Indicators for Hospitalization in Acute Pulmonary Embolism: Uncover the Association Between D-dimer Levels, Thrombus Volume and Radiomics.

BACKGROUND: The advent of advanced computed tomography (CT) technology and the field of radiomics has opened up new avenues in diagnostic assessments. Increasingly, there is substantial evidence advocating for the incorporation of quantitative imaging biomarkers in the clinical decision-making process. This study aimed to examine the correlation between D-dimer levels and thrombus size in acute pulmonary embolism (PE) combining dual-energy CT (DECT) and radiomics and to investigate the diagnostic utility of a machine learning classifier based on dual-energy computed tomography (DECT) radiomics for identifying patients with a complicated course, defined as at least hospitalization at IMC. METHODS: The study was conducted including 136 participants who underwent pulmonary artery CT angiography from January 2015 to March 2022. Based on DECT imaging, 107 radiomic features were extracted for each patient using standardized image processing. After dividing the dataset into training and test sets, stepwise feature reduction based on reproducibility, variable importance and correlation analyses were performed to select the most relevant features; these were used to train and validate the gradient-boosted tree models.Receiver operating characteristics (ROC) analysis was utilized to evaluate the association between volumetric, laboratory data and adverse outcomes. RESULTS: In the central PE group, we observed a significant correlation between thrombus volumetrics and D-dimer levels (p = 0.0037), as well as between thrombus volumetrics and hospitalization at the Intermediate Care Unit (IMC) (p = 0.0001). In contrast, no statistically significant differences were identified in thrombus sizes between patients who experienced complications and those who had a favorable course (p = 0.3162). The trained machine learning classifier achieved an accuracy of 61% and 55% in identifying patients with a complicated course, as indicated by an area under the ROC curve of 0.63 and 0.58. CONCLUSION: In conclusion, our findings indicate a positive correlation between D-dimer levels and central PE's pulmonary embolic burden. Thrombus volumetrics may serve as an indicator for complications and outcomes in acute PE patients. Thus, thrombus volumetrics, as opposed to D-dimers, could be an additional marker for evaluating embolic disease severity. Moreover, DECT-derived radiomic feature models show promise in identifying patients with a complicated course, such as hospitalization at IMC.

Imaging-based risk stratification of patients with pulmonary embolism based on dual-energy CT-derived radiomics.

BACKGROUND: Technological progress in the acquisition of medical images and the extraction of underlying quantitative imaging data has introduced exciting prospects for the diagnostic assessment of a wide range of conditions. This study aims to investigate the diagnostic utility of a machine learning classifier based on dual-energy computed tomography (DECT) radiomics for classifying pulmonary embolism (PE) severity and assessing the risk for early death. METHODS: Patients who underwent CT pulmonary angiogram (CTPA) between January 2015 and March 2022 were considered for inclusion in this study. Based on DECT imaging, 107 radiomic features were extracted for each patient using standardized image processing. After dividing the dataset into training and test sets, stepwise feature reduction based on reproducibility, variable importance and correlation analyses were performed to select the most relevant features; these were used to train and validate the gradient-boosted tree models. RESULTS: The trained machine learning classifier achieved a classification accuracy of .90 for identifying high-risk PE patients with an area under the receiver operating characteristic curve of .59. This CT-based radiomics signature showed good diagnostic accuracy for risk stratification in individuals presenting with central PE, particularly within higher risk groups. CONCLUSION: Models utilizing DECT-derived radiomics features can accurately stratify patients with pulmonary embolism into established clinical risk scores. This approach holds the potential to enhance patient management and optimize patient flow by assisting in the clinical decision-making process. It also offers the advantage of saving time and resources by leveraging existing imaging to eliminate the necessity for manual clinical scoring.

Multiparametric Evaluation of Radiomics Features and Dual-Energy CT Iodine Maps for Discrimination and Outcome Prediction of Thymic Masses.

RATIONALE AND OBJECTIVES: To investigate the diagnostic value of radiomics features and dual-source dual-energy CT (DECT) based material decomposition in differentiating low-risk thymomas, high-risk thymomas, and thymic carcinomas. MATERIALS AND METHODS: This retrospective study included 32 patients (16 males, mean age 66 ± 14 years) with pathologically confirmed thymic masses who underwent contrast-enhanced DECT between 10/2014 and 01/2023. Two experienced readers evaluated all patients regarding conventional radiomics features, as well as DECT-based features, including attenuation (HU), iodine density (mg/mL), and fat fraction (%). Data comparisons were performed using analysis of variance and chi-square statistic tests. Receiver operating characteristic curve analysis and Cox-regression tests were used to discriminate between low-risk/high-risk thymomas and thymic carcinomas. RESULTS: Of the 32 thymic tumors, 12 (38%) were low-risk thymomas, 11 (34%) were high-risk thymomas, and 9 (28%) were thymic carcinomas. Values differed significantly between low-risk thymoma, high-risk thymoma, and thymic carcinoma regarding DECT-based features (p ≤ 0.023) and 30 radiomics features (p ≤ 0.037). The area under the curve to differentiate between low-risk/high-risk thymomas and thymic cancer was 0.998 (95% CI, 0.915-1.000; p < 0.001) for the combination of DECT imaging parameters and radiomics features, yielding a sensitivity of 100% and specificity of 96%. During a follow-up of 60 months (IQR, 35-60 months), the multiparametric approach including radiomics features, DECT parameters, and clinical parameters showed an excellent prognostic power to predict all-cause mortality (c-index = 0.978 [95% CI, 0.958-0.998], p = 0.003). CONCLUSION: A multiparametric approach including conventional radiomics features and DECT-based features facilitates accurate, non-invasive discrimination between low-risk/high-risk thymomas and thymic carcinomas.

Cancer patients with venous thromboembolism: Diagnostic and prognostic value of elevated D-dimers.

BACKGROUND: D-dimer testing is known to have a high sensitivity at simultaneously low specificity, resulting in nonspecific elevations in a variety of conditions. METHODS: This retrospective study sought to assess diagnostic and prognostic features of D-dimers in cancer patients referred to the emergency department for suspected pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 526 patients with a final adjudicated diagnosis of PE (n = 83) and DVT (n = 69) were enrolled, whereas 374 patients served as the comparative group, in which venous thromboembolism (VTE) has been excluded. RESULTS: For the identification of VTE, D-dimers yielded the highest positive predictive value of 96% (95% confidence interval (CI), 85-99) at concentrations of 9.9 mg/L and a negative predictive value of 100% at .6 mg/L (95% CI, 97-100). At the established rule-out cut-off level of .5 mg/L, D-dimers were found to be very sensitive (100%) at a moderate specificity of nearly 65%. Using an optimised cut-off value of 4.9 mg/L increased the specificity to 95% for the detection of life-threatening VTE at the cost of moderate sensitivities (64%). During a median follow-up of 30 months, D-dimers positively correlated with the reoccurrence of VTE (p = .0299) and mortality in both cancer patients with VTE (p < .0001) and without VTE (p = .0008). CONCLUSIONS: Although D-dimer testing in cancer patients is discouraged by current guidelines, very high concentrations above the 10-fold upper reference limit contain diagnostic and prognostic information and might be helpful in risk assessment, while low concentrations remain useful for ruling out VTE.

Evaluation and application of organic micro-pollutants (OMPs) as indicators in karst system characterization.

This study presents chances and challenges associated with the application of organic micro-pollutants (OMPs) as indicators in karst system characterization. The methodology and options of possible indications were evaluated based on the interpretation of the spatial distribution of 54 compounds in groundwater in combination with a complex geological setting consisting of multiple aquifer horizons and tectonic faults. A high variety of OMPs are released mainly in an urban area leading to concentrations of several nanograms per liter up to micrograms per liter, which are detectable using a high-performance liquid chromatography with subsequent tandem mass spectrometry (HPLC-MS/MS) method. Since characteristic patterns of spatial distribution were repeatedly observed during a 2-year observation period, important criteria of the aforementioned indicator application are fulfilled. Triazoles, compounds with recent high emission rates, could be successfully applied for the identification of flow directions and the delineation of catchment areas. Concentrations and the number of OMPs are believed to be dependent on properties of covering rock layers. Therefore, OMPs can also be used as a validation tool for vulnerability mapping. Compounds, such as triazines, persistent in the system for more than two decades, demonstrate the interaction between different parts of the aquifer system and the hydraulic characteristics of a tectonic fault zone. Such indicator potentials complement those of artificial tracer tests. Point sources of OMPs and their impact on groundwater could be identified qualitatively. In combination with the interpretation of the geological setting, the distribution of OMPs provides essential information for the development of a conceptual hydrogeological model.

Investigating the dynamics of two herbicides at a karst spring in Germany: Consequences for sustainable raw water management.

While karst aquifers are considered as rapid flow and transport systems, their high potential for long-term storage is often ignored. However, to achieve a sustainable raw water quality for drinking water production, the understanding of this potential is highly essential. In this study, the transport dynamics of the two herbicides metazachlor and atrazine as well as a degradation product of the latter (desethylatrazine) were investigated at a karst spring over 1 year. Even 20 years after its ban in Germany, atrazine and its degradation product were almost always detectable in the spring water in the low ng L(-1) range (up to 5.2ng L(-1)). Metazachlor could only be detected after precipitation events, and the observed concentrations (up to 82.9ng L(-1)) are significantly higher than atrazine or desethylatrazine. Comparing the dynamics of the herbicides with the inorganic ions Ca(2+), Mg(2+) and electrical conductivity, a positive correlation of atrazine with these parameters could be observed. From this observation, atrazine is concluded to be located within the aquifer matrix. To achieve a sustainable raw water management at karst springs, the rapidness of these systems needs to be highlighted as well as their long-term storage potential. Persistent substances or transformation products are prone to deteriorate the raw water quality for decades.

Occurrence and spatial distribution of organic micro-pollutants in a complex hydrogeological karst system during low flow and high flow periods, results of a two-year study.

Fifty-four different organic micro-pollutants (OMPs) including pharmaceuticals, pesticides, corrosion inhibitors and other typical wastewater compounds such as caffeine are repeatedly analyzed in approximately fifty groundwater observation points in a complex faulted and fractured carbonate aquifer system consisting of three spring catchment areas. With the applied HPLC-MS/MS method, achieving method quantification limits (MQL) of 1.2-28 ng L(-1), forty-four of the OMPs are detected in groundwater. Regarding the vertical distribution in the aquifer system the highest variety of OMPs occurs in the shallow aquifer. Most frequently detected compounds are atrazine together with the metabolites of several triazines, desethylatrazine (DEA) and desisopropylatrazine (DIA), the corrosion inhibitors 1H-benzotriazole and tolytriazoles and as pharmaceutical residues the anti-epileptic drug carbamazepine as well as the analgesic drug phenazone. Median OMP concentrations are in the range of 20-40 ng L(-1) with occasionally and locally higher concentrations of up to 6000 ng L(-1). Defined combinations of OMPs occur repeatedly in the same observation wells and allow to distinguish different input functions. The comparison of detection frequency with the number of prescribed doses gives information about the specific persistence of pharmaceuticals. The analgesic phenazone exhibits a peculiar high detection frequency, although it is recently not prescribed in significant amounts. The detection of the estrogen antagonist tamoxifen (6-17 ng L(-1)) in a groundwater flow system is reported for the first time.

Identification of the attenuation potential of a karst aquifer by an artificial dualtracer experiment with caffeine.

Little is known with respect to the attenuation capacity of karst aquifers. Even less is known about the risk posed by emerging micropollutants in these systems. In order to identify the attenuation potential of karst aquifers in-situ and to estimate the risk posed by micropollutants, a dualtracer test was conducted in this study in order to investigate differential transport in the subsurface: The reactive compound caffeine was used as a tracer to indicate the attenuation capacity within the aquifer in-situ. Due to the low limit of quantification, only small amounts of caffeine needed to be injected. To calibrate a model and to visualize the attenuation of caffeine a conservative reference tracer (uranine) is injected simultaneously. The methodology is tested in a well-characterised karst system in southwest Germany. The results indicate a significantly higher attenuation rate than was expected for karst aquifers. The attenuation is decribed as a first-order process. The corresponding half-life is 104 h. This low half-life suggests that a generally assumed low natural attenuation capacity of karst aquifers is unjustified. The observed mass loss of caffeine illustrates the potential of caffeine to be used as reactive tracer for indicating in-situ attenuation capacity within highly hydraulically conductive systems, such as karst aquifers. Due to the high attenuation rate of caffeine it does not pose a threat as a long-time contaminant. In combination with a conservative reference tracer an economical and environmentally benign method is presented in this manuscript for the in-situ determination of the attenuation capacity of highly conductive aquifer systems.

Caffeine as an indicator for the quantification of untreated wastewater in karst systems.

Contamination from untreated wastewater leakage and related bacterial contamination poses a threat to drinking water quality. However, a quantification of the magnitude of leakage is difficult. The objective of this work is to provide a highly sensitive methodology for the estimation of the mass of untreated wastewater entering karst aquifers with rapid recharge. For this purpose a balance approach is adapted. It is based on the mass flow of caffeine in spring water, the load of caffeine in untreated wastewater and the daily water consumption per person in a spring catchment area. Caffeine is a source-specific indicator for wastewater, consumed and discharged in quantities allowing detection in a karst spring. The methodology was applied to estimate the amount of leaking and infiltrating wastewater to a well investigated karst aquifer on a daily basis. The calculated mean volume of untreated wastewater entering the aquifer was found to be 2.2 ± 0.5 m(3) d(-1) (undiluted wastewater). It corresponds to approximately 0.4% of the total amount of wastewater within the spring catchment.

Multitracer test approach to characterize reactive transport in karst aquifers.

A method to estimate reactive transport parameters as well as geometric conduit parameters from a multitracer test in a karst aquifer is provided. For this purpose, a calibration strategy was developed applying the two-region nonequilibrium model CXTFIT. The ambiguity of the model calibration was reduced by first calibrating the model with respect to conservative tracer breakthrough and later transferring conservative transport parameters to the reactive model calibration. The reactive transport parameters were only allowed to be within a defined sensible range to get reasonable calibration values. This calibration strategy was applied to breakthrough curves obtained from a large-scale multitracer test, which was performed in a karst aquifer of the Swabian Alb, Germany. The multitracer test was conducted by the simultaneous injection of uranine, sulforhodamine G, and tinopal CBS-X. The model succeeds to represent the tracer breakthrough curves (TBCs) of uranine and sulforhodamine G and verifies that tracer-rock interactions preferably occur in the immobile fluid region, although the fraction of this region amounts to only 3.5% of the total water. However, the model failed to account for the long tailing observed in the TBC of tinopal CBS-X. Sensitivity analyses reveal that model results for the conservative tracer transport are most sensitive to average velocity and volume fraction of the mobile fluid region, while dispersion and mass transfer coefficients are least influential. Consequently, reactive tracer calibration allows the determination of sorption sites in the mobile and immobile fluid region at small retardation coefficients.

Process-based interpretation of tracer tests in carbonate aquifers.

A tracer test in a carbonate aquifer is analyzed using the method of moments and two analytical advection-dispersion models (ADMs) as well as a numerical model. The numerical model is a coupled continuum-pipe flow and transport model that accounts for two different flow components in karstified carbonate aquifers, i.e., rapid and often turbulent conduit flow and Darcian flow in the fissured porous rock. All techniques employed provide reasonable fits to the tracer breakthrough curve (TBC) measured at a spring. The resulting parameter estimates are compared to investigate how each conceptual model of flow and transport processes that forms the basis of the analyses affects the interpretation of the tracer test. Numerical modeling results suggest that the method of moments and the analytical ADMs tend to overestimate the conduit volume because part of the water discharged at the spring is wrongly attributed to the conduit system if flow in the fissured porous rock is ignored. In addition, numerical modeling suggests that mixing of the two flow components accounts for part of the dispersion apparent in the measured TBC, while the remaining part can be attributed to Taylor dispersion. These processes, however, cannot reasonably explain the tail of the TBC. Instead, retention in immobile-fluid regions as included in a nonequilibrium ADM provides a possible explanation.