AU2007100353A4 - Multy scale human holographic-spectroscopic imaging via stimulation with multiple optical imaging sources - Google Patents

Description

EDITORIAL NOTE The description starts on page 1 and finishes at page 24. It continues from page 31 to page 34.

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0 Australia Patents Act 1990 INNOVATION PATENT SPECIFICATION Invention Title: Multi-scale human holographic spectroscopic imaging via stimulation with multiple optical imaging sources.

Applicants Professor Paul B Fitzgerald (Bayside Health, The Alfred), Dr. Arkady S. Lipkin (HNDT&LIQC PTY.LTD.).

Inventors Professor Paul B Fitzgerald, Dr. Arkady S. Lipkin.

The invention following Provisional Patent Application number 2006902270, Filed on 2 May 2006.

-11- The invention is described in the in the following statement: 0 DATED 25 April, 2007 Multi-scale human holographic spectroscopic imaging via stimulation Swith multiple optical imaging sources.

Field of Invention The present invention relates to the field of Near infrared (NIR) light holographic imaging of the human brain and human organs via stimulation with coherent Multiple Optical Imaging sources and amplification of emission intrinsic changes in the electromagnetically and NI optical properties of electrically andlor metabolically active tissue. Medical Device Development the innovation aims to develop a new method for the assessment of the structure and function of the brain and bodily organs including the heart and blood vessels. This capacity may be applied to studying correlation between the activity of distant organs such as the brain and heart. This will have application to medical diagnosis, neuroscience research applications and the targeting of physical treatments of heart and brain diseases. In addition there will be potential applications for the diagnosis of brain and heart disease in the relationship between these using NIR and infrared light together with radio and microwave radiation.

Introduction Over recent years a number of forms of optical imaging have been developed for assessing brain function (near infrared spectroscopy (NIRS), optical tomography and topographic imaging). All of these techniques utilize NIRS techniques which involve the application of near-infrared (NIR) radiation to assess the contribution of certain homophobes in the brain to the scattering and absorption of the applied c NIR radiation. Refraction light passes through a transparent substance, O such biological tissues, its speed is reduced, and it is measurements undergo refractive index; SCurrent State of the Art In SThese include computed tomography magnetic resonance imaging S(MRI) and optical imaging applications (near infrared spectroscopy, optical tomography and topographic imaging). CT and MRI are widely used in the imaging of the human brain for the purpose of the diagnosis of disease and the investigation of normal and abnormal function.

Although these techniques have substantial utility, there are limits of currently available technology. These include limits of the capacity of MRI to image functional change over small time scales whilst retaining structural (spatial) resolution. Current optical applications can measure functional activity at fine spatial resolution but only in restricted regions of the brain at any one time. In addition, the presentation of threedimensional brain images from techniques such as CT and MRI requires the reconstruction of these images from multiple two-dimensional images. Thus the data is never 'complete' as the space between image 'slices' is 'filled in' in the image reconstruction process. In addition there are practical problems with several of the currently utilized techniques. For example, CT involves the use of radiation that can result in tissue damage on a dose related basis. MRI can not be done in the presence of ferrous metals or medical devices such as pacemakers, limiting its application in some patient and study populations.

A number of recent imaging techniques have adapted the use of none ionizing near infra red radiation for the imaging of superficial brain structures with high temporal resolution. NIRS techniques involve the application of near-infrared (NIR) radiation to monitor the degree of oxygenation of certain metabolites. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well t defined, and which are present in sufficient quantities to contribute O significant attenuation to measurements of transmitted light. However, 0 there are major limitations with current optical imaging techniques: current techniques have relatively low spatial resolution. Each Soptodelsensor only assesses a small area of the cortex. To study larger Sareas requires the application of multiple optodes, the application of which is complicated and requires expensive instrumentation.

0- There is a significant limitation in the depth of penetration of the NIR used and hence a major limitation in the brain regions that may be studied. For practical purposes, this is restricted to superficial layers of the cortex in adult subjects preventing any form of tomography or 3 dimensional reconstructions of brain images. The issue of depth penetration is also heightened by boundary issues relating to the need for NIR to pass through a low attenuating CSF layer prior to entry into the brain.

Various types of emission dynamic functional imaging were developed under supervision Dr. E.Godik (Russian technology consultant in USA) a general illustration of physical fields and radiations arising around the human in the process of a vital activity we see in FIGURE 1,a (the bodv)l,b(the head); The infrared thermal radiation (red) characterizes functioning of the capillary blood flow network in the skin which ensures thermoregulation of the body. The chemoluminescence (green) characterizes saturation of tissues with oxygen and the level of antioxidants. In addition, a chemical "microatmosphere" is formed near the body by exhaled air, skin respiration. The radiothermal (orange) and acoustothermal (brown) radiations carry information on temperature dynamics of internal organs. bioelectric activity of the heart, brain, and muscles. Russian group under supervision Dr Y.V.Guluev together with 0 Dr E.Godik in last 25 years crieted following new emission imaging: c dynamic infrared thermo vision (1983), infrared thermoencephaloscopy O (1984), electrical impedance mapping (1984), acoustic thermography (1985), magnetic mapping of heart (1086), mapping of evoked magnetic field of the brain (1987), Microwave thermal mapping (1987) dynamic breast imaging (1995), opticb-mechanical breast imaging (1999).

SElectromaghetic radiation (EMR), the first observation of Selectromagnetic emissions from material under stress was made in 1933 S(Urusovskaja, 1969) and from oil (O.Kuznetsov 1979) and brain modeling liquid (Sudakov 1980). Since then a number of authors have investigated the emissions from different organic and polymer materials under laboratory conditions and have witnessed high counts of EMR and NI emission. For example the frequency range over which emissions is between 1 kHz and 10 MHz with wavelengths from 30m to +300 km.

Cress et al (1987) found that maximum EMR occurred over the frequency range 0.5 1 MHz. Earlier research by Hanson et al (1981) had detected EMR during the catastrophic failure of quartz material. The number of different theories being proposed: theory among them states that the fracturing of atomic bonds during the failure process is the likely cause of the emissions another theory is substantiated by the mirroring of NI light and electromagnetic emissions by acoustic emissions (1977 ,A.Lipkin, A. Rutman). Also theory polarization electrical field of the coherent light intensities light with soliton energy electric currents that flow in the brain are necessary particular for low frequency electromagnetic (EM) emissions; Exiton acoustic response, ultrasound emissions, electromagnetic emissions and thermal emissions utilizing all of these phenomena 's would have to be capable acoustic or electromagnetic, as an indication of micro-damage of brain a number of inherent problems relating to its use in a diagnostic and methods, and their applications in biomedical science and clinical

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Spractice with research and development as interferometer and holography, diffractometry and coherent light microscopy, speckle O technologies, low-coherence interferometer and tomography was used.

Applications of coherence domain optical methods for the investigation of all types of living tissues and phantoms are expected to be m presented. The holographic NI optical instruments based on coherent t' light interaction with scattering media was used for medical noninvasive 0 diagnosis and monitoring of diseases The optoacoustic effect and its applications for analysis in optoacoustic Sspectrometry (OAS) and for the study of emission of sample types organic material and biological tissues of near-infrared spectral region absorption spectra. V. Pustovoit (1985-2005) described several OAS spectrometers in the literature. O.Kusnetsov, A.Lipkin (2000-2003) used temperature and the associated acoustic emissions to detect the presence of temporal changes in the medium, or in diagnostic mode, where the temporal change in the medium is quantified. The emission in near-infrared spectral region O.Kusnetsov (Moscow, Russia) a recent articles describes a comparison between a new method for the determination of the oxidative stability of oils and brain density modeling liquid and pore structure at temperatures, based on nearinfrared emission spectroscopy (NIRES), and the Rancimat method. In the NIRES-based method, the induction time (IT) is determined by means of the variation of the emission band at 2900 nm during heating.

The similar results in the NIRES-based method indicate that benzophenone probably belongs to a different class of compounds peak for the reduction of the carbonyl group in m-nitrobenzaldehyde was obviously distorted by the tail of the first reduction peak change in the reduction mechanism, but the results obtained here were very encouraging. Work supported by the Office of Naval Research.

Optoacoustic Spectrometry in the Near-Infrared Region M. J. Adams," B.

C. Beadle, and G. F. Kirkbright Chemistry Department, Imperial College of Science and Technology, (London Innovative target Project of Prof. P. Fitzgerald Dr. A. Lipkin is method O monitoring real time neuronal activity of brain experimentally starting in 1970 year by Gulyaev, Yu.V., and Godik, (Russia) Radio physical Approach Mapping of evoked magnetic field of the brain (1987) infrared Sthermoencephaloscopy, thermography using silicon detectors.

0 The project Prof. P. Fitzgerald Dr. A. Lipkin near 4 years already going O internationally with number high level researches. The anticipated next step will involve the development of a final prototype and the conduct of clinical testing activities by International Team.

In Australia will assemble the major hardware components for the project including all of the NI optical imaging devices. International cooperation with Prof.A. Bobrov, Prof. V. Cheblanov, Institute of Biophysics, Y.Alexandrov Institute Physihology will progress theory and experiments for following method of diagnosing a living organism by multimodal functional mapping of the living organism (USA, Patent).

Current methods for Brain Stimulation The last 10 years has seen the development of a variety of novel forms of brain stimulation that are being trialed for the investigation and treatment of various neurological and psychiatric disorders. These techniques include transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS), deep brain stimulation (DBS) and direct current electrical stimulation. Neurobiological effects to exposure of nonionizing electromagnetic fields by radio wave and microwave radiation (Gillard J.1976, Holodov Y.A.1979, WillamsonS.J.1989, Sounders R.D.1991, SudakovK.B. 1997). Spectral radiance irradiance of Nonlinear media with Nonlinear optical applications brain tissues covered by F&L, ranging brain data storage and brain NI photonic band recognition; The gain 02 hydrogen relationship for the first Stokes component 1,13

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m the pump source length wave 1,06 m Pulse energy, 1 J max. Pulse length.12ns D beam 10mm the source was and laser Nd. has been O reported by Yu.l. Karev jornal Kvant.Electrone .Moscow.6(10)2274 in 1979 Since the late 1990s, an increasing number of researchers have used c NIRS and other diffuse optical tomographic (DOT) techniques in brain 0 mapping studies (Rubeh, Wenzel et al. 1997) (Sakatani, Chen et al. 1999) 0 (Obrig, Wolf et al. 1996) (Colier, Quaresima et al. 1999) (Kleinschmidt, Obrig et al. 1996) (Hirth, Obrig 6t al. 1996) (Sato, Takeuchi et al. 1999), as well as in studies of clinical applications related to brain function. The former have used visual, auditory and somatosensory stimuli to identify areas of the brain associated with certain cognitive functions; other areas of investigation include the motor system and language. The latter have addressed the prevention and treatment of seizures (Steinhoff, Herrendorf et al. 1996) (Adelson, Nemoto et al. 1999) (Sokol, Markand et al. 2000) (Watanabe, Maki et al. 2000) and psychiatric concerns such as depression (Okada, Takahashi et al. 1996) (Eschweiler, Wegerer et al.

2000) (Matsuo, Kato et al. 2000), Alzheimer's disease (Hock, Villringer et al. 1996) (Fallgatter, Roesler et al. 1997) (Hock, Villringer et al. 1997) (Hanlon, Itzkan et al. 1999) and schizophrenia (Okada, Tokumitsu et al.

1994) (Fallgatter and Strik 2000), as well as stroke rehabilitation (Vernieri, Rosato et al. 1999) (Chen, Li et al. 2000) (Nemoto, Yonas et al.

2000) (Saitou, Yanagi et al. 2000). See Boas 2004 for a review of clinical applications related to brain function.

In 1974 -1977 Dr.A. Zabludovsky length wave 1,06 m pumping through rate brain blood vessel in 02 in H20 the first Stokes component 1,13 m this was Raman effect super luminescent emission measurement under scalp rate brain. In 1975 as joint experiments of Dr.A. Zabludovsky done together with A. Rutman ,A.Lipkin (MVMI,Moscow). the experiments with calibration plazmatron and background HeNe laser together with holographic sensoring for NI emission 07-1,2 m radiation. This

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Scalibration with measuring NI light results was using together with data base for discovery vision phenomen Mrs. Rosa Kuleshova A. Rutman O ,A.Lipkin Material SO AN SSSR,Novosibirsk, 1976.

Although some of these brain stimulation techniques are showing considerable promise in the treatment of certain psychiatric disorders, m there are considedable limitations in their practical applications. These 0 include, but are not limited to, the depth of stimulation with superficial O techniques such as the TMS and electrical stimulation and the invasive nature of techniques such as DBS. Clearly neuropsychiatric disorders involve a range of brain areas that include regions that are amenable to stimulation with techniques that are able to penetrate only superficial areas of the cortex as well as brain regions that a much deeper. Recent research has also clearly indicated that many major neuropsychiatric disorders involve distributed networks of brain regions that are currently not able to be stimulated with techniques focused on only one brain area. A substantive advance in the use of brain simulation techniques to treat these disorders requires the development of novel techniques that are able to non-invasively stimulate a variety of regions in of the brain. These regions need to be both superficial and deep and adequate techniques should be able to stimulate multiple areas simultaneously to modulate the networks that are known to be involved in the pathophysiology of these diseases. An additional limitation in current techniques is the lack of capacity to adequately target these methods In parallel to the development of these Stimulation and future new treatments, we are rapidly increasing our knowledge about the pathophysiological basis of a number of these disorders. Interestingly, there is growing evidence that a number of brain disorders may directly arise from mechanisms that result in abnormal synchronous oscillations of groups of nerve cells in the brain. For example, in schizophrenia it appears that problems with fundamental aspects of memory may relate to an abnormality in the capacity of frontal areas of t the brain to oscillate appropriately in frequencies between 20 and 60 Hz.

O There is also a suggestion of abnormal of oscillatory patterns in depression and other disorders. This oscillatory activity may play a critical role in normal brain function in the integration of perception Sfrom multiple sensory systems and in linking information processing Sbetween distributed brain regions. Therefore, it is possible that the capacity to change the frequency of brain oscillations across multiple brain regions simultaneously may have a critical role in therapeutic applications of brain stimulation techniques.

Human tissues contain a variety of substances whose refraction (is not only absorption) spectra at NIR wavelengths are well defined A.Lipkin, P.Fitzgerald (2005-2007), and which are present in sufficient quantities to contribute significant attenuation to measurements of coherent NI transmitted light. The concentration of some absorbers, such as water, melanin, and bilirubin, remain virtually constant with time. However, some absorbing compounds, such as oxygenated haemoglobin (HbO2), deoxyhaemoglobin (deHb), and oxidised cytochrome oxidase (CtOx), have concentrations in tissue which are strongly linked to tissue oxygenation and metabolism and hence change over time with brain activity and metabolism. Importantly, these compounds determine is not only of absorption but the majority coherent refraction of NIR light by diffraction sensoring A.Lipkin P. Fitzgerald (2005-2007) in the spectrum of 650-1000 nm. Absorption of coherent radiation at greater wavelengths is dominant but coherent refraction within this range, it is give possibility to differentiate changes in the concentrations of these individual components by NI holographic imaging with stimulation as assessment of brain activity related changes in perfusion.

l0 Up to now peripheral blood cell and platelet models, CSF studies, postmortem samples very considerable limitations here are not detectable Sanatomical or functional brain abnormalities of psychiatric patients with o subtle anatomical abnormalities brain regions involved in mood regulation. The emission of infrared radiation from the exposed human Scerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02 degrees The language and sensorimotor Scortex was identified by standard mapping methods (cortical stimulation, median nerve somatosensory-evoked potential, functional Smagnetic resonance imaging), which were compared with infrared functional localization. The temperature gradients measured during surgery are dominated by changes in local cerebral blood flow associated with evoked functional activation. The distribution observed via infrared mapping is consistent with distributed and complex functional representation of the cerebral cortex, rather than the traditional concept of discrete functional loci demonstrated by brief cortical stimulation during surgery and by noninvasive functional imaging techniques. By providing information on the spatial and temporal patterns of sensory-motor and language representation, infrared imaging may prove to be a useful approach to study brain function.

years Y.V.Guluev,O.V.Betskii,V.Herepenin Russia (Institute of Radio Engineering and Electronics of the RAN using electrical impedance stimulation mapping for brain and body measurements, Prof A.Bygaev with Prof S Ternovoy leaders of project heart correlation. And there are following experiments all made in Russia and Australia together with Dr.A.Lipkin Prof.P.Fitzgerald: Spectroscopic measurement using NIR and infrared light together with radio &microwave radiation and for calibration of the NI optical light across each relevant wavelength; These sources confirm the feasibility

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of the principles of holographic imaging can be produced for laser I near

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Sinfrared light and as such as really examples of holographic coherent tomography.

O Dr.A.Zabludovsky, Dr.A.Bazian, in Institute of Higher Nervous Activity and Neurophysiology using infrared thermoencephaloscopy and by, Y.Alexandrov Institute with Dr.A.Lipkin Prof.P. Fitzgerald developing Sholographic nearinfraredencephaloscopy for identification of Znc specific transpdrt proteins allowed us to examine effects of low Zn Sintake on tissue Zn level, brain Zn uptake, and zinc transporter expression and localization in neonatal rat brain. An important principle Sof the system is that is uses highly coherent light at multiple wavelengths to produce and image coherent photon scattering. When coherent light passes through tissue, the degree of coherence falls with distance due to the interaction between the light and substance it passes through. The distance that light of a particular wavelength passes before the coherence is substantially degraded is referred to as the length of coherence (LOC).

The controls and calibration procedures are used coherent light and NIR tomography holographic spectroscopic measurement of brain function with heart correlation measurements to monitor the accuracy and quality of data collected and transmitted. THSM with NIR additional measurements can be made with calibration, and a report are generated on a cardiology tests with brain function test simultaneously.

THSM with NIR Calibrations Telecardiology will be experimented with commercially available telemedicine devices and telecommunications technologies.

The goal is to develop a new calibration system with an integrated sensor-based the design and implementation of a new prototyped, integrated sensors portable wireless systems. The integrated sensorbased THSM with NIR wireless- devices using analog/digital signal i2 acquisition monitor home based heart patients. The prototyped system is intended to provide an alternative to the current limited-in-purpose c wired-based devices for monitoring patients.

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Summary of the Invention This invention has been devised to provide enhanced capacity for imaging of the human brain and body including the capacity to image both the human brain and body organs simultaneously. The invention Cinvolves the imaging of effects created by stimulation of the brain with non-ionizing radiation (including but not limited to infrared, near Sinfrared, optical and microwave frequencies). The imaging is of emitted energy created as electrons are stimulated to move to a higher energy state by the applied radiation and then fall back to their original energy state. This involves imaging of the spectrum, phase and intensity of emitted photons. Emission images are obtained in each of the three energy spectra: Optical this image is of changes in gas ionization around the surface of the head, Infrared this image arises from photons stimulated in the superficial cortical region (3 cm penetration), Microwave this is obtained from effects in the whole brain as the applied energy from the microwave radiation induces dipole realignment through the entire brain. In addition, the applied energy from the microwave stimulation induces dipole realignment through the entire brain. Dipoles exist throughout the brain as the result of differences in ion concentrations in extra cellular space related to nerve cell firing. The electromagnetic field induced by the microwave source will be used to produce an alignment of these dipoles. The energy emitted as these decay to their usual state will be imaged by the impact of the emitted energy on the microwave and infrared diffraction fringes in the holographic images.

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The signal will be generated by the stimulation of metals within the brain at appropriate frequencies (widely distributed brain metals include (copper, iron and zinc) as well as the stimulation of fundamental brain elements including water, oxygen, carbon dioxide, hydrogen, calcium, 0 sodium, potassium, chloride and phosphate. Stimulation will also be 0possible for Rubidium and Cesium. The interferometer producing excited atoms of brain elements is the amplifier of brain emission effect.

Cc The mirrors of the interferometer act as resonators for the emission of S' this energy signal.

The system involves the use of optical imaging components for stimulation of the brain'orbody) across these multiple wavelengths and the detection of the-emitted signals. These are~rocessed and analyzed spectroscopically and then can be represented I analysed in analogue or digital format.

This technology relies on the use of nuclear spectroscopic imaging principles that have previously been applied in the imaging of metals held in gaseous suspension but have not been applied to human imaging. In the basic use of this technology, changes in electron energy level and spin in certain metals induced by laser stimulation are measured with the use of infrared or near infrared spectroscopy. The current invention uses the unique properties of a set of large scale optical components with fine diffraction resolution to apply these measurement techniques at a markedly increased scale. These are able to be applied to: image the whole brain through the measurement of metals widely distributed in brain tissue image processes associated with specific diseases through the imaging of specific metals involved in the pathophysiology of the disease in question image specific metabolic or pathological processes through imaging of metals involved in these processes image the distribution and effects of endogenously administered O compounds I metals such as lithium carbonate image the direct effects of therapeutic brain stimulation techniques such as transcranial magnetic stimulation on the magnetic properties of Sbrain tissue electron spin in metals in the brain regions stimulated Sby TMS pulses).

t The system may be used to generate a holographic brain simulation 0 model: this is a multi-scale dynamical diffraction grating (hologram): this will provide a representation of the brain image in a three dimensional dynamic diffraction grating. The holographic simulation model of the brain is a dynamical three dimensional electromagnetic interference diffraction grating that arises from the use of coherent waves applied to electromagnetic and acoustical stationary field (for example, a microwave holographic grating gradients).

The radiation of light onto a substance results in several physical phenomena including alteration of the physical nature of the object onto which the light is projected. This can occur in at least 2 ways: Fluorescence is a luminescence that is mostly found as an optical phenomenon in cold bodies, in which the molecular absorption of a photon triggers the emission of another photon with a longer wavelength. The spectral range energy difference between the absorbed and emitted photons ends up as molecular vibrations. Usually the absorbed photon is in the ultraviolet range, and the emitted light is in the visible range, but this depends on the absorbance curve and Stokes shift of the particular fluorophore. Fluorescence is named after the mineral fluorite, composed of calcium fluoride, which often exhibits this phenomenon.(Godik E.,Gyluev Y.V) Superlumenescent amplification (second Stokes component) used conversion efficiency pump energy by Raman laser, The spectral range molecular vibrations rotational or atom 0of gas (metal vapours).For example with Nd laser as pump sources and orthohydrogen as an active medium.(Rabinovitz P.1979). In optical O spectroscopy characteristics of lanthanide-ion as a probe of the structure, vibronic spectra of the lanthanide compounds values of linear and nonlinear susceptibilities of molecular organic materials and for Sthin film organic electroluminescent effect. Most molecules do not m fluoresce, but all molecules absorb (for example Zn,Fe,Mn ,Cu) energy Stransfer of molecules exited by light. Brain coherent phase function analysis by near infrared light emission and scattering and use of 0 acoustical simulation at low frequency to enhance the effect emission of blood within the cerebral blood vessels The reversion of the wave front and the characteristics of the substance- Echo effect (wave front; reversion) this phenomena refers to the production of atomic level emissions produced when stimulating light produces a shift in the energy state of electrons in the object. This emission has the conjugated wave front with respect to that of the incident light. Therefore, as the light passes back through the same amplifiers resonator and the entire holographic laser systems, the phase distortions introduced in the forward passage become cancelled out. As a result the out coming wave reproduces in each of its cross sections the angular spectrum and the transverse distribution of the primary radiation (Zeldovich B.Ya 1972). Stimulation capable of producing these effects arises through the use of highly coherent interferometer radiation sources applied through large aperture optical components (Lipkin A.S.1976). This system produced the complete spatially polarised reversion of the wave front and pointed out how to counteract the depolarisation which often occurs in light and NIR holographic laser amplifiers resonator.(Beldyugin I.N.1976)Scattering of coherent light and NIR phase restoring in real time in paths through biological tissues under definite conditions, the backscattered radiation at a shifted (Stokes) frequency will have a wave front phase shift comes to 1000-100 of sm -1.The degree of coherence of light and NIR is inversely proportional to the threshold nature of stimulated Mandelstam 0 -Brillounin scattering limits the coherent power of signal to be handled.

The length which a specific frequency of light penetrates a substance is dependent of optical system produced the complete spatially polarised Sreversion of the wave front and the characteristics of the substance.

Also the length of coherence (LOC) of light varies inversely with the Spulse width I duration of the light. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well defined, and which are present in sufficient quantities to contribute significant attenuation to measurements of transmitted light. The concentration of some absorbers, such as water, melanin, and bilirubin, remain virtually constant with time. However, some absorbing compounds, such as oxygenated hemoglobin (HbO2), deoxyhaemoglobin (deHb), and oxidised cytochrome oxidase (CtOx), have concentrations in tissue which are strongly linked to tissue oxygenation and metabolism and hence change over time with brain activity and metabolism. Importantly, these compounds determine the majority of absorption of NIR light in the spectrum of 650-1000 nm.

Absorption of radiation at greater wavelengths is dominated by water and at lower wavelengths by Hb. In addition, due to differential absorption of HbO2 and deHb within this range, it is possible to differentiate changes in the concentrations of these individual components allowing as assessment of brain activity related changes in perfusion.

Embodiment of the system The system consists of the following components: 1. A "3D angle" model frame to support the tomography and spectroscopic equipment with placement of a subjects head within the 'bore' of the tomography device with the subject either sitting upright in a chair or lying prone.

c 2. Holographic tomography system with 6 apertures. NIR tomography 0 Telescope Holographic Interferometers with physical phenomena maximizes diffraction resolution by increase size apertures of mirrors.

(6 apertures 100 mm one by one used for each 500 mm telescope Sreflector) (2 aperture 500 mm telescopes reflector by 1000 mm 2 Stelescope reflector).

3. The active feet back via stimulation with follow three forms of spectroscopy: S Optical and Near Infrared Acoustic-optical spectrometer this allow the measurement of the integral of time, frequency and magnitude of emitted radiation.

S Optical and Near Infrared Holographic spectroscopy with three diffraction gratings this allows analogue imaging (localization) of the spectra of emissions Infrared imaging spectroscopy this allows the imaging (localization) of infrared spectral emissions 4. Optical fibers with miniature interferometers for placement in the nasal cavity and ears for the purpose of the application of NIR light and the measurement of emissions through the same sites. These may utilise portable holographic laserlwhite light prism Moire; portable a micro speckle holographic system: portable, holographic shift interferometer: portable a holographic polarizing grating with sources of laser near infrared light, Portable Schlieren Holographic Speckle with active feet back via stimulation.

Photochromy emulsion exposure and calibration volume-phase grating to allow holographic selection. NIR light will be subject to refraction through an appropriate performance volume-phase grating to allow holographic selective imaging of emissions in the spectrum of 600-1000nm wavelength. The first order holographic spectroscopic images data from multiple spatial locations oriented so that the first O order is at a maximum. These advantages will include in the maximize N_ spatial and temporal resolution of spectral components and that will be O achieved with the device. Holographic Diffraction Grating was design and orientated for optimize the first order holographic spectroscopic images data from multiple spatial locations.

6. The system will include specific analogue to digital conversion and Ssoft ware to digitise the first order holographic spectroscopic images data from multiple spatial locations oriented so that the first order is at a 0 maximum. The software will allow the integration of images and c spectroscopy data from the multiple sources and presentation in a variety of formats.

7. The holographic system with active feet back via stimulation for the measurement of head movement in during measurements and feedback stabilization to minimize optical noise of human brain imaging for "3D angle" model.

Images can be generated at a number of scales (1mm, 10mm, 100mm and 1000mm). Different measurement modalities incorporating specific physical phenomena will be used to assess each of four scales: a) 1mm: Atomic, infrared, near-infrared spectroscopy (Will enable not only to detect various metals within the brain but also quantify their atomic spin. Hence, to also calibrate various biological molecules encompassing the specific metals pertaining to neurons, synaptic terminals and hemoglobin).

b) 10mm: Holographic Scattering tomography and micro-speckle tomography I imaging I (Will measure protein structures, cell structures neurons], synapses and small blood vessels within the brain).

"9 t c) 100mm: Spectrum Holographic Tomography I imaging I (will measure structural aspects such as sub-cortical and neocortical regions). Note: Measurement of residual properties.

O d) 1000mm: Spectrum Holographic Tomography with multi attachment laser I imaging I (will measure the whole brain on a global basis). Note: this modality relates to the holographic model of the brain, involving Sfunction Memory: LTM. STM) and structure _Images obtained across scales will be integrated in a multi-scale dynamical functional model I diffraction grating, provide resonance effects at multiple scaleslsizes.

Examples of calibration multiple scale effects with active feet back via stimulation: S1lpm- 0.6 laser light 0,7 up to 3 pm -near infrared and infrared 10 pm microwave 0 1 mm scale acoustical stimulation This invention has been devised to provide enhanced capacity for imaging of the human brain and body including the capacity to image both the human brain and body organs simultaneously. The invention involves the imaging of effects created by stimulation of the brain with non-ionizing radiation (including but not limited to infrared, near infrared, optical and microwave frequencies). The imaging is of emitted energy created as electrons are stimulated to move to a higher energy state by the applied radiation and then fall back to their original energy state. This involves imaging of the spectrum, phase and intensity of emitted photons. Emission images are obtained in each of the three energy spectra: Optical this image is of changes in gas ionization around the surface of the head, Infrared this image arises from o photons stimulated in the superficial cortical region (3 cm penetration), Microwave this is obtained from effects in the whole brain as the c applied energy from the microwave radiation induces dipole realignment O through the entire brain. In addition, the applied energy from the microwave stimulation induces dipole realignment through the entire brain. Dipoles exist throughout the brain as the result of differences in Sion concentrations in extracellular space related to nerve cell firing. The Selectromagnetic field induced by the microwave source will be used to _produce an alignment of these dipoles. The energy emitted as these decay to their usual state will be imaged by the impact of the emitted (energy on the microwave and infrared diffraction fringes in the holographic images. Calibration analogue conversion censors signal holographic spectroscopic images to digital data from multiple spatial locations oriented so that the first order is at a maximum.

Set-up model NIR tomography Optical Calibration by Telescope Holographic Interferometers with physical phenomena maximize diffraction resolution by increase size apertures of mirrors (6 apertures 100 mm one by one used for each 500 mm telescope reflector), (2 aperture 500 mm telescopes reflector by 1000 mm 2 telescope reflector).

The 50cm aperture Holographic interferometer will be calibrated by a 100cm holographic interferometer with active feet back via stimulation.Laser spectroscopy systems will be calibrated via an acoustic-optical spectrometer The signal will be generated by the stimulation of metals within the brain at appropriate frequencies (widely distributed brain metals include copper, iron and zinc) as well as the stimulation of fundamental brain elements including water, oxygen, carbon dioxide, hydrogen, calcium, sodium, potassium, chloride and phosphate. The interferometer producing excited atoms of brain elements is the amplifier of brain 0emission effect. The mirrors of the interferometer act as resonators for c the emission of this energy signal.

O An optional component will be the provision of one or more additional signals through areas of the head designed to avoid attenuation of the stimulation signal inside the cranial cavity. This Sprocess will enhance the capacity for signal localization and the Salteration of areas of conductivity and allow the creation of a 3D interferometer grating within the skull. This includes the potential provision of a stimulation signal through a probe placed in the nose or (N ears (uni or bilaterally) where signal would enter the brain through the cribriform plate or holes in the exit/entry points in the base of the skull occupied by cranial nerves and blood vessels. Stimulation could also be focused into the brain through stimulation of cerebral blood vessels outside of the cranial cavity. This will be done with infrared radiation with active feet back via stimulation.

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T~7A) iL La Spectral Imaging and Analysis of Spectral Emission Radiation and Absorption The combination of both pseudo coherent emission (pseudo-laser effect) and pseudo coherent absorption physical effects 22 0Emission effect with minimal noise NIR tomographies Optical Calibration by Telescope Holographic Interferometers with physical phenomena maximize diffraction resolution by increase size apertures of mirrors.

The calibration system will also utilize histogram analysis for the special statistical analysis of signal irregularities. Estimation of spectral and 0correlation characteristics of the signal and noise. Using the calculation Cof spectra and auto and cross correlation properties of the signal and noise. Hypothesis that signal is absent when the observed data contain nothing but noise: f, This hypothesis is called zero hypotheses. It is designated asH 0 Using the observed data, it is possible to calculate distribution density for each hypothesis: in signal free area (hypothesisH!) and in the area containing a signal (hypothesisH,). Such distribution densities are conditional, and are, respectively, designated as P (FIH 0 and P where F is vector of observations F 2 fy)- The useful SIGNAL, or ANOMALY, is the shape of the field in which useful information on this field is manifested. NOISE is every distortion of the field in which makes the signal detection more difficult.

For waves a multiplication modelf Is used. Taking a logarithm of this model leads to the same additive model log f logS, logn, for potential fields, the data present the following model f.=Sire g Si l o c n i where SIr,, is regional component of the field, is is a local (residual) component of the field, n, are observational and measurement errors.

23 t For combination of K signals, for example K reflected waves, a mathematical model can be expressed as k

C

O f[i)'f S(ti- t)+n(ti) _k=l Where wave parameters a k are determined by different depth factors.

The mathematical model for quantitative interpretation is expressed as f where is a vector of parameters, including physical properties, depth and geometrical dimensions of the sought object.

(Stimulation source is Complex Multi-coherent Broad-spectrum laser echo emission This component describes a completely novel way of imaging brain structure and function. A model of brain structure and function is created by imaging of the laser/echo effect created through the application of broad spectral coherent radiation. The echo effect is a broad-spectrum laser emission with focusing and enhancing of the energy output. By the stimulation of electrons are resonance frequency, a change to a higher energy level is induced resulting in a release of photons during decay to a lower energy level.

Coherent radiation stimulation will be applied across a broad multi-scale spectrum extending from microwave (100 pm) through infrared (3 pm) to visible laser light (0.4-0.7 pm).

The model allows the imaging of two separate components: a. A holographic image: This includes measurement of the magnitudelintensity, phase, polarisation and spectrum of the reflection and diffraction of the applied radiation.

2H b. Echo Image Direct imaging of the photons released through the laser echo effect.

c) This involves imaging of the spectrum, phase and intensity of emitted 0 photons.

An additional component will involve the use of acoustical simulation at Slow frequency to enhance the laser effect emission of blood with an Sarterial systems is applied to cardiac and brain imaging.

31 DESCRIPTION OF FIGURES FIGURE la. Block diagram of holographic spectroscopic imaging via C_ stimulation with coherent amplification of human emission defined by Dr.

o Arkady S. Lipkin, Prof. Paul Fitzgerald (2005-2007) FIGURE lb. Block diagram of holographic spectroscopic imaging via Sstimulation with coherent amplification of human emission defined by Dr.

Arkady S. Lipkin, Prof. Paul Fitzgerald (2005-2007) FIGURE 2. The photo imaging of physical field's emission and radiations S arising around the human body in the process of a vital activity defined by Dr Yuri V. Gyluev together with Dr. Eduard Godik -General illustration of physical fields and radiations arising around the human in the process of a vital activity. The infrared thermal radiation (red) characterizes functioning of the capillary blood flow network in the skin which ensures thermoregulation of the body. The radio thermal (orange) and acoustothermal (brown) radiations carry information on temperature dynamics of internal organs bioelectric activity of the heart, brain, and muscles. The chemo luminescence (green) characterizes saturation of tissues with oxygen and the level of anti-oxidants. In addition, a chemical "micro atmosphere" is formed near the body by exhaled air, skin respiration FIGURE 3. Microwave holography image of 2 D slice of brain from 3D software "Holo-brain Coscade" by Petrov Lipkin Nikitin).The O.V.Betskii, V.Cherepenin, Russia (Institute of Radio Engineering and Electronics of the RAN) leaders of new experiments of project using electrical impedance stimulation mapping for brain and body measurements have made in Russia and Australia together with Dr. A.

Lipkin Prof.P.Fitzgerald(2005-2007): FIGURE 4. Near Infrared Holography tomography image of 2 D slice of brain from 3D software-" Holo-brain 3D classification software (Cheremisina S Petrov Nikitin Lipkin Kuznetsov using optical spatial filtering and O temporal modulated techniques of holographic spectroscopic imaging via stimulation with coherent amplification of human emission defined by A. Lipkin, P. Fitzgerald (2005-2007) 0 FIGURE 5. The 2D photo of suede 3D image of brain projected to Furrier O Screen using Limpkin's Stereo Holographic movie ,image processing by 3D cascade( HOLO) software (Petrov Lipkin Nikitin) Holographic image is Srecorded for forming acoustical hologram and converting into a form suitable NI optical holographic set up using optical spatial filtering and temporal modulated techniques in real time by holographic spectroscopic imaging via stimulation with coherent amplification of human emission defined by A. Lipkin, P. Fitzgerald (2005-2007) FIGURE 6. The photos of 3D images processing by"3D HOLO Coscade" software (Petrov, Nikitin, Lipkin Kuznetsov) Holographic of brain images is recorded for forming acoustical hologram and converting into a form suitable optical holographic set up using optical spatial filtering and temporal modulated techniques in real time by holographic spectroscopic imaging via stimulation with coherent amplification of human emission defined by A. Lipkin, P. Fitzgerald (2005-2007).

FIGURE 7. 3D image of brain sources using NI modulated techniques in real time by holographic spectroscopic imaging via stimulation with coherent amplification of human emission techniques in real time by holographic spectroscopic imaging with coherent amplification of human emission defined by A. Lipkin, P. Fitzgerald (2005-2007). The image processing by "reverse problem solution" holographic model of brain 33 using 3D Cascade -HOLO software (Petrov, Nikitin, Cheremisina, Lipkin

O

S Kuznetsov).

O FIGURE 8. The image of brain sources using NI modulated techniques in real time by holographic spectroscopic imaging via stimulation with coherent amplification of human emission techniques in real time by m holographic spectroscopic imaging with coherent amplification of human m emission defined by A. Lipkin, P. Fitzgerald (2005-2007). The image S processing by "Petrov problem solution" holographic model of brain using version No2 of 3D Cascade HOLO software (Petrov, Nikitin, Lipkin- SKuznetsov).

FIGURE 9. The Furrier Screen from Lipkin's Stereo Holographic movie method using for holographic spectroscopic imaging via stimulation with coherent amplification of human emission defined by A. Lipkin, P.

Fitzgerald (2005-2007).

FIGURE 10. FIGURE image of brain cross section projected to Furrier Screen of 2D slice of brain from Lipkin"s Stereo Holographic movie method .NI Multiple Frequency Holographic Tomography with combination of acoustical hologram. The image processing by "Petrov problem solution" holographic model of brain using version No2 of 3D Cascade HOLO software (Petrov, Nikitin, Lipkin Kuznetsov). The holographic spectroscopic imaging via stimulation with coherent amplification of human emission defined by A. Lipkin, P. Fitzgerald (2005-2007).

FIGURE 11. The image of brain cross section projected to Furrier Screen of 2D slice of brain image using Lipkin"s Stereo Holographic movie method .The Near Infrared Multiple Frequency Holographic Tomography with combination of acoustical hologram and electrical impedance stimulation mapping. The image processing by "Petrov problem solution" holographic 31? t model of brain using version No2 of 3D Cascade HOLO software (Petrov,

O

S Nikitin, Lipkin Kuznetsov).The holographic spectroscopic imaging via S stimulation with coherent amplification of human emission defined by A.

O Lipkin, P. Fitzgerald (2005-2007).

FIGURE 12a. The Near Infrared skin projections photo of the functional m tests of the human body with reaction to physical exertion (Prof A. Bygaev 0 Dr. E. Godik with Prof S. Ternovoy) leaders of new experiments of project the brain correlation function with heart function have made in Russia and Australia together with Dr. A. Lipkin Prof. P. Fitzgerald: FIGURE 12b.The figure of heart with anomaly (by Prof S. Ternovoy) clinical experiments of project the brain correlation function with heart function have made in Russia and Australia together with Dr. A. Lipkin Prof. P.

Fitzgerald FIGURE 13. Holographic tomography system together with NIR tomography telescope holographic Interferometers with physical phenomena of reflection telescopes mirrors .The Optical fibbers with miniature interferometers for placement in the nasal cavity and ears for the purpose of the application of NIR light and the measurement of emissions through the same sites. Portable, holographic shift interferometer: portable a holographic polarizing grating with sources of laser near infrared light, portable Schlieren Holographic Speckle interferometer.

FIGURE 14. Holographic tomography system together with NIR tomography telescope holographic Interferometers with physical phenomena of reflection telescopes mirrors in Laboratory HNDT Pty. Ltd. Melbourne, Australia

Claims (4)

1. A devices and technology application human holographic O spectroscopic imaging via stimulation with multiple NI light sources will be the provision of one or more stimulation signals through areas of the head designed to avoid attenuation of the stimulation signal inside the cranial cavity. This process will enhance the capacity for signal Slocalization and the alteration of areas of conductivity and allow the Screation of NI and microwave coherent energy distribution in form a 3D interferometer grating within the skull; said this includes the potential provision of a stimulation signal through a probe placed in the nose or ears (uni or bilaterally) where signal would enter the brain through the cribriform plate or holes in the exit/entry points in the base of the skull occupied by cranial nerves and blood vessels; said stimulation could also be focused into the brain through stimulation of cerebral blood vessels with direct resonance interaction microwave radiation induced by hemoglobin after blood scattering and absorption by NI radiation to said this energy microwave radiation induced by NI radiation produce an effect on hydration of protein molecules with change functionally state; said scattering of coherent light and NIR phase restoring in real time in paths through biological tissues under definite conditions, the backscattered radiation at a shifted (Stokes) frequency to said a wave front phase shift comes to 1000-100 of sm -1 to said degree of coherence of light and NIR is inversely proportional to the threshold nature of stimulated Mandelstam -Brillounin scattering limits to said coherent power of signal to be handled by spectroscopic imaging via stimulation with multiple optical imaging sources.

2. A devices and technology as claimed in claim 1, wherein used the NI light HNDT Calibration Tomography Holographic Imaging Sensors O system said for measurements correlation brain and heart function via Sstimulation to said also be focused into the brain through stimulation of o cerebral blood vessels with direct resonance interaction microwave O radiation induced by hemoglobin after blood scattering and absorption 0 by coherent NI radiation said this induced microwave radiation will used :said in the measurement of disturbances of brain electromagnetic I fields and heart electromagnetic fields with Multi-component STelemedicine sensors; said will used stimulation signal through a probe placed in the nose or O ears (uni or bilaterally) where signal would enter the brain through the Scribriform plate or holes in the exitlentry points in the base of the skull occupied by cranial nerves and blood vessels; said in the measurement by a single multi-component sensor this single sensor will be doing measurement of brain activity and will include individual sensors for the detection of near infrared, magnetic and ultrasonic signals to said sensor will be connected by a single fiber to an analog to digital conversion device that to said allow digitization of the signal and transfer to specific database designed for the integration of multi-component signals; said application the multi-component brain sensor to said integrated with a standard near infrared device and used in the measurement of disturbances of brain electromagnetic fields produced said by transcranial magnetic stimulation (TMS); said this application the NI light system will made visualization measurements by Tomography Holographic Interferometer devices for the calibration of the blood pressure sensor devices;

3. A devices and technology as claimed in claim 1 and 2, wherein the used via stimulation has been devised to provide enhanced capacity for imaging of the human brain and body including the capacity to image 0both the human brain and body organs simultaneously; t said non-ionizing radiation including but not limited to infrared, near O infrared, optical and microwave frequencies to said NIR light sinxrotron beam light components, Infrared and Low -Intensity to said transmiting MM wave radiation; Ssaid involves imaging of the spectrum, phase and intensity of emitted Sphotons to said imaging is of emitted energy created as electrons are 0 stimulated to move to a higher energy state by the applied radiation and then fall back to their original energy state to said emission images are 0obtained in each of the three energy spectra; said NI optical image is of changes in gas ionization around the surface of the head to said infrared image arises from photons stimulated in the superficial cortical region to said 3 cm penetration to said Microwave effects in the whole brain as the applied energy from the microwave radiation induces dipole realignment said through the entire brain; said the applied energy from the microwave stimulation induces dipole realignment through the entire brain to said dipoles exist throughout the brain as the result of differences in ion concentrations in extra cellular space related to nerve cell firing; said the electromagnetic field induced by the microwave source to said produce an alignment of these dipoles and energy emitted as these decay to their usual state to said imaged by the impact of the emitted energy on the microwave and infrared diffraction fringes in the holographic images;

4. A devices and technology as claimed in claim 1, 2 and 3, wherein the used via stimulation has been devised to provide enhanced capacity for imaging of the human brain and body including the capacity to image to said using NIR and infrared light together with radio &microwave 2-8 t radiation to said for calibration of the NI optical light across each relevant wavelength; c said the principles of holographic imaging to said produced for laser I O near infrared light and to said of multiple optical imaging sources holographic coherent tomography to said NI Light will be applied in the optical spectra to said measuring in the surface plane outside of the Sskull and to said infrared measuring within the first 3 cm of the cortex); Ssaid holographic images at longer wavelength obtained with the Smicrowave interferometer to said holographic images of the whole brain and body organs to said holographic images of this sort created through the application of coherent radiation of the spectra to said images are obtained through the induction of standard diffraction interferometer fringes, interferometer speckles and to said through the measurement of particular coherent micro-speckle to said equivalent of individual speckles; said to obtain and integrate holographic images generated from the measurement of emissions from the brain or body to said arise from intrinsic brain or bodily activity said do not arise form stimulation of tissue; said hologram images are obtained using a holographic tomography interferometer together with two large (D =0,5m, D=l.Om) holographic interferometers to said measurement of the magnitudelintensity, phase, polarization and spectrum of the reflection and diffraction of the applied radiation.; A method, devices and technology according to any one of the presiding claims, wherein the used imaging via stimulation with multiple NI light degree of coherence of light and NIR is inversely proportional to the threshold nature of stimulated Mandelstam Brillounin scattering limits the coherent power of signal to be handled and applied said a specific frequency of light penetrates a substance is dependent of optical system produced the complete spatially polarized reversion of c the wave front and the characteristics of the substance to said. the O length of coherence (LOC) of light varies inversely with the pulse width duration of the light; said Human tissues contain a variety of substances whose absorption Sspectra at NIR wavelengths are well defined, and which are present in sufficient quantities to contribute significant attenuation to Smeasurements of transmitted light to said scattering of coherent light and NIR phase restoring in real time in paths through biological tissues Sunder definite conditions to said the backscattered radiation at a shifted (Stokes) frequency will have a wave front phase shift; said in live tissue plasma membranes the coherent NI light together with coherent excitation accoustoelectric oscillations to said created accoustoelectric membrane stimulation to said this energy microwave radiation induced by NI radiation produce an effect on serialization to said with convective motion of blood gives raise the capillary effect with change neurons functionally state; said biochemical reaction governed protein molecules synthesis immunocompetent substances to said also produced an effect in cell metabolism with stimulation the ATP synthesis; said image the whole brain through the measurement of metals widely distributed in brain tissue; said image processes associated with specific diseases through the imaging of specific metals involved in the pathophysiology of the disease in question; said image specific metabolic or pathological processes through imaging of metals involved in these processes; said image the distribution and effects of endogenously administered compounds I metals such as lithium carbonate; 3o t said image the direct effects of therapeutic brain stimulation techniques O Ssuch as transcranial magnetic stimulation on the magnetic properties of brain tissue to said electron spin in metals in the brain regions O stimulated by TMS pulses; DATED 25 April, 2007 SProfessor Paul B Fitzgerald (Bayside Health, the Alfred), 0 Dr Arkady S. Lipkin (HNDT& LIQC Pty Ltd) SBehalf of Holographic Non-Destructive Testing L-lnternational Quality Control Pty Ltd Hi/ ^L Signature of Dr Arkady Lipkin