[go: up one dir, main page]

WO2018184251A1 - Méthode et dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires - Google Patents

Méthode et dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires Download PDF

Info

Publication number
WO2018184251A1
WO2018184251A1 PCT/CN2017/079904 CN2017079904W WO2018184251A1 WO 2018184251 A1 WO2018184251 A1 WO 2018184251A1 CN 2017079904 W CN2017079904 W CN 2017079904W WO 2018184251 A1 WO2018184251 A1 WO 2018184251A1
Authority
WO
WIPO (PCT)
Prior art keywords
photon
quantum
state
data
tissue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/079904
Other languages
English (en)
Chinese (zh)
Inventor
董孝峰
祝海龙
孙媌媌
宋靖涛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boruitaike Science And Technology (ningbo) Co Ltd
Original Assignee
Boruitaike Science And Technology (ningbo) Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boruitaike Science And Technology (ningbo) Co Ltd filed Critical Boruitaike Science And Technology (ningbo) Co Ltd
Publication of WO2018184251A1 publication Critical patent/WO2018184251A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence

Definitions

  • the invention relates to the field of medical detection, in particular to a method and a device for detecting brain function and detecting brain tissue components.
  • Medical imaging in the field of medical testing is an important auxiliary tool for medical workers to make diagnosis. Medical imaging has undergone three stages: structural imaging, functional imaging, and molecular imaging.
  • Anatomical imaging is generally obtained by X-Ray, CT, MRI, USI, and physiological information (such as metabolic information) that cannot be observed by morphology is imaged by SPECT, PET, fMRI, and fNIRS using computer reconstruction techniques (computational imaging techniques).
  • Computational imaging technology is the basis for the realization of optical molecular imaging.
  • spatial spatial modulation and statistical models are usually included in the computational imaging and reconstruction process.
  • Different biological tissues have different absorption and scattering effects on different spectral bands.
  • Different numbers of photons emitted or transmitted by different targets have different parameters of absorption and scattering of tissues and molecular cells, so as to detect the emission or transmission of targets.
  • a certain number of photons can enable people to extract corresponding effective biological information, which is the scientific meaning given by the visualization results of molecular optical imaging technology.
  • the further development of biological tissue photonics provides a scientific and practical physics model for the propagation of light in biological tissues.
  • Molecular imaging detects weak electromagnetic signals or mechanical signals of specific report photon-induced reaction life characteristics in living organisms. Through signal amplification and medical image processing and analysis, human-computer interaction is used to finally realize the visualization of life processes at the molecular level.
  • physiological information usually cannot It is directly observed, but the anatomical structure is reconstructed by including X-Ray, CT, and MRI data.
  • Physiological information including thermal activity and bioelectrical activity, are displayed in an understandable way for medical personnel to observe.
  • Optical molecular imaging technology has been widely used, such as blood oxygen distribution in the brain, nerve cell activity, early diagnosis of tumors, and drug targets. It is also used in gene sequencing and cytology testing.
  • brain tissue components, brain function activities and linear state information of the light quantum such as brain tissue moisture content determination, lymphocyte count, can not guarantee the brain tissue components and brain function information The reliability and accuracy of the measured data.
  • the technical problem to be solved by the present invention is that in practical applications, not all brain tissue components, brain function activities and the state information of the photon are linear, so that the measurement data of the brain tissue components and brain function information cannot be reliably ensured. Degree and accuracy issues.
  • the technical solution adopted by the present invention is to provide a device for functional imaging and brain tissue component detection, including:
  • a photo quantum modulation unit for modulating and encoding a photon
  • An entangled state light quantum preparation unit that modulates an optical quantum outputted by the optical quantum modulation unit to generate an entangled photon pair of one or more frequencies and counts the photon;
  • a firing unit that separates and emits an entangled quantum pair, one of which is emitted to the detected brain tissue
  • a photon state detecting unit receives another photon emitted by the transmitting unit, detects the photon state and count, and stores the state and count of the photon in a time series manner;
  • Knowledge base the establishment and storage of data structures for the relationship between light quantum states and organizational components, organizational thermal activities, and organization of bioelectrical activities
  • a knowledge base training unit opening a training interface of the knowledge base, and training the knowledge base by using the light quantum state data stored in the time series recorded by the photo quantum state detecting unit;
  • the calculating unit calculates the composition, thermal activity, and bioelectrical activity state data of the corresponding brain tissue by using the knowledge of the knowledge base and the state information of the photo quantum state detecting unit, and further transforms the data into data that can be used for reconstruction imaging.
  • Imaging data
  • An imaging unit that reconstructs tissue composition, tissue thermal activity, and biological using the imaging data An image of the electrical activity data and displayed.
  • the modulation method for modulating the frequency and encoding of the optical quantum includes a frequency stepping method and a fixed frequency method.
  • a photon is emitted to the brain tissue after being detected, and is subjected to reflection, refraction, scattering, absorption, and actinization, and the state of the photon is continuously changed by the tissue; the photoquantum state detecting unit detects another photon. a state in which light quantum state information into the brain tissue that is continuously changed by the brain tissue, absorbed by the brain tissue, or de-coherent with the photon emitted to the photoquantum state detecting unit is acquired.
  • the data schema of the knowledge of the knowledge base is organized and constructed by means including, but not limited to, a neural network or a support vector machine.
  • the invention also provides a method for brain function imaging and brain tissue component detection, comprising the following steps:
  • Step S10 establishing a knowledge base, constructing and storing knowledge of relationship between light quantum state and organizational components, tissue thermal activity, and organizing bioelectrical activities;
  • Step S20 modulating the photon to generate an entangled photon pair of one or more frequencies, and counting the photon;
  • Step S30 separating the entangled quantum pairs, and emitting one photon emission to the detected brain tissue, and another photon emission to the photon quantum state detecting unit;
  • Step S40 The photo-quantum state detecting unit detects another received photon state, records the detected photon state and count in time series, and trains the knowledge base by using the saved photon state data;
  • Step S50 using the knowledge of the knowledge base and the light quantum state information stored in a time series manner to calculate the corresponding brain tissue components, thermal activity, bioelectric activity state data, and convert the data into imaging data;
  • Step S60 reconstructing a medical image of the tissue component, the tissue thermal activity, and the bioelectric activity using the imaging data, and displaying.
  • the invention introduces a nonlinear analysis calculation method based on knowledge judgment organization component, and approximates an accurate value through a machine learning algorithm such as a neural network and a support vector machine method.
  • a machine learning algorithm such as a neural network and a support vector machine method.
  • FIG. 1 is a structural block diagram of a device for detecting brain function and detecting brain tissue components according to the present invention
  • FIG. 2 is a flow chart of a method for brain function imaging and brain tissue component detection provided by the present invention.
  • the invention adopts multi-wavelength entangled light photon as a detecting light source, and detects the composition of brain tissue and the thermal activity and bioelectric activity of brain tissue.
  • Quantum entanglement is a phenomenon in which particles interact with each other in a system composed of two or more particles. It describes that two or more particles are entangled with each other. Even if they are far apart, the behavior of one particle will affect the other. The state, such as when one of the operating states changes, the other will immediately change the corresponding state.
  • the properties of quantum entanglement can be used for information transfer, and the application of Time-Correlated Single Photon Counting Techn. (TCSPC) and Time Series recording techniques provides the possibility to continuously observe and record photon states. .
  • TCSPC Time-Correlated Single Photon Counting Techn.
  • the light quantum is emitted into the tissue, and is reflected, refracted, scattered, absorbed by the tissue components. And actinic, changing the state of the photon, capturing the photon or examining the state of the photon entangled with the photon, obtaining data within the tissue, and further analyzing the computational reconstruction imaging; unlike conventional imaging based on the absorption of photons by biological tissue, the present invention is based on The statistics of the quantum state of light, by recording multiple states of the photon, finally reveal the tissue composition information and the tissue thermal activity information, which has nothing to do with the photon itself, only the photon acts as a messenger;
  • Optical imaging is the projection of the first-order correlation information of the light field in the plane
  • the dual-light quantum imaging is the projection of the second-order correlation information of the light field in the plane, and the geometrical relationship of the optical imaging and the dual-photo quantum reaction remains unchanged; It is to analyze and calculate the state information of the detected quantum to obtain the component data, thermal activity, and bioelectric activity data of the organization, and to reconstruct the image according to the calculated data; the data of the recorded state has no spatial structure information, and the spatial geometric relationship of the graphic during reconstruction imaging needs Obtained by calculation;
  • the present invention realizes multi-band spectral detection molecular characteristic spectrum, indirectly calculates absorption spectrum of brain tissue molecules, analyzes brain tissue components by scattering spectrum, and analyzes and records brain activity to realize functional imaging and component imaging; meanwhile, the present invention is also based on The non-linear analysis and calculation method of knowledge judgment organization components, combined with machine learning algorithms (including but not limited to neural network, support vector machine method) approximation, training data to improve measurement reliability and accuracy, with training samples As the collection grows larger, the measurement becomes more powerful and accurate, and the advantage of this knowledge-based approach is that correlation can be suggested even if there is no direct effect.
  • machine learning algorithms including but not limited to neural network, support vector machine method
  • the invention provides a device for brain function imaging and brain tissue component detection, which is used for brain tissue component analysis and tissue function analysis, including photo quantum modulation unit, entangled photon quantum preparation unit, emission unit, and photon quantum state.
  • a detection unit a knowledge base training unit, a knowledge base management unit, a calculation unit, and an imaging unit. among them,
  • the optical quantum modulation unit is configured to modulate and encode the optical quantum, and the modulation method includes a frequency stepping mode and a fixed frequency mode.
  • An entangled photon quantum preparation unit processes the photon outputted by the optical quantum modulation unit to generate an entangled photon pair A(a1, a2) of one or more frequencies, and counts the photon, since the optical quantum entanglement is not 100% entangled, Probabilistic events, by counting the quantum of light, can be used to perform probability statistics, thereby statistically coherent probability, or entanglement probability.
  • the transmitting unit separates the entangled quantum pair A, one photon a1 is emitted to the detected brain tissue, and the other photon a2 is emitted to the photoquantum state detecting unit.
  • the photon state detecting unit detects the received photon a2 state and count, and records the photon state and count, and the recorded photon state and count are stored in a time series manner.
  • the photon a1 enters the brain tissue and is subjected to reflection, refraction, scattering, absorption, and actinization.
  • the state of the photon a1 is continuously changed by the tissue or absorbed or decohered by the brain tissue, and the photon state detecting unit detects the photon a2 state.
  • the a1 state information is acquired, and the state of a1 has temporal correlation, and the state of a1 (a1) is recorded in a time series manner.
  • observing the photon a2 state can obtain the state information (a1) of the photon a1, that is, one photon state changes, and the other state also changes, when the photon a2 and the photon a1 disappear.
  • the state information (a1) of the photon a1 that is, one photon state changes
  • the other state also changes, when the photon a2 and the photon a1 disappear.
  • Knowledge base the establishment and storage of data structures of light quantum states and organizational components, organizational thermal activities, and knowledge of the relationship between bioelectrical activities, the data structure of this knowledge through neural networks or support
  • the machine learning engine training knowledge model method such as measuring machine is organized and constructed; for example, the knowledge of blood oxygen concentration relationship is analyzed by near-infrared absorption spectrum.
  • the knowledge base training unit opens the training interface of the knowledge base and trains the knowledge base by using the light quantum state data (a2) stored in the time series recorded by the light quantum state detecting unit; the knowledge base training unit is the training engine of the knowledge base, and is the construction knowledge
  • the mathematical model of the library matches the machine learning model.
  • the calculation unit calculates the composition, thermal activity, and bioelectric activity state data of the corresponding brain tissue by using the knowledge of the knowledge base and the state information (a2) of the photoquant state detection unit, and further converts the data into an image that can be used for reconstruction imaging. data.
  • the state information (a2) of the photon is not linearly related to the composition, thermal activity, and bioelectrical activity state of the brain tissue, but is calculated by the correlation established by the knowledge base based on the empirical calculation method.
  • the empirical calculation method will increase with the amount of machine learning and training samples, so that the calculation results will become more and more accurate, so as to meet the requirements of general disease qualitative diagnosis and general fine-grain quantitative diagnosis, such as brain tissue moisture content determination, Lymphocyte count.
  • the imaging unit reconstructs the medical image by using the imaging data, and realizes that the tissue composition, the tissue thermal activity, and the bioelectric activity data are presented to the medical staff in an understandable manner.
  • the invention introduces a nonlinear analysis calculation method based on knowledge judgment organization component, and approximates an accurate value through a machine learning algorithm (including but not limited to, for example, a neural network, a support vector machine method), and the advantage of the knowledge-based approximation method is that even if there is no direct effect There is also a correlation between the factors.
  • a machine learning algorithm including but not limited to, for example, a neural network, a support vector machine method
  • the present invention provides a method for brain function imaging and brain tissue component detection, comprising the following steps:
  • Step S10 Establish a knowledge base, and establish and store knowledge about the relationship between the quantum state of the light and the tissue composition, the tissue thermal activity, and the organization of the bioelectric activity.
  • Step S20 modulating the photon to generate an entangled photon of one or more frequencies Pair, light quantum pulses, and count the light quanta.
  • Step S30 separating the entangled quantum pair and the optical quantum pulse, one photon a1 is emitted to the detected brain tissue, and the other photon is emitted to the photon quantum state detecting unit.
  • Step S40 The photon state detecting unit detects the received other photon state, records the detected photon state and count in time series, and trains the knowledge base using the saved photon state data.
  • Step S50 calculating the composition, thermal activity, and bioelectric activity state data of the corresponding brain tissue by using the knowledge of the knowledge base and the state information of the photo quantum state detecting unit, and further converting the data into imaging data that can be used for reconstructing imaging.
  • Step S60 reconstructing the medical image by using the imaging data, and realizing the tissue composition, the tissue thermal activity, and the bioelectric activity data to be displayed to the medical staff in an understandable manner, for example, rebuilding the virtual person by the computer, and reconstructing the composition of the tissue and the tissue heat on the basis of the virtual person.
  • Activity biological nerve activity image.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medical Informatics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

L'invention concerne une méthode et un dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires. La méthode comprend : la construction et le stockage d'une base de connaissances orientée connaissance des relations entre des états quantiques et les composants tissulaires, activités thermiques et activités bioélectriques des tissus cérébraux ; la modulation et la génération d'une paire quantique à l'état intriqué ; la séparation de la paire quantique à l'état intriqué où l'un des quanta est transmis à un tissu cérébral détecté, et l'autre à une unité de détection d'états quantiques ; la détection par l'unité de détection d'états quantiques d'un état quantique reçu, l'enregistrement des états quantiques détectés dans un ordre chronologique, et comptabilisation ; la production de données relatives aux activités, activités thermiques, et activités bioélectriques du tissu cérébral par calcul à l'aide des connaissances dans la base de connaissances et des informations relatives à l'état quantique obtenues par détection et leur conversion en données d'imagerie ; et la reconstruction d'images à l'aide des données d'imagerie et leur affichage. La fiabilité et la précision des données de mesure sont efficacement augmentées par l'utilisation d'une méthode d'approche par connaissances.
PCT/CN2017/079904 2017-04-05 2017-04-10 Méthode et dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires Ceased WO2018184251A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201710218476.6 2017-04-05
CN201710218476.6A CN106955089B (zh) 2017-04-05 2017-04-05 一种脑功能成像和脑组织成分检测的方法及装置

Publications (1)

Publication Number Publication Date
WO2018184251A1 true WO2018184251A1 (fr) 2018-10-11

Family

ID=59483466

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/079904 Ceased WO2018184251A1 (fr) 2017-04-05 2017-04-10 Méthode et dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires

Country Status (2)

Country Link
CN (1) CN106955089B (fr)
WO (1) WO2018184251A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109464122B (zh) * 2018-11-05 2022-02-18 西南大学 基于多模态数据的个体核心特质预测系统及方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1013929C1 (nl) * 1999-12-22 2001-06-25 Univ Groningen Apparaat en methode voor het verrichten van optische metingen die niet-lokaal uitgelezen worden, onder gebruikmaking van bundels van verstrengelde fotonen.
US20100010343A1 (en) * 2005-02-25 2010-01-14 Intramedical Imaging, Llc Detection of radiation labeled sites using a radiation detection probe or camera incorporating a solid state photo-multiplier
CN103023578A (zh) * 2012-12-11 2013-04-03 上海卫星工程研究所 基于光量子通信技术的深空探测通信系统
US20150112170A1 (en) * 2013-10-17 2015-04-23 Amerson, Llc Device and method for non-invasive glucose monitoring
CN104707150A (zh) * 2013-12-11 2015-06-17 中国科学院上海药物研究所 肿瘤酶激活的量子点探针及其制备方法与用途
CN105832292A (zh) * 2016-03-15 2016-08-10 西安邮电大学 基于量子超弦引擎的中晚期癌症成像检测系统及方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070203655A1 (en) * 2006-02-27 2007-08-30 Huping Hu Method and apparatus for producing quantum entanglement and non-local effects of substances
US8269978B2 (en) * 2007-11-12 2012-09-18 The Boeing Company Imaging with nondegenerate frequency-entangled photons
CN102495467A (zh) * 2011-11-11 2012-06-13 上海电机学院 一种利用混沌激光的时间关联特性进行成像的方法及装置
CN102998260B (zh) * 2012-12-17 2014-10-01 西北大学 一种基于双光子纠缠的太赫兹波成像装置
CN103357112B (zh) * 2013-07-05 2015-02-18 西安邮电大学 基于量子纠缠传态的脊髓损伤神经信号中继系统及方法
WO2015080568A1 (fr) * 2013-11-27 2015-06-04 Mimos Berhad Système pour la détermination de paramètres sanguins physiologiques
CN103763038B (zh) * 2013-12-31 2016-04-13 西北大学 一种基于量子双光子纠缠的太赫兹波通信装置

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1013929C1 (nl) * 1999-12-22 2001-06-25 Univ Groningen Apparaat en methode voor het verrichten van optische metingen die niet-lokaal uitgelezen worden, onder gebruikmaking van bundels van verstrengelde fotonen.
US20100010343A1 (en) * 2005-02-25 2010-01-14 Intramedical Imaging, Llc Detection of radiation labeled sites using a radiation detection probe or camera incorporating a solid state photo-multiplier
CN103023578A (zh) * 2012-12-11 2013-04-03 上海卫星工程研究所 基于光量子通信技术的深空探测通信系统
US20150112170A1 (en) * 2013-10-17 2015-04-23 Amerson, Llc Device and method for non-invasive glucose monitoring
CN104707150A (zh) * 2013-12-11 2015-06-17 中国科学院上海药物研究所 肿瘤酶激活的量子点探针及其制备方法与用途
CN105832292A (zh) * 2016-03-15 2016-08-10 西安邮电大学 基于量子超弦引擎的中晚期癌症成像检测系统及方法

Also Published As

Publication number Publication date
CN106955089B (zh) 2019-05-24
CN106955089A (zh) 2017-07-18

Similar Documents

Publication Publication Date Title
Abdalmalak et al. Can time-resolved NIRS provide the sensitivity to detect brain activity during motor imagery consistently?
US20160235372A1 (en) Portable cancer diagnostic device and system
KR20090024808A (ko) 치매 및 치매성 장애의 평가
JP2021532846A (ja) 光トモグラフィを使用する経腹的胎児オキシメトリの遂行
US20070244395A1 (en) Systems and methods for multi-spectral bioluminescence tomography
EP3946034A1 (fr) Procédés et dispositifs d'imagerie magnétique pour examiner la fonction corticale du cerveau humain
Ban et al. Heterodyne frequency‐domain multispectral diffuse optical tomography of breast cancer in the parallel‐plane transmission geometry
EP2945529A1 (fr) Systèmes et procédés de surveillance sanitaire non invasive
CN115474930B (zh) 一种基于高光谱图像重建的无创血红蛋白检测方法
WO2001020305A1 (fr) Procede et systeme d'imagerie de la dynamique d'un milieu de dispersion
Robinson et al. Diffuse correlation spectroscopy beyond the water peak enabled by cross-correlation of the signals from InGaAs/InP single photon detectors
Abed et al. The future of internet of things for anomalies detection using thermography
CN114025253A (zh) 一种基于真实世界研究的药物疗效评估系统
KR102340152B1 (ko) 피판술 후 조직 괴사 및 손상의 조기 예측 시스템 및 그 방법
WO2018184251A1 (fr) Méthode et dispositif pour l'imagerie fonctionnelle du cerveau et la détection de ses composants tissulaires
Tseng et al. Cloud-based artificial intelligence system for large-scale arrhythmia screening
Saikia et al. K-means clustering for unsupervised participant grouping from fNIRS brain signal in working memory task
US20040001662A1 (en) Method of and apparatus for measuring oscillatory motion
Tonmoy et al. Estimation of oxygen saturation from PPG signal using smartphone recording
Kedir et al. Spectranet: A deep model for skin oxygenation measurement from multi-spectral data
JP5451072B2 (ja) 空間分解オキシメトリ
CN210776809U (zh) 一种望诊图像质量评价系统、设备及存储介质
Kudla et al. Spatiotemporal Image Correlation With Spherical Sampling and High‐Definition Flow: New 4‐Dimensional Method for Assessment of Tissue Vascularization Changes During the Cardiac Cycle: Reproducibility Analysis
Peller et al. Hyperspectral Imaging Based on Compressive Sensing: Determining Cancer Margins in Human Pancreatic Tissue ex Vivo, a Pilot Study
CN113303787A (zh) 基于红外成像技术的压疮伤口检测计算系统

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17904892

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 20.01.20)

122 Ep: pct application non-entry in european phase

Ref document number: 17904892

Country of ref document: EP

Kind code of ref document: A1