Quantitative Analysis of the Time-Intensity Curve of Contrast-Enhanced Ultrasound of the Liver: Differentiation of Benign and Malignant Liver Lesions.

BACKGROUND: To evaluate the diagnostic accuracy of quantitative perfusion parameters in contrast-enhanced ultrasound to differentiate malignant from benign liver lesions. METHODS: In this retrospective study 134 patients with a total of 139 focal liver lesions were included who underwent contrast enhanced ultrasound (CEUS) between 2008 and 2018. All examinations were performed by a single radiologist with more than 15 years of experience using a second-generation blood pool contrast agent. The standard of reference was histopathology (n = 60), MRI or CT (n = 75) or long-term CEUS follow up (n = 4). For post processing regions of interests were drawn both inside of target lesions and the liver background. Time-intensity curves were fitted to the CEUS DICOM dataset and the rise time (RT) of contrast enhancement until peak enhancement, and a late-phase ratio (LPR) of signal intensities within the lesion and the background tissue, were calculated and compared between malignant and benign liver lesion using Student's t-test. Quantitative parameters were evaluated with respect to their diagnostic accuracy using receiver operator characteristic curves. Both features were then combined in a logistic regression model and the cumulated accuracy was assessed. RESULTS: RT of benign lesions (14.8 ± 13.8 s, p = 0.005), and in a subgroup analysis, particular hemangiomas (23.4 ± 16.2 s, p < 0.001) differed significantly to malignant lesions (9.3 ± 3.8 s). The LPR was significantly different between benign (1.59 ± 1.59, p < 0.001) and malignant lesions (0.38 ± 0.23). Logistic regression analysis with RT and LPR combined showed a high diagnostic accuracy of quantitative CEUS parameters with areas under the curve of 0.923 (benign vs. malignant) and 0.929 (hemangioma vs. malignant. CONCLUSIONS: Quantified CEUS parameters are helpful to differentiate malignant from benign liver lesions, in particular in case of atypical hemangiomas.

Diagnostic Value of CEUS Prompting Liver Biopsy: Histopathological Correlation of Hepatic Lesions with Ambiguous Imaging Characteristics.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) allows for dynamic analysis of vascularization patterns of unclear hepatic lesions. Our study aimed to evaluate the diagnostic performance of CEUS for further characterizing suspicious liver lesions by comparing findings from CEUS examinations with corresponding histopathology. METHODS: Between 2005 and 2016, 160 patients with unclear liver lesions underwent CEUS followed by liver biopsy. All examinations were performed by an experienced consultant radiologist (EFSUMB Level 3) and included native B-mode ultrasound, Color Doppler, and CEUS. A second-generation blood pool contrast agent was applied for CEUS. RESULTS: CEUS was successfully performed in all patients without occurrence of any adverse side effects. CEUS showed a sensitivity of 94.5%, a specificity of 70.6%, a true positive rate of 87.3%, and a true negative rate of 85.7% compared to histopathological results as the reference standard. CONCLUSIONS: CEUS represents a safe imaging modality with a high diagnostic accuracy in assessing both-benign and malignant-liver lesions compared to corresponding histopathological results.

Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

Non-diabetic chronic kidney disease influences retinal microvasculature.

BACKGROUND: Chronic kidney disease (CKD) is characterized by increased cerebrovascular risk. Retinal vessel analysis (RVA) is an accepted measure of the retinal microvasculature, mirrors hypertension and cardiovascular morbidity. Epidemiological studies demonstrate narrower retinal arterioles with declining renal function. The effect of CKD on the retinal microcirculation remains uncertain. METHODS: RVA was performed in 34 non-diabetic CKD patients and 33 age-matched volunteers with normal renal function. Retinal photographs were digitized, vascular lumen diameters measured and the ratio of retinal arteriolar and venular lumen diameters (AVR) calculated. Office blood pressure (BP) was measured and cardiovascular risk factors assessed. RESULTS: AVR was lower in CKD patients as compared to age-matched volunteers (0.77 +/- 0.05 vs. 0.86 +/- 0.06; p < 0.05). In particular, retinal arterioles were narrower in CKD patients as compared to volunteers (169.6 +/- 20.4 vs. 189.5 +/- 14.2 microm; p < 0.01). In CKD, estimated glomerular filtration rate, BP and renin-angiotensin system blocker independently predicted AVR. Moreover, retinal arteriolar diameter independently predicted renal function (beta = 0.33; p < 0.05). CONCLUSION: CKD narrowed retinal arterioles suggesting an extended effect of CKD on the cerebral microvasculature. This study shows that in CKD patients, renal function, BP status and renin-angiotensin system blockade independently predict AVR as a marker for microvascular damage and that retinal microvasculature can predict renal function.

Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy.

BACKGROUND: Inflammation contributes to cardiovascular complications in type 2 diabetes, which are often characterized by microvascular alterations. We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy. METHODS: MRP8/14 was measured in 43 patients with type 2 diabetes and nephropathy. Additionally, the inflammatory markers Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) were quantified. To detect microvascular alterations proteinuria and retinal vessel caliber were used as classical and novel marker, respectively. Proteinuria was quantified by protein-creatinine ratio (PCR); retinal vessel caliber was quantified after retina photography on digitalized retina pictures. RESULTS: MRP8/14 was positively associated with inflammation (r = 0.57), proteinuria (r = 0.40) and retinal arterial caliber (r = 0.48). Type 2 diabetic patients with MRP8/14 values above the median of 5.8 microg/ml demonstrated higher proteinuria and larger retinal artery caliber than patients with MRP8/14 values below the median (logPCR: -0.51 +/- 0.52 versus -0.96 +/- 0.46, P < 0.01; retinal artery lumen (microm): 178.3 +/- 14.1 versus 162.7 +/- 14.9 P < 0.01). Both groups did not differ with regard to metabolic factors and blood pressure. MRP8/14 was an independent predictor of retinal artery caliber in multivariate stepwise regression analysis (beta = 0.607) and was positively associated with IL-6 (r = 0.57, P < 0.001) and TNF-alpha (r = 0.36, P < 0.05). CONCLUSION: MRP8/14--a marker for transendothelial migration--describes not only the state of inflammation in diabetic nephropathy, but additionally the degree of microvascular alterations in the glomerular and retinal bed. Therefore, MRP8/14 may be a potentially selective novel biomarker for microcirculatory defects in diabetic nephropathy.