Description:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(See Section 10 and Rule 13)

Title of invention:
METHODS AND SYSTEMS FOR FLUID RETENTION ANALYSIS IN CHRONIC KIDNEY CARE

Applicant:
Tata Consultancy Services Limited
A company Incorporated in India under the Companies Act, 1956
Having address:
Nirmal Building, 9th Floor,
Nariman Point, Mumbai 400021,
Maharashtra, India

The following specification particularly describes the invention and the manner in which it is to be performed.
TECHNICAL FIELD
The disclosure herein generally relates to Chronic Kidney Disease (CKD), and, more particularly, to methods and systems for fluid retention analysis in Chronic Kidney Care using Generative Artificial Intelligence (AI) aided by Physics based modelling.

BACKGROUND
As per the World Health Organization projects CKD is predicted to be the 5th most common chronic disease in 2040. Causes of CKD are multi-factorial and diverse, but early-stage symptoms are often few and silent. Progression rates are highly variable, but patients encounter both an increased risk for end-stage kidney disease (ESKD) as well as increased cardiovascular risk. End-stage kidney disease incidence is generally low, but every single case carries a significant burden of illness and healthcare costs, making prevention by early intervention both desirable and worthwhile.
Major symptoms of the kidney failure include but are not limited to itchy skin or rashes, muscle cramps, feeling sick to your stomach or throwing up, not feeling hungry than normal, swelling in your feet and ankles, urinating (peeing) more or less than normal, foamy, frothy, or bubbly-looking urine, trouble catching your breath, and trouble falling or staying asleep. Since most of the ailments are silent and variant in nature pinpointing a universal cause or biomarker is difficult. Hence, the conventional techniques for detecting the CKD in the subject lack with efficiency and accuracy. Moreover, getting patient health data brings privacy and security issues. Cost is a big factor for organizations doing the research, development, and implementation of such digital biomarkers as well as for patients who need to procure these devices.

SUMMARY
Embodiments of the present disclosure present technological improvements as solutions to one or more of the above-mentioned technical problems recognized by the inventors in conventional systems.
In an aspect, a processor-implemented method for fluid retention analysis in Chronic Kidney Care is provided. The method including the steps of: receiving (i) a data associated with one or more Photoplethysmography (PPG) based biomarkers, (ii) a data associated with a varying blood volume between a systole and a diastole, and (iii) one or more reference PPG signals data, wherein each of the one or more reference PPG signals is recorded for one more predefined bio-parameters; instantiating a physics-based PPG simulation model with (i) the data associated with the one or more Photoplethysmography (PPG) based biomarkers, and (ii) the data associated with the varying blood volume between the systole and the diastole, to obtain a pulsatile PPG model; generating one or more pulsatile PPG signals, using the pulsatile PPG model; training a PlethAugment-based conditional generative adversarial network (CGAN) model comprising a generator and a discriminator, with (i) the one or more pulsatile PPG signals and (ii) the one or more reference PPG signals, to obtain a trained CKD detection model, wherein the generator and the discriminator are trained in tandem, and wherein the training comprises: (a) passing (i) each of the one or more pulsatile PPG signals and (ii) each of the one or more reference PPG signals, to the generator, to obtain (i) one or more encoded pulsatile PPG signals and (ii) one or more encoded reference PPG signals; (b) passing (i) an encoded pulsatile PPG signal of the one or more encoded pulsatile PPG signals and (ii) the one or more encoded reference PPG signals, at each iteration, to the discriminator, to determine a value of a loss function of the PlethAugment-based CGAN model; (c) backpropagating one or more network weights of the PlethAugment-based CGAN model, based on the value of the loss function; and (d) repeating the steps (b) through (c) for each of the one or more encoded pulsatile PPG signals, to obtain the trained CKD detection model; receiving an input PPG signal of a subject whose CKD is to be detected; and passing the input PPG signal of the subject to the trained CKD detection model, to detect a presence or an absence of the CKD in the subject.
In another aspect, a system for fluid retention analysis in Chronic Kidney Care is provided. The system includes: a memory storing instructions; one or more Input/Output (I/O) interfaces; and one or more hardware processors coupled to the memory via the one or more I/O interfaces, wherein the one or more hardware processors are configured by the instructions to: receive (i) a data associated with one or more Photoplethysmography (PPG) based biomarkers, (ii) a data associated with a varying blood volume between a systole and a diastole, and (iii) one or more reference PPG signals data, wherein each of the one or more reference PPG signals is recorded for one more predefined bio-parameters; instantiate a physics-based PPG simulation model with (i) the data associated with the one or more Photoplethysmography (PPG) based biomarkers, and (ii) the data associated with the varying blood volume between the systole and the diastole, to obtain a pulsatile PPG model; generate one or more pulsatile PPG signals, using the pulsatile PPG model; train a PlethAugment-based conditional generative adversarial network (CGAN) model comprising a generator and a discriminator, with (i) the one or more pulsatile PPG signals and (ii) the one or more reference PPG signals, to obtain a trained CKD detection model, wherein the generator and the discriminator are trained in tandem, and wherein the training comprises: (a) passing (i) each of the one or more pulsatile PPG signals and (ii) each of the one or more reference PPG signals, to the generator, to obtain (i) one or more encoded pulsatile PPG signals and (ii) one or more encoded reference PPG signals; (b) passing (i) an encoded pulsatile PPG signal of the one or more encoded pulsatile PPG signals and (ii) the one or more encoded reference PPG signals, at each iteration, to the discriminator, to determine a value of a loss function of the PlethAugment-based CGAN model; (c) backpropagating one or more network weights of the PlethAugment-based CGAN model, based on the value of the loss function; and (d) repeating the steps (b) through (c) for each of the one or more encoded pulsatile PPG signals, to obtain the trained CKD detection model; receive an input PPG signal of a subject whose CKD is to be detected; and pass the input PPG signal of the subject to the trained CKD detection model, to detect a presence or an absence of the CKD in the subject.
In yet another aspect, there is provided a computer program product comprising a non-transitory computer readable medium having a computer readable program embodied therein, wherein the computer readable program, when executed on a computing device, causes the computing device to: receive (i) a data associated with one or more Photoplethysmography (PPG) based biomarkers, (ii) a data associated with a varying blood volume between a systole and a diastole, and (iii) one or more reference PPG signals data, wherein each of the one or more reference PPG signals is recorded for one more predefined bio-parameters; instantiate a physics-based PPG simulation model with (i) the data associated with the one or more Photoplethysmography (PPG) based biomarkers, and (ii) the data associated with the varying blood volume between the systole and the diastole, to obtain a pulsatile PPG model; generate one or more pulsatile PPG signals, using the pulsatile PPG model; train a PlethAugment-based conditional generative adversarial network (CGAN) model comprising a generator and a discriminator, with (i) the one or more pulsatile PPG signals and (ii) the one or more reference PPG signals, to obtain a trained CKD detection model, wherein the generator and the discriminator are trained in tandem, and wherein the training comprises: (a) passing (i) each of the one or more pulsatile PPG signals and (ii) each of the one or more reference PPG signals, to the generator, to obtain (i) one or more encoded pulsatile PPG signals and (ii) one or more encoded reference PPG signals; (b) passing (i) an encoded pulsatile PPG signal of the one or more encoded pulsatile PPG signals and (ii) the one or more encoded reference PPG signals, at each iteration, to the discriminator, to determine a value of a loss function of the PlethAugment-based CGAN model; (c) backpropagating one or more network weights of the PlethAugment-based CGAN model, based on the value of the loss function; and (d) repeating the steps (b) through (c) for each of the one or more encoded pulsatile PPG signals, to obtain the trained CKD detection model; receive an input PPG signal of a subject whose CKD is to be detected; and pass the input PPG signal of the subject to the trained CKD detection model, to detect a presence or an absence of the CKD in the subject.
In an embodiment, the generator is an auto-encoder, and the discriminator is a time-series Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) model.
In an embodiment, the loss function of the PlethAugment-based CGAN model is a sum of a generator loss and a discriminator loss, and wherein the generator loss is defined as a function of reconstruction loss, and the discriminator loss is defined as function of Binary Cross-Entropy loss.

BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate exemplary embodiments and, together with the description, serve to explain the disclosed principles:
FIG. 1 is an exemplary block diagram of a system for fluid retention analysis in Chronic Kidney Care, in accordance with some embodiments of the present disclosure.
FIGS. 2A-2B illustrate exemplary flow diagrams of a processor-implemented method for fluid retention analysis in Chronic Kidney Care, using the system of FIG. 1, in accordance with some embodiments of the present disclosure.
FIG. 3 shows an exemplary physics-based PPG simulation model, in accordance with some embodiments of the present disclosure.
FIG. 4 is a flowchart showing the steps for obtaining the pulsatile PPG model by instantiating the physics-based PPG simulation model, in accordance with some embodiments of the present disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS
Exemplary embodiments are described with reference to the accompanying drawings. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. Wherever convenient, the same reference numbers are used throughout the drawings to refer to the same or like parts. While examples and features of disclosed principles are described herein, modifications, adaptations, and other implementations are possible without departing from the scope of the disclosed embodiments.
There are various recommended approaches for creating a digital biomarker that can be utilized for chronic kidney disease (CKD) detection. Some of them include Omics-based approach, Genetic markers, use of digital biomarkers, and a combination of biomarkers. The Omics-based approach uses technologies such as genomics, transcriptomics, proteomics, and metabolomics to identify potential biomarkers associated with CKD. These technologies allow for a comprehensive analysis of different molecular components and pathways involved in CKD. For example, transcriptomic analysis can identify biomarkers that indicate the risk of disease progression, while proteomic analysis can help identify kidney-derived proteins that could serve as biomarkers of renal dysfunction. By combining data from multiple omics approaches, we can gain a better understanding of CKD and identify potential biomarkers.
Some of genetic markers, such as genes and genetic variants, have been linked to the risk or early detection of CKD. For instance, certain genetic variants in the APOL1 gene are strongly associated with non-diabetic CKD and can be used for risk prediction. Genetic testing for these variants can help identify individuals at high risk for CKD development and progression. Additionally, studying genetic markers in ethnic minorities, who may have a higher genetic risk, can provide valuable insights for early intervention and disease management.
Biomedical signals such as Photoplethysmography (PPG) signals can be used to identify digital biomarkers which act as proxy to fluid retention since PPG is a volumetric measurement. A deep learning model will be used to discriminate between normal and abnormally high fluid levels in the tissue, which is indicative of CKD.
Since CKD is a complex disease with multiple factors involved, relying on a single biomarker may not be enough for accurate diagnosis and risk assessment. Therefore, a panel of biomarkers that includes genetic markers, proteins, metabolites, and other molecular components may be necessary to achieve high sensitivity and specificity in diagnosing CKD and identifying individuals at high risk of progression. By combining multiple biomarkers, we can capture the various changes that occur throughout the course of the disease and obtain a more comprehensive understanding of CKD.
The present disclosure solves the technical problems in the art with the methods and systems for fluid retention analysis in Chronic Kidney Care, which discloses a comprehensive approach involving omics technologies, genetic markers, and a combination of biomarkers can help in creating a specific digital biomarker for CKD detection.
The methods and systems of the present disclosure propose an in-silico model-based approach which is used to fuel a Generative AI engine to generate physiological signals pertaining to CKD for various stages across demographics. The in-silico model is a computer-based model that uses a physics-based model such as a Monte Carlo forward modelling to simulate the Photoplethysmography (PPG) signal. This model can mimic the water content in parts of the body like the finger and how it changes with the development and spread of chronic kidney disease (CKD). The methods and systems of the present disclosure work in three stages. In the first stage, a standard PPG waveform is simulated using the physics-based model and compared it to reference experimental PPGs to make sure that the simulated PPG signals are accurate. In the second stage, a Generative Adversarial Network (GAN) model is trained using the simulated PPG data and the reference experimental PPG data. In the third and the last stage, the discriminator model of the trained GAN model is employed to evaluate and analyze the test dataset of the subject whose CKD is to be detected.
Referring now to the drawings, and more particularly to FIG. 1 through FIG. 4, where similar reference characters denote corresponding features consistently throughout the figures, there are shown preferred embodiments, and these embodiments are described in the context of the following exemplary system and/or method.
FIG. 1 is an exemplary block diagram of a system 100 for generating for fluid retention analysis in Chronic Kidney Care, in accordance with some embodiments of the present disclosure. In an embodiment, the system 100 includes or is otherwise in communication with one or more hardware processors 104, communication interface device(s) or input/output (I/O) interface(s) 106, and one or more data storage devices or memory 102 operatively coupled to the one or more hardware processors 104. The one or more hardware processors 104, the memory 102, and the I/O interface(s) 106 may be coupled to a system bus 108 or a similar mechanism.
The I/O interface(s) 106 may include a variety of software and hardware interfaces, for example, a web interface, a graphical user interface (GUI), and the like. The I/O interface(s) 106 may include a variety of software and hardware interfaces, for example, interfaces for peripheral device(s), such as a keyboard, a mouse, an external memory, a plurality of sensor devices, a printer and the like. Further, the I/O interface(s) 106 may enable the system 100 to communicate with other devices, such as web servers and external databases.
The I/O interface(s) 106 can facilitate multiple communications within a wide variety of networks and protocol types, including wired networks, for example, local area network (LAN), cable, etc., and wireless networks, such as Wireless LAN (WLAN), cellular, or satellite. For the purpose, the I/O interface(s) 106 may include one or more ports for connecting a number of computing systems with one another or to another server computer. Further, the I/O interface(s) 106 may include one or more ports for connecting a number of devices to one another or to another server.
The one or more hardware processors 104 may be implemented as one or more microprocessors, microcomputers, microcontrollers, digital signal processors, central processing units, state machines, logic circuitries, and/or any devices that manipulate signals based on operational instructions. Among other capabilities, the one or more hardware processors 104 are configured to fetch and execute computer-readable instructions stored in the memory 102. In the context of the present disclosure, the expressions ‘processors’ and ‘hardware processors’ may be used interchangeably. In an embodiment, the system 100 can be implemented in a variety of computing systems, such as laptop computers, portable computers, notebooks, hand-held devices, workstations, mainframe computers, servers, a network cloud and the like.
The memory 102 may include any computer-readable medium known in the art including, for example, volatile memory, such as static random access memory (SRAM) and dynamic random access memory (DRAM), and/or non-volatile memory, such as read only memory (ROM), erasable programmable ROM, flash memories, hard disks, optical disks, and magnetic tapes. In an embodiment, the memory 102 includes a plurality of modules 102a and a repository 102b for storing data processed, received, and generated by one or more of the plurality of modules 102a. The plurality of modules 102a may include routines, programs, objects, components, data structures, and so on, which perform particular tasks or implement particular abstract data types.
The plurality of modules 102a may include programs or computer-readable instructions or coded instructions that supplement applications or functions performed by the system 100. The plurality of modules 102a may also be used as, signal processor(s), state machine(s), logic circuitries, and/or any other device or component that manipulates signals based on operational instructions. Further, the plurality of modules 102a can be used by hardware, by computer-readable instructions executed by the one or more hardware processors 104, or by a combination thereof. In an embodiment, the plurality of modules 102a can include various sub-modules (not shown in FIG. 1). Further, the memory 102 may include information pertaining to input(s)/output(s) of each step performed by the processor(s) 104 of the system 100 and methods of the present disclosure.
The repository 102b may include a database or a data engine. Further, the repository 102b amongst other things, may serve as a database or includes a plurality of databases for storing the data that is processed, received, or generated as a result of the execution of the plurality of modules 102a. Although the repository 102b is shown internal to the system 100, it will be noted that, in alternate embodiments, the repository 102b can also be implemented external to the system 100, where the repository 102b may be stored within an external database (not shown in FIG. 1) communicatively coupled to the system 100. The data contained within such external database may be periodically updated. For example, data may be added into the external database and/or existing data may be modified and/or non-useful data may be deleted from the external database. In one example, the data may be stored in an external system, such as a Lightweight Directory Access Protocol (LDAP) directory and a Relational Database Management System (RDBMS). In another embodiment, the data stored in the repository 102b may be distributed between the system 100 and the external database.
Referring to FIGS. 2A-2B, components and functionalities of the system 100 are described in accordance with an example embodiment of the present disclosure. For example, FIGS. 2A-2B illustrate exemplary flow diagrams of a processor-implemented method 200 for fluid retention analysis in Chronic Kidney Care, using the system of FIG. 1, in accordance with some embodiments of the present disclosure. Although the steps of the method 200 shown in FIGS. 2A-2B including process steps, method steps, techniques or the like may be described in a sequential order, such processes, methods, and techniques may be configured to work in alternate orders. In other words, any sequence or order of steps that may be described does not necessarily indicate a requirement that the steps be performed in that order. The steps of processes described herein may be performed in any practical order. Further, some steps may be performed simultaneously, or some steps may be performed alone or independently.
At step 202 of the method 200, the one or more hardware processors 104 of the system 100 are configured to receive a data associated with one or more Photoplethysmography (PPG) based biomarkers, a data associated with a varying blood volume between a systole and a diastole, and one or more reference PPG signals. The one or more Photoplethysmography (PPG) based biomarkers refer to a combination of biomarkers that can help in creating a specific digital biomarker for CKD detection.
A comprehensive data-set that includes information about patients with CKD, including their medical history, clinical measurements, laboratory results, imaging data, and any other relevant information. This data-set will serve as the foundation for identifying the one or more potential biomarkers. In an embodiment, the one or more Photoplethysmography (PPG) based biomarkers include but are not limited to creatine, water content, and Beta-protein. The data associated with one or more Photoplethysmography (PPG) based biomarkers are the records of the biomarkers available from the PPG signals.
The data associated with the varying blood volume between the systole and the diastole refers to the variations in the input blood volume between the systole and the diastole. Here the input blood volume V_b is considered such that the volume fraction of arterial and venous blood is equally distributed, i.e., V_A:V_V=1:1. The one or more reference PPG signals are the real PPG signals that are recorded for one more predefined bio-parameters. In an embodiment, the one more predefined bio-parameters considered for recording the one or more reference PPG signals include but are not limited to age of the subjects, weight of the subjects, gender of the subjects, skin-tone of the subjects, fluid retention levels of the subjects, and body mass index (BMI) of the subjects. Here the subject refers to the living being including human beings and animals and including with and without CKD.
At step 204 of the method 200, the one or more hardware processors 104 of the system 100 are configured to instantiate a physics-based PPG simulation model with (i) the data associated with the one or more Photoplethysmography (PPG) based biomarkers, and (ii) the data associated with the varying blood volume between the systole and the diastole received at step 202 of the method 200. In the present disclosure, a Monte Carlo simulation model is used as the physics-based PPG simulation model. After the instantiation with the data associated with the one or more Photoplethysmography (PPG) based biomarkers, and (ii) the data associated with the varying blood volume between the systole and the diastole received, the physics-based PPG simulation model becomes a pulsatile PPG model which can be able to generate the dynamic PPG signals.
The physics-based PPG simulation model in general is a static light-tissue interaction-based PPG simulator. A traditional PPG sensor illuminates a tissue-section, usually, of a peripheral part of the body, by optical radiation, and the reflected/ transmitted light, is collected continuously along the cardiac cycles as the PPG signal. The physics-based PPG simulation model simulates the propagation of light through the heterogeneous tissue-section of the peripheral section of the body (e.g., fingertip) utilizing the forward Monte Carlo modeling strategy.
FIG. 3 shows an exemplary physics-based PPG simulation model, in accordance with some embodiments of the present disclosure. As shown in FIG. 3, the pathway of photons through tissue is determined by the geometrical configuration, i.e., how the sensor is placed on the tissue; and the anatomical configuration, i.e., the layer-stratification of the tissue-region of interest (ROI). In the present disclosure, a reflectance mode PPG sensor is assumed to be placed on the fingertip. The ROI is presented in a three-dimensional Cartesian co-ordinate plane, where the optical source of the sensor is placed at the origin of the co-ordinate system and the optical detector is placed as a distance d from the source. The detailed heterogeneous layer and sublayer stratification along with the various vascular distribution at different layers is considered.
In the given anatomical and geometrical configuration, the optical pathway through tissue is simulated by the random sampling of the probability of the interactions between light and tissue (e.g., absorption and scattering). The functional steps of the PPG simulator are:
Step 1: A photon packet with an initial direction and position co-ordinate and an initial statistical weight w=1 is launched onto the tissue surface.
Step 2: After the initial correction for the reflection at the tissue surface, the photon packet is propagated through a step-size (l), calculated by random sampling of the probability of photon absorption and scattering coefficients (µ_a and µ_s), i.e.,
l=(ln?(?))/(µ_a+µ_s ) (1)
where ? is a computer-generated pseudo-random number (0