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Medical Devices

Category
Technology Name
Briefcase
Scientist
1795
Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small,...

Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small, difficult-to-reach, spaces for medical and other applications. Multimode fibers are being explored as ultra-thin lensless replacements for the commonly used endoscopes. The difficulty with imaging or focusing light through a multimode fiber is phase randomization of light propagating through the fiber, which results in a complex speckle pattern at the fiber output. To overcome this obstacle, an access to both fiber ends is required for pre-calibration.

A novel endoscopic method that was developed by Prof. Silberberg at the Weizmann Institute of Science allows light focusing through a multimode fiber by approaching solely the proximal end and retrieving information about the distal end using non-linear optical feedback.

Applications


·         Clinical imaging of narrow cavities (blood vessels, respiratory system, joints, etc.)

·         Selective targeting and burning of fluorescent targets (imaging and treatment)  


Advantages


  • Ultra-thin (micro-meter scale) and flexible

  • Lensless endoscopy

  • High resolution and accuracy


Technology's Essence


We consider a two-photon lensless multimode fiber-based endoscope, where an ultrashort pulse is delivered to a fluorescently tagged sample through the fiber. The pulses excite two photon fluorescence (2PF) from a 2PF screen placed against the fiber distal end. The back-propagated 2PF that is collected by the same fiber is separated from the excitation light at the proximal end by a dichroic mirror (DM), and the Fourier-transformed image of the fiber facet is recorded by an EMCCD camera. It is then used as feedback for a wavefront-shaping optimization algorithm, controlling a spatial light modulator (SLM) at the proximal fiber end. The nature of the light propagation in the fiber allows for scanning and controlling the focus position at the fiber distal end.

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  • Prof. Yaron Silberberg
1800
A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses. The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt...

A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses.

The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt stimulations. This may allow TMS-EEG to be used as a diagnostic tool for various neurologic and psychiatric conditions.

However, large electric artifacts are induced in the EEG by the TMS, which are unrelated to brain activity and obscure crucial stages of the brain's response. These artifacts are orders of magnitude larger than the physiological brain activity, and persist from a few to hundreds of milliseconds. However, no generally accepted algorithm is available that can remove the artifacts without unintentionally and significally altering physiological information.

The software designed according to the model along with a friendly GUI is a powerful tool for the TMS-EEG field. The software has tested and proven to be effective on real datasets measured on psychiatric patients.

Applications


  • TMS triggered EEG diagnostics

Advantages


  • Easy to use software with a GUI
  • Exposes the full EEG from the brain

Technology's Essence


The new software tool is based on the observation that, contrary to expectation, the decay of the electrode voltage after the TMS pulse is a power law in time rather than an exponential. A model based on two dimensional diffusion of the accumulated charge from the high electric
fields of the TMS in the skin was built. This model reproduces the artifact precisely, including the many perplexing artifact shapes that are seen on the different electrodes. Artifact removal software based on this model exposes the full EEG from the brain, as validated by continuously reconstructing 50Hz signals that are the same magnitude as the brain signals.

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  • Prof. Elisha Moses
1540
A novel TMS method that eliminates the restrictions of angular positioning, exciting more neurons per area of stimuli, in further areas of the brain.   Current TMS methods and TMS methods under development, suffer shortcomings of a highly specific directional electric field, which demands a precisely...

A novel TMS method that eliminates the restrictions of angular positioning, exciting more neurons per area of stimuli, in further areas of the brain.

 

Current TMS methods and TMS methods under development, suffer shortcomings of a highly specific directional electric field, which demands a precisely targeted application. Current methods are extremely sensitive to the movements of the patient or the device. Once a position is established the patient must remain still for the treatment. Furthermore, stable and reproducible positioning is costly and time-consuming.

 

Researchers at the Weizmann Institute developed a method to induce a rotating magnetic field in TMS applications, yielding optimal targeting of brain regions where correct orientation cannot be determined (e.g. via motor feedback). This innovative method can also stimulate brain regions with no preferred axonal orientation, and open new applications in diagnostics and research in neuronal cultures and rats, previously unresponsive to conventional TMS.

Applications


  • Accurate, cost-effective, enhanced rfTMS devices for treatment of depression, migraines and other mental disorders.
  • A novel model system in rats and neuronal cultures for development of diagnostics and therapeutics.

Advantages


  • Exciting more neurons in the same area of stimulation
  • Accessing areas in the brain that are currently unresponsive to conventional TMS.
  • No positional restrictions
  • Requires less voltage

Technology's Essence


The theory behind this technology involves the understanding that neural response is direction dependent. Neurons whose axons are parallel to the magnetic field will be most significantly stimulated. Additionally, factors of magnetic field, rise time and neural cooperatively play a role. All these are addressed by a rotating magnetic field creating anisotropy of angles that match the neurons’ orientation and the excitation of dendrites by applying pulses of the order of 1ms. This solution offers greater control over the TMS system.

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  • Prof. Elisha Moses
1604
Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic...

Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic tool that offers views into deep tissues at exquisite spatial resolution. Recently, MRI has emerged as a valuable tool for monitoring the expression of genes by utilizing metal-complexed MRI agents to display transgene activity in vivo. However, administration of metal complexes into tissues and cells is challenging. Intra-cellular metalloproteins such as Ferritin have been utilized as endogenous MRI contrast agents, but offer relatively low sensitivity. The present technology provides a novel Ferritin-based transgene with enhanced MRI contrast.

 

Applications


  • Non-invasive imaging of gene expression in transgenic mice models.
  • Monitoring target gene expression in pre-clinical studies.
  • Long-term cell labeling and tracking.
  • Visualization of cellular- and gene-based therapeutics.

Advantages


  • Does not require delivery of exogenous substrate.
  • Enhanced MRI contrast over current Ferritin-based reporters.
  • Conversion to magnetite is achieved in physiological conditions and not by synthetic modification or by extreme heating. 

Technology's Essence


Ferritin, the main Iron storage intracellular protein, contains a paramagnetic ferryhydrate core, and thus was proposed as an endogenous MRI reporter gene. However, Ferritin provides relatively low sensitivity. One way to increase sensitivity of Ferritin is to convert the non-crystalline ferrihydrate in its core into crystal magnetite as has been done chemically, to form magneto-ferritin. The current method enhances the magnetic properties of Ferritin by engineering a Ferritin protein fused to a bacteria-derived peptide. This novel recombinant fusion protein facilitates conversion of ferrihydrate into crystal magnetite and by this induces MRI contrast. The new construct can serve for monitoring delivery and differentiation of cells in vivo in cellular based therapy. 

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  • Prof. Michal Neeman
1450
An MRI-based Non-invasive real-time depiction of Blood-Brain Barrier (BBB) abnormalities that enables a wide range of diagnostic, therapeutic and drug development applications.The BBB is a capillary barrier that protects the brain from fluctuations in blood chemistry and passage of certain particles...

An MRI-based Non-invasive real-time depiction of Blood-Brain Barrier (BBB) abnormalities that enables a wide range of diagnostic, therapeutic and drug development applications.
The BBB is a capillary barrier that protects the brain from fluctuations in blood chemistry and passage of certain particles between bloodstream and the brain. Selective delivery of compounds across the BBB by means of temporary/local BBB disruption is an emerging field. Therefore, means to monitor the BBB function non-invasively and in real-time are essential.Using existing MRI systems and state-of-the-art analytical tools, the methodology enables dynamic depiction of BBB physiological behavior, providing means to monitor changes in BBB permeability as wells as characterization of CNS pathologies. 

Applications


  • Assessment of CNS disorders – Diagnosis, Staging etc.

  • Monitoring the development of CNS disorders & response to treatment

  • Monitoring the effects of compounds or technologies on the BBB

  • Determine BBB function under certain physiological conditions  

  • Drug development:
    •  Modification of molecules to improve passage through the BBB.
    • Apply for the development of compounds/devices that affect BBB functioning.


Advantages


  • Non-invasive, real-time, 3D depiction of BBB functioning

  • Sensitivity to slight BBB abnormalities, undetected by conventional MRI

  • Acquired in parallel to conventional MRI enabling high resolution anatomical depiction

  • Can be acquired on available conventional clinical/pre-clinical MR systems using conventional data acquisition software


Technology's Essence


A methodology for analyzing the blood-brain barrier’s behavior, based on a detectable standard dose of MRI contrast agent. The methodology uses plurality of MRI images acquired from a subject’s brain over a predetermined time period, in order to asses BBB function in a uniquely sensitive manner. The system offers a combination of a data acquisition protocol and an offline software package, operating as an “add-on” to existing MRI systems. The system compares series of MRI constructed intensity maps, using different metrics to sensitively detect dissimilarities. The output is BBB functioning maps, depicting regions of BBB abnormalities.

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  • Prof. Talila Volk
  • Dr. David Israeli
1151
A method to significantly shorten acquisition times of high-quality MRI images. Multidimensional nuclear magnetic resonance (NMR) is used nowadays in many applications (e.g., discovery of new pharmaceutical drugs, characterization of new catalysts, and investigation of the structure and dynamics of...

A method to significantly shorten acquisition times of high-quality MRI images.

Multidimensional nuclear magnetic resonance (NMR) is used nowadays in many applications (e.g., discovery of new pharmaceutical drugs, characterization of new catalysts, and investigation of the structure and dynamics of proteins). One drawback of this technique is that, by contrast to one-dimensional spectroscpic methods, multidimensional NMR requires relatively long measurement times associated with hundreds or thousands of scans. This places certain kinds of rapidly-changing systems in Chemistry outside the scope of the technique. Long acquisition times also make this technique ill-suited for in vivo analyses and for clinical measurements in combination with magnetic resonance imaging (MRI). The current technology allows for the acquisition of multidimentional NMR scans using a single continuous scan, thereby shortening the time needed to acquire high-quality MRI images.

Applications


  • In vivo diagnostics

  • High-throughput proteomics/metabonomics

  • NMR of unstable chemical systems

  • Metabolic dynamics

  • High-resolution NMR in tabletop systems

  • Extensions to non-MR spectroscopies


Advantages


  • Can shorten the acquisition time of any multidimensional spectroscopy experiment by orders of magnitude
  • Compatible with the majority of multidimensional pulse sequences
  • Can be implemented using conventional NMR and MRI hardware

Technology's Essence


The outlined approach, called ultrafast multidimensional NMR, significantly expedites the analysis of the electromagnetic sounds produced, making it possible to acquire complete multidimensional NMR spectra within a fraction of a second. This technology “slices up” the molecular sample into numerous thin layers and then simultaneously performs all the measurements required on every one of these slices. The protocol then integrates these measurements according to their precise location, generating an image that amounts to a full multidimensional spectrum from the entire sample.

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  • Prof. Lucio Frydman