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Volumetric Measurement of Tumors
David F. Yankelevitz, MD
Why Measure Tumor Volumes?
• Surrogate for knowing the amount of viable
tumor
• Implied is this:
– Larger volumes, therefore progression
– Smaller volumes, therefore response
How do we measure volumes?
• Surrogates
– Uni-dimension (RECIST)
– Bi-dimension (WHO)
– Tri-dimension
• Genuine volume measurements
Advantages of Volume Measurements
• Greater proportional change
– 26% diameter increase corresponds to 100%
volume increase
• Measurement of asymmetric growth
• Tumor volume doubling time
Expected Change in Diameter
Days to ERCT Initial
from initial
nodule
CT
diameter
(mm)
Doubling time (days)
30
90
120
150
180
28
12.41
(24 vs
93%)
10.75
10.55
10.44
10.37
(4 vs
12%)
10
Asymmetric Growth
•
•
•
•
Area: 36.5 mm2
Perimeter: 22.7 mm
Length: 8.27 mm
Width: 5.62 mm
•
•
•
•
Area: 36.6 mm2
Perimeter: 23.4 mm
Length: 8.23 mm
Width: 5.66 mm
• SPN (6.9 mm) at baseline and 36 days later
• Virtually unchanged according to 2D metrics
• Apparently benign (DT=9700)
Volumetric Analysis
• 3D analysis reveals significant growth along scanner axis!
(DT = 104, malignant)
8 mm Stable Nodule
Volumetric Growth Rate Analysis
• 8 mm stable pulmonary nodule at baseline and 181 days later
• MVGI = 0.57%
10 mm Malignant Nodule
Volumetric Growth Rate Analysis
• 10 mm malignant pulmonary nodule at baseline and 32 days later
• MVGI = 22.0% -- Squamous Cell Carcinoma
Inputs Into Volume Estimates
• Accuracy of measuring device (machine)
– Inplane (x,y), out of plane (z)
• Ability to define borders of target (anatomic)
– Removal of attached structures
• CAD
– Defining edges
• Margin of tumor
• Adjacent edema/inflammation
– Stability of structures
10mm Slice Thickness (Anisotropic)
© ELCAP 2002
5mm Slice Thickness
© ELCAP 2002
2.5mm Slice Thickness
© ELCAP 2002
1mm Slice Thickness
© ELCAP 2002
Headline
SOMATOM
Sensation 64
6 sec for 400 mm
64 x 0.6mm (2x32)
Resolution 0.4 mm
Rotation 0.37 sec
120 kV / 100 mAs
Courtesy of University of Erlangen, Department of Radiology and Institute of Medical Physics
Headline
SOMATOM
Sensation 64
6 sec for 400 mm
64 x 0.6mm (2x32)
Resolution 0.4 mm
Rotation 0.37 sec
120 kV / 100 mAs
Courtesy of University of Erlangen, Department of Radiology and Institute of Medical Physics
Volumetric CT Scanning
Accuracy of Area Measurements
Deformable Synthetic Nodules
Volumetric Measurement - Synthetic Nodules
• Volume Error:
(3-6 mm) = 1.1% RMS, 2.8% max
(6-11 mm) = 0.5% RMS, 0.9% max
• Function of nodule size
Yankelevitz, et al. Radiology 2000
Removal of Attached Structures
Jan 27 1999, (X,Y) resolution: 0.1875 mm, Slice thickness : 1 mm
Images ©1999, ELCAP Lab, Weill Medical College of Cornell University
Solid Nodule Segmentation
Solid Nodule Segmentation
Volumetric Doubling Time Estimation
74-Day Doubling Time
Images ©1999, ELCAP Lab, Weill Medical College of Cornell University
Limitations of Segmentation
Part-Solid Nodule: Complex Segmentation
Abutting Pleura: Limitations of Segmentation
Nonsolid Nodule: Indistinct Border
Less Natural Contrast
SPICULATED NODULE
Instructions to Thoracic Radiologists were
“Draw the Boundary of the Nodule”
SPICULATED NODULE
Expert Number 1 Contour
SPICULATED NODULE
Expert Number 2 Contour
SPICULATED NODULE
Comparison of Contours
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Patient Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Nonsolid nodule:
Adenocarcinoma, bronchioloalveolar subtype
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Motion Artifact – Cardiac Motion
Images ©1996-2002, ELCAP Lab, Weill Medical College of Cornell University
Nodule Growth Rates
• Exponential Growth Model
• Nodule Doubling Time (DT)
• Traditional 2D Approximation
Appropriate Time to Follow-up CT
• When should the follow-up CT be done?
where k(d) is the reliably-detectable percent
volume change, a function of initial nodule size
k(d) = two standard deviations of PVC in stable
nodules by size category
DTD = 400 days for baseline cases
DTD = upper bound on doubling time for repeat cases
example: 208 days for 3 mm nodule
Time to Follow-up CT
Appropriate time to follow-up CT by initial nodule size detected on
baseline or repeat screening
Size (mm)
2-5
5-8
8 - 11
k(d) (%)
37.0
21.2
15.0
Time to Follow-up CT (days) for
nodules detected on
Baseline
Repeat
182
95
111
26
81
12
Review of Literature
• Limited data on comparison of 3D volume
measurements to 2D or 1D, notably for large
lesions
• Most report that volume is better for large
‘well-defined’ abnormalities
• Limited impact on change in category for
RECIST
Summary
• Technology has greatly improved
– Measuring device
– Image processing
• Little work has been done in regard to complex
abnormalities
• Potential to markedly improve response
estimates
Volumetric Measurement of In Vivo Nodules
• Although we had quantified the relative error in
phantom nodule measurement by size, the
error for in vivo nodules must be greater
– partial volume
– vascular geometry
– motion artifacts
Assessment of In Vivo Volume Estimates
• Rescanning in short interval
– Smallest change in true nodule volume
– Difficult study due to dose concerns
• Stable nodules
– Scans more easily obtained (screening)
– Accounts for small errors in patient
positioning and scanner calibration drift
Cases
• 262 HRCT scans of 120 stable nodules
– Standard dose, small FOV, HRCT
– Nodules 2-11 mm in diameter
– Determination of stability based on radiologist
evaluation over period of 2 or more years
– Assessment of technical artifacts
• Incomplete acquisition
• System error
– Assessment of motion artifacts
• Five-point scale
• Patient motion (gross movement, respiration)
• Cardiac motion
• 20 HRCT scans of 10 malignant nodules
Artifacts
Motion artifact and technical artifact in 262 CT scans by initial nodule size
Technical
Artifact
Motion Artifact Score
None
Minimal
Moderate Pronounced Severe
Any
Artifact
Size (mm)
2-5
5-8
8 - 11
3
1
1
55
21
5
8
4
1
2
7
5
7
2
0
1
1
0
Any size
5
81
13
14
9
2
21
15
7
26 (22%) of cases had to be excluded due to technical or motion artifacts
Stable Nodules
Frequency distribution of 94 stable nodules by initial size and time to
follow-up CT
Time to Follow-up CT (months)
0-6
6 - 12
12 - 30
Any Interval
2-5
5-8
8 - 11
21
11
2
29
12
2
13
2
2
63
25
6
Any size
34
43
17
94
Size (mm)
Monthly Volumetric Growth Index
• Monthly Volumetric Growth Index, MVGI
– Percent change in volume per month
– Remaps growth estimates into two distinct classes
Reeves, et al. RSNA 2001
Nodule Growth Rates
MVGI = 32.5
MVGI = 15.1
MVGI = 4.3
MVGI of Stable Nodules
Mean and standard deviation of monthly volumetric growth index of 94
stable nodules by initial size and time to follow-up CT
Time to Follow-up CT (months)
0 - 6 6 - 12 12 - 30
Any Interval
Size (mm)
2-5
5-8
8 - 11
Mean
-0.05
-0.32
-0.68
SD
2.48
1.82
2.36
Mean
0.20
0.82
0.05
SD
2.28
1.54
0.74
Mean
-0.33
-0.11
-0.23
SD
1.60
0.49
0.68
Mean
0.01
0.24
-0.13
SD
2.21
1.68
1.23
Any Size
-0.17
2.22
0.37
2.04
-0.24
1.41
0.06
2.02
Overall mean
0.06%
Std. Err. of the Mean
0.21%
MVGI of Stable Nodules
Mean and standard deviation of monthly volumetric growth index of 94
stable nodules by initial size and time to follow-up CT
Time to Follow-up CT (months)
0 - 6 6 - 12 12 - 30
Any Interval
Size (mm)
2-5
5-8
8 - 11
Mean
-0.05
-0.32
-0.68
SD
2.48
1.82
2.36
Mean
0.20
0.82
0.05
SD
2.28
1.54
0.74
Mean
-0.33
-0.11
-0.23
SD
1.60
0.49
0.68
Mean
0.01
0.24
-0.13
SD
2.21
1.68
1.23
Any Size
-0.17
2.22
0.37
2.04
-0.24
1.41
0.06
2.02
• SD decreases with increasing size
• SD decreases with increasing time to follow-up CT
PVC of Stable Nodules
Mean and standard deviation of percent volume change of 94 stable
nodules by initial size and time to follow-up CT
Time to Follow-up CT (months)
0 - 6 6 - 12 12 - 30
Size (mm)
2-5
5-8
8 - 11
Any Size
Any Interval
Mean
1.15
-0.88
-5.53
SD
10.5
6.02
9.11
Mean
3.54
5.86
-1.02
SD
20.0
12.9
6.29
Mean
-0.17
-3.74
-1.86
SD
25.2
13.1
10.0
Mean
1.98
2.13
-1.56
SD
18.5
10.6
7.47
0.15
9.09
3.98
17.7
-0.35
22.3
1.79
16.1
PVC of Stable Nodules
Mean and standard deviation of percent volume change of 94 stable
nodules by initial size and time to follow-up CT
Time to Follow-up CT (months)
0 - 6 6 - 12 12 - 30
Size (mm)
2-5
5-8
8 - 11
Any Size
Any Interval
Mean
1.15
-0.88
-5.53
SD
10.5
6.02
9.11
Mean
3.54
5.86
-1.02
SD
20.0
12.9
6.29
Mean
-0.17
-3.74
-1.86
SD
25.2
13.1
10.0
Mean
1.98
2.13
-1.56
SD
18.5
10.6
7.47
0.15
9.09
3.98
17.7
-0.35
22.3
1.79
16.1
• SD decreases with increasing size
• SD increases with increasing time to follow-up CT
Malignant Nodules
Monthly volumetric growth index of 10 malignant nodules with initial size,
time to follow-up CT, and histologic diagnosis
Initial
Time to Follow-up
Size (mm)
CT (days)
MVGI (%)
Histologic
Diagnosis
Case
Detection
1
2
3
4
Baseline
Baseline
Baseline
Baseline
9.3
10.4
11.1
8.3
20
32
84
197
51.2
22.0
18.7
7.73
Adenocarcinoma
Squamous Cell
Large Cell
Adenocarcinoma
5
6
7
8
9
10
Repeat
Repeat
Repeat
Repeat
Repeat
Repeat
2.8
10.6
5.1
6.9
7.3
9.8
58
12
33
36
42
34
37.3
36.5
33.3
22.4
5.37
5.01
Adenocarcinoma
Squamous Cell
Adenocarcinoma
Adenocarcinoma
Adenocarcinoma
Large Cell
Comparison of MVGI Values
• All of the stable nodules had values within two
standard deviations of the corresponding
mean value by size, while each of the 10
malignant nodules exceeded that
corresponding value.
Conclusions
• The mean value of MVGI for stable nodules was
0.06% and its standard error was 0.21%.
• All of the stable nodules had values within two
standard deviations of the corresponding mean value
by size, while each of the 10 malignant nodules
exceeded that corresponding value.
• Conclusion: Three-dimensional computer methods
can be used to reliably characterize growth in small
solid pulmonary nodules. Factors affecting the
reproducibility of growth rate estimates include the
initial nodule size, the timing of the follow-up scan, and
the presence of patient-induced or technical artifacts.