Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 months' observation using advanced image analysis of 3T MRI?

D. J. Hunter, M. A. Bowes, C. B. Eaton, A. P. Holmes, H. Mann, Chian K Kwoh, R. A. Maciewicz, J. Samuels, J. C. Waterton

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose: Prior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1-2 years duration. We hypothesized that smaller, shorter duration, "Proof of Concept" (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3. T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur. Methods: Multi-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren-Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness - ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF-ThCtAB), with changes in other regions considered as secondary endpoints. Results: Anatomical mal-alignment ranged from -1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF-ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was -2.1% [95% confidence interval (CI) (-4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (-2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT-ThCtAB) at 6 month follow-up (-1.5%, 95% CI [-2.9, -0.2]), but was not significant at the 5% level after correction for multiple comparisons. Conclusions: The small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed.

Original languageEnglish (US)
Pages (from-to)677-683
Number of pages7
JournalOsteoarthritis and Cartilage
Volume18
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

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Knee Osteoarthritis
Cartilage
Magnetic resonance
Image analysis
Magnetic Resonance Imaging
Observation
Imaging techniques
Thigh
Confidence Intervals
Knee
Biomarkers
Analysis of variance (ANOVA)
Analysis of Variance
Body Mass Index
Bone and Bones
Statistical Models
Tibia
Osteoarthritis
Femur
Magnetic resonance imaging

Keywords

  • Cartilage thickness
  • Magnetic resonance imaging
  • Osteoarthritis

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 months' observation using advanced image analysis of 3T MRI? / Hunter, D. J.; Bowes, M. A.; Eaton, C. B.; Holmes, A. P.; Mann, H.; Kwoh, Chian K; Maciewicz, R. A.; Samuels, J.; Waterton, J. C.

In: Osteoarthritis and Cartilage, Vol. 18, No. 5, 05.2010, p. 677-683.

Research output: Contribution to journalArticle

Hunter, D. J. ; Bowes, M. A. ; Eaton, C. B. ; Holmes, A. P. ; Mann, H. ; Kwoh, Chian K ; Maciewicz, R. A. ; Samuels, J. ; Waterton, J. C. / Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 months' observation using advanced image analysis of 3T MRI?. In: Osteoarthritis and Cartilage. 2010 ; Vol. 18, No. 5. pp. 677-683.
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abstract = "Purpose: Prior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1-2 years duration. We hypothesized that smaller, shorter duration, {"}Proof of Concept{"} (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3. T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur. Methods: Multi-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren-Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness - ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF-ThCtAB), with changes in other regions considered as secondary endpoints. Results: Anatomical mal-alignment ranged from -1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5{\%} level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF-ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was -2.1{\%} [95{\%} confidence interval (CI) (-4.4{\%}, +0.2{\%})]. The change over 6 months was 0.0{\%} [95{\%} CI (-2.7{\%}, +2.8{\%})]. The 95{\%} CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT-ThCtAB) at 6 month follow-up (-1.5{\%}, 95{\%} CI [-2.9, -0.2]), but was not significant at the 5{\%} level after correction for multiple comparisons. Conclusions: The small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed.",
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author = "Hunter, {D. J.} and Bowes, {M. A.} and Eaton, {C. B.} and Holmes, {A. P.} and H. Mann and Kwoh, {Chian K} and Maciewicz, {R. A.} and J. Samuels and Waterton, {J. C.}",
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TY - JOUR

T1 - Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 months' observation using advanced image analysis of 3T MRI?

AU - Hunter, D. J.

AU - Bowes, M. A.

AU - Eaton, C. B.

AU - Holmes, A. P.

AU - Mann, H.

AU - Kwoh, Chian K

AU - Maciewicz, R. A.

AU - Samuels, J.

AU - Waterton, J. C.

PY - 2010/5

Y1 - 2010/5

N2 - Purpose: Prior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1-2 years duration. We hypothesized that smaller, shorter duration, "Proof of Concept" (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3. T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur. Methods: Multi-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren-Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness - ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF-ThCtAB), with changes in other regions considered as secondary endpoints. Results: Anatomical mal-alignment ranged from -1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF-ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was -2.1% [95% confidence interval (CI) (-4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (-2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT-ThCtAB) at 6 month follow-up (-1.5%, 95% CI [-2.9, -0.2]), but was not significant at the 5% level after correction for multiple comparisons. Conclusions: The small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed.

AB - Purpose: Prior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1-2 years duration. We hypothesized that smaller, shorter duration, "Proof of Concept" (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3. T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur. Methods: Multi-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren-Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness - ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF-ThCtAB), with changes in other regions considered as secondary endpoints. Results: Anatomical mal-alignment ranged from -1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF-ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was -2.1% [95% confidence interval (CI) (-4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (-2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT-ThCtAB) at 6 month follow-up (-1.5%, 95% CI [-2.9, -0.2]), but was not significant at the 5% level after correction for multiple comparisons. Conclusions: The small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed.

KW - Cartilage thickness

KW - Magnetic resonance imaging

KW - Osteoarthritis

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