Increased photon emission from the head while imagining light in the dark is correlated with changes in electroencephalographic power: support for Bókkon's biophoton hypothesis

Bókkon's hypothesis that photons released from chemical processes within the brain produce biophysical pictures during visual imagery has been supported experimentally. In the present study measurements by a photomultiplier tube also demonstrated significant increases in ultraweak photon emissions (UPEs) or biophotons equivalent to about 5×10(-11)W/m(2) from the right sides of volunteer's heads when they imagined light in a very dark environment compared to when they did not. Simultaneous variations in regional quantitative electroencephalographic spectral power (μV(2)/Hz) and total energy in the range of ～10(-12)J from concurrent biophoton emissions were strongly correlated (r=0.95). The calculated energy was equivalent to that associated with action potentials from about 10(7) cerebral cortical neurons. We suggest these results support Bókkon's hypothesis that specific visual imagery is strongly correlated with ultraweak photon emission coupled to brain activity.     

Spontaneous ultraweak photon emission imaging of oxidative metabolic processes in human skin: effect of molecular oxygen and antioxidant defense system

All living organisms emit spontaneous ultraweak photon emission as a result of cellular metabolic processes. In this study, the involvement of reactive oxygen species (ROS) formed as the byproduct of oxidative metabolic processes in spontaneous ultraweak photon emission was studied in human hand skin. The effect of molecular oxygen and ROS scavengers on spontaneous ultraweak photon emission from human skin was monitored using a highly sensitive photomultiplier tube and charged coupled device camera. When spontaneous ultraweak photon emission was measured under anaerobic conditions, the photon emission was decreased, whereas under hyperaerobic condition the enhancement in photon emission was observed. Spontaneous ultraweak photon emission measured after topical application of glutathione, α-tocopherol, ascorbate, and coenzyme Q10 was observed to be decreased. These results reveal that ROS formed during the cellular metabolic processes in the epidermal cells play a significant role in the spontaneous ultraweak photon emission. It is proposed that spontaneous ultraweak photon emission can be used as a noninvasive tool for the temporal and spatial monitoring of the oxidative metabolic processes and intrinsic antioxidant system in human skin.     

In vivo imaging of spontaneous ultraweak photon emission from a rat's brain correlated with cerebral energy metabolism and oxidative stress.

Living cells spontaneously emit ultraweak light during the process of metabolic reactions associated with the physiological state. The first demonstration of two-dimensional in vivo imaging of ultraweak photon emission from a rat's brain, using a highly sensitive photon counting apparatus, is reported in this paper. It was found that the emission intensity correlates with the electroencephalographic activity that was measured on the cortical surface and this intensity is associated with the cerebral blood flow and hyperoxia. To clarify the mechanism of photon emission, intensity changes from whole brain slices were examined under various conditions. The removal of glucose from the incubation medium suppressed the photon emission, and adding 50 mM potassium ions led to temporal enhancement of emission and subsequent depression. Rotenone (20 microM), an inhibitor of the mitochondrial electron transport chain, increased photon emission, indicating electron leakage from the respiratory chain. These results suggest that the photon emission from the brain slices originates from the energy metabolism of the inner mitochondrial respiratory chain through the production of reactive oxygen. Imaging of ultraweak photon emission from a brain constitutes a novel method, with the potential to extract pathophysiological information associated with neural metabolism and oxidative dysfunction of the neural cells.     

Hypothesis about brilliant lights by bioluminescent photons in near death experiences

In near death experiences (NDEs), seeing a brilliant light may arise in the recovery period following cardiac arrest, but the subjects can think that these experiences had happened during the actual period itself. Here we hypothesize a biophysical explanation about the encounter with a brilliant light in NDEs. Accordingly, meeting brilliant light in NDEs is due to the reperfusion that induces unregulated overproduction of free radicals and excited biomolecules among them in numerous parts in the visual system. Unregulated free radicals and excited species can produce a transient increase of bioluminescent photons in different areas of the visual system. If this excess of bioluminescent photon emission exceeds a threshold, they can appear as (phosphene) lights in our mind. In other words, seeing a brilliant light in NDEs may due to bioluminescent photons simultaneously generated in the recovery phase of numerous areas of the visual system and the brain interprets these intrinsic bioluminescent photons as if they were originated from the external visual world. Although our biophysical explanation about brilliant light phenomenon in NDEs can be promising, we do not reject further potential notions.     

Experimental measurement of time-dependent photon scatter for diffuse optical tomography

Time-resolved measurement of early arriving photons through diffusive media has been shown to effectively reduce the high degree of light scatter in biological tissue. However, the experimentally achievable reduction in photon scatter and the impact of time-gated detection on instrument noise performance is not well understood. We measure time-dependent photon density sensitivity functions (PDSFs) between a pulsed laser source and a photomultiplier tube operating in time-correlated single-photon-counting mode. Our data show that with our system, measurement of early arriving photons reduces the full width half maximum of PDSFs on average by about 40 to 60% versus quasicontinuous wave photons over a range of experimental conditions similar to those encountered in small animal tomography, corresponding to a 64 to 84% reduction in PDSF volume. Factoring in noise considerations, the optimal operating point of our instrument is determined to be about the 10% point on the rising edge of the transmitted intensity curve. Time-dependent Monte Carlo simulations and the time-resolved diffusion approximation are used to model photon propagation and are evaluated for agreement with experimental data.     

A temporal and spatial analysis of cavitation on mechanical heart valves by observing faint light emission

Cavitation on mechanical heart valves (MHVs) could cause the mechanical failure of the occluder. A simple and reliable in vitro test method to evaluate cavitation potential must be developed. The bubble implosion damages the MHV material; thus, observing the behavior of the bubble implosion is essential. According to sonoluminescence, the collapsing cavity emits faint light. Therefore, in this study, the bubble collapse was analyzed both temporally and spatially by observing faint light emission. A photon counting system has been developed using a photomultiplier tube (H7360-01, Hamamatsu Photonics, Japan). The highest time resolution of this system is 5 microsec. A quartz optical fiber bundle of 2 mm diameter can be connected to this photomultiplier tube and traversed two-dimensionally over the MHV. The closure of the MHV triggers the photon counter, and the photons through 500 beats are recorded and integrated. A 20 mm Bj?rk-Shiley valve was submerged in a water tank containing 10 L deionized water, and the pressure difference of 120 mm Hg was exerted on the valve at a rate of 60 bpm with a pulse duplicator. Approximately 700 microsec after the valve closure, light emission was detected along the edge of the occluder on the inflow side in the major orifice. Then, approximately 1,000 microsec after the closure, light along the occluder's edge in the minor orifice was recorded as well. Compared with the analysis, using a stroboscope and a high-speed camera, faint light was emitted from the collapsing cavities. In conclusion, sonoluminescnece was successfully observed around the MHV, and the photon counting technique and the traversing mechanism of the optical fiber bundle revealed the temporal and spatial distribution of the cavity collapse on the MHV.     

The statistical distribution of the number of counted scintillation photons in digital silicon photomultipliers: model and validation

In the design and application of scintillation detectors based on silicon photomultipliers (SiPMs), e.g. in positron emission tomography imaging, it is important to understand and quantify the non-proportionality of the SiPM response due to saturation, crosstalk and dark counts. A new type of SiPM, the so-called digital silicon photomultiplier (dSiPM), has recently been introduced. Here, we develop a model of the probability distribution of the number of fired microcells, i.e. the number of counted scintillation photons, in response to a given amount of energy deposited in a scintillator optically coupled to a dSiPM. Based on physical and functional principles, the model elucidates the statistical behavior of dSiPMs. The model takes into account the photon detection efficiency of the detector; the light yield, excess variance and time profile of the scintillator; and the crosstalk probability, dark count rate, integration time and the number of microcells of the dSiPM. Furthermore, relations for the expectation value and the variance of the number of fired cells are deduced. These relations are applied in the experimental validation of the model using a dSiPM coupled to a LSO:Ce,Ca scintillator. Finally, we propose an accurate method for the correction of energy spectra measured with dSiPM-based scintillation detectors.     

Scattering suppression and confocal detection in multifocal multiphoton microscopy

We have developed a new descanned parallel (32-fold) pinhole and photomultiplier detection array for multifocal multiphoton microscopy that effectively reduces the blurring effect originating from scattered fluorescence photons in strongly scattering biological media. With this method, we achieve a fourfold improvement in photon statistics for detecting ballistic photons and an increase in spatial resolution by 21% in the lateral and 35% in the axial direction compared to single-beam non-descanned multiphoton microscopy. The new detection concept has been applied to plant leaves and pollen grains to verify the improvements in imaging quality.     

Visualization of nitric oxide formation in cell cultures and living tissue

We have visualized nitric oxide (NO) released from cell cultures and living tissue. NO was visualized by a reaction with luminol and hydrogen peroxide to yield photons which were counted using a microscope coupled to a photon counting camera. Murine macrophages were activated with interferon-gamma (IFN-gamma) and endotoxin (LPS). Cultured endothelial cells were stimulated with bradykinin, and neurones in the guinea-pig myenteric plexus and the rabbit hypogastric nerve trunk were electrically stimulated. There was a marked increase in photons emitted from the cultured cells as well as from the living tissues during stimulation. The stimulation-induced photon emission was markedly reduced by inhibition of nitric oxide synthase (NOS); removal of L-arginine from the medium also decreased photon counts. The present method allowed integration times in the order of minutes to improve signal-to-noise ratio. However, the high sensitivity of this method also makes it possible to generate an image in seconds, allowing the production of real time films. Photon emission was enhanced under conditions known to increase NO production, and diminished in the presence of NO inhibitors. Thus, this method has demonstrated specificity for the L-arginine:NO pathway from a wide range of biological sources such as cultured cells and living tissues, and has the potential for real time imaging of NO formation, with high temporal and spatial resolution.     

Contrast in diaphanography of the breast

Diaphanography is an imaging technique used in diagnosis of breast disease including cancer. The breast is illuminated with low intensity light and the transmission pattern of red and near-infrared radiation is detected, amplified, reconstructed and displayed in a monitor. The instrumentation for diaphanography has evolved empirically, mostly through clinical practice, without a very clear understanding of the scientific basis of the technique. This research is concerned with investigating theoretically the dependence of the contrast produced by a lesion in a diaphanography image on the size, depth at which a tumor is located, photon energy, and photon angular flux distribution. Contrast calculations using the DOT computer code in a two-dimensional geometry showed that decreasing the size of a tumor by 50% decreases the contrast by a factor of 3 and 4 for 695- and 853-nm photons, respectively. Decreasing the size of the normal tissue where a tumor is imbedded by 25% (from 4 to 3 cm) does not change the contrast very much (less than 20%) for both 695- and 853-nm photons. The contrast for 950- and 695-nm photons is comparable while the values for 853-nm photons are smaller by a factor of 5 for similar cases. The contrast was also found to be dependent on the angle at which the diffuse light is detected after it transverses the host tissue, maximum contrast was found for 695- and 853-nm photons at about 55 degrees. For a detection angle of 77 degrees the contrast observed is 3X and 12X smaller for 695- and 853-nm photons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative comparison of click beetle and firefly luciferases for in vivo bioluminescence imaging

For bioluminescence imaging (BLI) of small animals, the most commonly used luciferase is Fluc from the firefly, but recently, green (CBGr99) and red (CBRed) click beetle luciferases became available. Because signal attenuation by tissues is lower for red light, red luciferases appear to be advantageous for BLI, but this has not been thoroughly tested. We compare different luciferases for BLI. For this purpose, cell transfectants are generated expressing comparable amounts of CBGr99, CBRed, or Fluc. This is achieved by coexpression of the luciferase with eGFP using the bicistronic 2A system, which results in stoichiometric coexpression of the respective proteins. In vitro, the CBGr99 transfectant exhibits the strongest total photon yield. For in vivo BLI, the transfectants are injected into mice at different locations. At a subcutaneous position, CBGr99 is clearly superior to the other luciferases. When the tumor cells are located in the peritoneum or lung, where more absorption by tissue occurs, CBGr99 and CBRed transfected cells emit a comparable number of red photons and are superior to Fluc, but CBGr99 reaches the maximum of the light emission faster than CBRed. Thus, although CBGr99 emits mainly green light, the high yield of total and red photons makes it an excellent candidate for BLI.     

Dosimetric characterization of radionuclides for systemic tumor therapy: influence of particle range, photon emission, and subcellular distribution

Various radionuclides have been proposed for systemic tumor therapy. However, in most dosimetric analysis of proposed radionuclides the charged particles are taken into consideration while the potential photons are ignored. The photons will cause undesirable irradiation of normal tissue, and increase the probability of toxicity in, e.g., the bone marrow. The aim of this study was to investigate the dosimetric properties according to particle range, photon emission, and subcellular radionuclide distribution, of a selection of radionuclides used or proposed for radionuclide therapy, and to investigate the possibility of dividing radionuclides into groups according to their dosimetric properties. The absorbed dose rate to the tumors divided by the absorbed dose rate to the normal tissue (TND) was estimated for different tumor sizes in a mathematical model of the human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres of different sizes (1 ng-100 g). The radionuclides were either assumed to be uniformly distributed throughout the entire tumor and normal tissue, or located in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of the normal cells. Fifty-nine radionuclides were studied together with monoenergetic electrons, positrons, and alpha particles. The tumor and normal tissue were assumed to be of water density. The activity concentration ratio between the tumor and normal tissue was assumed to be 25. The radionuclides emitting low-energy electrons combined with a low photon contribution, and the alpha emitters showed high TND values for most tumor sizes. Electrons with higher energy gave reduced TND values for small tumors, while a higher photon contribution reduced the TND values for large tumors. Radionuclides with high photon contributions showed low TND value for all tumor sizes studied. The radionuclides studied could be divided into four main groups according to their TND values: beta emitters, Auger electron emitters, photon emitters, and alpha emitters. The TND values of the beta emitters were not affected by the subcellular distribution of the radionuclide. The TND values of the Auger electron emitters were affected by the subcellular radionuclide distribution. The photon emitters showed low TND values that were only slightly affected by the subcellular radionuclide distribution. The alpha emitters showed high TND values that were only slightly affected by the subcellular radionuclide distribution. This dosimetric characterization of radionuclides may be valuable in choosing the appropriate radionuclides for specific therapeutic applications.     

Design of a fast multileaf collimator for radiobiological optimized IMRT with scanned beams of photons, electrons, and light ions

Intensity modulated radiation therapy is rapidly becoming the treatment of choice for most tumors with respect to minimizing damage to the normal tissues and maximizing tumor control. Today, intensity modulated beams are most commonly delivered using segmental multileaf collimation, although an increasing number of radiation therapy departments are employing dynamic multileaf collimation. The irradiation time using dynamic multileaf collimation depends strongly on the nature of the desired dose distribution, and it is difficult to reduce this time to less than the sum of the irradiation times for all individual peak heights using dynamic leaf collimation [Svensson et al., Phys. Med. Biol. 39, 37-61 (1994)]. Therefore, the intensity modulation will considerably increase the total treatment time. A more cost-effective procedure for rapid intensity modulation is using narrow scanned photon, electron, and light ion beams in combination with fast multileaf collimator penumbra trimming. With this approach, the irradiation time is largely independent of the complexity of the desired intensity distribution and, in the case of photon beams, may even be shorter than with uniform beams. The intensity modulation is achieved primarily by scanning of a narrow elementary photon pencil beam generated by directing a narrow well focused high energy electron beam onto a thin bremsstrahlung target. In the present study, the design of a fast low-weight multileaf collimator that is capable of further sharpening the penumbra at the edge of the elementary scanned beam has been simulated, in order to minimize the dose or radiation response of healthy tissues. In the case of photon beams, such a multileaf collimator can be placed relatively close to the bremsstrahlung target to minimize its size. It can also be flat and thin, i.e., only 15-25 mm thick in the direction of the beam with edges made of tungsten or preferably osmium to optimize the sharpening of the penumbra. The low height of the collimator will minimize edge scatter from glancing incidence. The major portions of the collimator leafs can then be made of steel or even aluminum, so that the total weight of the multileaf collimator will be as low as 10 kg, which may even allow high-speed collimation in real time in synchrony with organ movements. To demonstrate the efficiency of this collimator design in combination with pencil beam scanning, optimal radiobiological treatments of an advanced cervix cancer were simulated. Different geometrical collimator designs were tested for bremsstrahlung, electron, and light ion beams. With a 10 mm half-width elementary scanned photon beam and a steel collimator with tungsten edges, it was possible to make as effective treatments as obtained with intensity modulated beams of full resolution, i.e., here 5 mm resolution in the fluence map. In combination with narrow pencil beam scanning, such a collimator may provide ideal delivery of photons, electrons, or light ions for radiation therapy synchronized to breathing and other organ motions. These high-energy photon and light ion beams may allow three-dimensional in vivo verification of delivery and thereby clinical implementation of the BioArt approach using Biologically Optimized three-dimensional in vivo predictive Assay based adaptive Radiation Therapy [Brahme, Acta Oncol. 42, 123-126 (2003)].     

Photon spectral characteristics of a new double-walled iodine-125 source.

The photon spectral characteristics of a recently designed Iodine-125 source have been measured. The source has a physical length of 5 mm and a diameter of 0.8 mm. A thin tungsten filament coated with radioactive Iodine-125 is used as a radiographic marker and is encapsulated in a double wall titanium shell of uniform thickness all around. The photon spectral characteristics, measured with an intrinsic germanium (Ge) detector coupled to a multichannel analyzer, reveal that the seed emits the 27.4-keV K alpha and 31.4-keV K beta x rays and 35.5-keV gamma photons from the decay of Iodine-125. Because of their low energy, the tungsten x rays are not observed in the spectrum. The anisotropy of the radiation fluence for each of the above-mentioned photon energies was measured in planes containing the seed short and long axes. The 4 pi-averaged anisotropy factor for the total radiation fluence, i.e., sum of the above three photon energies is 0.92. The photon intensity radiated along the seed long axis is approximately equal to the intensity in the seed transverse direction due to the absence of end welds. The new Iodine-125 source is characterized by good radiographic visualization, greater structural strength due to double wall encapsulation design, and emission of more isotropic Iodine-125 photon spectrum.     

超微弱生物光子辐射的实验及分析方法研究

我们概括了近年来在植物、人体等多方面的研究方法,详细介绍了建立在相干理论基础上的超微弱光子根据发光强度不同与弛豫过程不同两方面,总结了唯象模型下的压缩态参数估计、光子统计熵、双曲弛豫公式、衰减参数的四种分析方法。为促进超微弱光子辐射的进一步发展,为实验设计和分析提供一个较为完整的体系。     

A practical method for depth of interaction determination in monolithic scintillator PET detectors

Several new methods for determining the depth of interaction (DOI) of annihilation photons in monolithic scintillator detectors with single-sided, multi-pixel readout are investigated. The aim is to develop a DOI decoding method that allows for practical implementation in a positron emission tomography system. Specifically, calibration data, obtained with perpendicularly incident gamma photons only, are being used. Furthermore, neither detector modifications nor a priori knowledge of the light transport and/or signal variances is required. For this purpose, a clustering approach is utilized in combination with different parameters correlated with the DOI, such as the degree of similarity to a set of reference light distributions, the measured intensity on the sensor pixel(s) closest to the interaction position and the peak intensity of the measured light distribution. The proposed methods were tested experimentally on a detector comprised of a 20 mm × 20 mm × 12 mm polished LYSO:Ce crystal coupled to a 4 × 4 multi-anode photomultiplier. The method based on the linearly interpolated measured intensities on the sensor pixels closest to the estimated (x, y)-coordinate outperformed the other methods, yielding DOI resolutions between ～1 and ～4.5 mm FWHM depending on the DOI, the (x, y) resolution and the amount of reference data used.     

Correlated histogram representation of Monte Carlo derived medical accelerator photon-output phase space.

We present a method for condensing the photon energy and angular distributions obtained from Monte Carlo simulations of medical accelerators. This method represents the output as a series of correlated histograms and as such is well-suited for inclusion as the photon-source package for Monte Carlo codes used to determine the dose distributions in photon teletherapy. The method accounts for the isocenter-plane variations of the photon energy spectral distributions with increasing distance from the beam central axis for radiation produced in the bremsstrahlung target as well as for radiation scattered by the various treatment machine components within the accelerator head. Comparison of the isocenter energy fluence computed by this algorithm with that of the underlying full-physics Monte Carlo photon phase space indicates that energy fluence errors are less than 1% of the maximum energy fluence for a range of open-field sizes. Comparison of jaw-edge penumbrae shows that the angular distributions of the photons are accurately reproduced. The Monte Carlo sampling efficiency (the fraction of generated photons which clear the collimator jaws) of the algorithm is approximately 83% for an open 10x10 field, rising to approximately 96% for an open 40x40 field. Data file sizes for a typical medical accelerator, at a given energy, are approximately 150 kB, compared to the 1 GB size of the underlying full-physics phase space file.     

Photon spectrometry for the determination of the dose-rate constant of low-energy photon-emitting brachytherapy sources

Accurate determination of dose-rate constant (lambda) for interstitial brachytherapy sources emitting low-energy photons (< 50 keV) has remained a challenge in radiation dosimetry because of the lack of a suitable absolute dosimeter for accurate measurement of the dose rates near these sources. Indeed, a consensus value of lambda taken as the arithmetic mean of the dose-rate constants determined by different research groups and dosimetry techniques has to be used at present for each source model in order to minimize the uncertainties associated with individual determinations of lambda. Because the dosimetric properties of a source are fundamentally determined by the characteristics of the photons emitted by the source, a new technique based on photon spectrometry was developed in this work for the determination of dose-rate constant. The photon spectrometry technique utilized a high-resolution gamma-ray spectrometer to measure source-specific photon characteristics emitted by the low-energy sources and determine their dose-rate constants based on the measured photon-energy spectra and known dose-deposition properties of mono-energetic photons in water. This technique eliminates many of the difficulties arising from detector size, the energy dependence of detector sensitivity, and the use of non-water-equivalent solid phantoms in absolute dose rate measurements. It also circumvents the uncertainties that might be associated with the source modeling in Monte Carlo simulation techniques. It was shown that the estimated overall uncertainty of the photon spectrometry technique was less than 4%, which is significantly smaller than the reported 8-10% uncertainty associated with the current thermo-luminescent dosimetry technique. In addition, the photon spectrometry technique was found to be stable and quick in lambda determination after initial setup and calibration. A dose-rate constant can be determined in less than two hours for each source. These features make it ideal to determine the dose-rate constant of each source model from a larger and more representative sample of actual sources and to use it as a quality assurance resource for periodic monitoring of the constancy of lambda for brachytherapy sources used in patient treatments.     

Improved photomultiplier tube for positron emission tomography

The paper describes an investigation in which it is shown that small positive voltage pulses applied to an external conductor placed against the photocathode of a photomultiplier tube can be used to switch the photocathode completely off for the duration of the pulses. This suggests that a photomultiplier tube with a multisegment photocathode can be constructed, the individual cathode segments of which can be switched off independently by means of such pulses. A theoretical explanation for the effect is provided with the aid of a simple circuit model for the photocathode. Analysis of the model also shows that it is possible to identify the particular cathode segment in which a photon is detected when a pulse is recorded at the phototube's anode. A phototube with these characteristics can have important implications for positron emission tomography, as it can provide improved spatial resolution, simultaneous multislice capability and the ability to eliminate distortion due to dead-time effects at high count rates.     

Water-equivalent plastic scintillation detectors for high-energy beam dosimetry: I. Physical characteristics and theoretical consideration.

A minimally perturbing plastic scintillation detector has been developed for the dosimetry of high-energy beams in radiotherapy. The detector system consists of two identical parallel sets of radiation-resistant optical fibre bundles, each connected to independent photomultiplier tubes (PMTs). One fibre bundle is connected to a miniature water equivalent plastic scintillator and so scintillation as well as Cerenkov light generated in the fibres is detected at its PMT. The other 'background' bundle is not connected to the scintillator and so only Cerenkov light is detected by its PMT. The background signal is subtracted to yield only the signal from the scintillator. The water-equivalence of plastic scintillation detectors is studied for photon and electron beams in the radiotherapy range. Application of Burlin cavity theory shows that the energy dependence of such detectors is expected to be better than the commonly used systems (ionization chambers, LiF thermoluminescent dosimeters, film and Si diodes). It is also shown that they are not affected by temperature variations and exhibit much less radiation damage than either photon or electron diode detectors.