Faculty Bibliography

PURPOSE/OBJECTIVE:To test the performance of dual-energy computed tomography (CT) in the assessment of marrow adipose tissue (MAT) content of the lumbar spine by using proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy as a reference standard and to determine the influence of MAT on the assessment of bone mineral density (BMD). MATERIALS AND METHODS/METHODS:This study was institutional review board approved and complied with HIPAA guidelines. Written informed consent was obtained. Twelve obese osteopenic but otherwise healthy subjects (mean age ± standard deviation, 43 years ± 13) underwent 3-T (1)H MR spectroscopy of the L2 vertebra by using a point-resolved spatially localized spectroscopy sequence without water suppression. The L2 vertebra was scanned with dual-energy CT (80 and 140 kV) by using a dual-source multi-detector row CT scanner with a calibration phantom. Mean basis material composition relative to the phantom was estimated in the L2 vertebra. Volumetric BMD was measured with and without correction for MAT. Bland-Altman 95% limits of agreement and Pearson correlation coefficients were calculated. RESULTS:There was excellent agreement between (1)H MR spectroscopy and dual-energy CT, with a mean difference in fat fraction of -0.02 between the techniques, with a 95% confidence interval of -0.24, 0.20. There was a strong correlation between marrow fat fraction obtained with (1)H MR spectroscopy and that obtained with dual-energy CT (r = 0.91, P < .001). The presence of MAT led to underestimation of BMD, and this bias increased with increasing MAT content (P < .001). CONCLUSION/CONCLUSIONS:Dual-energy CT can be used to assess MAT content and BMD of the lumbar spine in a single examination and provides data that closely agree and correlate with (1)H MR spectroscopy data.

OBJECTIVES/OBJECTIVE:To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. METHODS:A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. RESULTS:We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). CONCLUSIONS:SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. KEY POINTS/CONCLUSIONS:• SABM occurs in several underlying conditions, most commonly anorexia nervosa and cachexia. • Abnormal marrow signal is often misinterpreted as technical error requiring unnecessary repeat imaging. • SABM is frequently associated with stress fractures. • Fractures in SABM can be obscured by marrow signal abnormality on MRI.

Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Proximal, but not distal tibial, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal 'regulated' MAT (rMAT) as single adipocytes interspersed with active haematopoiesis, whereas distal 'constitutive' MAT (cMAT) has low haematopoiesis, contains larger adipocytes, develops earlier and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, haematopoiesis and whole-body metabolism.

CONTEXT/BACKGROUND:Various fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking. METHODS:We used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18-25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week. MAIN OUTCOME MEASURES/METHODS:VAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture. RESULTS:Groups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = -0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = -0.44, p = 0.01; r = -0.36, p = 0.02), and vBMD of the radius and tibia (r = -0.49, p = 0.002; r = -0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ -0.42, p ≤ 0.01) and tibia (r ≤ -0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model. CONCLUSIONS:VAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.

OBJECTIVE:To describe MRI features of an entity consisting of medial knee pain and edema between the posteromedial femoral condyle (PMFC), sartorius and/or gracilis tendons and determine whether reduced tendon-bone distances may account for these findings. METHODS:We retrospectively identified MRI cases of edema between the PMFC, sartorius and/or gracilis tendons (25 subjects, 26 knees). Two musculoskeletal radiologists independently graded edema and measured the sartorius- and gracilis-PMFC distances and knee flexion angle. Age- and gender-matched subjects with normal knee MRIs (27 subjects, 27 knees) served as controls for measurements. Statistical analyses compared abnormal to control subjects. RESULTS:Sartorius-PMFC and gracilis-PMFC spaces were narrower in abnormal compared to control subjects (1.6 ± 1.0 vs. 2.1 ± 1.2 mm, P = 0.04; 2.3 ± 2.0 vs. 4.6 ± 3.0 mm, P = 0.002, respectively). The knee flexion angle was similar between groups (P > 0.05). In subjects with clinical information, medial knee pain was the main complaint in 58 % (15/26) of abnormal subjects, with 42 % (11/26) having clinical suspicion of medial meniscal tear. Edema between the PMFC, sartorius and/or gracilis was mild in 54 % (14/26), moderate in 35 % (9/26) and severe in 12 % (3/26), and it was most frequent deep to both the sartorius and gracilis (50 %, 13/26). CONCLUSIONS:Edema between the PMFC, sartorius and/or gracilis tendons identified on knee MRI may be associated with medial knee pain and may represent a friction syndrome.

OBJECTIVE:To demonstrate the normal appearance of the ligamentum teres on MR arthrography (MRA) and evaluate the accuracy of MRA in detecting ligamentum teres tears with arthroscopic correlation. MATERIALS AND METHODS/METHODS:Institutional Review Board approval was obtained with a waiver for informed consent because of the retrospective study design. A total of 165 cases in 159 patients (111 females, 48 males; mean age 41 ± 12 years) who underwent both MRA and hip arthroscopy were evaluated for appearance of the ligamentum teres, including the size, number of bundles, and ligamentum teres tears. Marrow edema of the fovea capitis adjacent to the ligamentum teres insertion and the presence of hip plicae were also recorded. RESULTS:The mean thickness and length of the ligamentum teres were 3.5 ± 1.5 mm and 25.2 ± 3.8 mm, respectively. Sensitivity, specificity, positive and negative predictive value, and accuracy of MRA for the detection of ligamentum teres tears were 78, 97, 74, 97, and 95%, respectively. CONCLUSION/CONCLUSIONS:MRA is an accurate method to evaluate the normal morphology and to detect tears of the ligamentum teres.

OBJECTIVE:To measure FDG uptake in visceral (VAT) and subcutaneous (SAT) adipose tissue of metabolically healthy obese (MHO) and metabolically abnormal obese (MAO) compared to metabolically healthy lean (MHL) subjects. Given that MHO has increased metabolic risk, it was hypothesized that MHO and MAO display similar VAT FDG uptake. METHODS:The 18F-FDG-PET/CT studies of 141 adults (n = 60 MHL, n = 20 MHO, n = 61 MAO) were examined to determine VAT and SAT volumes and FDG uptake. Data on CVD risk factors (BMI, abdominal circumference, blood pressure, serum lipids, and fasting plasma glucose) were collected. RESULTS:MHO and MAO had similar VAT FDG uptake (P = 0.74), both significantly lower than MHL (P < 0.01) independent of age and gender. SAT FDG uptake was similar across all groups (P > 0.2) independent of age and gender. In all groups, VAT FDG uptake was higher than SAT (P < 0.0001). In separate sub-analyses of obese groups, VAT FDG uptake was more broadly negatively associated with whole-body adiposity than SAT FDG uptake, and FDG uptake in abdominal adipose depots was positively associated with liver density (P < 0.05). CONCLUSIONS:FDG uptake in VAT of MHO is similar to MAO and lower than MHL, suggesting these subjects may present similar VAT dysfunction.

We aimed to test the hypothesis that noninvasive fat density by computed tomography (CT) increases after Roux-en-Y gastric bypass (RYGB) and correlates with improved cardiometabolic risk. We examined 21 obese adults before and 12 months after RYGB and 16 obese nonsurgical controls followed for 12 months. Visceral (VAT) and subcutaneous adipose tissue (SAT) density increased after RYGB (P < 0.0001) while remaining stable in controls (P ≥ 0.1). In RYGB subjects, 12-month increase in VAT density correlated with decreased C-reactive protein (CRP) independent of change in VAT area or BMI (both P < 0.05). Twelve-month increase in SAT density correlated with increased HDL cholesterol independent of change in SAT area (P = 0.048), BMI (P = 0.03), or statin use (P = 0.002), and 1 unit increase in SAT density had increased odds of higher total abdominal fat loss (P = 0.002).

OBJECTIVE:To assess MRI measures to quantify pelvic morphology that may predispose to ischiofemoral impingement (IFI). We hypothesized that patients with IFI have a wider interischial distance and an increased femoral neck angle compared with normal controls. MATERIALS AND METHODS/METHODS:The study was IRB-approved and complied with HIPAA guidelines. IFI was diagnosed based on clinical findings (hip or buttock pain) and ipsilateral edema of the quadratus femoris muscle on MRI. Control subjects did not report isolated hip/buttock pain and underwent MRI for surveillance of neoplasms or to exclude pelvic fractures. Two MSK radiologists measured the ischiofemoral (IF) and quadratus femoris (QF) distance, the ischial angle as a measure of inter-ischial distance, and the femoral neck angle. The quadratus femoris muscle was evaluated for edema. Groups were compared using ANOVA. Multivariate standard least-squares regression modeling was used to control for age and gender. RESULTS:The study group comprised 84 patients with IFI (53 ± 16 years, 73 female, 11 male) and 51 controls (52 ± 16 years, 33 female, 18 male). Thirteen out of 84 patients (15%) had bilateral IFI. Patients with IFI had decreased IF and QF distance (p < 0.0001), increased ischial angle (p = 0.004), and increased femoral neck angle (p = 0.02) compared with controls, independent of age and gender. CONCLUSION/CONCLUSIONS:Patients with IFI have increased ischial and femoral neck angles compared with controls. These anatomical variations in pelvic morphology may predispose to IFI. MRI is a useful method of not only assessing the osseous and soft-tissue abnormalities associated with IFI, but also of quantifying anatomical variations in pelvic morphology that can predispose to IFI.

CONTEXT/BACKGROUND:Obesity is associated with diminished GH secretion, which may result in the overdiagnosis of adult GH deficiency (GHD) in overweight/obese pituitary patients. However, there are no body mass index (BMI)-specific peak GH cutoffs for the glucagon stimulation test (GST), the favored dynamic test for assessing adult GHD in the United States. OBJECTIVE:The objective of the study was to determine a peak GH cutoff level for the diagnosis of adult GHD in overweight/obese individuals using the GST. DESIGN/METHODS:This was a retrospective, cross-sectional study. SETTING/METHODS:The study was conducted at Massachusetts General Hospital and Oregon Health and Science University. METHODS:A total of 108 subjects with a BMI ≥ 25 kg/m(2) were studied: healthy controls (n = 47), subjects with total pituitary deficiency (TPD) (n = 20, ≥ 3 non-GH pituitary hormone deficiencies), and subjects with partial pituitary deficiency (PPD) (n = 41, 1-2 non-GH pituitary hormone deficiencies). INTERVENTION/METHODS:The intervention consisted of a standard 4-hour GST. MAIN OUTCOME MEASURES/METHODS:The main outcome measure was peak GH level on GST. RESULTS:Using the standard peak GH cutoff of 3 ng/mL, 95% of TPD cases (19 of 20), 80% of PPD (33 of 41), and 45% of controls (21 of 47) were classified as GHD. In receiver-operator characteristic curve analysis (controls vs TPD), a peak GH value of 0.94 ng/mL provided the greatest sensitivity (90%) and specificity (94%). Using a peak GH cutoff of 1 ng/mL, 6% of controls (3 of 47), 59% of PPDs (24 of 41), and 90% of TPDs (18 of 20) were classified as GHD. BMI (R = -0.35, P = .02) and visceral adipose tissue (R = -0.32, P = .03) negatively correlated with peak GH levels in controls. CONCLUSION/CONCLUSIONS:A large proportion of healthy overweight/obese individuals (45%) failed the GST using the standard 3 ng/mL GH cutoff. Overweight/obese pituitary patients are at risk of being misclassified as GHD using this cutoff level. A 1-ng/mL GH cutoff may reduce the overdiagnosis of adult GHD in overweight/obese patients.