Innovation Future Specialist
Brain Health Blog: Medical
Quick Innovative Ideas
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This lists modern medical innovations and ideas to assist in brain health. It focuses on the technical aspects of microscopic visualisation (including fibre tracts) during cancerous (glioma) tumour resection surgery, and innovations to improve the rate of success.
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2019 January
Brain visualisation during cancer surgery: state of the art and beyond!
An introduction to the most advanced microscopic visualisation techniques during brain surgery; with innovations for even better solutions in the future, including innovative surgical techniques for post resection to prevent the return of cancerous tumours (e.g. gliomas).
This report and the associated blog have been developed by Dr Adam Bostock, Innovation Future Specialist.
Note that NHS staff in the UK can get additional support on this, or other aspects of innovation, via Innovation Future Specialist, at unbeatable prices.
2019 Jan 17
Tags: BrainFibre MRI TeraHz Spectrum Fluorescence OCT Hologram ConfocalRefl OpticFibre Polarised SpinOrbital Dye AI Treatment
2018 October
Proposed: advanced integrated systems
Innovation Future Specialist proposes an integrated system with state of the art optics, illumination, spectroscopy, image enhancement, and AI processing.
A schematic of three approaches: (a) basic microscopy; (b) multiple colour laser illumination with modern microscopy and digital image enhancement; and (c) approach (b) plus spectroscopy and AI processing.
In (c) the surgeon can switch between display modes: raw image; enhanced image; fibre tract view; and glioma view. In this schematic green illustrates the fibre view and red for glioma view. The AI system derives these views using image and spectroscopy data.
2018 Oct 18
Tags: BrainFibre Spectrum Fluorescence OCT Hologram ConfocalRefl Polarised Dye AI
Idea: Develop targeted (cancer) drugs that have multiple criteria
A safer and more effective approach to cancer treatment.
To ensure that chemo- or immuno-therapy only targets where it is intended and only specific (cancer) cells, develop systems that must meet multiple criteria to become active (deploy its treatment payload). For example:
- Identifies specific cell type
- Identifies specific cancerous attribute; and/or
- Highlight the target area for activation, e.g. by spraying or painting on a chemical/biological substance; or defining the area by magnetic field, electromagnetic illumination, or ultrasound.
A minimum of two criteria should be met to improve patient safety, reduce morbidity, and improve efficacy. Given the improved safety feature (of specific targeting) more powerful chemical/biological treatments can be delivered.
2018 Oct 16
Tags: Treatment
A targeted approach to treating glioma
With this new method, surgeons would remove the tumour, then implant micro-particles that attack remaining cancer cells.
2018 Oct 16
Tags: Treatment
Idea: laser scan across spectrum and use an AI to identify tissue types
A machine learning (AI) system could be taught the spectral signatures of every tissue type (both healthy and cancerous brain cells, axons, vessels, etc.). It would then be able to distinguish these in vivo via a standard microscopy technique (e.g. confocal reflectance).
Spectral information can be obtained by broadband (e.g. white light) illumination and a diffraction grating (or other spectroscopy technique). However, the author suspects that using a narrow band monochromatic laser source (that scans across the electromagnetic spectrum) might collect more details and yield better results. Either way this technique would be useful to identify tissue types.
Once the AI has been trained then a similar approach can be used in vivo to identify tissue types at the microscopic level. However, to speed up this process the laser only needs to illuminate at those specific wavelengths that correspond to the unique characteristics of known tissue types. (For example, if all tissue types reflect light at 550nm then the laser can skip this wavelengths.)
2018 Oct 16
Tags: Spectrum ConfocalRefl AI
Polarized Raman microscopy imaging: Capabilities and challenges for cancer research
The approach presented here opens new possibilities in monitoring biochemical composition, structures and symmetry of vibrations in biological tissues.
2018 Oct 16
Tags: BrainFibre Spectrum Fluorescence Polarised
Impact of Intraoperative Stimulation Brain Mapping on Glioma Surgery Outcome: A Meta-Analysis
Meta study of Intraoperative Stimulation Brain Mapping (ISM).
Conclusion: Glioma resections using ISM are associated with fewer late severe neurologic deficits and more extensive resection, and they involve eloquent locations more frequently. This indicates that ISM should be universally implemented as standard of care for glioma surgery.
2018 Oct 16
Tags: Treatment
Idea: Pixel/mask object "interference"
When the pixel, or mask, size corresponds to the size of regular features in an image and one moves relative to the other striking contrast patterns are observed during movement.
For example, this effect can be observed when looking through regularly spaced railings on a fence, which has similar railings behind it. As you move a dynamic contrast pattern appears. This same effect can be applied at the small scale by: (a) having an image sensor array with spacing comparable to the diameter of axons (brain fibres) placed near the tissue under observation; or (b) having a mask with holes of similar size near the tissue (with traditional optical focusing and image detection behind the mask). In both cases the structure is made to vibrate slightly (perhaps just a few micrometres in amplitude).
The "interference" effect is dynamic and expected to be distinctly noticeable when this arrangement is place over tissue containing a bundle of brain fibres and the vibrations are activated. At a low frequency (< 10 Hz) of vibration the surgeon should see this effect. Alternatively, the dynamic image could be fed to a machine learning system that has been taught to recognise this effect, and it would highlight the areas of the image that contain fibre tracts.
2018 Oct 8
Tags: BrainFibre AI
Idea: AI to model cells and predict detectable cancer attributes
The use of AI to model the cell has been pioneered. This approach could be extended to model changes to the cell when it becomes cancerous.
Such a model might predict cell attributes (e.g. in glioma) that can be detected in its spectral signature (i.e. the presence of unique chemicals or a significant change in the quantity or ratio of certain chemicals). A spectral microscope setup could then be used with traditional or machine learning algorithms to highlight the presence of cancerous cells.
Such AI predictions could also be used to develop specific dyes that have an affinity for those attributes.
2018 Oct 8
Tags: Spectrum AI Dye
Idea: Monochrome and polarised light source
The clarity of an image (e.g. of brain fibres) could be enhanced by using monochromatic and polarised light sources.
It has been demonstrated that polarised light can be useful for microscopic imaging of brain tissue [see Polarised].
Further benefits may be achieved by also using a monochromatic light source, because chromatic aberrations in lenses can be avoided. [It is recognised that achromatic lens systems exist; but removing this need for achromatic lenses might provide extra flexibility and opportunities in other aspects of the optics.] This also removes chromatic issues associated with the tissue being observed.
However, it has been shown that to detect full fibre tracts at least three colours are required. So the system could quickly take three monochromatic (and polarised) images of the tissue and digitally assemble those into one image, in real time.
This approach is compatible with existing microscope technologies (e.g. OCT, Confocal reflectance, and holographic).
This approach can be combined with machine learning to automatically identify fibre tracts. [It would be interesting to investigate if machine learning performed best on the combined (three colour) image, or directly using the three monochrome images instead.]
2018 Oct 5
Tags: BrainFibre Spectrum OCT Hologram ConfocalRefl Polarised AI
Idea: Targeted chemotherapy in the tumour cavity
After resection, the surface of the tumour cavity could be coated with bio-chemical substance that targets any remaining glioma cells. This could be painted on, injected in, or jet spray injected.
Techniques now exist to target specific sites of cancerous cells, e.g. using the immune system or "nano-bots" with a site specific marker and payload.
2018 Oct 5
Tags: Treatment
Idea: Improved image contrast
Improved contrast of fibres in the image, to clearly outline fibre tracts.
Machine learning systems are now able to provide amazing levels of image enhancement (e.g. contrast). For example, an image taken in low light levels appeared black to the (human) observer; yet the AI processed image yielded a clear image (without the high levels of noise expected from conventional image processing techniques).
This approach may be used just to enhance the image; but it can also be taken further to learn specifically about fibres and outline them.
2018 Oct 5
Tags: BrainFibre AI
Idea: Draw surgical path on image: instructions for robot
Following the bulk resection, the fine surgery to remove diffuse cancerous cells can be planned by the surgeon drawing on the screen (over the brain image) where the robot should remove tissue.
Given that the final part of the surgery requires a great deal of care and accuracy, the proven accuracy of robotic surgical equipment could be very useful here. It is proposed that the microscopic images are relayed to a screen that allows the surgeon to draw areas of the image that should be surgically removed by the robot.
To optimise the accuracy of this approach, the spatial registration by the robot should match that of the microscope (or the space that corresponded to its field of view when the image was taken). As the action of removing the microscope followed by the insertion of a robotic device might displace the brain tissue (and offset registration) there might be a need to develop an integrated endoscope that includes both the optical and surgical components. If it is acceptable to remove (or neutralise) the tissue with heat ablation then it is possible to use the same (or similar) optics for imaging and treatment. The laser power, focused on the (3D) point of interest, would be increased to destroy the cancerous tissue. This is similar to 2 or 3 photon microscopy but with a higher power from the laser beam.
It is possible that this approach could be automated to a significant degree, and quickly deliver accurate surgery with effective patient outcomes. A machine learning system could automatically process the microscopic image and graphically superimpose its proposed surgical actions. The surgeon could either approve those actions at the click of a button, or (as outlined above) draw a modified set of surgical actions.
2018 Oct 5
Tags: AI Treatment
Fibre affinity dye: contrast or fluorescence
Apply dyes that have a specific affinity for brain fibres. These may be contrast agents or fluorescent dyes that glow when stimulated. For example: fluoromyelin dye. This aims to outline the presence of fibre tracts.
2018 Oct 3
Tags: BrainFibre Dye
Third harmonic generation (3 photon) microscopy
Three photons can be used to stimulate an atom/molecule, just like two photon microscopy. This provides an opportunity for additional spectral information and chemical identification.
Like two photon microscopy, a laser beam is focused to a point in 3D space in the sample, and the fluorescent emissions identify material at that point. A scanning mechanism is used to cover all points in the sample, and provide an image.
Scanning an area 1 cm x 1 cm might take approximately one minute. To speed this up see: Fast identification of fibre tracts.
2018 Oct 3
Tags: Spectrum Fluorescence
Idea: Fast identification of fibre tracts
Using any state of the art scanning microscopy technology, a faster scan is used by only scanning intermittent points in the sample. The resulting sparsely populated image data is then processed by a machine learning system that has learnt how to identify fibre tracts (given such images). [See also: Automatic identification of fibre tracts]
2018 Oct 3
Tags: BrainFibre ConfocalRefl AI
Idea: Automatic identification of fibre tracts
Using any state of the art microscopy technology, fibre tracts are automatically identified. The image data is processed by a machine learning system that has learnt how to identify fibre tracts in images.
These are shown to the surgeon visually, e.g. by either overlaying a colour for the fibre tract area, colouring each fibre, and/or enhancing the contrast of the fibres. The surgeon can toggle between this and the raw image view.
Note that machine learning algorithms can be trained on any type of optical data (e.g. images in the visible range, infrared, and spectral [and hence chemical] information). Machine learning has been shown, many times, to perform very well at image processing and identifying specific features in an image. It is anticipated that an algorithm that has access to a rich data source might perform better than others (e.g. holographic and/or spectral imaging).
This approach could be extended to include the identification of other important features (e.g. cell types, glioma, and vessels).
2018 Oct 3
Tags: BrainFibre Spectrum Fluorescence OCT Hologram ConfocalRefl Polarised Dye AI
Idea: Transdifferentiation to deal with remaining glioma cells (and deliver a better prognosis)
It has been shown that cells can be converted to neurons via bio-chemical transdifferentiation. What if we convert glioma cells to neurons...?
On the assumption that, generally, neurons do not divide into new cells and are locked in position (by their links to other neurons), this offers a potential solution to dealing with those cancerous glioma cells that may be left behind after tumour resection surgery. The theory being that these static cells cannot propagate the cancer.
After the resection, the surgeon can apply the chemicals across the surface of the entire cavity. This may involve painting them on, injecting them in, or using jet injection (spray) to quickly achieve coverage and sufficient depth into the surface.
Transdifferentiation has been tested in animal models. Now research is required in humans (safety and efficacy). If successful this might have a significant impact on the future treatment of gliomas.
2018 Oct 3
Tags: Treatment
Idea: Sound induced oscillations to alter spectral characteristics of fibres
Altering the birefringence and/or interference properties of the axon's myelin sheath.
A study that resolved brain fibres noticed that multiple (laser) frequencies were required to detect the full tract of each fibre. They hypothesised that one reason for this was that the thickness of the myelin sheath causes interference [like the colours of a soap bubble] and varying thickness might be responsible for their visibility at different wavelengths (colours). Based on this, if the fibres were made to oscillate then the thickness might vary slightly, which would change the colour at which they were perceived (the colour oscillating in tune to the driving frequency or sound).
The study needed three laser colours to observe fibre tracts. So using these colours, an electronic imaging system could detect parts of fibres appearing and disappearing while the sound is applied. This dynamic aspect would distinguish the fibres from other matter in the brain, and so provide a clearer outline of where the fibres were.
The author of this idea does not know the resonant frequency of brain fibres, but experimentation with a laser and doppler detection of the reflections, would provide this information. Hopefully, an ultrasonic frequency might suffice and so allow a quiet operating environment :-)
The sound need not be continuous; it could be pulsed. This also allows the potential to time the effect (as the sound wave moves through the sample) and so determine the presence of fibre as a function of depth.
Similarly, stress on some birefringent materials might change their optical properties (e.g. refractive index and/or polarisation). Consequently, oscillations might create changes in the optical properties of fibres. [See: Polarised]
Note: A further area of potential research is the oscillating impact on optical methods that rely on angles of incidence and (fibre) reflection (as outlined elsewhere in this blog).
2018 Oct 3
Tags: BrainFibre Spectrum OCT Polarised
2018 September
Idea: Chromatography enhanced microscopy
Using a mixture of coloured (or fluorescent) dyes, each of varying molecular lengths and colours, to resolve images at different depths in a sample.
A multicoloured mixture of dyes is applied to the surface of the sample and allowed to diffuse into the sample. The theory being that the long molecules diffuse slowly into the sample; whereas the shorter ones diffuse quicker. This means that the colour of the shortest molecules is shown more strongly as a function of depth into the sample. The mixture may contain coloured dyes and/or fluorescent dyes. The resulting colour coded depths may be utilised in conjunction with various microscopic imaging techniques; and digital image enhancement and classification technologies.
In addition, it might be that the fibre tracts in the brain support capillary motion and so allow the dye to enhance the contrast of these tracts. This is a possible area of research: to what extent does this occur; and can the effect be enhanced by using specific molecules (e.g. those that have an affinity for the myelin sheath around axons).
2018 Sep 28
Tags: BrainFibre Fluorescence Dye
Idea: Fibre contrast enhanced microscopy
A fibre tract contrast enhancing dye (or fluorescent dye) is applied to the surface of the sample and allowed to diffuse into the sample.
It is assumed that the fibre tracts in the brain might support capillary motion and so allow the dye to follow these tracts and enhance the contrast of these tracts. This is a possible area of research: to what extent does this occur; and can the effect be enhanced by using specific molecules (e.g. those that have an affinity for the myelin sheath around axons).
2018 Sep 28
Tags: BrainFibre Fluorescence Dye
Idea: Multiple optimum angles of illumination and observation
Dynamically positioning the light source and objective (lens) at optimal angles to resolve fibre tracts more clearly.
This is inspired by the clear illustrations, all around us, that demonstrate the angle of incidence is equal to the angle of reflection (for well defined structures and significantly abrupt changes in refractive index).
It might be that, for some orientations of fibre tracts, the optimum angle for illumination and observation are not at 90 degrees to the sample's surface, but instead at angles relative to the orientation of the fibre tracts.
A relatively simple way to do this would be to use a multi-core fibre optic cable (in an endoscope). The fibres would be arranged in a circle at the distal end (near the sample) and each would focus towards the centre of the circle and down on to the sample (e.g. at 45 degrees). The control system would sequentially illuminate just one fibre core at a time, and detect the scattered image received by all the other fibres. The image processing system could then either (a) select the best single image from one individual fibre; or (b) combine all of the images simultaneously to digitally derive an optimum image of the fibre tracts.
In the case of (a) a relatively simple contrast test might be all that is required to select the best image (the best positioned fibre core). (Simple contrast evaluating technologies have been in use for many years in self-focusing cameras; and these might inspire a similar technique for this application.)
In the case of (b) this could be achieved by using relatively standard (3D) geometric imaging algorithms, or by using an AI system (similar to brain fibre tracing systems).
2018 Sep 28
Tags: BrainFibre OpticFibre AI
Idea: Multiple optimum angles of illumination and observation (holographic)
Positioning the light source and objective at optimal angles to resolve holographic images of fibre tracts more clearly.
Based on the above idea, but using holography. Each fibre core would carry its own holographic image. Digital imaging technology would then select the best hologram or combine holograms; using relatively standard imaging algorithms and/or AI.
See also examples of holographic imaging using fibre optics (select the Hologram filter on this page).
2018 Sep 28
Tags: BrainFibre Hologram OpticFibre AI
AI in Healthcare
Practical information for using AI in healthcare; and its achievements to date.
2018 Sep 26
Tags: AI
"Lightning" microscopic image enhancement
Improved high resolution colour images by digitally enhancing raw confocal microscopy images.
2018 Sep 26
Tags: ConfocalRefl
Optical Coherence Tomography/Gastroenterology: Advanced OCT: Next-gen OCT for the esophagus
OCT: 3mm image depth; 7 micrometre resolution.
This approach provides noninvasive and comprehensive depth imaging to improve the detection of esophageal cancer, and hopes to enable screening in addition to assessment. It provides cross-sectional imaging in real time. OCT meets an imaging need, from a resolution and depth perspective, that is not met by ultrasound, confocal microscopy, or white-light endoscopy. A form of OCT can image 3 mm deep into the mucosa, with 7 μm resolution.
Laser: wavelength sweep (1265 to 1355 nm in 20 microseconds) achieved by an intra-cavity tunable filter based on a spinning polygon mirror.
Inside the imaging console, light reflected back from the tissue (via the optical probe) is combined (interfered) with light from a reference reflector. The beat frequency between these two interfering beams is directly proportional to the depth of the reflection from the tissue.
2018 Sep 24
Tags: OCT OpticFibre
Stephen Boppart: Developing new optical imaging techniques for clinical use
This can be used to identify remaining cells in a tumour cavity. It uses OCT and an innovative approach that measures mechanical deformations for tissue classification.
2018 Sep 24
Tags: OCT OpticFibre
Differential interference contrast microscopy
This uses two polarised beams of illumination (which are slightly spatially offset) to interfere and give a 3D looking edge to objects. This may be useful to enhance contrast.
2018 Sep 24
Tags: Polarised
Chemical Probes for Visualizing Intact Animal and Human Brain Tissue
This refers to ex-vivo applications, but it provides useful background information; and it might inspire in-vivo applications.
Smart probes change their fluorescent spectra when bound to a target. For example, thioflavin T and other amyloid probes fluoresce only when bound to amyloids. Lipophilic tracers are amphiphilic molecules that insert into the cell membranes of neurons or other cells, where they diffuse along the membrane to achieve a cell-tracing effect [examples given].
2018 Sep 24
Tags: Spectrum Fluorescence Dye
Chapter Two - Fluorescence-Based In Situ Quantitative Imaging for Cellular Lipids
To achieve quantitative in situ imaging of various lipids, a ratiometric analysis using fluorescence biosensors, each of which is composed of an engineered lipid-binding protein and a covalently attached solvatochromic fluorophore. To cover a wide range of lipid concentration, lipid-binding proteins are engineered to have variable dynamic ranges. These tunable sensors allow robust and sensitive in situ quantitative lipid imaging in mammalian cells, including cell membranes.
2018 Sep 24
Tags: Fluorescence Dye
Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy
SCoRe Microscopy: Spectral confocal reflectance microscopy
This describes a technique for high-resolution in vivo imaging of myelinated axons in the brain, spinal cord and peripheral nerve that requires no fluorescent labelling. This method, based on SCoRe, uses a conventional laser-scanning confocal system to generate images by merging the simultaneously reflected signals from multiple lasers of different wavelengths.
Striking colour patterns unique to individual myelinated fibers are generated that facilitate their tracing in dense axonal areas. These patterns highlight nodes of Ranvier and Schmidt-Lanterman incisures and can be used to detect various myelin pathologies. Brain imaging up to 400 micrometres deep captured de novo myelination of mouse cortical axons in vivo. They also established the feasibility of imaging myelinated axons in the human cerebral cortex. SCoRe adds a powerful component to the evolving toolbox for imaging myelination in living animals and potentially in humans.
This suggests the feasibility of imaging myelinated axons in human tissue with high resolution, low laser power and no dye administration.
2018 Sep 24
Tags: BrainFibre Spectrum ConfocalRefl
Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy
Imaging technique for visualising tumour margins during surgery: stimulated Raman scattering (SRS) microscopy.
This demonstrates the ability of SRS microscopy, a non-destructive, label-free optical method, to reveal glioma infiltration. This revealed human brain tumour infiltration in fresh, unprocessed surgical specimens. SRS detected tumour infiltration in near-perfect agreement with standard H&E light microscopy. The unique chemical contrast specific to SRS microscopy enables tumour detection by revealing quantifiable alterations in tissue cellularity, axonal density and protein:lipid ratio in tumour-infiltrated tissues.
To ensure that SRS microscopic data can be easily used in brain tumour surgery, without the need for expert interpretation, they created a classifier based on cellularity, axonal density and protein:lipid ratio in SRS images. It is capable of detecting tumour infiltration with 97.5% sensitivity and 98.5% specificity. Importantly, quantitative SRS microscopy detects the spread of tumour cells, even in brain tissue surrounding a tumour that appears grossly normal. By accurately revealing tumour infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumour surgery.
SRS microscopy holds promise for in vivo application because of its ability to generate microscopic images in situ without removing or processing the tissue.
2018 Sep 24
Tags: BrainFibre Spectrum Fluorescence
High-Speed Coherent Raman Fingerprint Imaging of Biological Tissues
Broadband coherent anti-Stokes Raman scattering (BCARS).
An imaging platform based on BCARS has been developed which provides an advantageous combination of speed, sensitivity and spectral breadth. The system utilises a configuration of laser sources that probe the entire biologically-relevant Raman window with high spectral resolution. It strongly and efficiently stimulates Raman transitions within the typically weak "fingerprint" region using intra-pulse 3-colour excitation, and utilises the non-resonant background to heterodyne amplify weak Raman signals. It demonstrated high-speed chemical imaging in 2D and 3D views of ... interfaces between xenograft brain tumours and the surrounding healthy brain matter.
Alternate narrowband techniques such as coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) are limited, in comparison to this approach.
Fig 1: Coherent Raman Imaging with BCARS microspectroscopy
The spectrometer detection range is sufficiently broad (> 250 nm) to acquire signal from BCARS as well as other nonlinear processes, such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF), providing an additional layer of information for spectral interpretation.
The spectral analysis allows chemical identification and classification of tumour and normal brain matter. See: Fig 4: Histopathology using broadband CRI
2018 Sep 24
Tags: Spectrum Fluorescence
Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy
Stimulated Raman scattering (SRS) microscopy.
This describes the use of SRS microscopy for differentiating healthy human and mouse brain tissue from tumour-infiltrated brain, based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumour from non-neoplastic tissue based on their different Raman spectra. The study demonstrated a correlation between SRS and H&E microscopy for detection of glioma infiltration (κ=0.98). SRS microscopy was applied in vivo in mice during surgery to reveal tumour margins that were undetectable under standard operative conditions. By providing rapid intra-operative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumour boundaries are visually indistinct.
2018 Sep 24
Tags: Spectrum Fluorescence
Intraoperative confocal microscopy for brain tumors: a feasibility analysis in humans.
A feasibility analysis of the intra-operative (handheld) confocal microscope for brain tumour resection.
Thirty-three patients with brain tumour treatment were examined. All patients received an intravenous bolus of sodium fluorescein before confocal imaging with a probe. Optical biopsies were obtained within each tumour and along the tumour-brain interfaces. Corresponding pathologic specimens were then excised and processed. These data was compared by a neuropathologist to identify the concordance for tumour histology, grade, and margins.
The study concluded that intra-operative confocal microscopy is a practical technology for the resection of human brain tumours. Preliminary analysis demonstrates reliability for a variety of lesions in identifying tumour cells and the tumour-brain interface. Further refinement of this technology depends upon the approval of tumour-specific fluorescent contrast agents for human use.
2018 Sep 24
Tags: ConfocalRefl
Optical Analysis of Glioma: Fourier-Transform Infrared Spectroscopy Reveals the IDH1 Mutation Status
Somatic mutations in the human cytosolic isocitrate dehydrogenase 1 (IDH1) gene cause profound changes in cell metabolism and are a common feature of gliomas with unprecedented predictive and prognostic impact. Fourier-transform infrared spectroscopy addresses the molecular composition of cells and tissue and was investigated to deduct the IDH1 mutation status. Spectroscopy reveals the IDH1 genotype of glioma. Because it can provide information in seconds, an implementation into the intra-operative workflow might allow simple and rapid online diagnosis of the IDH1 genotype. The intra-operative confirmation of IDH1 mutation status might guide the decision to pursue definitive neurosurgical resection and guide future in situ therapies of infiltrative gliomas.
2018 Sep 24
Tags: Spectrum
Spatio-spectral classification of hyperspectral images for brain cancer detection during surgical operations
Classification maps were validated by specialists. Results showed accurate delineation of the tumour area. (Machine learning used)
Hyper-spectral imaging is a non-contact, non-ionizing and non-invasive technique suitable for medical diagnosis. This study presents the development of a novel classification method taking into account the spatial and spectral characteristics of the hyper-spectral images to help neurosurgeons to accurately determine the tumour boundaries in surgical-time during the resection, avoiding excessive excision of normal tissue or unintentionally leaving residual tumour. The algorithm proposed in this study to approach an efficient solution consists of a hybrid framework that combines both supervised and unsupervised machine learning methods.
The algorithm was accelerated to derive classifications in surgical-time during the neurosurgical operation. The preliminary system obtained classification results in ~1 minute. Further acceleration could provide the results in less than one second by using an heterogeneous high performance computing system, thus obtaining real-time results.
2018 Sep 24
Tags: Spectrum AI
Automated white matter fiber tract identification in patients with brain tumors
This method is designed to be relatively robust to challenges in neurosurgical tractography, which include peritumoral edema, displacement, and mass effect caused by mass lesions. It consists of:
1) Learn a data-driven white matter parcellation or fibre cluster atlas using group-wise registration and spectral clustering of multi-fibre tractography from healthy controls. Key fibre tract clusters are identified in the atlas.
2) Patient-specific fibre tracts are automatically identified using tractography-based registration to the atlas and spectral embedding of patient tractography.
Results indicate good generalization of the data-driven atlas to patients: 80% of the 800 fibre clusters were identified in all 18 patients, and 94% of the 800 fibre clusters were found in 16 or more of the 18 patients. All patient-specific activations were within 3 mm of the corresponding language or motor tract. Overall, our results indicate the potential of an automated method for identifying fibre tracts of interest for neurosurgical planning, even in patients with mass lesions.
2018 Sep 24
Tags: BrainFibre
TRAFIC: fiber tract classification using deep learning
TRAFIC is a fully automated tool for the labelling and classification of brain fibre tracts.
It classifies new fibres using a neural network trained using shape features computed from previously traced and manually corrected fibre tracts. It is independent from a DTI Atlas as it is applied to already traced fibres. This work is motivated by medical applications where the process of extracting fibres from a DTI atlas, or classifying fibres manually is time consuming and requires knowledge about brain anatomy.
2018 Sep 24
Tags: BrainFibre AI
High-Resolution Fiber and Fiber Tract Imaging Using Polarized Light Microscopy in the Human, Monkey, Rat, and Mouse Brain
Polarized light imaging enables ultra-high resolution visualisation of nerve fibres in postmortem brains by the birefringent property of myelin.
3D orientation of fibres can be determined in serial sections throughout the brain. Examples of fibre architecture with an unprecedented spatial resolution both in the white matter and within the cerebral cortex. Crossing of fibres can be directly visualised without any assumptions or modelling, and fibres can be followed from the white matter into the most superficial layers of the cortex. Even extremely small fibre tracts are visible. Furthermore, the fibre architecture within the cerebral cortex provides a new approach for its parcellation into areas with distinct distribution, orientation, and density patterns of nerve fibres.
2018 Sep 24
Tags: BrainFibre Polarised
Submersible holographic microscope
Digital inline holographic microscopy
Recognition resolution: 20 μm. Field of view: Up to 4.2 mm. Image types: Intensity, amplitude, and phase images – including Quantitative Phase. Spatial sampling: 2048 x 2048 pixels (hologram). Image acquisition rate: Real-time imaging: 22 fps. Imaged object size: From 2 μm to 2 mm recommended. This product is deployed in a aquatic environment, but it does illustrate the ability of holographic microscopy.
2018 Sep 24
Tags: Hologram
Flat lens promises possible revolution in optics
Tiny meta-material device can magnify nano-scale objects and gives a sharp focus.
Just 2 mm (but could be up to 12 inch) across and far thinner than a human hair, the tiny device can magnify nano-scale objects and gives a sharper focus than top-end microscope lenses. It is a thin layer of transparent quartz coated in millions of tiny pillars, each just tens of nanometres across and hundreds high. "The quality of our images is actually better than with a state-of-the-art objective lens. I think it is no exaggeration to say that this is potentially revolutionary." Those comparisons were made against top-end lenses used in research microscopes, designed to achieve absolute maximum magnification. The focal spot of the flat lens was typically 30% sharper than its competition, meaning that in a lab setting, finer details can be revealed.
2018 Sep 24
Tags:
Miniature optical planar camera based on a wide-angle metasurface doublet corrected for monochromatic aberrations
Meta-material miniature flat camera with a monolithic meta-surface lens doublet and an image sensor.
Optical meta-surfaces are two-dimensional arrays of nano-scatterers that modify optical wave-fronts at sub-wavelength spatial resolution. They are poised to revolutionise optics by enabling complex low-cost systems where multiple meta-surfaces are lithographically stacked and integrated with electronics. For imaging applications, meta-surface stacks can perform sophisticated image corrections and can be directly integrated with image sensors.
A demonstration of this concept includes a miniature flat camera integrating a monolithic meta-surface lens doublet corrected for monochromatic aberrations, and an image sensor. The doublet lens, which acts as a fish-eye photographic objective, has a small f-number of 0.9, an angle-of-view larger than 60 × 60 degrees, and operates at 850 nm wavelength with 70% focusing efficiency. The camera exhibits nearly diffraction-limited image quality, which indicates the potential of this technology in the development of optical systems for microscopy, photography, and computer vision.
2018 Sep 24
Tags:
A broadband achromatic metalens for focusing and imaging in the visible
Meta-material lens.
By judicious design of nano-fins on a surface, it is possible to achieve a transmissive achromatic meta-lens with large bandwidth. This demonstrates diffraction limited achromatic focusing and achromatic imaging from 470 to 670 nm. The meta-lens comprises only a single layer of nano-structures whose thickness is on the order of the wavelength, and does not involve spatial multiplexing or cascading. While this initial design (numerical aperture of 0.2) has an efficiency of about 20% at 500 nm, the report discusses ways in which the approach may be further optimised to meet the demand of future applications.
2018 Sep 24
Tags:
Compact, Light-weight and Cost-effective Microscope based on Lensless Incoherent Holography for Telemedicine Applications
UCLA engineer invents world's smallest, lightest tele-medicine microscope, based on holography.
This describes the invention of a novel lens-less imaging technology. It is described as the world's smallest and lightest microscope for tele-medicine applications. Instead of using a lens to magnify objects, it generates holographic images of cells by employing a light-emitting diode to illuminate the objects and a digital sensor array to capture their images. It can also be cheaply converted into a differential interference contrast microscope.
It achieves sub-cellular resolution over a large field of view; based on digital in-line holography. As it generates a hologram this provides 3D images and auto focus (digitally select the focal plane). It can scan and image surfaces extremely rapidly, without any vertical mechanical movement and does not need any lenses, bulky optical/mechanical components or coherent sources such as lasers. Instead, it uses a simple LED and a compact opto-electronic sensor-array.
It achieves ~ 1 to 2 micrometre resolution; and a field of view of ∼24 mm2, which constitutes ~10 fold improvement compared to a typical 10× objective lens.
2018 Sep 24
Tags: Hologram
Digital in-line holography for biological applications
This routinely achieves both lateral and depth resolution, at least at the micron level, in three-dimensional imaging. The experimental and numerical procedures have been incorporated into a program package with a very fast reconstruction algorithm that is now capable of real-time reconstruction.
2018 Sep 24
Tags: Hologram
Openwater technology
Holographic screens can be used to project focused images [or focus light on a given spot].
This uses LCDs with pixels small enough to create reconstructive holographic images, which the inventors claim can neutralize the scattering and enable scanning at MRI resolution and depth. This can be used to focus light to any area of interest in the brain (to irradiate tumours for example).
2018 Sep 24
Tags: Hologram Treatment
Scientists study light to create technologies of the future
In addition to linear polarisation there is spin and orbital angular momentum. It is proposed to use such beams for early cancer detection.
2018 Sep 24
Tags: SpinOrbital
Idea: Suck out malignant cells
Suck out malignant cells via a needle like probe. Potential benefits: Prevents scattering of malignant cells during surgery. Reduced damage to surrounding cells, and no potentially toxic byproducts (e.g. compared to a high temperature heating method).
2018 Sep 24
Tags: Treatment
Idea: Pressure spray / inject transdifferentiation chemicals: zap infused glioma cells
Idea: Pressure jet spray / inject transdifferentiation chemicals to convert remaining (malignant) cells, after tumour resection, from glial cells to neurons.
Research has shown that cells can be converted to neurons: Transdifferentiation Can Create An Endless Supply of Brain Cells - And Fast.
Potential benefits: assuming these new neurons do not duplicate and remain fixed in position (and the treatment is safe and effective), this could prevent the cancer from spreading.
Search for transdifferentiation of glial cells.
2018 Sep 24
Tags: Treatment
Terahertz reflectometry imaging for low and high grade gliomas
TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.
TRI images presented tumour regions with high terahertz reflection signals compared with normal brain regions. The researchers claim they could find the presence of tumour in all cases by TRI images. The wavelength of terahertz electromagnetic waves is a few hundred-μm, so TRI may be more suitable as a macroscopic imaging tool of gliomas. While TRI may not be able to delineate tumor margin at the cellular level, it has the potential to macroscopically delineate foci-glioma margins.
Handheld TRI devices have been already developed, so the neurosurgeons could utilize these tools to locate tumors during operation.
2018 Sep 24
Tags: TeraHz
A miniaturized fiber-coupled terahertz endoscope system
The cross section of the endoscope including generator and detector head is (2 x 4 mm) x 6 mm, which is small enough to be inserted into a human body.
2018 Sep 24
Tags: TeraHz
Implantable Drug-Making Cells
Imagine lining the tumour resection cavity with a system that delivers local chemotherapy (or transdifferentiation chemicals)...
2018 Sep 24
Tags: Treatment
How ablation destroys cancer to prolong lives
Clean up the post-resection cells with microwave ablation, which works by radiating an energy field out of the tip of the needle into the tumour, heating the water within the cancer cells until they are destroyed - you can tune the shape and diameter of that field to prescribe exactly how deep it goes into the tissue.
2018 Sep 24
Tags: Treatment
Post resection in-situ chemotherapy
Clean up the post-resection cells with an applied layer of chemotherapy; or jet sprayed/injected chemotherapy.
2018 Sep 24
Tags: Treatment
Utility of Microwave Ablation in Brain Tumor Surgery: Preliminary Report of Twenty Two
The use of Microwaves in Brain Surgery.
This uses a thin antenna. Energy was applied for 1 to 3 minutes and the antenna reached 70-90 degrees Celsius. The cortical brain surface temperature registered 32 to 34 degrees Celsius during the ablation process. Cavitation and ablation was observed, and adjacent vascular and brain structures were preserved. The researchers concluded that Microwave Ablation is excellent tool for brain tumour surgery. It was safe in all cases (no additional neurological deficit was detected). It resulted in decreased intra-tumoural blood flow, therefore enabling the micro-surgical resection.
2018 Sep 24
Tags: Treatment
MRI features predict p53 status in lower-grade gliomas via a machine-learning approach
The study demonstrated that MR image texture features are predictive of mutation status in lower-grade gliomas. Thus, it can be used to facilitate pre-surgical molecular pathological diagnosis.
2018 Sep 24
Tags: MRI AI
Endoscopic microscopy
Delicate brain surgery can benefit from the use of an in-situ microscope, and in difficult to reach places (such as deep within the brain) this might require a microscope integrated into an endoscope.
Optical microscopes can render magnified images that have sufficient resolution to identify individual brain fibres, such as the axons of neurons.
Endoscopes are the long tubes that can reach places deep inside the body via a small external orifice, and are able to include visualisation and surgical tools; and flexible, controllable, attributes to aid navigation and orientation. Illumination and visualisation can be provided by optical fibres.
2018 Sep 21
Tags: BrainFibre OpticFibre
High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging
Ultra narrow fibre optic microscope: 50 micrometre field of view.
Multimode fibre-based endoscopy for deep brain in vivo imaging has been demonstrated by utilising holographic control of light propagation in complex media, which allows a hair-thin multimode optical fibre to be used as an ultra-narrow imaging tool. Compared to current endoscopes based on GRIN lenses or fibre bundles, this concept offers a footprint reduction exceeding an order of magnitude, together with a significant enhancement in resolution. The demonstration used fluorescent imaging and provided a 50 micrometre field of view.
2018 Sep 21
Tags: Fluorescence Hologram OpticFibre
Performances of endoscopic holography with a multicore optical fiber
An optical fibre system that features a resolution of 5 micrometre objects at a 4-mm observation distance.
2018 Sep 21
Tags: Hologram OpticFibre
Endoscopic holography with a muticore optical fiber applied to biomedical imaging
Capable of resolving 5 micrometre objects at a 4 mm distance. The observation of an object through a turbid medium was improved by the holographic technique.
An in situ holographic technique based on the use of a flexible miniaturized endoscope (diameter less than 1 mm) was developed for medical applications. The holographic system features a multicore optical fiber (MCF) coupled to a CCD camera to record the hologram. The hologram is formed by reflection on the tip of the MCF. Capable of resolving 5 micrometre objects at a 4 mm distance. The observation of an object through a turbid medium was improved by the holographic technique. Images of biological tissues demonstrated the ability to perform coherent imaging of cells, potentially providing major contribution to in vivo and in situ spectroscopic diagnostic capabilities at the microscopic scale.
2018 Sep 21
Tags: Spectrum Hologram OpticFibre
Endoscopic microscopy
A 2002 review of endoscopic microscopy: reflectance confocal microscopy (RCM) and optical coherence tomography (OCT); fluorescence; and contrast agents.
Contrast agents based on gold nanoparticles with probe molecules that have a high affinity for specific cellular biomarkers may have potential. The scattering of labeled SiHa cells is so strong that it can easily be observed using only a low magnification objective (10X or 20X) and a regular laser pointer as an illumination source.
2018 Sep 21
Tags: OCT ConfocalRefl OpticFibre Dye
Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope
Small (7mm, 21mm) microscope objective for endoscopic use, with diffraction-limited performance at 1064 nm.
An endoscopic confocal microscope requires a high-performance, miniaturized microscope objective. We present the design of a miniature water-immersion microscope objective that is approximately 10 times smaller in length than a typical commercial objective. The miniature objective is 7 mm in outer diameter and 21 mm in length from object to image. It is used in a fiber confocal reflectance microscope. The miniature microscope objective has a numerical aperture of 1.0. It delivers diffraction-limited performance at 1064 nm. Micrometre-level resolution has been experimentally demonstrated.
2018 Sep 21
Tags: ConfocalRefl OpticFibre
Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo
All optical components have 1 mm dimensions. Micrometre resolution. Frame rates: 25 Hz. Field-of-view: 200 microns.
A small, lightweight two-photon fiberscope demonstrated its suitability for functional imaging in the intact brain. The device consists of a hollow-core photonic crystal fiber for efficient delivery of near-IR femtosecond laser pulses, a spiral fiber-scanner for resonant beam steering, and a gradient-index lens system for fluorescence excitation, dichroic beam splitting, and signal collection. Fluorescence light is remotely detected using a standard photomultiplier tube. All optical components have 1 mm dimensions and the microscope's headpiece weighs only 0.6 grams. The instrument achieves micrometre resolution at frame rates of typically 25 Hz with a field-of-view of up to 200 microns. It provided functional imaging of calcium signals in Purkinje cell dendrites in the cerebellum of anesthetized rats.
The article also contains a useful introduction to relevant technologies.
2018 Sep 21
Tags: BrainFibre Fluorescence OpticFibre
Fiber optic in vivo imaging in the mammalian nervous system
A useful review. Submillimeter-diameter endoscopes, or microendoscopes.
Cylindrically shaped Gradient-Index (GRIN) lenses act like optical fibers in the sense that they transmit light between distal locations using total internal reflection. Their refractive index declines gradually from its highest value on the cylindrical axis to values 1–6% lower at the radial periphery. So a GRIN microendoscope can project a real image of the specimen without using a fiber bundle array and achieve a resolution of ~ 0.9 micrometres.
OCT can be integrated within fiber optic hardware to utilise portable instruments and miniature probes.
2018 Sep 21
Tags: OpticFibre Fluorescence OCT
Optical biopsy of GI lesions by reflectance-type laser-scanning confocal microscopy
Laser-scanning confocal microscopy is a noninvasive method of optical imaging that can provide an instant microscopic image of untreated tissue under endoscopy.
2018 Sep 21
Tags: ConfocalRefl
Third harmonic generation imaging for fast, label-free pathology of human brain tumors
This shows that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality in fresh, unstained human brain tissue could be clearly recognized. It demonstrates THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumour boundaries. THG imaging is thus a promising tool for optical biopsies.
Multi-photon imaging modalities including SHG and THG have been successfully miniaturized into micro-endoscopic multi-photon imaging devices enabling in situ analysis of tissue.
This demonstrates that ex-vivo human brain tissue images similar to those obtained using a normal microscope can be obtained using a 7.5 mm long THG/SHG bioptic needle. The lenses were in a housing with outer diameter of 1.4 mm and total length of 7.5 mm. It was used for focusing of 1200 nm pulses and collecting back-scattered harmonic and fluorescence photons.
The results show that the use of such a needle for in situ optical sampling for optimal resection of gliomas is indeed a viable prospect.
2018 Sep 21
Tags: Fluorescence OpticFibre