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Optimized technical considerations for acquiring high-quality FDG studies with a dual-headed gamma camera.

OBJECTIVE: This retrospective analysis was designed to optimize the parameters and techniques required to successfully perform high-quality coincidence imaging in a general nuclear medicine department using a dual-headed gamma camera. METHOD: Coincidence imaging was performed on 33 patients after an intravenous injection of 3.0-5.0 mCi fluoro-2-deoxyglucose (18F-FDG). Data for all subjects were evaluated to determine which technical considerations contributed to an overall improvement in image quality. RESULTS: After reviewing the data for the 33 subjects, several modified techniques were implemented and parameters were adjusted that enhanced the overall quality of the images. The extremely short half-life of 18F restricts the opportunity to repeat studies that were delayed, interrupted or technically substandard. CONCLUSION: The review of the data indicated that strict adherence to protocol is necessary to achieve optimal results while attempting to incorporate this new imaging modality into a typical nuclear medicine department.

Fluorodeoxyglucose F18↗

Future trends in heating technology of deep-seated tumors.

Hyperthermia techniques and equipment have developed into a level of sophistication requiring special training and operator skills. Recent advances electromagnetic and ultrasound heating techniques are multi-applicator arrays, both external and invasive. These arrays are most effective when individual channel power control can be utilized to improve the heating pattern control during treatment. A preview of future capabilities shows that more selective tumor heating is possible with the advanced equipment. The role of computer pretreatment planning is a valuable aid in operator training as well as optimization of parameters. The current development of regional heating is in the deep focal heating by external focused arrays. The SIGMA 60 cylindrical dipole array deep steerable focal zone is described and test data presented showing the selective focusing obtained. A small invasive targeting E-field sensor is used to optimize phase and amplitude of the array to improve the selective heating in the target zone. These patented techniques and devices are expected to reduce systemic toxicity and increase tumor temperatures with lower power input. Future equipment development is predicted to include many types of hyperthermia devices and techniques. This trend suggests that systems must be designed to simplify the operator's tasks and improve the heating pattern controls. The computer power and control will become much more important in these future systems.

Electromagnetic Phenomena↗

Large-scale single-cell trapping and imaging using microwell arrays.

High-throughput single-cell measurements of cellular responses are of great importance for a variety of applications including drug testing, toxicology, and basic cell biology. We present an optimization study for trapping single cells with high efficiency in large arrays of microwells. The method is compatible with standard fluorescence microscopy equipment and is not dependent on, but is compatible with, cell adherence. We have characterized microwell occupancy by cells for a range of microwell dimensions and seeding parameters and optimized it for fibroblasts (as a model of adherent cell) and rat basophilic leukemia cells (as a model of nonadherent cell). We have been able to obtain phase-contrast and fluorescence micrographs with more than 18,000 single cells per image using a 4x objective.

Animals↗

Influence of membrane differential filtration on the natural course of age-related macular degeneration: a randomized trial.

PURPOSE: Membrane differential filtration is able to optimize rheologic parameters by eliminating high molecular weight proteins and lipoproteins from the blood. Following the hypothesis that these changes result in an improvement of the microcirculation, the authors tested the efficacy of membrane differential filtration in improving visual function in patients with age-related macular degeneration (ARMD). METHODS: Forty patients (40 eyes) were randomized into two groups. The treatment group was treated five times over a period of 21 weeks. In both groups, 9/20 of the eyes showed subfoveolar subretinal neovascularization. The main parameter of the study was visual acuity (VA). Electroretinogram (ERG), electrooculogram, and macular visual evoked potentials were also recorded. Plasma and whole blood viscosity and erythrocyte aggregation were measured. RESULTS: The 20 patients treated repeatedly over a period of 21 weeks showed a mean improvement of 0.63 lines (SD 1.8) of VA on Early Treatment Diabetic Retinopathy Study charts. The control group showed a deterioration of 0.94 lines (SD 1.7) compared to VA at baseline examination. The amplitude of the ERG photopic a-wave and the flicker ERG was significantly increased. The rheologic parameters were lowered in all treated patients. CONCLUSION: Repetitive treatment with membrane differential filtration is able to improve visual acuity of patients with ARMD and the natural course of this disease. Several questions arise from the results of this study. Further research will show if it is possible to optimize the selection of patients for subgroups with predictive responses through morphologic and functional tests and how to create an optimized and individual treatment strategy determined by the quality, intensity, and frequency of treatment sessions.

Aged↗

Late fields of the magnetocardiographic QRS complex as indicators of propensity to sustained ventricular tachycardia after myocardial infarction.

INTRODUCTION: Magnetocardiographic (MCG) mapping is a new method to record cardiac signals. This study examined the association of MCG late fields with the propensity to sustained ventricular tachycardia (VT) after myocardial infarction (MI). METHODS AND RESULTS: One hundred patients with remote MI were studied, 38 with and 62 without history of VT. High-resolution MCG and signal-averaged ECG (SAECG) as a comparative method were recorded. Time-domain parameters describing the abnormal low-amplitude end QRS activity, MCG late fields, and SAECG late potentials were analyzed. Late field parameters differed significantly between the patient groups: filtered QRS duration was 137 +/- 26 msec in the VT group and 110 +/- 18 msec in the control group (P < 0.001), and root mean square amplitude of the last 40 msec was 260 +/- 170 and 510 +/- 360 fT (P < 0.001), respectively. The optimal MCG parameter combination yielded a sensitivity of 92% and a specificity of 61% in classification to the VT group, whereas those for SAECG were 63% and 66%. In a subgroup of 63 patients with marked left ventricular dysfunction and comparable stage of coronary heart disease, only MCG (sensitivity 73%, specificity 67%) but not SAECG could assign a patient to the VT group. CONCLUSION: Late fields of the MCG QRS complex indicate propensity to life-threatening arrhythmias in post-MI patients. This discriminative ability persists in the presence of severe left ventricular dysfunction where ECG late potentials lose their informative value. MCG late field analysis is a potential new method for noninvasive risk assessment in post-MI patients.

Electrocardiography↗

The margin for error when releasing the asymmetric bars for dismounts.

It has previously been shown that male gymnasts using the "scooped" giant circling technique were able to flatten the path followed by their mass center, resulting in a larger margin for error when releasing the high bar (Hiley and Yeadon, 2003a). The circling technique prior to performing double layout somersault dismounts from the asymmetric bars in women's artistic gymnastics appears to be similar to the "traditional" technique used by some male gymnasts on the high bar. It was speculated that as a result the female gymnasts would have margins for error similar to those of male gymnasts who use the traditional technique. However, it is unclear how the technique of the female gymnasts is affected by the need to avoid the lower bar. A 4-segment planar simulation model of the gymnast and upper bar was used to determine the margins for error when releasing the bar for 9 double layout somersault dismounts at the Sydney 2000 Olympics. The elastic properties of the gymnast and bar were modeled using damped linear springs. Model parameters, primarily the inertia and spring parameters, were optimized to obtain a close match between simulated and actual performances in terms of rotation angle (1.2 degrees), bar displacement (0.011 m), and release velocities (<1%). Each matching simulation was used to determine the time window around the actual point of release for which the model had appropriate release parameters to complete the dismount successfully. The margins for error of the 9 female gymnasts (release window 43-102 ms) were comparable to those of the 3 male gymnasts using the traditional technique (release window 79-84 ms).

Adolescent↗

Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices.

Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19-21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7-0.8 microFcm-2, Ri was 170-340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2-0.3 space constants, and those of the apical tufts were 0.4-0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.

Animals↗

Theoretical optimization by genetic algorithm of delayed extraction parameters for a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer.

This paper presents the application of a genetic algorithm (GA) to optimize the operating parameters, namely pulse voltage and extraction delay time, when using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). Simulations predict the presence of several combinations of these parameters that give a local maximum. The aim is to locate the optimal combination (a global maximum) of pulse voltage and extraction time delay in order to focus the ions of a particular m/z value to achieve the best resolution in a given instrumental geometry. The GA locates the global maximum quickly. The results indicate that it may be possible to achieve very high resolving power by using delayed extraction (DE)-MALDI-TOFMS with parameters obtained from the GA.

Algorithms↗

Comparison of two optimization methods to derive energy parameters for protein folding: perceptron and Z score.

Two methods were proposed recently to derive energy parameters from known native protein conformations and corresponding sets of decoys. One is based on finding, by means of a perceptron learning scheme, energy parameters such that the native conformations have lower energies than the decoys. The second method maximizes the difference between the native energy and the average energy of the decoys, measured in terms of the width of the decoys' energy distribution (Z-score). Whereas the perceptron method is sensitive mainly to "outlier" (i.e., extremal) decoys, the Z-score optimization is governed by the high density regions in decoy-space. We compare the two methods by deriving contact energies for two very different sets of decoys: the first obtained for model lattice proteins and the second by threading. We find that the potentials derived by the two methods are of similar quality and fairly closely related. This finding indicates that standard, naturally occurring sets of decoys are distributed in a way that yields robust energy parameters (that are quite insensitive to the particular method used to derive them). The main practical implication of this finding is that it is not necessary to fine-tune the potential search method to the particular set of decoys used.

Algorithms↗

Co-registration of stereotactic MRI and isofieldlines during deep brain stimulation.

OBJECT: The parameter adjustment process during deep brain stimulation (DBS) for dystonia remains time consuming and based on clinical observation alone. The aim was to correlate the electric field with the GPi anatomy to be able to study the stimulated volume. METHODS: We developed a computer-assisted method (model) for visualizing electric field in reference to the stereotactic space. Electric field values were correlated with the GPi anatomy (stereotactic Magnetic Resonance Imaging) in one reference patient. RESULTS: Using this methodology it becomes possible to correlate the electric field distributions for patient specific parameters with the anatomical information. The application to one patient showed that the 0.1V/mm isofieldline fits best with the lateral GPi borders at the level of the stimulated contacts. CONCLUSIONS: The electric field is a crucial parameter as it is assumed to be responsible for triggering action potentials. Electric field visualisation allows the calculation of the stimulated volume for a given isoline. Its application to our whole patient population might help in determining a threshold for obtaining a therapeutic effect, to date unknown, and consequently in optimizing the parameter setting in each patient.

Brain↗

Effect of different inertial parameter sets on joint moment calculation during stair ascending and descending.

The reliability of internal joint moment calculation in gait analysis during daily living activities is fundamental for clinical decisions based on joint function. This calculation, obtained by means of the inverse dynamics, depends on several modelling factors, such as assumptions on the segments and on the relevant joints constituting the kinematic chain. In this study, the effect of five different sets of inertial parameters on three-dimensional calculation of lower limb joint moments was investigated during the stair ascending and descending of 10 young subjects. The lower limb was represented as a chain of three rigid segments: foot, shank and thigh. The inertial parameters sets were taken from the literature. The root mean square value over the step cycle of the difference between joint moments calculated at the lower limb with different inertial parameter sets expressed in percentage of their corresponding range was computed. The results showed small differences between ex vivo and in vivo data, between data from different populations and among different modality of inertial parameters acquisition. The root mean square value was negligible at the ankle and increased as moving proximally among the joints: the maximum was 21.8% in the internal/external rotation moment at the hip. In order to achieve accurate estimate of lower limb joint moments other factors should be investigated rather than optimal inertial parameter set.

Adult↗

Pharmacokinetic model-driven infusion of fentanyl in children.

BACKGROUND: This study determined the accuracy of previously defined adult fentanyl pharmacokinetics in children having surgery; from this population, the pharmacokinetics of fentanyl were characterized in children when administered via a computerized assisted continuous-infusion device. METHODS: Twenty children between the ages of 2.7 and 11 y scheduled to undergo elective noncardiac surgery were studied. After induction, anesthesia was maintained with 60% nitrous oxide in oxygen supplemented with fentanyl (n = 10) or fentanyl plus isoflurane (n = 10). Fentanyl was administered via computerized assisted continuous-infusion to target concentrations determined by clinical requirements. Plasma fentanyl concentrations were measured and used to evaluate the performance of the fentanyl pharmacokinetics and then to determine a new set of pharmacokinetic parameters and the variance in the context-sensitive half-times simulated for these patients. RESULTS: The original adult fentanyl pharmacokinetics resulted in a positive bias (10.4%), indicating that measured concentrations were mostly greater than predicted. A two-compartment model with age and weight as covariates provided the optimal pharmacokinetic parameters. These resulted in a residual performance error of -1.1% and a median absolute performance error of 17.4%. The context-sensitive times determined from this pediatric population were considerably shorter than the context-sensitive times previously published for adults. CONCLUSIONS: The pharmacokinetics of fentanyl administered by computerized assisted continuous-infusion differ between adults and children. The newly derived parameters are probably more suitable to determine infusion schemes of up to 4 h in children between the ages of 2 and 11 y.

Anesthetics, Intravenous↗

2-Step IMAT and 2-Step IMRT: a geometrical approach.

The purpose of this paper is to develop a method that reduces the number of segments for intensity modulated arc therapy (IMAT) and intensity modulated radiotherapy (IMRT) for concave target volumes (TV). The aim was to utilize no more than two intensity levels per organ at risk (OAR) and to derive both optimal segment widths and weights from geometric considerations. Brahme's model of an annular target surrounding a circular OAR was used as test model. Brahme's solution was substituted by a single segment added to a simple field blocking the OAR. Width and weight of the segment were the free parameters to optimize. The objective function to minimize was the root mean square (rms) error of the dose in the target volume. One boundary condition was--neglecting scatter--"zero-dose" to the OAR. The resulting rules for width and weight of the additive segment are referred to as "optimized 2-Step IMAT" and "2-Step IMRT." The recommendations were applied to some simplified plans representing clinical cases using a commercial planning system. Optimized 2-Step IMAT improved the rms by a factor of 4 with respect to techniques simply blocking the OAR. The additional segment reduced the rms below 3% for cases with gaps between OAR and TV larger than 8% of the TV diameter. The results for 2-Step IMAT are applicable to IMRT and aperture modulated arc therapy (AMAT). 2-Step IMAT can be utilized for noncylindrical cases and for more than one OAR. A geometrical and topological approach to IMAT and IMRT can be useful to understand fluence profiles. The results could be applied to ameliorate other topology-based procedures used in some planning systems. Basic mechanisms of 2-Step IMAT can assist with the creation of rules for adaptive IMRT to compensate for patient motion.

Algorithms↗

Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode.

The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo. A critical component of this technique is the electrode configuration. Electroporation parameters were optimized for transgene expression with minimal tissue damage with a novel electrode. The highest transgene expression and efficiency of individual cell transformation with minimal damage was produced with eight 150 ms pulses at field strength of 100 V/cm. This electrode design offers the potential for easier and more reproducible electrically mediated cutaneous plasmid delivery than the simple electrodes currently commercially available. This electrode can be a valuable tool in determining the applicability of electrically mediated cutaneous gene transfer.

Animals↗

High-precision isotope ratio mass spectrometry and stable isotope precursors for tracer studies in cell culture.

The use of stable isotope-labeled tracers is demonstrated in an in vitro system with analysis by high-precision isotope ratio mass spectrometry (IRMS), using n-3 long-chain polyunsaturated fatty acid (LCP) biosynthesis from [U-(13)C]18:3n-3 (18:3n-3*) in Y79 human retinoblastoma cells as a model system. The cells were cultured as a suspension in RPMI 1640 medium supplemented with 15% fetal calf serum at 37 degrees C with 5% CO(2) in air. They were harvested by sedimentation and cell lipids were extracted to determine the presence of 18:3n-3* metabolites using gas chromatography-combustion (GCC)-IRMS. As the dose of 18:3n-3* was systematically increased from treatment to treatment, the atom percent excess and the amounts of biosynthesized LCP* increased, while the percentage dose in each n-3 LCP* remained constant. Cultures incubated with 0.5 micromol (10 microM) of albumin-bound 18:3n-3, composed of 18:3n-3* diluted 1/60 or 1/100 with natural abundance 18:3n-3, yielded products with enrichments about 1.5 at.% excess (delta(13)C(PDB) < 1500 per thousand), which is optimal for high-precision measurements. Kinetics in Y79 cells incubated with 18:3n-3* showed that n-3 LCP* incorporation increased over time; 18:3n-3*, 20:5n-3*, 22:5n-3*, and 22:6n-3* were detected at all time points with the 1/60 dilution. These data document experimental parameters for optimal stable isotope use and IRMS detection for in vitro tracer methodology.

Carbon Isotopes↗

Aging effect on the phase evolution of water-based sol-gel hydroxyapatite.

In a number of recent reports on the synthesis of sol-gel hydroxyapatite, aging of the precursor solution has been found to be critical in developing an apatitic phase. Critical aging time is required to complete reaction between Ca and P molecular precursors to form a desired intermediate complex that permits a further transformation to apatite phase under appropriate thermal treatment. In this investigation, we employed a water-based sol-gel process recently developed to fabricate hydroxyapatite at relatively low temperatures. The aging effect on apatite formation was systematically studied in terms of aging time and temperature. Experimental results show that the aging time is considerably reduced as aging temperature rises. Long-term thermal aging was unfavorable for apatite formation. The optimal aging parameters for apatite formation were experimentally determined, which was further consolidated into a phase evolution map. Aging kinetic was investigated by monitoring the variation of solution pH, following the determination of an apparent activation energy, which has a value as high as 10.35 kcal/mol, for the chemical reaction occurring upon aging. Optimal solution chemistry was elucidated based on the corresponding phase evolution map.

Biocompatible Materials↗

Optimization of gradient elution conditions in multicomponent preparative liquid chromatography.

Gradient elution is widely applied in analytical chromatography to reduce the separation time and/or to improve the selectivity. Increasingly the potential of modulating the solvent strength during gradient operation is exploited in preparative liquid chromatography. The purpose of this paper is to investigate theoretically the effect of optimizing free parameters available in gradient chromatography (extents and shapes of gradients) on the productivity of isolating a target component in a multicomponent mixture. An equilibrium stage model was used to quantify and compare different modes of operation (isocratic and various variants of gradient elution). By combining experimental design and artificial neural network concepts, optimal conditions were identified for the production of the second eluting component in a ternary mixture. The strong impact of the shape of gradients on process performance is elucidated.

Chromatography, Liquid↗

Characterization of the parallel rod floor apparatus to test motor incoordination in mice.

Impairment of motor coordination, or ataxia, is a prominent effect of alcohol ingestion in humans. To date, many models have been created to examine this phenomenon in animals. Evidence suggests that the tasks thought to measure this behavior in mice actually measure different components of this complex trait. We have characterized the parallel rod floor apparatus to quantify ethanol-induced motor incoordination. Using genetically heterogeneous mice, we evaluated the influence of rod diameter and inter-rod distance on dose-related ethanol-induced motor incoordination to select parameters that optimized testing procedures. We then used the DBA/2J and C57BL/6J inbred strains of mice to examine the effect of 2 g/kg of ethanol, by serially testing mice on two floor types, separated by 1 week. Finally, we tested eight inbred strains of mice on four floor types to examine patterns of strain sensitivity to 2 g/kg of intraperitoneal ethanol and determined the test parameters that maximized strain effect size. Motor incoordination varied depending on the floor type and strain. When data from strain 129S1/SvlmJ were removed from the analyses because of their extreme behavior, the greatest strain effect size was observed on one floor type during the first 10 min of testing after 2 g/kg of intraperitoneal ethanol. These findings suggest that the parallel rod floor apparatus provides a useful means for examining ethanol-induced motor incoordination in mice but that specific testing procedures are important for optimizing detection of motor incoordination and genetic influences.

Animals↗