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BackgroundTo evaluate the anatomic site(s) of initial disease progression in patients with castration resistant metastatic prostate cancer (mCRPC) in the presence or absence of pre-treatment visceral metastases while on systemic therapy.MethodsThis is a retrospective cohort study of mCRPC patients who have baseline and at least one follow up bone scan and CT chest, abdomen and pelvis (CAP). Disease progression was determined by RECIST and/or ≥ 30% increase in automated bone scan lesion area score. Kaplan-Meier plot was used to estimate the median progression free survival and log-rank tests were used to compare anatomic sites.ResultsOf 203 patients, 61 (30%) had pre-treatment visceral metastases. Patients with baseline visceral disease were 1.5 times more likely to develop disease progression (HR = 1.53; 95% CI, 1.03-2.26). Disease progression was a result of worsening bone scan disease (42% (16/38)) versus visceral (32% (12/38)) or lymph node disease (3% (1/38)) by CT or a combination thereof (23% (9/38)). Median time to progression (TTP) did not differ by anatomic location of initial progression (p = 0.86). Development of new lesions occurred in 50% of those visceral patients with soft tissue only progression and was associated with a significantly longer TTP (3.1 months (2.8-4.3 months) than those with worsening of pre-existing lesions (1.8 months (1.6-2.7 months); p = 0.04.ConclusionsPatients with pre-treatment visceral metastases in mCRPC are more likely to experience disease progression of bone disease with the initial anatomic site of progression similar to those without baseline visceral involvement.

PurposeThe purpose of this work was to estimate and compare breast and lung doses of chest CT scans using organ-based tube current modulation (OBTCM) to those from conventional, attenuation-based automatic tube current modulation (ATCM) across a range of patient sizes.MethodsThirty-four patients (17 females, 17 males) who underwent clinically indicated CT chest/abdomen/pelvis (CAP) examinations employing OBTCM were collected from two multi-detector row CT scanners. Patient size metric was assessed as water equivalent diameter (Dw ) taken at the center of the scan volume. Breast and lung tissues were segmented from patient image data to create voxelized models for use in a Monte Carlo transport code. The OBTCM schemes for the chest portion were extracted from the raw projection data. ATCM schemes were estimated using a recently developed method. Breast and lung doses for each TCM scenario were estimated for each patient model. CTDIvol -normalized breast (nDbreast ) and lung (nDlung ) doses were subsequently calculated. The differences between OBTCM and ATCM normalized organ dose estimates were tested using linear regression models that included CT scanner and Dw as covariates.ResultsMean dose reduction from OBTCM in nDbreast was significant after adjusting for the scanner models and patient size (P = 0.047). When pooled with females and male patient, mean dose reduction from OBTCM in nDlung was observed to be trending after adjusting for the scanner model and patient size (P = 0.085).ConclusionsOne specific manufacturer's OBTCM was analyzed. OBTCM was observed to significantly decrease normalized breast relative to a modeled version of that same manufacturer's ATCM scheme. However, significant dose savings were not observed in lung dose over all. Results from this study support the use of OBTCM chest protocols for females only.

ObjectivesTo determine whether repeated administration of the macrocyclic gadolinium-based contrast agent (GBCA) gadobutrol in children is associated with T1-weighted hyperintensity within the dentate nucleus, an imaging surrogate for gadolinium deposition.MethodsWith institutional review board approval, we identified a cohort of eight patients aged 18 years or younger who underwent at least four gadobutrol-enhanced magnetic resonance imaging (MRI) examinations of the brain from 2013 to 2017. For comparison, we identified a cohort of 19 patients who underwent at least four gadopentetate dimeglumine-enhanced MRI examinations. For each examination, both dentate nuclei were contoured on unenhanced images; the mean dentate-to-pons signal intensity (DN-P SI) ratio was calculated. DN-P SI ratios from the first and last MRI exams were compared using Wilcoxon signed ranks tests and linear regression analyses.ResultsIn the gadobutrol cohort, there was no significant change in the mean DN-P SI ratio from the first to the last scan (1.02 vs 1.02, p = 1.00). In the gadopentetate dimeglumine cohort, there was a significant increase in the mean DN-P SI ratio from the first to the last scan (1.05 vs 1.13, p = 0.003). After controlling for potentially confounding variables, the change in DN-P SI ratio from the first to the last scan was significantly lower for patients in the gadobutrol group than in the gadopentetate dimeglumine group (β = -0.08, p = 0.04).ConclusionsRepeated administration of the macrocyclic GBCA gadobutrol in children was not associated with T1-weighted dentate hyperintensity, while the repeated administration of the linear GBCA gadopentetate dimeglumine was associated with T1-weighted dentate hyperintensity, presumably due to gadolinium deposition.Key points• Gadolinium-based contrast agents are routinely used in magnetic resonance imaging. • Repeated administration of the macrocyclic agent gadobutrol in children was not associated with T1-weighted dentate hyperintensity.

Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis. © RSNA, 2017.

PurposeCardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL).MethodsLV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method.ResultsPeak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH.ConclusionBreath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

RationaleThe Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood.ObjectivesTo prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus.MethodsWe determined the baseline to 12-month change in computed tomographic image-derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans.Measurements and main resultsThere was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image-derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. -0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point.ConclusionsCollectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying.

Lack of classifier robustness is a barrier to widespread adoption of computer-aided diagnosis systems for computed tomography (CT). We propose a novel Robustness-Driven Feature Selection (RDFS) algorithm that preferentially selects features robust to variations in CT technical factors. We evaluated RDFS in CT classification of fibrotic interstitial lung disease using 3D texture features. CTs were collected for 99 adult subjects separated into three datasets: training, multi-reconstruction, testing. Two thoracic radiologists provided cubic volumes of interest corresponding to six classes: pulmonary fibrosis, ground-glass opacity, honeycombing, normal lung parenchyma, airway, vessel. The multi-reconstruction dataset consisted of CT raw sinogram data reconstructed by systematically varying slice thickness, reconstruction kernel, and tube current (using a synthetic reduced-tube-current algorithm). Two support vector machine classifiers were created, one using RDFS ("with-RDFS") and one not ("without-RDFS"). Classifier robustness was compared on the multi-reconstruction dataset, using Cohen's kappa to assess classification agreement against a reference reconstruction. Classifier performance was compared on the testing dataset using the extended g-mean (EGM) measure. With-RDFS exhibited superior robustness (kappa 0.899-0.989) compared to without-RDFS (kappa 0.827-0.968). Both classifiers demonstrated similar performance on the testing dataset (EGM 0.778 for with-RDFS; 0.785 for without-RDFS), indicating that RDFS does not compromise classifier performance when discarding nonrobust features. RDFS is highly effective at improving classifier robustness against slice thickness, reconstruction kernel, and tube current without sacrificing performance, a result that has implications for multicenter clinical trials that rely on accurate and reproducible quantitative analysis of CT images collected under varied conditions across multiple sites, scanners, and timepoints.

UnlabelledMicrovascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N = 72) or LT (N = 85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (κ = 0.705; P 147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P 147 months), and in LT patients within Milan criteria (P 147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P = 0.001; 27% vs. 62%).ConclusionRVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.

PurposeTo evaluate the relationship between left ventricular (LV) twist, shear, and twist-per-volume and the severity of mitral regurgitation (MR). Primary MR is a valvular disorder that induces LV dysfunction. There exist several measures of LV rotational mechanics, but it remains unclear which measure of LV dysfunction best accords with the severity of MR. We hypothesized that LV systolic twist-per-volume slope would decrease with increasing severity of MR because of both decreases in rotational mechanics and increases in stroke volumes.Materials and methodsNormal subjects (n = 54), moderate MR patients (n = 29), and severe MR patients (n = 54) were studied. Magnetic resonance imaging (MRI) was performed on a 1.5T scanner and grid-tagged LV images were collected at the LV base and LV apex. Measures of LV rotational mechanics were derived from tagged images using Fourier Analysis of STimulated echoes (FAST).ResultsPeak systolic twist-per-volume slope was significantly different for all pairwise comparisons (P < 0.0001) and compared to normal subjects (-0.14 ± 0.05°/mL) was decreased in moderate MR (-0.12 ± 0.04°/mL) and further decreased in severe MR (-0.07 ± 0.03°/mL).ConclusionPeak systolic twist-per-volume slope significantly decreased with increasing severity of MR and is therefore a suitable quantitative imaging biomarker for LV dysfunction in patients with MR.

PurposeMeasuring the size of nodules on chest CT is important for lung cancer staging and measuring therapy response. 3D volumetry has been proposed as a more robust alternative to 1D and 2D sizing methods. There have also been substantial advances in methods to reduce radiation dose in CT. The purpose of this work was to investigate the effect of dose reduction and reconstruction methods on variability in 3D lung-nodule volumetry.MethodsReduced-dose CT scans were simulated by applying a noise-addition tool to the raw (sinogram) data from clinically indicated patient scans acquired on a multidetector-row CT scanner (Definition Flash, Siemens Healthcare). Scans were simulated at 25%, 10%, and 3% of the dose of their clinical protocol (CTDIvol of 20.9 mGy), corresponding to CTDIvol values of 5.2, 2.1, and 0.6 mGy. Simulated reduced-dose data were reconstructed with both conventional filtered backprojection (B45 kernel) and iterative reconstruction methods (SAFIRE: I44 strength 3 and I50 strength 3). Three lab technologist readers contoured "measurable" nodules in 33 patients under each of the different acquisition/reconstruction conditions in a blinded study design. Of the 33 measurable nodules, 17 were used to estimate repeatability with their clinical reference protocol, as well as interdose and inter-reconstruction-method reproducibilities. The authors compared the resulting distributions of proportional differences across dose and reconstruction methods by analyzing their means, standard deviations (SDs), and t-test and F-test results.ResultsThe clinical-dose repeatability experiment yielded a mean proportional difference of 1.1% and SD of 5.5%. The interdose reproducibility experiments gave mean differences ranging from -5.6% to -1.7% and SDs ranging from 6.3% to 9.9%. The inter-reconstruction-method reproducibility experiments gave mean differences of 2.0% (I44 strength 3) and -0.3% (I50 strength 3), and SDs were identical at 7.3%. For the subset of repeatability cases, inter-reconstruction-method mean/SD pairs were (1.4%, 6.3%) and (-0.7%, 7.2%) for I44 strength 3 and I50 strength 3, respectively. Analysis of representative nodules confirmed that reader variability appeared unaffected by dose or reconstruction method.ConclusionsLung-nodule volumetry was extremely robust to the radiation-dose level, down to the minimum scanner-supported dose settings. In addition, volumetry was robust to the reconstruction methods used in this study, which included both conventional filtered backprojection and iterative methods.

PurposeTask Group 204 introduced effective diameter (ED) as the patient size metric used to correlate size-specific-dose-estimates. However, this size metric fails to account for patient attenuation properties and has been suggested to be replaced by an attenuation-based size metric, water equivalent diameter (DW). The purpose of this study is to investigate different size metrics, effective diameter, and water equivalent diameter, in combination with regional descriptions of scanner output to establish the most appropriate size metric to be used as a predictor for organ dose in tube current modulated CT exams.Methods101 thoracic and 82 abdomen/pelvis scans from clinically indicated CT exams were collected retrospectively from a multidetector row CT (Sensation 64, Siemens Healthcare) with Institutional Review Board approval to generate voxelized patient models. Fully irradiated organs (lung and breasts in thoracic scans and liver, kidneys, and spleen in abdominal scans) were segmented and used as tally regions in Monte Carlo simulations for reporting organ dose. Along with image data, raw projection data were collected to obtain tube current information for simulating tube current modulation scans using Monte Carlo methods. Additionally, previously described patient size metrics [ED, DW, and approximated water equivalent diameter (DWa)] were calculated for each patient and reported in three different ways: a single value averaged over the entire scan, a single value averaged over the region of interest, and a single value from a location in the middle of the scan volume. Organ doses were normalized by an appropriate mAs weighted CTDIvol to reflect regional variation of tube current. Linear regression analysis was used to evaluate the correlations between normalized organ doses and each size metric.ResultsFor the abdominal organs, the correlations between normalized organ dose and size metric were overall slightly higher for all three differently (global, regional, and middle slice) reported DW and DWa than they were for ED, but the differences were not statistically significant. However, for lung dose, computed correlations using water equivalent diameter calculated in the middle of the image data (DW,middle) and averaged over the low attenuating region of lung (DW,regional) were statistically significantly higher than correlations of normalized lung dose with ED.ConclusionsTo conclude, effective diameter and water equivalent diameter are very similar in abdominal regions; however, their difference becomes noticeable in lungs. Water equivalent diameter, specifically reported as a regional average and middle of scan volume, was shown to be better predictors of lung dose. Therefore, an attenuation-based size metric (water equivalent diameter) is recommended because it is more robust across different anatomic regions. Additionally, it was observed that the regional size metric reported as a single value averaged over a region of interest and the size metric calculated from a single slice/image chosen from the middle of the scan volume are highly correlated for these specific patient models and scan types.

BackgroundNitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model.MethodsThe effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL).ResultsNitroxoline inhibited the proliferation and invasion of glioblastoma cells in a time- and dose-dependent manner in vitro. Growth inhibition was associated with cell-cycle arrest in G1/G0 phase and induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of treatment, whereas tumor volumes doubled in control mice. Histological examination revealed 15%-20% TUNEL-positive cells in nitroxoline-treated mice, compared with ∼5% in the control group.ConclusionNitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. As an already FDA-approved treatment for urinary tract infections with a known safety profile, nitroxoline could move quickly into clinical trials pending confirmatory studies.

PurposeTo compare the capability to aid prediction of clinical outcome measures, including progression-free survival (PFS) and overall survival (OS), between volumetric estimates from contrast material-enhanced (CE) T1-weighted subtraction maps and traditional segmentation in a randomized multicenter clinical trial of recurrent glioblastoma (GBM) patients treated with bevacizumab.Materials and methodsAll patients participating in this study signed institutional review board-approved informed consent at their respective institutions prior to enrolling in the multicenter clinical trial. One-hundred sixty patients with recurrent GBM enrolled as part of a HIPAA-compliant, multicenter clinical trial (AVF3708 g, BRAIN trial). Contrast-enhancing tumor volumes and change in volumes as a response to therapy were quantified by using either conventional segmentation or CE T1-weighted subtraction maps created by voxel-by-voxel subtraction of intensity-normalized nonenhanced T1-weighted images from CE T1-weighted images. These volumes were then tested as predictors of PFS and OS by using log-rank univariate analysis, the multivariate Cox proportional hazards regression model, and receiver operating characteristic analysis.ResultsUse of CE T1-weighted subtraction maps qualitatively improved visualization and improved quantification of tumor volume after bevacizumab treatment. Significant trends between the volume of tumor and change in tumor volume after therapy on CE T1-weighted subtraction maps were found for both PFS and OS (pretreatment volume < 15 cm(3), P < .003; posttreatment volume < 7.5 cm(3), P < .05; percentage change in volume > 25%, P = .004 for PFS and P = .053 for OS). CE T1-weighted subtraction maps were significantly better at aiding prediction of 6-month PFS and 12-month OS compared with conventional segmentation by using receiver operating characteristic analysis (P < .05).ConclusionUse of CE T1-weighted subtraction maps improved visualization and aided better prediction of patient survival in recurrent GBM treated with bevacizumab compared with conventional segmentation of CE T1-weighted images. Clinical trial registration no. NCT00345163. Online supplemental material is available for this article.

The purpose of this study was to use a retrospective nonlinear distortion correction technique and evaluate the changes in DTI metrics in areas of interest in and around GBM tumors. A total of 24 histologically confirmed GBM patients with pre-operative 20-direction DTI scans were examined. Variability in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in normal tissue before and after distortion correction were examined. Changes in mean, median and variance of ADC and FA in contrast enhancing and T2/FLAIR ROIs were also examined with and without distortion correction. Results suggest the intra-subject SDs of ADC and FA decreased in normal tissue after the application of distortion correction (P

PurposeTo assess the intra- and interscan reproducibility of LV twist using FAST. Assessing the reproducibility of the measurement of new MRI biomarkers is an important part of validation. Fourier Analysis of STimulated Echoes (FAST) is a new MRI tissue tagging method that has recently been shown to compare favorably with conventional estimates of left ventricular (LV) twist from cardiac tagged images, but with significantly reduced user interaction time.Materials and methodsHealthy volunteers (N = 10) were scanned twice using FAST over 1 week. On day 1, two measurements of LV twist were collected for intrascan comparisons. Measurements for LV twist were again collected on day 8 for interscan assessment. LV short-axis tagged images were acquired on a 3 Tesla (T) scanner to ensure detectability of tags during early and mid-diastole. Peak LV twist is reported as mean ± SD. Reproducibility was assessed using the concordance correlation coefficient (CCC) and the repeatability coefficient (RC) (95% confidence interval [CI] range).ResultsMean peak twist measurements were 13.4 ± 4.3° (day 1, scan 1), 13.6 ± 3.7° (day 1, scan 2), and 13.0 ± 2.7° (day 8). Bland-Altman analysis resulted in intra- and interscan bias and 95% CI of -0.6° [-1.0°, 1.6°] and 1.4° (-1.0°, 3.0°), respectively. The Bland-Altman RC for peak LV twist was 2.6° and 4.0° for intra- and interscan, respectively. The CCC was 0.9 and 0.6 for peak LV twist for intra- and interscan, respectively.ConclusionFAST is a semi-automated method that provides a quick and quantitative assessment of LV systolic and diastolic twist that demonstrates high intrascan and moderate interscan reproducibility in preliminary studies.

Rationale and objectivesTo estimate and statistically compare the bias and variance of radiologists measuring the size of spherical and complex synthetic nodules.Materials and methodsThis study did not require the institutional review board approval. Six radiologists estimated the size of 10 synthetic nodules embedded within an anthropomorphic thorax phantom from computed tomography scans at 0.8- and 5-mm slice thicknesses. The readers measured the nodule size using unidimensional (1D) longest in-slice dimension, bidimensional (2D) area from longest in-slice and longest perpendicular dimension, and three-dimensional (3D) semiautomated volume. Intercomparisons of bias (difference between average and true size) and variance among methods were performed after converting the 2D and 3D estimates to a compatible 1D scale.ResultsThe relative biases of radiologists with the 3D tool were -1.8%, -0.4%, -0.7%, -0.4%, and -1.6% for 10-mm spherical, 20-mm spherical, 20-mm elliptical, 10-mm lobulated, and 10-mm spiculated nodules compared to 1.4%, -0.1%, -26.5%, -7.8%, and -39.8% for 1D. The three-dimensional measurements were significantly less biased than 1D for elliptical, lobulated, and spiculated nodules. The relative standard deviations for 3D were 7.5%, 3.9%, 3.6%, 9.7%, and 8.3% compared to 5.7%, 2.6%, 20.3%, 5.3%, and 16.4% for 1D. Unidimensional sizing was significantly less variable than 3D for the lobulated nodule and significantly more variable for the ellipsoid and spiculated nodules. Three-dimensional bias and variability were smaller for thin 0.8-mm slice data compared to thick 5.0-mm data.ConclusionsThe study shows that radiologist-controlled 3D volumetric lesion sizing can not only achieve smaller bias but also achieve similar or smaller variability compared to 1D sizing, especially for complex lesion shapes.

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III–IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity.

We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 × 10(-6)mm(2)/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L 0.71 versus ADC-L >1,209 and LCP

ObjectivesTo propose and evaluate a technique for automatic quantification of fissural completeness from chest computed tomography (CT) in a database of subjects with severe emphysema.MethodsNinety-six CT studies of patients with severe emphysema were included. The lungs, fissures and lobes were automatically segmented. The completeness of the fissures was calculated as the percentage of the lobar border defined by a fissure. The completeness score of the automatic method was compared with a visual consensus read by three radiologists using boxplots, rank sum tests and ROC analysis.ResultsThe consensus read found 49% (47/96), 15% (14/96) and 67% (64/96) of the right major, right minor and left major fissures to be complete. For all fissures visually assessed as being complete the automatic method resulted in significantly higher completeness scores (mean 92.78%) than for those assessed as being partial or absent (mean 77.16%; all p values

Abstract Background The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA). Methods To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay. Results Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve. Conclusions The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.