Faculty Bibliography

BACKGROUND: A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4. METHOD: Thirty adolescents with MDD (19 females; 13 medication-free/naive; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls. RESULTS: Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p<0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded. CONCLUSIONS: Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow

Purpose: To compare the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging with that of contrast material-enhanced (CE) MR imaging and to assess the performance of these examinations combined for the characterization of renal lesions, with MR follow-up and histopathologic analysis as the reference standards. Materials and Methods: The institutional review board waived the requirement of informed patient consent for this retrospective HIPAA-compliant study. One hundred nine renal lesions in 64 patients (46 men, 18 women; mean age, 60.7 years) were evaluated with CE MR imaging and breath-hold DW imaging performed with various b values. Renal lesions were characterized with use of CE MR criteria, and apparent diffusion coefficients (ADCs) were measured. The ADCs of benign and malignant lesions were compared at Mann-Whitney testing. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of DW imaging and CE MR imaging in the diagnosis of renal cell carcinoma (RCC). Results: The 109 renal lesions-81 benign lesions and 28 RCCs-had a mean diameter of 4.2 cm +/- 2.5 (standard deviation). The mean ADC for RCCs (1.41 x 10(-3) mm(2)/sec +/- 0.61) was significantly lower (P < .0001) than that for benign lesions (2.23 x 10(-3) mm(2)/sec +/- 0.87) at DW imaging performed with b values of 0, 400, and 800 sec/mm(2). At a cutoff ADC of less than or equal to 1.92 x 10(-3) mm(2)/sec, the area under the ROC curve (AUC), sensitivity, and specificity of DW imaging for the diagnosis of RCCs (excluding angiomyolipomas) were 0.856, 86%, and 80%, respectively. The corresponding AUC, sensitivity, and specificity of CE MR imaging were 0.944, 100%, and 89%, respectively. Combined DW and CE MR imaging had 96% specificity. The AUC for the DW imaging-based diagnosis of solid RCC versus oncocytoma was 0.854. Papillary RCCs had lower ADCs than nonpapillary RCCs. Conclusion: DW imaging can be used to characterize renal lesions; however, compared with CE MR imaging, it is less accurate. DW imaging can be used to differentiate solid RCCs from oncocytomas and characterize the histologic subtypes of RCC. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2512080880/DC1 (c) RSNA, 2009

OBJECTIVE: Dual-source CT improves temporal resolution, and theoretically improves the diagnostic image quality of coronary artery examinations without requiring preexamination beta-blockade. The purpose of our study was to show the improved diagnostic image quality of dual-source CT compared with single-source CT despite the absence of preexamination beta-blockade in the dual-source CT group. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients who underwent coronary artery evaluation with either single-source CT or dual-source CT at our institution between February 2005 and October 2006. Examination reports were analyzed for the presence of image artifacts, and image quality was graded on a 3-point scale (no, mild, or severe artifact). Type of artifact (motion, calcium, quantum mottle) was also noted. RESULTS: Examinations (339 single-source CT and 126 dual-source CT) of 465 patients were analyzed. Artifact was reported in 39.8% of examinations using single-source CT and in 29.4% of examinations using dual-source CT (p < 0.05). The number of examinations with motion artifact was significantly higher with single-source CT than with dual-source CT (15.9% vs 4.8%; p < 0.001) despite significantly higher heart rates in the dual-source CT group (59.4 +/- 8.4 vs 68.6 +/- 14.6 beats per minute; p < 0.001). No patients in the dual-source CT group received preexamination beta-blockade compared with 81% of patients in the single-source CT group. The presence of severe (nondiagnostic) calcium artifact was also significantly reduced in the dual-source CT group (13.0% vs 3.2%; p < 0.001). CONCLUSION: Dual-source CT provides significantly better diagnostic image quality than single-source CT despite higher heart rates in the dual-source CT group. These findings support the use of dual-source CT for coronary artery imaging without the need for preexamination beta-blockade

PURPOSE: To retrospectively evaluate the sensitivity and specificity of several morphologic findings that may be seen with cystic pancreatic lesions, in the diagnosis of pseudocyst at magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was institutional review board approved and HIPAA compliant. From January 1, 2005, to December 31, 2007, electronic radiology and pathology databases were searched to identify patients with pancreatic cystic neoplasms or pseudocysts who underwent pancreatic MR imaging. Twenty-two patients with cystic pancreatic neoplasms that were confirmed at surgical resection (n = 12) or endoscopic ultrasonography (US) with cystic fluid analysis (n = 10) were identified. Of 20 patients with pancreatic pseudocysts, seven had pseudocysts that were identified at pathologic resection and 13 had a clinical history of pancreatitis, with initial computed tomography (CT) revealing no pancreatic cyst and subsequent follow-up MR imaging depicting cystic lesions. Two abdominal radiologists independently and randomly evaluated each case for presence or absence of septa and internal dependent debris and for external cyst morphology on axial and coronal T2-weighted images and three-dimensional gradient-echo T1-weighted images obtained before and after intravenous contrast agent administration. Logistic regression for correlated data was used to assess the usefulness of internal debris, external morphology, and septa for differentiating cystic neoplasms from pseudocysts. RESULTS: The readers' assessments of the presence or absence of cystic debris were concordant for 40 (95%) of the 42 patients, with a kappa coefficient of 0.889, which indicated nearly perfect agreement. Thirteen (93%) of 14 lesions found to have debris by either or both readers were pseudocysts, and only one (4%) of the 22 cystic neoplasms had debris. Both readers were more likely to identify septa within cystic neoplasms than within pseudocysts; however, the difference was not significant for either reader. The readers were more likely to observe microlobulated morphology in cystic neoplasms than in pseudocysts, with the difference between these lesion types, in terms of prevalence of microlobulated morphology, exhibiting a trend toward-but not reaching-statistical significance (P = .0627). CONCLUSION: Presence of internal dependent debris appears to be a highly specific MR finding for the diagnosis of pancreatic pseudocyst

OBJECTIVE: The purpose of this study was to identify the CT features of mucocele of the appendix coexisting with acute appendicitis and to determine whether this entity can be differentiated from acute appendicitis without mucocele. MATERIALS AND METHODS: CT scans of 70 patients (12 with acute appendicitis with mucocele, 29 with acute appendicitis without mucocele, 29 with a normal appendix) were retrospectively interpreted by two readers. The appendix was evaluated for maximal luminal diameter, cystic dilatation, luminal attenuation, appendicolith, mural calcification and enhancement, periappendiceal fat stranding, fluid, and lymphadenopathy. CT findings were compared by use of Mann-Whitney U and Fisher's exact tests. Receiver operating characteristics analysis was performed to assess the diagnostic utility of appendiceal luminal diameter in differentiating acute appendicitis with from that without coexisting mucocele. RESULTS: Cystic dilatation of the appendix and maximal luminal diameter achieved statistical significance (p < 0.05) for the diagnosis of acute appendicitis with mucocele. Mural calcification achieved statistical significance for one reader (p = 0.0049) and a statistical trend for the other (p < 0.1). A maximal luminal diameter greater than 1.3 cm had a sensitivity of 71.4%, specificity of 94.6%, and overall diagnostic accuracy of 88.2% for the diagnosis of acute appendicitis with mucocele. CONCLUSION: Although there is overlap with acute appendicitis without mucocele, CT features suggestive of coexisting mucocele in patients with acute appendicitis include cystic dilatation of the appendix, mural calcification, and a luminal diameter greater than 1.3 cm

OBJECTIVE: To determine the reliability of the House-Brackmann facial nerve grading scale in the setting of differential function across its branches. STUDY DESIGN: Prospective. SUBJECTS AND METHODS: Eleven physicians with different levels of clinical experience and three upper-level medical students were provided with digital video clips of 11 patients with differential facial nerve functioning, and asked to report facial nerve function as a traditional global score and as a regional score on the basis of the House-Brackmann scale for the forehead, eye, nose, and mouth. Agreements between the traditional global score and the regional scores, as well as inter-rater agreement, were analyzed. RESULTS: In patients with variable facial weakness, a single House-Brackmann score did not fully communicate facial function. The single House-Brackmann score most strongly correlated with the regional scoring of the nose/midface (59%), followed by the mouth (51%), eye (48%), and forehead (35%). Overall inter-reader reliability was relatively strong for the midface (kappa = 0.503) and global scores (kappa = 0.541), followed by the mouth (k = 0.419), the forehead (k = 0.330), and the eye (k = 0.302). There was a marked tendency for reader agreement to increase among those with more clinical experience. CONCLUSION: Regional assessment using the House-Brackmann grading scale more fully communicates facial function and increases in reliability with experience

PURPOSE: Immunoregulatory and suppressive mechanisms represent major obstacles to the success of immunotherapy in cancer patients. We have shown that the combination of radiotherapy to the primary tumor and CTL-associated protein 4 (CTLA-4) blockade induces antitumor immunity, inhibiting metastases and extending the survival of mice bearing the poorly immunogenic and highly metastatic 4T1 mammary carcinoma. Similarly to patients with metastatic cancer, however, mice were seldom cured. Here we tested the hypothesis that invariant natural killer T (iNKT) cells, a subset with unique regulatory functions, can regulate the response to radiotherapy and CTLA-4 blockade. EXPERIMENTAL DESIGN: The growth of 4T1 primary tumors and lung metastases was compared in wild-type and iNKT cell-deficient (iNKT-/-) mice. Treatment was started on day 13 when the primary tumors were palpable. Mice received radiotherapy to the primary tumor in two doses of 12 Gy in combination or not with 9H10 monoclonal antibody against CTLA-4. Response to treatment was assessed by measuring primary tumor growth delay/regression, survival, and number of lung metastases. RESULTS: The response to radiotherapy plus 9H10 was markedly enhanced in the absence of iNKT cells, with 50% of iNKT-/- versus 0% of wild-type mice showing complete tumor regression, long-term survival, and resistance to a challenge with 4T1 cells. Administration of the iNKT cell activator alpha-galactosylceramide did not enhance the response of wild-type mice to radiotherapy plus 9H10. Tumor-infiltrating iNKT cells were markedly reduced in wild-type mice treated with radiotherapy plus 9H10. CONCLUSIONS: iNKT cells play a major role in regulating the response to treatment with local radiotherapy and CTLA-4 blockade

OBJECTIVE: The purpose of our study was to determine whether gadolinium is necessary in the follow-up evaluation of pancreatic cystic lesions. MATERIALS AND METHODS: Fifty-six patients with pancreatic cystic lesions detected on initial MRI and who underwent follow-up MRI were identified. Mean cyst size was 1.9 cm, and mean follow-up was 9.1 months. MRI included multiacquisition T1- and T2-weighted sequences before contrast administration and 3D fat-suppressed T1-weighted images before and after gadolinium administration. Two radiologists independently reviewed the entire initial examination and follow-up MRI using only unenhanced T1- and T2-weighted sequences from the second examination. Each radiologist made one of three recommendations: 1, no follow-up necessary or follow-up imaging in 6-12 months; 2, cyst aspiration; or 3, cyst resection. Four weeks later, imaging studies were reevaluated with the contrast-enhanced images from the second examination. A second recommendation using the same outcomes was made. Interobserver and intraobserver variations for the same patient were summarized in terms of kappa coefficients and the percentage of times the decisions were concordant. A 95% CI for the percentage of times management decisions would change without and with gadolinium was calculated. RESULTS: Concordance between the two different readers for the interpretations (when using the same MRI interpretation technique for follow-up surveillance) was 87.5% with a kappa coefficient to assess interobserver variation of 0.075, suggesting only slight agreement between the two readers. However, treatment recommendations provided by a single reader with and without information from the contrast-enhanced images were discordant only 4.5% of the time. Recommendations were concordant without and with gadolinium 95.5% (107/112; kappa=0.67) of the time, suggesting substantial agreement. A retrospective consensus review of the five cases in which gadolinium effected a change in the observer's recommendation was performed. There was nothing on the gadolinium-enhanced sequences that would specifically alter a change in a management decision, and it is likely that the changes in management decisions in these five cases were simply related to expected variations in categorizing lesions rather than to the use of gadolinium. CONCLUSION: The use of gadolinium has minimal impact in the follow-up MR assessment of pancreatic cystic lesions

OBJECTIVES: The purpose of this study is to determine if the performance of the first implanted member of a family predicts the performance of subsequently implanted family members. STUDY DESIGN: Retrospective chart review. METHODS: Seventy-one cochlear implant recipients, each belonging to a family with two or more implanted members, were the subjects of this study. Routine audiometric measurements and age-appropriate speech perception tests were performed pre- and postoperatively. In addition, length of deafness, age at implantation, etiology, and length of device usage were correlated to outcome. RESULTS: All implant recipients within a family showed improvement postimplantation, and the predictive component between family members was strong. Presence of GJB2 mutations and greater age at implantation were predictive of poorer rehabilitative outcome, while length of device usage was associated with improved speech perception scores. CONCLUSIONS: On average, if the first implanted family member performs well with a cochlear implant, those following will do well; however, GJB2-related deafness and increased age at implantation are associated with poorer outcome. These findings have important implications for members of families considering cochlear implantation