Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. METHODS: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36). FINDINGS: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by -94·21 ng/mL (95% interval estimate -161·83 to -35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by -72·02 ng/mL (-135·47 to -19·52) and increased abstinence from cannabis by 0·27 days per week (-0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. INTERPRETATION: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. FUNDING: Medical Research Council.

Treatment Setting Influences Treatment Modality for Urinary Stone Disease.

OBJECTIVE: To determine whether selection of treatment modality for urinary stone disease differs between primary and outreach healthcare centers, and if patient rurality predicts treatment modality. METHODS: We retrospectively evaluated Extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS) procedural data from the Iowa Office of Statewide Clinical Education Programs (OSCEP) and Iowa Hospital Association (IHA) databases from 2007 to 2014. Geographical data was used to analyze travel metrics and patient proximity to sites of stone treatment. Rural-urban commuting area (RUCA) codes were used to characterize patient rurality. Chi-square tests and t tests were used to compare ESWL and URS patients, and multilevel logistic regression model was used to assess influence of treatment setting on surgical modality. RESULTS: A total of 18,831 stone procedures were performed by urologists in Iowa on patients from Iowa (10,495 URS; 8336 ESWL). Around 2630 procedures occurred at outreach centers. Ureteroscopy comprised 59.7% of procedures at primary centers, but only 31.2% at outreach centers. On multilevel analysis, outreach location was associated with 2.236 OR toward ESWL (P <.001). Individual physician treatment patterns accounted for 32% of treatment variation. Patient rurality was not significantly associated with treatment modality as an independent factor (P = .879). CONCLUSIONS: Wide variation exists in urolithiasis treatment modality selection between outreach and primary centers. Outreach locations perform a significantly higher frequency of ESWL compared to URS, and much of the variation in treatment selection (32%) arises from individual physician practice patterns.

Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality.

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As such, there is a need for raw material tests to identify not only the type of oil but its quality. This paper describes two approaches to rapidly identifying and classifying lavender oil. First, the ISO Standard 11024 test method was evaluated in order to determine its suitability to assess lavender oil quality but due to its targeted and simplistic approach, it has the potential to miss classify oil quality. Second, utilizing the data generated by the ISO Standard 11024 test methodology, an untargeted chemometric predicative model was developed in order to rapidly assess and characterize lavender oils (Lavandulaangustifolia L.) for geographical/environmental adulteration that impact quality. Of the 170 compounds identified as per the ISO Standard 11024 test method utilizing GC-MS analyses, 15 unique compounds that greatly differentiate between the two classes of lavender were identified. Using these 15 compounds, a predicative multivariate chemometric model was developed that enabled lavender oil samples to be reliably differentiated based on quality. A misclassification analysis was performed and it was found that the predictions were sound (100% matching rate). Such an approach will enable producers, distributers, suppliers and manufactures to rapidly screen lavender essential oil. The authors concede that the validation and implementation of such an approach is more difficult than a conventional chromatographic assay. However, the rapid, reliable and less problematic screening is vastly superior and easily justifies any early implementation validation difficulties and costs.

A New Method for the Fast Analysis of Trihalomethanes in Tap and Recycled Waters Using Headspace Gas Chromatography with Micro-Electron Capture Detection.

Chemical disinfection of water supplies brings significant public health benefits by reducing microbial contamination. The process can however, result in the formation of toxic compounds through interactions between disinfectants and organic material in the source water. These new compounds are termed disinfection by-products (DBPs). The most common are the trihalomethanes (THMs) such as trichloromethane (chloroform), dichlorobromomethane, chlorodibromomethane and tribromomethane (bromoform); these are commonly reported as a single value for total trihalomethanes (TTHMs). Analysis of DBPs is commonly performed via time- and solvent-intensive sample preparation techniques such as liquid-liquid and solid phase extraction. In this study, a method using headspace gas chromatography with micro-electron capture detection was developed and applied for the analysis of THMs in drinking and recycled waters from across Melbourne (Victoria, Australia). The method allowed almost complete removal of the sample preparation step whilst maintaining trace level detection limits (>1 ppb). All drinking water samples had TTHM concentrations below the Australian regulatory limit of 250 µg/L but some were above the U.S. EPA limit of 60 µg/L. The highest TTHM concentration was 67.2 µg/L and lowest 22.9 µg/L. For recycled water, samples taken directly from treatment plants held significantly higher concentrations (153.2 µg/L TTHM) compared to samples from final use locations (4.9-9.3 µg/L).

Are deficits in cognition associated with psychotic-like experiences after cannabis?

Not all individuals who smoke cannabis report psychotic-like experiences. Given that risk factors for psychotic disorders are multifaceted, precipitating factors to psychotic-like experiences after cannabis are likely to be equally complex. Reduced neurocognitive performance is associated with both psychosis risk and cannabis use. Therefore, it is possible cognitive performance may differentiate those who report psychotic-like experiences after cannabis from those who do not. We determined whether those reporting psychotic/dysphoric experiences after cannabis had reduced neurocognitive performance compared to those reporting primarily euphoric experiences. METHODS: Participants were recruited on the basis of responses to the cannabis high captured by the Psychosis-Dysphoric and Euphoric experiences subscales from the Cannabis Experiences Questionnaire (CEQ). RESULTS: Compared to participants reporting primarily euphoric cannabis experiences (n = 36; 44% male; mean age (SD) = 28 (9) years), those who reported psychotic/dysphoric experiences (n = 40; 45% male; mean age (SD) = 26 (5) years) demonstrated significantly faster responses to a trial and error learning task. In the presence of distracters, those with psychotic/dysphoric experiences after cannabis made more errors on a Continuous Performance Task. CONCLUSIONS: Those who report psychotic/dysphoric experiences after cannabis have subtle inefficiencies in their cognitive processes. The multiple factors which predict vulnerability to psychotic-like experiences after cannabis require further investigation.

Widespread polybrominated diphenyl ether (PBDE) contamination of urban soils in Melbourne, Australia.

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in a variety of materials and products. PBDEs have been shown to accumulate in the environment and human populations while exhibiting a range of toxic effects. In this study, surface soil samples from 30 sites in the city of Melbourne, Australia, were analysed for PBDEs. Eight congeners of environmental concern (BDE-28, -47, -99, -100, -153, -154 -183 and -209) were assessed using selective pressurized liquid extraction (S-PLE) and gas chromatography coupled to triple quadrupole mass spectrometry (GC-MS/MS). PBDEs were detected in 29/30 samples with Σ8PBDE soil concentrations ranging nd-13,200 ng/g dw and Σ7PBDEs (excluding BDE-209) levels of nd-70.5 ng/g dw. Soils from waste disposal sites (n = 6) contained the highest median Σ7PBDE and Σ8PBDE concentrations, followed by manufacturing sites (n = 18) and then non-source sites (n = 6). Electronics recycling facilities contained the greatest levels of Σ8PBDEs by a significant margin (p < 0.05) to indicate that these industries are a potential source of contamination. BDE-209 was the dominant congener, contributing an average of 75.5% to Σ8PBDEs soil concentrations, followed by BDE-47, BDE-99 and BDE-183 at 7.90, 5.64 and 4.31%, respectively. Congener profiles reflected global estimates of Deca-BDE, Octa-BDE and Penta- BDE commercial production, with the most significant congener correlation existing between BDE-47 and BDE-99 (p < 0.001, r = 0.943). This first assessment of PBDEs in Melbourne soils indicates widespread contamination of the urban environment, including locations where direct sources to soil are not clear.

Comparison of rapid solvent extraction systems for the GC-MS/MS characterization of polycyclic aromatic hydrocarbons in aged, contaminated soil.

Polycyclic aromatic hydrocarbons (PAHs) are a major class of organic hydrocarbons with high molecular weight that originate from both natural and anthropogenic sources. Sixteen PAHs are included in the U.S Environmental Protection agency list of priority pollutants due to their mutagenic, carcinogenic, toxic and teratogenic properties. In this study, the development and optimization of a simplified and rapid solvent extraction for the characterisation of 16 USEPA priority poly aromatic hydrocarbons (PAHs) in aged contaminated soils was established with subsequent analysis by GC-MS/MS. •Five different extraction solvent systems: dichloromethane: acetone, chloroform: methanol, dichloromethane, acetone: hexane and hexane were assessed in terms of their ability to extract PAHs from aged PAH-contaminated soils.•Highest PAH concentrations were extracted using acetone: hexane and chloroform: methanol. Given the greater toxicity associated with chloroform: methanol, acetone: hexane appears the best choice of solvent extraction system.•This protocol enables efficient extraction of PAHs from aged weathered soils.

A candidate reference method using ICP-MS for sweat chloride quantification.

BACKGROUND: The aim of the study was to develop a method for sweat chloride (Cl) quantification using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to present to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) as a candidate reference method for the diagnosis of cystic fibrosis (CF). METHODS: Calibration standards were prepared from sodium chloride (NaCl) to cover the expected range of sweat Cl values. Germanium (Ge) and scandium (Sc) were selected as on-line (instrument based) internal standards (IS) and gallium (Ga) as the off-line (sample based) IS. The method was validated through linearity, accuracy and imprecision studies as well as enrolment into the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) for sweat electrolyte testing. RESULTS: Two variations of the ICP-MS method were developed, an on-line and off-line IS, and compared. Linearity was determined up to 225 mmol/L with a limit of quantitation of 7.4 mmol/L. The off-line IS demonstrated increased accuracy through the RCPAQAP performance assessment (CV of 1.9%, bias of 1.5 mmol/L) in comparison to the on-line IS (CV of 8.0%, bias of 3.8 mmol/L). Paired t-tests confirmed no significant differences between sample means of the two IS methods (p=0.53) or from each method against the RCPAQAP target values (p=0.08 and p=0.29). CONCLUSIONS: Both on and off-line IS methods generated highly reproducible results and excellent linear comparison to the RCPAQAP target results. ICP-MS is a highly accurate method with a low limit of quantitation for sweat Cl analysis and should be recognised as a candidate reference method for the monitoring and diagnosis of CF. Laboratories that currently practice sweat Cl analysis using ICP-MS should include an off-line IS to help negate any pre-analytical errors.

Model-guided therapy for hepatocellular carcinoma: a role for information technology in predictive, preventive and personalized medicine.

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM.

Analysis of the volatile organic compounds from leaves, flower spikes, and nectar of Australian grown Agastache rugosa.

BACKGROUND: The foraging choices of honey bees are influenced by many factors, such as floral aroma. The composition of volatile compounds influences the bioactivity of the aromatic plants and honey produced from them. In this study, Agastache rugosa was evaluated as part of a project to select the most promising medicinal plant species for production of bioactive honey. METHODS: Headspace solid-phase microextraction HS-SPME /GC-MS was optimized to identify the volatile bioactive compounds in the leaves, flower spikes, and for the first time, the flower nectar of Australian grown A. rugosa. RESULTS: Methyl chavicol (= estragole) was the predominant headspace volatile compound in the flowers with nectar, flower spikes, and leaves, with a total of 97.16%, 96.74% and 94.35%, respectively. Current results indicate that HS-SPME/GC-MS could be a useful tool for screening estragole concentration in herbal products. CONCLUSION: Recently, estragole was suspected to be carcinogenic and genotoxic, according to the European Union Committee on Herbal Medicinal Products. Further studies are needed on safe daily intake of Agastache as herbal tea or honey, as well as for topical uses.

Assessing the hydrocarbon degrading potential of indigenous bacteria isolated from crude oil tank bottom sludge and hydrocarbon-contaminated soil of Azzawiya oil refinery, Libya.

The disposal of hazardous crude oil tank bottom sludge (COTBS) represents a significant waste management burden for South Mediterranean countries. Currently, the application of biological systems (bioremediation) for the treatment of COTBS is not widely practiced in these countries. Therefore, this study aims to develop the potential for bioremediation in this region through assessment of the abilities of indigenous hydrocarbonoclastic microorganisms from Libyan Hamada COTBS for the biotreatment of Libyan COTBS-contaminated environments. Bacteria were isolated from COTBS, COTBS-contaminated soil, treated COTBS-contaminated soil, and uncontaminated soil using Bushnell Hass medium amended with Hamada crude oil (1 %) as the main carbon source. Overall, 49 bacterial phenotypes were detected, and their individual abilities to degrade Hamada crude and selected COBTS fractions (naphthalene, phenanthrene, eicosane, octadecane and hexane) were evaluated using MT2 Biolog plates. Analyses using average well colour development showed that ~90 % of bacterial isolates were capable of utilizing representative aromatic fractions compared to 51 % utilization of representative aliphatics. Interestingly, more hydrocarbonoclastic isolates were obtained from treated contaminated soils (42.9 %) than from COTBS (26.5 %) or COTBS-contaminated (30.6 %) and control (0 %) soils. Hierarchical cluster analysis (HCA) separated the isolates into two clusters with microorganisms in cluster 2 being 1.7- to 5-fold better at hydrocarbon degradation than those in cluster 1. Cluster 2 isolates belonged to the putative hydrocarbon-degrading genera; Pseudomonas, Bacillus, Arthrobacter and Brevundimonas with 57 % of these isolates being obtained from treated COTBS-contaminated soil. Overall, this study demonstrates that the potential for PAH degradation exists for the bioremediation of Hamada COTBS-contaminated environments in Libya. This represents the first report on the isolation of hydrocarbonoclastic bacteria from Libyan COTBS and COTBS-contaminated soil.

Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: a comparison of the safety of cryoablation and radiofrequency ablation.

PURPOSE: To compare the safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis. MATERIALS AND METHODS: This retrospective HIPAA-compliant study received institutional review board approval. Forty-two adult patients with cirrhosis underwent image-guided percutaneous ablation of hepatocellular carcinoma from 2003 to 2011. Twenty-five patients underwent 33 cryoablation procedures to treat 39 tumors, and 22 underwent 30 radiofrequency ablation procedures to treat 39 tumors. Five patients underwent both cryoablation and radiofrequency ablation procedures. Complication rates and severity per procedure were compared between the ablation groups. Potential confounding patient, procedure, and tumor-related variables were also compared. Statistical analyses included Kruskal-Wallis, Wilcoxon rank sum, and Fisher's exact tests. Two-sided P-values <0.05 were considered significant. RESULTS: The overall complication rates, 13 (39.4%) of 33 cryoablation procedures versus eight (26.7%) of 30 radiofrequency ablation procedures and severe/fatal complication rates, two (6.1%) of 33 cryoablation procedures versus one (3.3%) of 30 radiofrequency ablation procedures, were not significantly different between the ablation groups (both P=0.26). Severe complications included pneumothoraces requiring chest tube insertion during two cryoablation procedures. One death occurred within 90 days of a radiofrequency ablation procedure; all other complications were managed successfully. CONCLUSION: No significant difference was seen in the overall safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis.

Percutaneous imaging-guided cryoablation of liver tumors: predicting local progression on 24-hour MRI.

OBJECTIVE: The purpose of this study was to determine which MRI features observed 24 hours after technically successful percutaneous cryoablation of liver tumors predict subsequent local tumor progression and to describe the evolution of imaging findings after cryoablation. MATERIALS AND METHODS: Thirty-nine adult patients underwent technically successful imaging-guided percutaneous cryoablation of 54 liver tumors (hepatocellular carcinoma, 8; metastases, 46). MRI features pertaining to the tumor, ablation margin, and surrounding liver 24 hours after treatment were assessed independently by two readers. Fisher exact or Wilcoxon rank sum tests (significant p values < 0.05) were used to compare imaging features in patients with and without subsequent local tumor progression. Imaging features of the ablation margin, treated tumor, and surrounding liver were evaluated on serial MRI in the following year. RESULTS: A minimum ablation margin of 3 mm or less was observed in 11 (78.6%) of 14 tumors with and 15 of 40 (37.5%) without progression (p = 0.012). A blood vessel bridging the ablation margin was noted in 11 of 14 (78.6%) tumors with and nine of 40 (22.5%) without progression (p < 0.001). The incidence of tumor enhancement 24 hours after cryoablation was similar for tumors with (10/14, 71.4%) or without (25/40, 62.5%) local progression (p = 0.75). MRI enabled assessment of the entire cryoablation margin in 49 of 54 (90.7%) treated tumors. CONCLUSION: MRI features at 24 hours after liver cryoablation that were predictive of local tumor progression included a minimum ablation margin less than or equal to 3 mm and a blood vessel bridging the ablation margin. Persistent tumor enhancement is common after liver cryoablation and does not predict local tumor progression.

Metabolic profiling of yeast culture using gas chromatography coupled with orthogonal acceleration accurate mass time-of-flight mass spectrometry: application to biomarker discovery.

Yeast and yeast cultures are frequently used as additives in diets of dairy cows. Beneficial effects from the inclusion of yeast culture in diets for dairy mammals have been reported, and the aim of this study was to develop a comprehensive analytical method for the accurate mass identification of the 'global' metabolites in order to differentiate a variety of yeasts at varying growth stages (Diamond V XP, Yea-Sacc and Levucell). Microwave-assisted derivatization for metabolic profiling is demonstrated through the analysis of differing yeast samples developed for cattle feed, which include a wide range of metabolites of interest covering a large range of compound classes. Accurate identification of the components was undertaken using GC-oa-ToFMS (gas chromatography-orthogonal acceleration-time-of-flight mass spectrometry), followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) for data reduction and biomarker discovery. Semi-quantification (fold changes in relative peak areas) was reported for metabolites identified as possible discriminative biomarkers (p-value <0.05, fold change >2), including D-ribose (four fold decrease), myo-inositol (five fold increase), L-phenylalanine (three fold increase), glucopyranoside (two fold increase), fructose (three fold increase) and threitol (three fold increase) respectively.

MRI assessment of percutaneous ablation of liver tumors: value of subtraction images.

PURPOSE: To evaluate the value of subtraction images when using MRI to assess liver tumors treated with percutaneous ablation. MATERIALS AND METHODS: Following percutaneous ablation of 35 liver tumors, two abdominal radiologists, blinded to outcomes, independently reviewed follow-up MRI examinations for tumoral enhancement suggestive of residual/recurrent tumor and rated their confidence level. After one year, the readers reviewed the same examinations with added subtraction images. Accuracy of the detection of residual/recurrent tumor and contrast-to-noise ratios (CNR; for tumoral enhancement-to-liver, tumoral enhancement-to-ablation zone, and ablation zone-to-liver) were calculated with and without subtraction images and compared using Wilcoxon signed rank test. Interobserver variability was computed using Kappa (κ) statistics. RESULTS: Residual/recurrent tumor was present in 8 (23.5%) of 34 tumors. Accuracy of detecting residual/recurrent tumor with subtraction images and interobserver agreement (κ = 0.72, good) were better than accuracy of detecting residual/recurrent tumor and interobserver agreement (κ = 0.57, moderate) of enhanced MR images without subtraction. Mean CNR of subtraction images was significantly higher than that of enhanced MR images for tumoral enhancement-to-liver (0.2 ± 5 versus 11.6 ± 14.4, P = 0.03), tumoral enhancement-to-ablation zone (10.1 ± 12.5 versus 34.4 ± 29.4, P = 0.02), and ablation zone-to-liver (11.8 ± 13.3 versus 102.5 ± 238.4, P = 0.03). CONCLUSION: When using MRI, subtraction images help both detect and exclude residual/recurrent tumor following percutaneous liver ablations.

Radiofrequency ablation: technique and clinical applications.

Radiofrequency ablation is the most commonly used percutaneous ablation technique and well-documented in the literature on focal therapies. It has become the image-guided ablation method of choice because of its efficacy, safety, and ease of use. Radiofrequency ablation has shown promise in treating selected solid tumors, particularly those involving the liver, kidneys, lungs, and the musculoskeletal system. It is a minimally invasive technique often used in inoperable patients with other comorbidities. Radiofrequency ablation requires a minimal hospital stay or can be performed on an outpatient basis. The aim of this article is to review radiofrequency ablation techniques and their clinical applications.

Fully automatic 3D segmentation of iceball for image-guided cryoablation.

The efficient extraction of the cryoablation iceball from a time series of 3D images is crucial during cryoablation to assist the interventionalist in determining the coverage of the tumor by the ablated volume. Conventional semi-automatic segmentation tools such as ITK-SNAP and 3D Slicer's Fast Marching Segmentation can attain accurate iceball segmentation in retrospective studies, however, they are not ideal for intraprocedure real time segmentation, as they require time-consuming manual operations, such as the input of fiducials and the extent of the segmented region growth. In this paper, we present an innovative approach for the segmentation of the iceball during cryoablation, that executes a fully automatic computation. Our approach is based on the graph cuts segmentation framework, and incorporates prior information of iceball shape evolving in time, modeled using experimentally-derived iceball growth parameters. Modeling yields a shape prior mask image at each timepoint of the imaging time series for use in the segmentation. Segmentation results of our method and the ITK-SNAP method are compared for 8 timepoints in 2 cases. The results indicate that our fully automatic approach is accurate, robust and highly efficient compared to manual and semi-automatic approaches.

Estimated effective dose of CT-guided percutaneous cryoablation of liver tumors.

PURPOSE: To estimate effective dose during CT-guided cryoablation of liver tumors, and to assess which procedural factors contribute most to dose. MATERIALS AND METHODS: Our institutional review board approved this retrospective, HIPAA-compliant study. A total of 20 CT-guided percutaneous liver tumor cryoablation procedures were performed in 18 patients. Effective dose was determined by multiplying the dose length product for each CT scan obtained during the procedure by a conversion factor (0.015mSv/mGy-cm), and calculating the sum for each phase of the procedure: planning, targeting, monitoring, and post-ablation survey. Effective dose of each phase was compared using a repeated measures analysis. Using Spearman correlation coefficients, effective doses were correlated with procedural factors including number of scans, ratio of targeting distance to tumor size, anesthesia type, number of applicators, performance of ancillary procedures (hydrodissection and biopsy), and use of CT fluoroscopy. RESULTS: Effective dose per procedure was 72±18mSv. The effective dose of targeting (37.5±12.5mSv) was the largest component compared to the effective dose of the planning phase (4.8±2.2mSv), the monitoring phase (25.5±6.8mSv), and the post-ablation survey (4.1±1.9mSv) phase (p<0.05). Effective dose correlated positively only with the number of scans (p<0.01). CONCLUSIONS: The effective dose of CT-guided percutaneous cryoablation of liver tumors can be substantial. Reducing the number of scans during the procedure is likely to have the greatest effect on lowering dose.

Minimizing image misregistration during PET/CT-guided percutaneous interventions with monitored breath-hold PET and CT acquisitions.

PURPOSE: To validate a monitored, breath-hold positron emission tomography (PET)/computed tomography (CT) acquisition technique for the minimization of respiratory PET/CT image misregistration and lesion distortion during PET/CT-guided percutaneous interventional procedures. MATERIALS AND METHODS: Eleven patients referred for percutaneous biopsy or thermal ablation of tumors near the diaphragm were prospectively enrolled. Initial PET/CT scanning was performed by using a bellows device and monitored, same-level breath-holds for PET and CT acquisitions. Breath-hold PET consisted of nine 20-second breath-hold frames, yielding a 3-minute equivalent PET dataset. A second PET/CT scan was obtained without monitoring by using end-expiration breath-hold CT and free-breathing PET. PET/CT tumor misregistration and craniocaudal tumor diameter were measured on monitored and unmonitored PET/CT datasets. Data were analyzed by using nonparametric, two-sided, signed-rank statistical tests. RESULTS: Mean PET/CT image misregistrations in the craniocaudal, anteroposterior, and transverse planes were 2.6 mm (range, 0-7 mm), 3.3 mm (range, 1-8 mm), and 2.7 mm (range, 0-8 mm) with monitoring and 14.7 mm (range, 0-49 mm), 7.6 mm (range, 1-24 mm), and 4.0 mm (range, 0-12 mm) without monitoring, respectively. Differences were significant for craniocaudal (P = .0087) and anteroposterior (P = .014) planes, but not for the transverse plane (P = .23). Mean craniocaudal target diameter was 2.5 mm (range, -2 to 9 mm) larger (ie, distorted) for unmonitored versus monitored PET (P = .061). CONCLUSIONS: Acquiring PET/CT datasets with respiratory bellows-assisted, monitored breath-holds improves PET/CT image registration versus unmonitored PET/CT and may facilitate accurate targeting during PET/CT-guided interventions in anatomic regions subject to respiratory motion.