OCT-RAMAN - Optical Coherence Tomography and Raman Spectroscopy
in-vivo diagnostic for colon-rectal cancer
Coordinator: Marino Maciel
Workteam: J. H. Correia, Sara Pimenta, Eliana
Vieira, Manuel Silva, Carlos Silva, Carlos Lima, Carla Rolanda, Hugo Pereira,
Rúben Freitas
Funds: 239.996,25 €, FCT-Portugal R&D Center: CMEMS-UMinho Start: 1 July 2018. End: 30 November 2021 Summary: Colorectal cancer (CRC) is the second most
common cause of cancer death in Europe. Real-time polyp diagnosis offers the
potential to save enormous healthcare costs by enabling early onset of
treatment. Flat or serrated lesions are often missed entirely, as they are
difficult to identify and assess due to their featureless appearance. Current
colonoscopy technology, i.e., white light video and optical narrow band
imaging, is thus inadequate for in vivo detection and characterization of the
various types of (pre-) cancerous lesions found in the colon. The most
complete and reliable optical diagnosis would be sensitive to morphological
and biochemical changes. Unfortunately, no single optical method provides
both. OCT-RAMAN project provides a unique
combination of two existing label-free, non-ionizing, proven optical imaging
modalities into a single cost-effective platform that endoscopically provides
higher sensitivity and specificity than currently used colonoscopic imaging
techniques for diagnosis of CRC (see Fig.1). The optical coherence tomography
(OCT) technology provides in vivo morphological 3D information in real time
and possibility for measuring tumour borders/demarcation and depth. Raman
spectroscopy is a powerful tool for molecular analysis of disease. The
molecular information obtained can be used for discrimination of cell and
tissues types, diseased versus healthy tissues and changes in DNA. A high-speed, high-resolution swept-source
OCT engine at 1300 nm for optimum penetration depth will be implemented. The
3D OCT setup will be used on high speed (100 kHz - 1 MHz A-scan rate) for
high resolution sweep range (100 nm), long coherence length, and hence long
working distance with low signal noise ratio (SNR) loss in scanning depth.
This enables 3D morphologic optical biopsies. Raman device at 785 nm
excitation wavelength will be implemented with an optical fibre (200 µm
diameter) to deliver the excitation beam and multiple optical fibres to
collect the Raman signal. The Raman probe head will have a filter to exclude
background fluorescence from the fibre, and the collection part will include
a high-pass filter at 785 nm wavelength and a lens to increase the collection
efficiency. The project plan foresees system validation
and demonstration in ex-vivo analyses on freshly resected specimens
clinical settings and finally in vivo pre-clinical animal testing. The
expected original contributions are: -A new platform will be adapted from
off-the-shelf endoscopes; -Combining two optical technologies in the
same endoscope tool for enabling cost effective CRC diagnosis; -Reduction in size, ease-of-operation, and
cost-effectiveness of the light sources and probes in the same endoscope; -Developing flexible delivery probes for
enabling reaching lesions in hollow organs of the human body via endoscopes; -Optimizing laser power in Raman probes to be
used real-time in-vivo for maximum permissible exposure and temperature
increase avoiding tissue damage. The final project results: Patents - An European Patent
- EP 21218451, authors: J. H. Correia, M. J.
Maciel, "System for screening, diagnosis, or monitoring a
colorectal tissue and method thereof" 31 december 2021. - A Portuguese Patent - PT117009 was filled, Sistema de análise dos tecidos colorretais baseado na integração da tomografia de coerência ótica na coloscopia convencional, authors: Marino Maciel, J. H. Correia, issued on 12 March 2021. PhD Theses -PhD thesis, Sandra Beatriz Gonçalves, “µLED Optrode
for Acute Optogenetic Applications”, Programa Doutoral MIT-Portugal,
Fevereiro 2019.
- PhD thesis, Veríssimo Manuel Brandão Lima Santos
“Deteção automática de lesões no intestino delgado por análise de imagens
obtidas por cápsula endoscópica”, May 2020 Master Theses -MSc thesis, Nuno Miguel Santos Teixeira de Sousa,
“Fabrico de um Sistema para Eletrodeposição de Filmes Finos de Platina”,
Mestrado Integrado em Eng. Eletrónica Industrial, November 2018. -MSc thesis,
José Pedro de Oliveira Pereira, “Fabrico de um Filtro Ótico Integrado numa
Matriz de Fotodíodos de Silício para Aplicação em Sondas Neuronais November
2018. -MSc thesis,
Maria Daniela Santos Moreira, "Tomografia Dentária Computorizada",
Mestrado Integrado em Eng. Biomédica, Universidade do Minho, December 2018. -MSc thesis,
João Rui Martins Freitas, “Fabrico de Microlentes para Aplicação em
MicroLEDs”, Mestrado Integrado em Eng. Eletrónica Industrial e Computadores,
November 2019. - MSc thesis, Diogo Azevedo Pereira, Sistema de
comunicação ótica para dispositivos biomédicos, Mestrado Integrado em
Engenharia Biomédica – ramo de Eletrónica Médica pela Universidade do Minho,
February 2021. - MSc thesis, Ruben Brandão Freitas, Cápsula insuflável
para o tratamento da obesidade, Mestrado Integrado em Engenharia Biomédica –
ramo de Eletrónica Médica pela Universidade do Minho, March 2021. - MSc thesis, Bruno Miguel C. Esteves, Fabrico e
caracterização de um fotodetetor paraintegração numa sonda neuronal flexível,
Mestrado Integrado em Engenharia Biomédica – ramo de Eletrónica Médica pela
Universidade do Minho, March 2021. - MSc thesis, Hugo Martins Pereira, Magnetómetros
atómicos de bombeamento ótico para medição de campos magnéticos cerebrais,
Mestrado Integrado em Engenharia Biomédica – ramo de Eletrónica Médica pela
Universidade do Minho, March 2021. International
Conferences: M. J. Maciel, S. Pimenta, J. F.
Ribeiro, and J. H. Correia, “Design of a novel TiO2/Airgap-based polarizing
micro beam splitter cube,” in 29th Micromechanics and Microsystems Europe
Workshop (MME 2018), August 26-29, Smolenice, Eslováquia, 2018. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2018_mmaciel.pdf M. J. Maciel, M. F. Silva, S. Pimenta, and J. H.
Correia, “Detection of low-magnetic fields by rubidium (87 Rb) vapor cell,”
Proceedings MME 2019 Micromechanics and Microsystems Europe Conference,
Oxford. UK, pp. 7–12, 2019. URL:
http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2019_mmaciel.pdf M. F. Silva, S. Pimenta, J. A. Rodrigues, M. J.
Maciel, M. Ghaderi, L. M. Goncalves, G. de Graaf, R. F. Wolffenbuttel, J. H.
Correia,” UV optical filters based in magnesium”, Proceedings MME
2019-Micromechanics and Microsystems Europe Conference, Oxford. UK, pp.
73–78, 2019. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2019_msilva.pdf S. Pimenta, M. Maciel, A. Miranda, M. Cerqueira, P.
Alpuim, and J. Correia, “Raman Spectroscopy for Tumor Diagnosis in Mammary
Tissue,” in Proceedings of the 8th International Conference on Photonics,
Optics and Laser Technology, Photoptics, pp. 131–134, La Valleta, Malta,
2020. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/photoptics2020_spimenta.pdf International
Journal Papers: M.J. Maciel, C.C. Rosa, R.F. Wolffenbuttel, J.H.
Correia,"Optical Coherence Tomography within a single microsystem".
J. Phys. D. Appl. Phys.: IOP Publishing, Vol. 51, no. 36 ,
2018.IF=2.373, September 2018
AC Costa, S Pimenta, JF Ribeiro, MF Silva, RF
Wolffenbuttel, T Dong, Z Yang, JH Correia, “PDMS microlenses for focusing
light in Narrow Band Imaging diagnostic”, Sensors, MDPI, vol. 19, No. 1057,
March 2019. https://doi.org/10.3390/s19051057 M. J. Maciel, S. Pimenta, J. F. Ribeiro, and J. H.
Correia, “Design of a novel TiO2 /airgap-based polarizing micro beam splitter
cube,” J. Phys. Conf. Ser., vol. 1319, no.
012006, Sep. 2019. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/jphycs_2019_mmaciel.pdf S. Pimenta, S.
Cardoso, E. M. S. Castanheira, G. Minas, "Towards an on-chip optical
microsystem for spectroscopic detection of gastrointestinal dysplasia". Sensors &
Actuators: B. Chemical, Vol. 281, pp. 751-756, 2019. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/sa_b_spimenta.pdf J. A. Rodrigues, R. Amorim, M. F. Silva, F. Baltazar,
R. F. Wolffenbuttel, J. H. Correia, "Photodynamic Therapy at Low-Light
Fluence Rate: in vitro Assays on Colon Cancer Cells". IEEE Journal of
Selected Topics in Quantum Electronics, Vol. 25, pp. 1-6, 2019. URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/jstqe_2019_artur.pdf M. J. Maciel, N. M. Gomes, S. Pimenta, J. F.
Ribeiro, and J. H. Correia, “TiO2/airgap-based polarizing beam splitter:
design, simulation, and fabrication based on MEMS technologies,” Opt. Lasers
Eng., vol. 133, no. 106110, Oct. 2020. URL: https://www.sciencedirect.com/science/article/pii/S0143816619308814?via%3Dihub M. F. Silva, S. Pimenta, J.A. Rodrigues, J. R.
Freitas, M. Ghaderi, L. M. Goncalves, G. de Graaf, R. F. Wolffenbuttel, J.H.
Correia, Magnesium fluoride as low-refractive index material for
near-ultraviolet filters applied to optical sensors, Journal Vacuum, Vol. N.,
pp.-, August 2020. https://doi.org/10.1016/j.vacuum.2020.109673 J. R. Freitas, S. Pimenta, J.
F. Ribeiro, Tao Dong, Z. Yang, J. H. Correia, “Simulation, fabrication and
morphological characterization of a PDMS microlens for light collimation on
optrodes", Journal Optik, Vol. 227, article 166098, 1-8 pages, February 2021. https://doi.org/10.1016/j.ijleo.2020.166098 Bruno Esteves, S. Pimenta,
Eliana Vieira, J.F. Ribeiro, J. A. Rodrigues, J. H. Correia, “
SnOx and a-Si thin-films
based photodiode in a flexible substrate for visible spectral region ", Journal Materials
Letters, Vol. 286, article 129251, 1-4 pages, March 2021. J. H. Correia, J. A. Rodrigues, S.
Pimenta, T. Dong, and Z. Yang, “Photodynamic therapy review: Principles,
photosensitizers, applications, and future directions,” Pharmaceutics,
vol. 13, no. 9, pp. 1–16, 2021. https://doi.org/10.3390/pharmaceutics13091332 R. B. Freitas, J. A. Rodrigues, H.
Puga, and J. H. Correia, “Design, simulation, and fabrication of an
ingestible capsule with gastric balloon for obesity treatment,” Biomed.
Phys. Eng. Express, vol. 7, no. 5, p. 055024, Sep. 2021. https://doi.org/10.1088/2057-1976/ac1d88 M. J. Maciel, H. M. Pereira, S.
Pimenta, A. Miranda, E. J. Nunes-Pereira, and J. H. Correia, “Differentiation
between normal and tumor mammary glands with depth-resolved attenuation
coefficient from optical coherence tomography,” Biomed. Phys. Eng. Express,
vol. 8, no. 1, p. 15007, 2022. https://doi.org/10.1088/2057-1976/ac37ca
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