PET (SUV) Quantitative Imaging

[Pages:12]PET (SUV) Quantitative Imaging

10/25/2011 R. Doot

Robert K. Doot, PhD Senior Research Scientist Department of Radiology University of Washington

PET Quantitative Approaches: Outline

? Why quantify FDG PET uptake? ? Biochemistry and kinetics of FDG ? Approaches to quantitative analysis ? Factors that affect quantitative accuracy ? Quantitative imaging - what is required?

10/25/2011 R. Doot

Why Quantify PET Images?

Patient 1

Before Therapy

After Therapy

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Patient 2

FDG PET uptake predicts outcome of bone-dominant breast cancer

Time to progression

Time to skeletal-related event

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(Specht Br Ca Res Treat 2007)

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Why Quantify FDG Uptake?

? Helps identify malignancy ? Provides other information:

? Prognosis ? "Grade" ? Correlation with tumor biology ? Key for assessing response ? Why not? - no extra work

10/25/2011 R. Doot

Requirements for Quantitative Analysis of FDG PET Scans

? Attenuation-corrected scans ? Cross-calibration between PET

tomograph and dose calibrator ? ROI analysis software ? Standard imaging time after injection ? Measurement of plasma glucose

10/25/2011 R. Doot

FDG PET Quantitative Analysis

FDG Biochemistry, and Kinetics

10/25/2011 R. Doot

FDG: Tracer of Glucose Metabolism

Glucose

18F-fluorodeoxyglucose

(FDG)

Blood Cell

Glucose

Glucose-6P

FDG

FDG-6P

Glycolysis

Increased glycolysis commonly observed in cancer (Warburg 1930)

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Model of FDG Uptake

Blood Tissue

Blood FDG

Tissue FDG

PET Image

Trapped FDG-6P

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FDG Kinetics : Effect of Blood Clearance

High metabolism Medium metabolism

SUV

Metabolically Inactive Blood

FDG Injection

Time

Time is required for clearance from tissues without trapping

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(after Hamburg, JNM 35:1308, 1994)

Approaches to Quantifying FDG Uptake

10/25/2011 R. Doot

FDG PET Imaging Methods

Acquisition

Qualitative

Whole-body imaging

Analysis

Visual Inspection

Quantitative

Static Dynamic

10/25/2011 R. Doot

Standard Uptake Value (SUV) Glucose Metabolic Rate

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Glucose Metabolic Rate Estimation

Dynamic Imaging

Time

Region-of-Interest Analysis Time-Activity Curves

Kinetic Modeling

Glucose (FDG) Metabolic Rate

10/25/2011 R. Doot

Activity (?Ci/ml)

Time

Tissue Blood

FDG Tracer Kinetic Model: to Calculate Metabolic Rate (MRFDG)

Blood Tissue

Blood FDG

K1 k2

Tissue FDG

k3 k4

PET Image

Trapped FDG-6P

Glucose

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Flux Constant, Ki

MRFDG = [Glucose] Ki

Ki = K1k3/(k2+k3)

Activity Normalized

Activity Activity

Graphical (Patlak) Analysis

Flux

Blood Tracer

(Cb)

Tissue Tracer

T

Bound Tracer

B

Ct/Cb = Ki Cbd /Cb + (V0 +Vb)

ref: Patlak et al JCBFM 3:1, 1983

Blood

Slope = Ki

Tissue

10/25/2011 R. Doot

Simple Uptake Ratios: Standard Uptake Value (SUV)

SUV =

Average Tissue Uptake

Time

Tissue Tracer Activity (mCi/g)

(Injected Dose (mCi)/Pt weight (kg))

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Estimate of Tracer Availability

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SUV: An Illustration

Inject 7 mCi

(ID)

Into a 70 kg

water bucket (W)

Activity = 0.1 ? Ci/mL

Activity 0.1

SUV

=

= 1 g/mL

= ID/W

7/70

10/25/2011 R. Doot

Standard Uptake Value (SUV)

Tissue Tracer Activity (?Ci/g) SUV =

(Injected Dose (mCi)/Pt weight (kg))

Tissue Typical FDG SUV

Lung Bone Marrow Breast Liver Tumor

0.7 1.0 0.5 2.5 > 3-4

Zasadny, Radiology 189: 847,1993

10/25/2011 R. Doot

Why measure in SUV (an example)?

? PET scanner measures the radioactivity per unit volume ? Typically measured as kBq/ml or ?Ci/ml ? Interested in local areas with high or low uptake

70 kg water = 70 L

inject

10 mCi = 370 MBq

Net concentration = 370,000 kBq / 70,000 ml

= 5.3 kBq/ml

A very small object that takes up 5x net concentration, so its local concentration = 26.5 kBq/ml

10/25/2011 R. Doot

Impacts of injected dose & distrib. volumes

Injecting different amounts or changing volume will change concentration while relative uptake compared to background is constant

70 kg = 70 L

10 mCi = 370 MBq

concentration = 5.3 kBq/ml

26.5 kBq/ml

5 mCi = 185 MBq

10 mCi = 370 MBq

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concentration = 2.64 kBq/ml

13.2 kBq/ml

concentration = 10.6 kBq/ml

35 kg = 35 L

53.0 kBq/ml

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Standardized uptake values (SUVs)

Normalize by amounts injected per volume (i.e. weight) to get the same relative distribution with SUV = 1.0 for a uniform distribution

70 kg = 70 L

Overall SUV = 5.3 kBq/ml / (370MBq/70 Kg) = 1.0 g/ml

10 mCi = 370 MBq

5 mCi = 185 MBq 10 mCi = 370 MBq 10/25/2011 R. Doot

SUV = 5.0

SUV = 1.0 g/ml

SUV = 5.0

SUV = 1.0 g/ml

35 kg = 35 L

SUV = 5.0

Hot spot has same SUV values independent of activity injected or volume of distribution (i.e. patient size)

Measuring uptake: kBq/ml versus SUV

Same scale for kBq/ml

Same scale for SUV

10/25/2011 R. Doot

Slide Courtesy of Paul Kinahan

Liver values look more uniform between patients

SUV versus MRFDG to Measure

Response in Serial FDG PET Scans

% Change SUV vs % Change MRFDG in 39 Breast Cancer Pts with Neo-Adjuvant Therapy

0

r = 0.84

-20

but .....

Slope = 0.75

-40

(i.e., % change not equal)

SUV % Change

-60

-80

Slope: 0.75 ? 0.08

-100 -100 -80 -60 -40 -20 0

MRFDG % Change

(Doot J. Nucl. Med. 48:920, 2007)

10/25/2011 R. Doot

Intercept not at -100%

(SUV dose not go to 0)

Conclusion: SUV may underestimate response for low SUV tumors (< 3 pre-Rx)

Simpler Approaches to FDG Quantitative Analysis

Blood Tissue

PET Image

Blood FDG

Tissue FDG

Trapped FDG-6P

Uptake Ratio = Tracer in Tissue Tracer Available in Blood

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SUV Loses Sensitivity at Low Values

Ability to measure response depends on pre-therapy SUV

All Patients

Pre-Rx SUV < 3 Pre-Rx SUV > 3

Dynamic range for response reduced by 35% for low pre-Rx SUV

10(/D25o/2o01t1JR..NDouoct l. Med. 48:920, 2007)

FDG SUV

Factors Affecting Quantitative Precision and Accuracy

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SUV Error sources

5 sources of measure error: ? PET image acquisition and analysis ? Patient prep ? Dose calibrator ? Weight scale for patient ? Clocks synchronization

Tissue tracer activity concentration (?Ci/g)

SUV =

(Injected dose (mCi)) / Pt. weight (kg))

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PET Data Acquisition and Image Reconstruction

Acquire Projection Data

Organize Data Into Projections

(Sinograms)

Image of Tracer Concentration

Image Reconstruction

Coincidence Detection

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Scatter Correction Randoms Correction Attenuation Correction

Calibration to a Standard

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Scanner Calibration

Scan Phantom with Uniform Activity

Measure Aliquot of Activity in Dose Calibrator

or Well Counter

PET scanner calibrated quarterly and responsibility of hospital

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Physical effects in PET

? Spatial resolution limitations ? Positron range ? Angular deviation of annihilation photons ? Instrumentation limitations ? Depth-of-interaction in detector

? Count rate limitations ? Dead time ? Random Coincidences ? Scattered coincidences

? Photon attenuation

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Effects of Attenuation: Patient Study

reduced mediastinal

uptake

'hot' lungs

Nonuniform

liver

Enhanced skin uptake

PET without attenuation correction (no direct physical

meaning to values)

PET with attenuation correction (accurate)

CT image (accurate)

Summary: All quantitative corrections have to be applied. Attenuation correction is most important and the biggest potential source of error if things go wrong

10/25/2011 R. Doot

Slide Courtesy of Paul Kinahan

Effect of Attenuation on Image Quality

Thin

not Thin

Scans performed using the same scanner and protocols

10/25/2011 R. Doot

Slide Courtesy of Paul Kinahan

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