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Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa

Fazeli, Pouneh K; Bredella, Miriam A; Misra, Madhusmita; Meenaghan, Erinne; Rosen, Clifford J; Clemmons, David R; Breggia, Anne; Miller, Karen K; Klibanski, Anne
CONTEXT/BACKGROUND: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/METHODS:This was a cross-sectional study. SETTING/METHODS:The study was conducted at a clinical research center. PATIENTS/METHODS:Patients included 20 women with AN (26.8 +/- 1.5 yr) and 10 normal-weight controls (29.2 +/- 1.7 yr). INTERVENTIONS/METHODS:There were no interventions. MAIN OUTCOMES MEASURE/METHODS: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.
PMCID:2805488
PMID: 19850693
ISSN: 1945-7197
CID: 5600022

Breath-hold 1H-magnetic resonance spectroscopy for intrahepatic lipid quantification at 3 Tesla

Bredella, Miriam A; Ghomi, Reza Hosseini; Thomas, Bijoy J; Ouellette, Hugue A; Sahani, Dushyant V; Miller, Karen K; Torriani, Martin
OBJECTIVE:To compare breath-hold 1H-magnetic resonance spectroscopy (1H-MRS) with respiratory-gated 1H-MRS and computed tomography (CT) for quantification of hepatic lipid content. METHODS:Twenty-three premenopausal women underwent breath-hold point-resolved single-voxel 1H-MRS of the liver followed by respiratory-gated 1H-MRS at 3 Tesla and CT slice through the liver. Interscan variability for 1H-MRS was assessed in 6 volunteers. Pearson correlation coefficients, Bland-Altman 95% limit of agreement, and concordance correlation coefficients were calculated. RESULTS:There was a strong correlation between breath-hold and respiratory-gated 1H-MRS (r = 0.94, P < 0.0001; concordance correlation coefficient, 0.75). Using Bland-Altman analysis, all but 2 data points were within the limits of agreement. Both 1H-MRS techniques had low interscan variability. There was an inverse correlation of both 1H-MRS techniques with CT attenuation values of the liver. CONCLUSIONS:Breath-hold 1H-MRS is a reliable method to measure hepatic lipid content at 3 Tesla. Breath-hold 1H-MRS of the liver provides data that closely correlates with that obtained from longer-duration respiratory-gated technique.
PMCID:2877282
PMID: 20498538
ISSN: 1532-3145
CID: 5599892

Peak growth hormone-releasing hormone-arginine-stimulated growth hormone is inversely associated with intramyocellular and intrahepatic lipid content in premenopausal women with obesity

Bredella, Miriam A; Torriani, Martin; Thomas, Bijoy J; Ghomi, Reza Hosseini; Brick, Danielle J; Gerweck, Anu V; Miller, Karen K
CONTEXT/BACKGROUND:Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity. OBJECTIVE:To investigate the relationship between intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in premenopausal women with obesity. DESIGN AND SETTING/METHODS:We conducted a cross-sectional study at a clinical translational research center. PATIENTS/METHODS:Patients included 21 premenopausal women with obesity (mean body mass index, 34.0 +/- 4.5 kg/m(2)) and 17 normal-weight controls (mean body mass index, 21.9 +/- 2.0 kg/m(2)) of comparable mean age. MAIN OUTCOMES MEASURES/METHODS:IMCL and intrahepatic lipids were measured with proton magnetic resonance spectroscopy ((1)H-MRS). Body composition was measured with magnetic resonance imaging. Peak GH was measured after stimulation with GHRH-arginine. RESULTS:Obese subjects had higher IMCL, intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with normal-weight controls. There were strong inverse associations between peak GH and both IMCL and intrahepatic lipids independent of age and visceral adiposity. There were positive associations between IMCL and intrahepatic lipids with measures of insulin resistance and serum triglycerides. CONCLUSION/CONCLUSIONS:In premenopausal women with obesity, peak GH is inversely associated with IMCL and intrahepatic lipids independent of age and visceral adiposity. This suggests that low GH may contribute to insulin resistance in obesity through effects on muscle and intrahepatic lipids.
PMCID:2758723
PMID: 19602559
ISSN: 1945-7197
CID: 5599962

Reproducibility of trabecular structure analysis using flat-panel volume computed tomography

Cheung, Arnold C; Bredella, Miriam A; Al Khalaf, Ma'moun; Grasruck, Michael; Leidecker, Christianne; Gupta, Rajiv
PURPOSE/OBJECTIVE:To determine inter-scan, inter-reader and intra-reader variability of trabecular structure analysis using flat-panel volume computed tomography (fp-VCT) in cadaver knee specimens. METHODS:Five explanted knee specimens were imaged at three different time points using fp-VCT. Four parameters that quantify trabecular bone structure of the proximal tibia were measured by two observers at two different time points. Bland-Altman analysis was used to compute the inter-scan, inter-observer and intra-observer variability. RESULTS:Inter-scan variability was low, with a mean difference of 0% and a standard deviation less than 8.4% for each of the four parameters. The inter-observer and intra-observer variability was less than 2.8% +/- 8.5%. CONCLUSION/CONCLUSIONS:Fp-VCT is a method for assessing trabecular structure parameters with low inter-scan, inter-reader and intra-reader variability.
PMID: 19430779
ISSN: 1432-2161
CID: 5599922

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

Sheah, Kenneth; Bredella, Miriam A; Warner, Jon J P; Halpern, Elkan F; Palmer, William E
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 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/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/CONCLUSIONS: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.
PMID: 19696281
ISSN: 1546-3141
CID: 5599982

Relative growth hormone deficiency and cortisol excess are associated with increased cardiovascular risk markers in obese adolescent girls

Russell, M; Bredella, M; Tsai, P; Mendes, N; Miller, K K; Klibanski, A; Misra, M
CONTEXT/BACKGROUND:Obesity in adolescents is increasingly prevalent and its impact on cardiovascular risk important to determine. Hormonal predictors of cardiovascular risk markers in obese adolescents are not known. OBJECTIVE:Our objective was to examine whether relative GH deficiency and cortisol excess are determinants of increased cardiovascular risk markers in obese teenage girls. DESIGN AND SETTING/METHODS:A cross-sectional study was conducted at a clinical research center. STUDY PARTICIPANTS/METHODS:Thirty girls (15 obese girls and 15 normal-weight controls) 12-18 years old matched for maturity and race. MAIN OUTCOME MEASURES/METHODS:Inflammatory markers of cardiovascular risk including high-sensitivity C-reactive protein (hsCRP), TNF-alpha receptors 1 and 2, E-selectin, soluble intercellular adhesion molecule-1, and IL-6 were analyzed. Leptin, adiponectin, and 24-h urine free cortisol (UFC) were also measured. A GHRH-arginine stimulation test was performed. RESULTS:The hsCRP levels were higher in obese girls than controls (4.63 +/- 4.81 vs. 0.67 +/- 0.72 mg/liter; P = 0.002 after log conversion), as were other markers of cardiovascular risk. Eight of the 15 obese girls but no normal-weight girl had hsCRP higher than 3 mg/liter (P = 0.002). Body mass index sd score was higher than 4.0 in 87.5% of girls with hsCRP higher than 3 mg/liter and no girls with hsCRP less than 3 mg/liter. Girls with hsCRP higher than 3 mg/liter had higher UFC and lower peak GH compared with those with hsCRP less than 3 mg/liter. Peak GH was an important negative predictor of most markers of increased cardiovascular risk. In addition to peak GH, UFC and adiponectin independently predicted hsCRP. CONCLUSION/CONCLUSIONS:Relative GH deficiency and cortisol excess are significant contributors to increased levels of markers of cardiovascular risk in obese adolescent girls.
PMCID:2730871
PMID: 19435823
ISSN: 1945-7197
CID: 5602382

Medial patellar ossification after patellar instability: a radiographic finding indicative of prior patella subluxation/dislocation

Jerabek, Seth A; Asnis, Peter D; Bredella, Miriam A; Ouellette, Hugue A; Poon, Steven K; Gill, Thomas J
OBJECTIVE:To describe the correlation between medial patellar ossification and prior patella subluxation and/or dislocation. MATERIALS AND METHODS/METHODS:A retrospective billing database search identified 544 patients who had been diagnosed with patellar instability over a 13-year period. One hundred twenty-eight patients met the inclusion criteria. After review by a staff orthopedic surgeon and two musculoskeletal radiologists, 28 patients were found to have medial patellar ossification. The size and location of medial patellar ossification was recorded. RESULTS:Of the 28 patients (20 males, eight females, age 13-66 years, mean 28 years) who were found to have medial patellar ossification, 22 had radiographs, 16 had magnetic resonance imaging, and ten had both. The medial patellar ossification ranged in size from 2 to 18 mm with an average of 6.8 mm. Twelve were located in the medial patellofemoral ligament (MPFL), 14 in the medial joint capsule, and two in both the MPFL and joint capsule. Twenty-seven of 28 patients had a single ossification, and one patient had two ossifications. The timing from injury to first imaging of the lesion ranged from 10 days to a chronic history (> or = 35 years) of patellar instability. CONCLUSION/CONCLUSIONS:Medial patellar ossification correlates with a history of prior patella subluxation and/or dislocation. The medial ossification can be seen within the MPFL or the medial joint capsule, suggesting remote injury to these structures. The presence of this lesion will prompt physicians to evaluate for patellar instability.
PMID: 19205694
ISSN: 1432-2161
CID: 5599862

Ischiofemoral impingement syndrome: an entity with hip pain and abnormalities of the quadratus femoris muscle

Torriani, Martin; Souto, Silvio C L; Thomas, Bijoy J; Ouellette, Hugue; Bredella, Miriam A
OBJECTIVE:The purpose of this study was to describe the MRI findings of an entity in which patients present with hip pain, abnormal MR signal intensity of the quadratus femoris muscle, and narrowing of the ischiofemoral space. MATERIALS AND METHODS/METHODS:We reviewed MR images of 12 hips in nine patients with hip pain and abnormal MR signal intensity of the quadratus femoris muscle. Using axial MR images, two musculoskeletal radiologists measured the ischiofemoral and quadratus femoris spaces. We also examined changes to muscles and tendons for the presence of edema and tears. Data were compared with 11 hips in 10 control subjects. Statistical analyses determined interobserver variability and differences between groups. RESULTS:Subjects with an abnormal quadratus femoris muscle were all women 30-71 years old (mean age, 53 years) and had significantly narrower ischiofemoral spaces when compared with control subjects (13 +/- 5 vs 23 +/- 8 mm, respectively; p = 0.002). The quadratus femoris space was significantly narrower in affected subjects (7 +/- 3 vs 12 +/- 4 mm; p = 0.002). Abnormalities of the quadratus femoris muscle included edema (100%), partial tear (33%), and fatty infiltration (8%). The hamstring tendons of affected subjects showed evidence of edema (50%) and partial tears (25%). CONCLUSION/CONCLUSIONS:Ischiofemoral impingement may represent a cause of hip pain and should be considered in cases with MR signal abnormality of quadratus femoris muscle.
PMID: 19542413
ISSN: 1546-3141
CID: 5599942

Increased bone marrow fat in anorexia nervosa

Bredella, Miriam A; Fazeli, Pouneh K; Miller, Karen K; Misra, Madhusmita; Torriani, Martin; Thomas, Bijoy J; Ghomi, Reza Hosseini; Rosen, Clifford J; Klibanski, Anne
CONTEXT/BACKGROUND:Although women with anorexia nervosa (AN) have severe depletion of body fat, a paradoxical increase in bone marrow fat has been described. Recent data suggest that marrow fat measured by 1H-magnetic resonance spectroscopy (MRS) in combination with bone mineral density (BMD) may be more valuable than either parameter alone in detecting bone weakness. OBJECTIVE:The objective of the study was to investigate the effect of AN on accumulation of marrow fat in spine and femur using 1H-MRS and the relationship between marrow fat, BMD, and body composition in subjects with AN and normal-weight controls. DESIGN/METHODS:This was a cross-sectional study. SETTING/METHODS:The study was conducted at a referral center. PATIENTS/METHODS:Patients included 10 women with AN (29.8 +/- 7.6 yr) and 10 normal-weight age-matched women (29.2 +/- 5.2 yr). INTERVENTIONS/METHODS:There were no interventions. MAIN OUTCOMES MEASURE/METHODS:Marrow fat content of the fourth lumbar vertebra and femur measured by 1H-MRS. BMD of spine and hip measured by dual-energy x-ray absorptiometry. RESULTS:Subjects with AN had higher marrow fat at the fourth lumbar vertebra and femur compared with controls (P = 0.004-0.01). There was an inverse correlation between marrow fat of L4 and femur and BMD of the spine and hip (r = -0.56 to -0.71, P = 0.01-0.0002) and body mass index and sc adipose tissue of the thigh (r = -0.49 to -0.71, P = 0.03-0.0007). There was an inverse correlation between femur marrow fat and sc and total abdominal adipose tissue (r = -0.53 to -0.67, P = 0.003-0.03). CONCLUSION/CONCLUSIONS:Women with AN have greater lumbar and femoral marrow fat than controls, and marrow fat correlates inversely with BMD. This paradoxical increase in marrow fat at a time when sc and visceral fat are markedly reduced raises important questions about functional consequences of this process.
PMCID:2690416
PMID: 19318450
ISSN: 1945-7197
CID: 5599902

Tumor burden in patients with neurofibromatosis types 1 and 2 and schwannomatosis: determination on whole-body MR images

Cai, Wenli; Kassarjian, Ara; Bredella, Miriam A; Harris, Gordon J; Yoshida, Hiroyuki; Mautner, Victor F; Wenzel, Ralph; Plotkin, Scott R
PURPOSE/OBJECTIVE:To develop a three-dimensional (3D) segmentation and computerized volumetry technique for use in the assessment of neurofibromatosis and to assess the ability of this technique to aid in the calculation of tumor burden in patients with neurofibromatosis types 1 and 2 (NF1 and NF2, respectively) and schwannomatosis detected with whole-body magnetic resonance (MR) imaging. MATERIALS AND METHODS/METHODS:Institutional review board approval and written informed consent were obtained for this prospective HIPAA-compliant study. Fifty-two subjects (27 women, 25 men; mean age, 42 years +/- 15 [standard deviation]; age range, 24-86 years) underwent whole-body MR imaging performed with coronal short inversion time inversion-recovery (STIR) sequences. Whole-body tumor burden was estimated with a 3D segmentation method (the dynamic-threshold [DT] level set method) in 29 subjects (16 with NF1, six with NF2, and seven with schwannomatosis) in whom at least one nerve sheath tumor was reliably identified on MR images. Fifty tumors (25 plexiform and 25 discrete tumors) were randomly selected and subjected to manual and computerized volumetry to assess reliability. Ten plexiform tumors 5 cm or larger in diameter were retrospectively selected and segmented with three initialization methods for computerized volumetry and manually contoured by three radiologists to assess repeatability. Bland-Altman analysis was performed, and intraclass correlation coefficients (ICCs) were calculated. RESULTS:A total of 398 nerve sheath tumors (185 plexiform and 213 discrete tumors) were identified in 29 subjects. Volumetric measurements obtained with the computerized method and manual contouring were highly correlated (r(ICC) = 0.99). Bland-Altman analysis showed that computerized volumetry had a mean difference of -2.6% compared with manual volumetry. The repeatability coefficient of the computerized scheme was +/-5% compared with +/-30% for manual contouring. CONCLUSION/CONCLUSIONS:This 3D segmentation and computerized volumetry technique is reliable relative to manual segmentation and has the advantage of being less labor intensive and more repeatable. This technique can be paired with whole-body MR imaging to determine tumor burden in patients with neurofibromatosis. SUPPLEMENTAL MATERIAL/BACKGROUND:http://radiology.rsnajnls.org/cgi/content/full/250/3/665/DC1
PMID: 19244040
ISSN: 1527-1315
CID: 5599882