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T2*-weighted image (TE=4.9 ms) for a stage IV HNSCC patient (Pt No: 5). Marker lines represent image positions used in the assessment of motion correction. B: Time traces of nodal (LN) and primary (P) projections without (S(t)) and with motion correction (S(t)MOCO). Pronounced global motion (i.e. swallowing) is marked with an asterisk. Persistent motion artifacts present in the primary tumor are indicated with an arrow.

Scatter plots comparing individual MRI measurements (tumor volume, baseline R2* and percentage of fluctuating volume) against pathology (Hoechst 33342 uptake for perfusion, pimonidazole adduct formation for hypoxia) determined from the cohort of CALR xenografts.

Fluctuating volume percentages detected for HNSCC metastatic lymph node ROIs between two MR sessions 48 hours apart (solid lines - responders, dashed lines - non responders).

Examples of Ktrans and R2* distributions for fluctuating and non-fluctuating parts of human HNSCC (Patient No 5, N2). The non-enhancing part of the tumor (Ktrans = 0) is indicated with an asterisk.

Supplementary Figure Captions

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within human HNSCC classified as significantly fluctuating (tumor - top two rows) and without significant fluctuations (tumor - middle two rows, adjacent muscle - bottom row).

Example of coronal T2-weighted image of two simultaneously scanned mice bearing CALR HNSCC xenografts (mice IV and V, tumors are marked with arrows) and a phantom containing 1.5 mM gadoterate meglumine (Dotarem, Guerbet, Villepinte, France) in saline, acquired using the asymmetric high-resolution three element receive coil.

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within CALR HNSCC xenografts classified as significantly fluctuating (CALR tumor - top two rows) and without significant fluctuations (CALR tumor - middle two rows, adjacent muscle - bottom row).

BackgroundMost MRI radiomics studies to date, even multi-centre ones, have used “pure” datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in “real-world” scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice.MethodsOne hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests.ResultsPrediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9–51.8% (radiomic features from different combinations of image contrasts), and 26.7–35.6% (clinical plus radiomics features).ConclusionsRadiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.

Background Textural features extracted from MRI potentially provide prognostic information additional to volume for influencing surgical management of cervical cancer. Purpose To identify textural features that differ between cervical tumors above and below the volume threshold of eligibility for trachelectomy and determine their value in predicting recurrence in patients with low-volume tumors. Methods Of 378 patients with Stage1–2 cervical cancer imaged prospectively (3T, endovaginal coil), 125 had well-defined, histologically-confirmed squamous or adenocarcinomas with >100 voxels (>0.07 cm3) suitable for radiomic analysis. Regions-of-interest outlined the whole tumor on T2-W images and apparent diffusion coefficient (ADC) maps. Textural features based on grey-level co-occurrence matrices were compared (Mann-Whitney test with Bonferroni correction) between tumors greater (n = 46) or less (n = 79) than 4.19 cm3. Clustering eliminated correlated variables. Significantly different features were used to predict recurrence (regression modelling) in surgically-treated patients with low-volume tumors and compared with a model using clinico-pathological features. Results Textural features (Dissimilarity, Energy, ClusterProminence, ClusterShade, InverseVariance, Autocorrelation) in 6 of 10 clusters from T2-W and ADC data differed between high-volume (mean ± SD 15.3 ± 11.7 cm3) and low-volume (mean ± SD 1.3 ± 1.2 cm3) tumors. (p, Highlights • Texture features differed significantly between high-compared to low-volume cervical tumors (p

Purpose To evaluate robustness and repeatability of magnetic resonance imaging (MRI) texture features in water and tissue phantom test-retest study. Materials and methods Separate water and tissue phantoms were imaged twice with the same protocol in a test-retest experiment using a 1.5-T scanner. Protocols were acquired to favour signal-to-noise ratio and resolution. Forty-six features including first order statistics and second-order texture features were extracted, and repeatability was assessed by calculating the concordance correlation coefficient. Separately, base image noise and resolution were manipulated in an in silico experiment, and robustness of features was calculated by assessing percentage coefficient of variation and linear correlation of features with noise and resolution. These simulation data were compared with the acquired data. Features were classified by their degree (high, intermediate, or low) of robustness and repeatability. Results Eighty percent of the MRI features were repeatable (concordance correlation coefficient > 0.9) in the phantom test-retest experiment. The majority (approximately 90%) demonstrated a strong or intermediate correlation with image acquisition parameter, and 19/46 (41%) and 13/46 (28%) of features were highly robust to noise and resolution, respectively (coefficient of variation < 5%). Agreement between the acquired and simulation data varied, with the range of agreement within feature classes between 11 and 92%. Conclusion Most MRI features were repeatable in a phantom test-retest study. This phantom data may serve as a lower limit of feature MRI repeatability. Robustness of features varies with acquisition parameter, and appropriate features can be selected for clinical validation studies.

Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been used as imaging biomarkers in adults with high-grade gliomas (HGGs). We incorporated free-breathing DW-MRI and DCE-MRI, at a single time point, in the routine follow-up of five children (median age 9 years, range 8-15) with histologically confirmed HGG within a prospective imaging study. It was feasible to incorporate DW-MRI and DCE-MRI in routine assessments of children with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median ADC100-1000 significantly correlated with longer survival in our sample.

Objective To prospectively evaluate individual functional MRI metrics for the early prediction of pathological complete response (pCR) to neo-adjuvant chemotherapy (NAC) in breast cancer. Materials and methods Thirty-two women (median age 52 years; range 32–71 years) with biopsy proven breast cancer due to receive neo-adjuvant anthracycline and/or taxane-based chemotherapy were prospectively recruited following local research ethics committee approval and written informed consent. Breast MRI was performed prior to and after two cycles of NAC and pCR was assessed after surgery. The enhancement fraction (EF), tumour volume, initial area under the gadolinium curve (IAUGC), pharmacokinetic parameters ( K trans , k ep and v e ), the apparent diffusion coefficient (ADC) and R2* values, along with the percentage change in these parameters after two cycles were evaluated according to pCR status using an independent samples t-test. The area under the receiver operating characteristics curve (AUC) was calculated for each parameter. Linear discriminant analysis (LDA) determined the most important parameter in predicting pCR. Results A reduction in the EF (−41% ± 38%) and tumour volume (−80% ± 25%) after 2 cycles of NAC were significantly greater in those achieving pCR (p = 0.025, p = 0.011 respectively). A reduction in the EF of 7% after 2 cycles of NAC identified those more likely to achieve pCR (AUC 0.76). AUC changes in other parameters were tumour volume (0.77), IAUGC (0.64), K trans (0.60), k ep (0.68), v e (0.58), ADC (0.69) and R2* (0.41). Conclusion In a multi-parametric MRI model, the decrease in a non-model based vascular parameter the enhancement fraction as well as the tumour volume are the most important early predictors of pCR in breast cancer.

Objectives To determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma. Methods Female Sprague-Dawley rats (n=18) were administered with N-methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated. Excised tumours were histologically assessed for degree of necrosis, collagen, hypoxia and microvessel density. Significance level adjusted for multiple comparisons was p=0.0125. Results Significant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for ka and δ, r < -0.75, p < 0.001 for T1 and T1s, Pearson), indicating that MT is sensitive to collagen content in mammary carcinoma. Picrosirius red also correlated with the DWI parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T2* (r=-0.660, p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional-echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31 (microvessel density) staining did not correlate with any MR parameter assessed. Conclusions Magnetisation transfer MRI successfully detects collagen content in mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a prognostic marker, in clinical breast MRI examinations. Key Points • Magnetisation transfer imaging is sensitive to collagen content in mammary carcinoma. • Magnetisation transfer imaging to detect fibrosis in mammary carcinoma fibrosis is feasible. • IVIM diffusion does not correlate with microvessel density in preclinical mammary carcinoma. Electronic supplementary material The online version of this article (10.1007/s00330-017-5083-6) contains supplementary material, which is available to authorized users.

Objectives To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours. Methods Paediatric patients (30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083). Conclusion Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data. Key Points • ADC has good repeatability as low 5th centile of the histogram distribution. • High CV was observed for all parameters at extremes of histogram. • Parameters from the stretched exponential model showed low coefficients of variation. • The median ADC, D, DDC α , and DDC K are highly correlated and repeatable. • Perfusion/kurtosis parameters showed high CV variations across their histogram distributions.

This article describes a highly tailorable exposure assessment strategy for nanomaterials that enables effective and efficient exposure management (i.e., a strategy that can identify jobs or tasks that have clearly unacceptable exposures), while simultaneously requiring only a modest level of resources to conduct. The strategy is based on strategy general framework from AIHA® that is adapted for nanomaterials and seeks to ensure that the risks to workers handling nanomaterials are being managed properly. The strategy relies on a general framework as the basic foundation while building and elaborating on elements essential to an effective and efficient strategy to arrive at decisions based on collecting and interpreting available information. This article provides useful guidance on conducting workplace characterization; understanding exposure potential to nanomaterials; accounting methods for background aerosols; constructing SEGs; and selecting appropriate instrumentation for monitoring, providing appropriate choice of exposure limits, and describing criteria by which exposure management decisions should be made. The article is intended to be a practical guide for industrial hygienists for managing engineered nanomaterial risks in their workplaces.

To investigate whether early changes in vascular parameters determined with dynamic contrast material-enhanced magnetic resonance (MR) imaging after two cycles of neoadjuvant chemotherapy (NAC) are predictive of disease-free and overall survival in primary breast cancer.Institutional ethics approval and informed consent were obtained. Patients with primary breast cancer (median age, 45 years; age range, 22-70 years) recruited from January 2001 to September 2008 underwent dynamic contrast-enhanced MR imaging before and after two cycles of NAC. Quantitative and semiquantitative kinetic parameters were calculated, including the volume transfer constant (K(trans)) and the initial area under the gadolinium concentration-time curve over 60 seconds (IAUGC(60)). Cut points optimized to the receiver operating characteristic curve were used to dichotomize MR imaging data for Kaplan-Meier survival analysis. MR imaging parameters and known prognostic indicators in primary breast cancer were correlated with disease-free and overall survival by using the Cox proportional hazards model for univariate and multivariate analyses.MR imaging was performed before (n = 62) and after (n = 58) two cycles of NAC. The median follow-up time was 43.9 months for disease-free survival and 60.3 months for overall survival. There were 28 recurrences; 26 patients had distant metastases (two had additional local recurrence) and two had local recurrence only. There were 20 deaths, all of which were related to breast cancer. At univariate analysis, progesterone receptor status, the type of surgery performed, higher posttreatment K(trans) (P = .048), and larger posttreatment IAUGC(60) (P = .035) were significant predictors of worse disease-free survival. At multivariate analysis, progesterone receptor status (P = .002) and mean transit time (P = .025) were significant predictors of disease-free survival. Univariate analysis showed that clinical tumor stage (P = .005), progesterone receptor status (P = .025), and type of surgery performed (P = .017) were significant predictors of overall survival. Higher posttreatment K(trans) (P = .043), larger IAUGC(60) (P = .029), and larger tumor size at posttreatment MR imaging were predictive of worse overall survival (P = .018). Of these variables, K(trans) remained an independent indicator of overall survival (P = .038).Higher posttreatment tumor vascularization as depicted with dynamic contrast-enhanced MR imaging may be associated with higher recurrence and lower survival rates. Dynamic contrast-enhanced MR imaging parameters, in conjunction with traditional prognostic factors, have the potential to be prognostic biomarkers for disease-free and overall survival in primary breast cancer.

The detection and prognosis of prostate cancer in its early stages are critically important. It is therefore essential to improve the existing dynamic contrast-enhanced MRI (DCE MRI) techniques commonly used for the assessment of the tumour vascular environment. The goal of this study was to describe a method for the estimation of the arterial input function (AIF) in DCE MRI by measuring R-2* values in the femoral artery of patients with early-stage prostate cancer. The calculation of contrast agent concentrations was based on calibration curves determined in whole blood samples for a range of normal haematocrit (HCT) values (HCT 0.35-0.525). Individual AIFs corrected for HCT were compared with individual AIFs calibrated with a mean whole blood [R-2*-Gd-DTPA-BMA] [Gd-DTPA-BMA, gadolinium diethylenetriaminepentaacetate-bis(methylamide) (gadodiamide)] curve at an assumed HCT = 0.44, as well as a population AIF at an assumed HCT = 0.45. The area under the curve of the first-pass bolus ranged between 0.6 min mM at HCT = 0.53 and 1.3 min mM at HCT = 0.39. Significant differences in magnitude at peak contrast agent concentrations (HCT = 0.36, [Gd-DTPA-BMA](max) = 9 +/- 0.4 mM; HCT = 0.46, [Gd-DTPA-BMA](max) = 4.0 +/- 0.2 mM) were found. Using model-based simulations, the accuracy of the kinetic parameters estimated using individual AIFs corrected for HCT demonstrated that, for the use of individual calibration curves with HCT values differing by more than 10%, K-trans and k(ep) values were largely underestimated (up to 60% difference for K-trans). Moreover, blood volume estimates were severely underestimated. Estimates of kinetic parameters in early-stage prostate cancer patients demonstrated that the efflux rate constant (k(ep)) was influenced significantly by the definition of AIF. Regardless of whether an individually calibrated AIF or a population AIF (average of all individually calibrated AIFs) was used, pixel-by-pixel mapping of k(ep) and v(b) in the prostate gland appeared to be more sensitive than with the usual biexponential approach. Copyright (C) 2011 John Wiley & Sons, Ltd.

Triple-negative (ER-/PR-/HER2-) breast carcinomas (TNBC) are aggressive tumours with underexplored imaging features. This study investigates whether their vascular characteristics as assessed by dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI are distinct from the prognostically more favourable ER+/PR+/HER2- cancers.Patients with primary breast cancer underwent MRI before neoadjuvant chemotherapy and were identified as ER-/PR-/HER2- or ER+/PR+/HER2- from core biopsy specimens. MRI parameters reflecting tissue perfusion, permeability, and extracellular leakage space were measured. Values for inflow transfer constant (K(trans)), outflow rate constant (k(ep)), leakage space (v(e)), area under the gadolinium curve (IAUGC(60) ), relative blood volume (rBV) and flow (rBF), and Mean Transit Time (MTT) were compared across receptor status and with known prognostic variables.Thirty seven patients were assessable in total (16 ER-/PR-/HER2-, 21 ER+/PR+/HER2-). Lower v(e) (p = 0.001), shorter MTT (p = 0.007) and higher k(ep) values (p = 0.044) were observed in TNBC. v(e) was lower across all T stages, node-negative (p = 0.004) and low-grade TNBC (p = 0.037). v(e) was the best predictor of triple negativity (ROC AUC 0.80).TNBC possess characteristic features on imaging, with lower extracellular space (higher cell density) and higher contrast agent wash-out rate (higher vascular permeability) suggesting a distinctive phenotype detectable by MRI.

High-speed grinding with plated-CBN wheels generally requires the use of straight oils as the metal removal fluid to obtain the required performance. Unfortunately, the combination of straight oils and high speeds results in high mist generation. In this study, several grinding oils were tested for both performance and misting characteristics. Oils were chosen to cover a range of viscosities, additives, and oil types. Two fluids were also tested with antimisting polymers and showed significant decreases in mist after polymer addition. The distribution of the mist droplet size was also measured, which gives information about the mist generation mechanism; centrifugally produced aerosols are in the 1-10 μ m range, while condensation aerosols are in the 0.1-1 μ m range. Oil performance, as indicated by the power and force monitors, showed little difference between the oils. However, mist generation was highly variable across the eight tested oils. The generation of centrifugal aerosols was related to the vis...

During manufacturing, particles produced from industrial processes become airborne. These airborne emissions represent a challenge from an industrial hygiene and environmental standpoint. A study was undertaken to characterize the particles associated with a variety of manufacturing processes found in the auto industry. Air particulates were collected in five automotive plants covering ten manufacturing processes in the areas of casting, machining, heat treatment and assembly. Collection procedures provided information on air concentration, size distribution, and chemical composition of the airborne particulate matter for each process and insight into the physical and chemical processes that created those particles.

When applying pharmacokinetic (PK) models to dynamic contrast enhanced MRI (DCE-MRI) data it is important to appropriately deal with the enhancement onset time, because errors in the onset time will affect the PK parameter estimates. This paper presents a Bayesian approach to the estimation of the PK parameters k(ep) and K(trans) that robustly treats the onset time. This approach involves the computation of an analytically intractable integral, so two approximate methods are developed. The first uses adaptive numerical quadrature, which produces results accurate to a given tolerance, and the other a simple approximation with a summation. These approaches are compared with each other, and with the standard least-squares (LS) approach. The results of a Monte Carlo experiment show that the LS approach produces biased estimates when k(ep) is large and K(trans) is small, whereas both the Bayesian methods are unbiased. The two Bayesian methods produce very similar estimates, but the simple summation method requires less than half the computation time of either the LS, or the quadrature approximation. The standard deviation of the LS estimates is shown to be larger than either of the Bayesian estimates, while uncertainty estimates based around a Hessian approximation are shown to be too small for all three methods. A more detailed method of assessing the uncertainty of the Bayesian approach is described, and the results show that this is a more accurate description of the estimation uncertainty.

Magnetic Resonance Imaging Workbench (MRIW) allows analysis of T1- and T2*-weighted dynamic contrast-enhanced magnetic resonance imaging data sets to extract tissue permeability and perfusion characteristics by using standard pharmacokinetic models. Parametric maps are calculated from individual pixel enhancement curves in regions of interest (ROIs) and displayed as color overlays on the anatomic images. User-defined ROIs can be saved to ensure consistency of later reanalysis. Individual parametric maps are visualized together with user-selected parameter time-series plots. The following selections are available: overall ROI enhancement curve and fit, histogram, and individual pixel enhancement curve and fit. Summary data (transfer constant, leakage space, rate constant, integrated area under the gadolinium curve after 60 seconds, relative blood volume, relative blood flow, and mean transit time) may be exported to permanent storage along with per-pixel results for statistical analysis. Numerical values for parameters are displayed below the plot for easy reference. The dynamic range of plots and parametric map overlays is interactively adjustable. Viewing individual enhancement curves and parametric maps allows radiologists to investigate the heterogeneity of contrast agent kinetics for lesion characterization and to scrutinize serial changes in response to therapy. MRIW is written in IDL, enabling it to be used on a variety of computer systems.

Inter- and intraobserver variability in the evaluation of dynamic breast cancer MRI Purpose: To quantify variations within and between observers ascribable to manual region of interest (ROI) placement in patients with breast cancer undergoing dynamic MRI. Materials and Methods: Expert and nonexpert observers independently outlined tumor ROIs on 30 dynamic T-1-weighted (T1W) MRI scans on five occasions over two months. Lesion size (number of pixels) and kinetic parameter estimates, including the transfer constant (K-trans), were calculated for each ROI placement. Inter- and intraobserver variability was assessed with respect to the interval between drawings, lesion morphology, and observer experience. Results: For the nonexpert, the variability reduced with decreasing time intervals between ROI drawings (the coefficient of variance (wCV) values at two months, two weeks, one day, and same-day time intervals were respectively 11.6%, 10.7%, 4.8%, and 2.6% for lesion size, and 8.9%, 9.7%, 6.7%, and 3.2% for K-trans). For the expert observer, the variability was smaller overall and more constant, but improved for same-day ROI placements (region size wCV: 7.5%,6.2%,7.1%, and 3.7%; K-trans wCV: 5.4%,5.3%,5.6%, and 4.5%). Conclusion: Significant observer variability in manual ROI placement occurs in dynamic MRI of breast cancer. For serial patient studies, ROI placements should be outlined at the same sitting to minimize observer error.

Sampling of the full range of particle sizes was carried out on 16 processes in six different General Motors plants over a period of 2.5 years. This article deals with particle characterization from five of the processes that relate to machining, specifically, wet machining with water-based fluids from old and new technology processes, grinding with straight oils from old and new technology processes, and dry machining. The concentrations measured by different instruments were in reasonable agreement, although the light-scattering instrument generally produced higher values than filters. Of the processes studied, the old technology grinding using straight oils generated the highest particle concentrations. The new technology controls (enclosed, vented machines) were highly effective but more so for large particles than small particles. The particle size distribution was shifted to smaller particles with enclosed processes. Dry machining generated the largest particles of all processes studied.

The aim of the work is to evaluate a magnetic resonance imaging (MRI) thermometry sequence suitable for targeting of focused ultrasound (FUS) when used in vascular occlusion studies. A sliding window dual gradient echo (SW-dGRE) sequence was used. This sequence has the capability of monitoring both T1 relaxation and phase changes, which vary with temperature. Preliminary work involved quantification of the changes in T1 relaxation time with temperature and obtaining the PRF shift coefficient in polyacrylamide gel as it underwent an exothermic reaction during polymerization (avoiding the use of an external heat source). Temperature changes were visualized using thermal maps acquired with the sequence. For FUS guidance a thermal imaging technique is required with a temporal resolution

Objectives The objectives are to examine the reproducibility of functional MR imaging in children with solid tumours using quantitative parameters derived from diffusion-weighted (DW-) and dynamic contrast enhanced (DCE-) MRI. Methods Patients under 16-years-of age with confirmed diagnosis of solid tumours (n = 17) underwent free-breathing DW-MRI and DCE-MRI on a 1.5 T system, repeated 24 hours later. DW-MRI (6 b-values, 0-1000 sec/mm2) enabled monoexponential apparent diffusion coefficient estimation using all (ADC0-1000) and only ≥100 sec/mm2 (ADC100-1000) b-values. DCE-MRI was used to derive the transfer constant (Ktrans), the efflux constant (kep), the extracellular extravascular volume (ve), and the plasma fraction (vp), using a study cohort arterial input function (AIF) and the extended Tofts model. Initial area under the gadolinium enhancement curve and pre-contrast T1 were also calculated. Percentage coefficients of variation (CV) of all parameters were calculated. Results The most reproducible cohort parameters were ADC100-1000 (CV = 3.26 %), pre-contrast T1 (CV = 6.21 %), and Ktrans (CV = 15.23 %). The ADC100-1000 was more reproducible than ADC0-1000, especially extracranially (CV = 2.40 % vs. 2.78 %). The AIF (n = 9) derived from this paediatric population exhibited sharper and earlier first-pass and recirculation peaks compared with the literature’s adult population average. Conclusions Free-breathing functional imaging protocols including DW-MRI and DCE-MRI are well-tolerated in children aged 6 - 15 with good to moderate measurement reproducibility. Key Points • Diffusion MRI protocol is feasible and well-tolerated in a paediatric oncology population. • DCE-MRI for pharmacokinetic evaluation is feasible and well tolerated in a paediatric oncology population. • Paediatric arterial input function (AIF) shows systematic differences from the adult population-average AIF. • Variation of quantitative parameters from paired functional MRI measurements were within 20 %.

Control of occupational exposure to metalworking fluid mist generally involves enclosing the machining center and exhausting to an air cleaner that returns cleaned air to the workplace. To select an appropriate air cleaner, particle size and generation rate of the mists need to be known. Mist particle size and concentration were measured as a function of tool speed, fluid flow rate, and cutting rate at an enclosed machining center. A vertical machining center was totally enclosed and the air from this enclosure was exhausted into a duct where mist concentration and size distribution were measured using a time-of-flight aerosol spectrometer and a cascade impactor. Mist generation during the face milling of a 30 x 31-cm piece of aluminum with a 10-cm diameter face mill was studied. Machining parameters were varied as a 2 x 2 x 3 factorial experiment with these variables: coolant flow rate (18 and 44 m/sec), tool rpm (1900 and 3800 rpm), and metal removal (no removal, two teeth on face mill, and six teeth on face mill). Mist concentration increased with increasing tool speed and fluid application velocity. Whether the tool was actually removing metal did not affect the mist generation. Thus, mist generation is a function of fluid and tool motion. During a second experiment, effect of tool speed and diameter on mist generation was studied. Mist concentrations measured with the aerosol spectrometer were proportional to the 2 and 3.5 powers of the tool speed for the face mill and end mill, respectively. In both experiments the shape of the size distribution was largely unaffected by the experimental variables.

Author Summary Background. This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors. Methods. Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28. Results. Fifty-one patients received nintedanib 100–450 mg once daily (n = 40) or 250 mg b.i.d. (n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose-limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE-MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily. Conclusion. Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE-MRI. Disease stabilization >6 months was observed in 7 of 51 patients.

Due to their transient nature, short-term exposures can be difficult to detect and quantify using conventional monitoring techniques. Biological monitoring may be capable of registering such exposures and may also be used to estimate important toxicological parameters. This paper investigates relationships between methanol concentrations in the blood, urine, and breath of volunteers exposed to methanol vapor at 800 ppm for periods of 0.5, 1, 2, and 8 h. The results indicate factors that must be considered for interpretation of the results of biological monitoring. For methanol, concentrations are not proportional to the exposure duration due to metabolic and other elimination processes that occur concurrently with the exposure. First-order clearance models can be used with blood, breath, or urine concentrations to estimate exposures if the time that has elapsed since the exposure and the model parameters are known. The 0.5 to 2-h periods of exposure were used to estimate the half-life of methanol. Blood data gave a half-life of 1.44+/-0.33 h. Comparable but slightly more variable results were obtained using urine data corrected for voiding time (1.55+/-0.67h) and breath data corrected for mucous membrane desorption (1.40+/-0.38 h). Methanol concentrations in blood lagged some 15-30 min behind the termination of exposure, and concentrations in urine were further delayed. Although breath sampling may be convenient, breath concentrations reflect end-expired or alveolar air only if subjects are in a methanol-free environment for 30 min or more after the exposure. At earlier times, breath concentrations included contributions from airway desorption or diffusion processes. As based on multicompartmental models, the desorption processes have half-lives ranging between 0.6 and 5 min. Preliminary estimates of the mucous membrane reservoir indicate contributions of under 10% for a 0.5-h exposure and smaller effects for longer periods of exposure.

Biological monitoring of exposure to industrial chemicals commonly involves laboratory analyses of a toxicant or metabolites in urine. The American Conference of Governmental Industrial Hygienists has recommended biological exposure indices for methanol exposure based on methanol and formate in urine. The present study was designed primarily to evaluate methanol in urine and other potential biological determinants of methanol exposure. Volunteer subjects underwent controlled exposure to methanol vapor at different concentrations for approximately 8 hours to simulate a standard work shift. Urine was collected immediately prior to exposure sessions, during exposures, and immediately following cessation of exposures. Samples were analyzed for methanol, formate, specific gravity (SpGr), and creatinine. The following biological determinants were examined: total methanol excreted during the shift; mean concentration of methanol excreted during the shift (uncorrected, and corrected for SpGr and creatini...

A fundamental assumption of monitoring breath for a toxicant is that the concentration of the toxicant in breath is proportional to the concentration in blood. The present study was designed, in part, to assess the conditions under which measurement of methanol in breath would be useful for estimating the blood concentration of methanol following inhalation or dermal exposures to methanol. Paid volunteer subjects underwent controlled inhalation exposure to methanol vapor at various concentrations for 8 hours, or dermal exposures (without inhalation exposure) to methanol for varying periods of time. Blood and end-expiratory air were analyzed for methanol from samples obtained prior to exposures, and at various times during and after exposures. The results demonstrate that blood and breath concentrations of methanol are disproportional for varying periods of time during and following cessation of methanol exposure, depending on the route of exposure (dermal versus inhalation). In settings where the...

Objective: This paper describes a study aimed at characterizing the exposure to physical and chemical by-products from the deployment of airbag restraint systems. Design, Materials and Methods: Specifically, the levels of particulates and the composition of gases and bag fabric speed were measured in the passenger compartment following deployment of either a driver's side or driver's side/passenger's side airbag system. Measurements: A Fourier transform infrared analyzer (FTIR) and chemiluminescence analyzers were used for gas analysis, a cascade impactor and gravimetric filter measurements for aerosol determination and high-speed films to determine fabric speed. Main Results and Conclusions: The measured gases were found to be within the recommended guidelines for human exposures, but no guidelines exist for particle exposures of this magnitude (150-220 mg/m 3 ) but short duration. High-speed films were also taken of the deployments to obtain an estimate of the fabric speed as it leaves the module. The maximum average speed for both types of airbag was appoximately 100 mph and in both cases average speeds ranged from lows near 50 mph to highs of over 200 mph

Picture archiving and communication systems (PACS) provide limited flexibility for the development of novel research methods. By contrast, the research model of data access is more flexible but has vulnerabilities in numerous areas. No single monolithic application can fulfill the diverse and rapidly changing needs of the clinical imaging research community. Instead, the focus should be on the interoperability of preexisting systems. To a large extent, this can be achieved by means of a unified interface for storing and retrieving data. The concept of a research PACS combines the advantages of the clinical and research models of data access while eliminating the disadvantages. A research PACS streamlines the data management process. Instead of a single software program, it consists of a confederation of independent applications brought together by the ability to store and retrieve data in a common database. A prototype research PACS has been developed that is based on the Extensible Neuroimaging Archive Toolkit (XNAT) in association with two new in-house tools: a data selection tool and a data archiving tool. By taking as an example the comparison of regions of interest in multifunctional liver data, it was demonstrated that this framework allows a number of in-house and open-source applications originally designed to work on a stand-alone basis to be integrated into a unified workflow, with minimal redevelopment effort.

This paper discusses a novel model, based on Activity-Based Costing, developed to analyze and predict energy usage in the manufacturing industry. In this approach, we have modified a cost management tool called Activity-Based Costing (ABC) to include environmental aspects along with costs metrics. A case study was performed on a General Motors (GM) manufacturing facility to evaluate Demand and Response offers from a local utility company to demonstrate the utility of this approach. This study resulted in an ABC predictive energy model which can be used with emerging Smart Grid opportunities to provide a competitive advantage to the manufacturing industry.

To evaluate the effect on diffusion-weighted image-derived parameters in the apparent diffusion coefficient (ADC) and intra-voxel incoherent motion (IVIM) models from choice of either free-breathing or navigator-controlled acquisition.Imaging was performed with consent from healthy volunteers (n = 10) on a 1.5T Siemens Avanto scanner. Parameter-matched free-breathing and navigator-controlled diffusion-weighted images were acquired, without averaging in the console, for a total scan time of ∼10 minutes. Regions of interest were drawn for renal cortex, renal pyramid, whole kidney, liver, spleen, and paraspinal muscle. An ADC diffusion model for these regions was fitted for b-values ≥ 250 s/mm(2) , using a Levenberg-Marquardt algorithm, and an IVIM model was fitted for all images using a Bayesian method.ADC and IVIM parameters from the two acquisition regimes show no significant differences for the cohort; individual cases show occasional discrepancies, with outliers in parameter estimates arising more commonly from navigator-controlled scans. The navigator-controlled acquisitions showed, on average, a smaller range of movement for the kidneys (6.0 ± 1.4 vs. 10.0 ± 1.7 mm, P = 0.03), but also a smaller number of averages collected (3.9 ± 0.1 vs. 5.5 ± 0.2, P 0.01) in the allocated time.Navigator triggering offers no advantage in fitted diffusion parameters, whereas free-breathing appears to offer greater confidence in fitted diffusion parameters, with fewer outliers, for matched acquisition periods.

Purpose: To evaluate dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for monitoring and assessing treatment response in patients with neuroendocrine liver metastases treated using yttrium 90 (90Y)-labeled octreotide (90Y-DOTATOC). Materials and Methods: The study was approved by the local research and ethics committee and patient informed consent was obtained. Twenty patients with liver metastases from neuroendocrine tumors underwent T1-weighted DCE MR imaging of the liver before and at 2 months after intravenous 90Y-DOTATOC treatment. Regions of interest were drawn around target lesions, as well as along liver outlines for each patient. A dual-input single-compartment model was used to compute parameters including fractional distribution volume and the arterial flow fraction. Pre- and posttreatment values were compared using Wilcoxon signed rank test. Treatment response was defined as showing a greater than 50% reduction in the nadir chromogranin A level within the 1st year after treatment. Pretreatment values of responders and nonresponders were compared using the Mann-Whitney test. A two-tailed P value of .008 or less, which accounts for multiple testing, was considered to indicate a significant difference. Results: In responders, tumor and whole liver distribution volume significantly increased after treatment (median tumor distribution volume, 0.182 vs 0.244; median whole liver distribution volume, 0.175 vs 0.207; P = .008). The pretreatment whole liver distribution volume was significantly lower in responders (median, 0.175 vs 0.248; P = .003), while pretreatment tumor arterial flow fraction was significantly higher in responders (median, 1.000 vs 0.761, P = .006). Conclusion: DCE MR imaging may be used to monitor the effects of peptide receptor radiolabeled targeted therapy in patients with neuroendocrine tumors liver metastases; a lower pretreatment distribution volume and high arterial flow fraction was associated with a better response to treatment.

This study was conducted to determine if engineered nanoparticles are released into the air when nanocomposite parts are shredded for recycling. Test plaques made from polypropylene resin reinforced with either montmorillonite nanoclay or talc and from the same resin with no reinforcing material were shredded by a granulator inside a test apparatus. As the plaques were shredded, an ultrafine condensation particle counter; a diffusion charger; a photometer; an electrical mobility analyzer; and an optical particle counter measured number, lung-deposited surface area, and mass concentrations and size distributions by number in real-time. Overall, the particle levels produced were both stable and lower than found in some occupational environments. Although the lowest particle concentrations were observed when the talc-filled plaques were shredded, fewer nanoparticles were generated from the nanocomposite plaques than when the plain resin plaques were shredded. For example, the average particle number concentrations measured using the ultrafine condensation particle counter were 1300 particles/cm(3) for the talc-reinforced resin, 4280 particles/cm(3) for the nanoclay-reinforced resin, and 12,600 particles/cm(3) for the plain resin. Similarly, the average alveolar-deposited particle surface area concentrations measured using the diffusion charger were 4.0 μm(2)/cm(3) for the talc-reinforced resin, 8.5 μm(2)/cm(3) for the nanoclay-reinforced resin, and 26 μm(2)/cm(3) for the plain resin. For all three materials, count median diameters were near 10 nm during tests, which is smaller than should be found from the reinforcing materials. These findings suggest that recycling of nanoclay-reinforced plastics does not have a strong potential to generate more airborne nanoparticles than recycling of conventional plastics.

The smart grid enables two-way energy demand response capability through which utility service providers can offer customers special call options for energy load curtailment. If a utility customer has a capability to perform a rapid cost and benefit analysis of the offer in an optimal manner and accept the offer, the customer can earn both an option premium to participate, and a strike price for load curtailments when asked. However, today most industrial customers still lack the ability to perform such an optimal and rapid cost and benefit analysis. This paper proposes a stochastic-programming enabled decision process to be used to evaluate the impact of load curtailments within a required short response time. This approach can build agility into utility customers' energy decisions, thereby helping exploit the energy demand response capability and achieve strategic advantage over competitors. An illustrative example of the proposed decision process under a call-option based energy demand response scenario is presented.

Five human subjects were exposed to an atmosphere containing 200 ppm of methanol in a test chamber for 7 hours per day for 5 consecutive days (Monday through Friday). Ambient air in the chamber was monitored continuously for methanol, while urine was monitored for methanol and formic acid. Spot urine specimens were collected immediately before and immediately after exposure periods on Monday through Friday, and also on the Saturday and Sunday mornings following the week of exposure. Morning urine specimens obtained Tuesday through Saturday were collected approximately 16 hours following cessation of exposure on the preceding day. Mean urinary methanol concentrations were increased from baseline at the end of each exposure session (Monday through Friday), but had returned to baseline in samples collected 16 hours following cessation of exposure. The concentration of formic acid in morning urine specimens did not change significantly over the 7 days of this experiment. These results indicate that: ...

Understanding the potential health hazards associated with the manufacturing of metal matrix composite (MMC) materials at the R&D stage is important in the prevention of occupational diseases. In this study, the potential inhalation hazards associated with the squeeze casting of silicon carbide (SiC) whiskers and aluminum to form an MMC material were studied. Each of the process steps evaluated was conducted under controlled laboratory conditions. Most airborne concentrations of SiC whiskers, determined by aerosol sampling at or near the sources of highest possible emissions, were below 0.05 fibers/cc, below the current occupational exposure limits for fibrous materials. The potential to release fibers existed during the initial stage when the fibers were mixed mechanically with the organic binders and during the handling of the burnt-out preforms prior to squeeze casting. Once the whiskers were incorporated in either an organic or metallic matrix, the concentration of free airborne fibers was be...

To investigate the histopathologic and dynamic magnetic resonance (MR) imaging correlates of intrinsic susceptibility-weighted (ISW) MR imaging in patients with primary human breast adenocarcinoma and to assess the relationship between baseline transverse relaxation rate (R2*) and T2* relaxivity change (ΔR2*) and the response to neoadjuvant chemotherapy (NAC).Institutional ethics approval and informed consent were obtained. Between September 2001 and January 2008, 83 women (median age, 46 years; age range, 26-72 years) with breast cancer were recruited to undergo dynamic contrast medium-enhanced (DCE), dynamic susceptibility contrast-enhanced (DSC), and ISW MR imaging before and after two cycles of NAC. After excluding necrotic, infiltrating, and invasive lobular carcinomas, 31 patients were available for baseline assessment and 27 were available for response assessment. Transfer constant, leakage space, rate constant, initial area under the gadolinium concentration-time curve at 60 seconds, relative blood volume (rBV), relative blood flow (rBF), and R2* were calculated. Relationships between baseline R2* and histopathologic variables (tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor 2 status), tumor size, and dynamic MR imaging parameters were sought. Baseline adenocarcinoma R2* (n = 31) and ΔR2* (n = 27) were correlated with final pathologic response.Inverse correlations between baseline R2* and rBV (ρ = -0.48, P = .013) and rBF (ρ = -0.44, P = .024) were found, but not after NAC. No relationships were observed between baseline R2* and other kinetic imaging parameters, histopathologic characteristics, or tumor size (P.05). Baseline R2* values were lower in tumors than in normal breast tissue (31.8 sec(-1) vs 36.2 sec(-1), P = .017) but not after NAC. Increases in R2* were observed after treatment (31.1 sec(-1) vs 34.8 sec(-1), P = .006), with larger increases correlating with pathologic response. ΔR2* was not as effective as DCE or DSC MR imaging parameters in the prediction of response.R2* is influenced by blood volume in untreated breast adenocarcinomas. Increases in R2* after two cycles of NAC correlate with pathologic response. Therapy-induced uncoupling of the relationship between R2* and rBV and rBF is consistent with responding tumors becoming hypoxic early during treatment.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100421/-/DC1.

Purpose: To assess the reproducibility of relaxivity- and susceptibility-based dynamic contrast-enhanced magnetic resonance imaging (MRI) in the benign and malignant prostate gland and to correlate the kinetic parameters obtained. Materials and Methods: Twenty patients with prostate cancer underwent paired scans before and after androgen deprivation therapy. Quantitative parametric maps for T-1- and T-2*-weighted parameters were calculated (K-trans, k(ep),V-e, IAUC(60), rBV, rBF, and R-2*). The reproducibility of and correlation between each parameter were determined using standard methods at both timepoints. Results: T-1-derived parameters are more reproducible than T-2*-weighted measures, both becoming more variable following androgen deprivation (variance coefficients for prostate K-trans and rBF increased from 13.9%-15.8% and 42.5%-90.8%. respectively). Tumor R2* reproducibility improved after androgen ablation (23.3%-11.8%). IAUC(60) correlated strongly with K-trans, V-e, and k(ep) (all P < 0.001). R-2* did not correlate with other parameters. Conclusion: This study is the first to document the variability and repeatability of T-1- and T-2*-weighted dynamic MRI and intrinsic susceptibility-weighted MRI for the various regions of the human prostate gland before and after androgen deprivation. These data provide a valuable source of reference for groups that plan to use dynamic contrast enhanced MRI or intrinsic susceptibility weighted MRI for the assessment of treatment response in the benign or malignant prostate.

Interest has developed in the use of urinary formic acid as a biologic exposure index of occupational methanol exposure. Four human subjects were exposed to approximately 200 ppm of methanol in a test chamber for 6 hours. Ambient air in the chamber was monitored for methanol, while urine was monitored for formic acid. Urine specimens were collected immediately before, immediately after, and 16 hours following cessation of exposure to methanol. Mean urinary formic acid was increased from baseline at the end of the exposure session (though not significantly), but had returned to baseline in samples collected 16 hours following cessation of exposure. These results suggest that measurement of urinary formic acid in specimens collected 16 hours following cessation of exposure to methanol may not be an appropriate approach to biologically assess methanol exposure.

A transportable Fourier transform infrared (FTIR) spectrometer has been tested for analysis of methanol vapor in alveolar and ambient air. The instrument has been found to be accurate and precise for both uses. The regions used for methanol and CO2 quantification are in the vicinity of 950-1100 cm-1 and 2000-2100 cm-1, respectively. The results of a standard addition experiment show a correlation coefficient of 0.97-0.99 for methanol in alveolar or ambient air at the 30-200 ppm concentration level. For CO2 analysis in 23 alveolar air samples at the 6.1-7.6% concentration level, the mean difference in results between a nondispersive infrared (NDIR) spectrometer and the FTIR was -0.092% with a standard deviation of 0.273% (p greater than 0.1). Methanol concentrations in alveolar air paralleled simultaneous measurements of methanol concentration in blood. Overall, these preliminary results suggest that FTIR spectroscopy is a practical and efficient approach for simultaneous biological and area monitoring of human exposure to organic solvents.

Purpose: The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy. Methods and Materials: Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K{sup trans}]), leakage space (v{sub e}) and blood oxygenation (intrinsic relaxivity [R{sub 2}*]) were calculated. Results: Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K{sup trans} and 53% for v{sub e} By 3 months, significant increasesmore » in R{sub 2}* had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001). Conclusions: Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R{sub 2}* in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation.« less