Faculty Bibliography

Research examining bone marrow adipose tissue (BMAT) has rapidly expanded during the last two decades, leading to advances in knowledge on the role of BMAT in the pathogenesis of bone loss and endocrine disorders. Clinical imaging has played a crucial role for the in vivo assessment of BMAT, allowing non-invasive quantification and evaluation of BMAT composition. In the present work, we review different imaging methods for assessing properties of BMAT. Our aim is to review conventional magnetic resonance imaging (MRI), water-fat imaging, and single-voxel proton magnetic resonance spectroscopy (¹H-MRS), as well as computed tomography (CT)-based techniques, including single energy and dual energy CT. We will also discuss the clinical applications of these methods in type 2 diabetes mellitus, obesity and anorexia nervosa.

BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTSWe demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSIONHigh-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDINGNIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.

BACKGROUND:Musculoskeletal pain is a debilitating problem treated with image-guided corticosteroid injections. During the COVID-19 pandemic, multiple societies issued caution statements because of the unknown effect of corticosteroids on the patient's immune system. The purpose is to determine if image-guided corticosteroid injections administered during the COVID-19 lockdown phase were associated with a higher infection rate compared to the general population. MATERIALS AND METHODS/METHODS:In a prospective study, patients undergoing image-guided corticosteroid injections for pain management during the lockdown phase between April 15 and May 22, 2020, were enrolled. One month after the injection, patients were surveyed by telephone for any COVID-19-related symptoms, and the electronic medical record (EMR) was reviewed for symptoms and test results. RESULTS:Seventy-one subjects were recruited, 31 (44%) females, 40 (56%) males, ages 58 ± 17 (20-92) years. Follow-up was available in 66 (93%) of subjects, 60 (91%) by phone survey and EMR, 6 (9%) by EMR only, 45 ± 22 (19-83) days after injection. One (1/66, 1.52%; 95% CI 0.04-8.2%) 25-year-old male subject developed symptomatic infection 19 days after a tibiotalar injection. The prevalence of COVID-19 cases in the state of Massachusetts was 0.91% (62,726/6,892,503) during the study period. There was no significant difference in the rate of occurrence of new cases of COVID-19 infection between the corticosteroid injection group and the general population (p = 0.44). CONCLUSION/CONCLUSIONS:Image-guided corticosteroid injections for pain management performed during the lockdown phase of the COVID-19 pandemic were not associated with a higher infection rate compared to the general population.

AIMS/OBJECTIVE:Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1-NFATC2 or FUS-NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. METHODS AND RESULTS/RESULTS:Using RNA-based next-generation sequencing and/or fluorescence in-situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3-23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1-NFATC2 fusion (showing identical breakpoints to those in EWSR1-NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1-NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. CONCLUSIONS:More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy.

OBJECTIVE:To implement a multifaceted wellness program in an academic radiology department to prevent burnout and to assess initial outcomes with special focus on the challenges related to the coronavirus disease 2019 (COVID-19) pandemic. METHODS:A wellness program was established to address institutional and personal factors of burnout. The program focused on interventions to improve efficiency of practice, provide personal and career support, and create a culture of wellness. The components of the program were designed with input from radiology faculty, and the program was financially supported by the hospital's physician organization. A survey was performed 6 months after the initiation of the program to determine radiologist engagement and satisfaction. With the onset of the COVID-19 pandemic, a new survey was administered to identify needs of faculty and adjust initiatives. This study was exempt from institutional review board approval. RESULTS:The majority of radiologists (79%) agreed or strongly agreed that the wellness program provided opportunities to connect with coworkers. All radiologists agreed that the program was helpful and should be continued. During the COVID-19 pandemic, 49% of physicians requested initiatives focused on well-being, emotional health, and mindfulness to support them during the crisis. CONCLUSIONS:The implementation of a faculty wellness program in an academic radiology department addressed institutional and personal factors of burnout, allowed faculty to connect with coworkers, and was found to be helpful by all radiologists. The COVID-19 pandemic shifted needs to well-being and emotional health initiatives. Follow-up data are necessary to assess its effect on burnout reduction.

CONTEXT:Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD. METHODS AND MATERIALS:We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. RESULTS:Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08). CONCLUSION:We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.

OBJECTIVE:To implement a mentoring program for early career faculty in an academic radiology department and to assess its impact on career development. METHODS:A formal departmental mentoring program for early career faculty (instructors) who were paired with senior radiologists outside of their division was implemented. The program provided structured one-on-one mentoring, creation of a mentoring network, and opportunities for peer mentoring. A survey was conducted before and 1 year after initiation of the program. Historical data on promotion over 5 years before the implementation of the program was used to determine the impact on the rate of promotion. The study was exempt from institutional review board approval. RESULTS:Before and 1 year after implementation of the mentoring program, 57% versus 86% of instructors were satisfied with their mentor (P = .04); 43% versus 90% felt that by encouraging mentorship, the department valued their professional development (P = .001); 38% versus 86% felt that the department created an environment that promoted feedback and sharing of information (P = .002); and 43% versus 76% felt that faculty strove to support each other (P = .03). Since implementation of the program, 43% of instructors received grant funding, 50% received other awards, and 10 instructors were promoted to assistant professor, compared with an average of 4.2/y over the past 5 years. Of those, three were underrepresented minorities in medicine versus none in the previous 5 years. CONCLUSIONS:A mentoring program helped to advance the careers of early career and minority radiology faculty and helped create an atmosphere of more openness and support in the department.

UNLABELLED:In a population-based study, we found that computed tomography (CT)-based bone density and strength measures from the thoracic spine predicted new vertebral fracture as well as measures from the lumbar spine, suggesting that CT scans at either the thorax or abdominal regions are useful to assess vertebral fracture risk. INTRODUCTION/BACKGROUND:Prior studies have shown that computed tomography (CT)-based lumbar bone density and strength measurements predict incident vertebral fracture. This study investigated whether CT-based bone density and strength measurements from the thoracic spine predict incident vertebral fracture and compared the performance of thoracic and lumbar bone measurements to predict incident vertebral fracture. METHODS:This case-control study of community-based men and women (age 74.6 ± 6.6) included 135 cases with incident vertebral fracture at any level and 266 age- and sex-matched controls. We used baseline CT scans to measure integral and trabecular volumetric bone mineral density (vBMD) and vertebral strength (via finite element analysis, FEA) at the T8 and L2 levels. Association between these measurements and vertebral fracture was determined by using conditional logistic regression. Sensitivity and specificity for predicting incident vertebral fracture were determined for lumbar spine and thoracic bone measurements. RESULTS:Bone measurements from T8 and L2 predicted incident vertebral fracture equally well, regardless of fracture location. Specifically, for predicting vertebral fracture at any level, the odds ratio (per 1-SD decrease) for the vBMD and strength measurements at L2 and T8 ranged from 2.0 to 2.7 (p < 0.0001) and 1.8 to 2.8 (p < 0.0001), respectively. Results were similar when predicting fracture only in the thoracic versus the thoracolumbar spine. Lumbar and thoracic spine bone measurements had similar sensitivity and specificity for predicting incident vertebral fracture. CONCLUSION/CONCLUSIONS:These findings indicated that like those from the lumbar spine, CT-based bone density and strength measurements from the thoracic spine may be useful for identifying individuals at high risk for vertebral fracture.

PURPOSE:The prevalence of childhood obesity has increased over past decades with a concomitant increase in metabolic and bariatric surgery (MBS). While MBS in adults is associated with bone loss, only a few studies have examined the effect of MBS on the growing skeleton in adolescents. METHODS:This mini-review summarizes available data on the effects of the most commonly performed MBS (sleeve gastrectomy and gastric bypass) on bone in adolescents. A literature review was performed using PubMed for English-language articles. RESULTS:Dual-energy x-ray absorptiometry (DXA) measures of areal bone mineral density (aBMD) and BMD Z scores decreased following all MBS. Volumetric BMD (vBMD) by quantitative computed tomography (QCT) decreased at the lumbar spine while cortical vBMD of the distal radius and tibia increased over a year following sleeve gastrectomy (total vBMD did not change). Reductions in narrow neck and intertrochanteric cross-sectional area and cortical thickness were observed over this duration, and hip strength estimates were deleteriously impacted. Marrow adipose tissue (MAT) of the lumbar spine increased while MAT of the peripheral skeleton decreased a year following sleeve gastrectomy. The amount of weight loss and reductions in lean and fat mass correlated with bone loss at all sites, and with changes in bone microarchitecture at peripheral sites. CONCLUSION:MBS in adolescents is associated with aBMD reductions, and increases in MAT of the axial skeleton, while sleeve gastrectomy is associated with an increase in cortical vBMD and decrease in MAT of the peripheral skeleton. No reductions have been reported in peripheral strength estimates.