Faculty Bibliography

PURPOSE/OBJECTIVE:Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death for patients with neurofibromatosis type 1 (NF1). Identification of hypermetabolic lesions on PET may help identify patients at risk for MPNST. The objective of this study was to identify clinical and MRI-derived variables that predicted increased metabolic activity of neurofibromas in NF1 patients as determined by PET. METHODS:This prospective study included NF1 patients with neurofibromas of 5 cm in diameter or greater. All patients underwent whole-body MRI and F-FDG PET imaging. Tumor volume was calculated from the MR scans using a semiautomated 3-dimensional segmentation method. SUVmax's were calculated to quantify metabolic activity. Logistic regression analyses were performed to determine the relationship among SUVmax, tumor volume, location (extremity vs trunk), type (plexiform vs circumscribed), depth (superficial vs deep), patient age, and whole-body tumor burden. RESULTS:A total of 311 neurofibromas were identified in 19 NF1 patients (mean age, 38 years; range, 19-58 years). One extreme outlier was excluded from analysis. Whole-body tumor volumes ranged from 0.4 to 1182.4 mL. Fifty of 310 tumors were FDG-avid on PET (16%) with median SUVmax of 2.2 (range, 0.4-9.6). Metabolic activity (SUVmax >2.5) correlated with tumor location (deep > superficial, trunk > extremity) in tumors with PET avidity. CONCLUSIONS:In NF1 patients with neurofibromas of 5 cm or greater, the majority of internal tumors are not metabolically active on PET. Tumors with increased metabolic activity as defined by SUVmax greater than 2.5 (ie, suggestive of MPNST) are more likely to be deep and located within the trunk.

OBJECTIVE:To investigate the T2 relaxation values of the infrapatellar fat pad (IFP) after arthroscopic surgery. MATERIALS AND METHODS/METHODS:This study was approved by the institutional review board; all individuals signed informed consent. We performed MRI in 16 knees from 8 subjects. Prior to imaging, each subject had unilateral arthroscopic knee surgery and an asymptomatic non-operated contralateral knee. We used a 10-echo multiple-TE fast-spin echo pulse sequence for creation of T2 relaxation time maps. Two musculoskeletal radiologists independently placed regions of interest in the IFP, suprapatellar subcutaneous and deep intermuscular adipose tissue. Qualitative assessments were performed to assess fibrotic changes affecting patellar retinaculum and IFP. Statistical analyses of T2 values determined differences between groups, correlation with time after surgery, and cut-off values to differentiate groups. RESULTS:The average time between arthroscopy and imaging was 3.5 ± 0.4 years. IFP of knees with prior surgery had significantly shorter mean T2 values (133 ± 14 ms) compared with control knees (147 ± 8 ms, P = 0.03). There was no significant difference between operated and control knees regarding T2 values of suprapatellar subcutaneous (P = 0.3) or deep intermuscular adipose tissue (P = 0.2). There was no correlation between IFP T2 values and time after surgery (P > 0.2). IFP T2 values ≤ 139 ms had 75 % sensitivity and 88 % specificity in identifying prior arthroscopy. CONCLUSION/CONCLUSIONS:Shortening of T2 relaxation values is present in IFP chronically after arthroscopic surgery and may be an indicator of adipose tissue fibrosis.

Soft tissue angiofibroma is a recently described neoplasm that typically presents as a slowly growing, painless mass in the soft tissues of the lower extremities. Cytogenetic and molecular studies have identified a recurrent t(5;8) translocation. Treatment is simple excision. Existing data suggest that this tumor is benign and has a low rate of local recurrence. The radiologic and pathologic differential diagnoses for this lesion include both benign and malignant lesions, including plantar fibromatosis, tenosynovial giant cell tumor, fibroma of tendon sheath, epithelioid sarcoma, and low-grade myxofibrosarcoma. Proper identification of this benign lesion through radiologic and pathologic correlation is important to prevent misdiagnosis of a low-grade sarcoma.

BACKGROUND:Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL. METHODS:We examined 22 obese girls aged 13-21 years old for IR [defined as a homeostasis model assessment of insulin resistance (HOMA-IR) value >4. Phosphorus magnetic resonance spectroscopy (31P-MRS) and proton magnetic resonance spectroscopy (1H-MRS), respectively, were used to determine MF and IMCL of the soleus muscle along with magnetic resonance imaging (MRI) measures of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) in girls with HOMA-IR >4 (insulin-resistant group) versus HOMA-IR ≤ 4 (insulin-sensitive group). Serum lipids and waist-to-hip ratio (W/H) were also measured. RESULTS:Girls with IR (n=8) did not differ from the insulin-sensitive group (n=14) for age, bone age, weight, VAT, SAT, TAT, or IMCL. However, the insulin-resistant group had higher W/H. Additionally the insulin-resistance group had a lower log rate of postexercise phosphocreatine (PCr) recovery (ViPCr) and a higher log PCr recovery constant (tau), indicative of impaired MF. CONCLUSIONS:Obese girls with increased IR have impaired mitochondrial function. This association is not mediated by alterations in IMCL or adipose tissue. Further studies are necessary to determine whether there is a causal relation between impaired mitochondrial function and IR in obesity and mediators of such a relationship.

The osteogenic relationship between the lateral plantar process and the peroneal tubercle has been an uncertainty for researchers over several decades. While some argue there to be no developmental relationship between these two calcaneal structures, others have suggested that there is an inverse relationship, the lateral plantar process forming from a part of the peroneal tubercle. However, no previous studies have offered quantitative measurements to test these hypotheses. In this study, we measured the size of the peroneal tubercle, retrotrochlear eminence, and the size and area of the lateral plantar process in 73 subjects using magnetic resonance imaging (MRI). Navicular height was measured using weight-bearing radiographs as a measurement of longitudinal arch in 35 of these subjects. Age, body mass, and body mass index (BMI) were also recorded for all subjects. We determined that there was a significant positive correlation between the lateral plantar process and size of the peroneal tubercle, body mass, and BMI. Thus, assertions that there is an inverse relationship between the size of the lateral plantar process and the peroneal tubercle are here unfounded. We also determined there to be a positive correlation between the peroneal tubercle and both the size of the retrotrochlear eminence and the height of the navicular. In conclusion, we relate these novel findings to hominin fossil calcanei and discuss the evolutionary and biomechanical implications.

PURPOSE/OBJECTIVE:Recent studies suggest a link between brown adipose tissue (BAT) and bone. The purpose of our study was to investigate the effects of BAT on femoral bone structure. MATERIALS AND METHODS/METHODS:We studied 105 patients (19 m, 86 f. mean age 45.5±16.1 years) who underwent F18-FDG positron emission tomography/computed tomography (PET/CT) for benign etiologies (n=20) or follow-up of successfully treated malignancies (n=85); mean time between PET/CT and last form of treatment was 14.8±18.0 months. BAT volume by PET/CT; femoral bone structure by CT (total femoral cross-sectional area (CSA), cortical CSA); and thigh muscle CSA and thigh subcutaneous fat CSA by CT was assessed. RESULTS:There were positive correlations between BAT volume and total femoral CSA and cortical CSA, independent of age, BMI and history of malignancy (p<0.05). BAT volume correlated positively with thigh muscle CSA and thigh fat CSA (p<0.05). When total femoral CSA was entered as a dependent variable and BAT volume, age and BMI as independent variables in a forward stepwise regression model, BAT volume was the only predictor of total femoral CSA. When femoral cortical CSA was entered as a dependent variable and BAT volume, age and BMI as independent variables, BAT volume was the only predictor of femoral cortical CSA. CONCLUSION/CONCLUSIONS:BAT volume is a positive predictor of femoral bone structure and correlates positively with thigh muscle and subcutaneous fat, possibly mediated by muscle. These results provide further evidence of a positive effect of BAT on bone.

BACKGROUND:Obesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study's purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance. METHODS:22 obese girls 13-21 years old were followed for a randomized 6-month trial of rhGH vs. placebo/no treatment. At baseline and 6-months, DXA was performed for body composition, MRI to measure visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT), and fasting blood drawn for IGF-1, inflammatory cardiovascular risk markers [soluble intercellular adhesion molecule (sICAM), high sensitivity CRP], lipids and HbA1C. An oral glucose tolerance test (OGTT) was performed. Twelve girls completed the 6-month visit. Baseline and mean 6-month change were compared between the groups using the Student t-test and the relationship between variables was determined through multiple regression analysis. RESULTS:After 6-months, the rhGH group maintained IGF-1 levels, and had decreases in total cholesterol (p = 0.03), sICAM-1 (p = 0.04) and HbA1C (p = 0.03) compared to placebo/no treatment. The rhGH group trended towards greater decreases in LDL and 2-hour OGTT glucose. Glucose tolerance did not worsen with rhGH administration. CONCLUSIONS:Administering rhGH in small doses is able to stabilize IGF-1 levels in obesity. We have also shown that rhGH administration leads to an improvement in some markers of cardiovacular risk with without adversely affecting glucose tolerance. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT01169103.

OBJECTIVE:To examine the association between inframalleolar peroneal tendon abnormalities and an enlarged peroneal tubercle. MATERIALS AND METHODS/METHODS:Two independent readers evaluated consecutive ankle MR imaging studies to classify inframalleolar peroneal tendon findings as normal, tenosynovitis, partial tear or complete tear. The size and morphology of the peroneal tubercle was also recorded. We performed statistical analyses for inter-observer agreement and to assess differences in peroneal tubercle size between groups with and without peroneal tendon abnormalities. RESULTS:The study group comprised 121 subjects (mean age, 45.5 years) of whom 28% (34 out of 121) had lateral ankle symptoms. The peroneal tubercle was absent in 56% of subjects (68 out of 121). In subjects with a peroneal tubercle (>0 mm), the mean size was 3.5 mm (37% triangular and 7% plateau-shaped). Male subjects had significantly larger mean peroneal tubercle size than female subjects (2.1 ± 2.5 vs 1.2 ± 1.9 mm, P = 0.04). Overall, 26% (32 out of 121) of subjects had some peroneal tendon abnormality: 17% (20 out of 121) had tenosynovitis and 17 % (20 out of 121) had partial thickness tears. The peroneal tubercle size was significantly larger in subjects with peroneal tendon partial tears (P = 0.036), tenosynovitis (P < 0.001), and when both abnormalities were present (P = 0.007). ROC statistic showed 73% sensitivity and 74% specificity for detection of partial tears for peroneal tubercle size ≥4.3 mm. CONCLUSION/CONCLUSIONS:Our study shows a significantly larger peroneal tubercle in subjects with inframalleolar peroneal tendon abnormalities. A cut-off of 4.3 mm showed good sensitivity and specificity for the presence of partial tears of the peroneal tendon.

OBJECTIVE:To test a newly developed dual energy X-ray absorptiometry (DXA) method for abdominal fat depot quantification in subjects with anorexia nervosa (AN), normal weight, and obesity using CT as a gold standard. DESIGN AND METHODS/METHODS:135 premenopausal women (overweight/obese: n = 89, normal-weight: n = 27, AN: n = 19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA. RESULTS:There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal-weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group. CONCLUSION/CONCLUSIONS:A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum. However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals.

PURPOSE/OBJECTIVE:To investigate the associations between ectopic and serum lipid levels and bone marrow fat, as a marker of stem cell differentiation, in young obese men and women, with the hypothesis that ectopic and serum lipid levels would be positively associated with bone marrow fat. MATERIALS AND METHODS/METHODS:The study was institutional review board approved and complied with HIPAA guidelines. Written informed consent was obtained. The study group comprised 106 healthy young men and women (mean age, 33.7 years ± 6.8 [standard deviation]; range, 19-45 years; mean body mass index (BMI), 33.1 kg/m(2) ± 7.1; range, 18.1-48.8 kg/m(2)) who underwent hydrogen 1((1)H) magnetic resonance (MR) spectroscopy by using a point-resolved spatially localized spectroscopy sequence at 3.0 T of L4 for bone marrow fat content, of soleus muscle for intramyocellular lipids (IMCL), and liver for intrahepatic lipids (IHL), serum cholesterol level, serum triglyceride level, and measures of insulin resistance (IR). Exercise status was assessed with the Paffenbarger activity questionnaire. RESULTS:There was a positive correlation between bone marrow fat and IHL (r = 0.21, P = .048), IMCL (r = 0.27, P = .02), and serum triglyceride level (r = 0.33, P = .001), independent of BMI, age, IR, and exercise status (P < .05). High-density lipoprotein cholesterol levels were inversely associated with bone marrow fat content, independent of BMI, age, IR, and exercise status (r = -0.21, P = .019). CONCLUSION/CONCLUSIONS:Results of this study suggest that ectopic and serum lipid levels are positively associated with bone marrow fat in obese men and women.