Machine learning analysis of contrast-enhanced ultrasound (CEUS) for the diagnosis of acute graft dysfunction in kidney transplant recipients.

AIM: The aim of the study was to develop machine learning algorithms (MLA) for diagnosing acute graft dysfunction (AGD) in kidney transplant recipients based on contrast-enhanced ultrasound (CEUS) analysis of the graft.Materials and methods: This prospective study involved 71 patients with kidney transplant undergoing CEUS during follow-up. AGD wasdefined as an increase in serum creatinine levels of at least 25% compared to the baseline of the last three months. The control group consisted of patients with stable kidney graft function (SGF). The top five CEUS parameters that achieved the best discrimination between the AGD and SGF groups were selected based on ANOVA testing and then employed as input for training MLA (naïve Bayes (NB), k-nearest neighbors (k-NN), and logistic regression (LR)). The models were validated by leave-one-out cross-validation. RESULTS: Among the 111 CEUS analyses, 21 corresponded to the AGD group and 90 to the SGF group. CEUS analyses yielded 44 parameters, from which five were selected: the wash out rate in segmental arteries,time to peak in segmental arteries, medullary mean transit time, renal mean transit time, and medullary time to fall. These five parameters were employed as input for MLA, yielding an AUROC of 0.68 for NB and k-NN and 0.72 for LR. The inclusion of graft survival in the MLA significantly improved discrimination accuracy, yielding an AUROC of 0.79 for NB, 0.76 for k-NN,and 0.81 for LR. CONCLUSIONS: The use of MLA represents a promising strategy for analyzing CEUS-derived parameters in the setting AGD.

Metabolic Profiles and Blood Biomarkers to Discriminate between Benign Thyroid Nodules and Papillary Carcinoma, Based on UHPLC-QTOF-ESI+-MS Analysis.

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.

Pentacyclic Triterpenoid Phytochemicals with Anticancer Activity: Updated Studies on Mechanisms and Targeted Delivery.

Pentacyclic triterpenoids (TTs) represent a unique family of phytochemicals with interesting properties and pharmacological effects, with some representatives, such as betulinic acid (BA) and betulin (B), being mainly investigated as potential anticancer molecules. Considering the recent scientific and preclinical investigations, a review of their anticancer mechanisms, structure-related activity, and efficiency improved by their insertion in nanolipid vehicles for targeted delivery is presented. A systematic literature study about their effects on tumor cells in vitro and in vivo, as free molecules or encapsulated in liposomes or nanolipids, is discussed. A special approach is given to liposome-TTs and nanolipid-TTs complexes to be linked to microbubbles, known as contrast agents in ultrasonography. The production of such supramolecular conjugates to deliver the drugs to target cells via sonoporation represents a new scientific and applicative direction to improve TT efficiency, considering that they have limited availability as lipophilic molecules. Relevant and recent examples of in vitro and in vivo studies, as well as the challenges for the next steps towards the application of these complex delivery systems to tumor cells, are discussed, as are the challenges for the next steps towards the application of targeted delivery to tumor cells, opening new directions for innovative nanotechnological solutions.

Hepatocellular Carcinoma Recognition from Ultrasound Images Using Combinations of Conventional and Deep Learning Techniques.

Hepatocellular Carcinoma (HCC) is the most frequent malignant liver tumor and the third cause of cancer-related deaths worldwide. For many years, the golden standard for HCC diagnosis has been the needle biopsy, which is invasive and carries risks. Computerized methods are due to achieve a noninvasive, accurate HCC detection process based on medical images. We developed image analysis and recognition methods to perform automatic and computer-aided diagnosis of HCC. Conventional approaches that combined advanced texture analysis, mainly based on Generalized Co-occurrence Matrices (GCM) with traditional classifiers, as well as deep learning approaches based on Convolutional Neural Networks (CNN) and Stacked Denoising Autoencoders (SAE), were involved in our research. The best accuracy of 91% was achieved for B-mode ultrasound images through CNN by our research group. In this work, we combined the classical approaches with CNN techniques, within B-mode ultrasound images. The combination was performed at the classifier level. The CNN features obtained at the output of various convolution layers were combined with powerful textural features, then supervised classifiers were employed. The experiments were conducted on two datasets, acquired with different ultrasound machines. The best performance, above 98%, overpassed our previous results, as well as representative state-of-the-art results.

Automatic Segmentation of Periodontal Tissue Ultrasound Images with Artificial Intelligence: A Novel Method for Improving Dataset Quality.

This research aimed to evaluate Mask R-CNN and U-Net convolutional neural network models for pixel-level classification in order to perform the automatic segmentation of bi-dimensional images of US dental arches, identifying anatomical elements required for periodontal diagnosis. A secondary aim was to evaluate the efficiency of a correction method of the ground truth masks segmented by an operator, for improving the quality of the datasets used for training the neural network models, by 3D ultrasound reconstructions of the examined periodontal tissue. METHODS: Ultrasound periodontal investigations were performed for 52 teeth of 11 patients using a 3D ultrasound scanner prototype. The original ultrasound images were segmented by a low experienced operator using region growing-based segmentation algorithms. Three-dimensional ultrasound reconstructions were used for the quality check and correction of the segmentation. Mask R-CNN and U-NET were trained and used for prediction of periodontal tissue's elements identification. RESULTS: The average Intersection over Union ranged between 10% for the periodontal pocket and 75.6% for gingiva. Even though the original dataset contained 3417 images from 11 patients, and the corrected dataset only 2135 images from 5 patients, the prediction's accuracy is significantly better for the models trained with the corrected dataset. CONCLUSIONS: The proposed quality check and correction method by evaluating in the 3D space the operator's ground truth segmentation had a positive impact on the quality of the datasets demonstrated through higher IoU after retraining the models using the corrected dataset.

Thyroid Cancer Diagnostics Related to Occupational and Environmental Risk Factors: An Integrated Risk Assessment Approach.

There are still many questions remaining about the etiopathogenesis of thyroid cancer, the most common type of endocrine neoplasia. Numerous occupational and environmental exposures have been shown to represent important risk factors that increase its incidence. Updated information about thyroid cancer diagnostics related to occupational and environmental risk factors is reviewed here, considering an integrated risk assessment approach; new data concerning thyroid cancer etiology and pathogenesis mechanisms, diagnostic biomarkers and methodologies, and risk factors involved in its pathogenesis are presented. A special emphasis is dedicated to specific occupational risk factors and to the association between environmental risk agents and thyroid cancer development. The occupational environment is taken into consideration, i.e., the current workplace and previous jobs, as well as data regarding risk factors, e.g., age, gender, family history, lifestyle, use of chemicals, or radiation exposure outside the workplace. Finally, an integrative approach is presented, underlying the need for an accurate Risk Assessment Matrix based on a systematic questionnaire. We propose a complex experimental design that contains different inclusion and exclusion criteria for patient groups, detailed working protocols for achieving coherent and sustainable, well-defined research stages from sample collection to the identification of biomarkers, with correlations between specific oncometabolites integrated into the Risk Assessment Matrix.

Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI+MS.

Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI+ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the "lipogenic phenotype" specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.

Melatonin, an ubiquitous metabolic regulator: functions, mechanisms and effects on circadian disruption and degenerative diseases.

The last four decades, we assist to an increasing scientific interest on melatonin, a circadian hormone, a metabolic regulator which influences not only plants' metabolism and their defense against pathogens but mostly the animals and humans' metabolic pathways, their response to circadian disruption, stress and burnout syndrome. In humans, as a hormonal regulator, produced in the pineal grand as well in mitochondria, melatonin is involved in different, complex intracellular signaling pathways, with antioxidant and immune stimulating effects, proving to act as a circadian synchronizer, as a preventive and therapeutic agent in many degenerative diseases, and especially in hormone-dependent cancers. Preclinical or clinical studies showed recently the mechanisms involved in regulating the cellular activity, its role in aging and circadian disturbances and impact on degenerative diseases. Melatonin proved to have an anti-inflammatory, antiapoptotic and powerful antioxidant effect by subtle mechanisms in mitochondrial metabolic pathways. This overview includes recent and relevant literature data related to the impact of endogenous and exogeneous melatonin on the prevention of cancer progression and treatment of various degenerative diseases. Metabolomics, an emerging new omics' technology, based on high performance liquid chromatography coupled with mass spectrometry is presented as an encouraging technique to fingerprint and realize a precise evaluation and monitoring of the turnover of melatonin and its metabolites in different pathological circumstances.

Current status of imaging diagnosis in the transplanted kidney. A review of the literature with a special focus on contrast-enhanced ultrasonography.

OBJECTIVES: Ultrasonographic scanning is currently the most widespread imaging diagnostic procedure. The method provides real-time morphological, vascular and elastographic information in a non-invasive manner. In recent years, harmonic vascular examination has become accessible using intravenous contrast agents. In urological pathology, this procedure is used in the detection and evaluation of vascular and ischemic complications, in the classification of complex cysts according to the Bosniak system, also in the renal lesions with uncertain etiology and in acute pyelonephritis for the detection of abscesses. The contrast agent (SonoVue) is angiospecific and can be used in patients transplanted immediately after surgery without adverse effects or impaired renal function. Thus, it is desirable to be used in the nephrological pathology of the renal graft and to develop diagnostic models based on the evaluation of renal microvascularization, as well as the quantitative data resulting from the graphical representation of the specific parameters. The purpose of this review is to evaluate the current state of the literature regarding the place and role of contrast substance ultrasound in the early diagnosis of acute renal graft dysfunction and to make a differential diagnosis of this pathological entity. METHOD: This review quantifies the role of contrast ultrasound in the diagnosis of acute complications of the renal graft. The research was conducted based on the databases PubMed, MedScape, Cochrane, according to the search criteria such as contrast-enhanced ultrasound + kidney transplant, "time intensity curves" + "kidney transplant", filtered for the period 2004-2018. RESULTS: In the nephrological pathology of the renal graft, contrast-enhanced ultrasound is a valuable tool, superior to Doppler ultrasound in predicting the evolution of the renal graft, identifying very small early defects in renal microvascularization. A number of studies succeeded in identifying acute graft dysfunction, some of which establish its etiology - humoral rejection versus acute tubular necrosis. On the other hand, the contrast-enhanced ultrasound parameters do not have the ability to distinguish between cellular and humoral rejection. CONCLUSIONS: If, at present, the histopathological examination is the only one that can differentiate with certainty the cause of acute renal graft dysfunction, we consider that contrast-enhanced ultrasound, as a non-invasive imaging technique, opens a favorable perspective for increasing the survival of the renal graft and decreasing the complications in the renal transplant. The combination of other ultrasound techniques, together with contrast-enhanced ultrasound, could lead to the development of new diagnostic models.

Contrast-enhanced ultrasonography in the initial evaluation of the kidney graft function: a pilot study.

AIM: Our study aimed to assess the usefulness of contrast-enhanced ultrasound (CEUS) in the initial evaluation of the graft function. MATERIALS AND METHOD: A cross-sectional study was conducted in the early postoperative period on patients with kidney transplantation, between September 2017 to November 2018. Two groups of patients were investigated; delayed graft function (DGF) and early graft function (EGF). All patients were examined by grey scale, Doppler ultrasound and CEUS. RESULTS: Nineteen patients, aged from 23 to 64 years (mean age 50 years), 7 in the DGF group and 12 in the EGF group were evaluated. The resistive index (RI) show significantly higher values in the DGF group at the level of upper interlobar artery (p=0.025) and medium interlobar artery (p=0.02). The CEUS investigation shows a greater region of interest (ROI) area (p=0.02) and lower values for wash-out area under the curve (WoAUC) (p=0.047) and respectively wash-in and wash-out area under the curve (WiWoAUC) (p=0.031) for the DGF group. The quality of fit (QoF) proved lower in the DGF group either for evaluation of global graft (p=0.012), cortex (p=0.025), or medulla (p=0.009).A significant relationship among all patients was found between the glomerular filtration rate (GFR) [ml/min] and the renal artery fall time (FT) [s] (p=0.012), WoAUC [a.u.] (p=0.03), and WiWoAUC [a.u.] (p=0.024). The arterial QoF [%] was associated with the arterial ROI area (p=0.048). CONCLUSIONS: Intensity CEUS parameters WoAUC and WiWoAUC may be useful to diagnose and follow-up grafts with delayed function. Additional studies on larger cohorts are required for the recommendation of CEUS as a routine evaluation of the transplanted kidney.

Difficulties in diagnosing HIV-associated nephropathy in kidney transplanted patients. The role of ultrasound and CEUS.

A 62-year-old woman who underwent kidney transplantation in 2014 was diagnosed with HIV infection in 2018. Grey scale and Doppler ultrasound evaluation revealed a normal aspect of the allograft. Contrast-enhanced ultrasound detected a quick cortical contrast uptake followed by a rapid cortical wash-out. This behavior was interpreted as a sign of inflammation. Ten months after ultrasound evaluation the graft presented severe disfunction and the patient was reintroduced into the hemodialysis program.

Accuracy of endoscopic ultrasound-guided biopsy of focal liver lesions.

AIM: Endoscopic ultrasound (EUS) has become an indispensable method for diagnosis in gastroenterology and new indications for EUS continue to emerge. However, there are limited data regarding the accuracy of EUS-guided biopsy of hepatic focal lesions. The aim of this study was to assess the diagnostic yield of EUS-guided fine needle aspiration (FNA) of focal liver lesions. MATERIAL AND METHODS: We conducted a prospective study in which patients with focal liver lesions, detected by transabdominal ultrasound and computed tomography or magnetic resonance imaging, underwent EUS-guided FNA to determine the diagnostic yield of the procedure. RESULTS: In 47/48 of patients, the results of EUS-FNA were positive for malignancy, while in one case the acquired fragment was insufficient for appropriate histological analysis. Diagnostic yield was 0.98. In 83% of the cases biopsies were taken from the left lobe and in 17% from the right lobe with the same technical success rate. The most common diagnosis was metastatic adenocarcinoma of the pancreas (26% cases) followed by cholangiocarcinoma (17% cases). Concurrent sampling of other sites in addition to the liver and/or primary tumor was realized in 35% of the cases, with results that correlated with the liver biopsy and with the primary tumor biopsy. We reported no immediate or long-term complications in any of the patients. CONCLUSIONS: EUS guided fine needle aspiration/biopsy of focal liver lesions is safe, provides a very high diagnostic accuracy and should not be considered only as a rescue method after failure of percutaneous guided biopsies.

Ultrasound as the first imaging method in severe lung disease. Considerations about a case of pulmonary tuberculosis and review of the literature.

Abdominal ultrasound (US) performed as a "primary imaging procedure" is an important diagnostic tool in gastroenterol-ogy. Expanding the routine investigation to the lower thoracic region might sometimes accelerate the diagnosis in inconclusive manifestations such as pulmonary pathology.US is a valuable tool in evaluating patients with breathing difficulties, chest pain, hypoxia, or chest trauma. This paper presents the particular situation of a patient hospitalized in the gastroenterology depart-ment, where the US identified significant pulmonary alterations and changed the final diagnosis from a gastrointestinal disease to pleuro-pulmonary tuberculosis. A brief review of literature is also included, in relation to chest US.

Shear-Wave Elastography Variability Analysis and Relation with Kidney Allograft Dysfunction: A Single-Center Study.

Shear-wave elastography (SWE) showed the absence or presence of significant differences among stable kidney allograft function and allograft dysfunction. We evaluated the variability of kidney allograft stiffness in relation to allograft dysfunction, respectively, in terms of a correlation of stiffness with patients' characteristics. A single-center prospective study on patients who had undergone renal transplantation was conducted between October 2017 and November 2018. Patients were clinically classified as having a stable allograft function or allograft dysfunction. SWE examinations performed by the same radiologist with a LOGIQ E9 were evaluated. Ten measurements were done for Young's modulus (kPa) at the level of allograft cortex and another ten at the level of medulla. Eighty-three SWE examinations from 63 patients, 69 stable allografts, and 14 allografts with dysfunction were included in the analysis. The intra-examinations stiffness showed high variability, with the quantile covariation coefficient ranging from 2.21% to 45.04%. The inter-examinations stiffness showed heterogeneity (from 28.66% to 42.38%). The kidney allograft cortex stiffness showed significantly higher values in cases with dysfunction (median = 28.70 kPa, interquartile range (IQR) = (25.68-31.98) kPa) as compared to those with stable function (median = 20.99 kPa, interquartile range = (16.08-27.68) kPa; p-value = 0.0142). Allograft tissue stiffness (both cortex and medulla) was significantly negatively correlated with body mass index (-0.44, p-value < 0.0001 for allograft cortex and -0.42, p-value = 0.0001 for allograft medulla), and positively correlated with Proteinuria/Creatinuria ratio (0.33, p-value = 0.0021 for allograft cortex and 0.28, p-value = 0.0105 for allograft medulla) but remained statistically significant only in cases with stable function. The cortical tissue stiffness proved significantly higher values for patients with allograft dysfunction as compared to patients with stable function, but to evolve as an additional tool for the evaluation of patients with a kidney transplant and to change the clinical practice, more extensive studies are needed.

Greyscale and contrast enhanced ultrasonography for characterization of gastric malignant tumors.

AIMS: To evaluate the utility of grey scale ultrasonography (US) and contrast enhanced ultrasonography (CEUS) for characterization of malignant gastric tumors. MATERIAL AND METHODS: The study was conducted prospectively and it included a number of 30 patients with malignant gastric tumors diagnosed through upper tract endoscopy and biopsy: 25 adenocarcinomas, 3 lymphomas, and 2 stromal tumors. All the patients were examined by US, followed immediately by CEUS, using both oral and intravenous contrast agents. CEUS assessed the dynamics of the contrast agent during the arterial phase and the venous phase. The distribution characteristics of the contrast agent inside the region of interest (ROI) were also evaluated. Twenty four patients underwent surgery. RESULTS: Adenocarcinomas presented heterogeneous enhancement with variable pattern, followed by a delayed wash-out in almost all of the situations. Lymphomas presented a variable pattern, intensity and homogeneity of the enhancement, followed by delayed wash-out. Stromal tumors showed early arterial intense and homogenous enhancement followed by moderate wash-out in venous phase. CONCLUSIONS: Grey scale US and CEUS are useful methods in characterizing gastric tumors and contribute to a more adequate evaluation of the lesions. The dynamics of the contrast agent may be suggestive for the anatomopathological nature of the tumor. Larger studies will be necessary in order to determine thepractical value of the method.

Splenic cystic lymphangioma with atypical ultrasound findings.

Splenic lymphangiomas are rare benign tumors occurring more frequently in children. Because of their asymptomatic growth, splenic lymphangiomas are usually suspected based on incidental findings, the diagnosis relying on different imaging techniques and requiring histological confirmation. The rarity of the disease and its atypical imaging findings make the diagnosis of splenic lymphangiomas challenging. We describe the case of an isolated splenic cystic lymphangioma affecting an elderly female patient. The patient was asymptomatic and the blood tests were normal. The tumor appeared on gray-scale ultrasound as an inhomogeneous, mostly hyperechoic septated mass, which is atypical for a cystic lymphangioma. Contrast-enhanced ultrasound and contrast-enhanced computed tomography suggested the benign nature of the tumor and narrowed the diagnosis. The tumor received histopathological confirmation after splenectomy. Various CT and MRI findings in splenic lymphangiomas have been described, but very few reports regarding CEUS exist to this point.

Non-Invasive Assessment of Inflammation and Treatment Response in Patients with Crohn's Disease and Ulcerative Colitis using Contrast-Enhanced Ultrasonography Quantification.

BACKGROUND AND AIM: Novel biological therapies in Crohn's disease (CD) or Ulcerative colitis (UC) require a proper follow-up for the assessment of bowel inflammation. While endoscopy is the standard method, the imaging techniques using contrast, particularly contrast enhanced ultrasonography (CEUS), are better tolerated by the patients and can be used more frequently. Our aim was to find the usefulness of dynamic CEUS quantification as compared to endoscopy in the assessment of disease activity and in the follow-up under therapy of the patients suffering from either CD or UC. METHOD: We have prospectively evaluated 67 patients with UC and 46 with CD, diagnosed by ileo-colonoscopy and biopsy, comparing the endoscopic scores with clinical scores, C reactive protein (CRP), intestinal wall thickness, layer scores after CEUS and TIC parameters (using SonoLiver® software - Imax, RT, TTP, mTT and AUC). For 25 patients with UC and 13 with CD we performed comparisons of the parameters before and after 3 months of treatment and correlated them with the changes in the endoscopic scores. RESULTS: For UC, time-intensity curves (TIC) volume parameters (AUC) correlated better with endoscopy (ρ=0.64) than the clinical score (ρ =0.62). Other parameters such as CRP and thickness showed significant but less strong correlation, while TIC flow parameters (RT, TTP and mTT) did not show a significant correlation. Results were similar for CD (ρ=0.64 for Imax vs ρ=0.58 for CDAI). The best predictor for endoscopic improvement in both UC and CD was ln(AUC), with a Wilcoxon Z score of 3.76 and 2.61, respectively. There was also a good correlation between the difference of its values and the difference in endoscopic scores before and after the treatment (rho is 0.68 in UC and 0.73 in CD).

Investigation of Renal Cell Carcinoma by Contrast-Enhanced Ultrasound- Predictive Value of Time Intensity Curve Analysis in Establishing Local Tumor Invasion and Stage: A Pilot Study.

PURPOSE: Contrast-enhanced ultrasound (CEUS) allows for real-time examination of signal intensity changes in a region of interest (ROI) and quantification of contrast agent kinetics. This study assessed the predictive ability of time-intensity curve (TIC) parameters for local tumor invasion and T stage of renal cell carcinoma (RCC). MATERIALS AND METHODS: Renal tumors in 41 patients were examined by CEUS. Thirty-two met the inclusion criteria, with a total of 33 tumors (27 clear cell, 4 chromophobe, and 2 papillary type I). Nineteen (57.6%) tumors were included in group A (stages pT1 and pT2) and 14 (42.4%) in group B (stage pT3). ROIs were established as: whole tumor (TuW); tumor area with the highest signal intensity (TuMAX) and renal cortex (Ref). The TIC param­eters for each ROI were calculated as below: peak signal intensity, time to peak (TTP), rise time (RT), and mean transit time (MTT). They were analyzed as a whole value for each ROI and as a ratio between the different ROIs. RESULTS: There were significant differences between the tumors invading and not invading the renal sinus fat for TTP (TuW/Ref) [0.98 (0.67-1.25) vs. 1.18 (1.08-1.3), P < .05]. For differentiation between groups A and B, the following ratios were proven as predictors by univariate regression analysis: TTP (TuMAX/TuW); MTT (Tu­MAX/TuW); RT (TuMAX/TuW) (P = .03, P = .01 and P = .02, respectively). The value derived from the Receiver Operating Characteristic (ROC) curve for RT (TuMAX/TuW) was 0.8 with sensitivity = 78.6%, specificity = 89.5%, and cutoff value of > 0.91. CONCLUSION: TIC parameters were predictors of locally noninvasive and invasive RCC.

Contrast enhanced ultrasonography (CEUS) in the characterization of tumor microcirculation. Validation of the procedure in the animal experimental model.

AIM: The aims of this study are the development of a contrast enhanced ultrasonography (CEUS) protocol for rats' evaluation and the assessment of the potential benefits of CEUS in Walker 256 tumor rats. MATERIAL AND METHOD: In the study were used 36 albino Wistar rats grafted subcutaneously with Walker 256 tumor. The implementation of the ultrasound (US) guided injection technique (30 subjects - group A) was performed between 4 to 8 weeks after implantation. The contrast agent (CA) - Sono Vue (Bracco) - was administered either into the lateral vein of the tail or directly into the heart under US guidance. The US validation, focusing on CEUS (6 subjects - group B) was realized at 4 to 6 weeks after implantation. The US procedures aimed to obtain morphological (2D), vascular (color Doppler and pulsed Doppler) and angiospecific functional data (CEUS). The Vevo 2100 equipment was used for US and Time Intensity Curves (TIC) were analyzed with Sonoliver (TomTec). The tumor specimens which were resected after the last study underwent a pathology exam. RESULTS: A number of 23 successfully CEUS explorations were performed in 17 subjects (11 in group A and 6 in group B). Nineteen rats could not be evaluated (in 8 cases the tumor was not viable; 4 subjects died during CA administration; in 4 cases the administration line could not be obtained). In group B, CEUS was performed in 6 subjects at 4 weeks after implantation and in 5 subjects at 6 weeks. The statistical analysis of the TIC parameters identified significant differences between the Time to Peak, mean Transit Time and Rise Time parameters of the muscles and those of the tumor. CONCLUSIONS: CEUS was easily implemented on the studied tumor model and is adequate for the evaluation of tumor vascularity. US guided intracardiac administration of the CA is an easy and reproducible procedure. If the examination is performed at defined time intervals it detects the alterations within the tumor circulatory bed.