Faculty Bibliography

OBJECTIVE:To investigate the genotype-phenotype correlation between neurofibromatosis 1 (NF1) germline mutations and imaging features of neurofibromas on whole-body MRI (WBMRI) by using radiomics image analysis techniques. MATERIALS AND METHODS:Twenty-nine patients with NF1 who had known germline mutations determined by targeted next-generation sequencing were selected from a previous WBMRI study using coronal short tau inversion recovery sequence. Each tumor was segmented in WBMRI and a set of 59 imaging features was calculated using our in-house volumetric image analysis platform, 3DQI. A radiomics heatmap of 59 imaging features was analyzed to investigate the per-tumor and per-patient associations between the imaging features and mutation domains and mutation types. Linear mixed-effect models and one-way analysis of variance tests were performed to assess the similarity of tumor imaging features within mutation groups, between mutation groups, and between randomly selected groups. RESULTS:values of within-patient groups were more than 2 times higher than those between-patient groups. However, the numbers of SDFs between randomly selected groups were much lower (approximately 5.2%). CONCLUSION:genotype and imaging phenotype on WBMRI.

OBJECTIVE:The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients. MATERIALS/METHODS:Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV]). RESULTS:Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients. CONCLUSIONS:Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.

BACKGROUND:African Americans (AA) have more favorable bone density and microarchitecture compared to Whites (W), which may explain their observed lower fracture rates. Obesity has deleterious effects on bone microarchitecture and strength estimates and is associated with an increase in fracture risk. Adolescence and young adulthood are periods of active bone accrual and also periods characterized by an increasing prevalence of obesity. The effect of obesity on the relationship between race and bone parameters remains unclear, particularly in youth. OBJECTIVE:To assess differences in BMD, bone microarchitecture and strength estimates in AA and W adolescents and young adults with moderate to severe obesity. We hypothesized that racial differences in bone endpoints in lean youth would also be noted in youth with moderate to severe obesity. METHODS:who underwent dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT), extended cortical analysis (ECA) and micro-finite element analysis (FEA) to obtain measures of volumetric bone mineral density (vBMD), bone geometry, microarchitecture, and strength estimates at the distal radius and tibia. RESULTS:We found no differences between AA and W for total fat and lean mass, and areal BMD Z-scores (p > 0.05 for all). At the distal radius, no significant differences were detected in vBMD, bone geometry or microarchitecture (p > 0.05 for all); however, stiffness and failure load were higher in the AA group (p = 0.031 and 0.047 respectively). At the distal tibia, cortical vBMD was higher in AA vs. W (p = 0.012), while trabecular number was higher and trabecular separation lower in W vs. AA (p ≤ 0.028). Stiffness and failure load trended higher in AA vs. W (p = 0.052 and p = 0.048, respectively). Groups did not differ for any other bone parameter (p > 0.05). CONCLUSION:Racial differences in bone endpoints appear to be less marked in those with moderate to severe obesity, suggesting that effects of obesity may blunt the effect of race on bone endpoints.

PURPOSE/OBJECTIVE:To determine the effect of intra-articular corticosteroid injections on lumbar spine trabecular density. MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. We identified 50 patients (26 F, 24 M, mean age 69 ± 14 years) who had undergone at least three medium or large joint corticosteroid injections using insoluble corticosteroids and a subsequent non-contrast abdominal CT within 5 years of the first injection. About 126 age- and sex-matched controls without history of prior corticosteroid use who had undergone non-contrast abdominal CT were identified. Cumulative corticosteroid dose was calculated. Density measurements (HU) of trabecular bone of L1 to L4 were performed, and measurements of L1 were compared to established normative data. Groups were compared using a two-sided paired t-test or a chi-squared test. Linear regression analysis between cumulative corticosteroid dose and trabecular density was performed. RESULTS:Patients underwent a mean of 4 corticosteroid injections (range 3 to 11) with a mean cumulative corticosteroid dose of 232 ± 100 mg triamcinolone equivalent (range 120 mg to 480 mg). There was no significant difference in trabecular density of L1 to L4 between cases and controls, and there was no significant difference in trabecular density at L1 compared to normative data (p > 0.2). There was no association between cumulative intra-articular corticosteroid dose and mean lumbar trabecular density (p > 0.3). CONCLUSION/CONCLUSIONS:Patients who underwent repetitive intra-articular insoluble corticosteroid injections showed no increased risk of bone loss compared to controls. Cumulative intra-articular corticosteroid dose was not associated with lumbar trabecular density.

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.

PURPOSE/OBJECTIVE:To determine the value of anesthetic injection during hip MR arthrography (anesthetic MRA) to differentiate between intra- and extra-articular pathology in patients with hip pain. MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. We included 75 consecutive adult patients (46 women, mean age 38 ± 13 years) who were referred for MRA. All patients underwent a focused hip examination including active flexion, passive flexion, and passive flexion with internal and external rotation, immediately prior to injection. Anesthetic MRA was performed following fluoroscopically guided intra-articular injection of contrast mixed with anesthetic. Following the injection, the hip examination was repeated, and the pain response was recorded. Clinical records, including response to corticosteroid injections, physical therapy notes, and operative reports were reviewed for verification of intra- and extra-articular pathology as the source of hip pain (gold standard). The positive (PPV) and negative predictive values (NPP) of anesthetic MRA to differentiate between intra- and extra-articular pathology were calculated. RESULTS:On MRI, 41 patients had only intra-articular and 5 patients only extra-articular pathology, while 29 patients had both, intra- and extra-articular pathology. Forty-three patients had pain relief and 32 patients had no pain relief after anesthetic injection. PPV of anesthetic MRA to detect intra-articular pathology was 91% and NPV was 67%. CONCLUSION/CONCLUSIONS:Anesthetic MRA can be used as an adjunct to define the origin of hip pain. A positive response suggests intra-articular pathology which can be helpful to localize the source of pain in equivocal cases where both intra- and extra-articular pathology are evident on MRI.

BACKGROUND/OBJECTIVE:Less muscle mass has been associated with greater insulin resistance, but whether the association is independent of deleterious adipose depots in young adults with overweight/obesity who are at high risk for type 2 diabetes (T2DM) but are otherwise metabolically healthy is not known. The objective of this study was to determine whether muscle mass is independently associated with insulin sensitivity (IS) in young adults with overweight/obesity. SUBJECTS/METHODS:and metabolically healthy without T2DM. Primary independent variable: percent ideal appendicular lean mass (ALM) calculated as measured ALM divided by predicted ALM for age, weight, and height, calculated using validated NHANES data-based equation. Primary dependent variable: IS by Matsuda index. RESULTS:(mean ± SD). Individuals in the highest % ideal ALM tertile had mean IS 45% higher than the lowest tertile [6.94 ± 0.85 vs 4.80 ± 0.56 (mean ± SEM), p = 0.008] (sex interaction p = 0.003). Men in the highest % ideal ALM tertile had mean IS twice the lowest tertile (5.47 ± 0.68 vs 2.68 ± 0.34, p = 0.001), which remained significant controlling for visceral/subcutaneous and intermuscular adipose tissue, and intramyocellular and intrahepatic lipids (p = 0.03). The association was not significant in women. CONCLUSIONS:Muscle mass is associated with IS independent of detrimental adipose depots in young men with overweight/obesity, at risk for T2DM but currently metabolically healthy. Muscle mass relative to sex, age, weight, and height-specific norms may be used to ascertain individual T2DM risk associated with low muscle mass.

PURPOSE/OBJECTIVE:Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs). METHODS:We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes. RESULTS:Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33-26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression. CONCLUSION/CONCLUSIONS:Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.

CONTEXT:Sleeve gastrectomy (SG), the most common metabolic and bariatric surgery in adolescents, is associated with bone loss. Marrow adipose tissue (MAT) is a dynamic endocrine organ that responds to changes in nutrition and might serve as a novel biomarker for bone health. Two types of MAT have been described, which differ in anatomic location-proximal regulated MAT vs distal constitutive MAT. OBJECTIVE:To determine the effects of SG on volumetric bone mineral density (vBMD) and MAT in adolescents with obesity. We hypothesized that SG would lead to a decrease in vBMD and differential changes in MAT. DESIGN:12-month prospective study in 52 adolescents with moderate-to-severe obesity (38 female; mean age:17.5 ± 2.2 years; mean BMI 45.2 ± 7.0 kg/m2), comprising 26 subjects before and after SG and 26 nonsurgical controls. MAIN OUTCOME MEASURES:Lumbar vBMD by quantitative computed tomography; MAT of the lumbar spine, femur and tibia by proton magnetic resonance spectroscopy; abdominal fat and thigh muscle by magnetic resonance imaging. RESULTS:Adolescents lost 34.1 ± 13.1 kg after SG vs 0.3 ± 8.4 kg in the control group (P < 0.001). Lumbar vBMD decreased in the SG group (P = 0.04) and this change was associated with a reduction in weight and muscle area (P < 0.05) and an increase in lumbar MAT (P = 0.0002). MAT of the femur and tibia decreased after SG vs controls (P < 0.05); however, the differences were no longer significant after controlling for change in weight. CONCLUSION:SG in adolescents decreased lumbar vBMD associated with an increase in lumbar MAT and decrease in extremity MAT. This demonstrates differential changes of regulated MAT in the lumbar spine and constitutive MAT in the distal skeleton in adolescents in response to SG.

BACKGROUND:Sleeve gastrectomy (SG), the most commonly performed metabolic and bariatric surgery, is associated with reductions in areal bone mineral density at multiple sites, and changes in bone structure at the distal radius and tibia without reductions in strength estimates at these peripheral sites. Data are lacking regarding effects on hip strength estimates. OBJECTIVE:To evaluate effects of SG on measures of hip structural analysis in adolescents and young adults over 12 months using dual-energy x-ray absorptiometry. SETTINGS/METHODS:Translational and Clinical Research Center. METHODS:We enrolled 48 youth 14- to 22-years old with moderate-to-severe obesity; 24 underwent SG and 24 controls were followed without surgery (18 females, 6 males in each group). Hip structure was assessed using dual-energy x-ray absorptiometry at baseline and 12 months. Analyses are adjusted for age, sex, race, and the baseline bone measure. RESULTS:The SG group lost 25.9% weight versus .3% in controls. Compared with controls, SG had reductions in narrow neck, intertrochanteric and femoral shaft bone mineral density Z-scores (P ≤ .012). Furthermore, SG had greater reductions in narrow neck and intertrochanteric region (but not femoral shaft) cross-sectional area, cortical thickness, cross-sectional moment of inertia and section modulus, and increases in buckling ratio (P ≤ .039). Differences were attenuated after adjusting for 12-month body mass index change. At 12 months, differences were minimal after adjusting for age, sex, race, and weight. CONCLUSIONS:Over 12 months, SG had negative effects at the narrow neck and intertrochanteric regions of the hip, but not the femoral shaft. Reduced body mass index may compensate for these deleterious effects on bone.