Faculty Bibliography

OBJECTIVE: The purpose of our study was to determine the frequency and imaging features of atypical femoral fractures in a consecutive asymptomatic patient population on long-term bisphosphonate treatment and search for distinguishing clinical and laboratory parameters in the subset of patients with fractures. SUBJECTS AND METHODS: Two hundred femoral radiographs in 100 asymptomatic patients (93 women and seven men; age range, 47-94 years; mean age, 69.3 years) were prospectively reviewed by two radiologists. All patients had received bisphosphonate treatment for at least 3 years and had no history of pain or recent trauma. MRI studies were performed when a fracture was suspected on radiographs. Bone mineral density, serum calcium, albumin, 25-hydroxy vitamin D, intact parathyroid hormone (iPTH), serum C-telopeptide, and urine N-telopeptide values were obtained. RESULTS: Two of 100 patients (2%) had three insufficiency fractures. Both patients, 50 and 57 years old, were white, active, and had been receiving bisphosphonate therapy for 8 years. The patient with bilateral atypical femoral fractures showed typical features of bisphosphonate-related incomplete atypical femoral fractures. MRI confirmed the radiographic findings in both patients. The two patients with incomplete atypical femoral fractures were significantly younger than those without atypical femoral fractures. There were no significant differences among the fracture and nonfracture groups in terms of clinical or laboratory results, except for mean iPTH, which was significantly decreased in the fracture group. CONCLUSION: The 2% frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy is higher than suggested in the literature. Aside from age and mean iPTH, there were no significant differences in clinical or laboratory data between the two groups.

The compartment-specific lipid changes in femoral-tibial bone of healthy controls and mild osteoarthritis (OA) patients were quantified at 3.0 T. Healthy volunteers [Kellgren-Lawrence (KL) grade = 0; n = 15, 4 females, 11 males, mean age 39 +/- 16 years, age range = 24-78 years] and mild OA patients (KL = 1, 2; n = 26, 12 females, 14 males, mean age 61 +/- 14 years, age range = 27-80 years) were scanned on a 3 T scanner. Clinical proton density (PD)-weighted fast spin echo (FSE) images in the sagittal (without fat-saturation), axial and coronal (fat-saturation) planes were acquired for cartilage Whole-Organ MR Imaging Score (WORMS) grading. A voxel of 10 x 10 x 10 mm(3) was positioned in the medial and lateral compartments of the tibia [medial tibial (MT) and lateral tibial (LT)] and femur [medial femoral (MF) and lateral femoral (LF)] for MRS measurements using the single voxel-stimulated echo acquisition mode (STEAM) pulse sequence. All MRS data were processed with Java-based Magnetic Resonance User Interface (JMRUI). Wilcoxon's rank sum test and mixed model two-way analysis of variance (anova) were performed to determine significant differences between different compartments as well as examine the effect of OA grade and compartment, and their interactions. Generally, the MF compartment index of unsaturation was increased in healthy subjects compared with OA subjects (whether graded by KL or WORMS score). Differences between MF at KL0 and all other compartments at KL1 except LF approached statistical significance (p < 0.05). Differences in saturated lipids signals could be observed predominantly in the 2.03 p.p.m. frequency shift. Healthy controls in the MF compartment had the lowest saturated lipid signals, and mild OA patients with KL2 and WORMS5-6 in the MF compartment had the highest saturated lipid signals compared with other compartments at 2.03 p.p.m. (p < 0.05).

PURPOSE: To evaluate the feasibility of performing single breathhold three-dimensional (3D) thoracic noncontrast MR angiography (NC-MRA) using highly accelerated parallel imaging. MATERIALS AND METHODS: We developed a single breathhold NC MRA pulse sequence using balanced steady state free precession (SSFP) readout and highly accelerated parallel imaging. In 17 subjects, highly accelerated noncontrast MRA was compared against electrocardiogram-triggered contrast-enhanced MRA. Anonymized images were randomized for blinded review by two independent readers for image quality, artifact severity in eight defined vessel segments and aortic dimensions in six standard sites. NC-MRA and CE-MRA were compared in terms of these measures using paired sample t- and Wilcoxon tests. RESULTS: The overall image quality (3.21 +/- 0.68 for NC-MRA versus 3.12 +/- 0.71 for CE-MRA) and artifact (2.87 +/- 1.01 for NC-MRA versus 2.92 +/- 0.87 for CE-MRA) scores were not significantly different, but there were significant differences for the great vessel and coronary artery origins. NC-MRA demonstrated significantly lower aortic diameter measurements compared with CE-MRA; however, this difference was not considered clinically relevant (>3 mm difference) for less than 12% of segments, most commonly at the sinotubular junction. Mean total scan time was significantly lower for NC-MRA compared with CE-MRA (18.2 +/- 6.0 s versus 28.1 +/- 5.4 s, respectively; P < 0.05). CONCLUSION: Single breathhold NC-MRA is feasible and can be a useful alternative for evaluation and follow-up of thoracic aortic diseases. J. Magn. Reson. Imaging 2011;. (c) 2011 Wiley Periodicals, Inc

CONTEXT: Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of gamma-aminobutyric acid (GABA). OBJECTIVE: To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored. DESIGN: Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. SETTING: Two clinical research divisions at 2 teaching hospitals. PARTICIPANTS: Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12-19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. MAIN OUTCOME MEASURES: Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. RESULTS: Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t = 3.2; P < .003). When subjects with MDD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t = 4.08; P < .001; P(Tukey) < .001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = -0.50; P = .02), as well as for the entire participant sample including the control subjects (r = -0.54; P < .001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with MDD compared with controls (P = .04). CONCLUSIONS: These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature

To address the heterogeneous nature of adolescent major depression (MDD), we investigated anhedonia, a core symptom of MDD. We recently reported activation of the kynurenine pathway (KP), a central neuroimmunological pathway which metabolizes tryptophan (TRP) into kynurenine (KYN) en route to several neurotoxins, in a group of highly anhedonic MDD adolescents. In this study, we aimed to extend our prior work and examine the relationship between KP activity and anhedonia, measured quantitatively, in a group of MDD adolescents and in a combined group of MDD and healthy control adolescents. Thirty-six adolescents with MDD (22 medication-free) and 20 controls were included in the analysis. Anhedonia scores were generated based on clinician- and subject-rated assessments and a semi-structured clinician interview. Blood KP metabolites, collected in the AM after an overnight fast, were measured using high-performance liquid chromatography. The rate-limiting enzyme of the KP, indoleamine 2,3-dioxygenase (IDO), was estimated by the ratio of KYN/TRP. Pearson correlation tests were used to assess correlations between anhedonia scores and KP measures while controlling for MDD severity. IDO activity and anhedonia scores were positively correlated in the group psychotropic medication-free adolescents with MDD (r = 0.42, P = 0.05) and in a combined group of MDD subjects and healthy controls (including medicated patients: r = 0.30, P = 0.02; excluding medicated patients: r = 0.44, P = 0.004). In conclusions, our findings provide further support for the role for the KP, particularly IDO, in anhedonia in adolescent MDD. These results emphasize the importance of dimensional approaches in the investigation of psychiatric disorders

The longitudinal repeatability of proton MR spectroscopy ((1) H-MRS) in the healthy human brain at high fields over long periods is not established. Therefore, we assessed the inter- and intra-subject repeatability of (1) H-MRS in an approach suited for diffuse pathologies in 10 individuals, at 3T, annually for 3 years. Spectra from 480 voxels over 360 cm(3) ( approximately 30%) of the brain, were individually phased, frequency-aligned, and summed into one average spectrum. This dramatically increases metabolites' signal-to-noise-ratios while maintaining narrow linewidths that improve quantification precision. The resulting concentrations of the N-acetylaspartate, creatine, choline, and myo-inositol are: 8.9 +/- 0.8, 5.9 +/- 0.6, 1.4 +/- 0.1, and 4.5 +/- 0.5 mM (mean +/- standard-deviation). the inter-subject coefficients of variation are 8.7%, 10.2%, 10.7%, and 11.8%; and the longitudinal (intra-subject) coefficients of variation are lower still: 6.6%, 6.8%, 6.8%, and 10%, much better than the 35%, 44%, 55%, and 62% intra-voxel coefficients of variation. The biological and nonbiological components of the summed spectra coefficients of variation had similar contributions to the overall variance. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc

Purpose: To evaluate the ability of magnetization transfer (MT) contrast-prepared magnetic resonance (MR) imaging to help distinguish healthy from cirrhotic liver by using a spectrum of MT pulse frequency offsets. Materials and Methods: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all subjects. After optimization of the MT sequence by using agar phantoms with protein concentrations ranging from 0% to 4%, 20 patients with cirrhosis and portal hypertension and 20 healthy volunteers with no known liver disease underwent liver MR imaging that included eight separate breath-hold MT contrast sequences, each performed by using a different MT pulse frequency offset (range, 200-2500 Hz). Regions of interest were then placed to calculate the MT ratio for the liver, fat, and muscle in the volunteer group and for the liver in the cirrhosis group. Results: MT ratio increased with decreasing MT pulse frequency offset for each of the four phantoms and the assessed in vivo tissues, consistent with previous reports. At all frequency offsets, MT ratio increased with increasing phantom protein concentration. In volunteers, at frequency offsets greater than 400 Hz, the MT ratio was significantly greater for muscle (range, 34.4%-54.9%) and significantly lower for subcutaneous fat (range, 10.3%-12.6%), compared with that for the liver (range, 22.8%-46.9%; P < .001 all comparisons). However, the MT ratio was nearly identical between healthy (range, 26.0%-80.0%) and cirrhotic livers (range, 26.7%-81.2%) for all frequency offsets (P = .162-.737), aside from a minimal difference in MT ratio of 1.7% at a frequency offset of 2500 Hz (22.8% in healthy liver vs 24.5% in cirrhotic liver) that was not significant when the Bonferroni correction was applied (P = .015). Conclusion: Findings of this study confirm the ability of the MT contrast-prepared sequence to help distinguish substances of varying protein concentration and suggest that MT imaging is unlikely to be of clinical utility in differentiating healthy and cirrhotic livers. (c) RSNA, 2011

PURPOSE: To assess the utility of a 3D two-point Dixon sequence with water-fat decomposition for quantification of fat content of renal angiomyolipoma (AML). METHODS: 84 patients underwent renal MRI including 2D in-and-opposed-phase (IP and OP) sequence and 3D two-point Dixon sequence that generates four image sets [IP, OP, water-only (WO), and fat-only (FO)] within one breath-hold. Two radiologists reviewed 2D and 3D images during separate sessions to identify fat-containing renal masses measuring at least 1cm. For identified lesions subsequently confirmed to represent AML, ROIs were placed at matching locations on 2D and 3D images and used to calculate 2D and 3D SI(index) [(SI(IP)-SI(OP))/SI(IP)] and 3D fat fraction (FF) [SI(FO)/(SI(FO)+SI(WO))]. 2D and 3D SI(index) were compared with 3D FF using Pearson correlation coefficients. RESULTS: 41 AMLs were identified in 6 patients. While all were identified using the 3D sequence, 39 were identified using the 2D sequence, with the remaining 2 AMLs retrospectively visible on 2D images but measuring under 1cm. Among 32 AMLs with a 3D FF of over 50%, both 2D and 3D SI(index) showed a statistically significant inverse correlation with 3D FF (2D SI(index): r=-0.63, p=0.0010; 3D SI(index): r=-0.97, p<0.0001). CONCLUSION: 3D two-point Dixon sequence may provide a reasonable alternative to 2D dual-echo sequence for detection of renal AML and may have additional value for quantification of fat content of these lesions given the observation that 3D FF, unlike 2D and 3D SI(index), is not limited by ambiguity of water or fat dominance. This may assist clinical management of AML given evidence that fat content predicts embolization response

OBJECTIVES: To determine the efficacy of cochlear implantation (CI) in prelingually deafened adolescent children and to evaluate predictive variables for successful outcomes. DESIGN: Retrospective medical record review. PARTICIPANTS: Children aged 10 to 17 years with prelingual hearing loss (mean length of deafness, 11.5 years) who received a unilateral CI (mean age at CI, 12.9 years). Intervention Unilateral CI. MAIN OUTCOME MEASURES: Standard speech perception testing (Consonant-Nucleus-Consonant [CNC] monosyllabic word test and Hearing in Noise [HINT] sentence test) was performed preoperatively, 1 year postoperatively (year 1), and at the last follow-up/end of the study (EOS). RESULTS: There was a highly significant improvement in speech perception scores for both HINT sentence and CNC word testing from the preoperative testing to year 1 (mean change score, 51.10% and 32.23%, respectively; P < .001) and from the preoperative testing to EOS (mean change score, 60.02% and 38.73%, respectively; P < .001), with a significantly greater increase during the first year (P < .001). In addition, there was a highly significant correlation between improvements in performance scores on the CNC word and HINT sentence speech perception tests and both age at CI and length of deafness at the year 1 testing (P </=.009) but not from the year 1 testing to EOS testing. Adolescents with progressive deafness and those using oral communication before CI performed significantly better than age-matched peers. CONCLUSIONS: Adolescents with prelingual deafness undergoing unilateral CI show significant improvement in objective hearing outcome measures. Patients with shorter lengths of deafness and earlier age at CI tend to outperform their peers. In addition, patients with progressive deafness and those using oral communication have significantly better objective outcomes than their peers

Background: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. Objective: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients' disease course. Methods: The MSSS and average WBNAA loss rate (DeltaWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a 'benign' disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were 'non-benign': EDSS score higher than 3.0. Results: The two cohorts were indistinguishable in age and disease duration. Benign patients' EDSS and MSSS (2.1 +/- 0.7, 1.15 +/- 0.60) were significantly lower than non-benign (4.6 +/- 1.0, 3.6 +/- 1.2; both p < 10(-4)). Their respective average DeltaWBNAA, 0.10 +/- 0.16 and 0.11 +/- 0.12 mM/year, however, were not significantly different (p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, DeltaWBNAA is only sensitive (92.6%) but not specific (2.9%). Conclusion: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity