Image-Based Canine Skeletal Model for Bone Microdosimetry...

Image-Based Canine Skeletal Model for Bone

Microdosimetry in the UF Dog Phantom

Laura Padilla, M.S.NIH Fellow

University of FloridaJuly 15th, 2008

Dog Model• Advantages: Overall, best animal model for

radiopharmaceutical research– Large population available– Spontaneously occurring disease– Comparable anatomical scale– Histological and biochemical similarities– Lifespan (7 dog years = 1 human year! )

• Disadvantages: Lack of canine-specific dosimetry tools– MIRDOSE or OLINDA used

• Based on stylized human phantoms

MIRD SchemaMean Absorbed Dose (DR) to a target region (rT) from one

or more radionuclide sources (rS):DR(rT)=Σs(Ãs*SR(rT←rS) )

Ãs: Number of decays in the sourceSR(rT←rS): Radionuclide S valueThe subscript R indicates the radiation type

SR(rT←rS)=Σi(ΔR,i*ФR,i(rT←rS))

ΔR,i: Mean energy per decay (Ei*Yi)ФR,i(rT←rS): Specific Absorbed Fraction for T-S combination

SPECT images

Provided by software

Anatomy dependent

Phantom Differences

Canine model total body mass = 26 kgORNL 5y total body mass = 19.8 kgORNL 10y total body mass = 33.2 kg

J Nucl Med 2008; 49:446–452

Skeletal microdosimetry• Current phantom has homogenous skeleton• Accurate skeletal dosimetry

– Different targets for different diseases:• Active bone marrow

– leukemia• Skeletal endosteum

– bone cancer

– Data needed:• Skeletal microstructure• Masses of target regions

Skeletal Microdosimetry model

• 4 steps – Bone mass table– Macrostructure modeling– Microstructure dosimetry preparation– Dosimetry calculations

Bone Mass Table• Masses calculated:

– Mineral bone• Cortical bone• Trabecular bone

– Marrow• Active marrow• Inactive marrow

– Teeth• All masses corrected for miscellaneous tissues

(ICRP70)– Blood vessels and periosteum

Needed Data• Bone site volumes (Canine Values)• Densities (Human Values)

– Mineral Bone (1.92 g/cc from ICRU 46)– Active Marrow (1.03 g/cc from ICRU 46)– Inactive Marrow (0.98 g/cc from ICRU 46)– Dentine – Teeth density approximation from ICRP 89 (3 g/cc)

• Miscellaneous tissue mass (ICRP 70) (Human Values)• Volume Fractions (Canine Values)

– Cortical Bone Volume Fractions– Spongiosa Volume Fractions– Bone Volume Fractions (Trabecular bone)– Marrow Volume Fractions

• Cellularity Factors (Human Values)

Data Acquisition – CBVF and SVF• 14 Bone sites were scanned Ex-Vivo• Cortical bone, spongiosa and teeth (when

applicable) segmented using 3D-DoctorTM

– CBVF (Cortical Bone Volume Fraction)– SVF (Spongiosa Volume Fraction)– TeVF (Teeth Volume Fraction)

Data Acquisition – BVF and MVF

• MicroCT images obtained for 12 bone samples• BIDUserInterface software used to analyze

images– MVF (Marrow Volume Fraction)– BVF (Bone Volume Fraction)

Sample Marrow Bone1 Proximal Femur 60.13 39.872 Distal Femur 69.57 30.433 Proximal Humerus 74.89 25.114 Distal Humerus 51.61 48.395 Cranium (Parietal) 34.76 65.246 Pelvis 73.6 26.47 C-4 60.91 39.098 T-5 75.81 24.199 T-13 73.41 26.59

10 L-2 74.04 25.9611 Mandible 82.99 17.0112 Rib 71.14 28.86

VF (%)

Data Acquisition – Cellularity• No cellularity reference values for dogs

– Currently being estimated• 40-year-old values from ICRP 70 used

Skeletal Sites

SpongiosaVolume

(cc)BVF (% of

SV)Trabecular

Bone Mass (g)

Cortical Bone

Volume (cc)

Cortical Bone Mass (g)

Total Mineral

Mass (g)Cranium 22.75 65.24 27.87 134.03 251.68 279.55Mandible 22.36 17.01 7.14 46.45 87.22 94.36Scapulae 36.51 28.86 19.78 62.99 118.29 138.07Sternum 3.89 28.86 2.11 9.01 16.93 19.03Ribs 31.49 28.86 17.07 82.28 154.50 171.57Vertebrae (Cervical) 30.60 39.09 22.46 88.20 165.61 188.08Vertebrae (Thoracic) 55.22 25.39 26.33 74.62 140.12 166.45Vertebrae (Lumbar) 76.59 25.96 37.33 52.56 98.70 136.04Pelvis 67.85 26.40 33.64 62.03 116.48 150.12Vertebrae (Caudal) 6.76 25.96 3.30 20.06 37.67 40.96Femur

Proximal 28.52 39.87 21.35 13.85 26.01 47.36Shaft 29.46 0.00 0.00 25.95 48.73 48.73Distal 51.10 30.43 29.20 14.08 26.45 55.65

Tibia-FibulaTibia


FibulaProximal 2.32 30.43 1.33 0.88 1.66 2.99

Shaft 1.83 0.00 0.00 1.29 2.42 2.42Distal 1.50 30.43 0.86 0.65 1.22 2.08

Paw BonesHind paw bones 31.21 30.43 17.83 55.79 104.77 122.60

Front paw bones 24.03 48.39 21.84 42.97 80.68 102.52Humerus


Radius-UlnaRadius


UlnaProximal 12.30 48.39 11.18 12.97 24.36 35.54

Shaft 10.37 0.00 0.00 13.35 25.07 25.07Distal 1.73 48.39 1.57 3.17 5.96 7.53Total 728.06 375.01 959.12 1801.02 2176.03

Mineral Bone Trabecular Spongiosa Regions Cortical Bone RegionsResults

Lumbar V.

Rib

Distal Femur

Distal Humerus

Results Skeletal S ites M V F (% o f S V )T ota l M a rr ow Vo lu m e ( cc )

C el lu lar ity (% o f M V )

Ina ct ive M a rr ow M as s

( g)A ct i ve M arr ow

M a ss (g )C ran ium 34.76 7.91 38.00% 4.60 2.97M andib le 82.99 18.56 38.00% 10.79 6.96Sc apulae 71.14 25.97 38.00% 15.10 9.75Sternum 71.14 2.76 70.00% 0.78 1.91R ibs 71.14 22.40 70.00% 6.30 15.49Ver tebrae (C er vica l) 60.91 18.64 70.00% 5.24 12.89Ver tebrae (T horac ic) 74.61 41.20 70.00% 11.59 28.49Ver tebrae (Lum bar) 74.04 56.70 70.00% 15.95 39.21Pelvis 73.60 49.94 48.00% 24.35 23.68Ver tebrae (C audal) 74.04 5.01 70.00% 1.41 3.46F em ur

Pr oxim al 60.13 17.15 25.00% 12.06 4.23Shaft 100.00 29.46 0.00% 27.62 0.00D ista l 69.57 35.55 0.00% 33.34 0.00

T ib ia- Fibula 0.00T ib ia 0.00


F ibu la 0.00Pr oxim al 69.57 1.61 0.00% 1.51 0.00

Shaft 100.00 1.83 0.00% 1.72 0.00D ista l 69.57 1.05 0.00% 0.98 0.00

Paw Bones 0.00H ind paw bones 69.57 21.71 0.00% 20.36 0.00

F ront paw bones 51.61 12.40 0.00% 11.63 0.00Hum erus 0.00


Radius- U lnaRadius


U lnaPr oxim al 51.61 6.35 0.00% 5.95 0.00

Shaft 100.00 10.37 0.00% 9.72 0.00D ista l 51.61 0.89 0.00% 0.84 0.00T ota l 528.36 345.74 157.73

M arro w

Homogenous Calculated % differenceCranium 243.88 339.37 39.16%Mandible 114.96 152.02 32.24%Scapulae 139.29 162.92 16.96%Sternum 18.07 21.72 20.21%Ribs 159.28 193.36 21.40%Vertebrae (Cervical) 166.32 206.21 23.98%Vertebrae (Thorac ic) 181.78 206.52 13.61%Vertebrae (Lumbar) 180.81 191.20 5.75%Pelvis 181.83 198.14 8.97%Vertebrae (Caudal) 37.55 45.83 22.05%Femur

Proximal 59.32 63.66 7.32%Shaft 77.57 76.35 -1.57%Distal 91.26 88.98 -2.49%

Tibia-FibulaTibia

Proximal 57.35 63.76 11.18%Shaft 70.76 72.84 2.94%Distal 29.31 33.12 13.03%

FibulaProximal 4.48 4.50 0.43%

Shaft 4.36 4.13 -5.21%Distal 3.01 3.06 1.61%

Paw BonesHind paw bones 121.80 142.96 17.37%

Front paw bones 93.80 114.15 21.70%Humerus

Proximal 91.50 75.94 -17.00%Shaft 69.13 76.58 10.77%Distal 42.70 50.73 18.82%

Radius-UlnaRadius

Proximal 16.97 19.12 12.64%Shaft 40.46 41.51 2.60%Distal 30.50 38.30 25.58%

UlnaProximal 33.05 41.50 25.57%

Shaft 34.00 34.79 2.31%Distal 8.08 8.36 3.54%Total 2403.17 2771.67 15.33%

Homogeneous vs.

Detailed masses

* *

* Values in grams

Interesting Points

• The homogeneous skeletal density for this dog model is: 1.62 g/cc

• Active bone marrow mass represents 0.6% of dog’s total body weight – ICRP 70 data: 1.5% for 35 YO adult female– Value subject to change with updated

cellularity factors– Difference might be due to higher

extramedullar hematopoiesis in dogs

Macrostructure construction

Cervical V.

FemurPelvis Radius and Ulna

Conclusions

• Calculated homogenous bone density for dog skeleton is ~15% larger than that for humans

• Smaller active marrow mass might be due to larger extramedullar hematopoietic activity

• The accuracy of presented values could be improved if canine-specific data were available

• Skeletal dosimetry calculations should be completed in the next few months

Thank you

Any questions?

Image-Based Canine Skeletal Model for Bone Microdosimetry...

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