Heterogeneity Index Research Articles

A machine learning-based approach to predict energy layer for each field in spot-scanning proton arc therapy for lung cancer: A feasibility study.

Determining the optimal energy layer (EL) for each field, under considering both dose constraints and delivery efficiency, is crucial to promoting the development of proton arc therapy (PAT) technology. This study aimed to explore the feasibility and potential clinical benefits of utilizing machine learning (ML) technique to automatically select EL for each field in PAT plans of lung cancer. Proton Bragg peak position (BPP) was employed to characterize EL. The ground truth BPPs for each field were determined using the modified ELO-SPAT framework. Features in geometric, water-equivalent thicknesses (WET) and beamlet were defined and extracted. By analyzing the relationship between the extracted features and ground truth, a polynomial regression model with L2-norm regularization (Ridge regression) was constructed and trained. The performance of the regression model was reported as an error between the predictions and the ground truth. Besides, the predictions were used to make PAT plans (PAT_PRED). These plans were compared with those using the ground truth BPPs (PAT_TRUTH) and the mid-WET of the target volumes (PAT_MID) in terms of relative biological effectiveness-weighted dose (RWD) distributions. One hundred ten patients with lung cancer, a total of 7920 samples, were enrolled retrospectively, with 5940 cases randomly selected as the training set and the remaining 1980 cases as the testing set. Nine patients (648 samples) were collected additionally to evaluate the regression model in terms of plan quality and robustness. With regard to the prediction errors, the root mean squared errors and mean absolute errors between the ML-predicted and ground truth BPPs for the testing set were 9.165 and 6.572mm, respectively, indicating differences of approximately two to three ELs. As for plan quality, the PAT_TRUTH and PAT_PRED plans performed similarly in terms of plan robustness, target coverage and organs at risk (OARs) protection, with differences smaller than 0.5Gy(RBE). This trend was also observed for dose conformity and uniformity. The PAT_MID plans produced the lowest robustness index and lowest doses to OARs, along with the highest heterogeneity index, indicating better protection for OARs, improved plan robustness, but compromised dose homogeneity. Additionally, for relatively small tumor sizes, the PAT_MID plan demonstrated a notably poor dose conformity index. Within this cohort under investigation, our study demonstrated the feasibility of using ML technique to predict ELs for each field, offering a fast (within 2 s) and memory-efficient reduced way to select ELs for PAT plan.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Prognostic Value of Sublingual Microcirculation in Sepsis: A Systematic Review and Meta-analysis.

Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).

Spatial heterogeneity in tumor adhesion qualifies collective cell invasion

Collective cell invasion (CCI), a canon of most invasive solid tumors, is an emergent property of the interactions between cancer cells and their surrounding extracellular matrix (ECM). However, tumor populations invariably consist of cells expressing variable levels of adhesive proteins that mediate such interactions, disallowing an intuitive understanding of how tumor invasiveness at a multicellular scale is influenced by spatial heterogeneity of cell-cell and cell-ECM adhesion. Here, we have used a Cellular Potts model-based multiscale computational framework that is constructed on the histopathological principles of glandular cancers. In earlier efforts on homogenous cancer cell populations, this framework revealed the relative ranges of interactions, including cell-cell and cell-ECM adhesion that drove collective, dispersed, and mixed multimodal invasion. Here, we constitute a tumor core of two separate cell subsets showing distinct intra- and inter-subset cell-cell or cell-ECM adhesion strengths. These two subsets of cells are arranged to varying extents of spatial intermingling, which we call the heterogeneity index (HI). We observe that low and high inter-subset cell adhesion favors invasion of high-HI and low-HI intermingled populations with distinct intra-subset cell-cell adhesion strengths, respectively. In addition, for explored values of cell-ECM adhesion strengths, populations with high HI values collectively invade better than those with lower HI values. We then asked how spatial invasion is regulated by progressively intermingled cellular subsets that are epithelial, i.e., showed high cell-cell but poor cell-ECM adhesion, and mesenchymal, i.e., with reversed adhesion strengths to the former. Here too, inter-subset adhesion plays an important role in contextualizing the proportionate relationship between HI and invasion. An exception to this relationship is seen for cases of heterogeneous cell-ECM adhesion where sub-maximal HI patterns with higher outer localization of cells with stronger ECM adhesion collectively invade better than their relatively higher-HI counterparts. Our simulations also reveal how adhesion heterogeneity qualifies collective invasion, when either cell-cell or cell-ECM adhesion type is varied but results in an invasive dispersion when both adhesion types are simultaneously altered.

Ferumoxytol-enhanced MR venography for mapping lower-extremity venous networks and evaluating varicose veins in patients with diabetes.

Comprehensive evaluation of lower-extremity varicose veins (VVs) in patients with diabetes is crucial for treatment strategizing. The study aims to assess the feasibility of using ferumoxytol-enhanced MR venography (FE-MRV) for lower-extremity venous mapping and the detection of VVs in patients with diabetes. As part of a phase II clinical trial of a generic brand of ferumoxytol, documented patients with diabetes were enrolled and underwent FE-MRV on a 3-Τ MRI system. Two observers assessed FE-MRV images for image quality, signal intensity ratio (SIR), perforator (PV) diameter, and luminal signal uniformity in deep-to-superficial venous networks with the assessment of intra- and inter-rater reliability. FE-MRV was used to detect lower-extremity VVs. Eleven patients underwent FE-MRV without adverse events. The average image quality, as scored by the two observers who assessed 275 venous segments, was 3.4 ± 0.6. Two observers strongly agreed on image quality (κ = 0.90) and SIR measurements (interclass correlation coefficient [ICC]: 0.72) and had good agreement on PV diameter (ICC: 0.64). FE-MRV revealed uniform luminal signals in deep and saphenous venous networks (0.13 ± 0.05 vs 0.08 ± 0.03). Below-knee segments exhibited a significantly higher heterogeneity index than above-knee (p = 0.039) segments. Superficial VVs were observed in 55% (12/22)of legs in 64% (7/11)of patients. Calf muscle VVs were present in 64% (14/22)of legs in 9 patients. FE-MRV safely and robustly mapped entire lower-extremity venous networks, enabling the detection and pre-treatment evaluation of both superficial, and deep VVs in patients with diabetes. Ferumoxytol-enhanced magnetic resonance venography offers a "one-stop" imaging strategy for the detection and pre-operative evaluation of both superficial and deep VVs in diabetic patients. Diabetic patients with VVs are at a higher risk of ulcer-related complications. FE-MRV allowed rapid and comprehensive visualization of the lower-limb venous networks and abdominopelvic veins in diabetic patients. This technique allowed for the detection of superficial and deep VVs in diabetic patients before the development of severe peripheral artery disease.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey’s test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

A relação entre a heterogeneidade da paisagem e os serviços ecossistêmicos em Santa María Huatulco, Oaxaca, México

[Introduction]: The variability of geographic space, in terms of the horizontal structure of landscapes, influences ecology and suggests an association between landscape heterogeneity indices (LHI) and ecosystem services (ES). This relationship is crucial for conservation and sustainable development in Latin America, given the diversity of landscapes, from tropical forests to snow-capped mountains and deserts, which harbor a unique wealth of biodiversity and ecological functions. The objective of this study was to determine the relationship between LHI and ES. [Methodology]: Fourteen landscape heterogeneity indices and seven ecosystem services were calculated in Santa María Huatulco, Oaxaca, and related to the estimated ecosystem services for the same area. [Results]: The models showed a statistically significant relationship between LHI and ES, suggesting that certain LHI can influence the provision and distribution of ES. [Conclusions]: Therefore, understanding how LHI affect ES is essential to promote sustainable development in Latin America.

Utilizing collimated aperture with proton pencil beam scanning (PBS) for stereotactic radiotherapy.

Proton stereotactic radiosurgery (PSRS) has emerged as an innovative proton therapy modality aimed at achieving precise dose delivery with minimal impact on healthy tissues. This study explores the dosimetric outcomes of PSRS in comparison to traditional intensity-modulated proton therapy (IMPT) by focusing on cases with small target volumes. A custom-made aperture system designed for proton therapy, specifically tailored to small target volumes, was developed and implemented for this investigation. A prerequisite mechanical validation through an isocentricity test precedes dosimetric assessments, ensuring the seamless integration of mechanical and dosimetry analyses. Five patients were enrolled in the study, including two with choroid melanoma and three with arteriovenous malformations (AVM). Two treatment plans were meticulously executed for each patient, one utilizing a collimated aperture and the other without. Both plans were subjected to robust optimization, maintaining identical beam arrangements and consistent optimization parameters to account for setup errors of 2mm and range uncertainties of 3.5%. Plan evaluation metrics encompassing the Heterogeneity Index (HI), Paddick Conformity Index (CIPaddick), Gradient Index (GI), and the R50% index to evaluate alterations in low-dose volume distribution. The comparative analysis between PSRS and traditional PBS treatment revealed no significant differences in plan outcomes, with both modalities demonstrating comparable target coverage. However, collimated apertures resulted in discernible improvements in dose conformity, dose fall-off, and reduced low-dose volume. This study underscores the advantageous impact of the aperture system on proton therapy, particularly in cases involving small target volumes.

A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters.Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature – tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured.Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters.In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

Numerical Analysis of Air Supply Alternatives for Forced-Air Precooling of Agricultural Produce

Precooling agricultural produce is an intensive, energy-consuming process. To improve the efficiency of forced-air precooling and ultimately contribute to energy sustainability for postharvest storage of fresh produce, we designed three alternative air supply systems, simulated their cooling performances over a 96 h precooling process in a cold storage facility storing Chinese cabbages, and then compared their performances with a conventional design. All models were developed on a large scale on the basis of validated computational fluid dynamics models. The horizontal air supply scheme shortened the seven-eighths cooling time by 18.8%, and its maximum cooling rate increased by 19.7% compared to the conventional air supply scheme. The seven-eighths cooling time under another alternative design, the vertical air supply scheme, was 9.4% lower than the conventional, with the maximum cooling rate increasing by 10.5%. However, the maximum cooling rate of the last alternative design, the perforated ceiling air supply system, was 6.6% less than the conventional scheme, resulting in a 6.3% longer seven-eighths cooling time. The heterogeneity index of temperature implied that the horizontal air supply offered better overall cooling uniformity than the other designs, which can be attributed to its evenly distributed airflows and well-organized air movement paths, based on the combined analysis of temperature contours and air velocity contours at selected planes. Our findings are expected to provide practical guidelines for the refinement of the air supply system to improve its energy sustainability in forced-air precooling.

Histological analysis of the medial gastrocnemius muscle in young healthy children.

Introduction: Histological data on muscle fiber size and proportion in (very) young typically developing (TD) children is not well documented and data on capillarization and satellite cell content are also lacking. Aims: This study investigated the microscopic properties of the medial gastrocnemius muscle in growing TD children, grouped according to age and gender to provide normal reference values in healthy children. Methods: Microbiopsies of the medial gastrocnemius (MG) muscle were collected in 46 TD boys and girls aged 2-10years subdivided into 4 age groups (2-4, 4-6, 6-8 and 8-10years). Sections were immunostained to assess fiber type cross-sectional area (fCSA) and proportion, the number of satellite cells (SC), capillary to fiber ratio (C/F), capillary density for type I and II fiber (CFD), capillary domain, capillary-to-fiber perimeter exchange index (CFPE) and heterogeneity index. fCSA was normalized to fibula length2 and the coefficient of variation (CV) was calculated to reflect fCSA intrasubject variability. Results: Absolute fCSA of all fibers increased with age (r = 0.72, p < 0.001) but more in boys (+112%, p < 0.05) than in girls (+48%, p > 0.05) Normalized fCSA, CV and fiber proportion did not differ between age groups and gender. C/F was strongly correlated with age in boys (r = 0.83, p < 0.001), and to a lesser extent in girls (r = 0.37, p = 0.115), while other capillary parameters as well as the number of SC remained stable with increasing age in boys and girls. Discussion: This study provides reference values of histological measures in MG according to age in normally growing boys and girls. These data may be used as a reference to determine disease impact and efficacy of therapeutic approach on the muscle.

Quantitative Analysis of Diagenesis Control on the Spatial Heterogeneity of Sarvak Carbonate Formation, the Dezful Embayment of Zagros Basin, Western Iran

Summary The heterogeneity indices in conventional carbonate reservoirs are usually influenced by various diagenetic processes. The main aim of this study is to build 3D geological models of the diagenetic and heterogeneity indices addressing the role of diagenesis on spatial heterogeneity variations in the Sarvak carbonate reservoir of an Iranian oil field situated in the Dezful Embayment in the Zagros Basin. Vertical heterogeneity has been discussed in many studies, but the literature is limited on the 3D geological modeling of heterogeneity and providing spatial heterogeneity maps. In this study, we determined the main diagenetic parameters influencing the reservoir heterogeneity and constructed 3D geological models for evaluating the spatial heterogeneity. A couple of heterogeneity indices including the coefficients of variation (CVs) of porosity and permeability, Lorenz coefficient, and Dykstra-Parsons coefficient in cored intervals along with some diagenetic parameters were calculated and modeled. This study shows that lateral heterogeneity is mappable and correlatable with different diagenetic overprints along with shale volume, which controls the reservoir quality and spatial heterogeneity. It also indicates that lateral trends of the heterogeneity indices in different zones of the studied reservoir are influenced by other diagenetic parameters such as secondary porosity (SPI), dolomitization, cementation, and velocity deviation log (VDL, as a diagenetic index). Different diagenetic parameters control reservoir heterogeneity in each zone by decreasing or increasing the degree of the heterogeneity, some of which have dual constructive or destructive effects on heterogeneity indices. Moreover, the results show that the effect of shale volume on reservoir heterogeneity is significant, especially when the amount of the shale volume is notable.

Microcirculation-driven mitochondrion dysfunction during the progression of experimental sepsis

Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.

A comparative study of mono-exponential and advanced diffusion-weighted imaging in differentiating stage IA endometrial carcinoma from benign endometrial lesions

PurposeThe purpose of the current investigation is to compare the efficacy of different diffusion models and diffusion kurtosis imaging (DKI) in differentiating stage IA endometrial carcinoma (IAEC) from benign endometrial lesions (BELs).MethodsPatients with IAEC, endometrial hyperplasia (EH), or a thickened endometrium confirmed between May 2016 and August 2022 were retrospectively enrolled. All of the patients underwent a preoperative pelvic magnetic resonance imaging (MRI) examination. The apparent diffusion coefficient (ADC) from the mono-exponential model, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) from the bi-exponential model, distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index from the stretched-exponential model, diffusion coefficient (Dk) and diffusion kurtosis (K) from the DKI model were calculated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency.ResultsA total of 90 patients with IAEC and 91 patients with BELs were enrolled. The values of ADC, D, DDC and Dk were significantly lower and D* and K were significantly higher in cases of IAEC (p < 0.05). Multivariate analysis showed that K was the only predictor. The area under the ROC curve of K was 0.864, significantly higher compared with the ADC (0.601), D (0.811), D* (0.638), DDC (0.743) and Dk (0.675). The sensitivity, specificity and accuracy of K were 78.89%, 85.71% and 80.66%, respectively.ConclusionAdvanced diffusion-weighted imaging models have good performance for differentiating IAEC from EH and endometrial thickening. Among all of the diffusion parameters, K showed the best performance and was the only independent predictor. Diffusion kurtosis imaging was defined as the most valuable model in the current context.

Novel indices representing heterogeneous distributions of myocardial perfusion imaging

IntroductionHeterogeneous distribution in myocardial perfusion images (MPI) obtained by scintigraphy is often observed in cardiac diseases with normal myocardial perfusion. However, quantitative assessments of such heterogeneity have not been established. We hypothesized that the heterogeneity in MPI can be quantitatively evaluated through histogram analysis, calculating the standard deviation (SD), the 95% bandwidth (BW95%), and entropy.MethodsWe examined resting 99mTc-MIBI images in 20 healthy subjects and 29 patients with cardiac disease who had none or very-mild reduced myocardial perfusion evaluated as a low summed rest score (0 to 4, the range of the studied healthy subjects). Two nuclear medicine specialists blindly divided them into two groups: non-heterogeneity or heterogeneity group, based solely on their visual assessments of heterogeneity on splash and polar maps generated from single-photon emission computed tomography (SPECT) images. The %uptake was determined by dividing the tracer count of each pixel by the tracer count of the pixel with the highest value in the LV myocardium. SD, BW95%, and entropy from histogram patterns were analyzed from the polar map data array of each %uptake. We investigated whether heterogeneity could be assessed using SD, BW95, and entropy in two groups classified by visual assessments. Additionally, we evaluated the area under the curve (AUC) to identify heterogeneity in the receiver operating characteristic curve analysis.ResultsBased solely on visual assessments, 11 (22%) and 38 (78%) cases were classified into the non-heterogeneity and heterogeneity groups, respectively. The non-heterogeneity group consisted of only healthy subjects, and all patients with cardiac disease were classified into the heterogeneity group. The cases in the heterogeneity group had significantly higher values of heterogeneity indices (SD, BW95%, and entropy) in %uptake than those in the non-heterogeneity group (p < 0.05 for all). The AUCs of the heterogeneity indices were sufficiently high (AUCs > 0.90 for all) in distinguishing cases with visually heterogeneous distribution or patients with cardiac disease.ConclusionsHeterogeneity in MPI can be evaluated using SD, BW95%, and entropy through histogram analysis. These novel indices may help identify patients with subtle myocardial changes, even in images that show preserved perfusion (345/350).

Rational Design of a Portable Chemometric-Assisted Voltammetric Sensor Based on Ion-Imprinted Polymeric Film for Co(II) Determination in Water.

Herein, chemometric-assisted synthesis of electrochemical sensors based on electropolymerised ion-imprinted polymeric (e-IIP) films was explored. Co(II)-IIPs sensors were prepared by performing electropolymerisation procedures of polymerisation mixtures comprising varying concentrations of an electroactive o-aminophenol (o-AP) monomer and Co(II) ions, respectively, according to the Taguchi L9 experimental design, exploiting the simultaneous evaluation of other controlled parameters during electrosynthesis. Each e-IIP developed from Taguchi runs was compared with the respective non-imprinted polymer (NIP) films and fitted according to Langmuir-Freudlich isotherms. Distinctive patterns of low and high-affinity films were screened based on the qualities and properties of the developed IIPs in terms of binding kinetics (KD), imprinting factor, and the heterogeneity index of produced cavities. These results can provide a generic protocol for chemometric-assisted synthesis of e-IIPs based on poly-o-AP, providing highly stable, reproducible, and high-affinity imprinted polymeric films for monitoring purposes.

The Role of [18F]FDG PET/CT in the Characterization of Thymic Epithelial Tumors at Initial Stage.

Purpose: The aim of this study was to evaluate the potential role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUVmax, MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUVmax, TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUVmax, MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

The vegetation–topography heterogeneity coupling in the Loess Plateau, China

As a result of adaptation to the environment, the great environmental spatial heterogeneity leads to the high spatial heterogeneity of vegetation status. This coupling may be more apparent in water-limited drylands, where topography is the main determinant of small-scale variation in water availability and energy. Metrics describing this coupling may contribute to the detection of the extension of vegetation reshaped by human intervention and other driven forces. In this study, the heterogeneity index of coupling (HIC) was developed to indicate the coupling between spatial heterogeneity of vegetation status (Hv) and the spatial heterogeneity of topography (HT) in the Loess Plateau in northern China. The 16-day composed MODIS normalized vegetation index (NDVI) with a resolution of 250 m and SRTM DEM were employed to quantify the heterogeneity of vegetation status and the topographical heterogeneity. The results show that HIC varies among geomorphic zones, land cover types, and land cover change categories. Among all land cover types, HIC of sandy areas was the largest, followed by the HIC of the forest, shrub, farmland, and grassland. Among geomorphic zones, the highest HIC value appeared in plains with dense residential areas, followed by sandy land that is frequently reshaped by wind, rocky mountainous areas, hilly and gully loess plateaus, and loess tableland. It was revealed that the alternation of vegetation by human activities and natural disturbances shaped greater HIC. Results of this study approved the effectiveness of the HIC in reflecting the coupling of the vegetation status with topography at regional scale.

Multi-b-value DWI to evaluate the synergistic antiproliferation and anti-heterogeneity effects of bufalin plus sorafenib in an orthotopic HCC model

BackgroundMulti-b-value diffusion-weighted imaging (DWI) with different postprocessing models allows for evaluating hepatocellular carcinoma (HCC) proliferation, spatial heterogeneity, and feasibility of treatment strategies. We assessed synergistic effects of bufalin+sorafenib in orthotopic HCC-LM3 xenograft nude mice by using intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), a stretched exponential model (SEM), and a fractional-order calculus (FROC) model.MethodsTwenty-four orthotopic HCC-LM3 xenograft mice were divided into bufalin+sorafenib, bufalin, sorafenib treatment groups, and a control group. Multi-b-value DWI was performed using a 3-T scanner after 3 weeks’ treatment to obtain true diffusion coefficient Dt, pseudo-diffusion coefficient Dp, perfusion fraction f, mean diffusivity (MD), mean kurtosis (MK), distributed diffusion coefficient (DDC), heterogeneity index α, diffusion coefficient D, fractional order parameter β, and microstructural quantity μ. Necrotic fraction (NF), standard deviation (SD) of hematoxylin-eosin staining, and microvessel density (MVD) of anti-CD31 staining were evaluated. Correlations of DWI parameters with histopathological results were analyzed, and measurements were compared among four groups.ResultsIn the final 22 mice, f positively correlated with MVD (r = 0.679, p = 0.001). Significantly good correlations of MK (r = 0.677), α (r = -0.696), and β (r= -0.639) with SD were observed (all p < 0.010). f, MK, MVD, and SD were much lower, while MD, α, β, and NF were higher in bufalin plus sorafenib group than control group (all p < 0.050).ConclusionEvaluated by IVIM, DKI, SEM, and FROC, bufalin+sorafenib was found to inhibit tumor proliferation and angiogenesis and reduce spatial heterogeneity in HCC-LM3 models.Relevance statementMulti-b-value DWI provides potential metrics for evaluating the efficacy of treatment in HCC.Key points• Bufalin plus sorafenib combination may increase the effectiveness of HCC therapy.• Multi-b-value DWI depicted HCC proliferation, angiogenesis, and spatial heterogeneity.• Multi-b-value DWI may be a noninvasive method to assess HCC therapeutic efficacy.Graphical

Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer.

We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P < .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P < .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P < .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P < .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence. We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.