Miriam A Bredella

Publications of Miriam A Bredella

• Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa.

  Authors: Pouneh K Fazeli, Miriam A Bredella, Lauren Freedman, Bijoy J Thomas, Anne Breggia, Erinne Meenaghan, Clifford J Rosen, Anne Klibanski

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 04/2012;

  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 massWomen 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 with recovery from AN and 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 women who have recovered from AN (AN-R) compared to 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 as compared to AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R as compared to 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 demonstrated 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 as compared to nutritional sufficiency. © 2012 American Society for Bone and Mineral Research.

• MRI findings of treated bacterial septic arthritis.

  Authors: Guillaume Bierry, Ambrose J Huang, Connie Y Chang, Martin Torriani, Miriam A Bredella

  Skeletal radiology. 03/2012;

  INTRODUCTION: The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. MATERIALS AND METHODS: The study included 12INTRODUCTION: The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. MATERIALS AND METHODS: The study included 12 patients (8 male and 4 female; mean age 38 years, range 9-85) with 13 proven cases of bacterial septic arthritis. The joints involved were hip (n = 3), knee (n = 3), shoulder (n = 2), sacroiliac (n = 2), ankle (n = 1), wrist (n = 1), and elbow (n = 1). MRI examinations following surgical debridement and at initiation of antibiotic therapy and after successful treatment were compared for changes in effusion, synovium, bone, and periarticular soft tissues. Imaging findings were correlated with microbiological and clinical findings. RESULTS: Joint effusions were present in all joints at baseline and regressed significantly at follow-up MRI (p = 0.001). Abscesses were present in 5 cases (38 %), and their sizes decreased significantly at follow-up (p = 0.001). Synovial enhancement and thickening were observed in all joints at both baseline and follow-up MRI. Myositis/cellulitis was present in 10 cases (77 %) at baseline and in 8 cases (62 %) at follow-up MRI. Bone marrow edema was present in 10 joints (77 %) at baseline and persisted in 8 joints (62 %). Bone erosions were found in 8 joints (62 %) and persisted at follow-up MRI in all cases. CONCLUSION: The sizes of joint effusions and abscesses appear to be the factors with the most potential for monitoring therapy for septic arthritis, since both decreased significantly following successful treatment. Synovial thickening and enhancement, periarticular myositis/cellulitis, and bone marrow edema can persist even after resolution of the infection.

• Enchondromas in children: imaging appearance with pathological correlation.

  Authors: Guillaume Bierry, Darcy A Kerr, G Petur Nielsen, Andrew E Rosenberg, Ambrose J Huang, Martin Torriani, Miriam A Bredella

  Skeletal radiology. 02/2012;

  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 finalOBJECTIVE: 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: 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: Enchondromas in children are relatively large lesions, with frequent endosteal scalloping and rare matrix mineralization.

• Effects of growth hormone in women with abdominal adiposity: a 6-month randomized, double-blind, placebo-controlled trial.

  Authors: Miriam A Bredella, Eleanor Lin, Danielle J Brick, Anu V Gerweck, Lindsey M Harrington, Martin Torriani, Bijoy J Thomas, David A Schoenfeld, Anne Breggia, Clifford J Rosen, Linda C Hemphill, Zida Wu, Nader Rifai, Andrea L Utz, Karen Miller

  European journal of endocrinology / European Federation of Endocrine Societies. 01/2012;

  Objective: Abdominal adiposity is associated with increased cardiovascular risk and decreased growth hormone (GH) secretion. The objective of our study was to determine the effects of GH inObjective: Abdominal adiposity is associated with increased cardiovascular risk and decreased growth hormone (GH) secretion. The objective of our study was to determine the effects of GH in abdominally obese women on body composition and cardiovascular risk markers.Materials and Methods: In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs. placebo for six months. Primary endpoints were: 1) total abdominal (TAT) fat by CT (body composition) and 2) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, DXA 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 IGF-1 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, tPA, apoB, and apoB/LDL compared with placebo. Visceral adipose tissue decreased and IMCL increased within the GH group. Six-month change in IGF-1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2-hour glucose >200 mg/mL at 3 months; four subjects, three of whom were randomized to GH, had 2-hour glucose levels >200 mg/mL at study end.Conclusion: 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.

• Young Women with Cold-Activated Brown Adipose Tissue Have Higher Bone Mineral Density and Lower Pref-1 than Women without Brown Adipose Tissue: A Study in Women with Anorexia Nervosa, Women Recovered from Anorexia Nervosa, and Normal-Weight Women.

  Authors: Miriam A Bredella, Pouneh K Fazeli, Lauren M Freedman, Genevieve Calder, Hang Lee, Clifford J Rosen, Anne Klibanski

  The Journal of clinical endocrinology and metabolism. 01/2012;

  Context: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 andContext: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:This was a cross-sectional study at a clinical research center.Patients: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: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), T(3), and T(4) 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 T(3), 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: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.

• Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis.

  Authors: Scott R Plotkin, Miriam A Bredella, Wenli Cai, Ara Kassarjian, Gordon J Harris, Sonia Esparza, Vanessa L Merker, Lance L Munn, Alona Muzikansky, Manor Askenazi, Rosa Nguyen, Ralph Wenzel, Victor F Mautner

  PloS one. 01/2012; 7(4):e35711.

  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 limitedPatients 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. 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. 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 café-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). 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.

  Download

• Whole-body MRI in neurofibromatosis: incidental findings and prevalence of scoliosis.

  Authors: Jacob L Jaremko, Peter J Macmahon, Martin Torriani, Vanessa L Merker, Victor F Mautner, Scott R Plotkin, Miriam A Bredella

  Skeletal radiology. 12/2011;

  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 ANDOBJECTIVE: 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: 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.

  Download

• Trabecular structure analysis using C-arm CT: comparison with MDCT and flat-panel volume CT.

  Authors: Catherine M Phan, Eric A Macklin, Miriam A Bredella, Monica Dadrich, Paul Flechsig, Albert J Yoo, Joshua A Hirsch, Rajiv Gupta

  Skeletal radiology. 08/2011; 40(8):1065-72.

  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). FiveThis 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). 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). 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. C-arm CT is a reliable method for assessing trabecular bone architectural parameters with the exception of app.TbSp due to spatial resolution limitation.

• Lower leg muscle involvement in Duchenne muscular dystrophy: an MR imaging and spectroscopy study.

  Authors: Martin Torriani, Elise Townsend, Bijoy J Thomas, Miriam A Bredella, Reza H Ghomi, Brian S Tseng

  Skeletal radiology. 07/2011; 41(4):437-45.

  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. Nine boysTo 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. 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. 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). 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.

• Modular MR-compatible lower leg exercise device for whole-body scanners.

  Authors: Reza Hosseini Ghomi, Miriam A Bredella, Bijoy J Thomas, Karen K Miller, Martin Torriani

  Skeletal radiology. 01/2011; 40(10):1349-54.

  To develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner. An exercise device to provide isotonic resistance to plantar- or dorsiflexion wasTo develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner. 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. 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. 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.

• Adiponectin is inversely associated with intramyocellular and intrahepatic lipids in obese premenopausal women.

  Authors: Miriam A Bredella, Martin Torriani, Reza H Ghomi, Bijoy J Thomas, Danielle J Brick, Anu V Gerweck, Lindsey M Harrington, Karen K Miller

  Obesity (Silver Spring, Md.). 12/2010; 19(5):911-6.

  Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content inAdiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m(2)) who underwent (1)H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.

• Determinants of bone mineral density in obese premenopausal women.

  Authors: Miriam A Bredella, Martin Torriani, Reza Hosseini Ghomi, Bijoy J Thomas, Danielle J Brick, Anu V Gerweck, Lindsey M Harrington, Anne Breggia, Clifford J Rosen, Karen K Miller

  Bone. 12/2010; 48(4):748-54.

  Despite being a risk factor for cardiovascular disease and diabetes mellitus, obesity has been thought to protect against osteoporosis. However, recent studies have demonstrated a differential impactDespite being a risk factor for cardiovascular disease and diabetes mellitus, obesity has been thought to protect against osteoporosis. However, recent studies have demonstrated a differential impact of specific fat compartments on bone mineral density (BMD) with visceral adipose tissue (VAT) having potential detrimental effects on BMD. Visceral obesity is also associated with dysregulation of the GH/IGF-1 axis, an important regulator of bone homeostasis. The purpose of our study was to evaluate the differential effects of abdominal fat depots and muscle, vitamin D, and hormonal determinants, including insulin-like growth factor-1 (IGF-1), testosterone, and estradiol, on trabecular BMD of the lumbar spine. We studied 68 healthy obese premenopausal women (mean BMI, 36.7±4.2 kg/m(2)). Quantitative computed tomography (QCT) was used to assess body composition and lumbar trabecular BMD. There was an inverse association between BMD and VAT, independent of age and BMI (p=0.003). IGF-1 correlated positively with BMD and negatively with VAT and, in stepwise multivariate regression modeling, was the strongest predictor of BMD and procollagen type 1 amino-terminal propeptide (P1NP). Thigh muscle cross sectional area (CSA) and thigh muscle density were also associated with BMD (p<0.05), but 25-hydroxyvitamin D [25(OH)D], testosterone, free testosterone, and estradiol levels were not. 25(OH)D was associated inversely with BMI, total, and subcutaneous abdominal adipose tissue (p<0.05). These findings support the hypothesis that VAT exerts detrimental effects, whereas muscle mass exerts positive effects on BMD in premenopausal obese women. Moreover, our findings suggest that IGF-1 may be a mediator of the deleterious effects of VAT on bone health through effects on bone formation.

• Comparison of DXA and CT in the assessment of body composition in premenopausal women with obesity and anorexia nervosa.

  Authors: Miriam A Bredella, Reza Hosseini Ghomi, Bijoy J Thomas, Martin Torriani, Danielle J Brick, Anu V Gerweck, Madhusmita Misra, Anne Klibanski, Karen K Miller

  Obesity (Silver Spring, Md.). 11/2010; 18(11):2227-33.

  Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitorAccurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual-energy X-ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA-derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA- and CT-derived body composition measurements in AN, obese, and lean controls (r = 0.77-0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51-0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat.

• Women with anorexia nervosa: finite element and trabecular structure analysis by using flat-panel volume CT.

  Authors: Conor J Walsh, Catherine M Phan, Madhusmita Misra, Miriam A Bredella, Karen K Miller, Pouneh K Fazeli, Harun H Bayraktar, Anne Klibanski, Rajiv Gupta

  Radiology. 10/2010; 257(1):167-74.

  To use finite element modeling based on flat-panel volume computed tomography (CT) and bone mineral density (BMD) provided by dual-energy x-ray absorptiometry (DXA) to compare bone failure load,To use finite element modeling based on flat-panel volume computed tomography (CT) and bone mineral density (BMD) provided by dual-energy x-ray absorptiometry (DXA) to compare bone failure load, stiffness, and trabecular structure in women with anorexia nervosa (AN) and age-matched normal-weight control subjects. The study was approved by the institutional review board and complied with HIPAA guidelines. Informed consent was obtained. Fourteen women, eight with AN (mean age, 26.6 years) and six control subjects (mean age, 26.3 years), underwent flat-panel volume CT of the distal radius to determine apparent trabecular bone volume fraction (BV/TV), apparent trabecular number (TbN), apparent trabecular thickness (TbTh), and apparent trabecular separation (TbSp). Bone strength and stiffness were calculated from uniaxial compression tests by using finite element models created from flat-panel volume CT. DXA was used to determine BMD of the radius, lumbar spine, and hip. Means ± standard deviations of all variables were calculated for both groups and compared (Student t test). Univariate regression analysis and stepwise regression modeling were performed. Patients with AN had lower values for stiffness (284.77 kN/mm ± 76.14 vs 389.97 kN/mm ± 84.90, P = .04), failure load (4.98 kN ± 1.23 vs 7.01 kN ± 1.52, P = .02), BV/TV (0.32% ± 0.09 vs 0.44% ± 0.02, P = .007), and TbN (1.15 mm(-3) ± 0.20 vs 1.43 mm(-3) ± 0.13, P = .008) and higher values for TbSp (0.62 mm ± 0.20 vs 0.40 mm ± 0.04, P = .02) compared with normal-weight control subjects. TbTh was lower in women with AN (P = .1). BMD measurements were significantly lower for the AN group. BMD measurements and trabecular parameters (except TbTh) correlated with stiffness and failure load (r = 0.58 to 0.83). Failure load and stiffness are abnormal in women with AN compared with those in normal-weight control subjects and correlate with BMD and trabecular parameters.

• Throwing elbow in adults.

  Authors: Hugue A Ouellette, William Palmer, Martin Torriani, Miriam A Bredella

  Seminars in musculoskeletal radiology. 09/2010; 14(4):412-8.

  Biomechanics are central in understanding the pathophysiology and magnetic resonance (MR) imaging of overhead throwing athlete injuries. Repetitive excessive valgus forces at the elbow result inBiomechanics are central in understanding the pathophysiology and magnetic resonance (MR) imaging of overhead throwing athlete injuries. Repetitive excessive valgus forces at the elbow result in characteristic injuries due to medial joint distraction, lateral joint compression, and rotatory forces at the olecranon. MR imaging is useful for assessment of the throwing elbow in adults.

• Perspective: the bone-fat connection.

  Authors: Miriam A Bredella

  Skeletal radiology. 08/2010; 39(8):729-31.

• Comparison of 3.0 T proton magnetic resonance spectroscopy short and long echo-time measures of intramyocellular lipids in obese and normal-weight women.

  Authors: Miriam A Bredella, Reza Hosseini Ghomi, Bijoy J Thomas, Karen K Miller, Martin Torriani

  Journal of magnetic resonance imaging : JMRI. 08/2010; 32(2):388-93.

  To compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistanceTo compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistance in obese and normal-weight women. We quantified IMCL of tibialis anterior (TA) and soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight) using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec) echo times. Statistical analyses were performed to determine correlations of IMCL with body composition as determined by computed tomography (CT) and insulin resistance indices and to compare correlation coefficients from short and long echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of variation (CV) of short and long echo-time spectra were calculated. Short and long echo-time IMCL from TA and SOL significantly correlated with body mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver density (r = -0.39 to -0.50, P < 0.05), and glucose area under the curve as a measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no significant difference between correlation coefficients of short and long echo-time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly higher SNR (P < 0.0001) and lower CVs when compared to long echo-time acquisitions. Linewidth measures were not significantly different between groups. IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is useful to detect differences in muscle lipid content in obese and normal-weight subjects. In addition, IMCL correlates with body composition and markers of insulin resistance in this population with no significant difference in correlations between short and long echo-times. Short echo-time IMCL quantification of TA and SOL muscles at 3.0 T was superior to long echo-time due to better SNR and better reproducibility.

• Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women.

  Authors: Miriam A Bredella, Martin Torriani, Reza Hosseini Ghomi, Bijoy J Thomas, Danielle J Brick, Anu V Gerweck, Clifford J Rosen, Anne Klibanski, Karen K Miller

  Obesity (Silver Spring, Md.). 05/2010; 19(1):49-53.

  Recent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiationRecent studies have demonstrated an important physiologic link between bone and fat. Bone and fat cells arise from the same mesenchymal precursor cell within bone marrow, capable of differentiation into adipocytes or osteoblasts. Increased BMI appears to protect against osteoporosis. However, recent studies have suggested detrimental effects of visceral fat on bone health. Increased visceral fat may also be associated with decreased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels which are important for maintenance of bone homeostasis. The purpose of our study was to assess the relationship between vertebral bone marrow fat and trabecular bone mineral density (BMD), abdominal fat depots, GH and IGF-1 in premenopausal women with obesity. We studied 47 premenopausal women of various BMI (range: 18-41 kg/m², mean 30 ± 7 kg/m²) who underwent vertebral bone marrow fat measurement with proton magnetic resonance spectroscopy (1H-MRS), body composition, and trabecular BMD measurement with computed tomography (CT), and GH and IGF-1 levels. Women with high visceral fat had higher bone marrow fat than women with low visceral fat. There was a positive correlation between bone marrow fat and visceral fat, independent of BMD. There was an inverse association between vertebral bone marrow fat and trabecular BMD. Vertebral bone marrow fat was also inversely associated with IGF-1, independent of visceral fat. Our study showed that vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 and BMD. This suggests that the detrimental effect of visceral fat on bone health may be mediated in part by IGF-1 as an important regulator of the fat and bone lineage.

• Transverse Thickening Along the Articular Surface of the Rotator Cuff Consistent With the Rotator Cable: Identification With MR Arthrography and Relevance in Rotator Cuff Evaluation.

  Authors: Kenneth Sheah, Miriam A Bredella, Jon J P Warner, Elkan F Halpern, William E Palmer

  AJR. American journal of roentgenology. 10/2009; 193(3):679-86.

  OBJECTIVE: The purposes of this study were to describe the imaging appearance of transverse thickening along the articular surface of the supraspinatus and infraspinatus tendons presumed to representOBJECTIVE: The purposes of this study were to describe the imaging appearance of transverse thickening along the articular surface of the supraspinatus and infraspinatus tendons presumed to represent the rotator cable on MR arthrographic images obtained with the shoulder in abduction and external rotation (ABER) and in the non-ABER position and to assess the role of the rotator cable in the diagnosis of rotator cuff tears. MATERIALS AND METHODS: The study group comprised 54 patients who underwent arthroscopy of the shoulder and preoperative MR arthrography in which ABER images were obtained. Two blinded reviewers independently examined the ABER and non-ABER images for the presence of the rotator cable and rotator cuff tears. RESULTS: In intact rotator cuffs, the presumed rotator cable was not well visualized on non-ABER images. In one case of prominent rotator cable, MR arthrography showed no tear on non-ABER images, but at arthroscopy, a partial-thickness undersurface tear was found. On non-ABER images, both readers readily visualized the rotator cable in eight and 10 of 18 cases (44% and 56%) of partial-thickness undersurface tear and four of five cases (80%) of full-thickness tear. On ABER images, both readers readily visualized the rotator cable in 15 and 17 of 31 cases (48% and 55%) of intact cuff, 14 and 15 of 18 cases (78% and 83%) of undersurface tear, and four and five cases (80% and 100%) of full-thickness tear. Interobserver agreement on cable visualization was almost perfect (kappa = 0.86). CONCLUSION: On non-ABER MR arthrographic images, thickening along the articular side of the supraspinatus and infraspinatus tendons presumed to represent the rotator cable suggests the presence of a partial-thickness rotator cuff tear. On ABER images, the cable is well defined in intact and torn rotator cuffs.

• Preadipocyte Factor-1 Is Associated with Marrow Adiposity and Bone Mineral Density in Women with Anorexia Nervosa.

  Authors: Pouneh K Fazeli, Miriam A Bredella, Madhusmita Misra, Erinne Meenaghan, Clifford J Rosen, David R Clemmons, Anne Breggia, Karen K Miller, Anne Klibanski

  The Journal of clinical endocrinology and metabolism. 10/2009;

  Context: Despite having low visceral and sc fat depots, women with anorexia nervosa (AN) have elevated marrow fat mass, which is inversely associated with bone mineral density (BMD). Adipocytes andContext: Despite having low visceral and sc fat depots, women with anorexia nervosa (AN) have elevated marrow fat mass, which is inversely associated with bone mineral density (BMD). Adipocytes and osteoblasts differentiate from a common progenitor cell, the human mesenchymal stem cell. Therefore, understanding factors that regulate this differentiation process may provide insight into bone loss in AN. Objective: The objective of the study was to investigate the relationship between preadipocyte factor-1 (Pref-1), a member of the epidermal growth factor-like family of proteins and regulator of adipocyte and osteoblast differentiation, and fat depots and BMD in AN. Design: This was a cross-sectional study. Setting: The study was conducted at a clinical research center. Patients: Patients included 20 women with AN (26.8 +/- 1.5 yr) and 10 normal-weight controls (29.2 +/- 1.7 yr). Interventions: There were no interventions. Main Outcomes Measure: Pref-1, leptin, IGF-I, IGF binding protein (IGF-BP)-2 and estradiol levels were measured. BMD of the spine and hip was measured by dual-energy x-ray absorptiometry. Marrow fat content of the L4 vertebra and femur was measured by (1)H-magnetic resonance spectroscopy. Results: Pref-1 levels were significantly higher in AN compared with controls (P = 0.01). There was a positive correlation between Pref-1 and marrow fat of the proximal femoral metaphysis (R = 0.50, P = 0.01) and an inverse association between leptin and L4 marrow fat (R = -0.45, P < 0.05). There was an inverse association between Pref-1 and BMD of both the anteroposterior spine and lateral spine (R = -0.54, P = 0.003; R = -0.44, P = 0.02, respectively). Conclusions: Pref-1 is elevated in AN. Pref-1, IGF-I, IGF-BP2 and leptin are associated with marrow adiposity and BMD.