Autonomous Driving of Mobile Robots in Dynamic Environments Based on Deep Deterministic Policy Gradient: Reward Shaping and Hindsight Experience Replay.

In this paper, we propose a reinforcement learning-based end-to-end learning method for the autonomous driving of a mobile robot in a dynamic environment with obstacles. Applying two additional techniques for reinforcement learning simultaneously helps the mobile robot in finding an optimal policy to reach the destination without collisions. First, the multifunctional reward-shaping technique guides the agent toward the goal by utilizing information about the destination and obstacles. Next, employing the hindsight experience replay technique to address the experience imbalance caused by the sparse reward problem assists the agent in finding the optimal policy. We validated the proposed technique in both simulation and real-world environments. To assess the effectiveness of the proposed method, we compared experiments for five different cases.

Deep learning proton beam range estimation model for quality assurance based on two-dimensional scintillated light distributions in simulations.

BACKGROUND: Many studies have utilized optical camera systems with volumetric scintillators for quality assurances (QA) to estimate the proton beam range. However, previous analytically driven range estimation methods have the difficulty to derive the dose distributions from the scintillation images with quenching and optical effects. PURPOSE: In this study, a deep learning method utilized to QA was used to predict the beam range and spread-out Bragg peak (SOBP) for two-dimensional (2D) map conversion from the scintillation light distribution (LD) into the dose distribution in a water phantom. METHODS: The 2D residual U-net modeling for deep learning was used to predict the 2D water dose map from a 2D scintillation LD map. Monte Carlo simulations for dataset preparation were performed with varying monoenergetic proton beam energies, field sizes, and beam axis shifts. The LD was reconstructed using photons backpropagated from the aperture as a virtual lens. The SOBP samples were constructed based on monoenergetic dose distributions. The training set, including the validation set, consisted of 8659 image pairs of LD and water dose maps. After training, dose map prediction was performed using a 300 image pair test set generated under random conditions. The pairs of simulated and predicted dose maps were analyzed by Bragg peak fitting and gamma index maps to evaluate the model prediction. RESULT: The estimated beam range and SOBP width resolutions were 0.02 and 0.19 mm respectively for varying beam conditions, and the beam range and SOBP width deviations from the reference simulation result were less than 0.1 and 0.8 mm respectively. The simulated and predicted distributions showed good agreement in the gamma analysis, except for rare cases with failed gamma indices in the proximal and field-marginal regions. CONCLUSION: The deep learning conversion method using scintillation LDs in an optical camera system with a scintillator is feasible for estimating proton beam range and SOBP width with high accuracy.

Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study.

There have been many attempts in pharmaceutical industries and academia to improve the pharmacokinetic characteristics of anti-tumor small-molecule drugs by conjugating them with large molecules, such as monoclonal antibodies, called ADCs. In this context, albumin, one of the most abundant proteins in the blood, has also been proposed as a large molecule to be conjugated with anti-cancer small-molecule drugs. The half-life of albumin is 3 weeks in humans, and its distribution to tumors is higher than in normal tissues. However, few studies have been conducted for the in vivo prepared albumin-drug conjugates, possibly due to the lack of robust bioanalytical methods, which are critical for evaluating the ADME/PK properties of in vivo prepared albumin-drug conjugates. In this study, we developed a bioanalytical method of the albumin-conjugated MAC glucuronide phenol linked SN-38 ((2S,3S,4S,5R,6S)-6-(4-(((((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano [3',4':6,7] indolizino [1,2-b] quinolin-9-yl)oxy)methyl)(2 (methylsulfonyl)ethyl)carbamoyl)oxy)methyl)-2-(2-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylpropanamido)acetamido)phenoxy)-3,4,5-trihydroxytetra-hydro-2H-pyran-2-carboxylic acid) as a proof-of-concept. This method is based on immunoprecipitation using magnetic beads and the quantification of albumin-conjugated drug concentration using LC-qTOF/MS in mouse plasma. Finally, the developed method was applied to the in vivo intravenous (IV) mouse pharmacokinetic study of MAC glucuronide phenol-linked SN-38.

Investigation of In Vitro and In Vivo Metabolism of α-Amanitin in Rats Using Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method.

The purpose of this study is to investigate the difference of in vitro-in vivo correlation of α-amanitin from clearance perspectives as well as to explore the possibility of extra-hepatic metabolism of α-amanitin. First, a liquid chromatography-quadrupole-time-of-flight-mass spectrometric (LC-qTOF-MS) method for α-amanitin in rat plasma was developed and applied to evaluate the in vitro liver microsomal metabolic stability using rat and human liver microsomes and the pharmacokinetics of α-amanitin in rat. The predicted hepatic clearance of α-amanitin in rat liver microsomes was quite low (5.05 mL/min/kg), whereas its in vivo clearance in rat (14.0 mL/min/kg) was close to the borderline between low and moderate clearance. To find out the difference between in vitro and in vivo metabolism, in vitro and in vivo metabolite identification was also conducted. No significant metabolites were identified from the in vivo rat plasma and the major circulating entity in rat plasma was α-amanitin itself. No reactive metabolites such as GSH-adducts were detected either. A glucuronide metabolite was newly identified from the in vitro liver microsomes samples with a trace level. A semi-mass balance study was also conducted to understand the in vivo elimination pathway of α-amanitin and it showed that most α-amanitin was mainly eliminated in urine as intact which implies some unknown transporters in kidney might play a role in the elimination of α-amanitin in rat in vivo. Further studies with transporters in the kidney would be warranted to figure out the in vivo clearance mechanism of α-amanitin.

Deep Deterministic Policy Gradient-Based Autonomous Driving for Mobile Robots in Sparse Reward Environments.

In this paper, we propose a deep deterministic policy gradient (DDPG)-based path-planning method for mobile robots by applying the hindsight experience replay (HER) technique to overcome the performance degradation resulting from sparse reward problems occurring in autonomous driving mobile robots. The mobile robot in our analysis was a robot operating system-based TurtleBot3, and the experimental environment was a virtual simulation based on Gazebo. A fully connected neural network was used as the DDPG network based on the actor-critic architecture. Noise was added to the actor network. The robot recognized an unknown environment by measuring distances using a laser sensor and determined the optimized policy to reach its destination. The HER technique improved the learning performance by generating three new episodes with normal experience from a failed episode. The proposed method demonstrated that the HER technique could help mitigate the sparse reward problem; this was further corroborated by the successful autonomous driving results obtained after applying the proposed method to two reward systems, as well as actual experimental results.

A study of quantitative indicators for slice sorting in cine-mode 4DCT.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Fully Automatic Quantitative Measurement of 18F-FDG PET/CT in Thymic Epithelial Tumors Using a Convolutional Neural Network.

OBJECTIVES: The aim of this study was to develop a deep learning (DL)-based segmentation algorithm for automatic measurement of metabolic parameters of 18F-FDG PET/CT in thymic epithelial tumors (TETs), comparable performance to manual volumes of interest. PATIENTS AND METHODS: A total of 186 consecutive patients with resectable TETs and preoperative 18F-FDG PET/CT were retrospectively enrolled (145 thymomas, 41 thymic carcinomas). A quasi-3D U-net architecture was trained to resemble ground-truth volumes of interest. Segmentation performance was assessed using the Dice similarity coefficient. Agreements between manual and DL-based automated extraction of SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and 63 radiomics features were evaluated via concordance correlation coefficients (CCCs) and linear regression slopes. Diagnostic and prognostic values were compared in terms of area under the receiver operating characteristics curve (AUC) for thymic carcinoma and hazards ratios (HRs) for freedom from recurrence. RESULTS: The mean Dice similarity coefficient was 0.83 ± 0.34. Automatically measured SUVmax (slope, 0.97; CCC, 0.92), MTV (slope, 0.94; CCC, 0.96), and TLG (slope, 0.96; CCC, 0.96) were in good agreement with manual measurements. The mean CCC and slopes were 0.88 ± 0.06 and 0.89 ± 0.05, respectively, for the radiomics parameters. Automatically measured SUVmax, MTV, and TLG showed good diagnostic accuracy for thymic carcinoma (AUCs: SUVmax, 0.95; MTV, 0.85; TLG, 0.87) and significant prognostic value (HRs: SUVmax, 1.31 [95% confidence interval, 1.16-1.48]; MTV, 2.11 [1.09-4.06]; TLG, 1.90 [1.12-3.23]). No significant differences in the AUCs or HRs were found between automatic and manual measurements for any of the metabolic parameters. CONCLUSIONS: Our DL-based model provides comparable segmentation performance and metabolic parameter values to manual measurements in TETs.

Quantitative Analysis of Daporinad (FK866) and Its In Vitro and In Vivo Metabolite Identification Using Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.

Daporinad (FK866) is one of the highly specific inhibitors of nicotinamide phosphoribosyl transferase (NAMPT) and known to have its unique mechanism of action that induces the tumor cell apoptosis. In this study, a simple and sensitive liquid chromatography-quadrupole-time-of-flight-mass spectrometric (LC-qTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (DMPK) properties of Daporinad in mice. A simple protein precipitation method using acetonitrile (ACN) was used for the sample preparation and the pre-treated samples were separated by a C18 column. The calibration curve was evaluated in the range of 1.02~2220 ng/mL and the quadratic regression (weighted 1/concentration2) was used for the best fit of the curve with a correlation coefficient ≥ 0.99. The qualification run met the acceptance criteria of ±25% accuracy and precision values for QC samples. The dilution integrity was verified for 5, 10 and 30-fold dilution and the accuracy and precision of the dilution QC samples were also satisfactory within ±25% of the nominal values. The stability results indicated that Daporinad was stable for the following conditions: short-term (4 h), long-term (2 weeks), freeze/thaw (three cycles). This qualified method was successfully applied to intravenous (IV) pharmacokinetic (PK) studies of Daporinad in mice at doses of 5, 10 and 30 mg/kg. As a result, it showed a linear PK tendency in the dose range from 5 to 10 mg/kg, but a non-linear PK tendency in the dose of 30 mg/kg. In addition, in vitro and in vivo metabolite identification (Met ID) studies were conducted to understand the PK properties of Daporinad and the results showed that a total of 25 metabolites were identified as ten different types of metabolism in our experimental conditions. In conclusion, the LC-qTOF-MS assay was successfully developed for the quantification of Daporinad in mouse plasma as well as for its in vitro and in vivo metabolite identification.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour.

OBJECTIVES: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). METHODS: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. RESULTS: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. CONCLUSION: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. KEY POINTS: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

Assessments of the In Vitro and In Vivo Linker Stability and Catabolic Fate for the Ortho Hydroxy-Protected Aryl Sulfate Linker by Immuno-Affinity Capture Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometric Assay.

Antibody-drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely "bottom-up" and "middle-up" approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.

Qualification and application of liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of carisbamate in rat plasma and prediction of its human pharmacokinetics using physiologically based pharmacokinetic modeling.

Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.

Cyclic Loading Performance of Radius-Cut Double Coke-Shaped Strip Dampers.

Conventional slit dampers are widely used for the purpose of seismic retrofitting, however, the structure of these dampers is susceptible to fractures, due to stress concentration at the ends of the strips in the event of large earthquakes. To address this issue, a novel radius-cut coke-shaped strip damper featuring improved ductility is proposed herein. This damper was developed based on the moment distribution over the strip when both its ends were constrained. The height-to-width ratio of the strip was increased to induce bending rather than shear deformation, and the reduced beam section method was employed. A radius-cut section was used to intentionally focus the stress to induce the plastic hinge. This reduced the fracture fragility of the specimen, resulting in an increased inelastic deformation capacity. Cyclic loading tests were conducted to verify damping performance against earthquakes. Experiments and finite element analyses proved that the coke-shaped damper exhibits improved ductility. The final fracture occurred in the radius-cut section after sufficient energy dissipation during cyclic loading. The results also indicated further improvements in strength due to the membrane effect under cyclic loading, caused by the tensile resistance of the strip due to its constrained ends.

Assessment of Pharmacokinetics and Metabolism Profiles of SCH 58261 in Rats Using Liquid Chromatography-Mass Spectrometric Method.

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC-MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus™ simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus™ was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.

In Vitro, In Silico, and In Vivo Assessments of Pharmacokinetic Properties of ZM241385.

Parkinson's disease is one of the most common neurodegenerative diseases. Adenosine regulates the response to other neurotransmitters in the brain regions related to motor function. In the several subtypes of adenosine receptors, especially, adenosine 2A receptors (A2ARs) are involved in neurodegenerative conditions. ZM241385 is one of the selective non-xanthine A2AR antagonists with high affinity in the nanomolar range. This study describes the in vitro and in vivo pharmacokinetic properties of ZM241385 in rats. A liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qToF MS) method was developed for the determination of ZM241385 in rat plasma. In vivo IV administration studies showed that ZM241385 was rapidly eliminated in rats. However, the result of in vitro metabolic stability studies showed that ZM241385 had moderate clearance, suggesting that there is an extra clearance pathway in addition to hepatic clearance. In addition, in vivo PO administration studies demonstrated that ZM241385 had low exposure in rats. The results of semi-mass balance studies and the in silico PBPK modeling studies suggested that the low bioavailability of ZM241385 after oral administration in rats was due to the metabolism and by liver, kidney, and gut.

Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer.

OBJECTIVE: To compare the prognostic values of metabolic parameters from pretreatment PET/CT between limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC) patients. METHODS: Data on 118 newly diagnosed SCLC patients (50 LD and 68 ED) who underwent pretreatment positron emission tomography-computed tomography (PET/CT) were reviewed. For PET, metabolic parameters were measured for: (1) primary tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis; and (2) all tumor lesions, SUVmax of the hottest tumor, whole body metabolic tumor volume (WBMTV), and whole body total lesion glycolysis (WBTLG). Prognostic values of metabolic parameters and other clinical variables were analyzed to predict overall survival (OS). RESULTS: In LD, SUVmax of the primary tumor was an independent prognostic factor for OS. Patients with high SUVmax showed significantly worse OS than those with low SUVmax. In ED, WBMTV and WBTLG were independent prognostic factors for OS. Patients with high WBMTV or WBTLG showed significantly worse OS than those with low WBMTV or WBTLG. CONCLUSIONS: SUVmax of primary tumor was the only independent prognostic factor for OS in LD SCLC patients. WBMTV and WBTLG were independent prognostic factors in ED SCLC patients.

Discrepancies between coronary CT angiography and invasive coronary angiography with focus on culprit lesions which cause future cardiac events.

OBJECTIVES: To evaluate the clinical significance of discrepant lesions between coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) in a longitudinal study. METHODS: In 220 patients with suspected coronary artery disease (CAD) who underwent both 256-row CCTA and ICA, the obstructive CAD (≥ 50% stenosis) on CCTA was compared with that on ICA as the reference standard. We analysed the causes of the discrepancy between CCTA and ICA. During a 40-month follow-up period, major adverse cardiac events (MACE) were assessed. RESULTS: Discordance between CCTA and ICA was observed in 121 of the 3166 coronary artery segments (3.8%). Common causes were calcification (45.9%) and positive remodelling (PR) (29.6%) in 83 false positive lesions, and noise (40.0%) and motion artefact (37.8%) in 38 false negative lesions. MACE occurred in seven lesions among the discrepant lesions; six among the 29 PR lesions (20.7%) and one among the 53 calcified lesions (1.9%). With respect to the prediction power of MACE in an intermediate stenosis, the CCTA-related value including PR was higher than the ICA-related value. CONCLUSIONS: PR was a frequent cause of MACE among the false positive lesions on CCTA. Therefore, the presence of PR on CCTA may suggest clinical significance, although it can be missed by ICA. KEY POINTS: • Compared to ICA, PR in CCTA may be cause of false positive lesion. • CCTA-related value including PR shows higher prediction power of MACE than ICA-related value. • PR reflects atherosclerotic burden that can be related to cardiac events. • PR in CCTA should be observed carefully, even if it is false positive.

A satisfaction survey on cancer pain management using a self-reporting pain assessment tool.

BACKGROUND: Pain is one of the most common and distressing symptoms in patients with cancer, with a high prevalence of 90%. Appropriate pain assessment is very important in managing cancer pain. OBJECTIVE: The aims of this study were to (1) evaluate patient satisfaction with pain control therapy using a self-reporting pain assessment tool, (2) explore the usefulness of a self-reporting assessment tool for patients and physicians, and (3) evaluate patient perception of pain management and opioid analgesics. METHODS: We enrolled a total of 587 South Korean adult cancer patients hospitalized for five days or more. Pain assessment using a self-reporting pain assessment tool was performed by patients themselves from Day 1 to Day 5. The average pain intensity on a numeric rating scale (NRS) and the frequency of breakthrough pain between Day 1 and Day 5 were recorded with a self-reporting pain assessment tool. We evaluated patient satisfaction with pain control and the usefulness of a self-reporting pain assessment tool for patients and physicians on Day 5. RESULTS: Among the 587 enrolled patients, 551, excluding 36 patients who violated inclusion criteria, were analyzed. The pain satisfaction rate was 79.5%, and only 6.2% of assessed patients had a negative pain management index (PMI). However, symmetry analysis for pain intensity between patient and physician showed low agreement (kappa=0.21). The patients with dissatisfaction for cancer pain control expressed negative attitudes toward using opioid analgesics and misconceptions regarding pain management. The satisfaction for using a self-reporting pain assessment tool was 79.2% in patients and 86.4% in physicians, respectively. CONCLUSION: The use of a self-reporting pain assessment tool as a communication instrument provides an effective foundation for evaluating pain intensity in cancer pain management. A more individualized approach to patient education about pain management may improve patient outcome.

Small-animal PET imaging of isolated perfused rat heart.

UNLABELLED: The assessment of myocardial radiotracer kinetics, including cardiac extraction fraction and washout, requires the study of isolated perfused hearts to avoid analytic error due to tracer recirculation and systemic metabolites. Analysis of the isolated perfused rat heart by a high-resolution small-animal PET system may offer both reliable evaluation of cardiac tracer kinetics and tomographic images. METHODS: An isolated perfused heart system was modified to accommodate the small PET gantry bore size. Isolated rat hearts were perfused via the Langendorff method under a constant flow of Krebs-Henseleit buffer containing (18)F-FDG with a rate of 5 mL/min and placed in the field of view of the commercially available small-animal PET system. Dynamic PET imaging was then performed, with (18)F-FDG uptake in the isolated perfused heart verified by γ counter measurements. Additionally, a rat heart of myocardial infarction was also studied in this system with static PET imaging. RESULTS: Dynamic PET acquisition of the isolated heart under constant (18)F-FDG infusion demonstrated continuous increase of activity in the heart. Correlation between cardiac activity (MBq) measured with the PET system and measurements made with the γ counter were excellent (R(2) = 0.98, P < 0.001, n = 10). Tracer input rate (MBq/min) was also well correlated with cardiac tracer uptake rate (MBq/min) (R(2) = 0.87, P < 0.001, n = 12). PET imaging of the heart with myocardial infarction showed a clear tracer uptake defect corresponding to the location of scar tissue identified by autoradiography and histology. CONCLUSION: Combining the Langendorff method of isolated rat heart perfusion with high-resolution small-animal PET allows for the reliable quantification of myocardial tracer kinetics. This novel assay is readily adapted to available small-animal PET systems and may be useful for understanding myocardial PET tracer kinetics.

Circulating tumor cell microseparator based on lateral magnetophoresis and immunomagnetic nanobeads.

This paper presents a circulating tumor cell (CTC) microseparator for isolation of CTCs from human peripheral blood using immunomagnetic nanobeads with bound antiepithelial cell adhesive molecule (EpCAM) antibodies that specifically bind to epithelial cancer cells. The isolation is performed through lateral magnetophoresis, which is induced by high-gradient magnetic separation technology, involving a ferromagnetic wire array inlaid in the bottom substrate of a microchannel. Experimental results showed that the CTC microseparator isolates about 90% of spiked CTCs in human peripheral blood at a flow rate of up to 5 mL/h and purifies to approximately 97%. The overall isolation procedure was completed within 15 min for 200 µL of peripheral blood. CTCs from peripheral blood of patients with breast and lung cancers were isolated with the CTC microseparator, and the results were compared with those of healthy donors. Using a fluorescence-based viability assay, the viability of CTCs isolated from peripheral blood of patients with cancer was observed. In addition, the usefulness of the CTC microseparator for subsequent genetic assay was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of cancer-specific genes using CTCs isolated from patients with cancer.

Advances in PET myocardial perfusion imaging: F-18 labeled tracers.

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.