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6/30/2008 1 Factors Affecting Accurate Quantification In PET/CT Osama Mawlawi, Ph.D. O. Mawlawi MDACC Department of Imaging Physics MD Anderson Cancer Center O. Mawlawi MDACC 53 year old man with lymphoma with increased FDG uptake in the spleen and multiple intra and extra-thoracic nodes consistent with Multi-focal malignancy. Power of PET : Quantification O. Mawlawi MDACC Quantification: Power of PET Measured Data Random subtract Normalize Dead time O. Mawlawi MDACC Ideal measured data Correct Geometry Calculate/subtract scatter Correct Attenuation Dead time FBP or IR reconstruction calibration

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6/30/2008

1

Factors Affecting Accurate Quantification In PET/CT

Osama Mawlawi, Ph.D.

O. Mawlawi MDACC

Department of Imaging PhysicsMD Anderson Cancer Center

O. Mawlawi MDACC

53 year old man with lymphoma with increased FDG uptake in the spleen and multiple intra and extra-thoracic nodes consistent withMulti-focal malignancy.

Power of PET : Quantification

O. Mawlawi MDACC

Quantification: Power of PET

Measured Data

Random subtract

Normalize

Dead time

O. Mawlawi MDACC

Ideal measured data

Correct Geometry

Calculate/subtract scatter

Correct Attenuation

Dead time

FBP or IR reconstructioncalibration

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2

decay-corrected dose/ml of tumorSUVinjected dose/patient weight in grams

=

SUV

• The standardized uptake value (SUV) is

O. Mawlawi MDACC

p ( )one means of making PET results more quantitative.

• Tracer kinetic modeling is used extensively in quantitative PET (may include blood samples and dynamic imaging).

SUV Modifiers

• SUVbw (gm/ml)

O. Mawlawi MDACC

• SUVBSA (m2/ml)

• SUVLBM (gm/ml)

SUV Modifiers

• SUVig (gm/ml)

O. Mawlawi MDACC

Quantitative PET Performance Quantitative PET Performance

3 categories that “might” affect SUV measurements• Patient Compliance

– Fasting– Blood Glucose levels

• Scan Conditions

O. Mawlawi MDACC

– Scan time post injection– Patient anxiety/comfort during uptake (room temperature, etc.)– Patient motion during acquisition– PET/CT vs dedicated PET

• Intrinsic System Parameters and Capability– Calibration– QA – Maintenance of operating parameters– Performance characteristics of scanners – Partial Volume

effects– Image processing algorithms

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3

Improper Prep. Non fasting

• High protein/low carbs.• 6-8 glasses of water• 6 hrs fasting• Avoid strenuous exercise

O. Mawlawi MDACC

Fast Track Insulin Scan

• 70 ––150 mg/dL – Ideal• 150 ––200 mg/dL - clinical decision• > 200 mg/dL - cancel

O. Mawlawi MDACC

Muscle Uptake

O. Mawlawi MDACC

Crutch Utilized Left Side

Quantitative PET Performance Quantitative PET Performance

3 Categories that “might” affect SUV measurements• Patient Compliance

– Fasting– Blood Glucose levels

• Scan Conditions

O. Mawlawi MDACC

– Scan time post injection– Patient anxiety/comfort during uptake (room temperature, etc.)– Patient motion during acquisition– PET/CT vs Dedicated PET

• Intrinsic System Parameters and Capability– Calibration– QA – Maintenance of operating parameters– Performance characteristics of scanners – Partial Volume

Effects– Image processing algorithms

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4

N=20

Effect of Scan time post injection: Beast Cancer

O. Mawlawi MDACCBeaulieu S et al JNM 2003

PET-CT Normal “Brown” Fat

Max SUV 15.7

O. Mawlawi MDACC

Cor MIP Fused

Ax PETAx CT

Phantom Study

AxialCoronal Sagital Mip

Motion Effects

O. Mawlawi MDACC

Sphere (volume) Gated Static Error (%)1 (16.5 cc) 31624 33546 -6.1

2 (8.4 cc) 31316 21872 30.23 (4 cc) 29919 20607 31.14 (2 cc) 22857 13643 40.35 (1 cc) 19087 8264 56.7

6 (0.5 cc) 11897 5143 56.8

Patient Movement

Patient movement occurred

O. Mawlawi MDACC

occurred after the CT image was acquired.

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Impact of Whole-body Respiratory Gated PET/CT

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The max SUV of the lesion goes from 2 in the static image to 6 in the respiratory-gated image sequence

Static wholebody Single respiratory phase(1 of 7, so noisier)

1 cc lesion on CT

Courtesy of P Kinahan, UW

• Transmission – Noise due to low gamma ray flux from rod source

Disadvantages of dedicated PET imaging techniques

PET/CT vs Dedicated PET

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g y– Transmission is contaminated by emission data

• Scan duration– Time consuming (emission & transmission )– Increased patient movement (image blurring)

• Efficiency– Decreased patient throughput– Difficulty in accurately correlating images to other

diagnostic modalities

Short duration, low noise CT-based attenuation correction

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Attenuation MeasurementRod or Pin Source (Ge-68, T½= 271 days)

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Patient Transmission Scan

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PET-CT

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AttenuationCorrection

Inherent Image

Registration

• For CT values < 0 , materials are assumed to have an energy dependence similar to water

• For CT values > 0, material is assumed to have an 0.100

0.150

0.200

atio

n at

511

keV

Bone/WaterBone/Water

Converting CT Numbers to Converting CT Numbers to Attenuation ValuesAttenuation Values

O. Mawlawi MDACC

energy dependence similar to a mixture of bone and water

• The green line shows the effect of using water scaling for all materials

0.000

0.050

-1000 -500 0 500 1000CT number measured at 140kVp

Atte

nua

Water/air

PET/CT imaging artifacts are due to :PET/CT imaging artifacts are due to :

Respiratory motionRespiratory motionMetal implantsMetal implants

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ppTruncationTruncationContrast mediaContrast media

Breathing Artifact-Curvilinear Cold Areas

Photopenic Artifact

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CT PET FUSEDIMAGE NON AC

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Breathing ArtifactMismatch of lesion location between helical CT and PET

O. Mawlawi MDACCInaccurate attenuation correction inaccurate quantification

Mismatch between PET and CT – Cardiac Application

O. Mawlawi MDACC

Courtesy of J. Brunetti, Holly name

X-ray onoff

1st table position(0 - 2cm)

2nd table position(2 - 4 cm)

3rd table position(4 - 6 cm)

EE 50% EE 50%

EI 0% EI 0%

Respiratory singal

CT i

Average CT – 4D CT

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0 10 20 30 40 50 60 70 80 90%0 10 20 30 40 50 60 70 80 90%

Image averaging

4DCT averagingHelical CT

Helical CTwithout thorax

Combined helical andrespiration-averaged CT

CT images

4D-CT images

Respiration-averaged CT 2

1

Courtesy of Tinsu Pan, MDACC

Clinical Studies

Mismatch 1:

CT diaphragm position lower

than PET

Mismatch 1:

CT diaphragm position lower

than PET

+57%

O. Mawlawi MDACC

Mismatch 2:

CT diaphragm position higher

than PET

Mismatch 2:

CT diaphragm position higher

than PET

Courtesy of Tinsu Pan, MDACC

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8

4D-PET/CT

O. Mawlawi MDACC

4D PET/CT

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Phantom Study

AxialCoronal Sagital Mip

Motion Effects

O. Mawlawi MDACC

Sphere (volume) Gated Static Error (%)1 (16.5 cc) 31624 33546 -6.1

2 (8.4 cc) 31316 21872 30.23 (4 cc) 29919 20607 31.14 (2 cc) 22857 13643 40.35 (1 cc) 19087 8264 56.7

6 (0.5 cc) 11897 5143 56.8

METAL & CONTRAST artifactsMETAL & CONTRAST artifacts

For CT values < 0 , materials For CT values < 0 , materials are assumed to have an are assumed to have an energy dependence similar to energy dependence similar to water water For CT values > 0, material For CT values > 0, material is assumed to have an is assumed to have an 0.100

0.150

0.200

tion

at 5

11ke

V

Bone/WaterBone/Water

error

O. Mawlawi MDACC

energy dependence similar to energy dependence similar to a mixture of bone and watera mixture of bone and water

The green line shows the The green line shows the effect of using water scaling effect of using water scaling for all materialsfor all materials 0.000

0.050

-1000 -500 0 500 1000CT number measured at 140kVp

Atte

nuat

Water/air

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Metal ArtifactsMetal Artifacts

ArtifactArtifact

O. Mawlawi MDACCCT PET CTAC FUSED IMAGE

Metal ArtifactsMetal Artifacts

Cold spot

O. Mawlawi MDACC

CT SCAN PET AC NO AC

Transaxial

contrast bias

Contrast Effects

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Normal CT Contrast enhanced CT

Coronal

Contrast: Optiray 320, 100cc, 3cc/sec

Contrast ArtifactContrast Artifact-- Intravenous Intravenous Contrast injected

O. Mawlawi MDACCCT PET CTAC FUSED IMAGE

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With contrast Without contrast

O. Mawlawi MDACC

61 year male with history of esophageal cancer

SUV change

O. Mawlawi MDACC

1.23 to 1.9054% inc

PET Detector

PET 70cm image FOV

X-ray focal spot

CT and PET Fields of ViewCT and PET Fields of View

O. Mawlawi MDACC

CT Detector

CT 50cm Fully sampled FOV

Truncation ArtifactsTruncation ArtifactsOccur when objects extend outside the CT field Occur when objects extend outside the CT field of view (50cm), but are in the PET field of view of view (50cm), but are in the PET field of view (70cm). (70cm).

CT FOV

O. Mawlawi MDACC

Truncation artifacts are observed in very large patients or patients scanned with arms down.

PET FOV

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O. Mawlawi MDACC O. Mawlawi MDACC

SUVmax changed from 3.25 to 6.05

CT PET FUSED Attenuation map

Truncated

O. Mawlawi MDACC

54 yrs. male with history of metastatic melanoma of the skin. SUV changed from 3.25 to 6.05

Truncated corrected

Quantitative PET Performance Quantitative PET Performance

3 Factors that may affect SUV measurements• Patient Compliance

– Fasting– Blood Glucose levels

• Scan Conditions

O. Mawlawi MDACC

– Scan time post injection– Patient anxiety/comfort during uptake (room temperature, etc.)– Patient motion during acquisition– PET/CT vs dedicated PET

• Intrinsic System Operating Parameters– Calibration– QA – Maintenance of operating parameters– System performance characterization – Partial Volume – Image processing algorithms

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Coincidence CalibrationsCoincidence Calibrations• Well Counter Correction (WCC)

O. Mawlawi MDACC

Effects of Bad Blocks

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Effects of Bad Blocks

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Effects of Bad Blocks

O. Mawlawi MDACC

6/30/2008

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Normalized to Baseline for each Sphere

85

90

95

100

105

erce

nt

sphere37 mm

sphere28 mm

sphere22 mm

h

O. Mawlawi MDACC

65

70

75

80

base

line

final

base

line

M5blk4

M5blk5

M22

blk5

M5blk4

,5 M5blk

2,3

M5blk4

,5

M5blk4

,5 M9blk

4

M5blk4

,5 M6blk

4

M5blk4

,5 M22b

lk2,3

M5blk4

,5 M9blk

4,5

M5blk4

,5 M22b

lk4,5

M5blk4

,5 M22b

lk4

M5blk4

,5 M6blk

4,5

pe sphere17 mm

sphere13 mm

sphere10 mm

Normalization effects

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Good Norm Bad Norm

Effect of bad Normalization

SUVmax=4.5

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Increased activity due to error in normalization

Effect of wrong WCC

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6/30/2008

14

10

37 28

22

1713All spheres contain the same activity concentration Profile (10 mm)

%)

Effect on Partial voluming

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Standard 8 x 8 detector

HI-REZ 13 x 13 detectorSphere diameter

Rec

over

y (

100

50

0 10

37282217

13

Recovery coefficientsCourtesy of Siemens

a

b d f

c e

Effect of Reconstruction Algorithm

O. Mawlawi MDACC

(a) 2D-FBP; (b) 2D-OSEM; (c) 3D-RP; (d) 3D-IR; (e) 3D-FORE+FBP; (f) 3D-FORE+OSEM.

(x104) Sphere 1 Sphere 2 Sphere 3 Sphere 4 Sphere 5 Sphere 6

Algorithm a 3.03 2.74 2.52 2.30 1.75 1.12

Algorithm b 3.14 3.14 2.82 2.90 2.14 1.74

Algorithm c 2.83 2.76 2.62 2.41 1.60 1.07

Algorithm d 2.93 2.92 2.98 3.21 2.19 1.33

Algorithm e 2.78 2.75 2.64 2.40 1.59 1.10

Algorithm f 2.85 2.74 2.71 2.52 1.65 1.09

AC max under different reconstruction algorithms (Bq/cc)

A

3D IR 2it 20sub

B

3D FORE 2it 5sub

C D

O. Mawlawi MDACC

1 2 3 4 5 6

A 10.8 10.3 9.9 8.9 6.5 3.8

B 8.6 7.6 6.6 5.5 3.9 2.8

C 10.3 9.7 9.1 8.3 6.3 4.7

D 10.4 9.3 9.3 7.7 5.9 4.8

3D FORE 5it 28sub

3D FORE FBP

Max SUVbw in different spheres

A

2D OSEM

2it 20sub

B

2D OSEM

2it 28sub

C

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2D OSEM

4it 28sub

1 2 3 4 5 6

A 12.7 11.9 11.7 12.7 7.4 4.1

B 15.0 12.3 11.7 13.4 9.6 5.4

C 16.0 13.6 11.9 14.7 10.3 6.3

Max SUVbw in different spheres

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O. Mawlawi MDACC

Effect of acquisition time on convergence of reconstruction algorithm (2it 21ss)

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6

7

8

9 x 104

7

scan1scan2scan3scan4

2D 3D

10

12

14

16 x 104

7

scan1scan2scan3scan4

Effect of scan duration and count density on maximum AC

O. Mawlawi MDACC

0 20 40 60 80 100 120 140 160 1801

2

3

4

5

Duration(sec)

Max

d3

scan4

0 20 40 60 80 100 120 140 160 1800

2

4

6

8

Duration(sec)

Max

d3 scan4

Effect of smoothing on measured AC

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6/30/2008

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Effect of ROI type

O. Mawlawi MDACCCourtesy of P. Kinahan UW

Conclusion

• SUV is reproducible

• SUV is reliable as long as mediating factors

O. Mawlawi MDACC

SUV is reliable as long as mediating factors are accounted for

• Standardization across institutions might be a more difficult task