Vitamin D Metabolites: Analytical Challenges and Clinical Relevance.

Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC-MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC-MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.

Acute Exercise-Induced Circulating Haematopoietic Stem and Progenitor Cells in Cardiac Patients - A Case Series.

BACKGROUND: Exercise-induced circulating haematopoietic stem and progenitor cell (HPC) number has been discussed in the context of regeneration in heart disease patients. OBJECTIVE: The aim of this pilot study was to compare the effect of different exercise protocols usually applied in cardiac rehabilitation on the number of acute, exercise-induced HPCs, related to potential mediators, e.g. biomarkers of sympathetic and oxidative stress, and inflammation. METHODS: This is a case series comprising seven patients suffering from coronary heart disease (CHD) undertaken at the Center for Ambulant Cardiac Rehabilitation. Patients (n=6) performed two exercise modes (constant-load, CLE; high-intensity interval, HIIE) in randomised order. Venous blood was drawn before and immediately after each test to assess CD34+/CD45+ HPC number by flow cytometry and biomarkers in blood plasma. The primary outcome was the change in HPC number, the secondary outcomes were changes in sympathetic/oxidative stress and markers of inflammation. RESULTS: Both exercise modes resulted in a non-significant increase in HPC number after exercise, even when the results of both tests were combined. Overall, free norepinephrine increased significantly and was positively related to exercise-induced HPC number (r=0.70, p<0.05). Markers of sympathetic activation (fNE), oxidative stress (myeloperoxidase) and inflammation (interleukin-6) significantly increased after CLE and HIIE with no difference between tests. CONCLUSIONS: Interestingly, acute CLE and HIIE did not stimulate significant HPC mobilisation in CHD, although both exercise modes elevated circulating concentrations of sympathetic activation. Haematopoietic stem and progenitor cell mobilisation could be blunted due to disease-related bone-marrow exhaustion.

[Oxidative stress in bipolar affective disorder]. / Oxidativer Stress bei bipolar affektiver Störung. (corrected).

The results of mortality studies have indicated that medical conditions, such as cardiovascular disease, obesity and diabetes are the most important causes of mortality among patients with bipolar disorder. The reasons for the increased incidence and mortality are not fully understood. Oxidative stress and an inadequate antioxidative system might be one missing link and could also help to further elucidate the pathophysiological basis of bipolar disorder. This article provides a comprehensive review of oxidative stress in general and about the existing data for bipolar disorder. In addition information is given about possible therapeutic strategies to reduce oxidative stress and the use in bipolar disorder.

Determinants of circulating calcitriol in cardiovascular disease.

Circulating calcitriol may contribute to the risk of cardiovascular disease (CVD), but its regulation in patients with CVD is poorly characterized. We therefore aimed to assess determinants of circulating calcitriol in these patients. We analyzed 2183 independent samples from a large cohort of patients scheduled for coronary angiography and 1727 independent samples from different other cohorts from patients with a wide range of CVDs, including heart transplant candidates, to quantify the association of different parameters with circulating calcitriol. We performed univariable and multivariable linear regression analyses using the mathematical function that fitted best with circulating calcitriol. In the multivariable analysis of the large single cohort, nine parameters remained significant, explaining 30.0 % (32.4 % after exclusion of 22 potential outliers) of the variation in circulating calcitriol (r=0.548). Log-transformed 25-hydroxyvitamin D [25(OH)D] and log-transformed glomerular filtration rate were the strongest predictors, explaining 17.6 % and 6.6 %, respectively, of the variation in calcitriol. In the analysis of the combined other cohorts, including heart transplant candidates, the multivariable model explained a total of 42.6 % (46.1 % after exclusion of 21 potential outliers) of the variation in calcitriol (r=0.653) with log-transformed fibroblast growth factor-23 and log-transformed 25(OH)D explaining 29.0 % and 6.2 %, respectively. Circulating 25(OH)D was positively and FGF-23 inversely associated with circulating calcitriol. Although significant, PTH was only a weak predictor of calcitriol in both analyses (<2.5 %). In patients with CVD, FGF-23 and 25(OH)D are important independent determinants of circulating calcitriol. The relative importance of these two parameters may vary according to CVD severity. Future studies should focus on the clinical importance of regulating circulating calcitriol by different parameters.

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

BACKGROUND AND PURPOSE: Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine-related metabolic alterations. METHODS: Oxidative stress markers malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), carbonylated proteins, parameters of associated nitric oxide stress, inflammation, lipid- and glucose-metabolism were determined in the interictal phase in female patients with migraine and controls. RESULTS: We found significantly increased HNE levels in female migraineurs compared with controls. Logistic regression analyses of HNE revealed an odds ratio for migraine of 4.55. HNE showed significant correlations with the nitric oxide pathway, the insulin- and the lipid-metabolism. CONCLUSIONS: We show here that increased oxidative stress is associated with migraine and contributes to migraine-related metabolic risk like nitrosative stress, an atherogenic lipid profile and hyperinsulinemia. Our data suggest that oxidative stress may represent a key event in the pathophysiology of migraine and a suitable therapeutic target.

Sex differences in zonulin in affective disorders and associations with current mood symptoms.

INTRODUCTION: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.

Oxidative stress: Determination of 4-hydroxy-2-nonenal by gas chromatography/mass spectrometry in human and rat plasma.

The lipid peroxidation product 4-hydroxynonenal (HNE) is a biomarker of oxidative stress which is essentially involved in the pathophysiology of many diseases. The analysis of HNE is challenging because this aldehyde is extremely reactive and thus unstable. Hence, we adopted a gas chromatography-mass spectrometry (GC-MS) method based on derivatization of HNE with pentafluorobenzyl-hydroxylamine-HCl followed by trimethylsilylation to trimethylsilyl ethers. Ions representative for a negative ion chemical ionization mode were recorded at m/z = 152 for HNE and at m/z = 162 for the deuterated analogon (HNE-d11) as internal standard. This excellent stable and precise GC-MS method was carefully validated for HNE, and showed good linearity (r(2) = 0.998), and high specificity and sensitivity. Within-day precisions were 4.4-6.1% and between-day precisions were 5.2-10.2%. Accuracies were between 99% and 104% for the whole calibration range (2.5-250 nmol/L) of HNE. To examine the versatility of this modified GC-MS method, we analyzed HNE in ethylenediaminetetraacetic acid (EDTA) plasma in a well-defined collective of migraine patients; recently published. The results underline our former observations that women with migraine are afflicted with increased levels of HNE. Patients with thyroidal dysfunction showed no significant HNE alterations. This was confirmed by normal HNE EDTA plasma levels in hyper- und hypothyroid Sprague-Dawley rats. Taken together, the GC-MS method presented herein is of excellent quality to record oxidative stress-related bioactive HNE levels. This is important for a reorientation of oxidative stress analytics in other human diseases first of atherosclerosis and cancer.

Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages.

BACKGROUND: Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification. AIM: To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS). METHODS: Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes. RESULTS: Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20 years had significantly increased ALT levels if they were homozygote with the G allele. CONCLUSIONS: The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention.

CT-guided irreversible electroporation in an acute porcine liver model: effect of previous transarterial iodized oil tissue marking on technical parameters, 3D computed tomographic rendering of the electroporation zone, and histopathology.

PURPOSE: To evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance. METHODS: After Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann-Whitney test. Histopathological differences were assessed. RESULTS: Mean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm(3), and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm(3), and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone. CONCLUSION: There is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

Sphere-enhanced microwave ablation (sMWA) versus bland microwave ablation (bMWA): technical parameters, specific CT 3D rendering and histopathology.

PURPOSE: This study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA). METHODS: In six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 µm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output, ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL). RESULTS: Resulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm(3) for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm(3) for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features. CONCLUSIONS: Specific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION: Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS: Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS: The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION: Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

Toward knowledge-based liver surgery: holistic information processing for surgical decision support.

PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers worldwide. Given the diversity of options for liver cancer therapy, the choice of treatment depends on various parameters including patient condition, tumor size and location, liver function, and previous interventions. To address this issue, we present the first approach to treatment strategy planning based on holistic processing of patient-individual data, practical knowledge (i.e., case knowledge), and factual knowledge (e.g., clinical guidelines and studies). METHODS: The contributions of this paper are as follows: (1) a formalized dynamic patient model that incorporates all the heterogeneous data acquired for a specific patient in the whole course of disease treatment; (2) a concept for formalizing factual knowledge; and (3) a technical infrastructure that enables storing, accessing, and processing of heterogeneous data to support clinical decision making. RESULTS: Our patient model, which currently covers 602 patient-individual parameters, was successfully instantiated for 184 patients. It was sufficiently comprehensive to serve as the basis for the formalization of a total of 72 rules extracted from studies on patients with colorectal liver metastases or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses, the system derived an average of [Formula: see text] assertions per patient. CONCLUSION: The proposed concept paves the way for holistic treatment strategy planning by enabling joint storing and processing of heterogeneous data from various information sources.

MITK-US: real-time ultrasound support within MITK.

PURPOSE: Intra-procedural acquisition of the patient anatomy is a key technique in the context of computer-assisted interventions (CAI). Ultrasound (US) offers major advantages as an interventional imaging modality because it is real time and low cost and does not expose the patient or physician to harmful radiation. To advance US-related research, the purpose of this paper was to develop and evaluate an open-source framework for US-based CAI applications. MATERIALS AND METHODS: We developed the open-source software module MITK-US for acquiring and processing US data as part of the well-known medical imaging interaction toolkit (MITK). To demonstrate its utility, we applied the module to implement a new concept for US-guided needle insertion. Performance of the US module was assessed by determining frame rate and latency for both a simple sample application and a more complex needle guidance system. RESULTS: MITK-US has successfully been used to implement both sample applications. Modern laptops achieve frame rates above 24 frames per second. Latency is measured to be approximately 250 ms or less. CONCLUSION: MITK-US can be considered a viable rapid prototyping environment for US-based CAI applications.

Measurement of total and free malondialdehyde by gas-chromatography mass spectrometry--comparison with high-performance liquid chromatography methology.

Malondialdehyde (MDA) is considered to be a biomarker for enzymatic degradation and lipid peroxidation of polyunsaturated fatty acids. Usually, MDA determination from different biological materials is performed by reaction with thiobarbituric acid (TBA) followed by high-performance liquid chromatography (HPLC) analysis and fluorometric detection. As this method lacks specificity and sensitivity, we developed a gas chromatography-mass spectrometry (GC-MS) method based on derivatization of MDA with 2,4-dinitrophenylhydrazine. Representative ions in negative ion chemical ionization (NICI) mode were recorded at m/z 204 for MDA and at m/z 206 for the deuterated analogon (MDA-d2) as internal standard. This stable and precise GC-MS method showed good linearity (r² = 0.999) and higher specificity and sensitivity than the HPLC method and was validated for both total MDA (t-MDA) and free MDA (f-MDA). Within-day precisions were 1.8-5.4%, between-day precisions were 4.8-9.2%; and accuracies were between 99% and 101% for the whole calibration range (0.156-5.0 µmol/L for t-MDA and 0.039-0.625 µmol/L for f-MDA). Although comparison of t-MDA levels from GC-MS and HPLC results using Passing-Bablok regression analysis as well as Bland-Altman plot showed a correlation of the data, a tendency to increased results for the HPLC values was detectable, due to possible formation of unspecific products of the TBA reaction.

High risk vs. "metabolically healthy" phenotype in juvenile obesity - neck subcutaneous adipose tissue and serum uric acid are clinically relevant.

BACKGROUND: Since obesity and its associated co-morbidities do not only have effect on the individual patient, but also on society and the health system, it is of great importance to investigate this lifestyle-disease. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese patients as compared to healthy normal weight children and adolescents by means of a comprehensive anthropometric, laboratory and sonomorphological vascular assessment. MATERIALS AND METHODS: 299 study participants were derived from the prospective, observational study STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Arteriosclerosis). Standard anthropometric data were obtained for each subject. This study comprised different diagnostic steps: extended anthropometry (Lipometer®), carotid artery ultrasound, various laboratory measurements, blood pressure measurement, oral glucose tolerance test. Ow/ob juveniles were classified as "metabolically healthy" (no laboratory criteria of metabolic syndrome fulfilled) vs. "metabolically unhealthy" (≥ 3 criteria of metabolic syndrome). Results underwent statistical evaluation, including t-test or Mann-Whitney U-test, regression analysis and a p-value < 0.05 was considered statistically significant. RESULTS AND DISCUSSION: In the study's central European cohort only about 16% (n=48/299) of the overweight/obese juveniles can be regarded as metabolically healthy. About 36% (n=108/299) of the overweight/obese patients fulfilled the criteria for metabolic syndrome. High visceral fat stores (p<0.001) and their clinical surrogate waist circumference (p<0.001) determine an adverse metabolic phenotype. Several parameters, including uric acid (p<0.001), adiponectin (p<0.05), insulin resistance (HOMA-Index, p<0.001), nuchal SAT thickness (p<0.001), arteriosclerosis of the carotids (p<0.001), and others are responsible for the distinction between -metabolically healthy and unhealthy juveniles. Nevertheless, "healthy obesity" only defines a sub-phenotype of a disease effecting rising numbers of young patients. CONCLUSIONS: Since obesity in children and adolescents is not a consistent entity, it remains crucial to differ between metabolically healthy and unhealthy obese children in order to achieve appropriate intervention and prevention for our patients.

MITK diffusion imaging.

BACKGROUND: Diffusion-MRI provides a unique window on brain anatomy and insights into aspects of tissue structure in living humans that could not be studied previously. There is a major effort in this rapidly evolving field of research to develop the algorithmic tools necessary to cope with the complexity of the datasets. OBJECTIVES: This work illustrates our strategy that encompasses the development of a modularized and open software tool for data processing, visualization and interactive exploration in diffusion imaging research and aims at reinforcing sustainable evaluation and progress in the field. METHODS: In this paper, the usability and capabilities of a new application and toolkit component of the Medical Imaging and Interaction Toolkit (MITK, www.mitk.org), MITK-DI, are demonstrated using in-vivo datasets. RESULTS: MITK-DI provides a comprehensive software framework for high-performance data processing, analysis and interactive data exploration, which is designed in a modular, extensible fashion (using CTK) and in adherence to widely accepted coding standards (e.g. ITK, VTK). MITK-DI is available both as an open source software development toolkit and as a ready-to-use installable application. CONCLUSIONS: The open source release of the modular MITK-DI tools will increase verifiability and comparability within the research community and will also be an important step towards bringing many of the current techniques towards clinical application.

Super-micro-bland particle embolization combined with RF-ablation: angiographic, macroscopic and microscopic features in porcine kidneys.

PURPOSE: To describe angiographic, macroscopic and microscopic features of super-micro-bland particle embolization in combination with RF-ablation in kidneys. Thereby, a special focus was given on the impact of the sequence of the different procedural steps. MATERIALS AND METHODS: In ten pigs, super-micro-bland particle embolization combined with RF-ablation was carried out. Super-micro-bland embolization was performed with spherical particles of very small size and tight calibration (40 ± 10 µm). In the left kidneys, RF-ablations were performed before embolization (I). In the right kidneys, RF-ablations were performed after embolization (II). The animals were killed three hours after the procedures. Angiographic (e.g. vessel architecture), macroscopic (e.g. long and short axes of the RF-ablations) and microscopic (e.g. particle distribution) study goals were defined. RESULTS: Angiography detected almost no vessels in the center of the RF-ablations in I. In II, angiography could not define the RF-ablations. Macroscopy detected significantly larger long and short axes of the RF-ablations in II compared to I (52.2 ± 3.2 mm vs. 45.3 ± 6.9 mm [P<0.05] and 25.1 ± 3.5mm vs. 20.0 ± 1.9 mm [P<0.01], respectively). Microscopy detected irregular particle distribution at the rim of the RF-ablations in I. In II, microscopy detected homogeneous particle distribution at the rim of the RF-ablations. Microscopy detected no particles in the center of the RF-ablations in I and II. CONCLUSION: The sequence of the different procedural steps of super-micro-bland particle embolization combined with RF-ablation impacts angiographic, macroscopic and microscopic features in kidneys in the acute setting.

Microwave ablation of porcine kidneys in vivo: effect of two different ablation modes ("temperature control" and "power control") on procedural outcome.

PURPOSE: This study was designed to analyze the effect of two different ablation modes ("temperature control" and "power control") of a microwave system on procedural outcome in porcine kidneys in vivo. METHODS: A commercially available microwave system (Avecure Microwave Generator; MedWaves, San Diego, CA) was used. The system offers the possibility to ablate with two different ablation modes: temperature control and power control. Thirty-two microwave ablations were performed in 16 kidneys of 8 pigs. In each animal, one kidney was ablated twice by applying temperature control (ablation duration set point at 60 s, ablation temperature set point at 96°C, automatic power set point; group I). The other kidney was ablated twice by applying power control (ablation duration set point at 60 s, ablation temperature set point at 96°C, ablation power set point at 24 W; group II). Procedural outcome was analyzed: (1) technical success (e.g., system failures, duration of the ablation cycle), and (2) ablation geometry (e.g., long axis diameter, short axis diameter, and circularity). RESULTS: System failures occurred in 0% in group I and 13% in group II. Duration of the ablation cycle was 60±0 s in group I and 102±21 s in group II. Long axis diameter was 20.3±4.6 mm in group I and 19.8±3.5 mm in group II (not significant (NS)). Short axis diameter was 10.3±2 mm in group I and 10.5±2.4 mm in group II (NS). Circularity was 0.5±0.1 in group I and 0.5±0.1 in group II (NS). CONCLUSIONS: Microwave ablations performed with temperature control showed fewer system failures and were finished faster. Both ablation modes demonstrated no significant differences with respect to ablation geometry.

Renal artery embolization combined with radiofrequency ablation in a porcine kidney model: effect of small and narrowly calibrated microparticles as embolization material on coagulation diameter, volume, and shape.

The purpose of this study was to evaluate the effect of renal artery embolization with small and narrowly calibrated microparticles on the coagulation diameter, volume, and shape of radiofrequency ablations (RFAs) in porcine kidneys. Forty-eight RFAs were performed in 24 kidneys of 12 pigs. In 6 animals, bilateral renal artery embolization was performed with small and narrowly calibrated microparticles. Upper and lower kidney poles were ablated with identical system parameters. Applying three-dimensional segmentation software, RFAs were segmented on registered 2 mm-thin macroscopic slices. Length, depth, width, volume_segmented, and volume_calculated were determined to describe the size of the RFAs. To evaluate the shape of the RFAs, depth-to-width ratio (perfect symmetry-to-lesion length was indicated by a ratio of 1), sphericity ratio (perfect sphere was indicated by a sphericity ratio of 1), eccentricity (perfect sphere was indicated by an eccentricity of 0), and circularity (perfect circle was indicated by a circularity of 1) were determined. Embolized compared with nonembolized RFAs showed significantly greater depth (23.4 ± 3.6 vs. 17.2 ± 1.8 mm; p < 0.001) and width (20.1 ± 2.9 vs. 12.6 ± 3.7 mm; p < 0.001); significantly larger volume_segmented (8.6 ± 3.2 vs. 3.0 ± 0.7 ml; p < 0.001) and volume_calculated (8.4 ± 3.0 ml vs. 3.3 ± 1.1 ml; p < 0.001); significantly lower depth-to-width (1.17 ± 0.10 vs. 1.48 ± 0.44; p < 0.05), sphericity (1.55 ± 0.44 vs. 1.96 ± 0.43; p < 0.01), and eccentricity (0.84 ± 0.61 vs. 1.73 ± 0.91; p < 0.01) ratios; and significantly greater circularity (0.62 ± 0.14 vs. 0.45 ± 0.16; p < 0.01). Renal artery embolization with small and narrowly calibrated microparticles affected the coagulation diameter, volume, and shape of RFAs in porcine kidneys. Embolized RFAs were significantly larger and more spherical compared with nonembolized RFAs.