MRI texture analysis of acetabular cancellous bone can discriminate between normal, cam positive, and cam-FAI hips.

OBJECTIVES: To compare the MRI texture profile of acetabular subchondral bone in normal, asymptomatic cam positive, and symptomatic cam-FAI hips and determine the accuracy of a machine learning model for discriminating between the three hip classes. METHODS: A case-control, retrospective study was performed including 68 subjects (19 normal, 26 asymptomatic cam, 23 symptomatic cam-FAI). Acetabular subchondral bone of unilateral hip was contoured on 1.5 T MR images. Nine first-order 3D histogram and 16 s-order texture features were evaluated using specialized texture analysis software. Between-group differences were assessed using Kruskal-Wallis and Mann-Whitney U tests, and differences in proportions compared using chi-square and Fisher's exact tests. Gradient-boosted ensemble methods of decision trees were created and trained to discriminate between the three groups of hips, with percent accuracy calculated. RESULTS: Sixty-eight subjects (median age 32 (28-40), 60 male) were evaluated. Significant differences among all three groups were identified with first-order (4 features, all p ≤ 0.002) and second-order (11 features, all p ≤ 0.002) texture analyses. First-order texture analysis could differentiate between control and cam positive hip groups (4 features, all p ≤ 0.002). Second-order texture analysis could additionally differentiate between asymptomatic cam and symptomatic cam-FAI groups (10 features, all p ≤ 0.02). Machine learning models demonstrated high classification accuracy of 79% (SD 16) for discriminating among all three groups. CONCLUSION: Normal, asymptomatic cam positive, and cam-FAI hips can be discriminated based on their MRI texture profile of subchondral bone using descriptive statistics and machine learning algorithms. CLINICAL RELEVANCE STATEMENT: Texture analysis can be performed on routine MR images of the hip and used to identify early changes in bone architecture, differentiating morphologically abnormal from normal hips, prior to onset of symptoms. KEY POINTS: • MRI texture analysis is a technique for extracting quantitative data from routine MRI images. • MRI texture analysis demonstrates that there are different bone profiles between normal hips and those with femoroacetabular impingement. • Machine learning models can be used in conjunction with MRI texture analysis to accurately differentiate between normal hips and those with femoroacetabular impingement.

CT texture analysis of acetabular subchondral bone can discriminate between normal and cam-positive hips.

OBJECTIVES: The purpose of this study was to determine if the CT texture profile of acetabular subchondral bone differs between normal, asymptomatic cam-positive, and symptomatic cam-FAI hips. In addition, the utility of texture analysis to discriminate between the three hip statuses was explored using a machine learning approach. METHODS: IRB-approved, case-control study analyzing CT images in subjects with and without cam morphology from August 2010 to December 2013. Sixty-eight subjects were included: 19 normal controls, 26 asymptomatic cam, and 23 symptomatic cam-FAI. Acetabular subchondral bone was contoured on the sagittal oblique CT images using ImageJ ®. 3D histogram texture features (mean, variance, skewness, kurtosis, and percentiles) were evaluated using MaZda software. Groupwise differences were investigated using Kruskal-Wallis tests and Mann-Whitney U tests. Gradient-boosted decision trees were created and trained to discriminate between control and cam-positive hips. RESULTS: Both asymptomatic and symptomatic cam-FAI hips demonstrated significantly higher values of texture variance (p = 0.0007, p < 0.0001), 90th percentile (p = 0.007, p = 0.006), and 99th percentile (p = 0.009, p = 0.009), but significantly lower values of skewness (p = 0.0001, p = 0.0013) and kurtosis (p = 0.0001, p = 0.0001) compared to normal controls. There were no differences in texture profile between asymptomatic cam and symptomatic cam-FAI hips. Machine learning models demonstrated high classification accuracy for discriminating control hips from asymptomatic cam-positive (82%) and symptomatic cam-FAI (86%) hips. CONCLUSIONS: Texture analysis can discriminate between normal and cam-positive hips using conventional descriptive statistics, regression modeling, and machine learning algorithms. It has the potential to become an important tool in compositional analysis of hip subchondral trabecular bone in the context of FAI, and possibly serve as a biomarker of joint degeneration. KEY POINTS: • The CT texture profile of acetabular subchondral bone is significantly different between normal and cam-positive hips. • Texture analysis can detect changes in subchondral bone in asymptomatic cam-positive hips that are equal to that of symptomatic cam-FAI hips. • Texture analysis has the potential to become an important tool in compositional analysis of hip subchondral bone in the context of FAI and may serve as a biomarker in the study of joint physiology and biomechanics.

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial.

BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. FUNDING: Cancer Research UK, NIHR, MRC.