estimate” that entered popular media: •  Due to CT scans from 1991 to 1996, 0.4% of all cancers in

US may be attributable to radiation from CT •  Now, 1.5% to 2% of all cancers in US from CT…

This entire paper predicated on the results from the BEIR VII Phase 2 Report…

Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med. 2007; 357: 2277-2284. Alessio, 42

BEIR VII-Phase 2, Published 2006

•  National Academy of Science, 423 page report

•  Executive summary (35 pages): http://www.nap.edu/catalog/11340.html "



Alessio, 43 *BEIR VII-Phase 2 Report, National Research Council of the National Academies, 2006.

Risk Estimates for 100 mSv

•  Lifetime attributable risk of cancer incidence increases 1.3% per 100mSv •  Lifetime attributable risk of cancer mortality increases ~0.5% per 100mSv •  In keeping with ICRP 60 and 103, LAR of cancer mortality increases ~5% per 1sV

Alessio, 44

Risk of cancer incidence with a single 100 mSv exposure

*BEIR VII Phase 2 Report, National Research Council of the National Academies, 2006.

To explore LAR estimates, see the educational tool on my website: http://faculty.washington.edu/aalessio/doserisk/

Alessio, 45

•  On Jan 23, 2008, a 2-year boy was brought to ED after falling out of bed •  Child allegedly received 151 CT scans of same axial slice in a 65 minute imaging

session (estimated to have received 2.8-11 Gy) •  Two hours after exam, child developed radiation burns under eyes and bottom

half of face •  Family suing hospital for radiation burns and chromosome damage to his DNA

http://www.times-standard.com/localnews/ci_10962540 http://www.times-standard.com/ci_11841717

Alessio, 46

Alessio, 47 Alessio, 48

I. Patient Community •  Several medical errors have heightened awareness/fear of radiation dose (primarily from therapeutic

and CT applications) II. Regulatory Community

•  NCRP 160 Published March 2009, summarizing radiation exposure in USA in 2006 •  FDA released White Paper, February 2010:

Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging •  U.S. Congressional Subcommittee on Health Hearing, Feb 26, 2010 •  MITA launched initiative, March 1, 2010:

MITA CT Radiation Dose Check Initiative •  FDA Public Meeting, March 30-31, 2010

•  September 1, 2010: California Legislature Passes SB 1237 Radiation Protection Bill (establish protocols and safeguards to protect patients from being exposed to excess radiation during computed tomography (CT) scans )

III.  Radiology Community •  Image Gently (Guidelines, education, resources for CT, Flouro, and soon NM) •  Publication in newswires:

Muhogora et al, “Paediatric CT Examinations in 19 Developing Countries: Frequency and Radiation Dose.” Radiation Protection Dosimetry (2010)

•  Many, many publications



Alessio, 49

Patient asks, what is the probability that I may get cancer from this PET/CT procedure?

NM Technologist or Physician Response: WHAT IS CORRECT ANSWER?

A.  This exam gives you roughly 13mSv of effective dose… B.  This exam is equivalent to 650 chest x-rays… C.  This exam is equivalent to 4.5 years of background radiation… D.  I have no idea. E.  Please know that we take radiation dose very seriously and adhere to

the best practices in the field. We follow the standards of “as low as reasonable achievable” to maintain diagnostic utility. As a result, we have designed protocols to minimize radiation exposure. With our protocols you are receiving an exam that is equivalent to roughly 4.5 years of background radiation. OPTIONAL: No one knows the real relationship between this low-dose of radiation and cancer incidence. Very conservative estimates suggest that this increases your chance of additional cancer a very small amount, 0.2%.

Alessio, 50

Alessio’s Response:

FACT: No one knows the exact amount of cancer risk associated with very low levels of radiation, like the amount received in this exam. We do know for a fact that the risk of cancer is extremely low. The risk is so low that we would have to scan millions of patients and follow them their entire lifetime to establish these small risk factors.

THEORY: In the absence of an established connection, there are theories describing the association. One theory, which uses the most conservative estimates (worst-case risk estimates) is the linear no-threshold theory. Most scientific agency accept that this is a prudent working theory. Based on this theory, a conservative estimate of the additive lifetime risk of dying from cancer from the exam is 0.08%. When added baseline risk of 23.2% (males), the life time risk is now 23.3%.

Alessio, 51

•  Radiation dosing should follow same approach as regular pharmaceutical dosing: Over or under dosing is a medical error

•  Stay informed –  Understand basic dose metrics and how to minimize dose

with a procedure –  Make certain acquisition protocols follow current guidelines

(be intentional about radiation dosimetry) –  Stay abreast of latest literature and popular media response

Alessio, 52

What are sources of uncertainty in our dose and risk estimates? –  Dose estimates based on simulations and measurements of “average”, simplistic phantoms (average morphology, average biokinetics)

–  Effective dose estimates are based on limited knowledge of stochastic risk to tissues and risk of uniform whole-body irradiation

–  Risk estimates based on highly limited evidence requiring us to adopt prudent, conservative linear no-threshold model…This evidence will hopefully evolve

What are 3 recent major reports on radiation dosimetry?

–  BEIR VII-Phase 2 Report: Radiation induced cancer risk estimation Health risks from exposure to low levels of ionizing radiation — BEIR VII Phase 2. National Academies Press (2006).

–  ICRP 103: Recommendations on radiation exposure: dose limits, tissue weighting factors, risk. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP 37, 1-332 (2007).

–  NCRP 160: New radiation exposure estimates in USA (2009).

Thank You

Documents

Radiation in PET, SPECT, and CT NM Resident Lectures, Nov 28, 2011depts.washington.edu/imreslab/2011 Lectures/Alessio_DOSE... · 2012. 12. 21. · Radiation in PET, SPECT, and CT