1. Combining the strengths of UMIST and The Victoria University of Manchester Tom Williams, Chris Taylor Andrew Holmes, John Waterton, Rose Maciewicz Graham Vincent, Kevin de Souza, Chris Wolstenholme Population Studies of Knee Cartilage Thickness

2. Combining the strengths of UMIST and The Victoria University of Manchester Introduction Background “Focal Analysis of Knee Articular Cartilage Quantity and Quality” 4 th Year of AstraZeneca funded project Published at a number of conferences Mature Methodology Producing Journal Publications Contents Normal Range –Cartilage Thickness in Healthy Female Volunteers Disease Progression –Changes in Cartilage Thickness During Osteoarthritis Talk Objective Generate feedback

3. Combining the strengths of UMIST and The Victoria University of Manchester Normal Range of Cartilage Thickness Volunteers 19 healthy females age range 24-58 Scans 0.625x0.625x1.6mm sagital slices Segmentations (Radiographers) Inter-SiteIntra&Inter-Segmentor ‘N’ ‘S’ 5 TravellersBri: 5×2legs 5patients ×2legs ×3sites ×1repeat = 30 segs. 19patients ×1leg ×1site ×2repeats = 38 segs 19patients ×1leg ×1site ×2repeats = 38 segs Liv: 5×2legs Man: 5×2legs 5 Bristol5×1leg 5 Liverpool5×1leg 4 Manchester4×1leg

4. Combining the strengths of UMIST and The Victoria University of Manchester Methodology – Normal Range Optimal Statistical Shape Model Correspondences Registration Cartilage Thickness Maps Aggregate Thickness Maps Manual Segmentation 3D Surface BoneCartilage Normal Range of Cartilage Coverage and Thickness T1FatSupT2 ToscaEndPoint

5. Combining the strengths of UMIST and The Victoria University of Manchester Normal Range - Coverage Measurement Points –36,780 –1.2mm mean separation –6430 (17%) exhibit 90% cartilage coverage Full coverage on load bearing regions Variation in cartilage boundary Cartilage Coverage

6. Combining the strengths of UMIST and The Victoria University of Manchester Normal Range – Mean(StdDev) Each volunteer given equal weighting Thicker cartilage in load bearing regions Low and consistent standard deviation –Anomalies due to angle of intersection with cartilage Patella Femoral- Patella Medial Femoral Condile Medial Tibia StdDev Mean Thickness

7. Combining the strengths of UMIST and The Victoria University of Manchester Intra-Segmentor Repeatability Blinded segmentations Mean difference between duplicate cartilage segmentations of same images Good intra-segmentor repeatability –Mean 0.06mm ‘S’ Repeatability ‘N’ Repeatability

8. Combining the strengths of UMIST and The Victoria University of Manchester Repeatability Mean difference between segmentors mean thickness maps ‘N’ – ‘S’ ‘N’ tendency to segment thicker tibial and medial condile cartilage Inter-Site Inter- Segmentor ‘N’ single segmentations of travellers Root Mean Square of standard deviation of three image/segmentation pairs Uncertainty in femoral- patellal region

9. Combining the strengths of UMIST and The Victoria University of Manchester Disease Progression Trial 38 Female Osteoarthritis Patients Imaged at baseline and 6 months Duplicate cartilage segmentation by two novice segmentors on EndPoint No change in cartilage volume –Need for focal analysis

10. Combining the strengths of UMIST and The Victoria University of Manchester Disease Progression Methodology AAM Corresponded SurfacesRegistration Difference Maps Aggregate Maps Manual Segmentation 3D Surfaces BoneCartilage Statistical Analysis Automatic Segmentation Image Corresponded Thickness Maps

11. Combining the strengths of UMIST and The Victoria University of Manchester Disease Progression Coverage Coverage: all patients, both time-points Most coverage in load bearing regions Small areas exhibit 100% coverage Medial Femur and Patella particularly prone to cartilage loss Difficult to define region of interest analysis mask Cartilage Coverage Cartilage Coverage (quantised)

12. Combining the strengths of UMIST and The Victoria University of Manchester Inter-Trial Correspondence Normal bone model used to segment diseased bone images Normal coverage illustrated on Disease Mean Shapes Normal 90% coverage used as region of interest mask Normal Range Cartilage Coverage Analysis Region of Interest Mask

13. Combining the strengths of UMIST and The Victoria University of Manchester Mean Cartilage Thickness Baseline and 6 months mean cartilage thickness Thinner than normal range Baseline Mean Cartilage Thickness 6 Months Mean Cartilage Thickness (mm)Mean Normal2.21 Diseased1.89

14. Combining the strengths of UMIST and The Victoria University of Manchester Mean Thickness Change Mean change in thickness for all patients Blue: Thinning Red: Thickening/Swelling Evidence of thinning in Femur condiles and lateral tibia? No obvious pattern of change Mean Change in Cartilage Thickness StdDev of Change in Cartilage Thickness

15. Combining the strengths of UMIST and The Victoria University of Manchester Permutation Tests Perform non-centred Principal Components Analysis on Difference Thickness Maps Compute Mahalanobis distance from origin (no change) to population For n=1000 iterations –Negate the parameters of ½ of the population –Measure Mahalanobis distance to origin Compare permutations and true Mahalanobis distances to origin Provides evidence of real change No spatial information