SPATIO-TEMPORAL ANALYSIS OF THE SIGNIFICANT CHANGES IN

CARTILAGE MORPHOLOGY: DATA FROM THE OSTEOARTHRITIS

INITIATIVEJose Tamez-Pena1, Patricia Gonzalez2, Edward Schreyer2, Saara

Totterman2, 1Biomedicine, Tec de Monterrey, Monterrey, Nuevo Leon, Mexico;

2Qmetrics Technologies, Rochester, NY, USA

Objective

• Visualize, Follow and Quantitate the Areas of Cartilage Loss in an OA population

IntroductionProblem:

• Cartilage Thickness Changes are focal, spatially heterogeneous and bi-directional: Thinning and thickening

• Cohort studies look at population averages• The average of this heterogeneous data

has a very small responsivenessSolution:

• For a subject: Localize and isolate the changes

• For a cohort: Count map of the significant changes in cartilage thickness

Material & Methods

• Osteoarthritis Initiative (OAI) 3D DESS data sets: – Releases 0.C.2, 1.C.2 and 3.C.1 from Progression

cohort.• Three time points: Baseline, 12 month and 24 month.• 138 subjects with 3 time points

– Nonexposed Data Release 0.E.1, 1.E.1 and 3.E.1 (n=108)• Three time points: Baseline, 12 month and 24

month.

– OAI Pilot Scan-Rescan Longitudinal Data for the estimation of scan-rescan variability (n=24)

Multi-Atlas-Based Segmentation• Generate Atlas• Register and Segment Each MRI to the

Atlas (ITK registration modules)• Postprocess the segmentation to

match underlying MRI information.• Visually score the quality of the

segmentation.• Use the registration data to map each

segmentation to the atlas space• Subtract each mapped segmentation

to compute change in cartilage thickness

• Compute Significant Changes• Compute Cohort Averages

Quantitation

Standardized Analysis: Changes in Cartilage Thickness

-0.5 +0.5 -0.5 +0.5

Medial Lateral

Change Measurement: Significant Change Maps

Minus

Change Map

Scan-Rescan SDD MapSignificant Change Map

(Activation Map)

-0.5 +0.5

0.0 +0.5

-0.5 +0.5

-0.5 +0.5

Baseline24 Month

-0.75 +0.75-0.5 +0.5

=

The Scan-RescanStandard Deviation of the Differences (SDD) is used to mark changes in thickness values that higher than the scan-rescan paired errors ( Delta < -1.96*SDD )

Population Maps

Average ReferencedThickness

12 Month Change Map

24 Month Change Maps

Average Change Map

Significant ChangesPrevalence Map

-0.5 +0.5 -0.5 +0.5

0.0 0.3 0.0 0.3

-0.5 +0.5

+ =

24 Month Results

-0.25

+0.25

0.0

0.3

-0.5

+0.5

Nonexposed No Denuded Low Denuded High Denuded

n=103 n=51 n=43 n=43 20.6%

9.3%8.1% 11.6%

17.3% 14.7%

3.4%

6.8%

Baseline

24 MonthChange

24 MonthHeat Map

-0.5

+0.5

Nonexposed No-Denuded Low Denuded High Denuded

12M-BL 3.6% 5.4% 7.1% 9.1%

24M-BL 3.4% 7.8% 8.6% 11.0%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

Rela

tive

Area

Average Area of Femur Affected by Significant Changes

SRM=0.73P<0.001 P=0.007 P=0.054SRM=0.36

SRM=0.36

SRM=0.39

Nonexposed No-Denuded Low Denuded High Denuded

12M-BL 4.3% 5.9% 7.50% 8.20%

24M-BL 4.6% 7.9% 8.80% 9.50%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%Re

lativ

e Ar

ea

Average Area of Tibia Affected by Significant Changes

P<0.001

SRM=0.31

Nonexposed No Denuded Low Denuded High Denuded

12M-BL 22.3% 43.1% 76.7% 88.8%

24M-BL 19.4% 58.9% 76.7% 93.0%

0.0%10.0%20.0%30.0%40.0%50.0%60.0%70.0%80.0%90.0%

100.0%

Prop

ortio

n of

Sub

ject

s

Proportion of Subjects Whose Significant Changes were Greater Than

5% of the Femur Area

P=0.009 P=0.001

No Exposed No Denuded Low Denuded High Denuded

12M-BL 35.0% 51.0% 72.1% 72.1%

24M-BL 37.9% 56.9% 74.4% 67.4%

0.0%10.0%20.0%30.0%40.0%50.0%60.0%70.0%80.0%90.0%

100.0%Pr

opor

tion

of s

ubje

cts

Proportion of Subjects Whose Significant Changes were Greater Than

5% of the Tibia Area

P=0.038

Fisher’s Exact Test

Limitations

• Small OA population• Multi-atlas based segmentation is biased

towards atlas models– Less accurate at advanced OA cases– Higher noise at advanced OA cases

Conclusion

• The automated analysis methodology enabled the localization and mapping of the significant changes in cartilage Thickness.

• The significant changes are heterogeneous– Non Exposed OAI cohort did not change– OA subjects with no denuded areas had 2.4% of new

areas of cartilage loss every year. SRM=0.73

• The methodology indicated that not all subjects are affected by loss, and that the prevalence of loss is greater at more advanced OA groups.

Acknowledgements

• The OAI for all the imaging and clinical data

-0.5 +0.5 -0.5 +0.5

Baseline 24 Month Change Map

Change Measurement: Significant Change Maps

-0.75 +0.75