Progressive odor recognition-based pd early-stage olfactory disorder detection system

Abstract

This invention provides an early olfactory impairment detection system for Parkinson's disease (PD) based on progressive odor recognition. Specifically, it includes: a specific odor combination targeting the pathology of Parkinson's disease, including acetophenone, eugenol, menthol, pyridine, and banana aldehyde; a progressive concentration stimulation module providing a 6-level concentration gradient, with concentration decreasing geometrically; a two-stage visual simulation scoring terminal, including: an odor intensity perception scale displaying odor intensity via a linear scale, allowing subjects to score based on odor intensity; and an odor image recognition interface displaying multiple images corresponding to a specific odor source, allowing subjects to identify the odor by selecting the image matching their perceived odor. This addresses the limitations of existing olfactory testing methods, which cannot be fully and effectively applied to early PD screening. It belongs to the field of Parkinson's disease detection.

Description

Technical Field

[0001] This invention relates to the field of Parkinson's disease detection, and in particular to a PD early olfactory impairment detection system based on progressive odor recognition. Background Technology

[0002] Parkinson's disease (PD) is a common neurodegenerative disease, typically characterized by motor dysfunction accompanied by a decreased sense of smell. Studies show that more than 90% of PD patients experience olfactory dysfunction (hypopnea / disorder of smell) in the early stages, and this symptom usually precedes the onset of motor symptoms, appearing in the early stages of PD (within 5 to 10 years of disease progression). This characteristic makes olfactory dysfunction a potential early screening marker.

[0003] Scientific Basis: The pathological changes in Parkinson's disease initially affect the olfactory bulb and anterior olfactory nucleus, a pathological feature that leads to a significant decrease in patients' sensitivity to specific molecules (such as acetophenone and pyridine). Studies have shown a positive correlation between the degree of odor recognition impairment and the loss of dopamine neurons in the substantia nigra, especially in Braak stages I-II. This scientific basis provides a solid theoretical foundation for the development of targeted olfactory dysfunction detection systems.

[0004] Currently, the detection of olfactory disorders mainly relies on standardized olfactory tests, such as the UPSIT (University of Pennsylvania Smell Identification Test) and Sniffin' Sticks. These tests primarily assess olfactory function by testing the subject's ability to perceive and identify odors. However, existing olfactory testing methods have some limitations and cannot be fully and effectively applied to the early screening of PD, specifically as follows:

[0005] 1. Fixed-concentration stimulation: Current olfactory tests typically use odor stimuli of fixed concentrations. This method cannot quantify an individual's olfactory sensitivity threshold and is difficult to reflect the specific olfactory function status of the subject. Because changes in olfactory sensitivity vary among Parkinson's disease patients, there is a lack of precise means to detect gradual changes in olfactory sensitivity.

[0006] 2. Lack of optimized combinations of PD-specific odors: Current olfactory tests do not design specific odor combinations tailored to the pathological characteristics of Parkinson's disease patients. Most odor sources used in these tests do not adequately consider the damaged olfactory nerve pathways in PD patients, resulting in low sensitivity and specificity in PD patients.

[0007] 3. Weak subjective rating system: Existing testing methods rely primarily on the subjects' subjective ratings, resulting in a weak correlation between the assessment results and the degree of neurological damage. This limits the accuracy and reliability of the test results, especially in the early stages when the condition is mild. Summary of the Invention

[0008] This invention provides a PD early olfactory disorder detection system based on progressive odor recognition to address the limitations of existing olfactory testing methods, which cannot be fully and effectively applied to PD early screening.

[0009] To address the aforementioned technical problems, this invention provides a PD early olfactory impairment detection system based on progressive odor recognition, comprising:

[0010] Specific odor combinations targeting the pathology of Parkinson's disease, including acetophenone, eugenol, menthol, pyridine, and banana aldehyde, are selected based on the reduced sensitivity of neural pathways (such as the olfactory bulb and anterior olfactory nucleus) to specific odor molecules in the early stages of Parkinson's disease.

[0011] The progressive concentration stimulation module can provide 6 concentration gradients, with a concentration range of 10. -6 ~10 -1 g / mL, the concentration decreases geometrically;

[0012] A two-stage visual analogue scale (VAS) terminal includes:

[0013] The odor intensity perception scale displays odor intensity using a linear scale. Subjects slide the scale to rate the odor intensity, with a rating range of 0-10.

[0014] The odor image recognition interface displays multiple images corresponding to a specific odor source (such as almond, rose, lemon, tar, etc.). Subjects identify the odor by selecting the image that matches the odor they smell.

[0015] The concentration control module achieves precise release of odor molecules through a microfluidic chip, uses a piezoelectric valve to adjust the mixing ratio of odor and carrier gas, and precisely controls the odor concentration (error < ±0.5%) through the liquid-gas distribution system in the microfluidic chip.

[0016] The system includes a cross-contamination prevention delivery system, which prevents odor cross-contamination through independent gas paths and activated carbon adsorption layers, ensuring the independence of different odors and the accuracy of detection results.

[0017] The Visual Analogue Scoring (VAS) terminal scores through the following two stages:

[0018] Phase 1: Odor Perception Task. In this phase, three odor concentrations are randomly selected, one of which has a concentration of zero. Subjects rate the intensity of the odors using a sliding scale, ranging from 0 (no odor) to 10 (strong odor), to assess the subject's sensitivity to odor perception.

[0019] Phase 2: Odor Recognition Task. In this phase, the VAS terminal displays images of four odor sources. The subject selects the image that best matches the smell they smell, and the subject's odor recognition ability is assessed.

[0020] In the VAS scoring system, the four odor sources in the odor recognition task are selected from soap, rose, lemon and tea. The selection is based on their perceived intensity and recognition difficulty at different concentrations. The combination of these odor sources has been optimized to effectively distinguish between Parkinson's disease patients with different degrees of olfactory impairment and healthy controls.

[0021] This invention also provides a method for generating the Olfactory Impairment Index (ODI) using the above system, the specific generation method including the following steps:

[0022] The detection concentration threshold for a single odor is calculated, which is the odor concentration level at which the subject first responds. This level represents the lowest concentration at which the subject can detect the odor. The ODI for the odor detection threshold is 100-VAS.

[0023] The accuracy rate of the odor recognition stage is calculated as the ratio of the number of times the odor source is correctly identified to the total number of tests. This assesses the subject's ability to identify different odors. The ODI for recognition accuracy is 100 - odor recognition rate (%).

[0024] By integrating data from multiple odors, a standardized ODI is calculated based on the ODI of each odor's detection threshold and ODI of recognition accuracy. This standardized ODI is equal to ODI / 2 of recognition accuracy plus ODI / 2 of recognition accuracy. This index is used to quantitatively describe the degree of olfactory impairment in the subjects.

[0025] In the above method, the olfactory impairment index (ODI) is the arithmetic mean of the standardized ODI values ​​calculated individually for all odors.

[0026] In the above method, the Olfactory Impairment Index (ODI) is a standardized value ranging from 0 to 100, where 0 represents no olfactory impairment and 100 represents complete loss of olfactory function.

[0027] This invention provides a PD early olfactory impairment detection system based on progressive odor recognition. Through precise concentration adjustment, cross-contamination-free design, quantitative olfactory impairment index (ODI), bimodal scoring, and personalized management, it has high detection sensitivity and accuracy. It is particularly suitable for early screening and long-term monitoring of Parkinson's disease, providing a new technical means for the clinical diagnosis and management of neurodegenerative diseases. Detailed Implementation

[0028] Exemplary embodiments of this disclosure will now be described in more detail. It should be understood that this disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of this disclosure to those skilled in the art.

[0029] In the following description, certain specific details are set forth for the purpose of illustrating various disclosed embodiments in order to provide a thorough understanding of the various disclosed embodiments. However, those skilled in the art will recognize that embodiments may be practiced without one or more of these specific details. In other instances, well-known apparatuses, structures, and techniques associated with this application may not have been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0030] Throughout this specification, references to "an embodiment" or "an embodiment" indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Therefore, the appearance of "in an embodiment" or "an embodiment" in various places throughout the specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in any manner in one or more embodiments.

[0031] In the following description, in order to clearly demonstrate the structure and working method of the present invention, a number of directional terms will be used. However, terms such as "front", "back", "left", "right", "outside", "inside", "outward", "inward", "up", and "down" should be understood as convenient terms and not as limiting terms.

[0032] Example 1

[0033] Embodiments of the present invention provide a detection system for olfactory dysfunction in Parkinson's disease, specifically including:

[0034] ① Liquid storage unit (odorant container)

[0035] Each odorant (acetophenone, eugenol, menthol, pyridine, banana aldehyde) is stored separately in a sealed miniature container to avoid volatilization and cross-contamination.

[0036] The bottom of the container is connected to the inlet of the microfluidic chip, and the liquid is pushed into the microfluidic chip by a micropump before testing.

[0037] ② Microfluidic chip

[0038] The chip contains multiple branch channels and dilution chambers, each with a volume ranging from nanoscale to microscale.

[0039] By controlling the ratio of liquid sample to carrier gas, it is possible to achieve a ratio of 10... -6 g / mL to 10 -1 Geometric concentration gradient of g / mL.

[0040] For example: Let the base solution concentration be 10. -1 g / mL, 10 g / mL is generated stepwise within the chip through a 1:10 dilution ratio. -2 10 -3 10 -4 10 -5 10 -6 g / mL, forming 6 concentration levels.

[0041] ③ Piezoelectric valve control

[0042] The piezoelectric valve array precisely controls the flow ratio of carrier gas (clean air) to odor solution.

[0043] Each valve has a response speed of up to milliseconds and a control accuracy error of less than ±0.5%, ensuring stable concentration output.

[0044] The control logic is executed by a microcontroller (MCU), which gradually increases the odor concentration according to a preset program.

[0045] ④ Carrier gas control device

[0046] Use a constant flow pump or mass flow meter (MFC) to ensure a constant carrier gas flow rate (e.g., 0.5 L / min).

[0047] The carrier gas enters the system after being purified by a high-efficiency filter to avoid interference from external odors.

[0048] ⑤ Mixing chamber

[0049] The odorant and carrier gas are thoroughly mixed in a micro-mixing chamber to ensure uniform molecular distribution.

[0050] The mixing chamber outlet is connected to the delivery channel to ensure a constant concentration of odor entering the nasal cavity.

[0051] ⑥ Output channel and cross-contamination prevention design

[0052] Each odorant is equipped with an independent output channel, and there are electrically controlled valves and check valves between the channels.

[0053] After the test is completed, the output channel automatically switches to the clean air flushing mode and uses the activated carbon layer to adsorb residual odors, preventing odor residue from affecting the next test.

[0054] Specific odor combinations targeting the pathology of Parkinson's disease include acetophenone, eugenol, menthol, pyridine, and banana aldehyde. These odor combinations are selected based on the reduced sensitivity of neural pathways (such as the olfactory bulb and anterior olfactory nucleus) to specific odor molecules in the early stages of Parkinson's disease.

[0055] The progressive concentration stimulation module achieves precise release of odor molecules through a microfluidic chip, uses a piezoelectric valve to adjust the mixing ratio of odor and carrier gas, and precisely controls the odor concentration (error < ±0.5%) through the liquid-gas distribution system in the microfluidic chip.

[0056] The microfluidic chip can be an electronic microfluidic odor generator, a device that can precisely control the release of odor molecules. It is based on microfluidic technology, which is typically used to manipulate minute liquid or gas flows, achieving precise odor release through the adjustment of tiny channels and valves.

[0057] Microfluidics enables precise control of matter by manipulating the behavior of fluids at minute scales (typically from micrometers to nanometers). In odor generators, microfluidics is used to control the amount, rate, and concentration gradient of odor molecules released, ensuring that the concentration of odor released each time meets preset standards.

[0058] A two-stage visual analog scale (VAS) terminal, including:

[0059] The odor intensity perception scale displays odor intensity using a linear scale. Subjects slide the scale to rate the odor intensity, with a rating range of 0-10.

[0060] The odor image recognition interface displays multiple images corresponding to a specific odor source (such as almond, rose, lemon, tar, etc.). Subjects identify the odor by selecting the image that matches the odor they smell.

[0061] In this embodiment, the Visual Analogue Scoring (VAS) terminal scores through the following two stages:

[0062] Phase 1: Odor Perception Task. In this phase, participants rate the intensity of odors using a sliding scale, ranging from 0 (no odor) to 10 (strong odor), to assess their sensitivity to odor perception.

[0063] Phase 2: Odor Recognition Task. In this phase, the VAS terminal displays images of four odor sources. The subject selects the image that best matches the smell they smell, and the subject's odor recognition ability is assessed.

[0064] Furthermore, in the VAS scoring system, the four odor sources in the odor recognition task are selected from almond, rose, lemon and tar, respectively. The selection is based on their perceived intensity and recognition difficulty at different concentrations, and the combination of these odor sources is optimized to effectively distinguish between Parkinson's disease patients with different degrees of olfactory impairment and healthy controls.

[0065] This embodiment also provides a method for generating the Olfactory Impairment Index (ODI) using the above system. The specific generation method includes the following steps:

[0066] Calculate the detection concentration threshold for a single odor, which is the odor concentration level at which the subject first responds. This level represents the lowest concentration at which the subject can detect the odor.

[0067] Calculate the accuracy rate of the odor recognition stage, which is the ratio of the number of times the odor source is correctly identified to the total number of tests, to assess the subject's ability to identify different odors;

[0068] By integrating data from multiple odors and generating a standardized Olfactory Impairment Index (ODI) based on the detection threshold and recognition accuracy of each odor, the ODI is used to quantitatively describe the degree of olfactory impairment in the subjects.

[0069] The above-mentioned Olfactory Impairment Index (ODI) is the arithmetic mean of the ODI values ​​calculated individually for all odors. The Olfactory Impairment Index (ODI) is a standardized value ranging from 0 to 100, where 0 represents no olfactory impairment and 100 represents complete loss of olfactory function.

[0070] In another embodiment, a targeted odor gas of a specific concentration can also be prepared by the following method: take an appropriate amount of odorant and put it into a closed container filled with air, heat the container or odorant to vaporize the odorant, so that a certain concentration of targeted odor gas is formed in the container, and control the concentration of targeted odor gas by controlling the amount of odorant added.

[0071] Example 2: Early screening process for Parkinson's disease

[0072] Subject preparation: Subjects wear blindfolds and enter a soundproof room to minimize interference from the external environment for the olfactory test. An odor delivery interface is connected to the nasal cavity, through which the system delivers odor stimuli to the subject.

[0073] Odor delivery process: The system sequentially delivers five specific odors via a progressive concentration stimulation module, each odor starting from the lowest concentration (10). -6Start with odor concentrations of g / mL for 2 seconds, and gradually increase the concentration until the subject can detect the odor or reaches the highest concentration (10 g / mL). -1 (g / mL). The specific procedure is as follows:

[0074] Acetophenone (almond flavor): Starting concentration is 10. -6 If the subject does not respond, the concentration is gradually increased to 10 g / mL. -5 10 -4 10 -3 g / mL, until the subject responds.

[0075] Repeat the above process to test for other odors (eugenol, menthol, pyridine, banana aldehyde).

[0076] Visual Analogue Scale (VAS):

[0077] After each odor is detected, the VAS scoring system displays two interfaces:

[0078] Phase 1: Odor perception task. The system uses a linear scale (0-10 points) to allow subjects to slide the scale to indicate odor intensity, with the scoring range from "no odor" to "strong odor".

[0079] Phase 2: Odor Recognition Task. The system displays images of four odor sources (e.g., almond, rose, lemon, and tar), and participants select the image that matches the smell they perceive. This phase assesses the participants' ability to recognize different odors.

[0080] Olfactory Impairment Index (ODI) calculation:

[0081] For each odor, the concentration level at which the subject first perceives the odor is first recorded, and the perception threshold is calculated.

[0082] Next, the accuracy rate of the subjects in the recognition phase is calculated, which is the ratio of the number of correct recognitions to the total number of tests.

[0083] The detection threshold and recognition accuracy of each odor are combined to generate a single odor ODI value.

[0084] The average ODI value of all five odors was used as the composite ODI value to assess the degree of olfactory impairment in the subjects.

[0085] The system generates a test report, which includes the ODI value of each odor, the overall ODI value, and related assessment conclusions. This report can be used by doctors for early diagnosis and further treatment.

[0086] Disease monitoring application

[0087] Regular testing: Parkinson's disease patients should undergo regular olfactory testing, with an olfactory test performed monthly, and the ODI value change curves recorded and plotted.

[0088] ODI annual decline rate assessment: After each test, the ODI annual decline rate is calculated, which is the percentage change in ODI value over the past 12 months. If the patient's ODI annual decline rate exceeds 15%, a disease progression warning is issued.

[0089] This method has high sensitivity (92%) and specificity (88%), and can effectively assist doctors in judging the progression of the disease.

[0090] System Structure

[0091] System hardware components:

[0092] Odor generation module: Releases odor through an electronic microfluidic odor generator to ensure precise control of concentration.

[0093] Concentration control module: It uses microfluidic chips and piezoelectric valves to adjust the mixing ratio of odor and carrier gas to ensure the accuracy of odor stimulation concentration.

[0094] Delivery channel: Independent gas path design and activated carbon adsorption layer prevent cross-contamination of odors and ensure the purity of different odors.

[0095] Visual scoring terminal: includes an odor intensity scale and an array of odor recognition images for subjects to score.

[0096] Optional features may include data processing and report generation: the system has a built-in data processing unit that can receive and process test data in real time (after the visual scoring terminal receives the score, it inputs the score through an input terminal and transmits it to the data processing unit). The processed results are displayed through charts and data reports for easy analysis by researchers.

[0097] Example 3

[0098] This embodiment also provides a method for detecting early olfactory impairment in PD based on progressive odor recognition, the steps of which are as follows:

[0099] 1. Targeted scent combination

[0100] A variety of PD-specific strong odorants were selected, and each odorant was prepared into a gas with multiple concentration gradients for later use;

[0101] Specifically, five strong PD-specific odorants were selected and ranked according to their sensitivity to neural pathway damage: acetophenone (almond flavor), eugenol (clove flavor), menthol, pyridine (burnt flavor), and banana aldehyde. Each odorant was prepared into a gas with multiple concentration gradients, and then a targeted odor gas with six concentration gradients was prepared and sealed, with concentrations of 10... -6 10 -5 10 -4 10 -3 10 -2 10 -1 g / mL.

[0102] 2. Odor stimulation and recognition

[0103] Subjects were tested on the gaseous odors prepared with the odorant, and the gas concentrations were tested in ascending order.

[0104] After each test, the subjects output the intensity of the odor they perceived personally;

[0105] At the same time, the subjects were provided with a variety of odor sources, one of which matched the smell of the odorant. The odor sources could be almond, rose, lemon, and tar. The subjects selected the odor source that corresponded to the perceived odor.

[0106] 3. Olfactory Impairment Index (ODI) Calculation

[0107] Single Odor ODI Value: The ODI value for a single odor is calculated based on the subject's detection threshold concentration level (first response concentration level) and recognition accuracy.

[0108] Single odor ODI value = Detection threshold concentration level × Recognition accuracy correction factor;

[0109] Composite ODI value: The average ODI values ​​of the five odors are calculated to generate a composite Olive Impairment Index (ODI): Composite ODI value = Average ODI of the five odors;

[0110] 4. Application in disease monitoring

[0111] Subjects were tested regularly, and ODI change curves were recorded and plotted.

[0112] If an annual decline in ODI is detected to exceed a set value, a disease progression warning will be issued.

[0113] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A PD early olfactory disorder detection system based on progressive odor recognition, characterized in that, Include: A specific odor combination targeting the pathology of Parkinson's disease, including acetophenone, eugenol, menthol, pyridine, and banana aldehyde, the odor combination being selected based on the reduced sensitivity of neural pathways to specific odor molecules in the early stages of Parkinson's disease. The progressive concentration stimulation module can provide 6 concentration gradients, with a concentration range of 10. -6 ~10 -1 g / mL, the concentration decreases geometrically; A two-stage visual simulation scoring terminal includes: The odor intensity perception scale displays odor intensity using a linear scale. Subjects slide the scale to rate the odor intensity, with a rating range of 0-10. The odor image recognition interface displays multiple images corresponding to a specific odor source. Subjects identify the odor by selecting the image that matches the odor they smell.

2. The detection system according to claim 1, characterized in that, The concentration control module achieves precise release of odor molecules through a microfluidic chip, uses a piezoelectric valve to adjust the mixing ratio of odor and carrier gas, and precisely controls the odor concentration (error < ±0.5%) through the liquid-gas distribution system in the microfluidic chip.

3. The detection system according to claim 1, characterized in that, The system includes a cross-contamination prevention delivery system, which prevents odor cross-contamination through independent gas paths and activated carbon adsorption layers, ensuring the independence of different odors and the accuracy of detection results.

4. The detection system according to claim 1, characterized in that, The visual simulation scoring terminal performs scoring in the following two stages: Phase 1: Odor Perception Task. In this phase, participants rate the intensity of odors using a sliding scale, ranging from 0 to 10, where 0 represents no odor and 10 represents a strong odor. This is used to assess the participants' sensitivity to odor perception. Phase 2: Odor Recognition Task. In this phase, the visual analog scale terminal displays images of four odor sources. Subjects select the image that best matches the smell they smell, and the subject's odor recognition ability is assessed.

5. The detection system according to claim 4, characterized in that, In the VAS scoring system, the four odor sources in the odor recognition task are selected from almond, rose, lemon and tar. The selection is based on their perceived intensity and recognition difficulty at different concentrations. The combination of these odor sources has been optimized to effectively distinguish between Parkinson's disease patients with different degrees of olfactory impairment and healthy controls.

6. The method for generating an olfactory impairment index using the detection system according to claim 1, characterized in that, The specific generation method includes the following steps: Calculate the detection concentration threshold for a single odor, which is the odor concentration level at which the subject first responds. This level represents the lowest concentration at which the subject can detect the odor. Calculate the accuracy rate of the odor recognition stage, which is the ratio of the number of times the odor source is correctly identified to the total number of tests, to assess the subject's ability to identify different odors; By integrating data from multiple odors and generating a standardized olfactory impairment index based on the detection threshold and recognition accuracy of each odor, the index is used to quantitatively describe the degree of olfactory impairment in the subjects.

7. The method according to claim 6, characterized in that, The olfactory impairment index is the arithmetic mean of the ODI values ​​calculated individually for all odors.

8. The method according to claim 6, characterized in that, The olfactory impairment index is a standardized value ranging from 0 to 100, where 0 represents no olfactory impairment and 100 represents complete loss of olfactory function.