Fully automated CT imaging biomarkers for opportunistic prediction of future hip fractures.

OBJECTIVE: Assess automated CT imaging biomarkers in patients who went on to hip fracture, compared with controls. METHODS: In this retrospective case-control study, 6926 total patients underwent initial abdominal CT over a 20-year interval at one institution. A total of 1308 patients (mean age at initial CT, 70.5 ± 12.0 years; 64.4% female) went on to hip fracture (mean time to fracture, 5.2 years); 5618 were controls (mean age 70.3 ± 12.0 years; 61.2% female; mean follow-up interval 7.6 years). Validated fully automated quantitative CT algorithms for trabecular bone attenuation (at L1), skeletal muscle attenuation (at L3), and subcutaneous adipose tissue area (SAT) (at L3) were applied to all scans. Hazard ratios (HRs) comparing highest to lowest risk quartiles and receiver operating characteristic (ROC) curve analysis including area under the curve (AUC) were derived. RESULTS: Hip fracture HRs (95% CI) were 3.18 (2.69-3.76) for low trabecular bone HU, 1.50 (1.28-1.75) for low muscle HU, and 2.18 (1.86-2.56) for low SAT. 10-year ROC AUC values for predicting hip fracture were 0.702, 0.603, and 0.603 for these CT-based biomarkers, respectively. Multivariate combinations of these biomarkers further improved predictive value; the 10-year ROC AUC combining bone/muscle/SAT was 0.733, while combining muscle/SAT was 0.686. CONCLUSION: Opportunistic use of automated CT bone, muscle, and fat measures can identify patients at higher risk for future hip fracture, regardless of the indication for CT imaging. ADVANCES IN KNOWLEDGE: CT data can be leveraged opportunistically for further patient evaluation, with early intervention as needed. These novel AI tools analyse CT data to determine a patient's future hip fracture risk.

AI-generated CT body composition biomarkers associated with increased mortality risk in socioeconomically disadvantaged individuals.

PURPOSE: To evaluate the relationship between socioeconomic disadvantage using national area deprivation index (ADI) and CT-based body composition measures derived from fully automated artificial intelligence (AI) tools to identify body composition measures associated with increased risk for all-cause mortality and adverse cardiovascular events. METHODS: Fully automated AI body composition tools quantifying abdominal aortic calcium, abdominal fat (visceral [VAT], visceral-to-subcutaneous ratio [VSR]), and muscle attenuation (muscle HU) were applied to non-contrast CT examinations in adults undergoing screening CT colonography (CTC). Patients were partitioned into 5 socioeconomic groups based on the national ADI rank at the census block group level. Pearson correlation analysis was performed to determine the association between national ADI and body composition measures. One-way analysis of variance was used to compare means across groups. Odds ratios (ORs) were generated using high-risk, high specificity (90% specificity) body composition thresholds with the most disadvantaged groups being compared to the least disadvantaged group (ADI < 20). RESULTS: 7785 asymptomatic adults (mean age, 57 years; 4361:3424 F:M) underwent screening CTC from April 2004-December 2016. ADI rank data were available in 7644 patients. Median ADI was 31 (IQR 22-43). Aortic calcium, VAT, and VSR had positive correlation with ADI and muscle attenuation had a negative correlation with ADI (all p < .001). Compared with the least disadvantaged group, mean differences for the most disadvantaged group (ADI > 80) were: Aortic calcium (Agatston) = 567, VAT = 27 cm2, VSR = 0.1, and muscle HU = -6 HU (all p < .05). Compared with the least disadvantaged group, the most disadvantaged group had significantly higher odds of having high-risk body composition measures: Aortic calcium OR = 3.8, VAT OR = 2.5, VSR OR = 2.0, and muscle HU OR = 3.1(all p < .001). CONCLUSION: Fully automated CT body composition tools show that socioeconomic disadvantage is associated with high-risk body composition measures and can be used to identify individuals at increased risk for all-cause mortality and adverse cardiovascular events.

Comparing fully automated AI body composition measures derived from thin and thick slice CT image data.

PURPOSE: To compare fully automated artificial intelligence body composition measures derived from thin (1.25 mm) and thick (5 mm) slice abdominal CT data. METHODS: In this retrospective study, fully automated CT-based body composition algorithms for quantifying bone attenuation, muscle attenuation, muscle area, liver attenuation, liver volume, spleen volume, visceral-to-subcutaneous fat ratio (VSR) and aortic calcium were applied to both thin (1.25 × 0.625 mm) and thick (5 × 3 mm) abdominal CT series from two patient cohorts: unenhanced scans in asymptomatic adults undergoing colorectal cancer screening, and post-contrast scans in patients with colorectal cancer. Body composition measures derived from thin and thick slice data were compared, including correlation coefficients and Bland-Altman analysis. RESULTS: A total of 9882 CT scans (mean age, 57.0 years; 4527 women, 5355 men) were evaluated, including 8947 non-contrast and 935 contrast-enhanced CT exams. Very strong positive correlation was observed for all soft tissue measures: muscle attenuation (r2 = 0.97), muscle area (r2 = 0.98), liver attenuation (r2 = 0.99), liver volume (r2 = 0.98) and spleen volume (r2 = 0.99), VSR (r2 = 0.98), and aortic calcium (r2 = 0.92); (p < 0.001 for all). Moderate positive correlation was observed for bone attenuation (r2 = 0.35). Bland-Altman analysis showed strong agreement for muscle attenuation, muscle area, liver attenuation, liver volume and spleen volume. Mean percentage differences amongst body composition measures were less than 5% for VSR (4.6%), muscle area (- 0.5%), liver attenuation (0.4%) and liver volume (2.7%) and less than 10% for muscle attenuation (- 5.5%) and spleen volume (5.1%). For aortic calcium, thick slice overestimated for Agatston scores between 0 and 100 and > 400 burden in 3.1% and 0.3% relative to thin slice, respectively, but underestimated scores between 100 and 400. CONCLUSION: Automated body composition measures derived from thin and thick abdominal CT data are strongly correlated and show agreement, particularly for soft tissue applications, making it feasible to use either series for these CT-based body composition algorithms.

CT image-based biomarkers acquired by AI-based algorithms for the opportunistic prediction of falls.

Objective: Evaluate whether biomarkers measured by automated artificial intelligence (AI)-based algorithms are suggestive of future fall risk. Methods: In this retrospective age- and sex-matched case-control study, 9029 total patients underwent initial abdominal CT for a variety of indications over a 20-year interval at one institution. 3535 case patients (mean age at initial CT, 66.5 ± 9.6 years; 63.4% female) who went on to fall (mean interval to fall, 6.5 years) and 5494 controls (mean age at initial CT, 66.7 ± 9.8 years; 63.4% females; mean follow-up interval, 6.6 years) were included. Falls were identified by electronic health record review. Validated and fully automated quantitative CT algorithms for skeletal muscle, adipose tissue, and trabecular bone attenuation at the level of L1 were applied to all scans. Uni- and multivariate assessment included hazard ratios (HRs) and area under the receiver operating characteristic (AUROC) curve. Results: Fall HRs (with 95% CI) for low muscle Hounsfield unit, high total adipose area, and low bone Hounsfield unit were 1.82 (1.65-2.00), 1.31 (1.19-1.44) and 1.91 (1.74-2.11), respectively, and the 10-year AUROC values for predicting falls were 0.619, 0.556, and 0.639, respectively. Combining all these CT biomarkers further improved the predictive value, including 10-year AUROC of 0.657. Conclusion: Automated abdominal CT-based opportunistic measures of muscle, fat, and bone offer a novel approach to risk stratification for future falls, potentially by identifying patients with osteosarcopenic obesity. Advances in knowledge: There are few well-established clinical tools to predict falls. We use novel AI-based body composition algorithms to leverage incidental CT data to help determine a patient's future fall risk.

Fully automated CT-based adiposity assessment: comparison of the L1 and L3 vertebral levels for opportunistic prediction.

PURPOSE: The purpose of this study is to compare fully automated CT-based measures of adipose tissue at the L1 level versus the standard L3 level for predicting mortality, which would allow for use at both chest (L1) and abdominal (L3) CT. METHODS: This retrospective study of 9066 asymptomatic adults (mean age, 57.1 ± 7.8 [SD] years; 4020 men, 5046 women) undergoing unenhanced low-dose abdominal CT for colorectal cancer screening. A previously validated artificial intelligence (AI) tool was used to assess cross-sectional visceral and subcutaneous adipose tissue areas (SAT and VAT), as well as their ratio (VSR) at the L1 and L3 levels. Post-CT survival prediction was compared using area under the ROC curve (ROC AUC) and hazard ratios (HRs). RESULTS: Median clinical follow-up interval after CT was 8.8 years (interquartile range, 5.2-11.6 years), during which 5.9% died (532/9066). No significant difference (p > 0.05) for mortality was observed between L1 and L3 VAT and SAT at 10-year ROC AUC. However, L3 measures were significantly better for VSR at 10-year AUC (p < 0.001). HRs comparing worst-to-best quartiles for mortality at L1 vs. L3 were 2.12 (95% CI, 1.65-2.72) and 2.22 (1.74-2.83) for VAT; 1.20 (0.95-1.52) and 1.16 (0.92-1.46) for SAT; and 2.26 (1.7-2.93) and 3.05 (2.32-4.01) for VSR. In women, the corresponding HRs for VSR were 2.58 (1.80-3.69) (L1) and 4.49 (2.98-6.78) (L3). CONCLUSION: Automated CT-based measures of visceral fat (VAT and VSR) at L1 are predictive of survival, although overall measures of adiposity at L1 level are somewhat inferior to the standard L3-level measures. Utilizing predictive L1-level fat measures could expand opportunistic screening to chest CT imaging.

Utility of Fully Automated Body Composition Measures on Pretreatment Abdominal CT for Predicting Survival in Patients With Colorectal Cancer.

BACKGROUND. CT examinations contain opportunistic body composition data with potential prognostic utility. Previous studies have primarily used manual or semiautomated tools to evaluate body composition in patients with colorectal cancer (CRC). OBJECTIVE. The purpose of this article is to assess the utility of fully automated body composition measures derived from pretreatment CT examinations in predicting survival in patients with CRC. METHODS. This retrospective study included 1766 patients (mean age, 63.7 ± 14.4 [SD] years; 862 men, 904 women) diagnosed with CRC between January 2001 and September 2020 who underwent pretreatment abdominal CT. A panel of fully automated artificial intelligence-based algorithms was applied to portal venous phase images to quantify skeletal muscle attenuation at the L3 lumbar level, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area at L3, and abdominal aorta Agatston score (aortic calcium). The electronic health record was reviewed to identify patients who died of any cause (n = 848). ROC analyses and logistic regression analyses were used to identify predictors of survival, with attention to highest- and lowest-risk quartiles. RESULTS. Patients who died, compared with patients who survived, had lower median muscle attenuation (19.2 vs 26.2 HU, p < .001), SAT area (168.4 cm2 vs 197.6 cm2, p < .001), and aortic calcium (620 vs 182, p < .001). Measures with highest 5-year AUCs for predicting survival in patients without (n = 1303) and with (n = 463) metastatic disease were muscle attenuation (0.666 and 0.701, respectively) and aortic calcium (0.677 and 0.689, respectively). A combination of muscle attenuation, SAT area, and aortic calcium yielded 5-year AUCs of 0.758 and 0.732 in patients without and with metastases, respectively. Risk of death was increased (p < .05) in patients in the lowest quartile for muscle attenuation (hazard ratio [HR] = 1.55) and SAT area (HR = 1.81) and in the highest quartile for aortic calcium (HR = 1.37) and decreased (p < .05) in patients in the highest quartile for VAT area (HR = 0.79) and SAT area (HR = 0.76). In 423 patients with available BMI, BMI did not significantly predict death (p = .75). CONCLUSION. Fully automated CT-based body composition measures including muscle attenuation, SAT area, and aortic calcium predict survival in patients with CRC. CLINICAL IMPACT. Routine pretreatment body composition evaluation could improve initial risk stratification of patients with CRC.

Abdominal CT Body Composition Thresholds Using Automated AI Tools for Predicting 10-year Adverse Outcomes.

Background CT-based body composition measures derived from fully automated artificial intelligence tools are promising for opportunistic screening. However, body composition thresholds associated with adverse clinical outcomes are lacking. Purpose To determine population and sex-specific thresholds for muscle, abdominal fat, and abdominal aortic calcium measures at abdominal CT for predicting risk of death, adverse cardiovascular events, and fragility fractures. Materials and Methods In this retrospective single-center study, fully automated algorithms for quantifying skeletal muscle (L3 level), abdominal fat (L3 level), and abdominal aortic calcium were applied to noncontrast abdominal CT scans from asymptomatic adults screened from 2004 to 2016. Longitudinal follow-up documented subsequent death, adverse cardiovascular events (myocardial infarction, cerebrovascular event, and heart failure), and fragility fractures. Receiver operating characteristic (ROC) curve analysis was performed to derive thresholds for body composition measures to achieve optimal ROC curve performance and high specificity (90%) for 10-year risks. Results A total of 9223 asymptomatic adults (mean age, 57 years ± 7 [SD]; 5152 women and 4071 men) were evaluated (median follow-up, 9 years). Muscle attenuation and aortic calcium had the highest diagnostic performance for predicting death, with areas under the ROC curve of 0.76 for men (95% CI: 0.72, 0.79) and 0.72 for women (95% CI: 0.69, 0.76) for muscle attenuation. Sex-specific thresholds were higher in men than women (P < .001 for muscle attenuation for all outcomes). The highest-performing markers for risk of death were muscle attenuation in men (31 HU; 71% sensitivity [164 of 232 patients]; 72% specificity [1114 of 1543 patients]) and aortic calcium in women (Agatston score, 167; 70% sensitivity [152 of 218 patients]; 70% specificity [1427 of 2034 patients]). Ninety-percent specificity thresholds for muscle attenuation for both risk of death and fragility fractures were 23 HU (men) and 13 HU (women). For aortic calcium and risk of death and adverse cardiovascular events, 90% specificity Agatston score thresholds were 1475 (men) and 735 (women). Conclusion Sex-specific thresholds for automated abdominal CT-based body composition measures can be used to predict risk of death, adverse cardiovascular events, and fragility fractures. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Ohliger in this issue.

Sex-specific effects of cardiorespiratory fitness on age-related differences in cerebral hemodynamics.

There is a positive association between cardiorespiratory fitness and cognitive health, but the interaction between cardiorespiratory fitness and aging on cerebral hemodynamics is unclear. These potential interactions are further influenced by sex differences. The purpose of this study was to determine the sex-specific relationships between cardiorespiratory fitness, age, and cerebral hemodynamics in humans. Measurements of unilateral middle cerebral artery blood velocity (MCAv) and cerebral pulsatility index obtained using transcranial Doppler ultrasound and cardiorespiratory fitness [maximal oxygen consumption (V̇o2max)] obtained from maximal incremental exercise tests were retrieved from study records at three institutions. A total of 153 healthy participants were included in the analysis (age = 42 ± 20 yr, range = 18-83 yr). There was no association between V̇o2max and MCAv in all participants (P = 0.20). The association between V̇o2max and MCAv was positive in women, but no longer significant after age adjustment (univariate: P = 0.01; age-adjusted: P = 0.45). In addition, there was no association between V̇o2max and MCAv in men (univariate: P = 0.25, age-adjusted: P = 0.57). For V̇o2max and cerebral pulsatility index, there were significant negative associations in all participants (P < 0.001), in men (P < 0.001) and women (P < 0.001). This association remained significant when adjusting for age in women only (P = 0.03). In summary, higher cardiorespiratory fitness was associated with a lower cerebral pulsatility index in all participants, and the significance remained only in women when adjusting for age. Future studies are needed to determine the sex-specific impact of cardiorespiratory fitness improvements on cerebrovascular health.NEW & NOTEWORTHY We present data pooled from three institutions to study the impact of age, sex, and cardiorespiratory fitness on cerebral hemodynamics. Cardiorespiratory fitness was positively associated with middle cerebral artery blood velocity in women, but not in men. Furthermore, cardiorespiratory fitness was inversely associated with cerebral pulsatility index in both men and women, which remained significant in women when adjusting for age. These data suggest a sex-specific impact of cardiorespiratory fitness on resting cerebral hemodynamics.

Fully Automated Deep Learning Tool for Sarcopenia Assessment on CT: L1 Versus L3 Vertebral Level Muscle Measurements for Opportunistic Prediction of Adverse Clinical Outcomes.

BACKGROUND. Sarcopenia is associated with adverse clinical outcomes. CT-based skeletal muscle measurements for sarcopenia assessment are most commonly performed at the L3 vertebral level. OBJECTIVE. The purpose of this article is to compare the utility of fully automated deep learning CT-based muscle quantitation at the L1 versus L3 level for predicting future hip fractures and death. METHODS. This retrospective study included 9223 asymptomatic adults (mean age, 57 ± 8 [SD] years; 4071 men, 5152 women) who underwent unenhanced low-dose abdominal CT. A previously validated fully automated deep learning tool was used to assess muscle for myosteatosis (by mean attenuation) and myopenia (by cross-sectional area) at the L1 and L3 levels. Performance for predicting hip fractures and death was compared between L1 and L3 measures. Performance for predicting hip fractures and death was also evaluated using the established clinical risk scores from the fracture risk assessment tool (FRAX) and Framingham risk score (FRS), respectively. RESULTS. Median clinical follow-up interval after CT was 8.8 years (interquartile range, 5.1-11.6 years), yielding hip fractures and death in 219 (2.4%) and 549 (6.0%) patients, respectively. L1-level and L3-level muscle attenuation measurements were not different in 2-, 5-, or 10-year AUC for hip fracture (p = .18-.98) or death (p = .19-.95). For hip fracture, 5-year AUCs for L1-level muscle attenuation, L3-level muscle attenuation, and FRAX score were 0.717, 0.709, and 0.708, respectively. For death, 5-year AUCs for L1-level muscle attenuation, L3-level muscle attenuation, and FRS were 0.737, 0.721, and 0.688, respectively. Lowest quartile hazard ratios (HRs) for hip fracture were 2.20 (L1 attenuation), 2.45 (L3 attenuation), and 2.53 (FRAX score), and for death were 3.25 (L1 attenuation), 3.58 (L3 attenuation), and 2.82 (FRS). CT-based muscle cross-sectional area measurements at L1 and L3 were less predictive for hip fracture and death (5-year AUC ≤ 0.571; HR ≤ 1.56). CONCLUSION. Automated CT-based measurements of muscle attenuation for myosteatosis at the L1 level compare favorably with previously established L3-level measurements and clinical risk scores for predicting hip fracture and death. Assessment for myopenia was less predictive of outcomes at both levels. CLINICAL IMPACT. Alternative use of the L1 rather than L3 level for CT-based muscle measurements allows sarcopenia assessment using both chest and abdominal CT scans, greatly increasing the potential yield of opportunistic CT screening.

Automated assessment of longitudinal biomarker changes at abdominal CT: correlation with subsequent cardiovascular events in an asymptomatic adult screening cohort.

BACKGROUND: Cardiovascular (CV) disease is a major public health concern, and automated methods can potentially capture relevant longitudinal changes on CT for opportunistic CV screening purposes. METHODS: Fully-automated and validated algorithms that quantify abdominal fat, muscle, bone, liver, and aortic calcium were retrospectively applied to a longitudinal adult screening cohort undergoing serial non-contrast CT examination between 2005 and 2016. Downstream major adverse events (MI/CVA/CHF/death) were identified via algorithmic EHR search. Logistic regression, ROC curve, and Cox survival analyses assessed for associations between changes in CT variables and adverse events. RESULTS: Final cohort included 1949 adults (942 M/1007F; mean age, 56.2 ± 6.2 years at initial CT). Mean interval between CT scans was 5.8 ± 2.0 years. Mean clinical follow-up interval from initial CT was 10.4 ± 2.7 years. Major CV events occurred after follow-up CT in 230 total subjects (11.8%). Mean change in aortic calcium Agatston score was significantly higher in CV(+) cohort (591.6 ± 1095.3 vs. 261.1 ± 764.3), as was annualized Agatston change (120.5 ± 263.6 vs. 46.7 ± 143.9) (p < 0.001 for both). 5-year area under the ROC curve (AUC) for Agatston change was 0.611. Hazard ratio for Agatston score change > 500 was 2.8 (95% CI 1.5-4.0) relative to < 500. Agatston score change was the only significant univariate CT biomarker in the survival analysis. Changes in fat and bone measures added no meaningful prediction. CONCLUSION: Interval change in automated CT-based abdominal aortic calcium load represents a promising predictive longitudinal tool for assessing cardiovascular and mortality risks. Changes in other body composition measures were less predictive of adverse events.

Utility of Multiparametric CT for Identification of High-Risk NAFLD.

OBJECTIVE. The purpose of this study was to evaluate the utility of laboratory and CT metrics in identifying patients with high-risk nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS. Patients with biopsy-proven NAFLD who underwent CT within 1 year of biopsy were included. Histopathologic review was performed by an experienced gastrointestinal pathologist to determine steatosis, inflammation, and fibrosis. The presence of any lobular inflammation and hepatocyte ballooning was categorized as nonalcoholic steatohepatitis (NASH). Patients with NAFLD and advanced fibrosis (stage F3 or higher) were categorized as having high-risk NAFLD. Aspartate transaminase to platelet ratio index and Fibrosis-4 (FIB-4) laboratory scores were calculated. CT metrics included hepatic attenuation, liver segmental volume ratio (LSVR), splenic volume, liver surface nodularity score, and selected texture features. In addition, two readers subjectively assessed the presence of NASH (present or not present) and fibrosis (stages F0-F4). RESULTS. A total of 186 patients with NAFLD (mean age, 49 years; 74 men and 112 women) were included. Of these, 87 (47%) had NASH and 112 (60%) had moderate to severe steatosis. A total of 51 patients were classified as fibrosis stage F0, 42 as F1, 23 as F2, 37 as F3, and 33 as F4. Additionally, 70 (38%) had advanced fibrosis (stage F3 or F4) and were considered to have high-risk NAFLD. FIB-4 score correlated with fibrosis (ROC AUC of 0.75 for identifying high-risk NAFLD). Of the individual CT parameters, LSVR and splenic volume performed best (AUC of 0.69 for both for detecting high-risk NAFLD). Subjective reader assessment performed best among all parameters (AUCs of 0.78 for reader 1 and 0.79 for reader 2 for detecting high-risk NAFLD). FIB-4 and subjective scores were complementary (combined AUC of 0.82 for detecting high-risk NAFLD). For NASH assessment, FIB-4 performed best (AUC of 0.68), whereas the AUCs were less than 0.60 for all individual CT features and subjective assessments. CONCLUSION. FIB-4 and multiple CT findings can identify patients with high-risk NAFLD (advanced fibrosis or cirrhosis). However, the presence of NASH is elusive on CT.

Utilizing Fully Automated Abdominal CT-Based Biomarkers for Opportunistic Screening for Metabolic Syndrome in Adults Without Symptoms.

OBJECTIVE: Metabolic syndrome describes a constellation of reversible cardiometabolic abnormalities associated with cardiovascular risk and diabetes. The present study investigates the use of fully automated abdominal CT-based biometric measures for opportunistic identification of metabolic syndrome in adults without symptoms. MATERIALS AND METHODS: International Diabetes Federation criteria were applied to a cohort of 9223 adults without symptoms who underwent unenhanced abdominal CT. After patients with insufficient clinical data for diagnosis were excluded, the final cohort consisted of 7785 adults (mean age, 57.0 years; 4361 women and 3424 men). Previously validated and fully automated CT-based algorithms for quantifying muscle, visceral and subcutaneous fat, liver fat, and abdominal aortic calcification were applied to this final cohort. RESULTS: A total of 738 subjects (9.5% of all subjects; mean age, 56.7 years; 372 women and 366 men) met the clinical criteria for metabolic syndrome. Subsequent major cardiovascular events occurred more frequently in the cohort with metabolic syndrome (p < 0.001). Significant differences were observed between the two groups for all CT-based biomarkers (p < 0.001). Univariate L1-level total abdominal fat (area under the ROC curve [AUROC] = 0.909; odds ratio [OR] = 27.2), L3-level skeletal muscle index (AUROC = 0.776; OR = 5.8), and volumetric liver attenuation (AUROC = 0.738; OR = 5.1) performed well when compared with abdominal aortic calcification scoring (AUROC = 0.578; OR = 1.6). An L1-level total abdominal fat threshold of 460.6 cm2 was 80.1% sensitive and 85.4% specific for metabolic syndrome. For women, the AUROC was 0.930 when fat and muscle measures were combined. CONCLUSION: Fully automated quantitative tissue measures of fat, muscle, and liver derived from abdominal CT scans can help identify individuals who are at risk for metabolic syndrome. These visceral measures can be opportunistically applied to CT scans obtained for other clinical indications, and they may ultimately provide a more direct and useful definition of metabolic syndrome.

Automated CT biomarkers for opportunistic prediction of future cardiovascular events and mortality in an asymptomatic screening population: a retrospective cohort study.

Background: Body CT scans are frequently performed for a wide variety of clinical indications, but potentially valuable biometric information typically goes unused. We investigated the prognostic ability of automated CT-based body composition biomarkers derived from previously-developed deep-learning and feature-based algorithms for predicting major cardiovascular events and overall survival in an adult screening cohort, compared with clinical parameters. Methods: Mature and fully-automated CT-based algorithms with pre-defined metrics for quantifying aortic calcification, muscle density, visceral/subcutaneous fat, liver fat, and bone mineral density (BMD) were applied to a generally-healthy asymptomatic outpatient cohort of 9223 adults (mean age, 57.1 years; 5152 women) undergoing abdominal CT for routine colorectal cancer screening. Longitudinal clinical follow-up (median, 8.8 years; IQR, 5.1-11.6 years) documented subsequent major cardiovascular events or death in 19.7% (n=1831). Predictive ability of CT-based biomarkers was compared against the Framingham Risk Score (FRS) and body mass index (BMI). Findings: Significant differences were observed for all five automated CT-based body composition measures according to adverse events (p<0.001). Univariate 5-year AUROC (with 95% CI) for automated CT-based aortic calcification, muscle density, visceral/subcutaneous fat ratio, liver density, and vertebral density for predicting death were 0.743(0.705-0.780)/0.721(0.683-0.759)/0.661(0.625-0.697)/0.619 (0.582-0.656)/0.646(0.603-0.688), respectively, compared with 0.499(0.454-0.544) for BMI and 0.688(0.650-0.727) for FRS (p<0.05 for aortic calcification vs. FRS and BMI); all trends were similar for 2-year and 10-year ROC analyses. Univariate hazard ratios (with 95% CIs) for highest-risk quartile versus others for these same CT measures were 4.53(3.82-5.37) /3.58(3.02-4.23)/2.28(1.92-2.71)/1.82(1.52-2.17)/2.73(2.31-3.23), compared with 1.36(1.13-1.64) and 2.82(2.36-3.37) for BMI and FRS, respectively. Similar significant trends were observed for cardiovascular events. Multivariate combinations of CT biomarkers further improved prediction over clinical parameters (p<0.05 for AUROCs). For example, by combining aortic calcification, muscle density, and liver density, the 2-year AUROC for predicting overall survival was 0.811 (0.761-0.860). Interpretation: Fully-automated quantitative tissue biomarkers derived from CT scans can outperform established clinical parameters for pre-symptomatic risk stratification for future serious adverse events, and add opportunistic value to CT scans performed for other indications.

Automated Abdominal CT Imaging Biomarkers for Opportunistic Prediction of Future Major Osteoporotic Fractures in Asymptomatic Adults.

Background Body composition data from abdominal CT scans have the potential to opportunistically identify those at risk for future fracture. Purpose To apply automated bone, muscle, and fat tools to noncontrast CT to assess performance for predicting major osteoporotic fractures and to compare with the Fracture Risk Assessment Tool (FRAX) reference standard. Materials and Methods Fully automated bone attenuation (L1-level attenuation), muscle attenuation (L3-level attenuation), and fat (L1-level visceral-to-subcutaneous [V/S] ratio) measures were derived from noncontrast low-dose abdominal CT scans in a generally healthy asymptomatic adult outpatient cohort from 2004 to 2016. The FRAX score was calculated from data derived from an algorithmic electronic health record search. The cohort was assessed for subsequent future fragility fractures. Subset analysis was performed for patients evaluated with dual x-ray absorptiometry (n = 2106). Hazard ratios (HRs) and receiver operating characteristic curve analyses were performed. Results A total of 9223 adults were evaluated (mean age, 57 years ± 8 [standard deviation]; 5152 women) at CT and were followed over a median time of 8.8 years (interquartile range, 5.1-11.6 years), with documented subsequent major osteoporotic fractures in 7.4% (n = 686), including hip fractures in 2.4% (n = 219). Comparing the highest-risk quartile with the other three quartiles, HRs for bone attenuation, muscle attenuation, V/S fat ratio, and FRAX were 2.1, 1.9, 0.98, and 2.5 for any fragility fracture and 2.0, 2.5, 1.1, and 2.5 for femoral fractures, respectively (P < .001 for all except V/S ratio, which was P ≥ .51). Area under the receiver operating characteristic curve (AUC) values for fragility fracture were 0.71, 0.65, 0.51, and 0.72 at 2 years and 0.63, 0.62, 0.52, and 0.65 at 10 years, respectively. For hip fractures, 2-year AUC for muscle attenuation alone was 0.75 compared with 0.73 for FRAX (P = .43). Multivariable 2-year AUC combining bone and muscle attenuation was 0.73 for any fragility fracture and 0.76 for hip fractures, respectively (P ≥ .73 compared with FRAX). For the subset with dual x-ray absorptiometry T-scores, 2-year AUC was 0.74 for bone attenuation and 0.65 for FRAX (P = .11). Conclusion Automated bone and muscle imaging biomarkers derived from CT scans provided comparable performance to Fracture Risk Assessment Tool score for presymptomatic prediction of future osteoporotic fractures. Muscle attenuation alone provided effective hip fracture prediction. © RSNA, 2020 See also the editorial by Smith in this issue.

Joint Design with Providers of Clinical Decision Support for Value-Based Advanced Shoulder Imaging.

BACKGROUND: Provider orders for inappropriate advanced imaging, while rarely altering patient management, contribute enough to the strain on available health care resources, and therefore the United States Congress established the Appropriate Use Criteria Program. OBJECTIVES: To examine whether co-designing clinical decision support (CDS) with referring providers will reduce barriers to adoption and facilitate more appropriate shoulder ultrasound (US) over magnetic resonance imaging (MRI) in diagnosing Veteran shoulder pain, given similar efficacies and only 5% MRI follow-up rate after shoulder US. METHODS: We used a theory-driven, convergent parallel mixed-methods approach to prospectively (1) determine medical providers' reasons for selecting MRI over US in diagnosing shoulder pain and identify barriers to ordering US, (2) co-design CDS, informed by provider interviews, to prompt appropriate US use, and (3) assess CDS impact on shoulder imaging use. CDS effectiveness in guiding appropriate shoulder imaging was evaluated through monthly monitoring of ordering data at our quaternary care Veterans Hospital. Key outcome measures were appropriate MRI/US use rates and transition to ordering US by both musculoskeletal specialist and generalist providers. We assessed differences in ordering using a generalized estimating equations logistic regression model. We compared continuous measures using mixed effects analysis of variance with log-transformed data. RESULTS: During December 2016 to March 2018, 569 (395 MRI, 174 US) shoulder advanced imaging examinations were ordered by 111 providers. CDS "co-designed" in collaboration with providers increased US from 17% (58/335) to 50% (116/234) of all orders (p < 0.001), with concomitant decrease in MRI. Ordering appropriateness more than doubled from 31% (105/335) to 67% (157/234) following CDS (p < 0.001). Interviews confirmed that generalist providers want help in appropriately ordering advanced imaging. CONCLUSION: Partnering with medical providers to co-design CDS reduced barriers and prompted appropriate transition to US from MRI for shoulder pain diagnosis, promoting evidence-based practice. This approach can inform the development and implementation of other forms of CDS.

Missing data and sensitivity analysis for binary data with implications for sample size and power of randomized clinical trials.

Despite our best efforts, missing outcomes are common in randomized controlled clinical trials. The National Research Council's Committee on National Statistics panel report titled The Prevention and Treatment of Missing Data in Clinical Trials noted that further research is required to assess the impact of missing data on the power of clinical trials and how to set useful target rates and acceptable rates of missing data in clinical trials. In this article, using binary responses for illustration, we establish that conclusions based on statistical analyses that include only complete cases can be seriously misleading, and that the adverse impact of missing data grows not only with increasing rates of missingness but also with increasing sample size. We illustrate how principled sensitivity analysis can be used to assess the robustness of the conclusions. Finally, we illustrate how sample sizes can be adjusted to account for expected rates of missingness. We find that when sensitivity analyses are considered as part of the primary analysis, the required adjustments to the sample size are dramatically larger than those that are traditionally used. Furthermore, in some cases, especially in large trials with small target effect sizes, it is impossible to achieve the desired power.

A 12-year single-center retrospective analysis of antisiphon devices to prevent proximal ventricular shunt obstruction for hydrocephalus.

OBJECTIVE: Recent evidence points to gravity-dependent chronic shunt overdrainage as a significant, if not leading, cause of proximal shunt failure. Yet, shunt overdrainage or siphoning persists despite innovations in valve technology. The authors examined the effectiveness of adding resistance to flow in shunt systems via antisiphon devices (ASDs) in preventing proximal shunt obstruction. METHODS: A retrospective observational cohort study was completed on patients who had an ASD (or additional valve) added to their shunt system between 2004 and 2016. Detailed clinical, radiographic, and surgical findings were examined. Shunt failure rates were compared before and after ASD addition. RESULTS: Seventy-eight patients with shunted hydrocephalus were treated with placement of an ASD several centimeters distal to the primary valve. The records of 12 of these patients were analyzed separately due to a complex shunt revision history (i.e., > 10 lifetime shunt revisions). The authors found that adding an ASD decreased the 1-year ventricular catheter obstruction rates in the "simple" and "complex" groups by 67.3% and 75.8%, respectively, and the 5-year rates by 43.3% and 65.6%, respectively. The main long-term ASD complication was ASD removal for presumed valve pressure intolerance in 5 patients. CONCLUSIONS: Using an ASD may result in significant reductions in ventricular catheter shunt obstruction rates. If confirmed with prospective studies, this observation would lend further evidence that chronic shunt overdrainage is a central cause of shunt malfunction, and provide pilot data to establish clinical and laboratory studies that assess optimal ASD type, number, and position, and eventually develop shunt valve systems that are altogether resistant to siphoning.

Spinal subarachnoid space tapering in patients with syringomyelia.

BACKGROUND AND PURPOSE: Cervical spine tapering affects cerebrospinal fluid dynamics. Cervical spine taper ratios derived from anteroposterior diameters reportedly differ between patients with syringomyelia and controls. We attempted to verify the differences in diameter and to show differences in cross-sectional area between syringomyelia and controls. METHODS: Cervical spine magnetic resonance images in syringomyelia patients (idiopathic or Chiari I related) and control patients were examined. In each subject, the anteroposterior diameter of the spinal canal was measured at each cervical level, and C1-C4, C4-C7, and C1-C7 taper ratios were calculated. Differences in taper ratio between groups were tested for statistical significance with the t-test. Cross-sectional areas of the spinal canal were measured at each cervical spinal level, and tapering was calculated. RESULTS: Eighteen patients with idiopathic syringomyelia, 28 with Chiari I, and 29 controls were studied. Chiari and syringomyelia patients had significantly steeper diameter-based taper ratios than controls. The dural sac areas tapered proportionally with the diameter-based taper ratio in all groups. CONCLUSIONS: Cervical spine anteroposterior diameter tapering and dural sac cross-sectional areas tapering differ between syringomyelia patients and controls.

Quantitative Ultrasound Parameters Based on the Backscattered Echo Power Signal as Biomarkers of Cervical Remodeling: A Longitudinal Study in the Pregnant Rhesus Macaque.

Clinical prediction and especially prevention of abnormal birth timing, particularly pre-term, is poor. The cervix plays a key role in birth timing; it first serves as a rigid barrier to protect the developing fetus, then becomes the pathway to delivery of that fetus. Imaging biomarkers to define this remodeling process could provide insights to improve prediction of birth timing and elucidate novel targets for preventive therapies. Quantitative ultrasound (QUS) approaches that appear promising for this purpose include shear wave speed (SWS) estimation to quantify softness, as well as parameters based on backscattered power, such as the mean backscattered power difference (mBSPD) and specific attenuation coefficient (SAC), to quantify the organization of tissue microstructure. Invasive studies in rodents demonstrated that as pregnancy advances, cervical microstructure disorganizes as tissue softness and compliance increase. Our non-invasive studies in pregnant women and rhesus macaques suggested that QUS can detect these microstructural changes in vivo. Our previous study in the same cohort showed a progressive decline in SWS during pregnancy, consistent with increasing tissue softness, and we hypothesized that backscatter parameters would also decrease, consistent with increasing microstructural disorganization. In this study, we analyzed the mBSPD and SAC in the cervices of rhesus macaques (n = 18). We found that both mBSPD and SAC decreased throughout pregnancy (p < 0.001 for both parameters) and that the former appears to be a more reliable biomarker. In summary, biomarkers that can characterize tissue microstructural organization are promising for comprehensive characterization of cervical remodeling in pregnancy.

Ultrasound-Guided Microwave Ablation for the Management of Inguinal Neuralgia: A Preliminary Study with 1-Year Follow-up.

PURPOSE: To evaluate the feasibility and efficacy of ultrasound-guided microwave ablation for the treatment of inguinal neuralgia. MATERIALS AND METHODS: A retrospective review of 12 consecutive ultrasound-guided microwave ablation procedures was performed of 10 consecutive patients (8 men, 2 women; mean age, 41 years [range, 15-64 years]), between August 2012 and August 2016. Inclusion criteria for inguinal neuralgia included clinical diagnosis of chronic inguinal pain (average, 17.3 months [range, 6-46 months]) refractory to conservative treatment and a positive nerve block. Pain response-reduction of pain level and duration and percent pain reduction using a 10-point visual analog scale (VAS) at baseline and up to 12 months after the procedure-was measured. Nine patients had pain after the inguinal hernia repair, and 1 patient had pain from the femoral artery bypass procedure. The microwave ablation procedure targeted the ilioinguinal nerve in 7 cases, the genitofemoral nerve in 4 cases, and the iliohypogastric nerve in 1 case. RESULTS: Average baseline VAS pain score was 6.1 (standard deviation, 2.5). Improved pain levels immediately after the procedure and at 1, 6, and 12 months were statistically significant (P = .0037, .0037, .0038, .0058, respectively). Also, 91.7% (11/12) of the procedures resulted in immediate pain relief and at 1 month and 6 months. At 12 months, 83.3% (10/12) of patients had an average of 69% ± 31% pain reduction. Percent maximal pain reduction was 93% ± 14% (60%-100%), and the average duration of clinically significant pain reduction was 10.5 months (range, 0-12 months.). No complications or adverse outcomes occurred. CONCLUSIONS: Ultrasound-guided microwave ablation is an effective technique for the treatment of inguinal neuralgia after herniorrhaphy.