In Vivo Measurement In Vivo Measurement of Toxic Trace Elementsof Toxic Trace Elements

Dr. Fiona E. McNeillDr. Fiona E. McNeillMedical Physics and Applied Radiation SciencesMedical Physics and Applied Radiation Sciences

McMaster UniversityMcMaster University

The The ImportanceImportance of Toxic Metals Monitoringof Toxic Metals Monitoring

NorandaNoranda Inc'sInc's Brunswick Brunswick smelter produced 104,000 smelter produced 104,000 tonnes of refined lead in tonnes of refined lead in 2000, and monitored over 2000, and monitored over 500 workers for lead 500 workers for lead exposure. exposure.

Canada exported $48 billion worth of non-fuel minerals and mineral products in 2000. Canada is the world’s largest producerof uranium, the 3rd largest producer of copper, and produces zinc, lead, cadmium, platinum, gold…

“If it can’t be grown, it has to be mined”

Hamilton Hamilton –– Steel Town CanadaSteel Town Canada

Rationale for In Vivo MeasurementRationale for In Vivo Measurement

Stomach

Blood

Bone KidneyLiver

Urine

Brain

Excreted fractionLong term storage

Target Organs

Current ExposureRoutine monitoring is of blood and urine

Physics TechniquesPhysics Techniques

XX--Ray Fluorescence AnalysisRay Fluorescence AnalysisNeutron Activation AnalysisNeutron Activation AnalysisNuclear Resonance AbsorptionNuclear Resonance AbsorptionNeutron Inelastic ScatteringNeutron Inelastic ScatteringMRIMRI

XRF Principles XRF Principles -- Photoelectric EffectPhotoelectric Effect

Measurement of the characteristic xMeasurement of the characteristic x--rays identifies an element rays identifies an element and comparison with appropriate standards allows the amount of and comparison with appropriate standards allows the amount of the element to be quantifiedthe element to be quantified

0 400 800 1200 1600 2000MCA channel number

0

600

1200

1800

2400

3000 Number of Counts

α1

β1,3

β2

α2

Pb K x-rays

Ag K x-rays

β’s

α2,1

XX--Ray FluorescenceRay FluorescenceHeavy metals are particularly Heavy metals are particularly

suited to in vivo suited to in vivo measurement by XRF measurement by XRF because they have higher because they have higher energy xenergy x--rays and higher rays and higher fluorescence yields (ratio of fluorescence yields (ratio of xx--rays/Auger)rays/Auger)

Elements from iron (6 keV) to Elements from iron (6 keV) to uranium (122 k eV) have uranium (122 k eV) have been measured in vivo been measured in vivo

Iron and silver were measured Iron and silver were measured in the skin in the skin –– uranium and uranium and lead are measured in bonelead are measured in bone

0 20 40 60 80 100

Atomic Number

0

24

48

72

96

120

K Alpha1 Measured Energy

Curve is quadratic fit to data

In Vivo XRF In Vivo XRF -- Compton ScatteringCompton Scattering

After CollisionBefore Collision

scattered photon

Recoil Electron

Incident photon electron

E EE

m co

/

( cos )=

+ −1 12 ϑ

θ

In Vivo XRF In Vivo XRF -- Compton ScatteringCompton Scattering

After CollisionBefore Collision

scattered photon

Recoil Electron

Incident photon electron

θ

Compton scattering tends to dominate in vivo measurements because human tissue is predominantly low atomic number elements

109109Cd K XRF Bone Pb SystemCd K XRF Bone Pb System

50mm x 20 mm

HpGe Crystal

109-Cd Source

Sample

System is designed to be in backscatter geometry

in tungsten collimator

•109Cd emits 88.035 keV photons•30 eV above the absorption edge for lead.•The cross-section for photoelectric absorption is maximized.•Permits normalization of Pb x-rays to coherent scatter signal

109109Cd K XRF Bone Pb SystemCd K XRF Bone Pb System

Source/detector combination is placed up against a subject’s leg for 30 – 45 minutes.

109109Cd K XRF spectrumCd K XRF spectrum

54.00 61.20 68.40 75.60 82.80 90.00(Thousands)

Energy (eV)

10

100

1000

10000

100000

400000Compton Peak

Pb x-rays

The system is in a “back scatter” geometry

The mean scattering angle is 156°

The peak in the Compton distribution is at 65 keV

Pb x-ray energies are from72 -88 keV

E EE

m co

/

( cos )=

+ −1 12 ϑ

109109Cd K XRF spectrumCd K XRF spectrum

63.00 68.40 73.80 79.20 84.60 90.00(Thousands)

Energy (eV)

10

100

1000

10000

100000

400000

Pb alpha peaks

Pb beta peaks

Elastic PeakScatter

Compton

Peak

In vivo detection limit 8 μg Pb / g bone mineral

Effective Dose 40 nSv

Lead Exposure in Young AdultsLead Exposure in Young Adults

Precision versus BMIPrecision versus BMI

BMI (lb / in2)

ln (Precision)

0.20 0.32 0.44 0.56 0.68 0.80(E-1)

0.00

0.80

1.60

2.40

3.20

4.00

Bone Pb Precision versus AgeBone Pb Precision versus Age

Age (Years)

Precision

μg Pb / g bone mineral

5 19 33 47 61 752.00

4.20

6.40

8.60

10.80

13.00

Recent Improvements in Recent Improvements in PbPb Bone XRFBone XRF

50mm x 20 mm

HpGe Crystal

109-Cd Source

Sample

System is designed to be in backscatter geometry

in tungsten collimator

Change to multiple detector system to allow greater throughput with improved resolution. This has been shown to improve the detection limit by at least a factor of two, and has increased the dose by at least a factor of four

Gulf War Veterans Gulf War Veterans -- 19911991

An x-ray image of a soldier’s right thigh. The bright spots are fragments of shrapnel; it is not known whether they are uranium or not.

5757Co XRF U SystemCo XRF U System

emits 122 and 136 keV photons

HpGe Crystal

57-Co Source

Sample

U K x-rays: 95 - 104 keV

Median scattering angle = 156 degrees

in tungsten collimator

Peaks in Compton Scatter Distribution are at 84 and 90 keV

5757Co XRF U SpectrumCo XRF U Spectrum

70.00 80.80 91.60 102.40 113.20 124.00(Thousands)

Energy (eV)

100

1000

10000

100000

400000Compton Peaks

U x-rays

In vivo detection limit 18 μg U / g bone mineral

Effective Dose 60 nSv

XRF of Arsenic in SkinXRF of Arsenic in Skin

As in skinAs in skin

250 300 350 400 450 5000

400

800

1200

1600

2000

Quote from the World Health Organisation:

“Geneva, March 2002—The largest mass poisoning of a population in history is now underway in Bangladesh.”

Estimates of the number of people exposed are 30-77 million

XRF of Arsenic in SkinXRF of Arsenic in SkinAs in skinAs in skin

250 300 350 400 450 5000

400

800

1200

1600

2000

109109Cd source Cd source

Detection Limit = 3.5 Detection Limit = 3.5 ++ 0.2 0.2 ppmppm

8 mm phantoms 8 mm phantoms

Effective Dose = 0.28 Effective Dose = 0.28 ++ 0.02 0.02 µµSvSv

Background is from Compton Background is from Compton electrons from 88 electrons from 88 keVkeV gammagamma--rayray

125125I sourceI source

A A 125125I I brachytherapybrachytherapy sourcesourcewas used (was used (OncoSeedOncoSeed™™ modelmodel6711) which consists of 6711) which consists of 125125IIadsorbed onto silver and weldedadsorbed onto silver and weldedinto a titanium capsule.into a titanium capsule.In addition to a gammaIn addition to a gamma--ray atray at35.5 35.5 keVkeV, the source emits, the source emitstellurium and silver k xtellurium and silver k x--raysrays

125125I sourceI source

125125I source I source Phantom Detection Limit = Phantom Detection Limit = 2.3 2.3 ++ 0.1 0.1 ppmppm2 mm phantoms2 mm phantomsEffective Dose = Effective Dose = 5.5 5.5 ++ 0.8 0.8 nSvnSv

In vivoIn vivo MeasurementsMeasurementsPalm Detection Limit =Palm Detection Limit =2.5 2.5 ++ 0.5 0.5 ppmppmForearm Detection Limit =Forearm Detection Limit =2.6 2.6 ++ 0.5 0.5 ppmppm

In vivoIn vivo ConcernsConcernsPhantom thickness doesnPhantom thickness doesn’’t match t match

skin thicknessskin thicknessArsenic in phantoms is uniformly Arsenic in phantoms is uniformly

distributed with depth, in skin it distributed with depth, in skin it binds to keratin which varies in binds to keratin which varies in depth (decreasing away from depth (decreasing away from surface)surface)

Use Monte Carlo simulations to Use Monte Carlo simulations to make predictions on how make predictions on how thickness & distribution affect thickness & distribution affect measurementmeasurement

Used ultrasound to determine Used ultrasound to determine thickness of the skin thickness of the skin

Correction FactorCorrection Factor

Phant

CorrPhantCorr CountsSim

CountsSimMDLMDL ×=

Correction Factors range from 1.67 (2.6 mm palm, linear) to Correction Factors range from 1.67 (2.6 mm palm, linear) to 12.33 (0.8 mm forearm, exponential)12.33 (0.8 mm forearm, exponential)

Minimum Detectable Limits range from 4Minimum Detectable Limits range from 4.2 .2 ++ 0.8 ppm to 32.0 0.8 ppm to 32.0 ++6.2 ppm 6.2 ppm in terms of surface concentrationin terms of surface concentration

XX--Ray SetRay Set

Tube specificationsTube specifications50 kV, 1 50 kV, 1 mAmA, Mo target, Mo targetIf filtered with Mo foil,If filtered with Mo foil,beam is very similar tobeam is very similar tomammography units but mammography units but

with 1000x less currentwith 1000x less current

Direct MeasurementsDirect Measurements

Many Degrees of FreedomMany Degrees of Freedom

Choices of voltage, current, filter thickness, filter materialChoices of voltage, current, filter thickness, filter materialUsed Monte Carlo simulations to predict best resultsUsed Monte Carlo simulations to predict best results

dose1

backgroundareapeakMeritofFigure ×=

Experimental MDLExperimental MDL

35 kV, 0.8 35 kV, 0.8 mAmA, 200 mm Mo filter, 200 mm Mo filter

MiniumumMiniumum Detectable Limit =Detectable Limit =0.40 0.40 ++ 0.06 ppm0.06 ppmDoseDose 0.67 0.67 mSvmSv

Correction factors similar to Correction factors similar to 125125I, giving I, giving surface surface MDLsMDLs

of 0.65 of 0.65 ++ 0.10 ppm to 4.9 0.10 ppm to 4.9 ++ 0.7 0.7 ppmppm

Further improvementsFurther improvements can be made but in vivo measurements of n vivo measurements of exposed populations are now feasible.exposed populations are now feasible.

AcknowledgementsAcknowledgements

FacultyFaculty: David : David ChettleChettle, Bill , Bill PrestwichPrestwich, Colin Webber, Joanne , Colin Webber, Joanne OO’’Meara, Ana Meara, Ana PejovicPejovic--MilicMilic

PostPost--Doctoral FellowsDoctoral Fellows: Jimmy : Jimmy BBöörjessonrjesson, Ian , Ian StronachStronach, , Michelle Arnold, SoonMichelle Arnold, Soon--HynHyn ByunByun

Past and Present Graduate StudentsPast and Present Graduate Students: Joanne O: Joanne O’’Meara, David Meara, David Fleming, Michelle Arnold, Ana Fleming, Michelle Arnold, Ana PejovicPejovic--MilicMilic, Sean , Sean CarewCarew, , NieNie(Linda) (Linda) HuilingHuiling, Ryan , Ryan StudinskiStudinski, Aslam, , Aslam, DariaDaria ComsaComsa, Marija , Marija Popovic, Victor Popovic, Victor KreftKreft, , MariangelaMariangela ZamburliniZamburlini

McMaster KN Accelerator StaffMcMaster KN Accelerator Staff : Jim Stark, John Cave, Scott : Jim Stark, John Cave, Scott McMaster, Jason McMaster, Jason FalladownFalladown