Faculty Bibliography

BACKGROUND:Marrow adipose tissue (MAT) is increasingly recognized as an active and dynamic endocrine organ that responds to changes in nutrition and environmental milieu. Compared to normal weight controls, adolescent girls with anorexia nervosa have higher MAT content, which is associated with impaired skeletal integrity, but data are limited regarding MAT content in adolescents with obesity and how this interacts with bone endpoints. OBJECTIVE:To evaluate (i) MAT content in adolescents with obesity compared to normal-weight controls, (ii) the association of MAT with bone endpoints, and (iii) whether these associations of MAT are affected by body weight. METHODS:We assessed MAT, bone endpoints, and body composition in 60 adolescent girls 14-21 years old: 45 with obesity (OB) and 15 normal-weight controls (NW-C). We used (i) DXA to assess areal bone mineral density (aBMD) at the lumbar spine and total hip, and total body fat and lean mass, (ii) proton magnetic resonance spectroscopy (1H-MRS) to assess MAT at the 4th lumbar vertebra and femur, and MRI to assess visceral (VAT) and subcutaneous adipose tissue (SAT), (iii) high resolution peripheral quantitative CT (HR-pQCT) to assess volumetric BMD (vBMD), (iv) individual trabeculae segmentation to evaluate trabecular bone (plate-rod morphology), and (v) finite element analysis to assess stiffness (a strength estimate) at the distal radius and tibia. RESULTS:Groups did not differ for age or height. Weight, BMI, and areal BMD Z-scores at all sites were higher in the OB group (p<0.0001). MAT was lower in OB at the femoral diaphysis (p= <0.0001) and the lumbar spine (p=0.0039). For the whole group, MAT at the lumbar spine and femoral diaphysis was inversely associated with BMI, total fat mass, lean mass, and VAT. Even after controlling for body weight, independent inverse associations were observed of femoral diaphyseal and lumbar MAT with total tibial vBMD, and of lumbar MAT with radial trabecular vBMD. CONCLUSION:Adolescent girls with obesity have lower MAT than normal-weight controls despite having an excess of total body fat. These findings confirm that MAT is regulated uniquely from other adipose depots in obesity. MAT was inversely associated with vBMD, emphasizing an inverse relationship between MAT and bone even in adolescent girls with obesity.

OBJECTIVE:To demonstrate fluoroscopy dose reduction through both simulated injections on a phantom and patient injections. MATERIALS AND METHODS/METHODS:Our study was IRB-approved and HIPAA-compliant. Simulation on a phantom was used to estimate effective dose, entrance dose, and organ doses for hip joint injections without and with dose minimization technique (DMT). Additionally, 1,094 joint, bursae, and tendon sheath injections performed by three operators in the same fluoroscopy suite were evaluated both before and after application of DMT. Fluoroscopy time (FT), dose, and dose area product (DAP) of injections were compared using unpaired t-tests with P > 0.05 considered statistically significant. RESULTS:) for all three operators decreased with DMT and remained statistically significant when stratified by the two most common injections, glenohumeral and hip joint injections (P < 0.05). CONCLUSIONS:FT, effective dose, entrance dose, and DAP can be reduced with the use of simple easy-to-learn techniques, which will benefit both the patient and the radiologist.

OBJECTIVES:Plexiform neurofibromas (PNs) are complex, histologically benign peripheral nerve sheath tumors that are challenging to measure by simple line measurements. Computer-aided volumetric segmentation of PN has become the recommended method to assess response in clinical trials directed at PN. Different methods for volumetric analysis of PN have been developed. The goal of this study is to test the level of agreement in volume measurements and in interval changes using two separate methods of volumetric magnetic resonance imaging analysis. METHODS:Three independent volume measurements were performed on 15 PN imaged at three time-points using 3DQI software at Massachusetts General Hospital (MGH) and National Cancer Institute (NCI) and MEDx software at NCI. RESULTS:Median volume differences at each time-point comparing MGH-3DQI and NCI-3DQI were -0.5, -4.2, and -19.9 mL; comparing NCI-3DQI and NCI-MEDx were -21.0, -47.0, and -21.0 mL; comparing MGH-3DQI and NCI-MEDx were -10.0, -70.3, and -29.9 mL. Median differences in percentage change over time comparing MGH-3DQI and NCI-3DQI were -1.7, 1.1, and -1.0%; comparing NCI-3DQI and NCI-MEDx were -2.3, 3.3, and -1.1%; comparing MGH-3DQI and NCI-MEDx were -0.4, 2.0, and -1.5%. Volume differences were <20% of the mean of the two measurements in 117 of 135 comparisons (86.7%). Difference in interval change was <20% in 120 of the 135 comparisons (88.9%), while disease status classification was concordant in 115 of 135 comparisons (85.2%). CONCLUSIONS:The volumes, interval changes, and progression status classifications were in good agreement. The comparison of two volumetric analysis methods suggests no systematic differences in tumor assessment. A prospective comparison of the two methods is planned.

Marrow adipose tissue (MAT) in humans is distributed differentially across age and skeletal site. We have shown impaired microarchitecture and reduced bone strength at appendicular sites in conditions associated with high MAT of the axial skeleton in adults (including conditions of over- and undernutrition). Data are lacking regarding differences in MAT content of the appendicular versus the axial skeleton, and its relationship with bone microarchitecture and strength. Furthermore, data are conspicuously lacking in adolescents, a time when hematopoietic marrow is progressively converted to fatty marrow. The purpose of our study was to examine differential associations between appendicular (distal tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength estimates of the distal tibia in adolescents with obesity. We hypothesized that compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular skeleton (distal tibia) would show stronger associations with bone microarchitecture and strength estimates of the appendicular skeleton (distal tibia). We evaluated 32 adolescents and young adults (27 females) with obesity; with a mean age of 17.8 ± 2.1 years and median body mass index (BMI) of 41.34 kg/m², who underwent dual energy X-ray absorptiometry (DXA) for total fat mass, proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia for volumetric bone mineral density (vBMD) and microarchitecture, and micro finite element analysis (FEA) for distal tibial strength estimates. Linear correlations between bone parameters and MAT were determined using the Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was inversely associated with age (r = -0.36; p = 0.037). Total and trabecular vBMD and trabecular number at the distal tibia were inversely associated with MAT at the distal tibia (r = -0.39, p = 0.025; r = -0.51, p = 0.003; r = -0.42, p = 0.015 respectively) but not with lumbar spine MAT (r = -0.19, p = 0.27; r = -0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults with obesity, the associations between MAT and appendicular bone parameters differ depending on the site of MAT assessment i.e. axial vs. appendicular. Studies evaluating these endpoints in adolescents and young adults with obesity should take the site of MAT assessment into consideration.

The functional and evolutionary implications of primitive retentions in early hominin feet have been under debate since the discovery of Australopithecus afarensis. Ontogeny can provide insight into adult phenotypes, but juvenile early hominin foot fossils are exceptionally rare. We analyze a nearly complete, 3.32-million-year-old juvenile foot of A. afarensis (DIK-1-1f). We show that juvenile A. afarensis individuals already had many of the bipedal features found in adult specimens. However, they also had medial cuneiform traits associated with increased hallucal mobility and a more gracile calcaneal tuber, which is unexpected on the basis of known adult morphologies. Selection for traits functionally associated with juvenile pedal grasping may provide a new perspective on their retention in the more terrestrial adult A. afarensis.

OBJECTIVE:To evaluate clinical and radiological features of pathology-proven extraskeletal osteosarcomas. METHODS:This retrospective study was IRB-approved and HIPAA-compliant. Our pathology database was queried for cases of extraskeletal osteosarcoma. Tumor location, size, imaging appearance, presence of metastases, and clinical outcome were documented. RESULTS:Nineteen patients met inclusion criteria (age 59 ± 15 (range 28-85) years; 15 male, 4 female). Tumors occurred in the lower extremities (12 out of 19, 63%), pelvis/gluteal region (3 out of 19, 16%), upper extremity (2 out of 19, 5%), thorax (1 out of 19, 5%), and neck (1 out of 19, 5%). Two out of 19 (11%) patients had undergone radiation to the tumor site previously. According to pathology, 16 out of 19 tumors were high-grade (84%). Tumors presented as soft-tissue masses measuring 9.5 ± 6.8 (2-29) cm. Tumor mineralization was present in 5 out of 19 cases (26%) and local invasion was found in 1 out of 19 cases (6%). On MRI, tumors typically appeared hyperintense on T2-weighted sequences with enhancement in 15 out of 15 (100%) contrast-enhanced studies, and with central necrosis in 10 out of 19 (53%) cases. Low-grade tumors were smaller (<4 cm; 3 out of 3, 100%) and lacked central necrosis (3 out of 3, 100%). 8 out of 19 patients (42%) had metastases, most commonly to the lung (7 out of 19, 37%) and bone (2 out of 19,11%). Two out of 8 patients (25%) with metastases and 8 out of 11 (73%) without metastases achieved recurrence-free survival (mean follow-up 3.8 ± 4.0 [0.2-14.2]) years. No metastases or deaths occurred in patients with low-grade histology. CONCLUSIONS:Extraskeletal osteosarcomas are rare, typically high-grade malignancies that commonly metastasize to lung and bones. Low-grade tumors and those without metastases have a good prognosis. MRI appearance is nonspecific, with T2 hyperintense signal and heterogeneous enhancement. Unlike conventional osteosarcoma, mineralization is rare.

BACKGROUND:Altered bone microarchitecture and higher marrow adipose tissue (MAT) may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while 1H-magnetic resonance spectroscopy (1H-MRS) allows MAT evaluation. We have reported impaired microarchitecture at the non-weight bearing radius in adolescents with anorexia nervosa (AN) and that these changes may precede aBMD deficits. Data are lacking regarding effects of AN on microarchitecture and strength at the weight-bearing tibia in adolescents and young adults, and the impact of changes in microarchitecture and MAT on strength estimates. OBJECTIVE:To compare strength estimates at the distal tibia in adolescents/young adults with AN and controls in relation to vBMD, bone size and microarchitecture, and spine MAT. DESIGN AND METHODS/METHODS:This was a cross-sectional study of 47 adolescents/young adults with AN and 55 controls 14-24years old that assessed aBMD and body composition using DXA, and distal tibia vBMD, size, microarchitecture and strength estimates using HRpQCT, extended cortical analysis, individual trabecular segmentation, and finite element analysis. Lumbar spine MAT (1H-MRS) was assessed in a subset of 19 AN and 22 controls. RESULTS:Areal BMD Z-scores were lower in AN than controls. At the tibia, AN had greater cortical porosity, lower total and cortical vBMD, cortical area and thickness, trabecular number, and strength estimates than controls. Within AN, strength estimates were positively associated with lean mass, aBMD, vBMD, bone size and microarchitectural parameters. MAT was higher in AN, and associated inversely with strength estimates. CONCLUSIONS:Adolescents/young adults with AN have impaired microarchitecture at the weight-bearing tibia and higher spine MAT, associated with reduced bone strength.

BACKGROUND:There are limited predictors of prognosis in patients with clinically non-functioning pituitary adenomas (NFPAs). We hypothesized that MRI texture analysis may predict tumor recurrence or progression in patients with NFPAs undergoing transsphenoidal pituitary surgery (TSS). OBJECTIVE:To characterize texture parameters on preoperative MRI examinations in patients with NFPAs in relation to prognosis. METHODS:Retrospective study of patients with NFPAs who underwent TSS at our institution between 2009 and 2010. Clinical, radiological and histopathological data were extracted from electronic medical records. MRI texture analysis was performed on coronal T1-weighted non-enhanced MR images using ImageJ (NIH). MRI texture parameters were used to predict tumor recurrence or progression. Both logistic regression and Cox proportional hazard analyses were conducted to adjust for potential confounders. RESULTS: = 0.034) for recurrence or progression in comparison with tumors below the median. CONCLUSIONS:Our data suggest that MRI texture analysis can predict the risk of tumor recurrence or progression in patients with NFPAs.

Background Recent studies have suggested that the quantity and quality of adipose tissue and muscle, assessed on non-contrast computed tomography (CT), may serve as imaging biomarkers of survival in patients with and without neoplasms. Purpose To assess body composition measures that could serve as predictors of therapy response in patients with extremity soft tissue sarcomas treated with radiation therapy and surgery. Material and Methods The study was IRB-approved. Sixty patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT prior to radiation therapy and surgical resection. Cross-sectional areas and CT attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical information on predictors of tumor recurrence and post-surgical wound infections were recorded. Cox proportional hazard models were used to determine longitudinal associations between body composition and tumor recurrence/wound infections. Results Twenty-three tumor recurrences occurred over a follow-up period of 43 ± 35 months. Higher SAT and lower psoas attenuation were associated with tumor recurrence which remained significant after adjustment for covariates ( P ≤ 0.01). There were 13 post-surgical wound infections. Higher VAT and SAT attenuation were associated with post-surgical wound infections ( P < 0.04); however, VAT attenuation lost significance after adjustment for covariates. Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non-contrast CT may predict tumor recurrence and post-surgical infections in patients with extremity soft tissue sarcomas.

OBJECTIVE:To evaluate the significance of biceps tendon (BT) displacement and peri-bicipital hematoma on MRI in subjects with pectoralis major (PM) tears. We hypothesized that these features might be associated with tear severity at surgery. MATERIALS AND METHODS/METHODS:We retrospectively identified MRI cases with PM injury and reviewed clinical, imaging, and surgical records. MR images were reviewed independently by two musculoskeletal radiologists to determine anterior displacement of BT (BT-disp, in mm) and the presence of triangular-shaped peri-bicipital hematoma. Data were compared with an age- and sex-matched control group and correlated with surgical reports grouped by tear severity. RESULTS:We identified 46 subjects with PM injury (43 men, 3 women; mean age 34 ± 9 years), 26 of whom underwent surgical reconstruction, and 20 matched controls (P > 0.2). BT-disp was significantly higher in PM injury vs controls (P = 0.003), and in tendon vs myotendinous (MT) junction PM tears (P < 0.0001); however, MT junction tears vs controls were similar (P = 0.98). Higher BT-disp and presence of peri-bicipital hematoma correlated significantly with surgical reports describing full-thickness complete tears. BT-disp > 4.5 mm had 86% sensitivity and 75% specificity to detect the most severe tears on surgical reports, whereas the presence of peri-bicipital hematoma was the strongest predictor among both parameters. CONCLUSION/CONCLUSIONS:Anterior BT displacement and peri-bicipital hematoma are helpful indicators of full-thickness complete tears at the humeral insertion.