Scott J. Lee

Appearance of cholinergic myenteric neurons during enteric nervous system development: comparison of different ChAT fluorescent mouse reporter lines.

Cholinergic neurons have been identified with the acetylcholine synthetic enzyme choline acetyltransferase (ChAT). However, ChAT is difficult to localize in newly differentiated peripheral neurons making the study of cholinergic neuronal development problematic. Consequently, researchers have used mouse reporter lines to indicate the presence of ChAT.

Predicting Future Hip Fractures on Routine Abdominal CT Using Opportunistic Osteoporosis Screening Measures: A Matched Case-Control Study

OBJECTIVE Hip fracture is a major consequence of low bone mineral density, which is treatable but underdiagnosed. The purpose of this case-control study is to determine whether lumbar vertebral trabecular attenuation, vertebral compression fractures, and femoral neck T scores readily derived from abdominopelvic CT scans obtained for various indications are associated with future hip fragility fracture. MATERIALS AND METHODS A cohort of 204 patients with hip fracture (130 women and 74 men; mean age, 74.3 years) who had undergone abdominopelvic CT before fracture occurred (mean interval, 24.8 months) was compared with an age- and sex-matched control cohort without hip fracture. L1 trabecular attenuation, vertebral compression fractures of grades 2 and 3, and femoral neck T scores derived from asynchronous quantitative CT were recorded. The presence of one or more clinical risk factor for fracture was also recorded. Multivariate logistic regression models were used to determine the association of each measurement with the occurrence of hip fracture. RESULTS The mean L1 trabecular attenuation value, the presence of one or more vertebral compression fracture, and CT-derived femoral neck T scores were all significantly different in patients with hip fracture versus control subjects (p < 0.01). Logistic regression models showed a significant association of all measurements with hip fracture outcome after adjustments were made for age, sex, and the presence of one or more clinical risk factor. L1 trabecular attenuation and CT-derived femoral neck T scores showed moderate accuracy in differentiating case and control patients (AUC, 0.70 and 0.78, respectively). CONCLUSION L1 trabecular attenuation, CT-derived femoral neck T scores, and the presence of at least one vertebral compression fracture on CT are all associated with future hip fragility fracture in adults undergoing routine abdominopelvic CT for a variety of conditions.

Prevalence of Vertebral Compression Fractures on Routine CT Scans According to L1 Trabecular Attenuation: Determining Relevant Thresholds for Opportunistic Osteoporosis Screening

OBJECTIVE Radiologists interpreting body CT scans may be the first to identify osteoporosis and associated vertebral fractures. This study correlates L1 trabecular attenuation measurements with prevalent vertebral body fractures in older adults undergoing routine CT. MATERIALS AND METHODS Mean L1 trabecular attenuation was measured at thoracoabdominal CT in 1966 consecutive adults (983 men and 983 women) 65 years and older (mean age, 74.1 ± 6.6 [SD] years). Sagittal reconstructions and lateral scouts were analyzed for moderate or severe thoracolumbar vertebral compression fractures according to the Genant semiquantitative assessment method. The diagnostic performance of L1 attenuation for the evaluation of prevalent vertebral fractures was assessed, including ROC curve analysis. RESULTS A total of 162 (8.2%) individuals (mean age, 78.3 years; 66 men, 96 women) had at least one moderate or severe vertebral fracture. The mean L1 attenuation was 70.2 HU among patients with a prevalent fracture, whereas it was 132.3 HU among patients without fracture (p < 0.001). The prevalence of moderate or severe vertebral compression fractures was 32.5% when L1 attenuation was ≤ 90 HU. Prevalence increased to 49.2% with L1 attenuation of ≤ 50 HU. ROC curve analysis determined an optimal threshold of 90 HU (sensitivity = 86.9%, specificity = 83.9%), with a corresponding AUC of 0.895. The odds ratio of having a moderate or severe vertebral compression fracture was 31.9 for L1 attenuation ≤ 90 HU (95% CI, 20.2-50.5; p < 0.001). CONCLUSION Patients with moderate or severe vertebral compression fractures have significantly lower L1 attenuation values than patients who do not. L1 attenuation ≤ 90 HU may represent an optimal threshold for determining risk for osteoporotic vertebral fractures.

CT texture features of liver parenchyma for predicting development of metastatic disease and overall survival in patients with colorectal cancer

AbstractObjectivesTo determine if identifiable hepatic textural features are present at abdominal CT in patients with colorectal cancer (CRC) prior to the development of CT-detectable hepatic metastases.MethodsFour filtration–histogram texture features (standard deviation, skewness, entropy and kurtosis) were extracted from the liver parenchyma on portal venous phase CT images at staging and post-treatment surveillance. Surveillance scans corresponded to the last scan prior to the development of CT-detectable CRC liver metastases in 29 patients (median time interval, 6 months), and these were compared with interval-matched surveillance scans in 60 CRC patients who did not develop liver metastases. Predictive models of liver metastasis-free survival and overall survival were built using regularised Cox proportional hazards regression.ResultsTexture features did not significantly differ between cases and controls. For Cox models using all features as predictors, all coefficients were shrunk to zero, suggesting no association between any CT texture features and outcomes. Prognostic indices derived from entropy features at surveillance CT incorrectly classified patients into risk groups for future liver metastases (p < 0.001).ConclusionsOn surveillance CT scans immediately prior to the development of CRC liver metastases, we found no evidence suggesting that changes in identifiable hepatic texture features were predictive of their development.Key Points• No correlation between liver texture features and metastasis-free survival was observed. • Liver texture features incorrectly classified patients into risk groups for liver metastases. • Standardised texture analysis workflows need to be developed to improve research reproducibility.

Opportunistic Screening for Osteoporosis Using Body CT Scans Obtained for Other Indications: the UW Experience

Low bone mineral density (osteoporosis and osteopenia) leading to fragility fractures is associated with significant morbidity and mortality in our aging population. This condition is grossly underdiagnosed due to both insufficient screening and its silent nature prior to complicating fragility fractures. Body CT scans are commonly obtained among older adults for a wide variety of indications and contain rich data regarding bone health that are often ignored. At the University of Wisconsin, we have sought to harness this CT information for “opportunistic” osteoporosis screening. In this article, we review the various CT-based approaches we have taken to date, including routine assessment of the spine for both vertebral fractures and trabecular density, as well as assessment of the hip, deriving femoral neck T-scores that are essentially equivalent to dual-energy x-ray absorptiometry (DXA). Future directions of research and clinical implementation are also discussed.

Future Osteoporotic Fracture Risk Related to Lumbar Vertebral Trabecular Attenuation Measured at Routine Body CT: VERTEBRAL TRABECULAR ATTENUATION VALUES AND OSTEOPOROTIC FRACTURE RISK

We sought to determine if vertebral trabecular attenuation values measured on routine body computed tomography (CT) scans obtained for a variety of unrelated indications can predict future osteoporotic fractures at multiple skeletal sites. For this Health Insurance Portability and Accountability Act (HIPAA)‐compliant and Institutional Review Board (IRB)‐approved retrospective cohort study, trabecular attenuation of the first lumbar vertebra was measured in 1966 consecutive older adults who underwent chest and/or abdominal CT at a single institution over the course of 1 year. New pathologic fragility fractures that occurred after a patients CT study date were identified through an electronic health record database query using International Classification of Diseases (ICD)‐9 codes for vertebral, hip, and extremity fractures. Univariate and multivariate Cox proportional hazards regression were performed to determine the effect of L1 trabecular attenuation on fracture‐free survival. Age at CT, sex, and presence of a prior fragility fracture were included as confounders in multivariate survival analysis. Model discriminative capability was assessed through calculation of an optimism‐corrected concordance index. A total of 507 patients (mean age 73.4 ± 6.3 years; 277 women, 230 men) were included in the final analysis. The median post‐CT follow‐up interval was 5.8 years (interquartile range 2.1–11.0 years). Univariate analysis showed that L1 attenuation values ≤90 Hounsfield units (HU) are significantly associated with decreased fracture‐free survival (p < 0.001 by log‐rank test). After adjusting for age, sex, prior fracture, glucocorticoid use, bisphosphonate use, chronic kidney disease, tobacco use, ethanol abuse, cancer history, and rheumatoid arthritis history, multivariate analysis demonstrated a persistent modest effect of L1 attenuation on fracture‐free survival (hazard ratio [HR] = 0.63 per 10‐unit increase; 95% confidence interval [CI] 0.47–0.85). The model concordance index was 0.700. Ten‐year probabilities for major osteoporosis‐related fractures straddled the treatment threshold for most subcohorts over the observed L1 HU range. In conclusion, for patients undergoing body CT scanning for any indication, L1 vertebral trabecular attenuation is a simple measure that, when ≤90 HU, identifies patients with a significant decrease in fracture‐free survival.