DS0404 - Innovation biomédicale

Microrobotic nasal endoscopy by OCT: impact of smell deficiency on neurodegenerative diseases – NEMRO

Microrobotic nasal endoscopy by OCT: impact of smell deficiency on neurodegenerative diseases

This proposal refers to a transdisciplinarity and fundamental research project. It grounds itself in Engineering and Information Science (microrobotics) but with a strong anchor into the medical field (neurosciences). NEMRO addresses thus a vast research field, with both scientific and technological ambition, as well as a clear clinical application: neurodegenerative diseases (Alzheimer, Parkinson) and other pathologies with similar effects (drug addiction).

Context, position and objectives of the proposal

The scientific and technological challenges of the proposal include numerous aspects. This in terms of: 1) optimized medico-mechatronics design, precise, lightweight, biocompatible, non-invasive, 2) hybrid-actuated microrobotics device (2mm of diameter) ultra-precise, flexible with good dynamic and static behaviors, 3) non-invasive and non-contact submillimeter imaging system for 3D in-vivo visualization, and 4) exceed the current limits on the OCT systems acquisition frequency (about 10 frames/second) using the efficient mathematical methods called Compressed Sensing associated to innovative visual servoing approaches.<br />In others terms, NEMRO will develop a flexible miniature nasal endoscopy system based on a microrobot which will be able to position a fiber-based OCT probe in front of the olfactory mucosa with micrometer accuracy. This accuracy is needed by the in-vivo dynamic characterization, which implies 1) physical registration of cells between two examinations and 2) mosaicking of successive OCT slices into a coherent volume. Moreover, the microrobot will need to progress in an environment with unknown and patient-varying geometry and thus require exteroceptive sensing. Therefore, NEMRO will achieve image-based navigation through visual servoing techniques.

NEMRO scientific program is situated in the societal challenge 4 and challenges 7, in consequence cross-disciplinary approaches have to be considered to success the project. The project is built and structured according to a functional description of the NEMRO’s objectives:
(1) Conception of a miniature, flexible and actuated endoscopy system,
(2) Control of the endoscopy system equipped with the fiber-based OCT imaging system,
(3) Improvement of the OCT imaging system acquisition,
(4) Preclinical investigation and integration.
Therefore, NEMRO is organized in four scientific work packages:
WP0 – Management
WP1 – Mechatronics and Microrobotics Design,
WP2 – OCT Imaging System and Visual Servoing,
WP3 – Compressed Sensing using innovative visual servoing scheme,
WP4 – Preclinical Investigation and Integration,
WP5 – Dissemination and Exploitation.
Two partners are at least involved in each work package to ensure the cross-disciplinary approaches.
Also, each WP is organized in tasks which are led by the most involved and qualified person in the considered task. This organization is summarized below and detailed in the following.

Through the targeted medical objectives, NEMRO will be a project with high scientific potential, which can conduct to significant breakthroughs (better understanding of olfaction and neurodegenerative diseases, early diagnosis, non-invasive 3D optical biopsy) and open, in the future, new research paths (efficient therapy in neurodegenerative diseases). Technological innovations (high-speed OCT-based visual servoing, increased resolution for concentric tubes, lightweight flexible and miniature endonasal system) are also expected according to the multidisciplinary proposed approach. It constitutes a real opportunity to provide high-level scientific contribution in medical micro and mechatronics conception, advanced control, applied mathematics and high resolution and non-invasive 3D medical imaging techniques (fiber-based OCT), able to generate several relevant patents, and a real potential for industrial transfers. It also constitutes a real opportunity to provide high-level scientific publications (IJRR, IEEE T-RO, IEEE/ASME TMECH, IEEE Trans. Information Theory, Exp. Neurology J., J. of Neurology, IEEE ICRA, IEEE IROS, MICCAI etc.).
Another relevant aspect of NEMRO is the fact that the provided miniature endoscopic system for in-situ characterization (optical biopsy) of the olfactory mucosa allow to visualize nerve endings (nerve cells) by a non-invasive technique. Note that this is the only part of the human body where neurons are accessible without incision.
As regards to the economic impact, note that the neurodegenerative and relative diseases have affect, In France, about 860,000 persons (Alzheimer) and more than 120,000 (Parkinson). These numbers are rising steadily over the last decade creating an important societal malaise. In a recent report, the «Haute Autorité de Santé» has clearly underlined that therapy and diagnosis methods for these pathologies have received too few original scientific investigations over the last decade.

Beyond the diagnosis in the nose, the 2mm diameter endoscopy system will be suited to other microrobotized MIS methods in the brain, such as characterization and stimulation, intracranial tumors resection, or targeted drug delivery. The applications can be extended to others surgery domains (such as deep bronchioles, urethra access to the prostate, uterus, etc.) and to industrial applications (such as inspection of narrow curved spaces).

- international peer-review journals
2 (published) + 7 (under evaluation)
- book chapters
- international peer-review conferences
17 (published) + 3 (under review)
- national peer-review conferences
- popular journal articles
- popular conference articles
- others

Neurodegenerative and relative diseases have become the main priority of health authorities in developed and developing countries. In France only, about 860,000 persons suffer from the Alzheimer syndrome with 220,000 new cases reported each year, whereas more than 120,000 persons are affected by the Parkinson disease. However, in its latest report, the « Haute Autorité de Santé (HAS) », clearly underlined the lack of efficiency of the current treatments, that are more palliative than therapeutic. This is especially true when diagnosis comes too late, i.e. even at the first signs of memory and/or motricity loss. The HAS also underlined that screening and diagnosis methods for these pathologies have received too few novel scientific investigations over the last decade.

NEMRO project is part of the challenge of "Health and Well-Being" in its principal axis "Biomedical Innovation". It deals with the relationship between the neurodegenerative diseases and the olfactory deficiency. Several recent clinical studies (often statistical studies) have demonstrated an existing correlation between the loss of smell and the appearance of these pathologies. The olfactory deficit is a reliable precursor sign of a possible neuronal degeneration. Despite this significant advance in the understanding of neurodegenerative disease and related disorders, few ambitious scientific research to understand the origin, evolution and possible means to reverse these diseases by targeted therapies. The reasons for these studies remained at a clinical stage are many and varied. It is particularly difficult to access the olfactory mucosa located at the termination of the nasal walls with a diameter less than 3 mm. In addition to this is the lack of characterization/visualization techniques of the olfactory cells whose individual size is about a hundred micrometers.

NEMRO plans to develop a nasal endoscopy system equipped with a fiber-based OCT (Optical Coherence Tomography) imaging system. This nasal endoscope consists of a miniature robotic system (the diameter is less than 2 mm) and flexible. The design of the robot will be based on the use of a hybrid actuation: remote by a specific mechatronic system and an embedded actuation based on the use of electroactive materials (polymers). This system will provide an in-vivo dynamic characterization and non-invasive technique to perform 3D high resolution images (3D optical biopsies). These approaches will allow analyzing, with high accuracy (in 3D), the shape and the texture of the olfactory system, similar to histological studies. In a short term, this system gives a unique and reliable experimental investigation technique to understand/diagnosis of certain neurodegenerative diseases. It will also monitor the evolution, over time, the loss of smell and its effect on neuronal degeneration.

Through these medical goals, breaking with current practices in the diagnosis of neurodegenerative diseases, NEMRO will be a project with a high scientific potential, which can lead to significant breakthroughs (better understanding of olfaction, early diagnosis, etc.) and open new ways for scientific research (effective therapy). In addition to this, NEMRO provides high-level scientific contributions: intrinsically safe micromechatronics design, OCT-based control schemes, applied mathematical methods for Compressed Sensing. It will also be the same for technological innovations and contributions (miniature and flexible robotic endoscopy with hybrid actuation remote/embedded).

Project coordination

Brahim TAMADAZTE (Franche-Comté Electronique, Mécanique, Thermique et Optique - Sciences et Technologies/)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


FEMTO-ST Franche-Comté Electronique, Mécanique, Thermique et Optique - Sciences et Technologies/
LMB Laboratoire de Mathématiques de Besançon
CIC-IT-CHU Centre d’Investigation Clinique en Innovation Technologique de Besançon
INSA-ICube Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie

Help of the ANR 498,992 euros
Beginning and duration of the scientific project: September 2014 - 48 Months

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