Faculty Bibliography

OBJECTIVE:Enchondromas are benign lesions that may present with nonspecific features on imaging in children. Correlation of histology with imaging findings is often required to make the final diagnosis of a benign lesion. The aim of this study was to review imaging and pathological findings of enchondromas in children. MATERIALS AND METHODS/METHODS:Imaging examinations of 12 enchondromas in 11 patients (median age 14 years) were retrospectively reviewed. Imaging evaluation included an assessment of lesion size, relationship to the growth plate, mineralization, matrix and periosteal reaction, intrinsic MR signal characteristics, and intraosseous and soft-tissue edema. Pathological findings were reviewed. RESULTS:Lesions were located in the phalanx in 33% (4 out of 12), metacarpal in 25% (3 out of 12), femur in 33% (4 out of 12) and tibia in 8% cases (1 out of 12). The mean size was 28 mm (range, 11-70 mm). Matrix mineralization in a typical "rings-and-arcs" pattern was observed in 20% of the lesions with available radiographs/CT (2 out of 10). Lesions were expansive with endosteal scalloping in 75% of cases (9 out 12) and contacted the growth plate in 50% of cases (6 out of 12). All enchondromas in which MR imaging was available (5 out of 5) demonstrated typical cartilaginous matrix of lobules of high T2 signal, low T1 signal, and peripheral enhancement. CONCLUSION/CONCLUSIONS:Enchondromas in children are relatively large lesions, with frequent endosteal scalloping and rare matrix mineralization.

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1-a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiation-and fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal-weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by (1) H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = -0.71; p = 0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency.

OBJECTIVE:To demonstrate incidental findings and scoliosis on whole-body MRI (WBMRI) in patients with neurofibromatosis type 1 and 2 (NF1 & NF2, respectively), and schwannomatosis. MATERIALS AND METHODS/METHODS:Institutional review board approval and written informed consent were obtained for this prospective HIPAA-compliant study. A total of 247 subjects (141 with NF1, 55 with NF2, 51 with schwannomatosis; 132 women (53.5%); mean age, 41 years, range, 18-97 years) underwent WBMRI using coronal STIR (TR/TE: 4190/111 ms, TI: 150 ms) and T1-weighted images (TR/TE: 454/10 ms), 10-mm slice thickness, imaging time ~40 min. Images were reviewed for the presence of incidental findings, outside of nerve sheath tumors. The presence of scoliosis was recorded and curve morphology was assessed and quantified. RESULTS:Incidental findings other than scoliosis were recorded in 104/247 (42%) patients, most often affecting the musculoskeletal system (65/247 patients, 26%). We found 16/247 (6.5%) significant incidental findings likely to affect clinical management, including avascular necrosis of bone in eight patients (five with NF2), eight insufficiency fractures, and four non-neurogenic neoplasms (Hodgkin's lymphoma, liposarcoma, dermoid cyst, large uterine myoma requiring excision). Scoliosis was seen in 50/247 patients (20%), including 8/55 with NF2 (15%) and 11/51 with schwannomatosis (22%). CONCLUSIONS:Incidental findings in the neurofibromatoses frequently involve the skeleton. Given the relatively high incidence of unsuspected osteonecrosis and stress fractures, close attention to the skeleton on WBMRI is advised. In addition, knowledge of common incidental findings can help clinicians prepare patients who undergo WBMRI for potential unexpected findings.

OBJECTIVE:To describe the involvement of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) by using MR imaging (MRI) and spectroscopy (MRS) correlated to indices of functional status. SUBJECTS AND METHODS/METHODS:Nine boys with DMD (mean age, 11 years) and eight healthy age- and BMI-matched boys (mean age, 13 years) prospectively underwent lower leg MRI, 1H-MRS of tibialis anterior (TA) and soleus (SOL) for lipid fraction measures, and 31P-MRS for pH and high-energy phosphate measures. DMD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk. RESULTS:DMD subjects had highest fatty infiltration scores in peroneal muscles, followed by medial gastrocnemius and soleus. Compared to controls, DMD boys showed higher intramuscular fat (P = 0.04), lipid fractions of TA and SOL (P = 0.02 and 0.003, respectively), pH of anterior compartment (P = 0.0003), and lower phosphocreatine/inorganic phosphorus ratio of posterior compartment (P = 0.02). The Vignos rating correlated with TA (r = 0.79, P = 0.01) and SOL (r = 0.71, P = 0.03) lipid fractions. The 6MWT correlated with fatty infiltration scores of SOL (r = -0.76, P = 0.046), medial (r = -0.80, P = 0.03) and lateral (r = -0.84, P = 0.02) gastrocnemius, intramuscular fat (r = -0.80, P = 0.03), and SOL lipid fraction (r = -0.89, P = 0.007). Time to walk 10 m correlated with anterior compartment pH (r = 0.78, P = 0.04). CONCLUSION/CONCLUSIONS:Lower leg muscles of boys with DMD show a distinct involvement pattern and increased adiposity that correlates with functional status. Lower leg MRI and 1H-MRS studies may help to noninvasively demonstrate the severity of muscle involvement.

OBJECTIVE:Abdominal adiposity is associated with increased cardiovascular risk and decreased GH secretion. The objective of our study was to determine the effects of GH on body composition and cardiovascular risk markers in abdominally obese women. MATERIALS AND METHODS/METHODS:In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs placebo for 6 months. Primary endpoints were i) total abdominal (total abdominal adipose tissue, TAT) fat by computed tomography (CT) (body composition) and ii) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, dual-energy X-ray absorptiometry, and proton MR spectroscopy. Serum cardiovascular risk markers, carotid intima-media thickness, and endothelial function were measured. RESULTS:Mean 6-month GH dose was 1.7±0.1 mg/day, resulting in a mean IGF1 SDS increase from -1.7±0.08 to -0.1±0.3 in the GH group. GH administration decreased TAT and hsCRP compared with placebo. In addition, it increased thigh muscle mass and lean body mass and decreased subcutaneous abdominal and trunk fat, tissue plasminogen activator, apoB, and apoB/low-density lipoprotein compared with placebo. Visceral adipose tissue (VAT) decreased and intramyocellular lipid increased within the GH group. Six-month change in IGF1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2 h glucose >200 mg/ml at 3 months; four subjects, three of whom were randomized to GH, had 2 h glucose levels >200 mg/ml at the end of the study. CONCLUSION/CONCLUSIONS:GH administration in abdominally obese premenopausal women exerts beneficial effects on body composition and cardiovascular risk markers but is associated with a decrease in glucose tolerance in a minority of women.

CONTEXT/BACKGROUND:Anorexia nervosa (AN) is associated with depletion of body fat, loss of bone mineral density (BMD), and impaired thermogenesis. Brown adipose tissue (BAT) is lower in obese individuals and decreases during aging. Recent studies have suggested a link between BAT and bone metabolism. OBJECTIVE:Our objective was to investigate the presence and quantity of BAT in patients with AN, recovered AN (AN-R), and normal-weight controls and to study the relationship between BAT and BMD and body composition and investigate hormonal predictors of BAT. DESIGN AND SETTING/METHODS:This was a cross-sectional study at a clinical research center. PATIENTS/METHODS:Patients included 15 women: five with AN (mean age 30 ± 6.3 yr), five AN-R, and five healthy nonobese controls of comparable age. MAIN OUTCOME MEASURES/METHODS:Cold-activated BAT was determined by fluorodeoxyglucose-positron emission tomography/computed tomography. BMD of total-body, spine, and hip, fat and lean mass was determined by dual-energy x-ray absorptiometry. Single-slice magnetic resonance imaging at L4 was done for abdominal fat compartments, and preadipocyte factor-1 (Pref-1), T₃, and T₄ were measured. RESULTS:Within the AN group, one of five; in the AN-R group, two of five; and in the healthy nonobese control group, four of five subjects were BAT positive. Subjects were divided into groups based on the presence (n = 7) or absence (n = 8) of BAT. Both groups were of comparable age and body mass index. Women with BAT had higher total-body BMD, higher T₃, and lower Pref-1 compared with women without BAT. There was a positive correlation between BAT and BMD that remained significant after controlling for disease status and body mass index. CONCLUSION/CONCLUSIONS:Young women with AN have low cold-activated BAT, which may be due to impaired BAT thermogenesis. Young women with BAT have higher BMD and lower Pref-1 compared with women without BAT, suggesting that BAT may be involved in the regulation of stem cell differentiation into the bone lineage at the expense of adipogenesis.

CONTEXT/BACKGROUND:The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. DESIGN/METHODS:Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. RESULTS:Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. CONCLUSIONS:Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

PURPOSE: Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease. METHODS: We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors. RESULTS: WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of cafe-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10). CONCLUSION: WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations.

PURPOSE/OBJECTIVE:To develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner. MATERIALS AND METHODS/METHODS:An exercise device to provide isotonic resistance to plantar- or dorsiflexion was constructed from nonferrous materials and designed for easy setup and use in a clinical environment. Validation tests were performed during dynamic MR acquisitions. For this purpose, the device was tested on the posterior lower leg musculature of five subjects during 3 min of exercise at 30% of maximum voluntary plantarflexion during 31-phosphorus MR spectroscopy ((31)P-MRS). Measures of muscle phosphocreatine (PCr), inorganic phosphate (Pi), and pH were obtained before, during, and after the exercise protocol. RESULTS:At the end of exercise regimen, muscle PCr showed a 28% decrease from resting levels (to 21.8 ± 3.9 from 30.4 ± 3.0 mM) and the average PCr recovery rate was 35.3 ± 8.3 s. Muscle Pi concentrations increased 123% (to 14.6 ± 4.7 from 6.5 ± 3.3 mM) and pH decreased 1.5% (to 7.06 ± 0.14 from 7.17 ± 0.07) from resting levels. CONCLUSION/CONCLUSIONS:The described MR-compatible lower leg exercise was an effective tool for data acquisition during dynamic MR acquisitions of the calf muscles. The modular design allows for adaptation to other whole-body MR scanners and incorporation of custom-built mechanical or electronic interfaces and can be used for any MR protocol requiring dynamic evaluation of calf muscles.

PURPOSE/OBJECTIVE:This paper assesses interscan, interreader, and intrareader variability of C-arm CT and compares it to that of flat-panel volume-CT (fpVCT) and high-definition multi-detector-CT (HD-MDCT). METHODS:Five cadaver knee specimens were imaged using C-arm-CT, fpVCT, and HD-MDCT. Apparent (app.) trabecular bone volume fraction (BV/TV), app. trabecular number (TbN), app. trabecular spacing (TbSp), and app. trabecular thickness (TbTh) of the proximal tibia were measured by three readers. Interreader, intrareader, and interscan variability for C-arm CT was expressed as coefficient of variation (CV), standard deviation (SD), and intraclass correlation coefficient (ICC). RESULTS:With the exception of app.TbSp (CV: 7.05-9.35%, SD: 0.06-0.09, ICC: 0.89-0.94), the variability of C-arm CT was low (CV: 2.41-6.43%, SD: 0.01-0.048, ICC: 0.65-0.98). Its interreader reliability (CV: 2.66-4.55%, SD: 0.01-0.03, ICC: 0.81-0.95) was comparable to that of HD-MDCT (CV: 2.41-4.08%, SD: 0.014-0.016, ICC: 0.95-0.96), and fpVCT (CV: 3.13-5.63%, SD: 0.009-0.036, ICC: 0.64-0.98) for all parameters except app.TbSp. CONCLUSIONS:C-arm CT is a reliable method for assessing trabecular bone architectural parameters with the exception of app.TbSp due to spatial resolution limitation.