Multimodal evoked potentials in patients with pediatric leukodystrophy.
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In this chapter, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are reviewed. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model, and regularized linear inverse source estimates. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) and event-related (coupling of activated voxels) fMRI. As an example, these methods were applied to EEG (128 electrodes) and fMRI data, which were recorded in separate sessions while normal subjects executed voluntary right one-digit movements.
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We treated 114 patients with advanced inoperable head and neck cancer with a combined-modality protocol that included two cycles of chemotherapy followed by radiotherapy or three chemotherapy and in 18 patients with a radiosensitizing agent. At the beginning of the treatment all but one patient presented with a stage IV cancer. With a follow-up of 42-58 months, four patients are alive (three from the radiosensitizing group and one of the chemotherapy group). Complete response after the radiosensitizing agent correlated with superior prolonged disease-free survival in comparison to complete responses after chemotherapy at the level of p less than 0.009.
Pattern reversal visual, brain-stem auditory, and short latency median nerve somatosensory evoked potentials (EPs) were evaluated in a prospective study over 4 years in 20 patients with clinically definite sclerosis (MS). Standardized neurological examinations were done at regular intervals and correlated with EP findings. The highest incidence of EP abnormalities occurred in the visual system followed by the somatosensory and auditory systems. Clinical relapse was usually accompanied by EP deterioration, but clinical improvement often occurred without parallel EP recovery. EP changes were not always related to clinical symptoms and often took place during remission periods in the absence of clinical changes. There was no significant correlation between clinical and electrophysiological progression within any given sensory modality. The progression of clinical disability, however, showed a fairly good correlation with the overall progression of EP abnormalities. We conclude that EPs complement the neurological exam in the evaluation of MS and may have a place in the investigation of the effects of therapeutic agents on the neurological status in MS.
BACKGROUND: Little is understood about the evolution of structural and functional brain changes during the course of uncontrolled focal status epilepticus in humans. METHODS: We serially evaluated and treated a nine-year-old girl with refractory focal status epilepticus. Long-term EEG monitoring, MRI, MRA, SPECT, intraoperative visualization of affected cortex, and neuropathological examination of a biopsy specimen were conducted over a three year time span. Imaging changes were correlated with simultaneous treatment and EEG findings. RESULTS: The EEG monitoring showed almost continuous spike discharges emanating initially from the right frontocentral area. These EEG abnormalities were intermittently suppressed by treatment with anesthetics. Over time, additional brain areas developed epileptiform EEG abnormalities. Serial MRI studies demonstrated an evolution of changes from normal, through increased regional T2 signal to generalized atrophy. An MRA demonstrated dilatation of the middle cerebral artery stem on the right compared to the left with a broad distribution of flow-related enhancement. An 18FDG-PET scan showed a dramatically abnormal metabolic profile in the same right frontocentral areas, which modulated in response to treatment during the course of the illness. A right frontotemporal craniotomy revealed a markedly hyperemic cortical focus including vascular shunting. A sample of resected cortex showed severe gliosis and neuronal death. CONCLUSIONS: The co-registration of structural and functional imaging and its correlation with operative and pathological findings in this case illustrates the relentless progression of regional and generalized abnormalities in intractable focal status epilepticus that were only transiently modified by exhaustive therapeutic interventions. Increased flow through large vessels appeared to be shunted and did not translate into increased microvascular perfusion.
Incorporation of planar waveguide technology into a spectroelectrochemical sensor is described. In this sensor design, a potassium ion-exchanged BK7 glass waveguide was over-coated with a thin film of indium tin oxide (ITO) that served as an optically transparent electrode. A chemically selective film was spin-coated on top of the ITO film. The sensor supported five optical modes at 442 nm and three at 633 nm. Investigations on the impact of the ITO film on the optical properties of the waveguide and on the spectroelectrochemical performance of the sensor are reported. Sensing was based on the change in attenuation of light propagated through the waveguide resulting from an optically absorbing analyte. By applying either a triangular or square wave excitation potential waveform, electromodulation of the optical signal has been demonstrated with Fe(CN)6(3-/4-) as a model electroactive couple that partitions into a PDMDAAC-SiO2 film [where PDMDAAC = poly(dimethyldiallylammonium chloride)] and absorbs at 442 nm.
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A spectroelectrochemical sensor with attenuated total reflectance at an indium-doped tin oxide (ITO) optically transparent electrode coated with a thin film of Nafion has been demonstrated for the determination of aqueous iron ion. The novelty of this sensor stems from its ability to take up colorless iron ion (Fe2+) from solution and complex it with an organic ligand, 2,2'-bipyridine (bipy), that has been previously loaded in the optically transparent charge-selective Nafion film coating the electrode. The resulting complex ion, tris(2,2'-bipyridyl)iron(II), Fe(bipy)3(2+), absorbs strongly, making it easily detectable via optical spectroscopy. Fe(bipy)3(2+) loaded into the selective film is oxidized to colorless Fe(bipy)3(3+), which gives rise to an absorbance change for quantifying iron. This paper maps the development of this sensor, from the spectroelectrochemical characterization of the complex ion at an ITO optically transparent electrode to an analysis of the uptake, retention, and optical response of the complex ion in the Nafion film. Finally, an evaluation of the uptake of aqueous Fe2+ by the bipy-loaded Nafion film is reported. These data include preliminary results illustrating the dependence of the sensor response on differing concentrations of Fe2+ in solution.
An instrumental setup has been configured for a simultaneous real time recording of electrochemical, spectroelectrochemical, and mass data on an electrode from a single measurement for studies of complex electrochemical reaction mechanisms. This was achieved by combining a few pieces of equipment: a potentiostat/galvanostat for electrochemical measurements, the near-normal incidence reflectance spectrometer for spectroelectrochemical measurements, and a quartz crystal analyzer (QCA) for mass changes on the electrode. The latter two were coupled through a bifurcated optical fiber on the reflective QCA electrode. The experimental setup thus assembled was demonstrated to be very powerful in elucidating reaction mechanisms of the reaction sequence for a complex reaction, for example, electrochemical oxidation of aniline, which accompanies spectral, as well as weight, changes upon oxidation. The system was also applied to the study of the lithium intercalation reaction of tungsten trioxide thin films in a nonaqueous solution.
Palladium was electrodeposited onto lithographically patterned Si(100) "micro-channels" with dimensions of 2 microm (width) x 100 microm (length). The properties of these Pd-covered Si micro-channels for detecting dihydrogen gas were then evaluated. Pd electrodeposition was carried out under conditions favoring an instantaneous nucleation and growth mechanism. This strategy produced size-similar Pd particles at a coverage of (4-6) x 10(9) cm(-2) within the confines of the Si micro-channel. When the mean particle radius, ro, was smaller than a critical value (ro < rc = 70-85 nm), each Pd particle was well separated on the surface from adjacent particles, on average, and no response to H2 gas attributable to the micro-channel was observed. As Pd particles were grown larger, to a mean radius of ro approximately equal to rc, adjacent particles on the surface touched and the electrical resistance of the micro-channel dropped by several orders of magnitude. These "type 2" H2 sensors exhibited a rapid (< 1 s), reversible decrease in their resistance in response to exposure to H2 above 0.5%, but a minimum resistance was observed at 1-2%, and a resistance increase was seen at higher H2 concentration. This complex behavior resulted from the existence of three mechanisms for charge transport across the micro-channel. If still larger quantities of Pd were deposited, the Pd particle ensemble coalesced into an electrically continuous film. These "type 3" sensors became more resistive in the presence of H2, not more conductive as seen for sensors of types 1 and 2, but the amplitude of this response was smaller than seen for type 2 sensors.
A fluorescence spectroelectrochemical sensor capable of detecting very low concentrations of metal complexes is described. The sensor is based on a novel spectroelectrochemical sensor that incorporates multiple internal reflection spectroscopy at an optically transparent electrode (OTE) coated with a selective film to enhance detection limits by preconcentrating the analyte at the OTE surface. Nafion was used as the selective cation exchange film for detecting Ru(bpy)(3)(2+), the model analyte, which fluoresces at 605 nm when excited with a 441.6-nm HeCd laser. The unoptimized linear dynamic range of the sensor for Ru(bpy)(3)(2+) is between 1 x 10(-)(11) and 1 x 10(-)(7) M with a calculated 2 x 10(-)(13) M detection limit. The sensor employs extremely thin films ( approximately 12 nm) without significantly sacrificing its sensitivity. The sensor response is demonstrated with varying film thicknesses. A state-of-the-art flow cell design allows variable cell volumes as low as approximately 4 microL. Fluorescence of the sample can be controlled by electromodulation between 0.7 and 1.3 V. Sensor operation is not reversible for the chosen model film (Nafion) and sample (Ru(bpy)(3)(2+)) but it can be regenerated with ethanol for multiple uses.
We report herein an attenuated total reflectance (ATR) absorbance-based spectroelectrochemical sensor for tris(2,2'-bipyridyl)ruthenium(II) ion [Ru(bpy)(3)(2+)] that employs ultrathin (24-50 nm) Nafion films as the charge-selective layer. This film serves to sequester and preconcentrate the analyte at the optically transparent electrode surface such that it can be efficiently detected optically via electrochemical modulation. Our studies indicate that use of ultrathin films in tandem with continuous flow of sample solution through the cell compartment leads to a 100-500-fold enhancement in detection limit (10 nM) compared to earlier absorbance-based spectroelectrochemical sensors ( approximately 1-5 microM); markedly shorter analysis times also result. We report the dependence of the measured absorbance on sample flow rate and Nafion film thickness, and also provide calibration curves that illustrate the linear range and detection limits of the sensor using a 24 nm film at a constant sample flow rate of 0.07 mL/min.
The present study describes a stabilization of single quantum dot (QD) micelles by a "hydrophobic" silica precursor and an extension of a silica layer to form a silica shell around the micelle using "amphiphilic" and "hydrophilic" silica precursors. The obtained product consists of approximately 92% single nanocrystals (CdSe, CdSe/ZnS, or CdSe/ZnSe/ZnS QDs) into the silica micelles, coated with a silica shell. The thickness of the silica shell varies, starting from 3-4 nm. Increasing the shell thickness increases the photoluminescence characteristics of QDs in an aqueous solution. The silica-shelled single CdSe/ZnS QD micelles possess a comparatively high quantum yield in an aqueous solution, a controlled small size, sharp photoluminescence spectra (fwhm approximately 30 nm), an absence of aggregation, and a high transparency. The surface of the nanoparticles is amino-functionalized and ready for conjugation. A comparatively good biocompatibility is demonstrated. The nanoparticles show ability for intracellular delivery and are noncytotoxic during long-term incubation with viable cells in the absence of light exposure, which makes them appropriate for cell tracing and drug delivery. The presence of the hydrophobic layer between the QD and silica-shell ensures an incorporation of other hydrophobic molecules with interesting properties (e.g., hydrophobic paramagnetic substances, hydrophobic photosensitizers, membrane stabilizers, lipid-soluble antioxidants or prooxidants, other hydrophobic organic dyes, etc.) in the close proximity of the nanocrystal. Thus, it is possible to combine the characteristics of hybrid materials with the priority of small size. The silica-shelled single QD micelles are considered as a basis for fabrication of novel hybrid nanomaterials for industrial and life science applications, for example, nanobioprobes with dual modality for simultaneous application in different imaging techniques (e.g., fluorescent imaging and functional magnetic resonance imaging).
The use of a mediator to detect a nonabsorbing analyte during spectroelectrochemical modulation is demonstrated. The charge-selective composite film of Nafion-SiO2 was used to entrap the mediator, Ru(bipy)3(2+). The change in deltaA as detected by attenuated total reflection was then observed upon addition of the analyte, ascorbate. The effects of scan rate, concentration of mediator, film thickness, and analyte charge were studied to achieve optimal sensor conditions. The model sensor exhibited a linear range from 0.26 to 2.0 mM (R2 = 0.998).
The simulation of the optical response in spectroelectrochemical sensing has been investigated. The sensor consists of a sensing film coated on an optically transparent electrode (OTE). The mode of detection is attenuated total reflection. Only species that partition into the sensing film, undergo electrochemistry at the potentials applied to the OTE, and have changes in their absorbance at the wavelength of light propagated within the glass substrate of the OTE can be sensed. A fundamental question arises regarding the excitation potential waveforms employed to initiate the electrochemical changes observed. Historically, selection has been based solely upon the effectiveness of the waveform to quickly electrolyze any analyte observable by the optical detection method employed. In this report, additional requirements by which the waveform should be selected for use in a remote sensing configuration are discussed. The effectiveness of explicit finite difference simulation as a tool for investigating the applicability of three different excitation potential waveforms (square, triangle, sinusoid) is demonstrated. The simulated response is compared to experimental results obtained from a prototype sensing platform consisting of an indium tin oxide OTE coated with a cation-selective, sol-gel-derived Nafion composite film designed for the detection of a model analyte, tris(2,2'-bipyridyl)ruthenium(II) chloride. Using a diffusion coefficient determined from experimental data (5.8 x 10(-11) cm2 s for 5 x 10(-6) M Ru(bipy)3(2+)), the simulator program was able to accurately predict the magnitude of the absorbance change for each potential waveform (0.497 for square, 0.403 for triangular, and 0.421 for sinusoid), but underestimated the number of cycles required to approach steady state. The simulator program predicted 2 (square), 3 (triangle), and 5 cycles (sinusoid), while 5 (square), 15 (triangle), and 10 (sinusoid) cycles were observed experimentally.
Apoptosis, or programmed cell death, plays an important role in the etiology of a variety of diseases, including cancer. Visualization of apoptosis would allow both early detection of therapy efficiency and evaluation of disease progression. To that aim we developed a novel annexin A5-conjugated bimodal nanoparticle. The nanoparticle is composed of a quantum dot that is encapsulated in a paramagnetic micelle to enable its use both for optical imaging and MRI. Multiple recombinant human annexin A5 protein molecules were covalently coupled to the nanoparticle for targeting. In this study the specificity of the annexin A5-conjugated nanoparticles for apoptotic cells was demonstrated both with fluorescence microscopy and MRI, which confirms its potential for the detection of apoptosis with both imaging modalities in vivo.
A portable spectroelectrochemical sensor has been designed, evaluated, and demonstrated on a complex sample of radioactive waste. The sensor consisted of a black delrin sample compartment with a total internal sample volume of 800 microL, attached to an indium tin oxide coated glass multiple internal reflection optical element. Detection was by total internal reflection of light from a blue light emitting diode source. After a 10 min uptake for each standard, the sensor showed a linear response in absorbance change for 5 x 10(-5) to 5 x 10(-3) M ferrocyanide with electrochemical modulation by scanning at 20 mV/s from -0.30 V to +0.55 V vs a Ag/AgCl reference electrode. Due to the complex nature of Hanford radioactive tank waste samples containing ferrocyanide, a standard addition method was developed for analysis. The spectroelectrochemical sensor determined a concentration of 9.2 mM ferrocyanide for U-Plant-2 simulant solution containing 9.38 mM ferrocyanide that was prepared according to Hanford process flowsheets. A radioactive tank waste sample from Hanford Tank 241-C-112 was determined to be 1.0 mM in ferrocyanide using the spectroelectrochemical sensor. A value for the ferrocyanide concentration in the sample of 0.61 mM was determined by FTIR spectroscopy.