CDR3α drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection.

The T cell receptor (TCR) repertoire is an essential component of the CD8 T-cell immune response. Here, we seek to investigate factors that drive selection of TCR repertoires specific to the HLA-A2-restricted immunodominant epitope BRLF1109-117 (YVLDHLIVV) over the course of primary Epstein Barr virus (EBV) infection. Using single-cell paired TCRαß sequencing of tetramer sorted CD8 T cells ex vivo, we show at the clonal level that recognition of the HLA-A2-restricted BRLF1 (YVL-BR, BRLF-1109) epitope is mainly driven by the TCRα chain. For the first time, we identify a CDR3α (complementarity determining region 3 α) motif, KDTDKL, resulting from an obligate AV8.1-AJ34 pairing that was shared by all four individuals studied. This observation coupled with the fact that this public AV8.1-KDTDKL-AJ34 TCR pairs with multiple different TCRß chains within the same donor (median 4; range: 1-9), suggests that there are some unique structural features of the interaction between the YVL-BR/MHC and the AV8.1-KDTDKL-AJ34 TCR that leads to this high level of selection. Newly developed TCR motif algorithms identified a lysine at position 1 of the CDR3α motif that is highly conserved and likely important for antigen recognition. Crystal structure analysis of the YVL-BR/HLA-A2 complex revealed that the MHC-bound peptide bulges at position 4, exposing a negatively charged aspartic acid that may interact with the positively charged lysine of CDR3α. TCR cloning and site-directed mutagenesis of the CDR3α lysine ablated YVL-BR-tetramer staining and substantially reduced CD69 upregulation on TCR mutant-transduced cells following antigen-specific stimulation. Reduced activation of T cells expressing this CDR3 motif was also observed following exposure to mutated (D4A) peptide. In summary, we show that a highly public TCR repertoire to an immunodominant epitope of a common human virus is almost completely selected on the basis of CDR3α and provide a likely structural basis for the selection. These studies emphasize the importance of examining TCRα, as well as TCRß, in understanding the CD8 T cell receptor repertoire.

Computed tomography-guided percutaneous hook wire localization of pulmonary nodular lesions before video-assisted thoracoscopic surgery: Highlighting technical aspects.

OBJECTIVE: Confirming the histologic diagnosis of small pulmonary nodules or Ground-glass opacity nodules (GGNs) of unknown origin is difficult. These nodules are not always appropriate for percutaneous transthoracic needle biopsy. Preoperative localization of pulmonary lesions provides more precise target points to ensure complete surgical excision. The goal of the present study was to evaluate the validity and effectiveness of computed tomography-guided preoperative hook wire localization with our technique for video-assisted thoracoscopic surgery (VATS). METHODS: We retrospectively investigated 113 patients who had undergone preoperative hook wire localization before VATS resection for newly present or growing pulmonary nodular lesions between May 2007 and December 2016. Procedural and perioperative outcomes were assessed to evaluate the safety and efficacy of preoperative localization technique. RESULTS: A total of 113 pulmonary nodules were localized and successfully resected in all 113 patients. The mean diameter of nodules was 10.8 ± 6.1 mm (range, 3-28). The mean distance from the pleural surface was 20.2 ± 12.4 mm (range, 5-55). The mean procedure time of localization was 23.7 ± 6.3 min. Asymptomatic minimal pneumothorax and mild parenchymal hemorrhage occurred in 26 (23.0%) and 8 (7.1%) patients, respectively. There were 32 (28.3%) deep lung nodules, in which the distance to pleural surface was more than 25 mm. Wire dislodgement occurred in 4 (3.5%) patients. Complete resection of all lung lesions was achieved, and definite histological diagnosis was obtained in all patients. Pathologic examination revealed 42 (37.2%) primary lung cancers, 2 (1.8%) lymphomas, 53 (46.9%) metastases, 16 (14.1%) benign lesions. CONCLUSIONS: Preoperative percutaneous hook wire localization is a dependable and useful technique to facilitate positioning small and deep pulmonary nodules for thoracoscopic complete excision and accurate diagnosis.

Diagnostic Accuracy of Electrocardiogram-Gated Thoracic Computed Tomography Angiography without Heart Rate Control for Detection of Significant Coronary Artery Stenosis in Patients with Acute Ischemic Stroke: A Comparative Study.

Objective: To compare the diagnostic performance of electrocardiogram (ECG)-gated thoracic computed tomography angiography (TCTA) without heart rate (HR) control in ischemic stroke patients with coronary CTA (CCTA) in non-stroke patients for detection of significant coronary artery stenosis. Materials and Methods: From September 2009 through August 2014, we retrospectively enrolled 138 consecutive patients diagnosed with acute ischemic stroke who had undergone ECG-gated TCTA and conventional coronary angiography (CCA). Over the same period, we selected 167 non-stroke patients with suspected or known coronary artery disease who had undergone CCTA and CCA. With CCA as the reference standard, the diagnostic performance of TCTA and CCTA for identification of significant coronary stenosis (diameter reduction ≥ 50%) was calculated. Results: There was no significant difference in baseline characteristics between TCTA (n = 132) and CCTA (n = 164), except for the higher prevalence of atrial fibrillation in the stroke group. There was significant difference (p < 0.001) between TCTA and CCTA in average HR (68 ± 12 vs. 61 ± 10 beats per minute) and image quality score (1.3 ± 0.6 vs. 1.2 ± 0.6). Significant coronary stenosis was identified in 101 (77%) patients, 179 (45%) vessels, and 293 (15%) segments of stroke patients, and in 136 (83%) patients, 259 (53%) vessels, and 404 (16%) segments of non-stroke patients. Diagnostic performance on a per-vessel and per-patient basis was similar in both TCTA and CCTA groups. There was only significant difference in area under receiver-operating characteristic curve between TCTA and CCTA groups (0.79 vs. 0.87, p < 0.001) on per-segment basis. Conclusion: Electrocardiogram-gated TCTA without HR control facilitates the identification of significant coronary stenosis in patients with ischemic stroke.

Diagnostic performance of static single-scan stress perfusion cardiac computed tomography in detecting hemodynamically significant coronary artery stenosis: a comparison with combined invasive coronary angiography and cardiovascular magnetic resonance-myocardial perfusion imaging.

Background Non-invasive anatomical and physiological evaluations of coronary artery disease (CAD) may be obtained with static single-scan stress perfusion cardiac computed tomography (SSPCT). Purpose To determine the diagnostic performance of static SSPCT for identifying hemodynamically significant CAD. Material and Methods This prospective study included 29 patients with suspected or known CAD who underwent static SSPCT, cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI), and invasive coronary angiography (ICA). CT was performed as follows: (i) coronary calcium scan; (ii) static SSPCT for both coronary artery (coronary CT angiography [CCTA]) and myocardial perfusion (perfusion CT [PCT]) during adenosine infusion; (iii) late-phase scan. The diagnostic performance of CCTA alone, PCT alone, and SSPCT for the detection of a hemodynamically significant CAD (a perfusion defect in a vascular territory subtended by a coronary vessel with ≥ 50% stenosis) was compared with that of combined ICA/CMR-MPI representing the standard of reference. Results Twenty-three (79%) patients and 47 (54%) vascular territories manifested ischemia-causing coronary stenoses by combined ICA/CMR-MPI. The per-vessel sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curve (AUC) of the SSPCT were 92%, 88%, 90%, 90%, and 0.90, respectively, compared to those of the combined ICA/CMR-MPI. These values for the CCTA alone were 96%, 63%, 75%, 93%, and 0.79, respectively; and the values for the PCT alone were 94%, 83%, 86%, 92%, and 0.88, respectively. The AUC of SSPCT was significantly ( P = 0.013) higher than that of the CCTA alone. Conclusion Static SSPCT may facilitate detection of hemodynamically significant CAD.

Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope.

A keystone of antiviral immunity is CD8+ T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8+ T cells that help to control influenza in HLA-A2+ individuals. Here we show that CD8+ T cells use many distinct TCRs to recognize HLA-A2-M1, which enables the use of different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen. The vast majority of responding TCRs target a small cleft between HLA-A2 and the bound M1 peptide. These broad repertoires lead to plasticity in antigen recognition and protection against T cell clonal loss and viral escape.

Differences in Aortic Valve and Left Ventricular Parameters Related to the Severity of Myocardial Fibrosis in Patients with Severe Aortic Valve Stenosis.

OBJECTIVE: This study investigated the morphological and functional characteristics of the aortic valve and the left ventricular (LV) systolic functional parameters and myocardial mass related to the severity of myocardial fibrosis (MF) in patients with severe aortic valve stenosis (AS). MATERIALS AND METHODS: We retrospectively enrolled 81 patients (48 men; mean age: 59±12 years) with severe AS who underwent transthoracic echocardiography (TTE), cardiac computed tomography (CCT), and cardiovascular magnetic resonance (CMR) within 1 month and subsequent aortic valve surgery. Degree of MF was determined on delayed contrast-enhanced CMR with visual sub-segmental analysis-based quantification and was classified into three groups (no, mild, and severe) for identifying the differences in LV function and characteristics of the aortic valve. One-way ANOVA, Chi-square test or Fisher's exact test were used to compare variables of the three groups. Univariate multinomial logistic regression analysis was performed to determine the association between the severity of MF and variables on imaging modalities. RESULTS: Of 81 patients, 34 (42%) had MF (mild, n = 18; severe, n = 16). Aortic valve calcium volume score on CCT, aortic valve area, LV mass index, LV end-diastolic volume index on CMR, presence of mild aortic regurgitation (AR), transaortic mean pressure gradient, and peak velocity on TTE were significantly different among the three groups and were associated with severity of MF on a univariate multinomial logistic regression analysis. Aortic valve calcium grade was different (p = 0.008) among the three groups but not associated with severity of MF (p = 0.375). CONCLUSIONS: A multi-imaging approach shows that severe AS with MF is significantly associated with more severe calcific AS, higher LV end-diastolic volume, higher LV mass, and higher prevalence of mild AR.

Indirect CT Venography at 80 kVp with Sinogram-Affirmed Iterative Reconstruction Compared to 120 kVp with Filtered Back Projection: Assessment of Image Quality and Radiation Dose.

OBJECTIVE: To evaluate the image quality and radiation dose of indirect computed tomographic venography (CTV) using 80 kVp with sinogram-affirmed iterative reconstruction (SAFIRE) and 120 kVp with filtered back projection (FBP). MATERIALS AND METHODS: This retrospective study was approved by our institution and informed consent was waived. Sixty-one consecutive patients (M: F = 27: 34, mean age 60 ± 16, mean BMI 23.6 ± 3.6 kg/m2) underwent pelvic and lower extremity CTVs [group A (n = 31, 120 kVp, reconstructed with FBP) vs. group B (n = 30, 80 kVp, reconstructed with SAFIRE)]. The vascular enhancement, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared. Subjective image analysis for image quality and noise was performed by two radiologists. Radiation dose was compared between the two groups. RESULTS: Compared with group A, higher mean vascular enhancement was observed in the group B (group A vs. B, 118.8 ± 15.7 HU vs. 178.6 ± 39.6 HU, p < 0.001), as well as image noise (12.0 ± 3.8 HU vs. 17.9 ± 6.1 HU, p < 0.001) and CNR (5.1 ± 1.9 vs. 7.6 ± 3.0, p < 0.001). The SNRs were not significantly different in both groups (11.2 ± 4.8 vs. 10.8 ± 3.7, p = 0.617). There was no significant difference in subjective image quality between the two groups (all p > 0.05). The subjective image noise was higher in the group B (p = 0.036 in reader 1, p = 0.005 in reader 2). The inter-observer reliability for assessing subjective image quality was good (ICC 0.746~0.784, p < 0.001). The mean CT dose index volume (CTDIvol) and mean dose length product (DLP) were significantly lower in group B than group A [CTDIvol, 6.4 ± 1.3 vs. 2.2 ± 2.2 mGy (p < 0.001); DLP, 499.1 ± 116.0 vs. 133.1 ± 45.7 mGy × cm (p < 0.001)]. CONCLUSIONS: CTV using 80 kVp combined with SAFIRE provides lower radiation dose and improved CNR compared to CTV using 120 kVp with FBP.

Color radiography in lung nodule detection and characterization: comparison with conventional gray scale radiography.

BACKGROUND: To compare the capability of lung nodule detection and characterization between dual-energy radiography with color-representation (DCR) and conventional gray scale chest radiography (GSR). METHODS: A total of 130 paired chest radiographs (DCR and GSR) obtained from 65 patients (14 with normal scans and 51 with pulmonary nodules) were evaluated. After analysis, 45 non-calcified and 21 calcified nodules were identified. DCR was obtained by adding color space within material-decomposed data (blue for high attenuation and red for low attenuation) and by compounding the manipulated data to one color image. Three radiologists marked suggested nodules on radiographic images and assessed the level of confidence of lesion presence and probability of nodule calcification by using a nine-point rating scale. The jackknife active free-response receiver operating characteristics (JAFROC) analysis was used to evaluate lesion detectability, and multi-reader multi-case receiver operating characteristics (MRMC ROC) analysis was used for the evaluation of the accuracy of nodule calcification prediction. RESULTS: Figures of merit (FOM) from JAFROC was 0.807 for DCR and 0.811 for GSR, respectively; nodule detectability was not significantly different between DCR and GSR (p = 0.93). Areas under curve (AUC) from MRMC ROC were 0.944 for DCR and 0.828 for GSR, respectively; performance of DCR in predicting lung nodule calcification was significantly higher than that of GSR (p = 0.04). CONCLUSIONS: DCR showed similar performance in terms of lung nodule detection compared with GSR. However, DCR does provide a significant benefit in predicting the presence of nodule calcification.

Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography.

OBJECTIVE: The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). MATERIALS AND METHODS: We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. RESULTS: All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). CONCLUSION: Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV.

Virtual Non-Contrast CT Using Dual-Energy Spectral CT: Feasibility of Coronary Artery Calcium Scoring.

OBJECTIVE: To evaluate the feasibility of coronary artery calcium scoring based on three virtual noncontrast-enhanced (VNC) images derived from single-source spectral dual-energy CT (DECT) as compared with true noncontrast-enhanced (TNC) images. MATERIALS AND METHODS: This prospective study was conducted with the approval of our Institutional Review Board. Ninety-seven patients underwent noncontrast CT followed by contrast-enhanced chest CT using single-source spectral DECT. Iodine eliminated VNC images were reconstructed using two kinds of 2-material decomposition algorithms (material density iodine-water pair [MDW], material density iodine-calcium pair [MDC]) and a material suppressed algorithm (material suppressed iodine [MSI]). Two readers independently quantified calcium on VNC and TNC images. The Spearman correlation coefficient test and Bland-Altman method were used for statistical analyses. RESULTS: Coronary artery calcium scores from all three VNC images showed excellent correlation with those from the TNC images (Spearman's correlation coefficient [ρ] = 0.94, 0.88, and 0.89 for MDW, MDC, and MSI, respectively; p < 0.001 for all pairs). Measured coronary calcium volumes from VNC images also correlated well with those from TNC images (ρ = 0.92, 0.87, and 0.91 for MDW, MDC, and MSI, respectively; p < 0.001 for all pairs). Among the three VNC images, coronary calcium from MDW correlated best with that from TNC. The coronary artery calcium scores and volumes were significantly lower from the VNC images than from the TNC images (p < 0.001 for all pairs). CONCLUSION: The use of VNC images from contrast-enhanced CT using dual-energy material decomposition/suppression is feasible for coronary calcium scoring. The absolute value from VNC tends to be smaller than that from TNC.

Detection of skeletal muscle metastasis: torso FDG PET-CT versus contrast-enhanced chest or abdomen CT.

BACKGROUND: Skeletal muscle metastasis (SMM) in cancer patients has not been sufficiently evaluated regarding prevalence and proper method of detection. PURPOSE: To determine the prevalence of SMM and compare the diagnostic competencies for SMM of torso F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) and contrast-enhanced chest or abdomen CT. MATERIAL AND METHODS: We investigated 18,225 PET-CT studies of 6359 cancer patients performed from 2005 to 2012. The PET-CT studies describing potential SMM were retrieved and the corresponding medical records were reviewed. The gold standard for SMM was histopathologically-proven SMM or imaging study-based disease progression. The detectability of SMM was compared between PET-CT and contrast-enhanced CT. RESULTS: Twenty-six patients had 84 SMM lesions, representing a SMM prevalence of 0.41%. Lung cancer was the most common SMM-associated malignancy (54%) and the gluteal/pelvic girdle muscle was the most frequently involved SMM site (37%). All 84 SMM lesions were visualized on PET-CT (100%). Of these PET-CT positive 84 SMM lesions, 51 lesions were in the CT field of view (FOV) (61%), whereas 33 lesions were out of the CT FOV (39%). Among these 51 lesions, 17 lesions showed rim-enhancing nodules/masses (33%), eight lesions showed homogeneously enhancing nodules (16%), three lesions showed heterogeneously enhancing nodules (6%), and 23 SMM lesions (45%) were non-diagnostic by CT. All 51 SMM lesions within CT FOV were detected on PET-CT (100%), whereas only 28 were visualized on CT (54.9%), resulting in a significant difference (P < 0.005). On average, 2.6 more organs with concomitant metastases were found when SMM was revealed by PET-CT. CONCLUSION: The prevalence of SMM was as low as 0.41% in the current large cohort of cancer patients. Torso PET-CT was a more competent modality than contrast-enhanced CT in the detection of SMM.

Detection of cardiac myxomas with non-contrast chest CT.

BACKGROUND: Cardiac myxomas are sources of systemic embolism. Currently a large volume of chest CT and calcium-scoring CT scans are performed without contrast injection. PURPOSE: To evaluate the diagnostic capability of non-contrast CT covering heart in detecting cardiac myxomas. MATERIAL AND METHODS: This retrospective study included 36 non-contrast CT scans of 36 consecutive patients (16 men, 20 women) who underwent CT scan before surgery for left atrial myxomas and 20 patients without myxoma as a control group. Two independent readers who were blinded to medical information reviewed non-contrast CT scans of 36 patients with cardiac myxomas and 20 scans in the control group patients. They determined the presence of lesions suspicious of myxomas using a five-point scale. The other reader measured attenuation number in the non-calcific areas of the tumors and sizes of the masses on the non-contrast CT images. RESULTS: The average attenuation of cardiac myxoma (22.5 Hounsfield units [HU]; range, 8.9-32.9 HU) and adjacent unopacified blood (44.6 HU; range, 31.5-57 HU) were significantly different (P < 0.001). Twelve cardiac myxomas (31.6%) had internal calcification and all of them were detected by both of readers. Cardiac myxomas were measured smaller on non-contrast CT (mean, 3.5 cm; range, 1.1-9.7 cm) than on pathologic specimens (mean, 4.1 cm, 1.4-10.0 cm) (P < 0.001). Considering grade 3-5 on a five-grade scale as the detectability, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of non-contrast CT in detecting cardiac myxomas were 88.8%/86.1%, 95.0%/100%, 96.9%/100%, 82.6%/80.0%, and 91.1%/91.1%, by reader 1 and reader 2, respectively and there was good inter-observer reliability (kappa value = 0.92, P = 0.157). CONCLUSION: Non-contrast CT scan is useful for detecting cardiac myxomas. Therefore, radiologists should be familiar with imaging findings of cardiac myxomas on non-contrast CT.

Digital tomosynthesis of the thorax: the influence of respiratory motion artifacts on lung nodule detection.

BACKGROUND: Digital tomosynthesis considerably reduces problems created by overlapping anatomy compared with chest X-ray (CXR). However, digital tomosynthesis requires a longer scan time compared with CXR, and thus may be vulnerable to motion artifacts. PURPOSE: To compare the diagnostic performance of digital tomosynthesis in subjects with and without respiratory motion artifacts. MATERIAL AND METHODS: The institutional review board approved this retrospective study, and the requirement for written informed consent was waived. A total of 46 subjects with imaging containing respiratory motion artifacts were enrolled in this study, 18 of whom were positive and 28 of whom were negative for lung nodules on computed tomography (CT). The control group was comprised of 92 age-matched subjects with imaging devoid of motion artifacts. Of these, 36 were positive and 56 were negative for lung nodules on subsequent CT scan. The size criteria of nodules were 4-10 mm. Three chest radiologists independently evaluated the radiographs and digital tomosynthesis images for the presence of pulmonary nodules. Multireader multicase receiver-operating characteristic (ROC) analyses was used for statistical comparisons. RESULTS: Within the control group, the areas under curve (AUC) for observer performances in detecting lung nodules on digital tomosynthesis was higher than that on CXR (P = 0.017). Within the study group, there were no significant differences in AUCs for observer performances (P = 0.576). CONCLUSION: When no motion artifacts are present, the detection performance of nodules (4-10 mm) on digital tomosynthesis is significantly better than that on CXR, whereas there is not a significant difference in cases with motion artifacts.

Thoracic Castleman disease: computed tomography and clinical findings.

AIM: The objective of this study was to evaluate the clinicoradiological findings of thoracic Castleman disease. METHODS: The study included 34 patients (22 male and 12 female patients; mean age, 32 [SD, 18.1] years) with thoracic Castleman disease. Clinicoradiological findings of the 34 patients were analyzed. Regarding computed tomography findings, lesion number, location, degree of enhancement (moderate, >20 Hounsfield units than back muscle enhancement; high, >40 Hounsfield units), and associated findings were recorded. RESULTS: Of 34 patients, hyaline-vascular type (HVT) was found in 27 patients (79%), plasma cell type (PCT) in 5 patients (15%), and mixed type (6%) in 2 patients. In HVTs (n = 27), lesions were found, in decreasing order, in the lower neck (n = 9, 33%), pulmonary hilum (n = 6, 22%), and the upper paratracheal area (n = 4, 15%). Ten (37%) of 27 HVT patients had symptoms, whereas all (100%) with PCT had generalized symptoms. In 26 (96%) of 27 HVT patients, disease was unicentric, whereas it was multicentric in all PCT patients. Moderate to high degree of lesion enhancement was seen in 22 (92%) of 24 HVT patients and 4 (80%) of 5 PCT patients. Feeding vessels or draining veins were identified in 12 (44%) of 27 HVT patients and 2 (40%) of 5 PCT patients. The diseases were cured with surgical removal in HVT, whereas they showed variable prognosis in PCT. CONCLUSIONS: Irrespective of subtypes, Castleman disease is characterized radiologically by unicentric or multicentric enhancing lymph node enlargement; in HVT, they show good prognosis after surgical treatment, but in PCT, they show variable prognosis.

Tuberculous lymphadenitis of the thorax: comparisons of imaging findings between patients with and those without HIV infection.

OBJECTIVE: The purpose of this study was to discern differences in the clinical and radiologic presentations of intrathoracic tuberculous lymphadenitis in adult patients with and those without HIV infection. MATERIALS AND METHODS: Between 2000 and 2010, 66 patients (28 men, 38 women; mean age, 45 ± 13.9 years) were found to have intrathoracic tuberculous lymphadenitis. Of these patients, 17 (26%) (15 men, two women; mean age, 47 ± 9.9 years) were HIV-seropositive. Thoracic CT scans were evaluated for involved lymph node stations, long-axis diameter of involved lymph nodes, presence of central necrosis in enlarged nodes, and other associated findings. RESULTS: In HIV-positive patients, tuberculous lymphadenitis had more multifocal (mean number of involved nodal stations, 8.4 versus 3.6; p < 0.001) nodal involvement, had smaller nodes (mean long-axis diameter, 17 mm versus 21 mm; p = 0.004), and was more frequently associated with lung parenchymal lesions and extrathoracic lymph node and organ involvement (p < 0.05) than in HIV-negative patients. Tuberculous lymphadenitis was the sole manifestation of tuberculous infection in 22 of 49 (45%) HIV-negative patients and in 2 of 17 (12%) HIV-positive patients (p = 0.018). CONCLUSION: Tuberculous lymphadenitis in patients with HIV infection is characterized by multiple-station lymphadenitis with extensive lung parenchymal, extrathoracic lymph node, and extrathoracic organ involvement.

CT findings of late-onset noninfectious pulmonary complications in patients with pathologically proven graft-versus-host disease after allogeneic stem cell transplant.

OBJECTIVE: We retrospectively analyzed the CT features of late-onset noninfectious pulmonary complications in patients with pathologically proven graft-versus-host disease (GVHD) after allogeneic stem cell transplant (SCT). MATERIALS AND METHODS: We analyzed the CT features of late-onset noninfectious pulmonary complications in 14 patients with pathologic diagnoses of GVHD who survived disease free for more than 3 months after SCT. Late-onset noninfectious pulmonary complications were diagnosed by excluding pulmonary infection in these patients with respiratory symptoms and signs. The presence, extent, and distribution of CT features were evaluated in terms of geographic hypoattenuation, expiratory airtrapping, ground-glass attenuation (GGA), reticulation, crazy paving pattern, bronchiectasis, nodules, and honeycombing. Further disease classification was made on the basis of clinical, radiologic, and pulmonary function test results and histologic findings. The longitudinal changes of late-onset noninfectious pulmonary complications were followed with CT. RESULTS: The 14 patients with late-onset noninfectious pulmonary complications were classified into subgroups with bronchiolitis obliterans (BO) (n = 7), nonclassifiable interstitial pneumonia (n = 5), and combined BO and nonclassifiable interstitial pneumonia (n = 2). The CT features of nonclassifiable interstitial pneumonia were GGA (5/7, 71%), reticulation (4/7, 57%), and crazy paving pattern (4/7, 57%) with a peribronchovascular distribution (6/7, 86%). All patients with nonclassifiable interstitial pneumonia had progression of disease with an increased extent of traction bronchiectasis, reticulation, and honeycombing on follow-up CT scans (median follow-up period, 22 months). CONCLUSION: Although not commonly encountered, nonclassifiable interstitial pneumonia as a pattern of chronic GVHD should be included in the differential diagnosis of unexplained peribronchial GGA or progressive traction bronchiectasis after SCT.

Solitary pulmonary nodular lung adenocarcinoma: correlation of histopathologic scoring and patient survival with imaging biomarkers.

PURPOSE: To evaluate the usefulness of histopathologic scoring for survival prediction in patients with solitary pulmonary nodular (SPN) lung adenocarcinomas and to correlate the histopathologic scoring with the results of computed tomography (CT) and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT. MATERIALS AND METHODS: This retrospective study was institutional review board approved and the requirement for informed consent was waived. A total of 148 patients with SPN lung adenocarcinoma underwent PET/CT and CT. Correlations between histopathologic scores estimated by using two predominant histologic subtypes from each surgically resected specimen and the mass of the nodule at CT or maximum standardized uptake value (SUV(max)) at PET/CT were assessed. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences in each histopathologic subtype. RESULTS: In 135 (91%) patients, tumors had a mixed subtype. The most frequently observed histologic subtypes, in decreasing order, were acinar (51%), lepidic (18%), solid (10%), and papillary (9%). DFS rates at 5 years were higher than 90% for the group of patients with nodules that showed the lepidic growth pattern, and 50% for patients with nodules that showed the micropapillary pattern. The pathologic score proved to be a significant predictor of DFS (P < .001). Both SUV(max) and the mass of the nodule were closely correlated with pathologic score. CONCLUSION: Pathologic scoring appears to help predict DFS in patients with SPN lung adenocarcinoma and shows close correlation with imaging biomarkers including the mass of the nodule at CT and SUV(max) at PET/CT.

Assessment of response to radiotherapy for prostate cancer: value of diffusion-weighted MRI at 3 T.

OBJECTIVE: The objective of our study was to investigate the changes of apparent diffusion coefficient (ADC) values in prostate cancers before and after radiotherapy at 3 T using a phased-array coil. MATERIALS AND METHODS: Forty-nine patients with biopsy-proven prostate cancer who received radiotherapy underwent diffusion-weighted imaging (DWI) at 3 T and were included in the study. Biopsies in all patients were performed before the initial MRI examination (range, 15-35 days before MRI; mean, 23.4 days). All 49 patients underwent DWI (b values = 0 and 1,000 s/mm(2)) before and 1-5 months after the completion of radiotherapy. The changes in ADC values were measured for cancers and benign tissues before and after therapy. Additionally, the changes in serum prostate-specific antigen (PSA) levels were evaluated before and after therapy. RESULTS: A total of 57 cancers (peripheral zone, n = 45; transition zone, n = 12) were found in 46 patients. For the tumors, the mean ADC value after therapy (1.61 x 10(-3) mm(2)/s) was increased compared with the mean ADC value before therapy (1.0 x 10(-3) mm(2)/s) (p < 0.001). After radiotherapy, the mean ADC values of benign peripheral zones and of benign transition zones were statistically significantly decreased compared with those before radiotherapy (p < 0.05). Before treatment, a significant difference of ADC values between the tumors and benign tissues was found (p < 0.001), whereas there was no significant difference of ADC values between them after treatment (p > 0.1). The median PSA level after therapy (0.49 ng/mL) was decreased compared with the median PSA level before therapy (20.0 ng/mL). CONCLUSION: With the use of a 3-T MR scanner, our preliminary results suggest that ADC values may be useful as an imaging biomarker for monitoring therapeutic response of prostate cancer to radiotherapy.

Percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the diaphragm and gastrointestinal tracts with the use of artificial ascites: safety and technical efficacy in 143 patients.

The purpose of this study was to assess the feasibility, safety and efficacy of radiofrequency ablation (RFA) with the use of artificial ascites for hepatocellular carcinoma (HCC) adjacent to the diaphragm and gastrointestinal tract. One hundred forty-three patients with 181 HCCs who underwent US-guided percutaneous RFA with the use of artificial ascites were retrospectively reviewed. Among the 181 HCCs, 148 HCCs were defined as problematic nodules for two major reasons: poor sonic window or possible thermal injury. We artificially induced ascites before performing RFA by dripping 5% dextrose in a water solution. We assessed the technical success of introducing artificial ascites, technical feasibility of the use of artificial ascites and complications. The technical success rate, as well as the primary and secondary technique success rate, was assessed by regular follow-up CT examinations. RFA with artificial ascites was successfully achieved in 130 of 143 patients. The primary technique effectiveness was 85.3%. During follow-up (mean, 20.4 months), remote intrahepatic recurrence occurred in 49 patients and local tumor progression occurred in 15 patients. Three (2.1%) of the 143 patients experienced major complications (hemoperitoneum, lobar infarction and biloma) related to the RFA procedure. The use of artificial ascites is a simple and useful technique to minimize collateral thermal injury and to improve the sonic window.

Kidney-specific activity of the bovine uromodulin promoter.

A 10-kilobase (kb) lambda bacteriophage bovine genomic clone containing 5.4 kb of the 5'-flanking region, exons, and introns of bovine uromodulin gene was isolated. Transgenic mice containing 3.9 kb of the bovine uromodulin promoter and a lacZ reporter gene were generated by pronuclear microinjection. RT-PCR and northern blot analyses of transgene expression in various tissues of founder and F1 mice showed that the transgene was expressed exclusively in the kidney. In situ hybridization and histochemistry for lacZ demonstrated that transgene expression was restricted to tubule epithelial cells of the loop of Henle in the kidney. Stepwise 5' deletion analysis revealed that transfection of luciferase reporter constructs fused to various proximal 5'-flanking regions of the bovine uromodulin gene markedly increased luciferase activity in mouse renal epithelial cells but not in mesenchymal cells and that the most critical cis elements of the uromodulin gene are located within the 600 bp upstream region.