Post-contrast CT liver attenuation alone is superior to the liver-spleen difference for identifying moderate hepatic steatosis.

OBJECTIVE: To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values. MATERIALS AND METHODS: A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis. RESULTS: The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver-spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver-spleen difference of -40 HU and -10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate-severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001). CONCLUSION: Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less. CLINICAL RELEVANCE STATEMENT: Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection. KEY POINTS: The liver-spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver-spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older East Asian women should be lower than the value for Caucasians.

For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.

East Asians' T-scores for the diagnosis of osteoporosis should be calculated using ethnicity- and gender-specific BMD reference ranges: justifications.

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.

Inter-rater variability and repeatability in the assessment of the Tanner-Whitehouse classification of hand radiographs for the estimation of bone age.

OBJECTIVE: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method. MATERIALS AND METHODS: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency. RESULTS: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates. CONCLUSION: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

The association of lumbar disc degeneration with lumbar vertebral trabecular volumetric bone mineral density in an urban population of young and middle-aged community-dwelling Chinese adults: a cross-sectional study.

INTRODUCTION: Lumbar intervertebral disc degeneration (LDD) and osteoporosis (OP) are age-related conditions that induce low back pain and have an impact on quality of life. The relationship between LDD and changes in bone mineral density (BMD) is, however, contentious and ever-changing. The purpose of this study is to investigate the relationship between lumbar vertebral volumetric BMD (vBMD) and LDD in an urban population of young and middle-aged community-dwelling Chinese adults. MATERIALS AND METHODS: 719 participants were recruited from among the subjects enrolled in a 10-year longitudinal study of degeneration of the spine and knee being conducted at the Beijing Jishuitan Hospital. The severity of LDD was graded using the five-grade Pfirrmann classification, and lumbar vertebral vBMD was measured using quantitative computed tomography (QCT). The relationship between the grade of intervertebral disc degeneration and lumbar vertebral vBMD was analyzed, and multiple linear regression was performed to adjust for covariates. RESULTS: The mean lumbar vBMD decreased as the grade of LDD increased (171.5 g/cm3, 147.8 g/cm3, and 124.3 g/cm3, respectively; P < 0.001). After adjusting for age, a higher LDD stage was associated with a lower mean L2-L4 vBMD, although a statistically significant correlation was observed only in men (standardized coefficient ß = - 0.656, P = 0.004). In men, there was a negative correlation between single-vertebra vBMD and degeneration of adjacent intervertebral discs, particularly those involving the L3 vertebra (L2-3 disc: ß = - 0.333, P < 0.001, L3-4 disc: ß = - 0.398, P < 0.001), as well as the mean grade of the L2-4 discs (ß = - 0.448, P < 0.001). However, the L5-S1 disc had a smaller correlation with age than others, and no statistically significant associations with lumbar vBMD were observed in either men (ß = - 0.024, P = 0.729) or women (ß = - 0.057, P = 0.396). CONCLUSION: Our study found that the degree of LDD was negatively associated with lumbar trabecular vBMD, although (excepting the L5-S1 disc), the relationship was statistically significant only in men.

Detection of Moderate Hepatic Steatosis on Portal Venous Phase Contrast-Enhanced CT: Evaluation Using an Automated Artificial Intelligence Tool.

BACKGROUND. Precontrast CT is an established means of evaluating for hepatic steatosis; postcontrast CT has historically been limited for this purpose. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of portal venous phase postcontrast CT in detecting at least moderate hepatic steatosis using liver and spleen attenuation measurements determined by an automated artificial intelligence (AI) tool. METHODS. This retrospective study included 2917 patients (1381 men, 1536 women; mean age, 56.8 years) who underwent a CT examination that included at least two series through the liver. Examinations were obtained from an AI vendor's data lake of data from 24 centers in one U.S. health care network and 29 centers in one Israeli health care network. An automated deep learning tool extracted liver and spleen attenuation measurements. The reference for at least moderate steatosis was precontrast liver attenuation of less than 40 HU (i.e., estimated liver fat > 15%). A radiologist manually reviewed examinations with outlier AI results to confirm portal venous timing and identify issues impacting attenuation measurements. RESULTS. After outlier review, analysis included 2777 patients with portal venous phase images. Prevalence of at least moderate steatosis was 13.9% (387/2777). Patients without and with at least moderate steatosis, respectively, had mean postcontrast liver attenuation of 104.5 ± 18.1 (SD) HU and 67.1 ± 18.6 HU (p < .001); a mean difference in postcontrast attenuation between the liver and the spleen (hereafter, postcontrast liver-spleen attenuation difference) of -7.6 ± 16.4 (SD) HU and -31.8 ± 20.3 HU (p < .001); and mean liver enhancement of 49.3 ± 15.9 (SD) HU versus 38.6 ± 13.6 HU (p < .001). Diagnostic performance for the detection of at least moderate steatosis was higher for postcontrast liver attenuation (AUC = 0.938) than for the postcontrast liver-spleen attenuation difference (AUC = 0.832) (p < .001). For detection of at least moderate steatosis, postcontrast liver attenuation had sensitivity and specificity of 77.8% and 93.2%, respectively, at less than 80 HU and 90.5% and 78.4%, respectively, at less than 90 HU; the postcontrast liver-spleen attenuation difference had sensitivity and specificity of 71.4% and 79.3%, respectively, at less than -20 HU and 87.0% and 62.1%, respectively, at less than -10 HU. CONCLUSION. Postcontrast liver attenuation outperformed the postcontrast liver-spleen attenuation difference for detecting at least moderate steatosis in a heterogeneous patient sample, as evaluated using an automated AI tool. Splenic attenuation likely is not needed to assess for at least moderate steatosis on postcontrast images. CLINICAL IMPACT. The technique could promote early detection of clinically significant nonalcoholic fatty liver disease through individualized or large-scale opportunistic evaluation.

Hepatic Steatosis: CT-Based Prevalence in Adults in China and the United States and Associations With Age, Sex, and Body Mass Index.

BACKGROUND. Calibrated CT fat fraction (FFCT) measurements derived from un-enhanced abdominal CT reliably reflect liver fat content, allowing large-scale population-level investigations of steatosis prevalence and associations. OBJECTIVE. The purpose of this study was to compare the prevalence of hepatic steatosis, as assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). METHODS. This retrospective study included 3176 adults (1985 women and 1191 men) from seven Chinese provinces and 8748 adults (4834 women and 3914 men) from a single U.S. medical center, all drawn from previous studies. All participants were at least 40 years old and had undergone unenhanced abdominal CT in previous studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT measurements. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0-14.9%, 15.0-24.9%, and 25.0% or more, respectively. The two cohorts were compared. RESULTS. In the Chinese and U.S. cohorts, the median adjusted FFCT for women was 4.7% and 4.8%, respectively, and that for men was 5.8% and 6.2%, respectively. In the Chinese and U.S. cohorts, steatosis prevalence for women was 46.3% and 48.7%, respectively, whereas that for men was 58.9% and 61.9%, respectively. Severe steatosis prevalence was 0.9% and 1.8% for women and 0.2% and 2.6% for men in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades among women or men in the Chinese cohort, although it increased across age decades among women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r = 0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts, respectively, had mild steatosis, and 3.0% and 1.5% of those in the Chinese and U.S. cohorts, respectively, had moderate or severe steatosis. Among U.S. participants with a BMI of 40.0 or greater, 17.7% had normal liver content. CONCLUSION. Steatosis and severe steatosis had higher prevalence in the U.S. cohort than in the Chinese cohort in both women and men. BMI did not reliably predict steatosis. CLINICAL IMPACT. The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Accuracy, Linearity and Precision of Spine QCT vBMD Phantom Measurements for Different Brands of CT Scanner: A Multicentre Study.

We describe a multicenter study using the European Spine Phantom (ESP) to compare the accuracy, linearity and precision of QCT measurements of spine vBMD between different brands of scanner, different models of the same brand and identical units of the same model. Ten scans of the same ESP with repositioning were performed on forty CT scanners from five manufacturers in different hospitals across China, all calibrated with the Mindways QCT system. The three ESP vertebral bodies simulating low (L1), medium (L2) and high (L3) vBMD and their average (L1-3 vBMD) were compared with phantom values. Linearity was assessed using the standard error of the estimate derived from linear regression. Precision errors were expressed as the standard deviation of the ten measurements on each scanner. Median (IQR) vBMD over all forty CT scanners compared with phantom values were: L1: 52.2 (49.9-56.4) vs 51.0; L2: 104.4 (101.2-108.6) vs 102.2; L3: 201.4 (195.0-204.9) vs 200.4; L1-3: 119.3 (116.6-123.2) vs 117.9 mg/cm3. Statistically significant differences in L1-3 vBMD were found between different brands (p= 0.005) and between different models of the same brand and identical units of the same model (both p< 0.001). Cross-calibration using linear regression gave a good fit for all forty systems with a median standard error of the estimate of 1.7 mg/cm3. The median precision error for L1-3 vBMD was 0.61 mg/cm3. Statistically significant differences in spine vBMD measurements between different scanners reinforce the importance of cross-calibration in multi-center studies. Cross-calibration can be reliably performed using linear regression equations.

Liver Steatosis Categorization on Contrast-Enhanced CT Using a Fully Automated Deep Learning Volumetric Segmentation Tool: Evaluation in 1204 Healthy Adults Using Unenhanced CT as a Reference Standard.

BACKGROUND. Hepatic attenuation at unenhanced CT is linearly correlated with the MRI proton density fat fraction (PDFF). Liver fat quantification at contrast-enhanced CT is more challenging. OBJECTIVE. The purpose of this article is to evaluate liver steatosis categorization on contrast-enhanced CT using a fully automated deep learning volumetric hepatosplenic segmentation algorithm and unenhanced CT as the reference standard. METHODS. A fully automated volumetric hepatosplenic segmentation algorithm using 3D convolutional neural networks was applied to unenhanced and contrast-enhanced series from a sample of 1204 healthy adults (mean age, 45.2 years; 726 women, 478 men) undergoing CT evaluation for renal donation. The mean volumetric attenuation was computed from all designated liver and spleen voxels. PDFF was estimated from unenhanced CT attenuation and served as the reference standard. Contrast-enhanced attenuations were evaluated for detecting PDFF thresholds of 5% (mild steatosis, 10% and 15% (moderate steatosis); PDFF less than 5% was considered normal. RESULTS. Using unenhanced CT as reference, estimated PDFF was ≥ 5% (mild steatosis), ≥ 10%, and ≥ 15% (moderate steatosis) in 50.1% (n = 603), 12.5% (n = 151) and 4.8% (n = 58) of patients, respectively. ROC AUC values for predicting PDFF thresholds of 5%, 10%, and 15% using contrast-enhanced liver attenuation were 0.669, 0.854, and 0.962, respectively, and using contrast-enhanced liver-spleen attenuation difference were 0.662, 0.866, and 0.986, respectively. A total of 96.8% (90/93) of patients with contrast-enhanced liver attenuation less than 90 HU had steatosis (PDFF ≥ 5%); this threshold of less than 90 HU achieved sensitivity of 75.9% and specificity of 95.7% for moderate steatosis (PDFF ≥ 15%). Liver attenuation less than 100 HU achieved sensitivity of 34.0% and specificity of 94.2% for any steatosis (PDFF ≥ 5%). A total of 93.8% (30/32) of patients with contrast-enhanced liver-spleen attenuation difference 10 HU or less had moderate steatosis (PDFF ≥ 15%); a liver-spleen difference less than 5 HU achieved sensitivity of 91.4% and specificity of 95.0% for moderate steatosis. Liver-spleen difference less than 10 HU achieved sensitivity of 29.5% and specificity of 95.5% for any steatosis (PDFF ≥ 5%). CONCLUSION. Contrast-enhanced volumetric hepatosplenic attenuation derived using a fully automated deep learning CT tool may allow objective categoric assessment of hepatic steatosis. Accuracy was better for moderate than mild steatosis. Further confirmation using different scanning protocols and vendors is warranted. CLINICAL IMPACT. If these results are confirmed in independent patient samples, this automated approach could prove useful for both individualized and population-based steatosis assessment.

Liver Fat Content Measurement with Quantitative CT Validated against MRI Proton Density Fat Fraction: A Prospective Study of 400 Healthy Volunteers.

Background Although chemical shift-encoded (CSE) MRI proton density fat fraction (PDFF) is the current noninvasive reference standard for liver fat quantification, the liver is more frequently imaged with CT. Purpose To validate quantitative CT measurements of liver fat against the MRI PDFF reference standard. Materials and Methods In this prospective study, 400 healthy participants were recruited between August 2015 and July 2016. Each participant underwent same-day abdominal unenhanced quantitative CT with a calibration phantom and CSE 3.0-T MRI. CSE MRI liver fat measurements were used to calibrate an equation to adjust CT fat measurements and put them on the PDFF measurement scale. CT and PDFF liver fat measurements were plotted as histograms, medians, and interquartile ranges compared; scatterplots and Bland-Altman plots obtained; and Pearson correlation coefficients calculated. Receiver operating characteristic curves including areas under the curve were evaluated for mild (PDFF, 5%) and moderate (PDFF, 14%) steatosis thresholds for both raw and adjusted CT measurements. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results Four hundred volunteers (mean age, 52.6 years ± 15.2; 227 women) were evaluated. MRI PDFF measurements of liver fat ranged between 0% and 28%, with 41.5% (166 of 400) of participants with PDFF greater than 5%. Both raw and adjusted quantitative CT values correlated well with MRI PDFF (r2 = 0.79; P < .001). Bland-Altman analysis of adjusted CT values showed no slope or bias. Both raw and adjusted CT had areas under the receiver operating characteristic curve of 0.87 and 0.99, respectively, to identify participants with mild (PDFF, >5%) and moderate (PDFF, >14%) steatosis, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for unadjusted CT was 75.9% (126 of 166), 85.0% (199 of 234), 78.3% (126 of 161), and 83.3% (199 of 239), respectively, for PDFF greater than 5%; and 84.8% (28 of 33), 98.4% (361 of 367), 82.4% (28 of 34), and 98.6% (361 of 366), respectively, for PDFF greater than 14%. Results for adjusted CT were mostly identical. Conclusion Quantitative CT liver fat exhibited good correlation and accuracy with proton density fat fraction measured with chemical shift-encoded MRI. © RSNA, 2019 Online supplemental material is available for this article.

Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference.

OBJECTIVES: This study aimed to validate the accuracy and reliability of quantitative computed tomography (QCT) and chemical shift encoded magnetic resonance imaging (CSE-MRI) to assess hepatic steatosis. METHODS: Twenty-two geese with a wide range of hepatic steatosis were collected. After QCT and CSE-MRI examinations, the liver of each goose was removed and samples were taken from the left lobe, upper and lower half of the right lobe for biochemical measurement and histology. Fat percentages by QCT and proton density fat fraction by MRI (MRI-PDFF) were measured within the sample regions of biochemical measurement and histology. The accuracy of QCT and MR measurements were assessed through Spearman correlation coefficients (r) and Passing and Bablok regression equations using biochemical measurement as the "gold standard". RESULTS: Both QCT and MRI correlated highly with chemical extraction [r = 0.922 (p < 0.001) and r = 0.949 (p < 0.001) respectively]. Chemically extracted triglyceride was accurately predicted by both QCT liver fat percentages (Y = 0.6 + 0.866 × X) and by MRI-PDFF (Y = -1.8 + 0.773 × X). CONCLUSIONS: QCT and CSE-MRI measurements of goose liver fat were accurate and reliable compared with biochemical measurement. KEY POINTS: • QCT and CSE-MRI can measure liver fat content accurately and reliably • Histological grading of hepatic steatosis has larger sampling variability • QCT and CSE-MRI have potential in the clinical setting.

Obesity increases precision errors in total body dual-energy x-ray absorptiometry measurements.

Total body (TB) dual-energy X-ray absorptiometry (DXA) is increasingly being used to measure body composition in research and clinical settings. This study investigated the effect of body mass index (BMI) and body fat on precision errors for total and regional TB DXA measurements of bone mineral density, fat tissue, and lean tissue using the GE Lunar Prodigy (GE Healthcare, Bedford, UK). One hundred forty-four women with BMI's ranging from 18.5 to 45.9 kg/m(2) were recruited. Participants had duplicate DXA scans of the TB with repositioning between examinations. Participants were divided into 3 groups based on their BMI, and the root mean square standard deviation and the percentage coefficient of variation were calculated for each group. The root mean square standard deviation (percentage coefficient of variation) for the normal (<25 kg/m²; n = 76), overweight (25-30 kg/m²; n = 36), and obese (>30 kg/m²; n = 32) BMI groups, respectively, were total BMD (g/cm(2)): 0.009 (0.77%), 0.009 (0.69%), 0.011 (0.91%); total fat (g): 545 (2.98%), 486 (1.72%), 677 (1.55%); total lean (g): 551 (1.42%), 540 (1.34%), and 781 (1.68%). These results suggest that serial measurements in obese subjects should be treated with caution because the least significant change may be larger than anticipated.

Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Aromatase inhibitors prevent breast cancer in postmenopausal women at high risk of the disease but are associated with accelerated bone loss. We assessed effectiveness of oral risedronate for prevention of reduction in bone mineral density (BMD) after 3 years of follow-up in a subset of patients in the IBIS-II trial. METHODS: The double-blind IBIS-II trial recruited 3864 healthy, postmenopausal women at increased risk of breast cancer and randomly allocated them oral anastrozole (1 mg/day) or matched placebo. 1410 (36%) postmenopausal women were then enrolled in a bone substudy and stratified at baseline according to their lowest baseline T score at spine or femoral neck (stratum I: T score at least -1·0; stratum II: T score at least -2·5 but less than -1·0; stratum III: T score less than -2·5 but greater than -4·0). Women in stratum I were monitored only; women in stratum III were all given risedronate (35 mg/week). Women in stratum II were randomly assigned (1:1) to risedronate (35 mg/week) or matched placebo by use of a block randomisation schedule via a web-based programme. The primary outcome of this per-protocol analysis (done with all women with a baseline and 3 year DXA assessment) was the effect of risedronate versus placebo for osteopenic women in stratum II randomly allocated to anastrozole (1 mg/day). Secondary outcomes included effect of anastrozole (1 mg/day) on BMD in women not receiving risedronate (strata I and II) and in osteoporotic women who were all treated with risedronate (stratum III). The trial is ongoing, but no longer recruiting. This trial is registered, number ISRCTN31488319. FINDINGS: Between Feb 2, 2003, and Sept 30, 2010, 150 (58%) of 260 women in stratum II who had been randomly allocated to anastrozole and either risedronate or placebo had baseline and 3 year assessments. At the lumbar spine, 3 year mean BMD change for the 77 women receiving anastrozole/risedronate was 1·1% (95% CI 0·2 to 2·1) versus -2·6% (-4·0 to -1·3) for the 73 women receiving anastrozole/placebo (p<0·0001). For the total hip, 3 year mean BMD change for women receiving anastrozole/risedronate was -0·7% (-1·6 to 0·2) versus -3·5% (-4·6 to -2·3) for women receiving anastrozole/placebo (p=0·0001). 652 (65%) of 1008 women in strata I and II who were not randomly allocated to risedronate had both baseline and 3 year assessments. Women not receiving risedronate in stratum I and II who received anastrozole (310 women) had a significant BMD decrease after 3 years of follow-up compared with women who received placebo (342 women) at the lumbar spine (-4·0% [-4·5 to -3·4] vs -1·2% [-1·7 to -0·7], p<0·0001) and total hip (-4·0% [-4·4 to -3·6] vs -1·8% [-2·1 to -1·4], p<0·0001). 106 (79%) of 149 women in stratum III had a baseline and a 3 year assessment. The 46 women allocated to anastrozole had a modest BMD increase of 1·2% (-0·1 to 2·6) at the spine compared with a 3·9% (2·6 to 5·2) increase for the 60 women allocated to placebo (p=0·006). For the total hip, a small 0·3% (-0·9 to 1·5) increase was noted for women allocated anastrozole compared with a 1·5% (0·5 to 2·5) increase for women allocated placebo, but the difference was not significant (p=0·12). The most common adverse event reported was arthralgia (stratum I: 94 placebo and 114 anastrozole; stratum II: 39 placebo/placebo, 25 placebo/risedronate, 34 anastrozole/placebo, and 34 anastrozole/risedronate; stratum III: 21 placebo/risedronate, 17 anastrozole/risedronate). Other adverse events included hot flushes, alopecia, abdominal pain, and back pain. INTERPRETATION: Risedronate counterbalances the effect of anastrozole-induced bone loss in osteopenic and osteoporotic women and might be offered in combination with anastrozole treatment to provide an improved risk-benefit profile. FUNDING: Cancer Research UK (C569/A5032), National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca.

Imaging of site specific bone turnover in osteoporosis using positron emission tomography.

The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.

Body composition changes during breast cancer preventive treatment with anastrozole: Findings from the IBIS-II trial.

Background: Uptake to anastrozole for breast cancer prevention is low, partly due to women's concerns about side effects including gains in weight and specifically gains in body fat. Previous evidence does not link anastrozole with gains in weight, but there is a lack of data on any effects on body composition i.e. changes in fat and fat free mass. Here we assess association of anastrozole with body composition changes in a prospective sub-study from the second international breast intervention trial (IBIS-II). Methods: Participants had DXA scans at baseline and for five years of anastrozole/placebo and beyond (between March 2004 and September 2017. Primary outcomes were changes in body weight, body fat and fat free mass at 9-18 months. A linear model was used to estimate the size of a differential effect in these outcomes by randomised treatment allocation adjusted for baseline value and time since last scan, age, 10-year breast cancer risk, smoking and HRT status. Results: 203 postmenopausal women were recruited (n = 95 anastrozole, n = 108 placebo), mean age 58 years (SD = 5.4), BMI 28.0 kg/m2 (SD = 5.5). There was no evidence of a strong association between anastrozole or placebo and endpoints at 9-18 months; effect size (95 %CI) for anastrozole minus placebo for body weight (per/kg) -0.11 (-1.29-1.08); body fat 0.11 (-0.75-0.96) and fat free mass -0.30 (-0.79-0.19). Conclusions: There is unlikely to be a clinically significant change to body composition with anastrozole for breast cancer prevention.

Risk prediction of second hip fracture by bone and muscle density of the hip varies with time after first hip fracture: A prospective cohort study.

Purpose: Predictors of 'imminent' risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32-26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25-3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32-3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.