space radiation - umd

Space Radiation ENAE 697 - Space Human Factors and Life Support

U N I V E R S I T Y O FMARYLAND

Space Radiation• Sources of radiation• Biological effects• Approaches to shielding• Probabilistic estimation• Spacecraft shielding design• Recent revisions to understanding radiation effects

1

© 2017 David L. Akin - All rights reserved http://spacecraft.ssl.umd.edu

http://spacecraft.ssl.umd.edu



Issues of Human Radiation Exposure• Acute dosage effects• Carcinogenesis • Central nervous system effects• Chronic and degenerative tissue risks

2



The Origin of a Class X1 Solar Flare

3



Solar Radiation• Produced continuously (solar wind)• Increases dramatically during solar particle events

(SPEs) – Coronal ejections– Solar flares

• Primarily high-energy electrons and protons (10-500 MeV)

4



Image of Galaxy in Gamma Rays

5



Galactic Cosmic Rays• Atomic nuclei, stripped of electrons and

accelerated by supernova explosions to nearly the speed of light

• Constituents:– 90% protons– 9% alpha particles– 1% heavier elements

• Ionization potential proportional to square of charge (Fe26+=676 x p+)

6



Radiation in Free Space

7



Radiation Damage to DNA

8



Radiation Units• Dose D= absorbed radiation

• Dose equivalent H= effective absorbed radiation

• LET = Linear Energy Transfer <KeV/µ m>

9

1 Gray = 1Joule

kg= 100 rad = 10, 000

ergs

gm

1 Sievert = 1Joule

kg= 100 rem = 10, 000

ergs

gm

H = DQ rem = RBE � rad



Radiation Quality Factor

10

Radiation QX-rays 1

5 MeV γ-rays 0.51 MeV γ-rays 0.7

200 KeV γ-rays 1Electrons 1Protons 2-10

Neutrons 2-10α-particles 10-20

GCR 20+



Symptoms of Acute Radiation Exposure• “Radiation sickness”: headache, dizziness, malaise,

nausea, vomiting, diarrhea, lowered RBC and WBC counts, irritability, insomnia

• 50 rem (0.5 Sv)– Mild symptoms, mostly on first day– ~100% survival

• 100-200 rem (1-2 Sv)– Increase in severity and duration– 70% incidence of vomiting at 200 rem– 25%-35% drop in blood cell production– Mild bleeding, fever, and infection in 4-5 weeks

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Symptoms of Acute Radiation Exposure• 200-350 rem (2-3.5 Sv)

– Earlier and more severe symptoms– Moderate bleeding, fever, infection, and diarrhea at 4-5

weeks• 350-550 rem (3.5-5.5 Sv)

– Severe symptoms– Severe and prolonged vomiting - electrolyte imbalances– 50-90% mortality from damage to hematopoietic system

if untreated

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Symptoms of Acute Radiation Exposure• 550-750 rem (5.5-7.5 Sv)

– Severe vomiting and nausea on first day– Total destruction of blood-forming organs– Untreated survival time 2-3 weeks

• 750-1000 rem (7.5-10 Sv)– Survival time ~2 weeks– Severe nausea and vomiting over first three days– 75% prostrate by end of first week

• 1000-2000 rem (10-20 Sv)– Severe nausea and vomiting in 30 minutes

• 4500 rem (45 Sv)– Survival time as short as 32 hrs - 100% in one week

13



Long-Term Effects of Radiation Exposure• Radiation carcinogenesis

– Function of exposure, dosage, LET of radiation

• Radiation mutagenesis– Mutations in offspring– Mouse experiments show doubling in mutation rate at

15-30 rad (acute), 100 rad (chronic) exposures

• Radiation-induced cataracts– Observed correlation at 200 rad (acute), 550 rad (chronic)– Evidence of low onset (25 rad) at high LET

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Radiation Carcinogenesis• Manifestations

– Myelocytic leukemia– Cancer of breast, lung, thyroid, and bowel

• Latency in atomic bomb survivors– Leukemia: mean 14 yrs, range 5-20 years– All other cancers: mean 25 years

• Overall marginal cancer risk– 70-165 deaths/million people/rem/year– 100,000 people exposed to 10 rem (acute) -> 800

additional deaths (20,000 natural cancer deaths) - 4%

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U N I V E R S I T Y O FMARYLAND 16Francis Cucinotta, “What’s New in Space Radiation Research for Exploration?” NASA FISO, May 18, 2011



NASA Radiation Dose Limits

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SPE and GCR Shielding

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Shielding Depth, g/cm20 5 10 15 20 25 30 35

Dose

Equ

ivalen

t, rem

/yr

1

10

100

1000

10000GCR L. HydrogenGCR PolyethyleneGCR GraphiteGCR AluminumGCR RegolithSPE GraphiteSPE RegolithSPE L. Hydrogen

August 1972 SPE and GCR Solar Min

Francis Cucinotta, “What’s New in Space Radiation Risk Assessments for Exploration” NASA Future In-Space Operations Telecon, May 18, 2011



Density of Common Shielding

20

0

2

4

6

8

10

12

Polyethyle

neWate

rGr/E

p

Acrylic

s

AluminumLea

d



Comparative Thickness of Shields

21

0

1

2

3

Polyethyle

neWate

rGr/E

p

Acrylic

s

AluminumLea

d



Comparative Mass for Shielding

22

0

1

2

3

4

5

Polyeth

ylene

Water

Gr/Ep

Acrylics

Aluminu

mLe

ad



Shielding Materials and GCR

2325

MaterialE (Sv)

Solar Minimum SPE + Solar Maximum

10 g/cm2

Liquid H2 0.40 0.19Liquid CH4 0.50 0.30Polyethylene 0.52 0.33Water 0.53 0.35Epoxy 0.53 0.36Aluminum 0.57 0.43

20 g/cm2


40 g/cm2




Effective Dose Based on Shielding

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Francis A. Cucinotta, Myung-Hee Y. Kim, and Lei Ren, Managing Lunar and Mars Mission Radiation Risks Part I: Cancer Risks, Uncertainties, and Shielding Effectiveness NASA/TP-2005-213164, July, 2005



Shielding Materials Effect on GCR

25

–, Human Integration Design Handbook, NASA SP-2010-3407, Jan. 2010



Lunar Regolith Shielding for SPE

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Mars Regolith Shielding Effectiveness

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Radiation Exposure Induced Deaths

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Francis A. Cucinotta, Myung-Hee Y. Kim, and Lei Ren, Managing Lunar and Mars Mission Radiation Risks Part I: Cancer Risks, Uncertainties, and Shielding Effectiveness NASA/TP-2005-213164, July, 2005


U N I V E R S I T Y O FMARYLAND 33

3% Risk (REID)

6% Risk (REID)

95% CL 90% CL 95% CL 90% CLAge, y Males35 140 184 290 36145 150 196 311 39255 169 219 349 439Age, y Females35 88 116 187 23245 97 128 206 25555 113 146 234 293

Number of Days in Deep Space At Solar Minimum at 20 gm/cm2 shielding with a 95% or 90% confidence level to be below 3% or 6% REID (Avg US pop)

Deep Space Mortality Risks from

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SPE and GCR Shielding

30

Francis Cucinotta, “What’s New in Space Radiation Risk Assessments for Exploration” NASA Future In-Space Operations Telecon, May 18, 2011

Confidence Levels for Career Risks on ISSEXAMPLE: 45-yr.-Old Males; GCR and trapped proton exposures

Solar Max

Days on ISS0

(%) C

onfid

ence

tobe

bel

ow c

aree

r lim

it100

Current Uncertainties With Uncertainty Reduction

50

60

70

80

90

250 500 750 1000 250 500 750 1000

Days on ISS

Solar Max

Solar MinSolar Min

SAFE ZONE

45-Year Old Male: GCR and Trapped Proton Exposure


U N I V E R S I T Y O FMARYLAND 42Lora Bailey, “Radiation Studies for a Long Duration Deep Space Habitat” NASA FISO, Oct 31, 2012

3

NewEstimatesofRadiationsRisksareFavorableforMarsExploration:HoweverMajorScientificQuestionsRemainUnanswered

Francis A. CucinottaUniversity of Nevada, Las Vegas NV, USA

FutureIn-SpaceOperations(FISO)colloquium (July 13, 2016)

Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

Acknowledgements

• Funding:UniversityofNevada,LasVegas• UNLV:MuratAlp,ElliedonnaCacao

Outline

• Introduction• RadiationLimitsforAstronauts• CancerRiskEstimatesforDeepSpace• UnansweredScienceQuestionsinCancerRisks• Conclusions• BackupMaterialonSpaceEnvironmentsandShielding

49Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

50

Introduction to Space Radiation and Exploration

Spaceradiationisamajorchallengetoexploration:• Risksarehighlimitingmissionlengthorcrewselectionwithhighcosttoprotectagainstrisksanduncertainties

• Pastmissionshavenotledtoattributablerad-effectsexceptforcataracts,howeverforaMarsmissionmostcancersobservedwouldbeattributabletospaceradiation

Approachtosolvetheseproblems:• ProbabilisticriskassessmentframeworkforSpaceMissionDesign

• Hypothesis&Ground-basedresearch• MedicalPolicyFoundationsforSafety


Cosmic Ray Health Risks

• Risks:• AcuteRadiationSyndromes(ARS)

• Cancer• Cataracts• CentralNervousSystemEffects• CirculatoryDiseases• Othernormaltissueeffects

• Focus:HighChargeandEnergy(HZE)particleshaveuniquetrackstructuresleadingtoquantitativeandqualitativedifferencesinbiologicaleffectscomparedtoγ-rays.

CataractsinAstronauts

Time after first-mission, yr

5 10 15 20 25 30

Low-dose AstronautsHigh-dose Astronauts

Time after first-mission, yr

0 5 10 15 20 25 30

Pro

babi

lity

of C

atar

act

0.0

0.1

0.2

0.3

0.4

0.5

0.6

Low-dose AstroanautsHigh-Dose astronauts

All Cataracts Non-trace Cataracts

Probability of Cataracts after Space Flight


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Space Radiation Safety Requirements

• CongresshascharteredtheNationalCouncilonRadiationProtectionandMeasurements(NCRP)toguideFederalagenciesonradiationlimitsandprocedures

• SafetyPrinciplesofRiskJustification,RiskLimitationandALARA(aslowasreasonablyachievable)

• Crewsafety• limitof3%fatalcancerriskbasedon1989comparisonofrisksin“unsafe”industries

• NASAlimitsthe3%lifetimefatalityriskata95%confidenceleveltoprotectagainstuncertaintiesinriskprojections

• PlaceholderrequirementsinPELlimitCentralNervousSystem(CNS)andcirculatorydiseaserisksfromspaceradiation

• LimitssetMissionandVehicleRequirements• shielding,dosimetry,countermeasures,&crew


Requirements to Limit Radiation Mortality

• TheNationalCouncilonRadiationProtectionandMeasurements(NCRP)isCharteredbytheU.S.CongresstoguideGovt.AgenciesonRadiationSafety.

• In1989,NCRPrecommendedageatexposureandgenderbaseddoselimitsusinga3%fatalcancerriskasbasisfordoselimits(<1in33probabilityofoccupationaldeath).

• TheNCRPConsideredcomparisonstoaccidentaldeathsintheso-called“Safe”,“Less-Safe”and“Unsafe”IndustriesandconcludedDoseLimitsshouldlimitrisksimilarto“Less-safe”Industries.

• TheNCRPnotedthatsinceAstronautsfaceotherriskssimilarto“unsafe”industriesitwouldbeinappropriateforNASA’sradiationlimitstobesimilartorisksin“unsafe”industries.

• HoweverSafe,LessSafeandUnsafeIndustryriskscontinuetodecline.


Occupation AnnualFatalAccidentRateper100,000workers

(%LifetimeFatalityfor45-ycareer)1987a 1998b 2009c

SafeManufacturing 6(0.27%) 3(0.14) 2(0.1)Trade 5(0.23) 2(0.1) 4.3(0.2)Services 5(0.23) 1.5(<0.1) 2(0.1)Government 8(0.36) 2(0.1) 1.8(<0.1)LessSafeAgriculture 49(2.2) 22(1.0) 25.4(1.1)Mining 38(1.7) 24(1.1) 12.8(0.58)Construction 35(1.6) 14(0.63) 9.3(0.42)Transportation 28(1.3) 12(0.54) 11(0.5)ALL 10(0.45) 4(0.18) 2.8(0.13)

Annual Fatality Rates from Accidents in Different Occupations noted by NCRP Report 98 (1989)a, NCRP Report 132 (2000)b, and recent values from National Safety Councilc. Percent probabilities for occupational fatality for careers of 45 years are listed in parenthesis.

Risk in Less-Safe Industries have decreased to <1%


Alternative Comparative Risk Basis?• CurrentLossofCrew(LOC)riskforSpaceflightis1in270accordingtoNASA.

• AerospaceSafetyAdvisoryPanel(ASAP)recommendsNASAcanmakeinvestmentstoreduceLOCtolessthan1in750.

• TheLife-LossforRadiationDeathfromGamma-rayinducedcancersisestimatedat15-yearsforNever-smokerscomparedto40yearsforLOC.

• Life-LossforGCRishigherthangamma-rays.• Isthe1in33radiationlimitcomparabletoLOC(1in270)probabilitywhenadjustedforlife-loss?(ethics,euthanasia?)

• RisktoFiremanorsoldiersinIraqiwarzonesoldiers~0.5%• Note:Leadershipisfindingsolutionstospaceradiationproblem,whilewaivingradiationlimitsisnotleadership.


Mean Life-loss for Equivalent γ-ray exposure if Radiation Death Occurs for 18-months on ISS

(Female and Male Never-smokers)Tissue HT,Svor

Gy-EqLLE,y

Leukemia,Sv 0.151 23.1Stomach 0.235 16.3Colon 0.261 16.7Liver 0.229 13.5Bladder 0.231 11.2Lung 0.264 13.2Esophagus 0.249 15.1OralCavity 0.308 15.3Brain-CNS 0.286 18Thyroid 0.308 22Skin 0.282 11.8Remainder 0.264 12Breast 0.289 15.7Ovarian 0.241 17.9Uterine 0.241 17.1TotalCancer 0.244 15CVD,Gy-Eq 0.182 9.1IHD 0.182 9.5

Tissue HT,SvorGy-Eq

LLE,y

Leukemia,Sv 0.145 22.1Stomach 0.227 15.6Colon 0.251 16.4Liver 0.235 14Bladder 0.224 10.9Lung 0.245 13.6Esophagus 0.242 14.9OralCavity 0.261 15.8Brain-CNS 0.279 17Thyroid 0.261 20.8Skin 0.308 12Remainder 0.253 11.7Prostate 0.260 11.5TotalCancer 0.228 15CVD,Gy-Eq 0.174 9.8IHD 0.174 10.6

CVD=Cardiovascular disease, IHD=Ischemic Heart disease56


Uncertainties in Space Radiobiology Require New Knowledge and Approaches

•NCRPReports98,132,152notedriskestimateswerehighlyuncertainforGalacticCosmicRays(GCR).–UncertaintiestoolargeforEarthbasedmethodstobeappliedtoGCR

–NRCReportsin1996,1999and2008echotheseconcerns•Allexpertsagreethatknowledgeislimited:

–Unlikeotherdisciplineswherethefundamentalphysiologicalbasisofspaceflightbiomedicalproblemsislargelyknown,thescientificbasisofHZEparticleradiobiologyislargelyunknown

–DifferencesbetweenbiologicaldamageofHZEparticlesinspacevs.x-rays,limitsEarth-baseddataonhealtheffectsforspaceapplications


58

NASA Space Cancer Risk (NSCR) Model- 2012

• ReviewedbyU.S.NationalAcademyofSciences(NAS)

• 95%ConfidencelevelforLimitof3%RadiationExposureInducedDeath(REID)

• Notconservativeduetonon-cancerrisksyettobeevaluated

• Radiationqualitydescribedusingtrackstructuretheory

• PDF’sforuncertaintyevaluation• LeukemialowerQthanSolidcancer

• RedefinedagedependenceofriskusingBEIRVIIapproach

• UNSCEARLowLETRiskcoefficients• RisksforNever-Smokerstorepresenthealthyworkers

GCRdosesonMars

GCRdominateISSorganrisk

Z*2/β2

1 10 100 1000 10000

d(%

RE

ID)/d

(Z*2

/β2 )

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Solid CancerLeukemia


Space Radiation Environments• Galacticcosmicrays(GCR)penetratingprotonsandheavynuclei;abiologicalsciencechallenge

• shieldingisnoteffectiveduetosecondariesinshieldingandtissue

• largebiologicaluncertaintieslimitsabilitytoevaluaterisksaccurately

• Uncertaintiescloudunderstandingofeffectivenessofpossiblemitigations

• SolarParticleEvents(SPE):lowtomediumenergyprotons

• shieldingiseffective;optimizationneededtoreduceweight

• accurateeventalert,dosimetryandresponsesareessentialforcrewsafety

• improvedunderstandingofradiobiologyneededtoperformoptimization

59

• GCR dose and SPE probability are anti-correlated over 11-year solar cycle. • Hsolid is Organ Dose Equivalent for Solid cancer risks • Lines show times for 43 largest of ~400 SPE’s since 1950 (organ doses >10 mGy)


Comparison of MSL RAD Measurements to NASA Space Cancer Risk Model (NSCR-2012):

Comparison GCRDoseRate(mGy/day)

GCRDoseEquiv.Rate(mSv/day)

ModelCruisetoMars 0.445 1.80RADCruisetoMars(Zeitlinetal.2013)

0.481+0.08 1.84+0.33

ModelMarssurface(Kimetal.2014)

0.20 0.72

RADMarsSurface(Hassleretal.2014)

0.205+0.05 0.70+0.1760


Reference Population for Astronauts?

• AllprioranalysisusedtheAverageU.S.Populationasthereferencepopulationforastronauts.

• OurCancerriskmodelintroducedsomeaspectsofhealthworkereffectforriskprojections.

• adaptedbyNASAafterNASreviewin2012

• Astronautsshouldbeconsideredas“healthyworkers”,whichcouldmodifyriskestimates.

• LowercancerrisksmayoccurduetoimprovedBMI,exercise,diet,orearlydetectionfromimprovedhealthcarecomparedtoU.S.Average

• Morethan90%ofastronautsarenever-smokersandothersformersmokers

• Healthyworkereffectsaredifficulttoquantifywiththeexceptionofcancerratesfornever-smokers.

• RevisedNASAprojectionmodelstoconsiderestimatesofradiationrisksfornever-smokers


Healthy Worker Effects in Astronauts (N=339)(Cucinotta et al. 2013)

62NS = Never-Smoker; NW = Normal WeightFrancis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

Astronauts live very long due to low Circulatory Disease --even with low space doses (ave. 40 mSv)

Comparison SMRAstronauts vs. U.S. avg. 0.60 [0.34, 1.06]Astronauts vs. NS avg. 1.13 [0.64, 1.99]Astronauts vs NW avg. 0.60 [0.34, 1.05]Astronauts vs NS-NW Avg. 1.24 [0.70, 2.18]

Standard Cancer Mortality Ratio (SMR) for astronauts relative to other populations for Cancer

Comparison SMRAstronauts vs. U.S. avg. 0.33 [0.14, 0.80]Astronauts vs. NS avg. 0.43 [0.18, 1.04]Astronauts vs NW avg. 0.47 [0.19, 1.12]Astronauts vs NS-NW Avg. 0.67 [0.28, 1.62]

SMR for astronauts for Circulatory diseases

NS = never-smoker, NW = Normal Weight 63Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

64

Major Sources of Uncertainty

• Radiationqualityeffectsonbiologicaldamage(RBE–QF)• QualitativeandquantitativedifferencesofSpaceRadiationcomparedtox-rays

• Dependenceofriskondose-ratesinspace(DDREF)• BiologyofDNArepair,cellregulation

• Predictingsolarevents• Onset,temporal,andsizepredictions

• Extrapolationfromexperimentaldatatohumans

• Individualradiation-sensitivity• Genetic,dietaryand“healthyworker”effects

Nature Rev. Cancer (2008)


65

Fundamental Issue of Types of Radiation

• The ionizations and excitations in cells and tissue that occur are not distributed at random.

• They are stochastically produced but localized along the track of the incoming radiation.

• The pattern of this localization depends on the type of radiation involved.

• This means that different types of radiation will deposit different amounts of energy in the same space.

• The description of energy deposition at microscopic level is called Microdosimetry or Track Structure


The Dose and Dose-Rate Reduction Effectiveness Factor (DDREF)

• DDREFreducescancerriskestimates.

• DDREFestimatefromA-bombsurvivorsis1.3inNationalAcademyofScienceBEIRVIIReport.

• DDREFestimatefromanimalexperiments2to3.

66

BayesianAnalysisusingBEIRVIIPriorDistributionandmousedata


NASA Radiation Quality Function (NQF)-2012

• InternationalbodiesuseQFdependentonLETalone.• TrackstructureconceptsandexistingradiobiologydatausedtoguidechoiceonfunctionalformsforQF:

• MaximumeffectivenessperparticlecanbeestimatedbyexperimentsforRBEmaxandoccursat“saturationpoint”ofcrosssectionforanyZ

• Delta-rayeffectsforrelativisticparticlesaccountedforinQFmodel;higherZlesseffectiveatfixedLETcomparedtolowerZ

• PDFsaccountforvariationofthreeparametersvalues:(Σ0/αγ,m,andκ)basedonexistingbutlimitedradiobiologydata.PTDlowenergycorrection.Qmax~ Σ0/αγ

),(

)/(24.6)),(1( 0 EZP

LETEZPQNASA

γαΣ+−=

TD

m PZEZP ))/exp(1(),( 22* κβ−−=


Uncertainty Analysis

• Monte-Carlouncertaintyanalysisusesriskequationmodifiedbynormaldeviatesthatrepresentpossiblevaluesforkeyfactorsthatenterrepresentedbyprobabilitydistributionfunctions(PDF):

• defineX∈R(x)asarandomvariatethattakesonquantilesx1,x2,…,xnsuchthatp(xi)=P(X=xi)withthenormalizationconditionΣp(xi)=1.

• C(xi)isdefinedasthecumulativedistributionfunction,C(x),whichmapsXintotheuniformdistributionU(0,1),

• DefinetheinversecumulativedistributionfunctionC(x)-1toperforminversemappingofU(0,1)intox:x=C(x)-1

• PDFforQF,DDREF,Low-LETcancerrate,Organdose,etc.• ForaMonte-Carlotrial, ξ,RiskRateislike

0

0 ( , )R

R phys Q

D

x x xFLQRisk R age gender

DDREF xξ

ξ

⎧ ⎫⎪ ⎪= ⎨ ⎬

⎪ ⎪⎩ ⎭68


Risk for Exploration (Cucinotta et al. 2013) Cancer and Circulatory Disease

ISS = International Space Station; lower risk because GCR partially shielded By Earth Shadow and Magnetic Field Circulatory disease estimate from human data on Stroke and Ischemic Heart disease


PC = Probability of Causation at 10 years Post-exposure in these Calculations. If cancer is discovered In astronaut probability Radiation was the cause


Redefining QFs to Reduce Uncertainty

• QF’sarebasedonRBEmaxthatintroducesuncertaintyoflowdose-rategamma-rays.

• NSCR-2015redefinesQF’sagainstRBEforacutegamma-raysathigherdosesforsolidtumorsinmice.

• Numerousexperimentsshownodose-rateeffectathighLETforexposuretimes<2weeks

• BayesiananalysisusedtocorrelateDDREFformatchedsolidtumordata.

• Lowersriskanduncertaintyestimatesby25%and35%,respectively.


NSCR Revision : Track Structure Approach: “core” and “penumbra” in Biological Effects

),(

)/(24.6)),(1( 0 EZP

LETEZPQNASA

γαΣ+−=

),(),(),(EZQ

DDREFEZQ

DDREFEZQF

highlowAcute +=γ


Lack of dose-rate effect for heavy ions

73

Incidence of HCC (%) following Acute or Fractionated Exposures of 600 MeV/nucleon 56Fe Ions (Ullrich, Weil et al.)

0

10

20

30

40

50

60

0.2GyFeAcute 0.2GyFe3Fx 0.2GyFe6Fx

48hoursbetweenfractionsabout300micepergroup. 33

Harderian Gland Tumors following acute or fractionated Titanium Exposures in B6CF1 mice

(Blakeley, Chang et al. 2015)

33

0

Acute 0.13 Gy

5 FN 0.13 Gy

Acute 0.26 Gy

5 FN 0.052 Gy

% P

revalence

0

10

20

30

40

5fractionsat24hintervals


Tumor Model Sex Radiation, RBEmax DDREF RBEγAcuteHarderianGland* B6CF1mice F Fe,180(600MeV/u) 39.6+11.5

2728

--

2.17+1.1

--14

HarderianGland B6CF1mice F ArSOBP**,~200 27 - -Heptocellularcarconoma

CBAmice M Fe,155(1GeV/u) NotEstimated - 50.9+9.9

Heptocellularcarconoma

C3H/HeNCrlmice M Fe(600MeV/u),175 NotEstimated - 66.9+41.1

Heptocellularcarconoma

C3H/HeNCrlmice M Si,(300MeV/u),70 NotEstimated - 73.5+46.6

Lung BALB/cmice F Fissionneutrons 33+12 2.8 11.8Mammary Balbcmice F Fissionneutrons 18.5+6 1.9 9.7Pituitary RFMmice F Fissionneutrons 59+52 2.6 22.5HarderianGland RFMmice F Fissionneutrons 36+10 2.5 14.6AllEpithelial B6CF1mice M Fissionneutrons 28.3+4.0 2.3+0.3 12.1+4.5Lung B6CF1mice M Fissionneutrons 24.3+4.6 2.2+0.3 11.0+2Liver B6CF1mice M Fissionneutrons 39.1+12.1 2.0+0.3 19.3+5.6GlandularandReproductiveOrgans

B6CF1mice M Fissionneutrons 49.3+7.8 4.3+0.3 16.6+5.6

HarderianGland B6CF1mice M Fissionneutrons 50.7+10.8 4.7+0.3 12.1+2.9AllEpithelial B6CF1mice F Fissionneutrons 21.9+3.3 1.7+0.3 11.0+1.6Lung B6CF1mice F Fissionneutrons 18.1+4.2 1.8+0.3 10.3+2.2Liver B6CF1mice F Fissionneutrons 23.3+11.6 5.9+0.3 4.4+1.6GlandularReproduct B6CF1mice F Fissionneutrons 84.4+20.8 12.2+0.3 7.4+1

HarderianGland B6CF1mice F Fissionneutrons 61.9+31.5 8.7+0.3 5.8+1.2

Estimates of, RBEmax, the tumor specific DDREF, and RBEγAcute for low dose HZE particles or neutrons relative to acute γ-rays.

DataofFryetal.,Alpenetal..Weiletal.,Grahnetal.(24week)andUllrichetal.74


Reducing Uncertainty in QFmax parameter

RBEmax or RBEγAcute

1 10 100

%C

DF

0

20

40

60

80

100

RBEγAcute

RBEmax

Fit RBEγAcute

Fit RBEmax

CucinottaPLoSOne(2015)75Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

Revised NASA Quality Factor- 2015based on mouse solid tumor RBE data for neutrons and HZE particles against low dose-rate or acute gamma-rays

Cucinotta PloS One (2015)

RBEorQFforFissionneutronsareaveragedoverlowenergyproton,HIrecoilsetc.Spectra

ResultssuggestFissionneutronsandHZEIronhavesimilarRBEsandnotmaxeffectiveradiations 76


Centra

l Esti

mate

One S

igma

Upper

90% C

I

Upper

95% C

I

Saf

e D

ays

in S

pace

0

200

400

600

800

1000

NSCR-2014 FemalesNSCR-2012 FemalesNSCR-2014 MalesNSCR-2012 Males

Revised NSCR adds ~120 Safe Days in SpaceRisk and Uncertainties reduced ~30% in this new approach


Cucinotta et al., Life Sci Space Res (2015)Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

79

Predictionsofpercentageriskofexposureinduceddeath(%REID)for1-yearspacemissionsatdeepsolarminimum.


Major Unanswered Questions in Cancer Risk Estimates

1) ThereisalackofAnimalDataforHeavyionqualityfactorsformajortissuesinhumans(lung,breast,stomach,etc.).WillNASAeverfundsuchstudies?

2) ArethetumorsproducedbyHeavyionsandNeutronsmoremalignantthanthatofGamma-rays?

3) DoInverseDose-RateEffectsOccurforHighLETradiation?

4) DoNon-TargetedEffects(NTE)dominatedose-responsesatspacerelevantdoses?


1) Lack of Data for Human Tissues

• ExpertsagreethatMicearereasonablemodeltoestimateQualityFactorsandDose-Ratemodifiers.

• However,humandatasuggestsLung,Stomach,Breast,Colon,Bladderetc.dominatehumanradiationrisk.

• Mouseexperimentsshowwidevariationinradiationqualityeffectsfordifferenttumorsforgamma-raysandneutrons.

• NASAhasonlyfundeda1970’smodelofHarderianGlandtumorswith3ormoreparticlebeams.

• H.GlanddoesnotoccurinHumans.• Onlylimiteddataavailableforrelevanttumortypes!

• 21stCenturyMousemodelshavenotbeenfundedforriskestimates,onlylimitedmechanisticstudies.

• MajorimplicationsleadingtolargeuncertaintieswhichreflectsvariabilityinAvailabledataratherthanBestData.


2) Qualitative Differences in Cancer Risks from GCR

• RiskModelsonlyaccountforquantitativedifferencesusingQualityFactors(QFs)orPDFs

• IssuesemergingfromresearchstudiesofGCRSolidcancerrisks

• Earlierappearanceandaggressivetumorsnotseenwithcontrols,gamma-raysorprotoninducedtumors

• Non-linearresponseatlowdoseduetoNon-TargetedEffectsconfoundsconventionalparadigmsandRBEestimates

• SPE(proton)tumorsaresimilartobackgroundtumors


GCR Heavy ions produce more aggressive tumors compared to background or X-ray tumors

83

UTMB NSCOR- PI Robert Ullrich Shows much higher occurrence of metastatic Liver (HCC) tumors from GCR Fe or Si nuclei compared to gamma-rays or protons

Georgetown NSCOR- PI Al Fornace Shows much higher occurrence of invasive carcinomas tumors from GCR Fe nuclei compared to gamma-rays or protons


3) Inverse Dose-Rate Effects?

• StudieswithfissionneutronsdemonstratedanInversedose-rateeffectforsolidtumorsinmicewherechronicexposuresweremoreeffectivethanacuteexposures.

• Reportsofinversedose-rateeffectsvariedwithtissuetype,dose,sex,etc.

• Cellsterilizationeffectsareconfounder.• Notobservedwithgamma-raysorXrays.

• Short-termstudieswithHZEparticleshaveonlyconsidereddosefractionationanddonotsuggestaninverse-doserateeffectoccurs.

• Long-termchronicHZEparticleirradiationsimilartooldfissionneutronstudieshavenotbeenconducted

• NSCR-2015utilizesGrahnetal.24weekFissionneutrondata.Thereforeinversedose-rateeffectsshouldbereflectedinRBEvaluesconsidered,howeverlackingunderlyingunderstandingoftheeffect. 84


4) Non-Targeted Effects and GCR

• Non-targetedeffects(NTE)includegenomicinstabilityintheprogenyofirradiatedcellsandvariousbystandereffects

• NTEchallengeslinearmodelusedatNASAisapotentialgame-changeronroleofMissionlength,shieldingandbiologicalcountermeasures

• Non-linearor“flat”doseresponsesissuggestedformanynon-targetedeffectsatlowdose

• Epithelial-mesenchymaltransition(EMT)• Chromosomalaberrationsandmicro-nuclei• Mousesolidtumors• Geneexpressionandsignaling

• UnderstandingNTE’siscriticalresearchareatoreducecancerriskuncertainty

TheLancetOncology(2006)

ConventionalvsNTEDoseResponse


Broad Beam Heavy Ion Irradiation Leads to Non-Linear Response at low doses for Chromosome Aberrations in Human Fibroblasts but not Lymphocytes

Tracks per Cell Nucleus0.01 0.1 1 10

Sim

ple

Exc

hang

es p

er 1

00 c

ells

per

Tra

ck

0

5

10

15

20

25

Fe(600 MeV/u)O(55 MeV/u)

Tracks per Cell Nucleus

0.01 0.1 1 10

Sim

ple

Exc

hang

es p

er 1

00 c

ells

per

Tra

ck

0

20

40

60

80

Fe(300 MeV/u)Fe(450 MeV/u)

Conventional Model

Hada, George, Wang and Cucinotta, Radiat Res (2014)86


H. Gland Experiment Update

• E.BlakelyhascollecteddataonlowdoseirradiationofB6CF1micewithSi,Ti,andFeparticles.ThisispartlyacontinuationofexperimentfundedlargelybyDoEin1980sandearly1990s(FryandAlpen).

• MostcompletesetofHeavyiontumordata(p,He,Ne,Fe,Nb,La)

• UNLV(E.CacaoandF.Cucinotta)haveperformeddataanalysisofTEandNTEdoseresponsemodelsandRBEmaxandRBEγAcuteestimates.

• NewandoldGamma-raydataandFeparticledataarenotsignificantlydifferent;One-wayrepeatedNova:0.57and0.24,respectively.

• Oldexpt.usedpartialbodywithpituitaryisografts• Newexpt.wholebodywithdataonothertumorscollected


88

Parameter TE NTE1 NTE2P0 3.07+0.36(<10-4) 2.75+0.34(<10-4) 2.77+0.36(<10-4)α0,Gy-1 7.65+3.94(<0.058) 10.05+3.56(<0.007) 1.21+4.5(<0.789)α1,Gy-1(keV/µm)-1 1.25+0.14(<10-4) 0.90+0.21(<10-4) 1.07+0.14(<10-4)α2,(keV/µm)-1 0.0038+0.0004(<10-4) 0.0039+0.0009(<10-4) 0.0036+0.0003(<10-4)β,Gy-2 6.02+3.51(<0.093) 4.61+3.33(<0.173) 9.24+3.46(<0.01)λ0,Gy-1 0.243+0.07(<0.001) 0.219+0.078(<0.007) 0.286+0.0533(<10-4)λ1,Gy-1(keV/µm)-1 0.006+0.0036(<0.097) 0.0047+0.0059(<0.424) 0.0042+0.0037(<0.258)λ2,(keV/µm)-1 0.0043+0.0027

(<0.124)0.0051+0.0059(<0.391) 0.0045+0.0041(<0.277)

κ1,(keV/µm)-1 - 0.048+0.023(<0.038) 3.14+1.13(<0.008)κ2,(keV/µm)-1 - 0.0028+0.0019(<0.141) -

StatisticalTestsAdjustedR2 0.9248 0.9373 0.9337AIC 269.6 260.8 263.3BIC 285.9 281.3 281.7

Table 6. Parameter estimates for combined data sets for TE and NTE models for the dose response for percentage tumor prevalence. For each statistical test considered, which adjust for the differences in the number of model parameters, the model providing the optimal fit is shown in bold-face.


H. Tumor Fluence Response

89

NTE1model

%prevalence

0

22.5

45

67.5

90

trackspercellnuclei0.0001 0.001 0.01 0.1 1 10 100 1000 10000

H(expt)H(NTE1model)He(expt)He(NTE1model)Ne(expt)Ne(NTE1model)Si(expt)Si(NTE1model)Ti(expt)Ti(NTE1model)Fe(newexpt)Fe(oldexpt)Fe193(NTE1model)Fe253(expt)Fe253(NTE1model)Nb(expt)Nb(NTE1model)La(expt)La(NTE1model)gamma(old+newexpt)gamma(model)

alpha=f(LET)kappa=f(LET)lambda=f(LET)


H. Gland RBE Estimates in UNLV Combined Old and New Data Models (Chang et al. (2015))

90

Z LET,keV/µm RBEmax RBEγAcute RBE(NTE1)at0.1Gy

RBE(NTE1)at0.01Gy

1 0.4 1.78+0.92 0.90+0.44 0.92 1.112 1.6 2.10+0.98 1.06+0.46 1.14 1.90

10 25 7.86+2.07 3.96+0.81 5.19 16.26

14 70 16.28+3.81 8.21+1.34 11.25 38.56

22 107 21.07+4.86 10.63+1.69 14.81 52.46

26 175 26.18+6.13 13.20+2.16 18.86 69.75

26 193 26.91+6.36 13.57+2.26 19.50 72.87

26 253 28.01+6.87 14.13+2.53 20.70 79.84

41 464 23.34+6.89 11.77+2.86 18.45 78.53

57 953 8.61+3.92 4.34+1.84 7.83 39.21


Conclusions

• RevisedModelestimatessignificantlyreduceREIDpredictionsanduncertaintybands.

• Howeverlargequestionsremain:• Toomanyexperimentsatnon-relevantdoses(>0.2Gy)• ScarcityofHZEparticletumordata?• Inverse-doserateeffectsforchronicirradiation?• HigherlethalityofHZEparticletumors?• Non-targetedeffectsalteringshapeofdoseresponseandincreasingRBEestimates?

• Non-cancerriskscontributionstoREID?• Doeschronicinflammationoccuratlowdose?• Under-developedapproachestousetransgenicanimalsandothernewexperimentalmodelstoestimatehumanspaceradiationrisks?


Other material


93

Dose Response Models: Linear vs NTE?

• Non-TargetedEffect(NTE)paradigm’shaveemergedfordescribinglowdoseeffects,includingthresholdsandnon-lineardoseresponses

• ForHeavyChargedParticlesmostexperimentsperformedatlessthanonetrack/cellshowthatthebestrepresentativemodelisastep-function(Θ) plusalineardoseresponse:

R=R0+κΘ(Dth) +α Dose

• LowDoseexpts.showthatexpts.atmoderateorhighdosefindingalineardoseresponseshouldbechallengedandlikelynotusefulforNASA

• RBEsintheNTEmodelwillexceedlinearextrapolationbyalargeamount:

RBENTE=RBETE(1+Dcross/Dose);Dcrossisdose

whereTE=NTE


Components to Solution of Space Radiation Problem

94

Radiation Shielding Materials, Optimization, and

neutron minimization

▪ The current risk for a Mars mission is nearly 3-fold above acceptable risk levels ▪ Baseline DRM for a 1000 day mission has >3-fold uncertainties, assumes aluminum shielding, and radiation sensitivity of the U.S. average population

Dosimetry and Forecasting Ensure minimal SPE threat

Crew Selection Never-smokers, Screening for

sensitivity to GCR

Biological Mitigator’s New approaches to chronic, high

LET exposure protection

<1-fold (+100%)

15 %

50 %

30 %

Solar max. safety

Science understanding, radiobiology data-base for cancer, CNS, and other risks

Testing and validation

Biomarker developments, science discovery and verification, largely based on uncertainty reduction research

Drug testing and discovery, and validation based on uncertainty reduction research

Testing and validation

Uncertainty reduction Radiation quality effects, chronic

exposure, etc.

Solution Component Reduction Required Need

+σ

+σ

+σ


CNS Injury After High and Low Doses

• Higher Doses: • Generally restricted to white matter; • A late effect, appearing after a latent period; • Imaging and clinical changes; • Histology: demyelination, vascular damage, necrosis.

• Low Doses: Neurocognitive effects occur after radiation doses that do not result in overt tissue destruction:

• Progressive, currently untreatable and poorly understood;

• Hippocampal functions of learning, memory and spatial information processing;

• Other poorly understood - Unknown pathogenesis.


Low priorities - Space Physics and Acute Radiation Syndrome Research


2013 National Academy of Sciences Review of NSCR-2010 Model

“TheCommitteeconsidersthattheradiationenvironmentandshieldingtransportmodelsusedintheNASA’sproposedmodelareamajorstepforwardcomparedtopreviousmodelsused.Thisisespeciallythecaseforthestatisticalsolarparticleeventmodel.Thecurrentmodelshavebeendevelopedbymakingextensiveuseoftheavailabledataandrigorousmathematicalanalysis.Theuncertaintiesconservativelyallocatedtothespacephysicsparametersaredeemedtobeadequateatthistime,consideringthatthespacephysicsuncertaintiesareonlyaminorcontributortotheoverallcancerriskassessment.Althoughfurtherresearchinthisareacouldreducetheuncertainty,thelawofdiminishingreturnsmayprevail.”


Human Research Program – External Review (2010)

98

Cancer11:Whatarethemosteffectiveshieldingapproachestomitigatecancerrisks?The2012HRPExternalStandingReviewPanel(SRP)concluded:“ThisisnotproperlyagapintheHRPIRPbutanengineeringproblem.TheHRPIRPprovidesthescientificbasisonwhichshieldingevaluationscanbebased,butadditionalexperimentstodevelopshieldingarenotneeded.Inthefuture,acarefullydefinedmeasurementofarestrictedsetofcriticalparametersmaybeusefultovalidatesuchcalculations.TheSRPidentifiedthistaskasbeingoflowerpriorityandusingresourcesthatwouldbebetterappliedtothebiologicalinvestigations.”Cancer12:WhatlevelofaccuracydoNASA’sspaceenvironment,transportcodeandcrosssectionsdescriberadiationenvironmentsinspace(ISS,Lunar,orMars)?”ThePanelbelievesthat,atthistime,theaccuracyofpredictingparticlefluxesinspace(oftheorderof±15%)issufficientforriskpredictionandcouldnotbesignificantlyimprovedwithoutamajorinvestmentinresourcesbetterutilizedinaddressingothergaps.”


HRP External Review (2010)Cancer13:Whatarethemosteffectiveapproachestointegrateradiationshieldinganalysiscodeswithcollaborativeengineeringdesignenvironmentsusedbyspacecraftandplanetaryhabitatdesignefforts?SRP:“Thisisatechnologytransferproblemandnotaresearchproblem.Itshouldbeaddressedbytheappropriateengineeringprogramsandtheresourcesdevotedtoitwouldbebetterutilizedbyexpandingsupportofthehigherprioritygaps.”Acute–5:WhataretheoptimalSPEalertanddosimetrytechnologiesforEVAs?SRP:“Thisisatechnologyissue/engineeringproblem.Ifthisgapremains,theSRPrecommendsassigningitalowerpriority.Acute–6:Whatarethemosteffectiveshieldingapproachestomitigateacuteradiationrisks,howdoweknow,andimplement?SRP:“Thisisatechnologytransferproblemandnotaresearchproblem.Itshouldbeaddressedbytheappropriateengineeringprogramsandtheresourcesdevotedtoitwouldbebetterutilizedbyexpandingsupportofthehigherprioritygaps.”


GCR Environment Model

• LocalInter-stellarSpectra(LIS)(LeakyBoxModel)

• ModificationofCRISLeakyBoxmodel(Georgeetal.2009;Laveetal.,2013)

• ParkerTheoryofSolarModulation

])/()/(1[),(

2121

0αα

γ

EEEEEFEZFLIS ++

=− 2)15000/(

10 ]1[)( EeE −−+= γγγ


Ironχ2/n=4.9

E, MeV/u101 102 103 104 105

φ (E)

, 1/(M

eV/u

cm

2 sr s

)

10-12

10-11

10-10

10-9

10-8

10-7

Φ=0 MVΦ=200 MVΦ=300 MVΦ=500 MVΦ=850 MVCRIS (2009-10)CRIS (1996-97))CRIS (2001-03)HEAO3(1980)TRACER (2003)U. Chicago(1975)U. Minnesota (1977)UNH (1975)CREAM (2005)

Siliconχ2/n=4.3

E, MeV/u101 102 103 104 105

φ (E

), 1/

(MeV

/u c

m2 s

r s)

10-12

10-11

10-10

10-9

10-8

10-7

10-6

Φ=0 MV (LIS)Φ=250 MVΦ=350 MVΦ=550 MVΦ=900 MVCRIS (2009-10)CRIS (1996-97)CRIS (2002-03)HEAO-3 (1980)CREAM (2005)TRACER (2003)U. Minnesota (1977)UNH (1975)

Oxygenχ2/n=5.0

E, MeV/u101 102 103 104 105

φ (E)

, 1/(M

eV/u

cm

2 sr s

)

10-11

10-10

10-9

10-8

10-7

10-6

LISΦ=200 MVΦ=300 MVΦ=500 MVΦ=850 MVCRIS (2009-10)CRIS (1996-97)CRIS (2001-03)HEAO3 (1980)UNH(1975)TRACER (2003)

Titaniumχ2/n=6.6

E, MeV/u101 102 103 104 105

φ (E)

, 1/(M

eV/u

cm

2 sr s

)

10-13

10-12

10-11

10-10

10-9

10-8

10-7

LISΦ=200 MVΦ=300 MVΦ=500 MVΦ=850 MVCRIS (2009-10)CRIS (1996-97)CRIS (2001-03)HEAO3 (1980)U. Minnesota (1977)


Modulation Parameter Uncertainty-Fits to CRIS Data

Year1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

PH

I(MV

)

0

200

400

600

800

1000Fit IronFit SiliconFit NeonFit Oxygen

Monthly Average Modulation

Year1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

PH

I(MV

)

0

200

400

600

800

1000

1200


E,m

Sv

0

175

350

525

700

x,g/cm2

0 30 60 90 120

AnnualGCRatSolarMinimuminInterplanetarySpace

AnnualGCRatSolarMaximuminInterplanetarySpace

Aluminum

Polyethylene

AnnualExposureatLEO(51.6ox400km)atSolarMinimum

AnnualExposureatLEO(51.6ox400km)atSolarMaximum

AnnualEffectiveDoseforMales


Space Physics Over-Statements

104

Originalclaim

Correction:

Mewaldtpaperanalyzeddifferentsolarminspectrawithdifferentmethodsleadingtoover-statementof2009spectra;errorcorrectedinLaveetal.;APJ2013


The Carrington event not observed in most ice core nitrate recordsE. Wolff, J. Geophy Lett (2012)

• TheCarringtonEventof1859isconsideredtobeamongthelargestspaceweathereventsofthelast150years.Weshowthatonlyoneoutof14well-resolvedicecorerecordsfromGreenlandandAntarcticahasanitratespikedatedto1859.NosharpspikesareobservedintheAntarcticcoresstudiedhere.InGreenlandnumerousspikesareobservedinthe40yearssurrounding1859,butwhereotherchemistrywasmeasured,alllargespikeshavetheunequivocalsignal,includingco-locatedspikesinammonium,formate,blackcarbonandvanillicacid,ofbiomassburningplumes.Itseemscertainthatmostspikesinanearliercore,includingthatclaimedfor1859,arealsoduetobiomassburningplumes,andnottosolarenergeticparticle(SEP)events.WeconcludethataneventaslargeastheCarringtonEventdidnotleaveanobservable,widespreadimprintinnitrateinpolarice.NitratespikescannotbeusedtoderivethestatisticsofSEPs.


Solar protons a manageable issue with no significant acute risks

1.E+07

1.E+08

1.E+09

1.E+10

2/1/1954

2/1/1956

2/1/1958

2/1/1960

2/1/1962

2/1/1964

2/1/1966

2/1/1968

2/1/1970

2/1/1972

2/1/1974

2/1/1976

2/1/1978

2/1/1980

2/1/1982

2/1/1984

2/1/1986

2/1/1988

2/1/1990

2/1/1992

2/1/1994

2/1/1996

2/1/1998

2/1/2000

2/1/2002

2/1/2004

2/1/2006

Date

Φ60

, pro

tons

cm

-2

1.E+07

1.E+08

1.E+09

1.E+10

2/1/1954

2/1/1957

2/1/1960

2/1/1963

2/1/1966

2/1/1969

2/1/1972

2/1/1975

2/1/1978

2/1/1981

2/1/1984

2/1/1987

2/1/1990

2/1/1993

2/1/1996

2/1/1999

2/1/2002

2/1/2005

Date

Φ10

0, p

roto

ns c

m-2

1.E+07

1.E+08

1.E+09

1.E+10

1.E+11

2/1/1954

2/1/1957

2/1/1960

2/1/1963

2/1/1966

2/1/1969

2/1/1972

2/1/1975

2/1/1978

2/1/1981

2/1/1984

2/1/1987

2/1/1990

2/1/1993

2/1/1996

2/1/1999

2/1/2002

2/1/2005

Date

Φ30

, pro

tons

cm

-2

SPE onset date

Flux>30MeV

Flux>60MeV

Flux>100MeV

Kim,Feivesen,Cucinotta,2009106


Occurrence Of Extreme Solar Particle Events: Assessment From Historical Proxy DataUsoskin and Kovalstov, Astrophy J (2012)

107

100YearFluence


PredictingBFODosefromΦ30MeV(M.Y.Kimetal.)EquipmentRoom(5g/cm2Alum)inInterplanetarySpace

ToleranceLimitsbasedonVariabilityofDetailedEnergySpectra

SizeofSPE(>Φ30),protonscm-2

BFOdose,cGy

-Eq

10-2

102

101

100

10-1

103

1011108107 109 1010

Regressionfitwith90%tolerancelimits

■34historicallylargeSPEsoutof>400since1950

NASA30-dlimitatBFO

108

BFOdose,cGy

-Eq


SPE Blood forming organ doses with No shelter (Probability- D

BFO> 100 mGy per EVA) <1 x 10

-6

1) Dose-ratesaremodest(eventslast>10h)2) EVAterminationtime<2h3) ARSeasilymitigatedwithreal-timedosimetryandshielding

because>100MeVfluxistoosmall4) Spacecrafthaveareaswithatleast20g/cm2shielding5) ProbabilitytobeonanEVAduringanSPE<1x10-6 109


Storm shelters with ~40 g/cm2 shielding are practical

M.Y.Kim 110Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

Lung Cancer Risk

• Lungcancercomprisesthelargestfractionofhumanradiationfatalrisk(>30%).

• YaWangetal.haveusedaresistantmousemodel(C57BL/6)toreportonfirstHeavyionlungtumordata.

• ResultsshowlittleeffectofdosefractionationforO,Si,andFeparticlesat1Gy.

• Siparticlesproducemoreaggressivelungtumorscomparedtogamma-rays.

• Follow-upstudiesplannedatlowerdoses.

111Wangetal.RadiatRes(2014)Francis Cucinotta, “New Estimates of Radiation Risks…” NASA FISO, July 13, 2016

Argonne National Lab Inverse Dose-Rate Effect- D. Grahn et al, 1993

(24 or 60 week x 5 d/wk gamma or fission neutron)


Lung tumors: Inverse Dose-Rate Effect Found?




References• Francis Cucinotta, “New Estimates of Radiation Risks”

NASA Future In-Space Operations Working Group, May 18, 2011

• –, Human Integration Design Handbook, NASA SP-2010-3407, Jan. 2010

• Lora Bailey, “Radiation Studies for a Long Duration Deep Space Habitat” NASA Future In-Space Operations Working Group, Oct 31, 2012

• Francis A. Cucinotta, Myung-Hee Y. Kim, and Lei Ren, Managing Lunar and Mars Mission Radiation Risks Part I: Cancer Risks, Uncertainties, and Shielding Effectiveness NASA/TP-2005-213164, July, 2005

114

National Aeronautics and Space Administration

Mars Mission and Space Radiation Risks

Overview

Briefing to

NAC HEOMD/SMD Joint Committee

April 7, 2015

Steve Davison • HEOMD • NASA Headquarters

Space Radiation Presentations

Overview

• Mars Mission and Space Radiation Risks Steve Davison, NASA-HQ, 30 min

Health Standards Decision Framework David Liskowsky, NASA-HQ, 10 min•

Space Radiation Environment

• Introduction Chris St. Cyr, NASA-GSFC, 5 min

Solar Energetic Particles Allan Tylka, NASA-GSFC, 30 min

Comparison and Validation of GCR Models Tony Slaba, NASA-LaRC, 30 min

GCR Radiation Environment Predictions Nathan Schwadron, Univ. of NH, 30 min

Emerging GCR Data from AMS-2 Veronica Bindi, Univ. of Hawaii, 30 min

•

•

•

•

Radiation Health Risk Projections Eddie Semones, NASA-JSC, 45 min

• NCRP Recommendations, Permissible Exposure Limits, Space Radiation Cancer Risk Model,

Operations and In-Flight Solar Particle Event Mitigations

Space Radiation R&T for Risk Mitigation Lisa Simonsen, NASA-LaRC, 45 min

• Radiobiology Research Portfolio (Cancer, CNS, Cardio) and Spacecraft Shielding Design,

Analysis, and Optimization

2

Overview of Mars Mission Crew Health Risks

• Mission And Crew Health Risks Are Associated With Any Human Space Mission

– Briefing is focused on space exploration crew health risks associated with space

radiation

• Exploration Health Risks Have Been Identified, And Medical Standards Are In

Place To Protect Crew Health And Safety

– Further investigation and development is required for some areas, but this work

will likely be completed well before a Mars mission launches

• There Are No Crew Health Risks At This Time That Are Considered “mission-

stoppers” for a Human Mission to Mars

– The Agency will accept some level of crew health risk for a Mars mission, but that

risk will continue to be reduced through research and testing

• The Most Challenging Medical Standard To Meet For A Mars Mission Is That

Associated With The Risk Of Radiation-induced Cancer

– Research and technology development as part of NASA’s integrated radiation

protection portfolio will help to minimize this long-term crew health risk3

Human Spaceflight Risks are Driven by

Spaceflight Hazards

Distance from Earth

Drives the need for additional “autonomous” medical care

capacity – cannot come home for treatment

Hostile/

Closed Environment

Vehicle DesignEnvironmental – CO2 Levels, Toxic Exposures, Water, Food

Isolation & Confinement

Behavioral aspect of isolationSleep disorders

Space Radiation

Acute In-flight effectsLong-term cancer risk

CNS and Cardiovascular

Altered Gravity -Physiological Changes

Balance DisordersFluid Shifts

Visual AlterationsCardiovascular DeconditioningDecreased Immune Function

Muscle AtrophyBone Loss

4

Human System Risk Board (HSRB):

Human Risks of Spaceflight Summary

Altered Gravity Field1. Spaceflight-Induced Intracranial

Hypertension/Vision Alterations2. Renal Stone Formation 3. Impaired Control of

Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space Flight

4. Bone Fracture due to spaceflight Induced changes to bone

5. Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

6. Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity

7. Adverse Health Effects Due to Host-Microorganism Interactions

8. Urinary Retention9. Orthostatic Intolerance During Re-

Exposure to Gravity10.Cardiac Rhythm Problems11.Space Adaptation Back Pain

Radiation1. Risk of Space Radiation

Exposure on Human Health (cancer, acute, cardio, CNS)

Distance from Earth1. Adverse Health Outcomes

& Decrements in Performance due to inflight Medical Conditions

2. Ineffective or Toxic Medications due to Long Term Storage

—

Isolation1. Adverse Cognitive or

Behavioral Conditions & Psychiatric Disorders

2. Performance & Behavioral health Decrements Due to Inadequate Cooperation, Coordination, Communication, & Psychosocial Adaptation within a Team

Each risk will be controlled by a NASA standard to protect crew health and safety—

Hostile/Closed Environment-Spacecraft Design1. Acute & Chronic Carbon Dioxide

Exposure2. Performance decrement and crew illness

due to inadequate food and nutrition3. Reduced Crew Performance Due to

Inadequate Human-System Interaction Design (HSID)

4. Injury from Dynamic Loads5. Injury and Compromised Performance

due to EVA Operations6. Adverse Health & Performance Effects of

Celestial Dust Exposure7. Adverse Health Event Due to Altered

Immune Response8. Reduced Crew Performance Due to

Hypobaric Hypoxia9. Performance Decrements & Adverse

Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, & Work Overload

10.Decompression Sickness11.Toxic Exposure12.Hearing Loss Related to Spaceflight13.Injury from Sunlight Exposure14.Electrical shock/plasma

5

Mars Mission Human Health Risks

Based On The On-going Human System Risk Board (HSRB) Assessment, The Following Risks Are The Most Significant For A Mars Mission:

• Adverse affect on health space radiation exposure (long-term cancer risk)

spaceflight-induced vision alterationsrenal stone formation compromised health due to inadequate nutritionbone fracture due to spaceflight induced bone changesacute and chronic elevated carbon dioxide exposure

•

•

Post

Mission

Risks

Inability to provide in mission treatment/care lack of medical capabilitiesineffective medications due to long term storage

Adverse impact on performancedecrements in performance due to adverse behavioral conditions and training deficienciesimpaired performance due to reduced muscle and aerobic capacity, and sensorimotor adaptation

In-

Mission

Risks

6

Current Space Flight Health Standards

• NASA Should Be Able To Meet

All Fitness for Duty (FFD) And

Permissible Outcome Limits

(POL) Standards For A Mars

Mission

– Based on long-duration ISS

flight experience and

mitigation plans

• Meeting The Current Low Earth

Orbit (LEO) Space Radiation

Permissible Exposure Limit

(PEL) Standard Will Be

Challenging For A Mars

Mission

– NASA exposure limit is the

most conservative of all space

agencies

Area Type Standard

Bone POL Maintain bone mass at ≥-2SD

Cardiovascular FFD Maintain ≥75% of baseline VO2 max

Neurosensory FFD Control motion sickness, spatial disorientation, & sensorimotor deficits to allow operational tasks

Behavioral FFD Maintain nominal behaviors, cognitive test scores, adequate sleep

Immunology POL WBC > 5000/ul; CD4 + T > 2000/ul

Nutrition POL 90% of spaceflight-modified/USDA nutrient

requirements

Muscle FFD Maintain 80% of baseline muscle

strength

Radiation PEL ≤ 3% REID (Risk of Exposure Induced

Death, 95% C.I. 7

Space Radiation Challenge

Galactic cosmic rays (GCR) – penetrating protons and heavy nuclei

Solar Particle Events (SPE) – low to medium energy protons

What are the levels of

radiation in deep

space and how does

it change with time?

SMD R&D

Helio- & Astrophysics

Characterization/meas

urement

Modeling/Prediction &

Real-time Monitoring

How much radiation is inside the spacecraft, on Mars surface, and in the human body?

HEOMD R&D

Radiation Transport Code Development

Transport of radiation into body

Tissue/Organ doses

What are the health

risks associated

with radiation

exposure?

Cancer risks

Acute radiation

Non-cancer risks

How do we mitigate

these health risks?

NSRL research

Spacecraft Shielding

Bio-Countermeasures

Medical Standards

8

Space Radiation Health Risks

Health Risk Areas

CarcinogenesisSpace radiation exposure may cause

increased cancer morbidity or mortality risk in

astronauts

Status

Cancer risk model developed for mission risk

assessment

Model is being refined through research at

NASA Space Radiation Laboratory (NSRL)

Health standard established

Acute Radiation Syndromes from SPEsAcute (in-flight) radiation syndromes, which

may be clinically severe, may occur due to

occupational radiation exposure

Acute radiation health model has been

developed and is mature

Health standards established

Risk area is controlled with operational &

shielding mitigations

Degenerative Tissue EffectsRadiation exposure may result in effects to

cardiovascular system, as well as cataracts

Central Nervous System Risks (CNS)Acute and late radiation damage to the

central CNS may lead to changes in

cognition or neurological disorders

Non-cancer risks (Cardiovascular and CNS)

are currently being defined

Research is underway at NSRL and on ISS

to address these areas

Appropriate animal models needed to assess

clinical significance

9

Mars Mission Space Radiation Risks

Mars Missions May Expose Crews To Levels Of Radiation Beyond Those

Permitted By The Current LEO Cancer Risk Limit (≤ 3% REID, 95% C.I.)

• May increase the probability that a crewmember develops a cancer over their

lifetime and may also have undefined health effects to central nervous system

and/or cardiovascular system; these areas are currently under study

Mars Missions Cancer Risk Calculations

• Calculations use 900-Day conjunction class (long-stay) trajectory option for Mars

mission (500 days on Mars surface)

– Exposure levels are about the same for 600-Day opposition-class (short-stay)

trajectory option (30 days on Mars surface)

• Based on 2012 NASA Space Radiation Cancer Risk Model as recommended by

the National Council on Radiation Protection and reviewed by National Academies

– Model calculates risk of exposure induced death (REID) from space

radiation-induced cancer with significant uncertainties

Calculations take into range of solar conditions and shielding configuration

Mars surface calculations include shielding by the planet, atmosphere, &

lander

–

–

10

Post Mission Cancer Risk For A 900-day Mars Mission

Mars Mission Timing

Mission Shielding Configuration Calculated REID, 95% C.I. (Age=45, Male-Female)

Amount Above3% Standard

Solar Max Good shielding like ISS (20 g/cm2)w/no exposure from SPEs

4% - 6% 1% - 3%

Solar Max Good shielding like ISS (20 g/cm2) w/large SPE

5% - 7% 2% - 4%

Solar Min Good shielding like ISS (20 g/cm2) 7% - 10% 4% - 7%

NASA Standards Limit The Additional Risk Of Cancer Death By Radiation

Exposure, Not The Total Lifetime Risk Of Dying From Cancer

• Baseline lifetime risk of death from cancer (non-smokers)

– 16% males, 12% females

• After Mars Mission (solar max), Astronauts lifetime risk of death from cancer ~20%

Mars Space Radiation Risk For Solar Max Can Be Explained As Follows

• If 100 astronauts were exposed to the Mars mission space radiation, in a worst case (95%

confidence) 5 to 7 would die of cancer, later in life, attributable to their radiation exposure and

their life expectancy would be reduced by an average on the order of 15 years

Challenging to use a population-based risk model to estimate individual risk for the few

individuals that would undertake a Mars Mission 11

•

Radiation Protection Portfolio

Optimize human radiation protection by integrating research,

operations and development activities across the agency

Integrated Radiation Protection

Radiation Exposure Standard

OCHMO

Space Radiation Environment

SMD, Monitoring/Prediction Advances

External Advisory Panels

NCRP, NAS, SRP, NAC

Monitoring Devices

In flight Crew MonitoringDosimeter Technology Development

Shielding/Vehicle Design

Models to enable exposure assessment Shielding Optimization

Occupational Surveillance

Pre- and In- Mission CarePost Mission Screening/Treatment

Countermeasures

Advances in Nutrition/Pharmaceuticals

Analysis, Operations, Mission Planning

Radiation Assessment ModelsAssessment & Planning, SRAG

Space Radiation Biological Effects

Radiobiology research on cancer, CNS, and cardiovascular

12

Reducing Mars Mission Radiation Risks

NASA Is Working Across All Phases Of The Mars Mission To Minimize The Space Radiation Health Risk

Pre - Mission

Radiation FactorsIndividual Sensitivity –

Biomarkers*

Selection – age, gender

Model Projection of Risk

Space Radiation Envir. Model

In - Mission

Radiation FactorsShielding

Mission Duration

Solar Min vs. Max

Operational Planning

Dosimetry

Countermeasures*

- Pharmaceutical &

Nutritional

Post - Mission

Radiation FactorsOccupational Health Care

for Astronauts*

- Personalized Cancer

Screening, Biomarkers

- Cancer Treatment

Reduction in Total Risk Posture

*long-term

development

13

Reducing Radiation Health Risks

Space Radiation Research at NSRL

• Key to reducing the space radiation health effects uncertainties, refinement of cancer risk model, and understanding cardiovascular and CNS risks

•

•

•

•

•

•

LRO-CRaTER

radiation

measurements

Space Radiation Environment Characterization

LRO-CRaTER measurements of radiation environment

SEP real-time monitoring and characterization

MSL-RAD Measurements of radiation environment during transit and on the surface of Mars

Medical Approaches Applied Pre-/Post-Mission

Understanding the individual sensitivities and enhancing post mission care are the key areas that can significantly reduce the space radiation risk

MSL-RAD

radiation

measurements

on Mars

Exploration Space Radiation Storm Shelter Design and Real-time Radiation Alert System

Development of these capabilities for exploration missions can reduce crew exposure risk to SPEs to negligible levels

Mars Mission Design and Deep Space Propulsion

Reducing deep space transit times can reduce space radiation exposure and mitigate human health risks

NSRL simulates space cosmic

and solar radiation environment

14

Summary

Based on current mitigation plans for Crew Health and Performance Risks, NASA can support a Mars Mission

• Mars Mission Health Risks Have Been Identified And Medical Standards Are In Place To Protect Crew Health And Safety

– While there is a fair amount of forward work to do, there are no crew health risks at this time that can be considered “mission-stoppers”

There will be a level of crew health risk that will need to be accepted by the Agency to undertake a Mars mission, but that risk will continue to be reduced through R&D

–

• Based on present understanding of risks and standards

– Exercise countermeasure approaches (hardware & prescriptions) require further refinement/optimization to meet exploration mission, vehicle, and habitat designs

Additional data needed to fully quantify some risks (vision impairment, CO2 exposure)

Renal stone risk needs new intervention/treatment approaches

Some risks (nutrition, inflight medical conditions) require optimization in order to support a Mars Mission

Pharmaceutical & food stability/shelf life needs to be improved for a Mars Mission

Behavioral health and human factors impacts need to be further minimized

–

–

–

–

–

– The radiation standard would not currently be met 15

space radiation - umd

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