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Management of pediatric radiation dose using GE fluoroscopic equipment.

In this article, we present GE Healthcare's design philosophy and implementation of X-ray imaging systems with dose management for pediatric patients, as embodied in its current radiography and fluoroscopy and interventional cardiovascular X-ray product offerings. First, we present a basic framework of image quality and dose in the context of a cost-benefit trade-off, with the development of the concept of imaging dose efficiency. A set of key metrics of image quality and dose efficiency is presented, including X-ray source efficiency, detector quantum efficiency (DQE), detector dynamic range, and temporal response, with an explanation of the clinical relevance of each. Second, we present design methods for automatically selecting optimal X-ray technique parameters (kVp, mA, pulse width, and spectral filtration) in real time for various clinical applications. These methods are based on an optimization scheme where patient skin dose is minimized for a target desired image contrast-to-noise ratio. Operator display of skin dose and Dose-Area Product (DAP) is covered, as well. Third, system controls and predefined protocols available to the operator are explained in the context of dose management and the need to meet varying clinical procedure imaging demands. For example, fluoroscopic dose rate is adjustable over a range of 20:1 to adapt to different procedure requirements. Fourth, we discuss the impact of image processing techniques upon dose minimization. In particular, two such techniques, dynamic range compression through adaptive multiband spectral filtering and fluoroscopic noise reduction, are explored in some detail. Fifth, we review a list of system dose-reduction features, including automatic spectral filtration, virtual collimation, variable-rate pulsed fluoroscopic, grid and no-grid techniques, and fluoroscopic loop replay with store. In addition, we describe a new feature that automatically minimizes the patient-to-detector distance, along with an estimate of its dose reduction potential. Finally, two recently developed imaging techniques and their potential effect on dose utilization are discussed. Specifically, we discuss the dose benefits of rotational angiography and low frame rate imaging with advanced image processing in lieu of higher-dose digital subtraction.

Body Burden↗

Glutamate optical biosensor based on the immobilization of glutamate dehydrogenase in titanium dioxide sol-gel matrix.

A simple and novel titania sol-gel derived optical biosensor coupled with carboxy seminaphthorhodamine-1-dextran (SNARF-1-dextran) as the fluorescent dye was fabricated for the determination of glutamate in water and biological samples. The NADH-dependent glutamate dehydrogenase (GLDH) was trapped in titania sol-gel derived matrix prepared by vapor deposition method. In addition, scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to characterize the surface morphology of the spots. SEM and AFM images showed that the deposition of titania precursor at 27 degrees C for 6.5h was found to be suitable to form transparent titania sol-gel matrix to encapsulate GLDH and fluorescent probe. AFM images showed that the roughness of TiO(2) surface increased from 2.16 nm in the absence of GLDH and SNARF to 37.8 nm after the immobilization. The developed titania biosensor has good analytical performance with water samples. A dynamic range between 0.04 and 10mM with the detection limit of 5.5 microM were observed. The responses to glutamate in biological samples also showed good performances, and the dynamic range and detection limit were 0.02-10mM and 6.7 microM, respectively. High precision with relative standard deviations of 4.2 and 10.7% in water and biological samples, respectively, were also demonstrated. In addition, the biosensor showed a relatively high storage stability over more than 1 month. Results obtained in this study clearly demonstrate that this simple vapor deposition method can be successfully used to form transparent titania sol-gel film for the fabrication of glutamate biosensors that are suitable for optical detection of glutamate in water and biological samples.

Biosensing Techniques↗

Nafion-coated bismuth film and nafion-coated mercury film electrodes for anodic stripping voltammetry combined on-line with ICP-mass spectrometry.

Nafion-coated bismuth film electrodes (NCBFEs) and Nafion-coated mercury film electrodes (NCMFEs) were used to electrochemically preconcentrate metal analytes for subsequent analysis by inductively coupled plasma-mass spectrometry (ICP-MS). Either type of electrodes is part of a thin-layer electrochemical flow cell that is positioned upstream of a microconcentric nebulizer for the ICP-MS. Performances of these electrodes were compared in terms of the analytical "figures of merit" (e.g., dynamic ranges, reproducibility, hydrodynamic stability, and elimination of matrix effects detrimental to ICP-MS). The coupled technique (ASV-ICP-MS) is found to possess a wide dynamic range (at least 4 to 5 orders of magnitude) and to be reproducible. Both electrodes are much more stable than the thin mercury film electrode (TMFE) traditionally used for ASV-ICP-MS, with the lifetime of the NCBFE exceeding 8 h. Adopting these electrodes for ASV-ICP-MS overcomes the problems associated with a TMFE, the erosion of which decreases the sample throughput, affects the analysis precision, and contaminates conventional glass nebulizers and spray chambers of the spectrometer. The medium exchange procedure inherent in ASV is successfully implemented with a two-valve flow injection system for the accumulation of trace Cd2+ into the electrode from a certified seawater sample, followed by stripping Cd into a solution that is compatible to the ICP-MS operation.

Adsorption↗

Nonlinearities in auditory-nerve fiber responses to bandlimited noise.

Discharge rate was measured as a function of spectral level for noise bursts of one bandwidth and center frequency. Such rate-level functions were measured for a number of bandwidths; either the low- or high-cutoff frequencies were set at fiber characteristic frequency (CF). Rate-level functions were also measured, simultaneously, for single tones at CF. We define dynamic range as the range in descibels over which rate increases from 10% to 80% of the maximum driven rate to CF tones. When pooling data across CF in single cats, dynamic range is an increasing function of fiber threshold for CF tones and noise stimuli. Narrow bands of noise produce rate-level functions that are similar to those for CF tones. For noise bands centered above CF, rate-level functions become less steep as bandwidth is increased, and are always monotonic. For wide bands of noise centered below CF, rate-level functions can be nonmonotonic or appear to plateau at rates less than the saturation rate to CF tones. Thus, wide bands of noise centered above or below CF can produce lower discharge rates than do narrow bands at the same spectral level. This rate reduction has properties similar to those for two-tone suppression. The suppressive effects observed for bandlimited noise are most pronounced on low spontaneous units and least pronounced on high spontaneous units.

Acoustic Stimulation↗

Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals.

Inhibitory effects of GABA on K(+)-evoked Ca2+ influx into rat retinal bipolar cell terminals were studied using calcium imaging methods. Application of high K+ evokes a sustained, reversible increase in [Ca2+]i at bipolar cell terminals, which occurs mainly via dihydropyridine-sensitive (L-type) Ca2+ channels. There are at least two GABA receptor subtypes coexisting at bipolar cell terminals: a conventional GABAA receptor and a bicuculline/baclofen-insensitive GABA receptor. Activation of either GABA receptor inhibited the K(+)-evoked Ca2+ response. However, these two GABA receptor subtypes have distinct properties. GABAA receptors suppress the Ca2+ response only at relatively high concentrations of agonist, and with fas kinetics and a narrow dynamic range. In contrast, the bicuculline/baclofen-insensitive GABA receptors produce inhibition on the Ca2+ response at a much lower concentration of agonist, and with slow onset and a wider dynamic range. The pharmacologic profile of the bicuculline/baclofen-insensitive GABA receptor at bipolar cell terminals is most similar to the GABAC receptor reported by Feigenspan et al. (1993). Unlike the GABAC receptors described in other species, it is extremely insensitive to picrotoxin. Therefore, it may be appropriate to refer to this receptor as a picrotoxin-insensitive GABAc receptor. 3-Aminopropyl(methyl)phosphinic acid (3-APMPA) and 3-aminopropylphosphonic (3-APA), two phosphate analogs of GABA, selectively antagonize the picrotoxin-insensitive GABAc receptors but not the GABAA receptors in this system. These results imply a functional role for multiple GABA receptors in regulating synaptic transmission at bipolar cell terminals.

Animals↗

The expanding role of mass spectrometry in metabolite profiling and characterization.

Mass spectrometry has a strong history in drug-metabolite analysis and has recently emerged as the foremost technology in endogenous metabolite research. The advantages of mass spectrometry include a wide dynamic range, the ability to observe a diverse number of molecular species, and reproducible quantitative analysis. These attributes are important in addressing the issue of metabolite profiling, as the dynamic range easily exceeds nine orders of magnitude in biofluids, and the diversity of species ranges from simple amino acids to lipids to complex carbohydrates. The goals of the application of mass spectrometry range from basic biochemistry to clinical biomarker discovery with challenges in generating a comprehensive profile, data analysis, and structurally characterizing physiologically important metabolites. The precedent for this work has already been set in neonatal screening, as blood samples from millions of neonates are tested routinely by mass spectrometry as a diagnostic tool for inborn errors of metabolism. In this review, we will discuss the background from which contemporary metabolite research emerged, the techniques involved in this exciting area, and the current and future applications of this field.

Biomarkers↗

Electrochemical determination of azidothymidine in human whole blood.

An electrochemical method based on differential pulse voltammetry is presented for the determination of AZT in whole blood of fasted subjects. A protein-free supernatant of whole blood is prepared using HClO4 precipitation followed by neutralization with phosphate buffer. The AZT is reduced at a hanging mercury drop electrode. The linear dynamic range of standards in buffer is from the detection limit of 4.1 nM to 206.5 microM (1.1 to 55,200 ng/ml). However, in spiked blood samples the linear dynamic range is from 0.029 to 0.29 microM (7.75 to 77.5 ng/ml). The whole blood assay yields a recovery of 92.30 +/- 5.92% compared to the standard solution assay. After a 30-min preparation time, each sample can be analyzed in 10 min by a manual procedure.

Chemical Precipitation↗

Air versus bone conduction: an equal loudness investigation.

Air conduction (AC) versus bone conduction (BC) loudness balance testing was conducted at frequencies of 0.25, 0.5, 0.75, 1, 2, and 4 kHz for two groups: 23 normal hearing subjects and eight subjects with a mild to moderate pure sensorineural hearing loss. Narrow-band noise was presented interchangeably between earphones and a bone transducer fitted to the subjects. Loudness matching was carried out at each frequency and at the levels 30-80 dB hearing level (HL) (10 dB steps) in the following manner: the sound pressure from the earphones was fixed and the subject adjusted the output level of the bone transducer for equal loudness by bracketing the standard. The results revealed somewhat different loudness functions for AC and BC sound with a 6-10 dB difference in the AC and BC loudness functions for the normal hearing group over the dynamic range 30-80 dB HL at the frequencies 250-750 Hz. At the higher frequencies, 1-4 kHz, the difference was only 4-5 dB over the same dynamic range. Similar results were obtained for the sensorineural hearing-impaired group. The difference between the AC and the BC loudness functions may originate from changes with level of the AC sound path, e.g. contraction of the stapedius muscle, but also distortion from the bone transducer and tactile stimulation could have contributed to the results seen.

Acoustic Stimulation↗

Coding strategies in monkey V1 and inferior temporal cortices.

We would like to know whether the statistics of neuronal responses vary across cortical areas. We examined stimulus-elicited spike count response distributions in V1 and inferior temporal (IT) cortices of awake monkeys. In both areas, the distribution of spike counts for each stimulus was well described by a Gaussian distribution, with the log of the variance in the spike count linearly related to the log of the mean spike count. Two significant differences in response characteristics were found: both the range of spike counts and the slope of the log(variance) versus log(mean) regression were larger in V1 than in IT. However, neurons in the two areas transmitted approximately the same amount of information about the stimuli and had about the same channel capacity (the maximum possible transmitted information given noise in the responses). These results suggest that neurons in V1 use more variable signals over a larger dynamic range than IT neurons, which use less variable signals over a smaller dynamic range. The two coding strategies are approximately as effective in transmitting information.

Animals↗

Neural transduction in Xenopus laevis lateral line system.

1. The process of neural excitation in hair cell systems was studied in an in vitro preparation of the Xenopus laevis (African clawed toad) lateral line organ. A specially designed stimulus chamber was used to apply accurately controlled pressure, water movement, or electrical stimuli, and to record the neural responses of the two afferent fibers innervating each organ or stitch. The objective of the study was to determine the characteristics of the neural responses to these stimuli, and thus gain insight into the transduction process. 2. A sustained deflection of the hair cell cilia due to a constant flow of water past the capula resulted in a maintained change in the mean firing rate (MFR) of the afferent fibers. The data also demonstrated that the neural response was proportional to the velocity of the water flow and indicated that both deflection and movement of the cilia were the effective physiological stimuli for this hair cell system. 3. The preparations responded to sinusoidal water movements (past the capula) over the entire frequency range of the stimulus chamber, 0.1-130 Hz, and were most sensitive between 10 and 40 Hz. The variation of the MFR and the percent modulation indicated that the average dynamic range of each organ was 23.5 dB. 4. The thresholds, if any, for sustained pressure changes and for sinusoidal pressure variations in the absence of water movements were very high. Due to the limitations of the stimulus chamber it was not possible to generate pressure stimuli of sufficient magnitude to elicit a neural response without also generating suprathreshold water-movement stimuli. Sustained pressures had no detectable effect on the neural response to water-movement stimuli. 5. The preparations were very sensitive to electrical potentials applied across the toad skin on which the hair cells were located. Potentials which made the ciliated surfaces of the hair cells positive with respect to their bases increased the MFR of the fibers, whereas negative potentials decreased it. The responses to sinusoidal electrical stimuli were similar to responses to water-movement stimuli with respect to frequency and dynamic ranges. Thresholds as low as 100 muV peak to peak (p-p) for 16-Hz stimuli were found. 6. The characteristics of the neural responses to electrical stimulation as well as supporting data obtained from the studies of the effects of anoxia on the evoked responses indicate that the electrical stimulus acts on the hair cells or on the synapses, rather than directly on the nerve fibers. This finding suggests that receptor potentials or their associated currents play an important role in the process of neural excitation in hair cell systems.

Animals↗

Responses of DCN-PVCN neurons and auditory nerve fibers in unanesthetized decerebrate cats to AM and pure tones: analysis with autocorrelation/power-spectrum.

We investigated amplitude-modulated (AM) tone encoding behavior of dorsal and posteroventral cochlear-nucleus (DCN and PVCN) neurons and auditory nerve (AN) fibers in decerebrate unanesthetized cats. Some of the modulation transfer functions (MTFs) were narrowly-tuned band-pass functions; these included responses at moderate and high stimulus levels of DCN pause/build-type-III neurons and the following types of DCN and PVCN chopper neurons: chop-S and/or chop-type-I/III. Other MTFs were broad low-pass or complex functions. Chop-T neurons of the DCN and PVCN tended to exhibit low-pass or flat MTFs. The band-pass MTF neurons exhibited intrinsic oscillations (IOs) in responses to AM or pure tones. The IOs, which were detected in autocorrelation functions and power spectra, were closely correlated (r = 0.863) with the best envelope frequency (BEF). All of the AN fibers showed broad low-pass MTFs with some showing a rudimentary peak in the MTF. The MTFs of DCN-PVCN neurons and AN fibers showed, respectively: (1) BEFs ranging 50-500 Hz, and 400-1300 Hz; (2) upper cut-off frequencies ranging 200-1200 Hz, and 1600-3200 Hz. At stimulus levels of 60-85 dB SPL, maximum modulation gains were as high as 12 dB for DCN-PVCN neurons but were limited to below about 0 dB for AN fibers. The median dynamic ranges of DCN and PVCN neurons (51 and 42 dB, respectively) were substantially wider than those of the low and high spontaneous rate AN fibers (30 and 31 dB, respectively). The observation of higher modulation gain, wider dynamic range, and more narrowly-tuned MTF of DCN-PVCN neurons than AN fibers supports the concept that the capabilities to encode dynamic signals are enhanced in DCN-PVCN neurons compared with AN fibers.

Acoustic Stimulation↗

Indication for the need of flexible and frequency specific mapping functions in cochlear implant speech processors.

Categorical loudness scaling of electric and acoustic stimuli was performed in cochlear implant (CI) recipients equipped with Nucleus systems in order to achieve a normal loudness perception in the whole dynamic range of acoustic input. For each electrode, the lower and upper limits of electric stimulus were defined by the values corresponding to "very soft" and "too loud". Within this dynamic range, the stimulus strength intervals associated to the verbal categories "soft", "medium", "loud" and "very loud" were determined. The same loudness categories were used for the scaling of acoustic stimuli. From both scaling experiments, the transduction of the CI system can be assessed and the parameters of the individual mapping function yielding a normal loudness growth can be derived. Deviations from optimum mapping can be corrected at least partially by manipulating the parameters of the mapping function. In many cases, however, one mapping function is not sufficient for all channels. The results argue in favour of the development of flexible and channel-specific mapping function parameters in future CI systems.

Cochlear Implants↗

Quantitative real-time polymerase chain reaction for determination of plasmid copy number in bacteria.

A method for determination of plasmid copy number (PCN) in bacteria by real-time quantitative polymerase chain reaction (QPCR) was developed as an alternative to current PCN assays. Conventional methods for PCN estimation are generally not of high throughput, laborious, have low reproducibility, require large amounts of biological samples and are applicable only for a narrow dynamic range. Real-time QPCR, using the ABI Prism 7000, was able to sensitively detect the quantity of the pUC ori based plasmid, NS3, transformed into Escherichia coli host, DH5alpha, to be 411+/-6.1. The PCN of pBR322 plasmid DNA in DH5alpha was estimated to be 40+/-0.6 which is within its previously reported PCN range of approximately 30 to 70. QPCR was found to show good reproducibility and high sensitivity in detecting a two fold difference in template concentration, and a wide linear dynamic range covering 0.5 pg to 50 ng of DNA. PCNs of DH5alpha bearing plasmids pBR322 and NS3 computed from real-time QPCR assay were validated by that of agarose gel assay, and a marginal difference of only 13.0% and 10.7% was found for the two plasmids respectively. The QPCR assay was able to detect changes in PCN of plasmid producing DH5alpha during the course of a 2 l batch fermentation.

Culture Media↗

Acoustic-reflex growth and loudness.

Acoustic-reflex growth functions and loudness-balance judgments were obtained for three normal-hearing subjects with normal middle-ear function. The hypothesis that acoustic reflex-activating signals producing proportionately equal acoustic-impedance changes are judged equal in loudness was evaluated. The mean acoustic impedance and associated standard deviations were computed for the baseline (static) and activator (reflex) portions of each reflex event. An acoustic-impedance change exceeding two standard deviations of baseline was defined as the criterion acoustic-reflex response. Acoustic impedance was measured as a function of activator SPL for broadband noise and a 1000-Hz tone from criterion magnitude to the maximum acoustic impedance (or 120-dB SPL). This was defined as the dynamic range of reflex growth. Loudness-balance measurements were made for the 1000-Hz tone and broadband noise at SPL's representing 30, 50, and 70% of the individual dynamic range. The data supported the hypothesis.

Acoustic Impedance Tests↗

Relation between stimulus and response in frog olfactory receptor neurons in vivo.

The spiking activity of receptor neurons was recorded extracellularly in the frog olfactory epithelium in response to four odourants applied at precisely controlled concentrations. A set of criteria was formulated to define the spikes in the response. Four variables - latency, duration, number of interspike intervals and frequency - were determined to quantify the responses. They were studied at the single neuron, neuron population and ciliary membrane levels. The dose-response curves were determined using specific functions and their characteristics were evaluated. The characteristic molar concentrations at threshold or at maximum duration and the characteristics of variables, e.g. minimum latency or maximum frequency, have asymmetric histograms with peaks close to the origin and long tails. Dynamic ranges have even more asymmetric histograms, so that a significant fraction of neurons presents a much wider range than their one-decade peak. From these histograms, response properties of the whole neuron population can be inferred. In general, location along the concentration axis (thresholds), width (dynamic ranges) and heights of dose-response curves are independent, which explains the diversity of curves, prevents their global categorization and supports the qualitative coding of odourants. No evidence for odourant-independent types of neurons was found. Finally, receptor activation and ciliary membrane conductance were reconstructed in the framework of a model based on firing data, known mucus biochemical and neuron morpho-electrical characteristics. It is in agreement with independent determinations of Kd of odourant-receptor interaction and of conductance characteristics, and describes their statistical distributions in the neuron population.

Action Potentials↗

Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound.

BACKGROUND: OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. OBJECTIVES: To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. RESULTS: OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters.

Aorta, Abdominal↗

Signal coding in cochlear implants: exploiting stochastic effects of electrical stimulation.

Speech perception in quiet with cochlear implants has increased substantially over the past 17 years. If current trends continue, average monosyllabic word scores will be nearly 80% by 2010. These improvements are due to enhancements in speech processing strategies, to the implantation of patients with more residual hearing and shorter durations of deafness, and to unknown causes. Despite these improvements, speech perception in noise and music perception are still poor in most implant patients. These deficits may be partly due to poor representation of temporal fine structure by current speech processing strategies. It may be possible to improve both this representation and the dynamic range of electrical stimulation through the exploitation of stochastic effects produced by high-rate (eg, 5-kilopulse-per-second) pulse trains. Both the loudness growth and the dynamic range of low-frequency sinusoids have been enhanced via this technique. A laboratory speech processor using this strategy is under development. Although the clinical programming for such an algorithm is likely to be complex, some guidelines for the psychophysical and electrophysiological techniques necessary can be described now.

Cochlear Implants↗

Effects of chronic electrical stimulation on patients using a cochlear prosthesis.

Eighteen patients using the Nucleus multichannel cochlear prosthesis underwent annual evaluations for electrical thresholds, dynamic range, and speech recognition abilities for a period of 1 to 5 years. Results revealed no correlation between length of usage of a cochlear implant and electrical thresholds. The dynamic range was initially wider in the patients with open-set speech recognition, but narrowed in subsequent years. There was a correlation between length of deafness and postoperative performance.

Auditory Threshold↗