Nomograms combining computed tomography-based body composition changes with clinical prognostic factors to predict survival in locally advanced cervical cancer patients.

OBJECTIVE: To explore the value of body composition changes (BCC) measured by quantitative computed tomography (QCT) for evaluating the survival of patients with locally advanced cervical cancer (LACC) underwent concurrent chemoradiotherapy (CCRT), nomograms combined BCC with clinical prognostic factors (CPF) were constructed to predict overall survival (OS) and progression-free survival (PFS). METHODS: Eighty-eight patients with LACC were retrospectively selected. All patients underwent QCT scans before and after CCRT, bone mineral density (BMD), subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), paravertebral muscle area (PMA) were measured from two sets of computed tomography (CT) images, and change rates of these were calculated. RESULTS: Multivariate Cox regression analysis showed ΔBMD, ΔSFA, SCC-Ag, LNM were independent factors for OS (HR = 3.560, 5.870, 2.702, 2.499, respectively, all P < 0.05); ΔPMA, SCC-Ag, LNM were independent factors for PFS (HR = 2.915, 4.291, 2.902, respectively, all P < 0.05). Prognostic models of BCC combined with CPF had the highest predictive performance, and the area under the curve (AUC) for OS and PFS were 0.837, 0.846, respectively. The concordance index (C-index) of nomograms for OS and PFS were 0.834, 0.799, respectively. Calibration curves showed good agreement between the nomograms' predictive and actual OS and PFS, decision curve analysis (DCA) showed good clinical benefit of nomograms. CONCLUSION: CT-based body composition changes and CPF (SCC-Ag, LNM) were associated with survival in patients with LACC. The prognostic nomograms combined BCC with CPF were able to predict the OS and PFS in patients with LACC reliably.

Correlation between musculoskeletal mass and perfusion in patients with gastrointestinal malignancy: a preliminary study based on quantitative CT and CT perfusion.

BACKGROUND: To investigate the correlation between musculoskeletal mass and perfusion using quantitative computer tomography (QCT) and CT perfusion (CTP) in patients with gastrointestinal malignancy. METHODS: In this prospective study, 96 patients (mean age 66 years, range 25-90; 63.5% male) with gastrointestinal malignancy underwent QCT and CTP between May 2019 and February 2021. Bone mineral density (BMD) and body composition [perivertebral muscular mass index (PMI), skeletal muscular mass index (SMI) and muscular fat fraction] were evaluated through QCT. Musculoskeletal perfusion parameters were measured by CTP. Differences in these parameters between (or among) two (or three) groups (grouped by BMD, SMI, and TNM staging) were analyzed. RESULTS: There were significant differences in PMI and muscular fat fraction among normal (n = 30), osteopenia (n = 43), and osteoporosis (n = 23) groups (both P < 0.001). Blood flow (r = 0.336, P = 0.001; adjusted for age and gender, r = 0.383, P < 0.001), blood volume (r = 0.238, P = 0.011; adjusted for age and gender, r = 0.329, P = 0.001), and flow extraction product (r = 0.217, P = 0.034; adjusted for age and gender, r = 0.320, P = 0.002) vaules of vertebral perfusion showed positive correlation with BMD. However, the relationships between PMI and perfusion parameters of perivertebral muscle were not significant. No significant differences were found in musculoskeletal mass and perfusion parameters between different TNM staging. CONCLUSIONS: The changes of bone mass and perivertebral muscular mass in patients with gastrointestinal malignancy are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscular mass, increased muscular fat, and decreased bone perfusion. However, the changes of perfusion in vertebra and perivertebral muscles are asynchronous. Musculoskeletal mass and perfusion have no correlation with TNM staging of the patients with gastrointestinal malignancy. TRIAL REGISTRATION: SHSY-IEC-4.1/20-242/01 (Registered 09-12-2020, Retrospectively registered).

Quantitative Computed Tomography (QCT) of the Distal Forearm in Men Using a Spiral Whole-Body CT Scanner - Description of a Method and Reliability Assessment of the QCT Pro Software.

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.

Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (ß-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Improving bone strength prediction in human proximal femur specimens through geometrical characterization of trabecular bone microarchitecture and support vector regression.

We investigate the use of different trabecular bone descriptors and advanced machine learning tech niques to complement standard bone mineral density (BMD) measures derived from dual-energy x-ray absorptiometry (DXA) for improving clinical assessment of osteoporotic fracture risk. For this purpose, volumes of interest were extracted from the head, neck, and trochanter of 146 ex vivo proximal femur specimens on multidetector computer tomography. The trabecular bone captured was characterized with (1) statistical moments of the BMD distribution, (2) geometrical features derived from the scaling index method (SIM), and (3) morphometric parameters, such as bone fraction, trabecular thickness, etc. Feature sets comprising DXA BMD and such supplemental features were used to predict the failure load (FL) of the specimens, previously determined through biomechanical testing, with multiregression and support vector regression. Prediction performance was measured by the root mean square error (RMSE); correlation with measured FL was evaluated using the coefficient of determination R2. The best prediction performance was achieved by a combination of DXA BMD and SIM-derived geometric features derived from the femoral head (RMSE: 0.869 ± 0.121, R2: 0.68 ± 0.079), which was significantly better than DXA BMD alone (RMSE: 0.948 ± 0.119, R2: 0.61 ± 0.101) (p < 10-4). For multivariate feature sets, SVR outperformed multiregression (p < 0.05). These results suggest that supplementing standard DXA BMD measurements with sophisticated femoral trabecular bone characterization and supervised learning techniques can significantly improve biomechanical strength prediction in proximal femur specimens.

Comparisons of Hounsfield units and volumetric bone density in discriminating vertebral fractures on lumbar CT scans.

OBJECTIVES: To compare the performance of areal Hounsfield units (aHUs), volumetric Hounsfield units (vHUs), and volumetric bone mineral density (vBMD) by quantitative CT (QCT) in discriminating vertebral fractures (VFs) risk. METHODS: We retrospectively included CT scans of the lumbar spine 101 VFs cases (60 women, mean age: 64 ± 4 years; 41 men, mean age: 73 ± 10 years) and sex- and age-matched 101 control subjects (60 women, mean age: 64 ± 4 years; 41 men, mean age: 72 ± 7 years). In order to assess the discriminatory capability of aHU, vHU, and vBMD measurements at the L1 and L2 levels in identifying VFs, we conducted binary logistic regression and receiver operating characteristic (ROC) curve analyses in men and women. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: In both men and women with and without VFs, aHU, vHU, and vBMD were highly correlated with each other (r2 from 0.832 to 0.957, all P < .001). There was a statistically significant difference in aHU, vHU, and vBMD between subjects with and without VFs (P < .001). When age, gender, and BMI were taken into account as covariances and adjusted simultaneously, odds ratios (ORs) for aHU, vHU, and vBMD values, which represent the risk of VFs, were significant (P < .001). Compared with aHU and vHU, vBMD was more strongly associated with VF risk (vBMD: OR, 6.29; 95% CI, 3.83-10.35 vs vHU: OR, 3.64; 95% CI, 2.43-5.46 vs aHU: OR, 2.56; 95% CI, 1.79-3.67). In both men and women, further, vBMD had higher values for AUC, sensitivity, specificity, PPV, and NPV compared to vHU, with vHU in turn surpassing aHU. The area under the receiver operating characteristic curve (AUC) for discriminating VFs using the average aHU, vHU, and vBMD of 2 vertebrae was 0.72, 0.77, and 0.87 in men and 0.76, 0.79, and 0.86 in women. In both men and women, there exist statistically significant differences in the AUC when employing the 3 measurements-namely, aHU, vHU, and vBMD-to discriminate fractures (P < .05). CONCLUSIONS: The QCT-measured vBMD is more associated with acute VFs than vHU and aHU values of the lumbar spine. Although the use of vHU and aHU values for the diagnosis of osteoporosis and discriminating fracture risk is limited to scanner- and imaging protocol-specific, they have great potential for opportunistic osteoporosis screening, particularly vHU. ADVANCES IN KNOWLEDGE: The novelty of this study presents a comparison of the VF discriminative capabilities among aHU, vHU, and vBMD. The vHU values introduced in this study demonstrate a greater capacity to discriminate fractures compared to aHU, presenting an improved clinical choice. Although its discriminatory capability is slightly lower than that of vBMD, it is more convenient to measure and does not require specialized software.

MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease.

Objectives: Quantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years. Methods: Fully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2-13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8-103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5-10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5-10, BEI and A3 cross-sectionally and longitudinally. Results: WP5-10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28-0.7) to 0.54 (0.36-0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5-10 and A3 at each timepoint (P < 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003). Conclusions: Robust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.

Combination of vertebral bone quality scores from different magnetic resonance imaging sequences improves prognostic value for the estimation of osteoporosis.

BACKGROUND CONTEXT: Recent findings revealed a correlation between vertebral bone quality based on T1-weighted (VBQT1) magnetic resonance imaging (MRI) and volumetric bone mass density (vBMD) measured using quantitative computerized tomography. The coherence of VBQ for other MRI sequences, such as T2 or short tau inversion recovery (STIR), has not been examined. The combination of different VBQs has not been studied. PURPOSE: The aims of the study were to confirm the correlation between VBQT1 and vBMD and to examine VBQs from other MRI sequences and their combination with vBMD. STUDY DESIGN/SETTING: This was a retrospective cross-sectional study. PATIENT SAMPLE: The sample consisted of patients older than 18 years, who received treatment at a level-one university spine center of the German Spine Society for degenerative or traumatic reasons in 2017-2021. OUTCOME MEASURES: The outcome measures were the correlation of VBQs from different MRI sequences with vBMD and the association of VBQs with osteopenia/osteoporosis. METHODS: Patients' VBQ was calculated based on the signal intensities of the vertebral bodies L1-4 in T1-, T2-, and STIR-weighted MRI. The VBQ was standardized according to the signal intensity of the cerebrospinal fluid. The vBMD was determined using data from a calibrated scanner (SOMATOM Definition AS+) and processed with CliniQCT (Mindways Software, Inc., USA). Groups were divided according to vBMD into the following groups: (I) osteoporosis/osteopenia (< 120 mg/m3) and (II) healthy (≥120 mg/m3). An analysis of the correlation between various VBQs and vBMD as well as receiver operating characteristic (ROC) and binary regression analyses were performed for the prediction of osteoporosis/osteopenia. RESULTS: We included 136 patients (women: 56.6%) in the study (69.7 ± 15.0 years). According to vBMD, 108 patients (79.4%) had osteoporosis/osteopenia. Women were affected significantly more often than men (p = .045) and had significantly higher VBQT1 and VBQT2 values than men (VBQT1: p = .048; VBQT2: p = .013). VBQT1 and VBQT2 values were significantly higher in patients with osteoporosis/osteopenia than in healthy persons (VBQT1: p<.001; VBQT2: p = .025). VBQT1 and VBQT2 were significantly negatively correlated with vBMD with a moderate effect size (p<.001), while VBQSTIR was not significantly correlated with vBMD, although it showed a positive coherence. The combination of different VBQs in terms of VBQT1 × VBQT2 / VBQSTIR distinctly increased the effect size of the negative correlation with vBMD compared to VBQ alone. A cutoff value for VBQT1 × VBQT2 / VBQSTIR of 2.9179 achieved a sensitivity of 80.0%, a specificity of 75.0%, and an area under the curve (AUC) of 0.775 for the determination of osteoporosis. The mathematical model derived from the binary logistic regression showed an excellent AUC of 0.846. CONCLUSIONS: This study confirms a significant correlation between VBQT1 and vBMD. The combination of VBQs from different MRI sequences enhances the prognostic value of VBQ for the determination of osteoporosis. While safe clinical application of VBQ for the determination of osteoporosis requires further validation, VBQ might offer opportunistic estimation for further diagnostics.

The Role of Imaging in Predicting the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) remains a chronic debilitating disease with a significant negative societal impact, despite the expanding landscape of treatment options. This condition is often preceded by a phase of systemic autoimmunity with circulating autoantibodies, elevated pro-inflammatory cytokines, or subtle structural changes. The capability of identifying individuals in the preclinical phase of RA disease makes a "preventive window of opportunity" possible. Much recent work has focused on the role of imaging modalities including ultrasound (US), magnetic resonance imaging (MRI), and high-resolution peripheral quantitative computer tomography (HR-pQCT) in identifying at-risk individuals with or without early joint symptoms for the development of inflammatory arthritis. This article will review the evidence and discuss the challenges as well as opportunities of proactive risk assessment by imaging in RA.

Anatomical factors associated with femoral neck fractures of elderly Beijing women.

Analyses using newly developed structural measures of minimal model (aBMD, W, Sigma, Delta) in a Chinese female age-matched cohort of femoral neck fracture patients and non-fracture community controls resulted in improved fracture prediction, suggesting the usefulness of new variables, extending the value of widely available DXA technology. INTRODUCTION: We have developed a new approach to evaluate 2D femoral neck (FN) structure, the minimal model (MM). This model includes FNaBMD and FNWidth with two new internal structural measures, the standard deviation of normalized mineral mass projection profile distribution (FNSigma) and the displacement between center of mineral (CoM) mass and geometric center of mineral mass projection profile (FNDelta). METHODS: Differences in these four structural measurements together with age, weight, and height were compared in the contralateral hip of 285 FN fracture Chinese female patients and 261 age-matched community controls. Structural variables were calculated from DXA equivalent 2D images obtained from QCT scans analyzed using Mindways Software. RESULTS: Review of FN scanned profiles of fracture patients and controls identified substantial reduction in mineral mass in the superior segment of FN. Fracture participants were taller, weighed less, and had lower FNaBMD and larger FNDelta, due to a larger inferior displacement in the CoM, consistent with greater reduction in superior segment bone. Logistic regression identified increased height, reduced FNaBMD, increased FNDelta, and reduced FNSigma per SD as significant independent contributors to differentiating fracture from non-fracture. Area under ROC analysis identified significant improvement in discrimination with the addition of FNDelta and FNSigma to the model including age, height, weight, and FNaBMD (C statistic 0.87 and 0.84 respectively). CONCLUSIONS: These data extend previous data that identified the benefit of 2D FN internal structural information in discriminating those at increased future fracture risk from recently fractured individuals. These data support continuing investigation of MM analysis as a straightforward analytical approach adding value to DXA hip aBMD in predicting fracture risk.

pQCT bone geometry and strength: population epidemiology and concordance in Australian children aged 11-12 years and their parents.

OBJECTIVES: To describe the epidemiology and concordance of bone health in a population-based sample of Australian parent-child dyads at child age 11-12 years. DESIGN: Population-based cross-sectional study (the Child Health CheckPoint) nested between waves 6 and 7 of the Longitudinal Study of Australian Children (LSAC). SETTING: Assessment centres in seven cities around Australia, February 2015-March 2016. PARTICIPANTS: of all participating CheckPoint families (n=1874), bone data were available for 1222 dyads (1271 children, 50% girls; 1250 parents, 86% mothers). OUTCOME MEASURES: Peripheral quantitative CT (pQCT) of the non-dominant leg scanned at the 4% (distal) and 66% (mid-calf) tibial sites. Stratec XCT 2000 software generated estimates of bone density, geometry and polar stress-strain index.Parent-child concordance were assessed using Pearson's correlation coefficients and multivariable linear regression models. Percentiles were determined using survey weights. Survey weights and methods accounted for LSAC's complex sampling, stratification and clustering within postcodes. RESULTS: Concordances were greater for the geometric pQCT parameters (periosteal circumference 0.38, 95% CI 0.33 to 0.43; endosteal circumference 0.42, 95% CI 0.37 to 0.47; total cross-sectional area 0.37, 95% CI 0.32 to 0.42) than density (cortical density 0.25, 95% CI 0.19 to 0.30). Mother-child and father-child values were similar. Relationships attenuated only slightly on adjustment for age, sex and body mass index. Percentiles and concordance are presented for the whole sample and by sex. CONCLUSIONS: There is strong parent-child concordance in bone geometry and, to a lesser extent, density even before the period of peak adolescent bone deposition. This geometrical concordance suggests that future intergenerational bone studies could consider using pQCT rather than the more commonly used dual X-ray absorptiometry (DXA).

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

BACKGROUND: Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. METHODS: Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. RESULTS: During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. CONCLUSION: Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD.

Assessing Osteoporosis in the Young Adult.

Osteoporosis in the young adult is a relatively rare phenomenon, and its diagnosis needs careful assessment of the affected person. The emphasis in the assessment of bone health is gradually shifting from a simple quantitative assessment of bone mineral density to one that includes bone quality. This may be particularly important in the young adult, where the aetiological cause of osteoporosis may be a primary genetic condition or secondary to another chronic condition.