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-====== Mourad Project ======
-====== BBB ======
- Delivery of SPMNMs to CNS of rodents with artificially provoked epileptic seizures
-I. Introduction
-Our research group is formulating a manifold strategy, according to which, first, the SPMNMs aggregates will be given an aspect ratio (i.e. rods) to allow orientation of the  sub micron rods, under the effect of a μT magnetic moment. This orienting effect requires the use of a simple homogeneous magnetic field (parallel field lines) with low intensity, the kind of magnetic fields used found in epileptic focus. Resorting to the use of magnetic moments instead of magnetic force (geometrical gradient) is more likely to match the scenario met when pyramidal cells are propagating seizure like electrical activity.  Delivery of SPMNPs to CNS has been demonstrated using polymeric coating that are not reliable from a magnetic performance point of view, nor are the delivery techniques that rely on disruption of the BBB using focused ultrasound, due to the infectious risque that it entails. Part of our research hypothesis thus is the feasibility of bare SPMNMs through the BBB using static magnetic fields generated by Niodim-Yag permanent magnets attached to the head of the rodent at the time odf the intravenous delivery of the theragnostic agent.
-II. Motivation
-•	Can any shape SPM NM  reach the CNS without polymeric coating and under the effect of an external magnetic field.
-•	Answering this question is laying out the way for delivery technologies using the MRI's  system strong and static magnetic field.
-•	Could submicron rods be oriented in under the μT neuronal magnetic field
-•	Magnetic moment driven aggregation of SPMNMs requires parallel field lines ( neither convergent nor divergent thus no specific region of the brain is concerned).
-•	One new property is that nanorods exhibit is the fact that they are the most appropriate for use in presence of a magnetic field such as those present in an MRI system.
-•	Experimental work will be run on rats inoculated with epileptic precursors and no symptomatic conditions like disrupted BBB or blood hypotension
-III. Hypothesis
-When seizures take place, μT magnetic moments are able to orient the nanorods. Whereas in the rest of the brain, the fluid shear forces dominate and electric currents due to normal brain activity produce transient magnetic field that have no noticeable effect on the aggregation coefficient of NPs nor on the orientation of the NRs. Part of this study is to quantize the aggregation coefficient at the epileptic focus using rotational (rods & moments) and translational (particles & gradients) forces.
-) A static magnetic field applied on the scalp will allow delivery of SPMNM to CNS
-) The ratio of fluids shear forces on the SPM Poly/Met nanorod's surface to the magnetic moment generated by internal currents flow in pyramidal cells will depend on the position of the nanorod relatively to the epileptic focus.
-IV. Materials and methods
-Given well characterized SPM nanoparticles and SPM Polmeric or Metalic nanorods suspension in water.(purchased materials). In order to mimic MRI contrast agents like Gd(III) a concentration of 5 mg/m has to be prepared by dilution. We will carry out the following experiments based on t size and dispersion.
-.1 In vivo  experiments on the delivery of SPMNMs to rats CNS in submerged in a MRI static magnetic field
-The following experiment is conducted first using head mounted magnets. The delivery of particles to the brain due to magnetic influence on the BBB or the complex (BBB and Nps) will be elucidated. MRI will show hypointese regions in rat brains that account for successful delivery of the NPs.  In the second series of experiments, rats that were injected with the NPs in the past and that showed a history of epileptic activity following inoculation with epileptic triggering compounds, will be subjected to MRI protocol at different periods of time. Depending on the number of seizures, the aggregates will be more or less detectable. The focus will reveal its self after a right number of Nps has been deposited or trapped by the magnetic fields it harbours.
-Further studies are envisaged to explain the mechanism of retention of the NPs at the site of the focus. particles that will not deposit by the μT magnetic agglomeration will be cleared or biodegraded to join the naturally occurring brain iron in its fate.
-.2 Parameters
-•	Intensity and location of static magnetic field of the permanent Niodim-Yag magnets
-•	 SPMNPs magnetic moment and size and crystal structure
-•	Polymeric SPMNRs  asperct ratio and porosity and density of magnetic cores
-•	Metalic SPMNRs asperct ratio, criystal structure and magnetic moment
-•	number of injection times
-•	number of epileptic seizurs
-{{:resources:p2:1.pdf|}}
-====== Epilepsy ======
-MRI imaging of superparamagnetic particles and rods aggregates in the brain
-Application to epileptic theragnostics
-I. Introduction
-Detection of iron oxide nanoparticles agreggates in the brain is a routine procedure achieved successfully by Finlay et al. Strangely, Finlay used T1 relaxation time of the protons, whereas T2 is the most commonly used for MRI detection of SPM Iron Oxide in the RES system (liver, spleen, lymph nodes). T1 contrast agents are different from T2 contrast agents in a  sense that T1 agents have a locale effect on protons (only the protons that get into close contact with the high spin density element of the contrast agent that experience T1 shortening). In this perspective, encapsulation of T1 agents is inappropriate, because encapsulation limits proton (water) access to the high spin density element of the T1 agent. On the contrary, encapsulation (or confinement) of T2 contrast agents enhances the T2 shortening effect because T2 effect is not local. A sphere of 50 µm radius is under the effect of T2 shortening.
-II. Purpose
-•	SPM nanoparticles are proven to cross the BBB and to  have high deposition coefficient in brain tumors in-vivo. No evidence in the literature shows that Nanorods can cross the BBB and make its way to the neuronal tissues.
-•	No non functionnalization nanomaterials where used in detection of epileptic foci based on interaction of seizure's micro-Tesla fields ans nanomaterial's magnetic moment.
-•	If we use polymeric nanorods instead of pure iron-oxide nanorods We will have a larger radius if the SPMIOs are confined to a volume of the polymer fibber. The T2 effect is remote and reaches far beyond the 50 µm boundary. And T1 sequences are aplicable due to infiltration of protons into the nao-polymeric-rod.
-•	The larger the number of NMR signal sources is, the larger the amplitude of the signal is.
-•	MRI sequence sensitive to water diffusion (diffusion imaging) is susceptible to create Diffusion coefficient maps of the brain. The presence of Nanorods aggregates will create anisotropic diffusion expressed in the diffusion tensor (image based).
-•	Finally, we will investigate which of the two relaxation times is more appropriate in the brain in presence of the SPMOINPs when T2 effects are present, and to what extent is the T1 effect relevant for epileptic foci detection with nanoparticles. As for the rods (metallic or polymeric), we will optimize the diffusion gradients to become sensitive to the dynamics of diffusion of water molecules between the nanorods.
-III. Hypothesis Epileptic foci Quantization of SPMIO 1) NPs, 2) Nps based fpolymeric rods and 3) SPMIO metallic rods deposits is feasible in the brain using T2 effect  and diffusion maps. Inter-Ictal detection of epileptic seizure focus will be tagged by SPM nanomaterials aggregate that interacted with the μT magnetic fields generated in the Ictal phase .
-IV. Materials and methods
-Relaxation time (T2) will be quantified by nuclear magnetic resonance (RMN) for the proton in the presence of different concentration NPS NMs. This experiment will be ran in an identical magnetic field B0 to that developed by the MRI system at Sait-Luc Hospital (3 T). the NMR spectroscopic device is available at the Chemistry department of the University of Montreal. In order to achieve  SPMs NP aggregates detection, two possibilities will be explored: 1) A classical Spin Echo sequence will be implemented due to its robustness with respect to the static field inhomogeneity caused by the SPM Nms. 2) A new sequence will be developed and that is diffusion sensitive. A new kind of surface antennas could be necessary at this point, namely a metamaterial that is supposed to double the signal to noise ratio of the imaging sequences, especially when the aggregates size expected to form, following interaction of the the SPM NMs and the seizure driven μT magnetic fields, are expected to be small. Imaging tests will first be performed on a cylindrical MRI phantom made out of  bovine collagen and water. In channels of arbitrary geometries, manufactured according to our needs, SPM NMs solutions at physiologically relevant concentrations, will be deposited by their direct application on the internal surface of sad channels. Application of  μT fields will follow this step. The phantom will be put in the MRI system image acquisition.  The control the size (aspect ratio) of the NMs and the encapsulation process of SPMNPs in the Polymeric matrices matrices (e.g. PVA) will tremendously simplify the conditions onthe performance of the MRI system.
-.1 Preliminary experiments on the functional properties of the carriers
-Proton NMR spectroscopy at 3 T
-•	Without SPMNP (chemical shift, intensity signal )
-•	In presence of SPM NPs , Poly/Met nanorods( Off resonance effect, correlation sphere VS dose & size )
-.2 Spectroscopy and detection the resonance frequency of the SPM Nps, Poly/Met nanorods at 3T
-•	Dose dependent frequency shift (effect of concentration and aggregate size)
-•	sensitivity
-.3 MRI of a physiologically relevant dose of SPM Nps, Poly/Met nanorods in a gel phantom
-•	Preparation of the gel (bovine collagen or agar gel)
-•	Use of  high aspect ratio of SPM rods and Pol/Met nanorods
-•	Adjustment sequence parameters
-•	Perform post-acquisition image analysis of diffusion weighted imaging
-.4 Parameters
-SPMNPs concentration in aerosols, gel water content
-.6 Graphics expected
-•	Spectra of protons and SPM NMs resonances at 3 T
-•	Relaxivity of the SPM NMs on proton 1/T2 verses SPM NMs concentration
-•	Images of SPM NMs aggregates
-•	diffusion maps of the brain
-.7 Expected results
-•	Quantification of aggregates by MRI using T2 images of proton
-•	Evidence of an off-resonance effect of SPMNPs on proton resonance
-•	translation of diffusion coefficients into surgical coordinates.
-•	Correlation with histopathological findings and intended epilepsy triggering zones
-====== Interferometry ======
-Optical Characterization Of A Cantilever Array  : Toward Integrated Wave Front Correctors And Analyzers For Miniaturized Adaptive Optics Systems
-This paper presents the design, optimization and optical characterization of an array electrostatic actuators based MEMS to be used as an adaptive optics component of a portable retinal imaging device. The proposed wave-front corrector is implemented in (CMC) polymump technology and  features an array of cantilevers on which planar reflective gold thin films were deposited for characterization purposes.  The cantilevers relative deflections will be set based on the output of a wave-front analyzer to correct higher order optical aberrations. For the sake of achieving precise wave front correction, three cantilever sizes were implemented on the chip for a total of 64 cantilevers that will serve as actuators of a deformable mirror in future work.  Array of actuators are hindered by the off-plane initial misalignment phenomenon caused by thin films deposition process and mismatches between the cantilevers displacement due to size nonuniformities introduced by the fabrication process. The device total surface is XXX × XXX mm2. The COMSOL simulation of the modeled Large, medium and small size cantilevers predicted maximum deflections of 6, 4 and 2 um respectively at maximum DC voltages of XXX, XXX and XXX respectively. These values are verified by laser interferometry and shown that they can be considerably augmented by omitting the gold deposited layer in future versions of the device.
-====== brain surgery ======