Method for minimally invasive diagnosis of lower urinary tract symptoms

Abstract

The present invention relates to a method and apparatus for minimally invasive diagnosis of lower urinary tract symptoms. When the method for diagnosis of lower urinary tract symptoms according to the present invention is used, it is possible to overcome disadvantages of existing diagnostic methods, such as causing discomfort, trauma, or complications in patients, requiring a lot of space, requiring a long test time of about 50 minutes, and requiring a skilled examiner.

Description

Diagnostic method for partially invasive lower urinary tract symptoms

[0001] The present invention was carried out under project number S-2023-2017-000 with the support of Sungkyunkwan University, the research management agency for the said project is the Sungkyunkwan University Research Support Team, the research project name is "2022 Academic Year Future Convergence Research Support Project," the research project name is "[SKKU-SMC] Development of technology for diagnosing lower urinary tract symptoms (detrusor dysfunction, bladder outlet obstruction) in a non-invasive manner," and the research period is 2022.10.01-2024.09.30.

[0002] This patent application claims priority to Korean Patent Application No. 10-2024-0182238 filed with the Korean Intellectual Property Office on December 10, 2024, the disclosures of said patent application are incorporated herein by reference.

[0003] The present invention relates to a method and device for diagnosing partially invasive lower urinary tract symptoms.

[0004]

[0005] Throughout this specification, numerous papers and patent documents are referenced and cited. The disclosures of the cited papers and patent documents are incorporated by reference into this specification in their entirety to more clearly explain the state of the art to which the present invention pertains and the content of the present invention.

[0006] Normal urination is the result of a highly coordinated neural circuit between the brain, spinal cord, bladder, and urethral sphincter. Voiding dysfunction occurs due to nerve damage or dysfunction of the bladder or urethral sphincter, and the symptoms resulting from urinary dysfunction are called lower urinary tract symptoms.

[0007] Invasive urodynamic testing is required to accurately diagnose the causes of lower urinary tract symptoms. In particular, patients with a weakened urine stream suffer from severe lower urinary tract symptoms, but treatment strategies differ depending on whether these symptoms are caused by bladder outlet obstruction or detrusor underactivity. In other words, to accurately evaluate the respective causes despite the same symptoms, it is necessary to verify the actual pressure changes in the bladder muscle (detrusor) during urination. However, since bladder muscle pressure cannot be measured directly in practice, detrusor pressure is indirectly assessed by measuring real-time changes in intravesical pressure and intraabdominal pressure. To measure intravesical and intraabdominal pressure, a catheter is inserted into the urethra and anus to perform urodynamic testing. This procedure causes pain, discomfort, and shame for the patient and carries the risk of hematuria and urinary tract infection. In addition, there are disadvantages such as the high cost of the testing equipment, the large amount of space required for the test, and the fact that the test takes approximately 50 minutes. Furthermore, the proficiency of the person performing the test is crucial, so advanced specialized training and experience with many cases are required to independently and accurately diagnose a single patient.

[0008] Despite the rapid advancements in modern science, technology, and artificial intelligence, non-invasive methods have been proposed to replace urodynamic testing since its introduction in the early 1950s; however, there is currently no diagnostic method capable of replacing urodynamic testing. Therefore, there is a need for a diagnostic module that is non-invasive yet possesses high accuracy for differentiating the causes of lower urinary tract symptoms.

[0009]

[0010] The inventors have made diligent research efforts to develop a new type of non-invasive urodynamic testing method. As a result, they have completed the present invention by identifying that the type of lower urinary tract symptoms can be effectively diagnosed by analyzing only the changes in pressure within the urethra during urination.

[0011] Therefore, the objective of the present invention is to provide a method for providing information necessary for diagnosing lower urinary tract symptoms.

[0012] Another objective of the present invention is to provide a lower urinary tract symptom diagnosis device comprising a pressure measurement sensor within the urethra.

[0013] Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims, and drawings.

[0014]

[0015] The present invention provides the inventions of 1 to 19 below.

[0016] 1. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis that includes the following steps:

[0017] (a) a step of measuring the pressure inside the urethra during urination of a subject with lower urinary tract symptoms; and

[0018] (b) A step to determine the type of lower urinary tract symptoms by analyzing changes in pressure within the urethra during urethral contraction during urination.

[0019] 2. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein in 1, if the rate of decrease in pressure within the subject's urethra during the urethral contraction process is higher than that of a normal person, it is determined to be a bladder outlet obstruction type, and if the rate of decrease in pressure within the subject's urethra is not higher than that of a normal person, it is determined to be a detrusor muscle dysfunction type of lower urinary tract symptom.

[0020] 3. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein in 1 or 2, if the time at which the pressure inside the subject's urethra changes from positive pressure to negative pressure during the urethral contraction process during urination is faster than that of a normal person, it is determined to be a bladder outlet obstruction type, and if the time at which the pressure inside the subject's urethra changes from positive pressure to negative pressure is not faster than that of a normal person, it is determined to be a detrusor muscle dysfunction type of lower urinary tract symptom.

[0021] 4. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein, in any one of 1 to 3, the pressure within the urethra is measured at the lower part of the urethra.

[0022] 5. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein in any one of 1 to 4, the pressure within the urethra is measured between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively.

[0023] 6. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein, in any one of 1 to 5, the method for diagnosing or the method for providing information necessary for diagnosis further comprises the step of inputting the measured intraurethral pressure data into a machine learning-based AI model to determine the type of lower urinary tract symptoms.

[0024] 7. A method for diagnosing lower urinary tract symptoms or a method for providing information necessary for diagnosis, wherein, in any one of 1 to 6, the AI ​​model is an XGBoost and SHAP-based model.

[0025] 8. A lower urinary tract symptom diagnostic device comprising a pressure measuring sensor within the urethra.

[0026] 9. A lower urinary tract symptom diagnostic device according to 8, wherein the device comprises a urethral insertion catheter.

[0027] 10. A lower urinary tract symptom diagnostic device according to 8 or 9, wherein the device does not include a structure for insertion into the bladder, anus, or a combination thereof.

[0028] 11. A lower urinary tract symptom diagnostic device, wherein, in any one of 8 to 10, the urethral pressure measuring sensor measures changes in urethral pressure during urination.

[0029] 12. A lower urinary tract symptom diagnostic device, wherein, in any one of 8 to 11, the pressure within the urethra is measured at the lower part of the urethra.

[0030] 13. A lower urinary tract symptom diagnostic device, wherein in any one of 8 to 12, the pressure inside the urethra is measured between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively.

[0031] 14. A lower urinary tract symptom diagnostic device, wherein in any one of 8 to 13, the lower urinary tract symptom is a bladder outlet obstruction type or a detrusor muscle dysfunction type.

[0032] 15. The present invention is a lower urinary tract symptom diagnosis system comprising: (a) a pressure sensor inserted into the lower part of the urethra to measure changes in pressure within the urethra during urination; (b) a data processing unit that receives pressure data measured from the pressure sensor and analyzes the type of lower urinary tract symptom; and (c) a display unit that displays the analyzed type of lower urinary tract symptom to a user, wherein the system does not include a catheter inserted into the bladder or anus.

[0033] 16. A lower urinary tract symptom diagnosis system according to 15, wherein the data processing unit analyzes the type of lower urinary tract symptoms using a machine learning-based AI model on the measured pressure data.

[0034] 17. A lower urinary tract symptom diagnosis system, wherein the AI ​​model in 15 or 16 is an XGBoost and SHAP-based model.

[0035] 18. A lower urinary tract symptom diagnosis system in any one of 15 to 17, wherein the pressure sensor measures pressure between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively.

[0036] 19. A lower urinary tract symptom diagnosis system, wherein, in any one of 15 to 18, the pressure sensor and the data processing unit are configured in the form of a urethral insertion type catheter.

[0037]

[0038] In one aspect of the present invention, the present invention provides a method for providing information necessary for diagnosing lower urinary tract symptoms, comprising the following steps:

[0039] (a) a step of measuring the pressure inside the urethra during urination of a subject with lower urinary tract symptoms; and

[0040] (b) A step to determine the type of lower urinary tract symptoms by analyzing changes in pressure within the urethra during urethral contraction during urination.

[0041] In this specification, the term “lower urinary tract” refers collectively to the biological structures and organs below the bladder through which urine passes, including the bladder, the urethra including the urethral sphincter, and the urethral opening.

[0042] In this specification, the term "Lower urinary tract symptom (LUTS)" refers collectively to various symptoms that occur in relation to the storage and excretion of urine, such as difficulty initiating, residual urine, frequent urination, weak stream, tension during urination, nocturia, urgency, and intermittent urination.

[0043] In one embodiment of the present invention, the method for providing information necessary for diagnosing lower urinary tract symptoms involves analyzing the rate of decrease in intraurethral pressure during the urethral contraction process while voiding, and determining the lower urinary tract symptoms as a bladder outlet obstruction type if the rate of decrease in intraurethral pressure of the subject is higher than that of a normal person, and as a detrusor muscle dysfunction type if the rate of decrease in intraurethral pressure of the subject is not higher than that of a normal person.

[0044] Lower urinary tract symptoms can be classified into bladder outlet obstruction (BOO) and detrusor underactivity (DU). Bladder outlet obstruction refers to a condition where urinary drainage becomes difficult due to physical or functional impairment in the passage from the bladder through the urethra; this can be caused by conditions such as benign prostatic hyperplasia, urethral stenosis, or bladder neck spasm. Detrusor underactivity refers to a condition where the detrusor muscle, a bladder muscle, fails to contract sufficiently, resulting in the inability to smoothly drain urine. Advanced age, neurological causes (e.g., diabetic neuropathy, Parkinson's disease, spinal cord injury), and the use of certain medications can induce detrusor underactivity. As the contractile force of the detrusor muscle weakens, urine does not naturally drain from the bladder, and the bladder often fails to empty completely.

[0045] The treatment approaches for bladder outlet obstruction (BOO) and detrusor dysfunction (DU) differ. For bladder outlet obstruction, medication (alpha-blockers, 5-alpha-reductase inhibitors) or, if necessary, surgical methods (prostatectomy, urethral dilation) are used to resolve physical obstructions such as benign prostatic hyperplasia or urethral stenosis, thereby reducing resistance at the bladder outlet to facilitate smooth urination. On the other hand, detrusor dysfunction focuses on strengthening the contractility of the bladder muscles; while it may occasionally be supplemented with medications such as beta-3 adrenergic receptor agonists or cholinergics, their effectiveness may be limited, necessitating supportive approaches such as urinary assistive devices (intermittent self-catheterization) or electrical stimulation therapy. In other words, the treatment methods for bladder outlet obstruction and detrusor dysfunction differ, and identifying the type of lower urinary tract symptoms in the patient is necessary to select the appropriate treatment method.

[0046] In this specification, "when analyzing the rate of decrease in pressure within the urethra during the process of urethral contraction during urination, the rate of decrease in pressure within the subject's urethra is higher than that of a normal person" means that when the amount of urine decreases and the urethra contracts during the process of urination, the pressure within the urethra decreases, and the degree of pressure decrease in the subject is more rapid than that of a normal person. The rate of pressure decrease can be calculated by measuring the time required to change from the highest pressure level to the lowest pressure level within the urethra. A case where the rate of decrease in pressure within the subject's urethra is higher than that of a normal person may mean, for example, that the rate of decrease in pressure within the subject's urethra is 3% or more, 5% or more, 7% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, or 50% or more higher than that of a normal person. For example, it may be 3 to 100%, 3 to 90%, 3 to 80%, 3 to 70%, 3 to 60%, 3 to 50%, 3 to 40%, 3 to 30%, 3 to 20%, 3 to 10%, 10 to 100%, 20 to 100%, 30 to 100%, 40 to 100%, 50 to 100%, 60 to 100%, 70 to 100%, 80 to 100%, 90 to 100%, 10 to 90%, 10 to 80%, 10 to 70%, 20 to 60%, or 20 to 50% higher, but is not limited thereto.

[0047] In one embodiment of the present invention, if the point at which the pressure inside the subject's urethra changes from positive pressure to negative pressure is faster than that of a normal person during the process of urethral contraction during urination, it is determined to be a bladder outlet obstruction type, and if the point at which the pressure inside the subject's urethra changes from positive pressure to negative pressure is not faster than that of a normal person, it is determined to be a lower urinary tract symptom of detrusor muscle dysfunction type.

[0048] In cases where the subject's urethral pressure changes from positive to negative pressure quickly, the time at which the subject's urethral pressure changes from positive to negative pressure may be 3% or more, 5% or more, 7% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, or 50% or more faster than that of a normal person. For example, it may be 3 to 90%, 3 to 80%, 3 to 70%, 3 to 60%, 3 to 50%, 3 to 40%, 3 to 30%, 3 to 20%, 3 to 10%, 3 to 5%, 5 to 90%, 10 to 90%, 20 to 90%, 30 to 90%, 40 to 90%, 50 to 90%, 60 to 90%, 70 to 90%, 80 to 90%, 3 to 90%, 10 to 80%, 20 to 70%, 30 to 60%, or 40 to 50% faster, but is not limited thereto.

[0049] In one embodiment of the present invention, the pressure within the urethra is measured at the lower part of the urethra. The lower part of the urethra is, for example, a point 10% to 90% below the starting point of the urethra. The lower part of the urethra may be, for example, a point 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 20% to 90%, 30% to 90%, 40% to 90%, 50% to 90%, 60% to 90%, 70% to 90%, 80% to 90%, 20% to 80%, 30% to 70%, 40% to 60%, 20% to 40%, or 60% to 80% from the starting point of the urethra, but is not limited thereto. In this specification, the starting point of the urethra refers to the point where the urethra begins past the bladder, and the end point of the urethra refers to the point where urine is discharged from the body.

[0050] In one embodiment of the present invention, the present invention can effectively determine the type of lower urinary tract symptoms solely by measuring changes in pressure within the urethra, without measuring pressure within the bladder or abdominal pressure. Since the method for diagnosing lower urinary tract symptoms according to the present invention does not require the measurement of pressure within the bladder or abdominal pressure, there is no need to insert an internal pressure measuring device into the bladder or anus.

[0051] In one embodiment of the present invention, the pressure inside the urethra is measured between points 60 and 90 when the urethra is divided into 100 equal parts and the starting point and the ending point of the urethra are designated as points 1 and 100, respectively. The measurement points of the pressure inside the urethra may be, for example, points 60 to 90, 60 to 85, 60 to 80, 60 to 75, 60 to 70, 60 to 65, 65 to 90, 70 to 90, 75 to 90, 80 to 90, 85 to 90, 70 to 80, or 75 to 80, but are not limited thereto.

[0052] In one embodiment of the present invention, when the subject has a urethral obstruction, the measurement point of the pressure inside the urethra is measured at a point 1 to 10 cm from the urethral obstruction toward the lower part of the urethra. For example, the pressure inside the urethra is measured at a point 1 to 10 cm, 1 to 10 cm, 1 to 9 cm, 1 to 8 cm, 1 to 7 cm, 1 to 6 cm, 1 to 5 cm, 1 to 4 cm, 1 to 3 cm, 1 to 2 cm, 2 to 10 cm, 3 to 10 cm, 4 to 10 cm, 5 to 10 cm, 6 to 10 cm, 7 to 10 cm, 8 to 10 cm, 9 to 10 cm, 2 to 8 cm, 2 to 6 cm, or 2 to 4 cm from the urethral obstruction, but is not limited thereto.

[0053] In one embodiment of the present invention, the diagnostic method or the method for providing information necessary for diagnosis further includes the step of inputting the measured intraurethral pressure data into a machine learning-based AI model to determine the type of lower urinary tract symptoms.

[0054] The aforementioned AI model learns the time-series changes in input pressure data or pressure characteristics at specific points in time to classify whether the subject is of the bladder outlet obstruction (BOO) type or the detrusor dysfunction (DU) type. This AI-based analysis method is advantageous for improving diagnostic accuracy as it can quantify minute changes in intraurethral pressure.

[0055] In one embodiment of the present invention, the AI ​​model is an XGBoost and SHAP-based model.

[0056] In this invention, the XGBoost (eXtreme Gradient Boosting) model, one of the representative machine learning algorithms, can be utilized. This model is a decision tree-based ensemble learning algorithm that offers high classification performance and fast learning speed. Furthermore, by introducing SHAP (SHapley Additive exPlanations) to intuitively interpret the model's prediction results, the contribution of each input variable (e.g., pressure level at a specific point in time) to the final prediction result can be verified. The introduction of such explainable artificial intelligence (XAI) can also contribute to increasing the reliability of diagnoses by clinicians.

[0057] Furthermore, the inventors generated a large amount of pressure data corresponding to various lower urinary tract conditions (degree of obstruction, urethral diameter, pressure distribution, etc.) through numerical analysis and experiments, and trained an AI model based on this data. The trained model is configured to automatically determine the type of lower urinary tract symptoms by receiving urethral pressure data from a new subject. This implementation differentiates itself from existing diagnostic methods that relied on qualitative analysis by skilled physicians, and enables quantitative and reproducible diagnosis.

[0058]

[0059] In one aspect of the present invention, the present invention provides a lower urinary tract symptom diagnosis device comprising a pressure measuring sensor within the urethra.

[0060] The above diagnostic device may include conventional configurations that a conventional disease diagnostic device may include, such as a sensor module, a signal processing device, a data analysis module, a user interface, a data storage device, a communication module, and a power supply.

[0061] The above-described intraurethral pressure measuring sensor may include a structure for urethral insertion comprising a sensor. The intraurethral pressure measuring sensor of the present invention is inserted into the urethra and is not inserted into the bladder, anus, or a combination thereof.

[0062] The above diagnostic device does not include a structure for insertion into the bladder, anus, or a combination thereof.

[0063] In one embodiment of the present invention, the device includes a urethral insertion catheter.

[0064] The lower urinary tract symptom diagnosis device using a pressure sensor according to the present invention may include a pressure sensor covered by a catheter formed in the shape of a long, thin tube inserted into the urethra, and a line for inputting and outputting the signal of the pressure sensor, wherein only a predetermined pressure measuring portion of the pressure sensor is not covered by an outer sheath and is mounted at a predetermined location, and a voltage is applied to the pressure sensor through the input line of the input / output line, and the output voltage corresponding to the pressure change in the urethra measured by the pressure sensor is output through the output line, and the lower urinary tract symptom is diagnosed based on the pressure change in the urethra and the diagnosis and display thereof may be included.

[0065] In one embodiment of the present invention, the pressure measuring sensor in the urethra measures changes in pressure in the urethra during urination.

[0066] In one embodiment of the present invention, the pressure within the urethra is measured at the lower part of the urethra.

[0067] In one embodiment of the present invention, the pressure inside the urethra is measured between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively.

[0068] In one embodiment of the present invention, the lower urinary tract symptoms are of the bladder outlet obstruction type or the detrusor muscle dysfunction type.

[0069] The above diagnostic device includes a configuration for implementing a method for providing information necessary for diagnosing the above upper urinary tract symptoms, and redundant details are omitted to prevent excessive duplication in the specification.

[0070]

[0071] In one aspect of the present invention, the present invention provides a lower urinary tract symptom diagnosis system comprising: (a) a pressure sensor inserted into the lower part of the urethra to measure changes in pressure within the urethra during urination; (b) a data processing unit that receives pressure data measured from the pressure sensor and analyzes the type of lower urinary tract symptom; and (c) a display unit that displays the analyzed type of lower urinary tract symptom to a user, wherein the system does not include a catheter inserted into the bladder or anus.

[0072] In one embodiment of the present invention, the data processing unit analyzes the type of lower urinary tract symptoms using a machine learning-based AI model with measured pressure data.

[0073] In one embodiment of the present invention, the AI ​​model is an XGBoost and SHAP-based model, a lower urinary tract symptom diagnosis system.

[0074] In one embodiment of the present invention, the pressure sensor measures pressure between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively, in a lower urinary tract symptom diagnosis system.

[0075] In one embodiment of the present invention, the pressure sensor and the data processing unit are configured in the form of a urethral insertion type catheter, a lower urinary tract symptom diagnosis system.

[0076]

[0077] The features and advantages of the present invention are summarized as follows:

[0078] (a) The present invention provides a method for providing information necessary for diagnosing lower urinary tract symptoms.

[0079] (b) The present invention provides a lower urinary tract symptom diagnosis device comprising a pressure measurement sensor within the urethra.

[0080] (c) When using the lower urinary tract symptom diagnosis method of the present invention, the disadvantages of existing diagnostic methods, such as causing discomfort, trauma, and complications to the patient, occupying a large amount of space, taking a long time for the examination (approximately 50 minutes), and requiring a skilled examiner, can be overcome.

[0081]

[0082] Figure 1 shows examples of clinical data and voiding cystography images quantified through video urodynamic testing.

[0083] FIG. 2 shows (a) a schematic diagram of a lower urinary tract simulation flow visualization experimental apparatus and (b) a schematic diagram of a lower urinary tract simulation pressure measurement apparatus.

[0084] Figure 3a shows the lower urinary tract modeling for numerical analysis, and Figure 3b shows the physical factors derived through numerical analysis.

[0085] Figure 4 shows an overview of the derivation of key factors for the diagnosis of lower urinary tract symptoms based on numerical analysis results, AI, and XAI models.

[0086] Figure 5 shows (a) the elastic modulus of the urethra measured by Idzenga et al. (the curve indicated by the dotted line represents the average measurement of the pig urethra), and (b) a graph converting the data from Idzenga et al. into stress-strain. It showed a Young's modulus of approximately 50 kPa at 50 cmH2O.

[0087] Figure 6 shows (a) the setup for the flow visualization experiment, (b) the flow field derived through numerical analysis and the flow visualization experiment, and (c) the pressure back-calculated based on the flow field.

[0088] Figure 7a shows a video urodynamic image of bladder outlet obstruction, Figure 7b shows a video urodynamic image of detrusor dysfunction, Figures 7c to 7e show the urodynamic test results of bladder outlet obstruction, and Figures 7f to 7h show the urodynamic test results of detrusor dysfunction.

[0089] Figure 8 shows (a) the main factor derived through SHAP among XAI models. Excluding the noisy urethral end data, the pressure at position 79 is the main factor, (b) position 79 refers to the lower part of the obstruction located 29 mm away from the obstruction, and (c) the pressure at the lower part of the obstruction during the urination process derived through numerical analysis.

[0090] Figure 9 shows (a) a comparison of the distension shape of bladder outlet obstruction and detrusor dysfunction, and (b) the results of a comparison of inflow pressure between numerical analysis and experiment.

[0091] Figure 10 shows (a) a comparison of outflow pressure according to an inflow velocity in the form of a sine function, and (b) a comparison of outflow pressure according to an inflow velocity in the form of a ramp function.

[0092] FIG. 11 shows (a) a conventional invasive method for diagnosing lower urinary tract symptoms that requires inserting a pressure measuring catheter into the bladder and anus, and (b) a method for diagnosing lower urinary tract symptoms proposed in the present invention that involves inserting a pressure measuring catheter into the lower part of the obstruction.

[0093]

[0094]

[0095] The present invention will be described in more detail below through examples. These examples are intended solely to explain the invention more specifically, and it will be obvious to those skilled in the art that the scope of the invention is not limited by these examples according to the gist of the invention.

[0096]

[0097] Examples

[0098] Example 1: Materials and Method

[0099] 1-1. Securing Clinical Data from Patients with Lower Urinary Tract Symptoms

[0100] We aimed to collect data from patients requiring urodynamic testing due to lower urinary tract symptoms. Patients were classified into normal, bladder outlet obstruction, and detrusor dysfunction groups.

[0101] The following clinical information was collected from the patient.

[0102] a) Age and weight

[0103] b) Past medical history: hypertension, diabetes, history of neurological diagnosis, history of urinary tract cancer diagnosis, etc.

[0104] c) For men: Measurement of prostate size through prostate ultrasound results.

[0105] d) Confirm the patient's maximum urine flow rate, residual urine volume, and bladder efficiency through uroflowmetry.

[0106] During the urodynamic test, images of changes in the bladder outlet and urethra during voiding were obtained using a C-arm, and various parameters, analysis graphs, and image data of the urodynamic test were converted into a database as shown in Fig. 1.

[0107] a) Urethral pressure profile (UPP)

[0108] b) Uroflowmetry

[0109] c) Cystometry

[0110] d) Pressure-flow study

[0111]

[0112] 1-2 Development of Lower Urinary Tract Simulation and Flow Visualization Experiment Apparatus

[0113] An experimental apparatus was constructed using a polydimethylsiloxane (PDMS) chip and a controllable gear pump to simulate the mechanical properties of the urethra and the flow and pressure associated with bladder outlet obstruction and detrusor dysfunction. To fabricate the PDMS chip, a 3D model of the urethra was designed using computer-aided design (CAD) based on the bladder size, urethral length, and circumference from clinical data provided by SMC. In particular, bladder outlet obstruction was modeled considering various obstruction rates.

[0114] Polydimethylsiloxane (PDMS) was used to simulate the mechanical properties of the urethra. PDMS is a transparent polymer material that allows for the observation of internal flow and enables the fabrication of various shapes through curing. A lower urinary tract mold modeled with a 3D printer (UltiMaker S3, Ultimaker) was printed, and PDMS mixed at a 40:1 ratio was poured and cured to produce a lower urinary tract PDMS chip that matches the actual size and properties (Ea ~ 50 kPa) of the lower urinary tract.

[0115] To visualize the flow using Particle Image Velocimetry (PIV), a continuous wave laser was formed into a thin plane through two cylindrical lenses as shown in Fig. 2(a). Subsequently, the plane was aligned to pass through the center of the channel of the PDMS chip. The urination process was simulated using a gear pump and a liquid dispersed with fluorescent particles, and this process was filmed using a high-speed camera. The flow field within the channel was calculated by analyzing the captured continuous images. Subsequently, the inflow pressure was predicted by back-calculating the pressure from the tip of the urethra based on the flow field.

[0116] A system capable of controlling the flow rate of urine over time was fabricated as shown in Fig. 2(b) by connecting a gear pump (Regolo-Z Digital, ISMATEC) to the fabricated PDMS chip. The connected gear pump was precisely controlled using Python to implement the desired urine flow rate profile. In addition, pressure sensors (PTXPRESS2, Druck) were installed before and after the PDMS chip to construct a lower urinary tract simulation device capable of monitoring pressure and flow rate in real time.

[0117]

[0118] 1-3. Simulation of the Voiding Process and Derivation of Key Factors for Lower Urinary Tract Symptoms through Numerical Analysis

[0119] To train an AI model for diagnosing the causes of lower urinary tract symptoms, a large amount of physical factors, such as speed and pressure, is required for bladder outlet obstruction and detrusor dysfunction, respectively. To extract this large amount of data, the urination process was implemented through numerical analysis.

[0120] For efficient numerical analysis, a simplified lower urinary tract was modeled as shown in Fig. 3a by applying a 2D axisymmetric model. The thickness and length of the urethra from clinical data were referenced, and the obstruction radius and length were set considering the size of the prostate that causes obstruction. Fluid-structure interaction (FSI) analysis was performed to account for the interaction between urine and the urethra during the voiding process. For the fluid domain, a laminar flow model was applied considering the Reynolds number (Re ~ 1500).

[0121] Based on the numerical analysis results shown in Fig. 3b, fluid dynamic and solid dynamic factors such as position, velocity, stress, and pressure were derived according to position by dividing the area from the inlet (No. 1) to the outlet (No. 100) into 100 equal parts at 1 mm intervals. The derived physical factors were trained on the machine learning model XGBoost. XGBoost is an algorithm based on a Decision Tree model, which allows for the implementation of an efficient machine learning model due to its high accuracy and fast computation speed.

[0122] The importance of physical factors in determining the causes of lower urinary tract symptoms was evaluated by applying SHAP, a representative explainable AI (XAI), to a hyperparameter-optimized model. SHAP represents the influence of each feature on prediction as a numerical value based on Shapley values ​​from game theory. Through this, the predictions of AI models, often referred to as "black boxes," could be intuitively understood and interpreted.

[0123]

[0124] 1-4. Comparative Analysis of Data from Lower Urinary Tract Simulation Device and Clinical Data

[0125] The physical properties of the fabricated lower urinary tract-mimicking PDMS chip were verified to be similar to those of the actual lower urinary tract. The elastic modulus (N / m) and strain of the urethra were measured, and the average measurements represented by the dotted line in Fig. 5 (a) were converted into the stress-strain relationship, an engineering physical property, as shown in Fig. 5 (b), taking into account the diameter and length of the urethra. Considering that the maximum bladder pressure during voiding in the urodynamic test is 50 cmH2O when maximally distended, it was determined that the elastic modulus of the urethra ranges from 44.7 kPa to 56.6 kPa.

[0126]

[0127] Example 2: Derivation of Fluid Dynamics Factors through Flow Visualization

[0128] As shown in Fig. 6(a), the flow field was derived using PIVlab in MALAB 2023B (MathWorks) from continuous images inside the PDMS chip through an experiment visualizing the urination process. Pressure was calculated using the above flow field and the Navier-Stokes equations. Since pressure is a state function independent of the calculation path, the same inflow pressure is reached even when calculating pressure through different paths. In fact, as shown in Fig. 6(c), the result of calculating the inflow pressure from the outflow pressure through six different paths showed an error rate of 3% compared to the pressure from the numerical analysis.

[0129] Current non-invasive diagnostic methods based on flow visualization have limitations because video urodynamics capable of flow visualization in clinical practice requires the injection of contrast agent into the bladder.

[0130]

[0131] Example 3: Modeling of the lower urinary tract through video urodynamics

[0132] As shown in Figures 7a to 7h, the average values ​​of maximum flow, urethral diameter, and obstruction diameter were derived for each patient group based on 21 video urodynamic studies. For bladder outlet obstruction, data from 14 patients were referenced, showing an average maximum flow of 7.57 ± 0.57 mL / s, a urethral diameter of 9.15 ± 0.45 mm, and an obstruction diameter of 4.00 ± 0.29 mm. For detrusor dysfunction, data from 6 patients were referenced, showing an average maximum flow of 8.66 ± 2.32 mL / s and a urethral diameter of 10.83 ± 0.92 mm. The data from the remaining 1 patient were from a normal patient.

[0133]

[0134] Example 4: Simulation of the voiding process and identification of key factors of lower urinary tract symptoms through simulation

[0135] Multiple cases simulating the voiding process were established by applying different deviations to the size and flow rate of the urethra and obstruction for bladder outlet obstruction and detrusor dysfunction derived from video urodynamic testing. Numerical analysis was performed on a total of 5,455 cases, including 2,630 cases of bladder outlet obstruction and 2,825 cases of detrusor dysfunction. A dataset was constructed by deriving the pressure, stress, and their changes for each case at 1 mm intervals over a 100 mm section surrounding the obstruction.

[0136] The XGBoost model was trained based on the constructed dataset. K-fold cross-validation was used to more accurately evaluate the model's performance and prevent overfitting and biased evaluations. The bladder outlet obstruction and detrusor dysfunction groups in the dataset were divided into five folds; each fold was used once as evaluation data, and the remaining folds were used as training data. This process was repeated five times to calculate the average accuracy and evaluate the model's generalized performance, and the model with the highest accuracy was used for subsequent analysis.

[0137] As a result of applying SHAP to the optimized XGBoost model, excluding the urethral end data where significant noise appeared as in Fig. 8 (a), the pressure at a location 29 mm downward from the obstruction (position 79) was identified as the primary factor (Fig. 8 (b)). Looking at the analysis results in Fig. 8 (a), it was observed that red dots were distributed on the side where the SHAP value was less than 0, and blue dots were distributed on the side where it was greater than 0. In other words, this means that the higher the pressure, the higher the probability of detrusor dysfunction, and the lower the pressure, the higher the probability of bladder outlet obstruction.

[0138] Looking at Fig. 8(c) to see how the pressure at the lower end of the obstruction changes during the urination process, it was observed that in bladder outlet obstruction, a rapid drop in pressure occurs, and the point at which the pressure transitions from a positive (+) value to a negative (-) value occurs faster than in detrusor dysfunction. It was confirmed that this characteristic is more pronounced as the obstruction rate increases.

[0139] These differences are attributed to the fact that urethral distension exhibits different behaviors depending on the presence or absence of obstruction, as shown in Fig. 9 (a). During the process of increasing intraurethral pressure and flow rate, bladder outlet obstruction causes the area prior to the obstruction to expand intensively due to the obstruction. When pressure and flow rate decrease, the urethra begins to contract, inducing a rapid change in pressure. On the other hand, in the case of detrusor dysfunction, the urethra is deformed overall, and since the degree of deformation is very small, no pressure change occurs during urethral contraction. Therefore, the presence of obstruction can be distinguished by measuring the pressure at the lower end of the obstruction; in particular, through AI, it was confirmed that the area located 29 mm below the obstruction is the region where pressure changes are most pronounced.

[0140]

[0141] Example 5: Verification of key factors through experiment

[0142] Experiments were conducted to verify whether the results of numerical analysis and XAI would be valid in actual diagnosis. The experiment aimed to confirm whether the differences in key characteristics between bladder outlet obstruction and detrusor dysfunction were not limited to simulations but were valid for diagnosing the cause in the actual lower urinary tract. A PDMS chip of the same size and shape as in the simulation was connected to the constructed lower urinary tract simulation device, and the flow rate of the gear pump was controlled via Python code while simultaneously measuring the pressure before and after the PDMS chip.

[0143] As a result, when the flow rate of the sine function profile was input, the pressure measured at the front of the PDMS chip showed the same trend as the simulation results in both bladder outlet obstruction and detrusor dysfunction.

[0144] In the pressure measurement results after the PDMS chip, the aforementioned rapid pressure drop and the point at which the pressure switches from a positive (+) to a negative (-) value were confirmed. In fact, as shown in Figure 10 (a), in bladder outlet obstruction, it was observed that the pressure dropped rapidly at the moment the flow rate decreased, whereas in the case of detrusor dysfunction, the amount of change was small.

[0145] To maximize the instantaneous change in pressure, the flow rate of the ramp function profile was input as shown in Fig. 10 (b). Then, the pressure at the moment when the flow rate instantaneously decreased to zero was examined in detail. As a result, it was confirmed that the pressure decreased more significantly in cases of bladder outlet obstruction than in cases of detrusor dysfunction. Furthermore, considering that the value is negative, it is expected that it can be used as a criterion for diagnosing lower urinary tract symptoms.

[0146] Clinical trial methods could include directly measuring pressure at the base of the obstruction or predicting pressure changes by measuring physical factors such as strain. The direct pressure measurement method is expected to enable diagnosis via a partially invasive approach, involving the insertion of a catheter equipped with a pressure sensor into the urethra. On the other hand, the pressure measurement method based on strain requires measuring the amount of deformation in the penis; however, since the amount of deformation is not significant, it is expected to be difficult to use in actual diagnosis.

[0147]

[0148] Example 6: Verification of the possibility of diagnosing lower urinary tract symptoms through pressure measurement at the lower part of the obstruction

[0149] While existing invasive urodynamic testing measures pressure by inserting catheters into the bladder or anus, the proposed diagnostic method is a partially invasive approach that measures pressure only at the lower end of the obstruction. In particular, it is highly valuable as a diagnostic method because it does not pass through the sphincter, which is the area that causes pain to the patient during the catheter insertion process into the bladder. Furthermore, by incorporating a method to visualize the area near the prostate, it is considered to have high potential to develop into a more efficient and precise diagnostic method for lower urinary tract symptoms.

Claims

1. A method for providing information necessary for diagnosing lower urinary tract symptoms, including the following steps: (a) a step of measuring the pressure inside the urethra during urination of a subject with lower urinary tract symptoms; and (b) A step to determine the type of lower urinary tract symptoms by analyzing changes in pressure within the urethra during urethral contraction during urination.

2. A method for providing information necessary for diagnosing lower urinary tract symptoms, wherein in the first paragraph, if the rate of decrease in pressure within the subject's urethra during the process of urethral contraction during urination is higher than that of a normal person, it is determined to be a bladder outlet obstruction type, and if the rate of decrease in pressure within the subject's urethra is not higher than that of a normal person, it is determined to be a detrusor muscle dysfunction type of lower urinary tract symptom.

3. A method for providing information necessary for diagnosing lower urinary tract symptoms, wherein in the first paragraph, if the time at which the pressure inside the subject's urethra changes from positive pressure to negative pressure is faster than that of a normal person during the process of urethral contraction during urination, it is determined to be a bladder outlet obstruction type, and if the time at which the pressure inside the subject's urethra changes from positive pressure to negative pressure is not faster than that of a normal person, it is determined to be a detrusor muscle dysfunction type of lower urinary tract symptom.

4. A method for providing information necessary for diagnosing lower urinary tract symptoms, wherein the pressure within the urethra in paragraph 1 is measured in the lower part of the urethra.

5. A method for providing information necessary for diagnosing lower urinary tract symptoms, wherein the pressure within the urethra is measured between 60 and 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as 1 and 100, respectively.

6. A lower urinary tract symptom diagnostic device comprising a pressure measurement sensor within the urethra.

7. A lower urinary tract symptom diagnostic device according to claim 6, wherein the device comprises a urethral insertion catheter.

8. A lower urinary tract symptom diagnostic device according to claim 6, wherein the urethral pressure measuring sensor measures changes in urethral pressure during urination.

9. A lower urinary tract symptom diagnostic device according to claim 6, wherein the pressure within the urethra is measured at the lower part of the urethra.

10. A lower urinary tract symptom diagnostic device according to claim 6, wherein the pressure within the urethra is measured between point 60 and point 90 when the urethra is divided into 100 equal parts and the starting point and ending point of the urethra are designated as point 1 and point 100, respectively.

11. A lower urinary tract symptom diagnostic device according to claim 6, wherein the lower urinary tract symptom is of the bladder outlet obstruction type or the detrusor dysfunction type.

Images