WO2016101051A1

WO2016101051A1 - Olfactory stimulation system and method for detecting response signals to olfactory stimuli

Info

Publication number: WO2016101051A1
Application number: PCT/BR2015/000197
Authority: WO
Inventors: Marlise Araújo DOS SANTOS; Flávia Nathiely Silveira FACHEL; Bernardo serpa BORGES; Júlio César Marques DE LIMA
Original assignee: União Brasileira De Educação E Assistência , Mantenedora Da Pucrs
Priority date: 2014-12-23
Filing date: 2015-12-17
Publication date: 2016-06-30
Also published as: BR102014032403A2; BR102014032403B1

Abstract

The present invention pertains to the field of medical bioengineering and medicine, and provides an olfactory stimulation system compatible with magnetic resonance environments in that it comprises in its structure elements made of diamagnetic and/or polymeric materials, allowing the valve to be arranged near the sample storage means, and the latter to be arranged near the delivery means or the assessed individual, which reduces transportation delays, achieving more precise results and greater portability. The present invention further provides a method for detecting response signals to olfactory stimuli, with a reduced response time between the moment of release, adjustment or blending of aromatic samples, and the moment when the stimuli are recorded by the individual exposed to the sample.

Description

Patent Invention Descriptive Report

OLFATIVE STIMULUS SYSTEM AND PROCESS OF DETECTION OF OLFATIVE STIMULES RESPONSE SIGNALS

Field of the Invention

The present invention provides a system for olfactory stimulation compatible with magnetic resonance environments by comprising in its arrangement elements constructed of non-metallic materials, the valve may be arranged close to the subject for storage of the sample, and these near the delivery medium. , which reduces transport delays, enabling more accurate results and portability. The present invention belongs to the field of Biomedical Engineering and Medicine.

Background of the Invention

The brain functions involved in sensory perception have been of great interest to researchers in recent times, as it has been noted that many factors and / or pathological conditions can affect normal olfactory function. For this reason, several drugs have been reported to cause disturbance in the threshold of perception of odor and / or taste. Moreover, in space missions, the human body is exposed to a reduced gravitational force and during this exposure, signs and symptoms that are usually associated with the aging process, such as diminished or distorted perception of flavors and aromas, are perceived. .

In recent years, olfactory perception problems have also aroused great interest in the neurological field, especially due to the occurrence of olfactory dysfunction in patients with neurodegenerative diseases, such as Parkinson's, Alzheimer's, Multiple Sclerosis, among others. The high incidence of this dysfunction in these diseases makes the assessment of smell a new tool to aid in early diagnosis and / or differential of these diseases, which may lead to a more effective treatment and, consequently, may slow their progression.

In parallel, aroma in both perfumes, food and environments has been reported as a key factor for the acceptability and association of a product / brand by consumers, making the science of flavorings explored as a strategy for business marketing. In this sense, researchers are increasingly looking for alternative methods to evaluate the impact of these scents on the population, in order to attract and stimulate new consumers.

It is well known that the addition of flavorings in foods can reduce salt intake, a trigger for hypertensive crisis in hypertensive patients. Thus, the evaluation of the olfactory stimulus promotes the development of a differentiated nutritional research line for hypertensive patients.

The technology developed, in addition to the applications mentioned above, can be used in companies that have some occupational risk related to the possibility of olfactory loss in both admission and dismissal examinations. The current and growing demand for research involving the study of olfactory perception and olfactory threshold, both for clinical (assist in the early and / or differential diagnosis of neurodegenerative diseases, occupational risk), and for business marketing, associated with the possibility of Studies involving neuroimaging in Rio Grande do Sul, through the inauguration of the Brain Institute PUCRS, led the Joan Vernikos Aerospace Pharmacy Laboratory - PUCRS to initiate a new line of research involving olfactory stimulation and neuroimaging studies. In this sense, a robust, automated and instrumented system for olfactory stimulation compatible with the MRI environment was developed. This system aims to solve the problem involving the demand mentioned above, as it is a key tool in studies involving olfactory perception and olfactory threshold associated with the use of neuroimaging and electrophysiological experiments. For magnetic resonance imaging, however, metallic and magnetic objects are not allowed as they may cause interference with the collected data and also pose a risk to the patient being examined.

State-of-the-art flavor dosing equipment, however, comprises a series of valves formed of metal components and, therefore, the dosing valve should be arranged outside the resonant environment, increasing the distance between patient and patient. thus reducing the accuracy in collecting information about the response generated by the patient after the olfactory stimulus, which delays its arrival after its release from the sample container.

Within the patent scope, some relevant, but not anticipated, documents have been found, which will be described below.

[0010] The document entitled "Design and Testing of an Otfactory Stimulus Presentation Device for Use in Functional Magnetic Resonance Imaging (fMRI)" by Shawn Keating describes a Magnetic Resonance Imaging (RI) compatible device for the generation and presentation of olfactory stimulus for use in functional imaging of the olfactory response. The device is comprised of a perfumed liquid that is nebulized in a pressurized air balloon and subsequently transported through chemically inert tubes to a mask attached to the patient. The airflow is connected to the hospital's medical air tube and the air is split with a Y-connector, so that half of the flow is directed to one side of a control valve held at the back of the MRI port. and the other half in the Erlenmeyer balloon arm containing the aromatic fluid to be sprayed. When stimulus is supplied, the pressurized air flow causes the liquid to exceed the vapor pressure and convert it to the gaseous state inside the balloon, which differs from the present development by using a balloon in which the aromatic liquid becomes the gaseous state together with air and the use of a fragrant liquid is described, being limited to this structure. While the present development provides a structure comprising separate devices, a flow control valve having at least three odor samples, and a mixer, both made of non-metallic materials and disposed close to the patient.

The present invention differs from this document in that it describes a manual system with only one container for storing odorous substances, which restricts the application of increasing flavor thresholds and the perception of different substances simultaneously. While describing the use of a control valve, the system does not feature a hose responsible for cleaning and removing residual aroma. In addition, as it is a completely manual system, it does not have a supervisory system that allows the repeatability of the results, nor control of air temperature and humidity.

US 6325475 describes a micro-dispensing apparatus for inhaled airborne materials delivery to the individual and can generate optimal stimuli in a functional magnetic resonance imaging (fMRI) to assess brain metabolic responses, which can be produced. without the use of metal elements for use in fMRI. A constant aroma level can also be maintained for as long as necessary to accumulate informative metabolic images. The present invention differs from US 6325475 by utilizing a fluid reservoir; means for dispensing fluid from the reservoir; means for generating inhalation materials; and means for delivering patient airborne materials for inhalation, while the present development describes a structure comprising separate devices having flow control valves with at least three odor samples and samplers (A1, A2, A3), where the samples are stored and the place where the solution is in contact with the air, both developed with non-metallic materials and placed close to the patient, reducing the transport delay and allowing more accurate results, not specifying the distance in which the same would be the case of the subject under study. In addition, the system does not specify the presence of a humidity and temperature control unit, which for a direct nasal airway system is of paramount importance given the possibility of airway irritation.

[0013] The document entitled "Prototype Development and Evaluation for Neuroimaging Studies: Olfactory Stimulation" by Renata Mondini describes a prototype of a manual flavor delivery system, which has no humidity and temperature control nor a operation and drive monitoring system.

From what is clear from the researched literature, no documents were found anticipating or suggesting the teachings presented in the present invention, in its simplicity and innovative disposition, so that the solution proposed here has novelty and inventive activity before the state of the art.

Summary of the invention

The present invention provides a system for olfactory stimulation compatible with magnetic resonance environments by comprising in its arrangement elements constructed of non-metallic materials, which may be arranged close to the sample storage medium, and these near the delivery medium. which reduces transport delays for more accurate results and portability.

It is a first object of the present invention to provide a system for olfactory stimulation comprising:

- at least one valve (2) enabling the release of one or more flavors in an automated manner;

- at least one means for storing at least one sample (3); and

- means of delivery of the aromatic substance (4), the components defining the system being composed of diamagnetic and / or polymeric material. It is a second object of the invention to provide a method of detecting olfactory stimulus response signals using the system described above and comprising the steps of:

The. monitor responses to stimuli imposed on individuals; B. control the type and dosage of sample for administration to the subject's airway;

ç. record stimuli caused to the individual by contact with sample type and / or dosage,

the time between the completion of step b) and step c), and the response time of the subject stimulated by the sample lagged by less than one second.

[0018] These and other objects of the invention will be immediately appreciated by those skilled in the art and companies having an interest in the segment, and will be described in sufficient detail for their reproduction in the following description.

Brief Description of the Figures

Figure 1 shows a block diagram of an embodiment of the invention for providing three odors comprising three valves (2) represented by V1, V2, V3 and three sample storage means (3) represented by A1, A2, A3 , as also shown by the aerosol generator module (1), the aromatic substance delivery means (4) provided to the individual (iN).

Figure 2 shows an embodiment of the invention with a power transfer system (5) for automatically actuating the valves (2) connected by hoses to the sample storage means (3).

Figure 3 shows an embodiment of the three valves (2) each having their respective hole where the hoses are coupled to the air passage and the part where there is the energy transfer system (5).

Figure 4 shows an embodiment of the sample storage medium (3). Figure 5 shows a schematic diagram of the system of the present invention in a preferred embodiment.

Detailed Description of the Invention

The present invention enables the use of the system in various types of studies involving neuroimaging, due to its compatibility with the functional magnetic resonance environment which has many restrictions and therefore requires special care in the construction of the same, and associated electrophysiological experiments. perception of olfactory stimulus.

The present invention provides a system for olfactory stimulation compatible with MRI environments. It comprises in its disposition elements constructed with non-metallic and / or diamagnetic materials, the valve can be arranged close to the medium for sample storage, and these close to the delivery medium, which reduces the transport delay, allowing more accurate results, beyond its portability.

The olfactory stimulation system of the present invention comprises at least one valve (2), which enables one or more flavors to be released automatically, at least one means for storing the sample (3); and aromatic substance delivery means (4), to allow the release of a single aroma at different intensities, or a combination of different aromas in different proportions, so as to verify the reaction of the subject undergoing an olfactory stimulus test, for various flavor combinations, quickly and easily.

The function of the aerosol generator module (1) is to control the release of humidified and heated air, depending on the desired data.

Each valve (2) in the system has the function of controlling the release of an individually actuated aroma through the use of a mechanical energy transfer means (5), which may use electromechanical, pneumatic, and hydraulic conversion means. In one embodiment, the valves (2) are driven by a mechanical energy transfer means (5) using servomotors, cables and guides. The servomotors (controlled by the supervisory system) are responsible for the actuation of the valves, moving a screw that is coupled to the cables, in both directions, in order to pull or push them that are conditioned by the guide hoses, opening or closing the valves.

[0029] In one embodiment, the mechanical energy transfer means (5) consists of the use of a pullable inner cable concentrically mounted on a guide hose, both rigid, similar to the operation of a bicycle brake system.

The valves (2) are controlled by opening or closing by means of a mechanical energy transfer means (5) with the use of servomotors. The mechanical energy transfer system (5) is made with the use of cables made of diamagnetic material or synthetic polymers, as metal materials cannot be used within the fMRI environment. These cables are covered by a hose that serves as a guide and support and are connected to a movement system that uses a threaded bar coupled to the servomotors mentioned above.

These servomotors, being metallic, are in the external environment of the resonance room, and are controlled by a microcontroller that generates PWM signals for each of these, controlling the direction of rotation of the axis, causing the bar threaded bolt move forward or backward.

Servo motors have the ability to freely rotate their axes and each servo has a current monitoring system to prevent locking of the rotation axis and raising the current in the circuit, thus implementing a protection system. to engines as well as, the detection of the end of the threaded rod in both directions of movement (opening / closing the valves). The purpose of the valves (2) is to control the air flow from the aerosol generator (1) towards the samplers (A1, A2, A3), supports responsible for the storage and nebulization of odorous samples.

Preferably, but not limiting, the system comprises three samples for application in increasing flavor threshold tests and the distinction of different substances simultaneously, that is, allows the dosing and / or mixing of three sample types. For each sample, a sample storage medium (3) is associated, which is responsible for providing sample contact with air.

Aromatic substance delivery means (4) consists of any equipment capable of ensuring that the observed subject receives as little loss as possible from the samples used, such aromatic substance delivery means (4) being defined by at least one of the group defined by: masks, catheters, nasal glasses, and nasal cushion.

The system of the present invention further comprises a negative pressure system for cleaning and removing residual aroma within the system, used to eliminate residues from previous assays and thus ensuring that each assay is performed by considering only the sample or desired mixture. In one embodiment, the residual odor removal process is performed using a pump that draws in the air generating negative pressure, or oxygen cylinders, CPAPs or the like may also be used. This negative pressure system is triggered automatically (by communicating with a supervisory system) after the completion of each olfactory stimulus protocol.

The present invention has a portability feature because of its ease of assembly and flexibility.

In order to allow the use of the system of the present invention in magnetic resonance environments, the valves employed therein do not comprise metal, magnetic or paramagnetic components, aiming to allow the maintenance of this system close to the sample storage medium, or individual, reducing the transport delay, allowing more accurate results, besides its portability.

Another advantage is that the present invention makes it possible to expand the number of samples according to application needs and may employ a larger number of sample storage media when required, a greater combination of flavors and / or concentrations.

Example 1- Preferred Realization

In one embodiment of the invention, the system is basically composed of four parts described in the block diagram shown in Figure 1.

[0040] The first part of the system is composed of the aerosol generator (1), which is responsible for the release of the aerosolized sample through a pneumatic compressed air jet, which can be performed through medical oxygen cylinders, commercial nebulizers, ambient air. filtered, or preferably by CPAP equipment (which allows the release of humidified and heated air, causing less irritation to the nasal mucosa).

The second part is composed of at least three non-metallic valves (2), which can be expanded in number, enabling the release of one or more aromas simultaneously or not. These valves are individually actuated through the use of a mechanical energy transfer medium. In addition, they can be made of materials such as glass, acrylic, plastics, but preferably Teflon, and can be of size 80x80x80 mm (AxLxP) in a three-valve embodiment.

The third part of the system comprises the samplers (A1, A2, A3) which are the non-metallic sample storage means (3), parts where the samples are stored and where the solution contacts the air. These were sized to be close to the subject, thus avoiding delays in transport. Initially three samplers (A1, A2, A3) were prototyped, whose structure can be expanded according to the application, and whose materials can be glass, acrylic, plastics, but preferably by Teflon, in view of their chemical compatibility with the substances. can be 80x80x80 mm (AxLxP) in a three sampler embodiment (A1, A2, A3).

The last part comprises in the process of delivery of the aromatic substance, which, in this invention, can be performed through masks, catheters, nasal glasses, but preferably performed through a nasal cushion, which enables the stimulus employed in the subject. this study is only by this way, discarding possible losses of aromatic substances in the oral mucosa and the environment, which occurs when other techniques are employed.

The system, therefore, is preferably made of Teflon and without the use of metallic components, which in addition to featuring a robust system compatible with the Functional Magnetic Resonance environment, also makes it compatible with sterilization processes. The present invention, in addition to the above features, has a supervisory system for data visualization, integrated with a computer (based on already developed systems), which will also allow the control of the valve actuators using servomotors to transfer mechanical energy to the valves. The system will also have a synchronism signal to measure the time between the release of the aroma and the effective perception of the same by the subject, and the capture of the image when it is used.

Supervisory systems are generally the components responsible for allowing process information to be monitored and tracked. Such information is collected through data acquisition equipment and then manipulated, analyzed, stored and subsequently presented to the user. Thus, the user of the developed fMRI olfactory stimulus research instrument has a supervisory system for visualizing data and controlling the actuation of the valves, individually or jointly, as well as measuring the response time to the stimulus. , by communicating with the sync signal system. To this end, in one embodiment of the invention, the supervisory system was developed using a commercial platform, LabView, and is connected to the control hardware via a serial port. A simple communication protocol was implemented to allow the user to be able to exchange information between the computer (PC) and the control board in a friendly manner.

Claims

System for olfactory stimuli and detection process for olfactory stimuli response signals

1. System for olfactory stimulation characterized by:

- at least one means for storing at least one sample (3); and

- means of delivery of aromatic substance (4),

wherein the defining components of the system are composed of diamagnetic and / or polymeric material.

System according to claim 1, characterized in that it further comprises an aerosol generating module (1).

System according to Claim 2, characterized in that the aerosol generating module (1) controls the release of humidified and heated air.

System according to any one of Claims 1 to 3, characterized in that each valve (2) controls the release of an independently actuated aroma by the use of a mechanical energy transfer means (5).

A system according to any one of claims 1 to 4, characterized in that it comprises three samples for application in increasing aroma threshold tests and the perception of different substances simultaneously.

System according to any one of claims 1 to 5, characterized in that the sample storage medium (3) is responsible for providing the sample with air contact.

System according to any one of Claims 1 to 6, characterized in that the aromatic substance delivery means (4) is provided. through one of the group defined by: masks, catheters, nasal glasses, and nasal cushion.

System according to any one of claims 1 to 7, characterized in that it comprises negative pressure system for cleaning and removing residual aroma within the system.

Process for detecting olfactory stimulus response signals, characterized in that it makes use of the system described in claims 1 to 8 and comprises the steps of:

The. monitor responses to stimuli imposed on individuals; B. control the type and dosage of sample for individual airway administration;

the time between the completion of step b) and step c) and the response time of the subject stimulated by the sample lagged by less than 1 second.

Process for detecting olfactory stimulus response signals according to claim 9, characterized in that it comprises an additional step of evaluating the olfactory stimulus records obtained in step c) for defining dietary nutritional parameters for hypertensive individuals.