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.

Bone marrow adipose tissue (BMAT) resides within the bone marrow microenvironment where its function remains poorly understood. BMAT is elevated in anorexia nervosa, a disease model of chronic starvation, despite depletion of other fat depots. In addition to BMAT, the marrow microenvironment also consists of osteoblast and hematopoietic progenitors. BMAT is inversely associated with bone mineral density (BMD) in multiple populations including women with anorexia nervosa, and regulates hematopoiesis in animal models. We hypothesized that BMAT would be associated with circulating populations of hematopoietic cells (red and white blood cells) in humans and performed a post hoc analysis of two studies-a cross-sectional study and a longitudinal study-to investigate this hypothesis. We studied 89 premenopausal women cross-sectionally (median age [interquartile range], 27 [24.5, 31.7] years), including 35 with anorexia nervosa. We investigated associations between red blood cell (RBC) and white blood cell (WBC) counts and BMAT assessed by ¹ H-magnetic resonance spectroscopy, BMD assessed by DXA, and bone microarchitecture assessed by HR-pQCT. In addition, we analyzed longitudinal data in six premenopausal women with anorexia nervosa treated with transdermal estrogen for 6 months and measured changes in BMAT and blood cell counts during treatment. Cross-sectionally, BMAT was inversely associated with WBC and RBC counts. In contrast, BMD and parameters of bone microarchitecture were positively associated with WBC and RBC. In women with anorexia nervosa treated with transdermal estrogen for 6 months, decreases in BMAT were significantly associated with increases in both RBC and hematocrit (rho = -0.83, p = 0.04 for both). In conclusion, we show that BMAT is inversely associated with WBC and RBC in premenopausal women, and there is a potential association between longitudinal changes in BMAT and changes in RBC. These associations warrant further study and may provide further insight into the role and function of this understudied adipose depot. © 2020 American Society for Bone and Mineral Research.

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.

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.

BACKGROUND:Sleeve gastrectomy is the most commonly performed weight loss surgery in adolescents with moderate-to-severe obesity. While studies in adults have reported on the deleterious effects of gastric bypass surgery on bone structure and strength estimates, data are lacking for the impact of sleeve gastrectomy on these measures in adolescents. OBJECTIVE:To evaluate the impact of sleeve gastrectomy on bone outcomes in adolescents and young adults over 12 months using dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT). PARTICIPANTS AND METHODS:We enrolled 44 youth 14-22 years old with moderate to severe obesity; 22 underwent sleeve gastrectomy and 22 were followed without surgery (16 females and 6 males in each group). At baseline and 12 months, DXA was used to assess areal bone mineral density (aBMD), HRpQCT of the distal radius and tibia was performed to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess strength estimates (stiffness and failure load). These analyses were adjusted for age, sex, race and the bone measure at baseline. Fasting blood samples were assessed for calcium, phosphorus, and 25(OH) vitamin D (25OHD) levels. RESULTS:Over 12-months, the surgical group lost 27.2% of body weight compared to 0.1% in the non-surgical (control) group. Groups did not differ for changes in 25OHD levels (p = 0.186). Compared to controls, the surgical group had reductions in femoral neck and total hip aBMD Z-scores (p ≤ 0.0006). At the distal tibia, compared to controls, the surgical group had reductions in cortical area and thickness and trabecular number, and increases in trabecular area and separation (p ≤ 0.026). At the distal radius, the surgical group had greater reductions in trabecular vBMD, than controls (p = 0.010). The surgical group had an increase in cortical vBMD at both sites (p ≤ 0.040), possibly from a decrease in cortical porosity (p ≤ 0.024). Most, but not all, differences were attenuated after adjusting for 12-month change in BMI. Groups did not differ for changes in strength estimates over time, except that increases in tibial stiffness were lower in the surgical group (p = 0.044) after adjusting for 12-month change in BMI. CONCLUSIONS:Over 12 months, weight loss associated with sleeve gastrectomy in adolescents had negative effects on areal BMD and certain HRpQCT parameters. However, bone strength estimates remained stable, possibly because of a simultaneous decrease in cortical porosity and increase in cortical volumetric BMD. Additional research is necessary to determine the relative contribution(s) of weight loss and the metabolic effects of surgery on bone outcomes, and whether the observed effects on bone stabilize or progress over time.

OBJECTIVE:To evaluate organ dose and total effective dose of whole-body low-dose CT (WBLDCT) performed on different CT-scanner models in patients with multiple myeloma (MM) and to compare it to the effective dose of radiographic skeletal survey and representative diagnostic CTs. MATERIAL AND METHODS/METHODS:We retrospectively analyzed data from 228 patients (47.4% females, mean age 67.9 ± 10.4 years, mean weight 81.8 ± 22.4 kg) who underwent WBLDCT for the work-up or surveillance of MM. Patients were scanned using one of six multi-detector CT-scanners. Organ doses and total effective doses per scan were calculated using a commercially available dose-management platform (Radimetrics, Bayer Healthcare, Leverkusen, Germany). The median effective dose was compared to radiographic skeletal survey and representative diagnostic CTs. RESULTS:The mean effective dose of our WBLDCT-protocol was 4.82 mSv. A significantly higher effective dose was observed in females compared to males (4.95 vs. 4.70 mSv, P = 0.002). Mean organ dose ranged from 3.72 mSv (esophagus) to 13.09 mSv (skeleton). Mean effective dose varied amongst different CT-scanners (range 4.34-8.37 mSv). The median effective dose of WBLDCT was more than twice the dose of a skeletal survey (4.82 vs. 2.04 mSv), 23% higher than a diagnostic contrast-enhanced chest CT (3.9 mSv), 46% lower than a diagnostic contrast-enhanced abdomen/pelvis CT (9.0 mSv), and 45% lower than a lumbar spine CT (8.7 mSv). CONCLUSIONS:WBLDCT in MM has a higher effective dose than a radiographic skeletal survey, but a lower effective dose than diagnostic CTs of lumbar spine, abdomen and pelvis. This underlines the broad applicability of WBLDCT in the management of MM patients.

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.

OBJECTIVE:The purpose of our study was to determine the role of brown adipose tissue (BAT) in cancer progression. MATERIALS AND METHODS/METHODS:Our study was approved by our institutional review board and Health Insurance Portability and Accountability Act-compliant. Our study group comprised 132 cancer patients (116 f, 16 m; mean age 50 ± 16 years) who underwent F18-FDG PET/CT per standard clinical protocol, for staging or surveillance of cancer. We included patients who were BAT-positive on PET/CT and had clinical follow-up data available for at least 12 months or until tumor recurrence or tumor-related death, whichever occurred first. BAT volume by PET/CT was quantified by PET-CT Viewer shareware. Clinical information including tumor type, tumor recurrence, survival, and outside temperature at time of scan were recorded. Cox proportional hazard models were used to determine longitudinal associations between BAT volume and tumor recurrence/mortality. RESULTS:There were 55 tumor recurrences/tumor-related deaths over a median follow-up period of 71 (33; 110 interquartile range) months. Higher BAT volume was associated with an increased likelihood of tumor recurrence/tumor-associated mortality after adjustment for covariates (p = 0.03). CONCLUSION/CONCLUSIONS:BAT volume, assessed using routine PET/CT, is a predictor of tumor recurrence/mortality in patients with cancer, independent of other factors that can influence BAT activity, such as sex, age, BMI, or tumor type.

This paper summarizes the highlights of the Scientific Sessions of the 46th Annual Scientific Meeting of the International Skeletal Society (ISS) which was hosted in Vancouver, Canada, in September 2019.