Intravoxel incoherent motion and diffusion kurtosis imaging and their machine-learning-based texture analysis for detection and assessment of prostate cancer severity at 3 T.

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

Transformative and sustainable insights of agricultural waste-based adsorbents for water defluoridation: Biosorption dynamics, economic viability, and spent adsorbent management.

With the progression of civilization, the harmony within nature has been disrupted, giving rise to various ecocidal activities that are evident in every spheres of the earth. These activities have had a profound and far-reaching impact on global health. One significant example of this is the presence of fluoride in groundwater exceeding acceptable limits, resulting in the widespread occurrence of "Fluorosis" worldwide. It is imperative to mitigate the concentration of fluoride in drinking water to meet safety standards. While various defluoridation techniques exist, they often have drawbacks. Biosorption, being a simple, affordable and eco-friendly method, has gained preference for defluoridation. However, its limited commercialization underscores the pressing need for further research in this domain. This comprehensive review article offers a thorough examination of the defluoridation potential of agro-based adsorbents, encompassing their specific chemical compositions and preparation methods. The review presents an in-depth discussion of the factors influencing fluoride biosorption and conducts a detailed exploration of adsorption isotherm and adsorption kinetic models to gain a comprehensive understanding of the nature of the adsorption process. Furthermore, it evaluates the commercial viability through an assessment of regeneration potential and a cost analysis of these agro-adsorbents, with the aim of facilitating the scalability of the defluoridation process. The elucidation of the adsorption mechanism and recommendations for overcoming challenges in large-scale implementation offer a comprehensive outlook on this eco-friendly and sustainable approach to fluoride removal. In summary, this review article equips readers with a lucid understanding of agro-adsorbents, elucidates their ideal conditions for improved performance, offers a more profound insight into the fluoride biosorption mechanism, and introduces the concept of effective spent adsorbent management.

Radiologists' Rating for Comparative Qualitative Assessment of Intravoxel Incoherent Motion Using Novel Analysis Methods.

OBJECTIVE: The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion ( IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy. METHODS: Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters-diffusion coefficient ( D ), perfusion fraction ( f ), and perfusion coefficient ( D* )-were estimated using 5 IVIM analysis methods-(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation ( rs ). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV). RESULTS: BE + TV and BE + HPF produced significantly ( P < 10 -3 ) higher qualitative scores for D (fair-good [3.3-3.8]) than BE (poor [2.3]) and for D* (poor-fair [2.2-2.7]) and f (fair-good [3.2-3.8]) than BE, BESeg-2, and BESeg-1 ( D* : uninterpretable-poor [1.3-1.9] and f : poor-fair [1.5-3]). Interobserver agreement for qualitative scoring was rs = 0.48-0.59, P < 0.009. BE + TV and BE + HPF showed significantly ( P < 0.05) improved reproducibility in estimating D (wCV: 24%-31%, bCV: 21%-31% improvement) than the BE method and D* (wCV: 4%-19%, bCV: 5%-19% improvement) and f (wCV: 25%-49%, bCV: 25%-47% improvement) than BE, BESeg-2, and BESeg-1 methods. CONCLUSIONS: BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further.

Heavy metals distribution and ecological risk assessment including arsenic resistant PGPR in tidal mangrove ecosystem.

Heavy metals (HM) are the major proximate drivers of pollution in the mangrove ecosystem. Therefore, ecological risk (ER) due to HM distribution/concentration in core-sediment of Puzi mangrove region (Taiwan) was examined with tidal influence (TI) along with indigenous rhizospheric bacteria (IRB). The HM concentration was observed higher at active-tidal-sediment compared to partially-active-sediment. Geo-accumulation index (Igeo) and contamination factor (CF) indicated the tidal-sediment was highly contaminated with arsenic (As) and moderately contaminated with Lead (Pb) and Zinc (Zn). However, the pollution loading index (PLI) and degree of contamination (Cd) exhibited 'no pollution' and 'low-moderate degree of contamination', in the studied region respectively. The isolated IRB (Priestia megaterium, Bacillus safenis, Bacillus aerius, Bacillus subtilis, Bacillus velenzenesis, Bacillus lichenoformis, Kocuria palustris, Enterobacter hormaechei, Pseudomonus fulva, and Paenibacillus favisporus; accession number OM979069-OM979078) exhibited the arsenic resistant behavior with plant-growth-promoting characters (IAA, NH3, and P-solubilization), which can be used in mangrove reforestation and bioremediation of HM.

Transvaginal Shear Wave Elastography for Assessment of Endometrial and Subendometrial Pathologies: A Prospective Pilot Study.

OBJECTIVE: To assess the role of shear wave elastography (SWE) in characterizing different endometrial and subendometrial pathologies. METHODS: Seventy-three women with pathologically proven endometrial and subendometrial pathologies were enrolled in this prospective study and assessed with transvaginal SWE. The elasticity values (in kiloPascals), and the ratio of mean elasticity of the endometrial lesion to myometrial elasticity (E/M ratio) were compared in different pathologies. RESULTS: There was a statistically significant difference (P <.001) in the mean, minimum, and maximum elasticity of the pathologies as well as the E/M ratio (P <.00001). In the analysis of the subgroups, the mean elasticity of endometrial polyp was statistically significantly lower than other subgroups (P <.01), while submucosal leiomyoma and focal adenomyoma had significantly higher values than other subgroups (P <.01). No statistically significant difference was noted in the mean elasticity of carcinoma and hyperplasia (P-.19). CONCLUSION: SWE is a potential adjunct to ultrasound that provides an additional paradigm to characterize endometrial and subendometrial masses.

Risk Assessment of Perfluorooctane Sulfonate (PFOS) using Dynamic Age Dependent Physiologically based Pharmacokinetic Model (PBPK) across Human Lifetime.

The widespread use of Perfluorooctane sulfonate (PFOS) in everyday life, its long half-life, and the lipophilicity that makes it easily accumulate in the body, raises the question of its safe exposure among different population groups. There are currently enough epidemiological studies showing evidence of PFOS exposure and its associated adverse effects on humans. Moreover, it is already known that physiological changes along with age e.g. organ volume, renal blood flow, cardiac output and albumin concentrations affect chemicals body burden. Human biomonitoring cohort studies have reported PFOS concentrations in blood and autopsy tissue data with PFOS present in sensitive organs across all human lifespan. However, to interpret such biomonitoring data in the context of chemical risk assessment, it is necessary to have a mechanistic framework that explains show the physiological changes across age affects the concentration of chemical inside different tissues of the human body. PBPK model is widely and successfully used in the field of risk assessment. The objective of this manuscript is to develop a dynamic age-dependent PBPK model as an extension of the previously published adult PFOS model and utilize this model to predict and compare the PFOS tissue distribution and plasma concentration across different age groups. Different cohort study data were used for exposure dose reconstruction and evaluation of time-dependent concentration in sensitive organs. Predicted plasma concentration followed trends observed in biomonitoring data and model predictions showed the increased disposition of PFOS in the geriatric population. PFOS model is sensitive to parameters governing renal resorption and elimination across all ages, which is related to PFOS half-life in humans. This model provides an effective framework for improving the quantitative risk assessment of PFOS throughout the human lifetime, particularly in susceptible age groups. The dynamic age-dependent PBPK model provides a step forward for developing such kind of dynamic model for other perfluoroalkyl substances.

Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A real-life cohort from northern India.

BACKGROUND: The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. METHODS: Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. RESULTS: Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8-complete records unavailable; 3-received only single dose). Of 79 patients (mean age-40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn's disease; median follow-up-24 [12-39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden-16.5%; tubercular reactivation-12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5-45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). CONCLUSION: Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.

Intravoxel incoherent motion (IVIM) for response assessment in patients with osteosarcoma undergoing neoadjuvant chemotherapy.

PURPOSE: To explore the role of quantitative Intravoxel incoherent motion (IVIM) parameters and their histogram analysis in characterizing changes in Osteosarcoma receiving neoadjuvant chemotherapy (NACT) and evaluating therapeutic response. METHODS: Forty patients (N = 40; Male:Female = 30:10; Age = 17.7 ± 5.9years; Metastatic:localized = 17:23) with histologically confirmed Osteosarcoma treated with 3-cycles of NACT were analyzed prospectively. All patients underwent Diffusion weighted imaging (DWI) with 11 b-values (0-800 s/mm2) using 1.5 T MRI scanner at pre-treatment (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Non-invasive response evaluation of NACT was performed using RECIST1.1 criteria. Apparent-diffusion-coefficient (ADC) and IVIM parameters - Diffusion-coefficient (D), Perfusion-coefficient (D*) & Perfusion-fraction (f) and their relative percentage changes from time-point t0-t1 (Δ2) and t0-t2 (Δ2) were evaluated and histogram analysis was performed at three time-points and compared with respect to RECIST1.1 scores. RESULTS: Using RECIST1.1 criteria, 11 (27.5%), 21 (52.5%) and 8 (20%) patients were in Partial-responder (PR), Stable-disease (SD) and Progressive-disease (PD) groups respectively. Pre-NACT (t0), average ADC, D,D*&f in tumor volume were 1.36 ± 0.33 × 10-3 mm2/s, 1.3 ± 0.3 × 10-3 mm2/s, 28.44 ± 10.34 × 10-3 mm2/s & 13.95 ± 2.83% respectively. Using ANOVA test, during NACT (t1, t2), D*-variance (p = 0.038, 0.003) and f-skewness (p = 0.03, 0.03) and at t2, D*-entropy (p = 0.001) and f-entropy (p = 0.002) and their Δ2 changes (p = 0.001, 0.003) were statistically significant among response groups. At t1, D*-variance and f-skewness jointly showed AUC = 0.77 & 0.74 in classifying PR (Sensitivity = 73%; Specificity = 70%) and SD (Sensitivity = 74; Specificity = 75%) groups respectively in patient cohort. Δ1 & Δ2 changes of D*-mean, D*-variance, D*-entropy and f-entropy correlated well (0.5-0.6) with tumor-diameter and tumor-volume changes. CONCLUSIONS: Quantitative IVIM parameters, especially D* &f and their histogram analysis were informative and can be used as noninvasive surrogate markers for early response assessment during the course of NACT in Osteosarcoma.

Quantitative Sonoelastographic Assessment of the Normal Uterus Using Shear Wave Elastography: An Initial Experience.

OBJECTIVES: To describe the sonoelastographic characteristics of the normal endometrium, myometrium, and cervix and to assess their variability with age and different menstrual phases. METHODS: A total of 56 women were enrolled in this prospective study, who underwent transvaginal ultrasound examinations, including B-mode imaging and shear wave elastography. The elasticity parameters (in kilopascals) of the normal endometrium, myometrium, and cervix were studied. The variability of the mean elasticity value of the endometrium in different menstrual phases and age groups was analyzed. The variability of the mean elasticity of the cervix across different age groups was also studied. RESULTS: The mean age of the participants was 40 years (range, 25-69 years). The normal mean elasticity values ± SDs were 25.54 ± 8.56 kPa for the endometrium, 40.24 ± 8.59 kPa for the myometrium, and 18.90 ± 4.22 kPa for the cervix. A mean endometrial-to-myometrial elasticity ratio was calculated, which was found to be 0.65 ± 0.22. There was no significant difference in the mean endometrial elasticity values for women in different menstrual phases (P = .176) or in different age groups (P = .376). There was no significant difference in the mean cervical elasticity with age (P = .192). CONCLUSIONS: Shear wave elastography is a promising adjunct to ultrasound for the evaluation of the uterus, and the results from this study may provide normal data, which may further help in diagnosing various uterine diseases.

Development of a human physiologically based pharmacokinetic (PBPK) model for phthalate (DEHP) and its metabolites: A bottom up modeling approach.

DEHP exposure to human comes from different sources such as food, diet, cosmetics, toys, medical products, and food wraps. Recently, DEHP was categorized as non-persistent endocrine disrupting compounds (EDCs) by the world health organization (WHO). Rat experimental studies showed that phthalate and its metabolite(s) can cause hepatic, developmental and reproductive toxicity. In human, DEHP rapidly metabolizes into a toxic metabolite MEHP. This MEHP further metabolizes into the different chemical forms of 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP and phthalic acid. A simple DEHP pharmacokinetics model has been developed, but with a limited number of metabolites. A chemical like DEHP which extensively metabolised indicate the need of a detail metabolic kinetics study. A physiological based pharmacokinetics (PBPK) model of the DEHP considering all the major metabolites in human, has not been developed yet. The objective of this study is to develop a detailed human PBPK model for the DEHP and its major metabolites by using a bottom-up modelling approach with the integration of a in vitro metabolic data. This approach uses an in-vitro-in-vivo extrapolation (IVIVE) and a quantitative structure-activity relationship (QSAR) method for the parameterization of the model. Monte Carlo simulations were performed to estimate the impact of parametric uncertainty onto the model predictions. First, the model was calibrated using the control human kinetic study that represents the time course of DEHP metabolites concentration in both the blood and the urine. Then, the model was evaluated against the published independent data on different dosing scenarios. The results of model predictions for the DEHP metabolites in both the blood and the urine were well within the range of experimentally observed data. The model also captured the similar trend of time course profile to the observed data, shows model good predictability power. The current developed PBPK model can futher be used for the prediction of the time course of chemical concentrations for the different exposure scenarios not only in the blood and the urine but also in the other compartments. Moreover, this model can also be used to explore different biomonitoring studies for the human health risk assessment and might be useful for integrative toxicological study in improving exposure-target tissue dose-response relationship.

Diffusion-weighted MRI in assessment of renal dysfunction.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) in renal diseases is an evolving field and its potential is yet to be fully realized. PURPOSE: To study the relationship between apparent diffusion coefficient (ADC) values of renal parenchyma and serum markers of renal function and stage of chronic kidney disease (CKD). MATERIALS AND METHODS: A retrospective review was performed of all adult patients who underwent DW-MRI (at b-values of 0 and 500 s/mm(2)) for renal lesions from January 2009 to September 2010 and revealed 88 patients, of which 22 patients had renal dysfunction and 66 had normal renal function. Of these 22, 15 patients were known cases of CKD and were staged depending on disease severity. ADC values were determined for renal parenchyma and compared. Receiver operating characteristic (ROC) curves were drawn to establish cut-off ADC values. Pearson's correlation coefficient (R) was calculated between ADC and renal function parameters. RESULTS: ADC values in patients with renal dysfunction were significantly lower than in patients with normal renal function (2.1133 ± 0.2851 vs. 2.3198 ± 0.1246 (×10(-3) mm(2)/s)). ADC values lower than 2.0354 (×10(-3) mm(2)/s) were seen only with renal dysfunction and higher than 2.4516 (×10(-3) mm(2) /s) were seen only with normal function. There was significant inverse correlation between ADC and serum creatinine (R = -0.530), blood urea (R= -0.502), and significant linear correlation (R = 0.784) with estimated glomerular filtration rate (eGFR). ADC values showed a statistically significant decreasing trend with increasing stage of CKD. CONCLUSION: ADC values may serve as an additional marker for the presence and degree of renal dysfunction.

PET/CT colonography: a novel non-invasive technique for assessment of extent and activity of ulcerative colitis.

PURPOSE: Extent of involvement and activity of ulcerative colitis (UC) is best evaluated by colonoscopy. Colonoscopy however carries risk during acute exacerbation. We investigated the utility of PET/CT colonography for assessment of extent and activity of UC. METHODS: Within a 1-week window, 15 patients with mild to moderately active UC underwent colonoscopy and PET/CT colonography 60 min after injection of 10 mCi of (18)F-fluorodeoxyglucose (FDG). PET activity score based on the amount of FDG uptake and endoscopic mucosal activity in seven colonic segments of each patient was recorded. The mean maximum standardized uptake value (SUV(max)) of seven segments was compared with activity in liver. A PET activity grade of 0, 1, 2 or 3 was assigned to each region depending upon their SUV(max) ratio (colon segment to liver). RESULTS: The extent of disease was left-sided colitis in five and pancolitis in ten. The mean Ulcerative Colitis Disease Activity Index (UCDAI) was 7.6. The number of segments involved as per colonoscopic evaluation and PET/CT colonography was 67 and 66, respectively. There was a good correlation for extent evaluation between the two modalities (kappa 55.3%, p = 0.02). One patient had grade 0 PET activity, nine had grade 2 and five had grade 3 PET activity. In six patients, there was one to one correlation between PET activity grades with that of endoscopic grade. One patient showed activity in the sacroiliac joint suggesting active sacroiliitis. CONCLUSION: PET/CT colonography is a novel non-invasive technique for the assessment of extent and activity of the disease in patients with UC.

Tumor marker CA-125 as an evaluator and response indicator in ovarian cancer: its quantitative correlation with tumor volume.

BACKGROUND: The tumor marker Cancer Antigen 125 (CA 125), though not ovarian cancer specific, is widely used for the evaluation of suspected and under-treated ovarian cancer. Many studies show that serum CA 125 level demonstrates ovarian tumor burden and its response, but they lack quantitative correlation between the two. Instead, they rely on clinical or radiological assessment of gross tumor burden. This study examines ovarian tumor volumes and corresponding serum CA 125 values before and during chemotherapy. MATERIALS/METHODS: [corrected] Ovarian tumor volume was measured by CT scans at pre-chemotherapy and after each cycle of chemotherapy in 15 patients. Blood serum CA 125 was determined on the days of CT scans using a one-step immunoenzymatic assay. RESULTS: There was no statistically significant correlation (r = 0.18, p > 0.05) between ovarian tumor volumes and CA 125 among patients at pre-chemotherapy or any subsequent time. In individual patients, the reduction or increase in tumor volume correlated with the corresponding CA 125 values during chemotherapy in 85% (12 out of 14) of patients. Mean CA 125 halving time was 44.1 days, which correlated with tumor halving time (r = 0.63, p < 0.05). CONCLUSIONS: Values of CA 125 cannot be used for comparison of ovarian tumor mass among patients. However, serial estimation of CA 125 in individuals is fairly reliable in terms of the course of the tumor. CT scan is a more informative response indicator, but it is costly and hence may be supplemented by the easy and economical CA 125 estimation.