Analytical Coefficients Research Articles

Ocular Surface Disease Index Questionnaire (OSDI-Q), Unidimensionality, and Differential Item Functioning

Objective The OSDI-Q is a 12-item scale used instrument for DED prevalence, assess symptom severity, and impact on vision-related functioning. The research analysis investigates the precision, separation index and reliability of unidimensionality, and DEF, stratified by age and gender. The reliability analysis is to assess the internal consistency of the scale using Cronbach's α coefficient and McDonald's ω coefficient with item-rest correlations. Method 634 respondents took part in the OSDI questionaire. Rasch analysis was conducted using precision, separation index, and reliability for items and person, item and person fit statistics, assessing unidimensionality stratified by age and gender, and the use of SPSS to conduct the reliability analysis of the scale using analytical coefficients. Results The OSDI-Q items displayed robust reliability, with high PSI values of 7.63 and 0.98, respectively. Infit and outfit statistics were within acceptable ranges, explaining 39.90 % of variance. Differential item functioning was observed among the age groups involved. Additionally, the contrast in the principal component analysis of the unexplained variance exhibited an eigenvalue of 2.80 and a proportion of variance of 14%. DIF analysis showed significant differences for age groups of (16-26 years) and (27-40 years). The coefficients of Cronbach's and McDonald's are 0.85 for OSDI-Q demonstrated strong internal consistency. Conclusions OSDI-Q displayed appropriate infit and outfits. DIF analysis results of OSDI-Q of age group (16-26 years) performed better in poor vision while age group (27-40 years) performed better in areas with low humidity. Furthermore, the results of DIF analysis in males group performed better in driving at night, while the female group showed better performance in the questinaire. The OSDI-Q items scale reliability data for Cronbach's scale show high internal consistency and reliability. This research can help the medical communities to begin a better surge for medically integrated research.

Biological variation of capillary blood glucose: A systematic review.

Biological variation (BV) refers to changes in biochemical constituents in the blood or other biological fluids, indicative of body regulation via homeostatic processes. Intra- and interindividual BV data are essential for establishing analytical performance specifications and evaluating the significance between consecutive measurements of an analyte. Given this context, the present study conducted a systematic review of the intra- and interindividual BV of capillary blood glucose. Out of 461 initial studies identified, only 4 met the inclusion criteria for detailed analysis after excluding 419 for title irrelevance, 10 for duplication, 21 based on abstract content and 7 based on article content. Notably, none of the studies primarily focused on the intra- and interindividual BV of capillary blood glucose; rather, they reported it as a secondary outcome. Regarding fasting, data analyses revealed intra-individual BVs of 4.5 and 31.1% for healthy and diabetic individuals, respectively, and interindividual coefficient of variations of 4.7-5.8 and 12.9-16.3% for healthy and diabetic individuals, respectively. Only one study provided the analytical coefficient of variation, corroborating the recommended practices. Additionally, the fasting duration, meal standardization before sampling, and number and interval between collections varied among the studies. Hence, the results suggest that there are no reliable data on intra- and interindividual BVs for capillary blood glucose in the literature.

Validation of Neutrophil gelatinase-associated lipocalin (NGAL) for Diabetes-associated Acute Kidney Injury

Abstract Introduction/Objective This study aimed to evaluate the analytical and clinical performance of the BioPorto NGAL Test on the Beckman Coulter AU480 to correlate plasma neutrophil gelatinase-associated lipocalin levels (pNGAL) with clinical progression and severity of diabetes-associated acute kidney injury (AKI) with hospitalized patients at an East Central Georgia Medical Center Methods/Case Report Analytical validation of the BioPorto NGAL Test was carried out on the AU480 and was based on imprecision, limit of blank, limit of detection, functional sensitivity, carryover, and specificity. Clinical validation studies included 45 patients hospitalized between January and November 2023 with and without diabetes at risk for developing AKI. All patients’ pNGAL levels were measured at admission until 96 hours post admission. Receiver operating characteristics and likelihood ratio methods were used to determine optimal sensitivity, specificity, cutoff value, and the discriminatory power of pNGAL. Results (if a Case Study enter NA) The intra-assay and inter-assay imprecision percent relative standard deviation was between 0.8 (2.7%) and 3.7 (4.2%). The limit of blank and limit of detection of Bioporto NGAL was 2.2 ng/mL and 15.4 ng/mL, respectively. An analytical coefficient of variation of 20% corresponded to a pNGAL value of 9.9 ng/mL. The optimal cutoff value for pNGAL to predict AKI for patients with DM was 293 ng/mL, with a sensitivity of 80% and specificity of 87%; AUC: 0.85, p < 0.001. In a multivariate logistic regression model, pNGAL levels at 48 hours post admission were a risk factor for diabetes-associated AKI (OR 1.012, 95% CI:1.000 – 1.023; p = 0.051). Conclusion These results show that pNGAL levels at 48h are an independent risk factor for diabetes-associated AKI, and the optimal cutoff for this condition is 293 ng/mL. The optimal cutoff values for AKI for early diagnosis and risk stratification, along with its association with comorbidities, are important to improve patient outcomes and diagnosis accuracy.

Development of a numerical and analytical methodology for analyzing hybrid laminates with multi-oriented piezoelectric and structural layers

Piezoelectric materials can generate an electrical response under mechanical stress, functioning as sensors. Conversely, applying an electrical field to these materials enables precise motion control, making them effective as actuators. Using a proposed methodology, this work focuses on evaluating the effective properties of hybrid multi-oriented composite laminates consisting of structural and piezoelectric layers driven by monoclinic constitutive equations. Square unit cell model was used to calculate all coefficients of the material tensor. The finite element (FE) homogenization method and periodic boundary conditions implemented by node-to-node constraint equations are used to study a representative volume element (RVE) modeled as three-layer unit cell in the mesoscale. The pre-processing, FE analysis, and post-processing are conducted in the FE package ABAQUSⓇ through Python scripts. The computational approach yields results that align closely with the analytical effective coefficients derived from the Asymptotic Homogenization Method (AHM), demonstrating the robustness and accuracy of the proposed methodology.

A transient formulation of entropy and heat transfer coefficients of Newton's cooling law with the unifying entropy potential difference in compressible flows

The original Newton's law of cooling is considered an ideal convection model of a point source ignoring conduction, but its unknown convection conductance and inconsistent thermal potential difference make it difficult to further elucidate the transient heat transfer mechanism of convection because of the no-slip condition at the interface between a body and a fluid. For this purpose, both the convective entropy transfer theory and the hypothesis of the isothermal velocity sublayer are developed to recast Newton's law of cooling into a standard Ohm's law form via the unified entropy driving force and the unambiguous entropy transfer coefficient. An explicit expression for the transient heat transfer coefficient is presented theoretically and experimentally in compressible flows by virtue of the product of the free-stream velocity, the volumetric thermal capacity of the fluid, and the near-wall velocity constant. The unified thermal potential difference is established between the body temperature and the total temperature (reduced to the ambient temperature for incompressible fluids). The physical mechanism of convection mode in the original Newton's cooling law is reasonably explained by the entropy transfer theory and entropy transfer efficiency, and the formulae for the entropy flux vector driven by the standard entropy potential difference and the rate of entropy generation are obtained. The analytical heat transfer coefficients as well as the standard thermal driving forces are validated by comparison with the forced convection experiment with a maximum error of 4.6 % in incompressible flows and the previous Newton's benchmark cooling experiments with the maximum error of 6.7 % in compressible flows. The effects of radiation on the total heat transfer coefficient are also analyzed quantitatively.

Analytical and fine Monte Carlo Kerma coefficients evaluation for a wide range photon energy relevant to some chemotherapy agents

Simultaneously combination of chemotherapy drugs and ionizing radiations has become a common treatment method for advanced cancers. Tumor irradiation in presence of chemotherapy drugs can affect deposited energy within tissue. Hence, to evaluate how chemotherapy drugs affect the absorbed dose within tissues during chemoradiotherapy, Kerma coefficient values for 26 anti-cancer agents were estimated for photon energies ranging from 1 keV to 20 MeV through analytical analysis and Monte Carlo (MC) simulation approaches.Estimation of Kerma coefficients through MC simulation relevant to different chemotherapy drugs was performed with MCNPX V.2.6.0 MC code. Besides, Kerma coefficient values were calculated using the reported mass energy absorption coefficients, as the theoretical method. Significant statistical test was also employed to evaluate the accordance of obtained Kerma coefficients by two considered methods.Simulation results were consistent with evaluated Kerma coefficients by analytical method which minimum and maximum mean relative differences are found for Bevacizumab and Methotrexate, respectively. Furthermore, a significant correlation is found with chemical composition of selected chemotherapy drugs at considered photon energy range. Fluorouracil showed the closest Kerma ratio to unity among the studied anti-cancer drugs. Kerma coefficient ratios for most of selected drugs were close to unity at higher energy regions (100 keV–20 MeV) while greater values were found at lower photon energies (below 100 keV).From the results, presence of these anti-cancer agents can impact Kerma coefficient and subsequently alter the absorbed dose within tissue during the cancer treatment with chemoradiotherapy technique.

Derivation and Application of Analytical Coupling Loss Coefficient by Transfer Function in Soil–Building Vibration

Vibrations generated by railways may undergo amplification or reduction while traversing the foundations, floors, and spans of adjacent structures. This fluctuation in the vibration intensity, identified as a building’s coupling loss, is commonly considered in vibration forecasts through the utilization of universal frequency-independent adjustment parameters. This article employs a theoretical analytical approach to investigate the propagation characteristics of Rayleigh waves in elastic foundation soil, as well as the variations at the contact surface of buildings’ foundations. Analytical expressions for the coupling loss coefficient are derived to explore the displacement transfer relationship in the soil–structure interaction. To accurately and efficiently analyze the proposed buildings and site, the entire vibration propagation system is decoupled into substructure systems for independent analytical calculations. Theoretical analytical methods are utilized to obtain the displacement transfer functions between the soil and the structures through the refraction and transmission of waves. From a theoretical perspective, a thorough understanding of the interaction between soil and buildings is achieved. The influence of various variables related to railways and foundations on the building responses is analyzed. By comparing with measured data, the correctness of the analytical form of the coupling loss coefficient is validated, filling a gap in the literature due to the lack of analytical research on displacement transfer losses in soil–structure interactions.

Theoretical modeling of a bottom-raised oscillating surge wave energy converter structural loadings and power performances

This study presents theoretical formulations to evaluate the fundamental parameters and performance characteristics of a bottom-raised oscillating surge wave energy converter (OSWEC) device. Employing a flat plate assumption and potential flow formulation in elliptical coordinates, closed-form equations for the added mass, radiation damping, and excitation forces/torques in the relevant pitch-pitch and surge-pitch directions of motion are developed and used to calculate the system's response amplitude operator and the forces and moments acting on the foundation. The model is benchmarked against numerical simulations using WAMIT and WEC-Sim, showcasing excellent agreement. The sensitivity of plate thickness on the analytical hydrodynamic solutions is investigated over several thickness-to-width ratios ranging from 1:80 to 1:10. The results show that as the thickness of the benchmark OSWEC increases, the deviation of the analytical hydrodynamic coefficients from the numerical solutions grows from 3 % to 25 %. Differences in the excitation forces and torques, however, are contained within 12 %. While the flat plate assumption is a limitation of the proposed analytical model, the error is within a reasonable margin for use in the design space exploration phase before a higher-fidelity (and thus more computationally expensive) model is employed. A parametric study demonstrates the ability of the analytical model to quickly sweep over a domain of OSWEC dimensions, illustrating the analytical model's utility in the early phases of design.

Feasibility and performance of the staged Z-pinch: A one-dimensional study with FLASH and MACH2

Z-pinch platforms constitute a promising pathway to fusion energy research. Here, we present a one-dimensional numerical study of the staged Z-pinch (SZP) concept using the FLASH and MACH2 codes. We discuss the verification of the codes using two analytical benchmarks that include Z-pinch-relevant physics, building confidence on the codes' ability to model such experiments. Then, FLASH is used to simulate two different SZP configurations: a xenon gas-puff liner (SZP1*) and a silver solid liner (SZP2). The SZP2 results are compared against previously published MACH2 results, and a new code-to-code comparison on SZP1* is presented. Using an ideal equation of state and analytical transport coefficients, FLASH yields a fuel convergence ratio (CR) of approximately 39 and a mass-averaged fuel ion temperature slightly below 1 keV for the SZP2 scheme, significantly lower than the full-physics MACH2 prediction. For the new SZP1* configuration, full-physics FLASH simulations furnish large and inherently unstable CRs (>300) but achieve fuel ion temperatures of many kilo-electron volts. While MACH2 also predicts high temperatures, the fuel stagnates at a smaller CR. The integrated code-to-code comparison reveals how magnetic insulation, heat conduction, and radiation transport affect platform performance and the feasibility of the SZP concept.

Dynamic property evaluation of pipeline clamp based on analyzing the propagation characteristics of flexural wave in pipeline

The external clamp of hydraulic pipeline plays an important role in strengthening pipeline stiffness and improving vibration attenuation ability. In this study, wave propagation method is proposed to evaluate the translational and rotational stiffness and their loss factors of the clamp by analyzing the flexural wave propagation characteristics of pipeline. In order to validate the measured dynamic properties, experimental modal analysis was performed on the two-end elastically-supported pipeline. By modelling the pipeline with translational and rotational edge restraints, the analytical modal frequency parameters, wave numbers, and waveform coefficients were obtained. By comparing of the first-order flexural mode frequencies between experiment and analysis, the dynamic stiffness predicted by the wave propagation method was validated. The effects of the magnitude of torque, direction, clamping torque cycle, and clamp size on the complex dynamic properties of pipeline clamp were investigated. The proposed wave propagation method allows non-destructive continuous monitoring of a clamp stiffness, provides additional information about the vibration attenuation feature. It has advantages in clamp applications and is an effective methodology for measuring the dynamic properties of viscoelastic materials.

Computing compact finite difference formulas under radial basis functions with enhanced applicability

In this work, we use the combination of radial basis functions (RBFs) and polynomials to derive compact finite difference (FD) formulas. We use RBFs and integrated RBFs (IRBFs), to obtain two sets of formulas: RBF-Hermite FD (RBF-HFD) and IRBF weight formulas. The analytical coefficients and truncation errors for these formulations are computed for the first derivative, second derivative, and 2D Laplacian operator. Our presented approach expands the usability of the weights by introducing a general framework for deriving weighting formulas. Finally, the computational results underscore the effectiveness of the introduced approach.

Base pressure fluctuations on levitated freestream-aligned circular cylinder

Base pressure fluctuations associated with the large-scale wake structures behind a freestream-aligned circular cylinder and aerodynamic force fluctuations related to them are experimentally investigated in the wind tunnel tests. Measurements at ReD=6.97×104 and 1.04×105 were conducted using pressure-sensitive paint (PSP) and a magnetic suspension and balance system (MSBS) for creating a supportless condition. The obtained pressure fields were mainly analyzed by a modal decomposition combining azimuthal Fourier decomposition and proper orthogonal decomposition (POD). The pressure fluctuations caused by large-scale vortex shedding were observed from the results of frequency analysis for mode coefficients. The states of the fluctuations were classified into three patterns, which are anticlockwise/clockwise circular and flapping patterns. These patterns have been observed in the previous studies for velocity fluctuations in the wake of a freestream-aligned circular cylinder. The conditional sampling analysis revealed that the trend in the amplitude of the pressure fluctuations is different by the state, and the flapping pattern causes a large pressure difference across the cylinder axis. Furthermore, the relationship between the antisymmetric pressure fluctuations and lift fluctuations, which act in the lateral direction of the cylinder, is confirmed.

Approximation method for the potential composition of petroleum fractions

The paper gives a brief review of mathematical models of potential composition of oil fractions. The stages of obtaining approximating dependence of the fractional composition of oil are defined. A multicomponent mixture is represented as a discrete series of narrow hydrocarbon fractions. Each of them is characterized by its average boiling point. The results of approximation obtained for oil of different fields are given. The criterion for choosing dependence is the sum of squared deviations of factored values from experimental (reference) values. The following approximating dependencies of the curve of true boiling points for oil of different deposits are obtained. They are cubic parabola, power function, arctangence, exponentiation function, cubic parabola-arctangence. It is shown that the best results are obtained for combined ‘cubic parabolaarctangent’ model. In case of data deviation on oil fractional composition coming from chemical analytical laboratory coefficients are corrected in TBP approximation. Oil fractional composition awareness is important when choosing the direction of oil refining, in process and simulation modeling, when determining the top performance of processing units.

Methodological foundations of risk analysis and assessment in the public sector

The article offers the author's view on the development of risk assessment methodology in the public sector. Based on the analysis of generally accepted risk assessment methods, their comparative characteristics are given and an approach to the choice of risk assessment methods depending on groups of uncertainty factors is proposed. Due to the insufficiency of statistical and mathematical risk assessment tools, emphasis is placed on the system of calculation and analytical coefficients, in part of which an approach to the system of risk assessment indicators is proposed, depending on the type of public sector organization. Special attention is paid to the issue of determining an acceptable level of risk and a methodology for calculating it is proposed.

A-161 Analytical Performance of Reagents for Determination of Activated Partial Thromboplastin Time: A Sigma Metric Perspective

Abstract Background Sigma Metric (SM) assesses the degree of deviation of lab. tests from established specifications, combining Total Acceptable Error (ETa), imprecision and analytical bias. Quality criteria, defined by models of desirable specification, are used to determine the analytical performance of lab. tests. The concepts of biological variation are used as the preferred approach for establishing specifications. Reagents (RE) for the determination of activated partial thromboplastin time (APTT) use thromboplastin obtained from different tissue extracts and activation factors, being standardized to reduce the variability of the tests, and ensure equivalence of clinical diagnosis. This work evaluated three RE for APTT and the fulfillment of the desirable specifications of analytical quality, using the SM as an analysis tool. Material & methods APTT determinations were performed on the Sysmex®CS-2500 (Siemens Healthineers) with Actin®FS (AFS), Actin®FSL (FSL), and Pathromtin®SL (PSL) RE and bi-level Control Plasma N (CN) and Ci-Trol®2 Control (CI). Two different lots were used for each RE and control (CT), and the results were analyzed in RE-CT combination. We determined (a)analytical bias (Bias), from intra-assay imprecision determined by 30 repetitions in a single analytical run and by comparison with manufacturer's data, and (b)analytical coefficient of variation (CVa), from inter-assay imprecision, by triplicate in 3 periods each 3 h, for the 2 CT levels. Analytical quality specifications for APTT were selected in the literature, adopting desirable ETa values of 4.5% and minimum of 6.7%, obtained from a database for biological variation and acceptable limit of 15%, based on CLIA-CAP. SM was calculated with formula: Sigma = ETa–Bias/CVa, with graphic representation adapted from the Westgard’s model. Results For CVa, AFS and FSL results with CN and CI were <1.0%. PSL presented results above 1.0% for CN and CI. All RE presented results lower than those recommended by the manufacturer, respectively 4.0% for AFS; 3.0% for FSL; and 2.8% for PSL. For bias, a greater variation was observed for the combinations of RE and CT, ranging from 1.16% to 4.07%, being related to the differences between the averages obtained and the values defined in the leaflets. For the desirable specification of ETa (4.5%), 3 combinations of RE and CT level AFS-CN, FSL-CN and PSL-CI presented Sigma values >3 (respectively, 3.61, 3.87 and 3.33). When using the minimum specification (6.7%), the PSL-CN combination presented a Sigma = 2.06. With the CLIA-CAP specification, all RE and CT combinations had Sigma >6. Discussion All RE showed similar analytical performance when compared by SM, demonstrating that different commercial formulations for APTT determination do not show differences in analytical Bias and CVa determinations. The graphical representation by SM allows you to visually compare analytical imprecision and inaccuracy values. Conclusion All RE showed no differences in analytical performance, with SM being a visual tool for analyzing and comparing RE performance.

Validity and reliability of the Persian version of modified motivated strategies for learning questionnaire: a methodological study among medical students

BackgroundMedical undergraduates need to improve their techniques for learning in the different settings of learning in clinical rotations. Reflective learning, in which a person can learn from their experiences, is among the most well-known learning skills. In this study, we aim to translate the newly developed modified form of the motivated strategies for learning questionnaire (MSLQ) to Persian and evaluate its reliability and validity among medical students.MethodsThis study was performed on medical students in clinical stages at the Shiraz University of Medical Science in 2022. The modified MSLQ questionnaire was used in this study which is a 32-item tool measuring different aspects of self-reflecting, including self-orientation, feedback-seeking, critical thinking, and self-regulation. This questionnaire was translated into Persian properly. Cronbach’s alpha and confirmatory factor analysis were used to ascertain the reliability and validity of the tool.ResultsA total of 325 medical students consisting of 174 men and 151 women with an average age of 23.79 (± 2.21) were enrolled. Path diagrams of confirmatory factor analysis for both standardized regression coefficients and t-values and all the fitness indicators were in favor of the proper validation of the translated version. The overall Cronbach’s alpha for the questionnaire was 0.9, and the value for each of four subscales was above 0.7.ConclusionsOur study showed that the Persian-translated version of the modified MSLQ is valid and reliable without taking too much time and effort to implement. We recommend that the developed tool be distributed to medical students from other Iran universities.

Reflection dispersion of seismic waves at the ocean bottom due to mesoscopic-flow loss

Seismic reflections at the interface of heterogeneous porous media are significantly affected by the multi-scale fluid-flow losses. In this work, we study the seismic reflection dispersion from the ocean bottom separating seawater and heterogeneous porous seabed, described by the effective Biot theory where the mesoscopic loss is present. The analytical reflection coefficient is obtained based on the displacement potentials and suitable boundary conditions. Two reflection scenarios, including the water/water-bearing medium contact and water/gas-saturated medium interface, are considered. The shear-wave attenuation is also considered by using a Cole-Cole complex shear modulus. Numerical results showing the variation in reflection magnitude versus frequency and incidence angle are presented, revealing that the P-wave mesoscopic attenuation, complex shear modulus, boundary conditions and permeability can significantly affect the frequency and angle dependence of the reflection coefficients. Reflections at the water/gas-saturated medium interface exhibit quite different behaviors from those at the water/water-bearing medium contact. The open-pore interface gives frequency-dependent reflections, whereas in sealed-pore case, the reflection magnitudes remain unchanged for all frequencies, due to the fact that the interface degrades into a water/elastic solid one. The study can be relevant for reservoir prediction and fluid identification based on the reflected marine data.

An efficient analytical approach for steady-state upscaling of relative permeability and capillary pressure

Upscaling in petroleum reservoir simulation captures the dynamic behavior of fine-scale models at the coarse-scale in a volume average sense. Traditional upscaling of immiscible two-phase flow can be implemented by solving the fluid flow equations at steady state in the capillary or viscous limit in fine scale, which requires modeling the single-phase flow numerically many times and is computationally demanding. In this study, an analytical approach is proposed, to replace the numerical simulation, for computing the relative permeability. The key idea is to utilize the perturbation expansion technique and Fourier analysis to derive an explicit expression of the equivalent permeability. The analytical expression accounts for spatial correlations and is more accurate than the simple averaging and renormalization methods. It matches well with the numerical method in all cases for the upscaling of the relative permeability and capillary pressure. The developed method is also validated by comparing the pressure and saturation results from the coarse-scale and fine-scale models. In the base case of SPE10 benchmark test, the numerical upscaling takes 436 s, whereas the analytical upscaling takes 13.6 s, which is about 30 times faster than the numerical method. Moreover, the analytical coefficients just need to be computed once for the whole space in a given geostatistical model, which naturally leads to improved efficiency and is clearly favorable for petroleum reservoir simulations.

Reference intervals and stability of haptocorrin and holotranscobalamin in Danish children and elderly

BackgroundHaptocorrin (HC) and holotranscobalamin (holoTC) carry vitamin B12 (B12) in the circulation and can be useful biomarkers for evaluating B12 status. The concentration of both proteins depends on age, but data on reference intervals for children and the elderly are sparse. Similarly, not much is known about the effect of preanalytical factors. MethodsHC plasma samples from healthy elderly > 65 years (n = 124) were analysed, and both HC and holoTC were analysed in paediatric serum samples ≤ 18 years (n = 400). Furthermore, we investigated assay precision and stability. ResultsHC and holoTC were effected by age. We established reference intervals for HC: 2–10 years, 369–1237 pmol/L; 11–18 years, 314–1128 pmol/L; 65–82 years, 242–680 pmol/L and for holoTC: 2–10 years, 46–206 pmol/L; 11-18 years, 30–178 pmol/L. Analytical coefficients of variations of 6.0–6.8% and 7.9–15.7% were found for HC and holoTC, respectively. HC were affected when stored at room temperature and by freeze/thaw. HoloTC was stable at room temperature and after delayed centrifugation. ConclusionWe present novel 95% age-related reference limits for HC and HoloTC in children, and for HC both in children and elderly. Moreover, we found HoloTC to be fairly stable when stored, whereas HC was more vulnerable to preanalytical factors.

Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models

PurposeTumor hypoxia and other microenvironmental factors are key determinants of treatment resistance. Hypoxia positron emission tomography (PET) and functional magnetic resonance imaging (MRI) are established prognostic imaging modalities to identify radiation resistance in head-and-neck cancer (HNC). The aim of this preclinical study was to develop a multi-parametric imaging parameter specifically for focal radiotherapy (RT) dose escalation using HNC xenografts of different radiation sensitivities.MethodsA total of eight human HNC xenograft models were implanted into 68 immunodeficient mice. Combined PET/MRI using dynamic [18F]-fluoromisonidazole (FMISO) hypoxia PET, diffusion-weighted (DW), and dynamic contrast-enhanced MRI was carried out before and after fractionated RT (10 × 2 Gy). Imaging data were analyzed on voxel-basis using principal component (PC) analysis for dynamic data and apparent diffusion coefficients (ADCs) for DW-MRI. A data- and hypothesis-driven machine learning model was trained to identify clusters of high-risk subvolumes (HRSs) from multi-dimensional (1-5D) pre-clinical imaging data before and after RT. The stratification potential of each 1D to 5D model with respect to radiation sensitivity was evaluated using Cohen’s d-score and compared to classical features such as mean/peak/maximum standardized uptake values (SUVmean/peak/max) and tumor-to-muscle-ratios (TMRpeak/max) as well as minimum/valley/maximum/mean ADC.ResultsComplete 5D imaging data were available for 42 animals. The final preclinical model for HRS identification at baseline yielding the highest stratification potential was defined in 3D imaging space based on ADC and two FMISO PCs (p<0.001). In 1D imaging space, only clusters of ADC revealed significant stratification potential (p=0.002). Among all classical features, only ADCvalley showed significant correlation to radiation resistance (p=0.006). After 2 weeks of RT, FMISO_c1 showed significant correlation to radiation resistance (p=0.04).ConclusionA quantitative imaging metric was described in a preclinical study indicating that radiation-resistant subvolumes in HNC may be detected by clusters of ADC and FMISO using combined PET/MRI which are potential targets for future functional image-guided RT dose-painting approaches and require clinical validation.