System for flow measurement and control during transcatheter medical procedure and methods of use thereof

Abstract

The disclosure relates to systems and methods for flow measurement and control for transcatheter medical procedures such as embolization of a target tissue, organ, or vessel, specifically those involving targeted delivery of therapeutic agents to specific anatomical locations.

Description

SYSTEM FOR FLOW MEASUREMENT AND CONTROL DURING TRANSCATHETER MEDICAL PROCEDURE AND METHODS OF USE THEREOFBACKGROUND

[0001] This disclosure relates to a therapeutic agent delivery system for transcatheter injection procedures, including a flow measurement system and associated methods for controlled delivery of therapeutic agents to target locations within the body via catheter.

[0002] Transcatheter embolization represents a fundamental technique within interventional radiology and interventional oncology practice. The procedure employs various embolic materials including particulate agents, liquid embolic compounds, and metallic coils to achieve selective vascular occlusion. Catheters serve as the delivery conduit for these therapeutic materials to designated anatomical sites.

[0003] Nontarget embolization (NTE) refers to inadvertent deposition of embolic material in unintended vascular territories, either within the target organ or in separate organs. This complication poses significant clinical risk during transcatheter embolization procedures. Reflux of embolic material during inj ection, particularly when employing particulate or liquid agents, represents one frequently observed mechanism leading to nontarget embolization.

[0004] Reflux of particulate or other embolic agents is commonly associated with changes in local hemodynamics during the embolization phase. As progressive occlusion occurs within distal arterioles and capillary beds, proximal arterial resistance increases. Intravascular pressure within the arterial system reflects multiple hemodynamic variables including vessel caliber, systemic blood pressure, cardiac output, vessel wall compliance, and fluid properties. When downstream capillary beds undergo acute occlusion, increased resistance in the affected vascular distribution can promote blood flow redistribution to adjacent patent capillary networks, potentially facilitating migration of embolic material from previously treated vessels into collateral pathways.

[0005] Angiographically guided embolization under conditions of altered and sometime pulsatile intravascular pressure gradients has been observed to contribute to nontarget embolization events.Excessive injection force, whether applied manually or via mechanical injection devices, may produce not only reflux and nontarget deposition of embolic particles but also recanalization of previously embolized vessels, potentially resulting in renewed perfusion of target tissue.

[0006] The disclosed systems and methods intend to address these shortcomings.SUMMARY

[0007] Provided herein are systems for real-time flow measurement during a transcatheter injection procedure, and methods of use thereof for predefined and controlled delivering therapeutic agents into a target location within the body through a catheter.

[0008] Accordingly and in an exemplary implementation, provided herein is a flow measurement and control system for use in a transcatheter medical procedure adapted to administer a therapeutic agent to a target location within a body of a subject in need thereof, comprising: at least one catheter defining a longitudinal axis and having a proximal end in liquid communication with an infusion device, providing an unobstructed flow of the therapeutic agent through the catheter, and a distal end adapted, sized and configured to be inserted within the body, the system operable to administer the therapeutic agent to the target location; a plurality of sensors integrated within the catheter and axially spaced from each other, the plurality of sensors configured, in real time, to sense at least one flow parameter of the unobstructed flow of the therapeutic agent; and a central processing module (CPM), the CPM being in communication with the infusion device, and each of the plurality of axially spaced sensors, the CPM further comprises at least one processor in communication with a non-transitory memory device storing thereon a computer-readable medium with a set of executable instructions, configured, when executed by the at least one processor, to cause the CPM to: receive a signal from each of the plurality of sensors; measure the at least one flow parameter using at least two axially spaced sensors: and based on a measured difference between the signals received from each of the at least two sensors control flow parameter of the therapeutic agent, and / or a catheter-related parameter.

[0009] In another exemplary implementation, provided herein is a methodBRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG. 1, is a simplified schematic illustration of an exemplary implementation of a flow measurement system for a transcatheter medical procedure;

[0011] FIG. 2, is a simplified schematic illustration of another exemplary implementation of a flow measurement system for a transcatheter medical procedure; and

[0012] FIG. 3, is a schematic representation of an exemplary implementation the various CPM module.DETAILED DESCRIPTION

[0013] Provided herein are exemplary implementations of systems of flow measurement and control for transcatheter medical procedures, specifically those involving targeted delivery of therapeutic agents to specific anatomical locations. In interventional radiology and interventional oncology procedures, precise control over the delivery of therapeutic agents such as embolic materials, chemotherapeutic agents, or radiopharmaceuticals is critical to achieving optimal therapeutic outcomeswhile minimizing systemic exposure and complications. Existing catheter-based delivery systems often lack real-time feedback mechanisms to monitor and adjust flow parameters during agent administration, leading to unpredictable deposition patterns, incomplete target coverage, or inadvertent non-target embolization. The disclosure addresses these limitations by providing an integrated sensor-based flow measurement system with closed-loop control capability that enables continuous monitoring and dynamic adjustment of delivery parameters throughout the procedure.

[0014] The flow measurement and control system comprises at least one catheter that serves as the primary conduit for therapeutic agent delivery. The catheter defines a longitudinal axis extending from a proximal end to a distal end, establishing the primary direction of fluid flow and providing the structural framework for the integrated sensing elements. The catheter construction could utilize biocompatible polymer materials such as polyurethane, nylon, polyether block amide (PEBA), or polytetrafluoroethylene (PTFE) with durometer hardness values ranging from 40D to 72D on the Shore scale, selected to provide sufficient column strength for navigation and guidance through tortuous vascular anatomy, while maintaining flexibility to conform to vessel geometry. Wall thickness could range from 0.05 millimeters to 0.30 millimeters depending on the catheter outer diameter, which may vary from about 0.67 millimeters to about 2.33 millimeters (2 French to 7 French) to accommodate different clinical applications and vascular access sites. The catheter may further incorporate reinforcement elements such as braided stainless steel wire, nitinol coils, or embedded polymer fibers within the wall structure to enhance kink resistance and torque transmission while maintaining flexibility, with encountered braid angles typically between 30 and 60 degrees relative to the longitudinal axis.

[0015] Accordingly, the proximal end of the catheter, which establishes liquid communication with an infusion device, creates a sealed fluid pathway that prevents leakage and maintains pressure integrity throughout the delivery system. In certain exemplary implementations, the proximal connection interface may incorporate a standard luer lock fitting conforming to ISO 594 specifications, a threaded connector with O-ring seal, or a compression fitting that accommodates the catheter outer diameter with minimal dead volume. The connection geometry is adapted, sized and configured to ensure alignment between the catheter lumen and the infusion device outlet, maintaining concentricity to prevent flow disturbances at the interface. The infusion device may comprise, for example; a motorized syringe pump capable of delivering flow rates (depending on the size of the syringe), ranging from about 0.05 milliliters per minute to about 20 milliliters per minute with volumetric accuracy not exceeding ±2%, a peristaltic pump providing pulsatile flow with controllable pulse frequency, a pressure-regulated reservoir system maintaining constant driving pressure, or other similar infusion devices. The infusion device is configured to communicate electronically with the CPM, to receive control commands and may further incorporate motor load sensors, force sensors or pressure transducers to monitor delivery resistance.

[0016] The catheter provides an unobstructed flow path for the therapeutic agent. In the context of the disclosure, the term “unobstructed flow” means that the internal lumen maintains continuous patency without restrictions, valves, or geometric discontinuities that would impede fluid movement, create dead zones or turbulence unrelated to flowrate, where a therapeutic or other flowing agent could accumulate. The lumen inner diameter typically ranges from 0.3 millimeters to 1.8 millimeters depending on the catheter size and intended application, with surface roughness values below Ra=~1.6 pm configured to minimize flow resistance and prevent particle adhesion. The unobstructed flow characteristic ensures that therapeutic agents with varying rheological properties, including suspensions and / or simple and / or duplex emulsions of embolic microspheres ranging from 40 pm to 1200 pm in diameter, liquid embolics with viscosities from between about 5 centipoise to about 500 centipoise, or drug-eluting beads in carrier solutions, can be delivered without occlusion or unpredictable flow behavior. The lumen geometry remains substantially cylindrical throughout its length, though gradual tapers may be incorporated to optimize flow velocity profiles, typically with taper angles not exceeding 5 degrees to prevent flow separation.

[0017] Similarly, the distal end of the catheter is adapted, sized, and configured for insertion within the body of the subject, incorporating design features that facilitate intravascular navigation, positioning accuracy, and biocompatibility. The distal tip region may extend between about 5 millimeters (mm) and about 30 mm from the terminal opening and may incorporate a tapered outer profile to reduce vessel trauma during advancement, with tip outer diameters typically ranging between about 0.2 French and about 1 French smaller than the proximal catheter body. The tip configuration may feature a straight geometry for selective vessel cannulation, an angled configuration between about 30° and 900for directing flow toward specific vascular territories, or a curved shape with radius of curvature between about 5 mm and about 40 mm to facilitate navigation through branching anatomy. Radiopaque markers comprising, for example; platinum, gold, tungsten, or tantalum can be embedded in, or attached to the distal tip region to enable fluoroscopic visualization during positioning, with marker bands that could range from about 0.5 mm and about 3 mm in axial length and be positioned within about 5 mm of the distal end’s opening. The distal opening itself may incorporate beveled edges, at, for example, between 30° and about 45°, configured to reduce endothelial trauma during contact and to optimize flow distribution patterns as the agent exits into the target vasculature.

[0018] Further, the system operates to administer the therapeutic agent to the target location, operating as an integrated assembly where the catheter positioning, flow delivery, sensing, and control functions are configured to work in an integrated manner to achieve localized therapeutic agent deposition. The target location may be, for example; a tumor vasculature bed in hepatocellular carcinoma treatment, a uterine fibroid arterial supply, an arteriovenous malformation nidus, or other pathologicaltissue requiring selective embolization or drug delivery. The system is operable to enable the operator to advance the distal catheter tip to a position proximate to or within the target vasculature, for example, under fluoroscopic guidance, establish initial flow parameters on the infusion device, and then rely on automated sensing and control functions to maintain optimal delivery characteristics throughout the procedure.

[0019] In the context of the disclosure, the term embolization refers to a process or state in which a physiological lumen, blood vessel, organ, or other target tissue or location is obstructed by the lodgment of a material mass, which may be referred to as an embolus or embolic material. The term target tissue is intended to be broad and may be, for example, a blood vessel, organ, tumor, fibroid, cell mass, aneurysm, cancer, tumor, hypervascular tumor (cancerous or benign), aneurysm, aortic aneurysm, abdominal aortic aneurysm, peripheral aneurysm, hemostasis, vascular laceration, venous laceration, or tissue having a pathological condition. In the case where a target location is served by a blood vessel, embolization of the blood vessel that serves the target tissue causes the target tissue to be embolized, for example, embolization of blood vessels serving a tumor is considered to be an embolization of the tumor. Additionally, the embolization may take place in a target lumen, for instance a blood vessel, artery, vein, or other physiological lumen.

[0020] Facilitating the system’s operation, a plurality of sensors are integrated within the catheter structure, meaning they are incorporated into or embedded within the catheter wall or lumen in a manner that maintains structural integrity, without any flow obstruction, while enabling direct contact with, or proximity to the flowing therapeutic agent. Integration to the lumen wall distinguishes these sensors from external monitoring devices and ensures that measurements reflect actual flow conditions at the point of sensing and in real time, rather than proximal measurements that may not account for catheter compliance (or flexibility and pressure drops), flow resistance, or other dynamic factors. In certain exemplary implementations, the integration method may involve, for example; embedding thin-film sensor elements between catheter wall layers during a multi-layer extrusion or lamination process, positioning microelectromechanical systems (MEMS) sensor chips within recessed pockets machined into the catheter wall with subsequent overmolding, or utilizing laser micromachining to create sensor cavities that are then filled with sensing materials and sealed. Wire interconnections between sensors and proximal connection points can utilize stranded or solid conductor wires ranging between about 44 average wire gauge (AWG) and about 50 AW G, routed in helical or straight patterns within or along the catheter wall to minimize impact on flexibility and lumen diameter. Conductor insulation is further configured to withstand sterilization processes, comprising for example; polyimide, PTFE, or parylene coatings with dielectric strength of about 500 volts per 2.5 pm.

[0021] The plurality of sensors are axially spaced from each other along the catheter longitudinal axis, creating a distributed measurement array that enables differential sensing and spatial flow characterization. Axial spacing between adjacent sensors can range for example, between about 10 mm and about 150 mm depending on the catheter length, sensor type, and clinical application, with spacing selected to provide measurable signal differences under expected flow conditions while maintaining sufficient sensor quantity for comprehensive flow profde assessment. For catheters used for example, in hepatic artery embolization, sensor spacing of 30 millimeters to 80 millimeters can be used to provide effective resolution for detecting flow variations due to catheter tip position, vessel diameter changes, or developing occlusions. The specific axial positions of sensors may be predetermined during manufacturing to create uniform spacing intervals, or may be strategically positioned at locations corresponding to anticipated catheter regions of interest, such as positioning sensors near the distal tip, at the transition between catheter shaft segments of different flexibility, and at the proximal region where flow enters from the infusion device.

[0022] Accordingly, the plurality of sensors are each configured to sense, in real time, at least one flow parameter of the unobstructed flow of the therapeutic agent. In the context of the disclosure, “real-time sensing” means that measurements are acquired continuously or at sampling frequencies sufficient to capture dynamic flow changes as they occur during agent delivery, such as, for example, at rates ranging between about 1 Hz and about 1000 Hz depending on the parameter being measured and expected rate of change. Flow parameters that may be sensed include volumetric flow rate, flow velocity, pressure, temperature, fluid viscosity, electrical impedance, optical absorbance, or combinations thereof. When used, pressure sensors may comprise piezoresistive elements fabricated from doped silicon with pressure-dependent resistance changes, capacitive sensors where pressure-induced diaphragm deflection alters capacitance between electrodes, or piezoelectric materials generating voltage proportional to applied stress. For example: pressure sensor diaphragm dimensions could range between about 0.5 mm and about 3 mm in diameter with thickness ranging between about 10 pm and about 100 pm, providing pressure measurement ranges from 0 to 300 mmHg with resolution of 1 mmHg or better, likewise, flow velocity sensors may utilize thermal anemometry principles where a heated element experiences cooling proportional to flow velocity, with heating elements comprising for example, thin-film platinum or nickel resistors maintained at constant temperature above ambient fluid temperature, typically ranging between about 5 °C and about 20 °C above fluid temperature, and measuring the power required to maintain constant temperature as an indication of flow velocity. Alternative flow velocity sensing may employ ultrasonic transit time measurements, magnetic resonance, or optical techniques (e.g., TOF). Temperature sensors provide information about fluid temperature variations that may indicate mixing with blood, metabolic heat generation in tissue, or changes in agent viscosity, utilizing thermistor elements withnegative temperature coefficients or resistance temperature detectors with positive temperature coefficients, typically providing temperature resolution of 0.1 °C or better.

[0023] The central processing module (CPM) is configured and is operable as the computational and control hub of the system, integrating sensor data, executing control algorithms, and issuing commands to the infusion device to regulate delivery parameters. The CPM is in communication with the infusion device, establishing bidirectional data exchange through wired interfaces such as RS-232, RS-485, USB, or Ethernet connections, or in other exemplary implementations, through wireless protocols such as Bluetooth or proprietary radiofrequency links operating in the ISM bands. Communication with the infusion device can be configured to enable the CPM to issue flow rate commands, receive status information about delivered volume and current operating parameters, and implement closed-loop control where commanded flow rates are adjusted based on real-time sensor feedback. The communication interface can be configured to operate at data rates ranging between about 9600 baud and about 1 Mbaud, sufficient to transmit control commands and status updates, maintaining latency below 100 milliseconds (ms) to enable responsive control.

[0024] Additionally, the CPM is also in communication with each of the plurality of axially spaced sensors, receiving measurement signals that may be transmitted as analog voltage or current signals, digital data packets, or modulated signals encoded with sensor identification and measurement value. Sensor communication may be deployed with individual dedicated conductors for each sensor, multiplexed signal lines where sensors share common communication channels with time-division or (MAC) address-based selection, or bus architectures where sensors are coupled in parallel with individual addressability. Signal conditioning circuitry such as DSPs, which may be located proximally near the CPM or distributed along the catheter near the sensors, can be configured to perform amplification and / or normalization of low-level sensor signals, typically providing gain ranging between about 10 and about 1000, filtering to remove noise and interference, typically with low-pass cutoff frequencies ranging between about 10 Hz and about 500 Hz, analog-to-digital conversion with resolution ranging typically between 12 bits and 24 bits, and signal linearization to compensate for nonlinear sensor response characteristics. The communication architecture can be configured to maintain signal integrity over the catheter length, which may extend from about 65 centimeters (cm) for peripheral applications and about 150 cm for visceral interventions, implementing shielding, twisted-pair configurations, or differential signaling to minimize electromagnetic interference from fluoroscopy equipment and other sources in the interventional suite.

[0025] The CPM also comprises at least one processor, which may be a microcontroller unit integrating processing core, memory, and peripheral interfaces in a single integrated circuit, or a microprocessor requiring external support circuitry, a digital signal processor optimized for repetitivemathematical operations on streaming data, or a field-programmable gate array (FPGA), providing hardware-level parallel processing capability. The processor can be configured to operate at clock frequencies ranging between about 50 MHz and about 2 GHz, depending on computational requirements, with architectures such as ARM Cortex-M series for embedded control applications or ARM Cortex-A series for more complex processing and user interface management. The processor can be configured to execute instructions stored in memory at rates ranging between about 1 MIPS and about 1000 MIPS -sufficient to perform sensor data acquisition, signal processing, control algorithm execution, and communication functions within the real-time constraints of the application.

[0026] The processor is in communication with a non-transitory memory device, referring to a physical storage medium that retains data when power is removed, as distinguished from volatile memory such as RAM that requires continuous power to maintain stored information. The non-transitory memory device stores a computer-readable medium comprising the physical substrate that holds data in a format interpretable by the processor, which could be organized as binary patterns representing machine code instructions and data structures. Tire memory device may comprise for example; flash memory utilizing floating-gate transistors to store charge representing binary states with retention exceeding 10 years, EEPROM providing byte-level reprogrammability, magnetic storage, or other persistent storage technologies currently available or later developed. Memory capacity typically can range between about 64 kilobytes to several megabytes for program code storage, with additional RAM ranging from 16 kilobytes to several megabytes for runtime data storage and computational workspace. Furthermore, the computer-readable medium contains a set of executable instructions, referring in certain exemplary implementations to machine code or firmware that the processor can fetch, decode, and execute to perform the specified functions of data acquisition, measurement calculation, decision logic, and control output generation.

[0027] The executable instructions are configured, when executed by the at least one processor, to cause the GPM to receive a signal from each of the plurality of sensors, which involves initiating communication with each sensor through the communication interface, acquiring the sensor measurement data which may be transmitted, for example; as analog voltage levels ranging between 0 and 5 volts or 0 and 10 volts corresponding to the measured parameter range, digital values encoded as binary numbers representing the measurement, or modulated signals requiring demodulation. The receiving function can comprise, for example; error detection to identify corrupted or missing data, timestamping to associate measurements with acquisition time for temporal analysis, and buffering to temporarily store received data for subsequent processing. As indicated herein, the receiving function operates continuously or periodically at update rates sufficient to capture flow dynamics, and can be configured to create timeseries datasets for each sensor.

[0028] The executable instructions further cause the CPM to measure the at least one flow parameter using at least two axially spaced sensors. Measurement using multiple sensors enables differential sensing techniques that provide greater accuracy and information content than single-point measurements. For pressure measurement, the CPM can be configured to calculate pressure differential between two axially spaced sensors by subtracting the distal sensor pressure value from the proximal sensor pressure value, providing information about flow resistance and pressure drop across the catheter segment. This pressure differential would correlate with flow rate according to fluid dynamics principles, with the relationship depending on catheter geometry, fluid viscosity, and flow regime. For flow velocity measurement, the CPM may be configured to calculate velocity by measuring the transit time for thermal disturbances or flow features to travel between two axially spaced sensors, dividing the known sensor spacing by the measured transit time. Similarly, temperature measurements from axially spaced sensors can enable detection of temperature gradients that may indicate fluid mixing, heat loss to surrounding tissue, or changes in metabolic activity. The measurement function may apply calibration factors stored in memory to convert raw sensor signals into engineering units such as mmHg for pressure, mL / min for flow rate, or degrees Celsius for temperature, with calibration coefficients typically determined during manufacturing through comparison with reference measurement instruments traceable to national standards, and changing based on patient-specific machine-learning algorithms.

[0029] As indicated, the executable instructions cause the CPM to control at least one flow parameter of the therapeutic agent and / or a catheter-related parameter based on a measured difference between the signals received from each of the at least two sensors. In other words, the CPM can be configured to implement a closed-loop feedback algorithm that would compare the measured difference with target values or thresholds, and generates control commands to adjust system parameters to achieve or maintain desired operating conditions. As indicated, the measured difference may be a pressure differential, flow velocity difference, temperature gradient, or other differential parameter calculated from the at least two sensor signals. The control algorithm can be configured to implement proportional control where the control output magnitude is proportional to the error between measured and target values with proportional gain constants typically between 0.1 and 10, proportional-integral control adding an integration term that accumulates error over time to eliminate steady-state offset with integral time constants ranging between about 0.1 sec. and about 10 sec., or proportional -integral-derivative (PID) control adding a derivative term responsive to rate of change of error with derivative time constants ranging between 0.01 seconds and 1 second. The control algorithm can be configured to generate control commands that are transmitted to the infusion device to adjust flow rate upward or downward, in increments ranging between 0.01 mL / min and 1 mL / min per control cycle, to maintain pressuredifferential within a target range, to compensate for increasing flow resistance as embolization progresses, or to prevent excessive pressure that could cause vessel rupture or non-target embolization.

[0030] In another exemplary implementation, control of flow parameters may further involve, for example; modulating volumetric flow rate delivered by the infusion device to maintain constant pressure differential despite changing flow resistance, regulating pressure at the catheter rip to remain below threshold values that would cause vessel damage (e.g., burst), adjusting flow pulsatility by varying (peristaltic) pump speed in cyclic patterns to enhance agent distribution, or temporarily halting flow when sensor signals indicate occlusion or reflux. Control of catheter-related parameters may also involve generating alerts or notifications to the operator when sensor measurements indicate catheter rip displacement based on sudden pressure or flow changes, when temperature measurements suggest catheter tip position relative to metabolically active tissue, or when flow resistance increases beyond thresholds indicating need for catheter repositioning. The control function operates continuously throughout the therapeutic agent delivery procedure, executing control cycles at the frequencies disclosed, providing dynamic adjustment that adapts to changing anatomical conditions, progressive embolization effects, and variations in agent properties, and all in real-time.

[0031] Alternative implementations of the catheter may incorporate additional lumens for guidewire passage, contrast injection, or pressure measurement reference, with dual-lumen configurations featuring a primary lumen for therapeutic agent delivery with inner diameter ranging for example between about 0.4 mm and about 1.5 mm and a secondary lumen for guidewire, sized with inner diameter of between about 0.35 mm and about 0.90 mm. Sensor types may further include combinations of pressure, temperature, impedance, and optical sensors providing complementary measurement modalities for comprehensive flow characterization. The number of sensors may range from two to ten or more, with increased sensor count providing enhanced spatial resolution for flow profile reconstruction. The CPM may also incorporate wireless communication capability for remote monitoring, touchscreen user interfaces for parameter entry and real-time display of sensor measurements and trends, and data logging functions storing complete procedure records for subsequent analysis and documentation. Manufacturing of the integrated sensor catheter could involve precision processes including micro-injection molding of catheter components with dimensional tolerances within plus or minus 0.025 millimeters, laser welding or thermal bonding of catheter segments with bond strength exceeding 5 Newtons for catheters in the 5 French size range, and automated conductor routing and connection with pull strength exceeding 0.5 Newtons for conductor-to-sensor joints. Sterilization compatibility requires that all materials and assembled components withstand ethylene oxide exposure, gamma irradiation to 25 kGy minimum dose, or electron beam sterilization without degradation of mechanical properties or electrical performance.

[0032] Accordingly and in another exemplary implementation, provided herein is a flow measurement and control system for use in a transcatheter medical procedure adapted to administer a therapeutic agent to a target location within a body of a subject in need thereof, comprising: at least one catheter defining a longitudinal axis and having a proximal end in liquid communication with an infusion device, providing an unobstructed flow of the therapeutic agent through the catheter, and a distal end adapted, sized and configured to be inserted within the body, the system operable to administer the therapeutic agent to the target location; a plurality of sensors integrated within the catheter and axially spaced from each other, the plurality of sensors configured, in real time, to sense at least one flow parameter of the unobstructed flow of the therapeutic agent; and a central processing module (CPM), the CPM being in communication with the infusion device, and each of the plurality of axially spaced sensors, the CPM further comprises at least one processor in communication with a non-transitory memory device storing thereon a computer-readable medium with a set of executable instructions, configured, when executed by the at least one processor, to cause the CPM to: receive a signal from each of the plurality of sensors; measure the at least one flow parameter using at least two axially spaced sensors; and based on a measured difference between the signals received from each of the at least two sensors control flow parameter of the therapeutic agent, and / or a catheter-related parameter.

[0033] In addition, a machine learning module is integrated within the set of executable instructions used in the systems disclosed, which provides advanced computational capabilities for realtime analysis and predictive control of therapeutic agent delivery through the catheter system (see e.g., 300, FIG.3). The real-time signal processing module 301 operates continuously to receive, filter, and condition raw sensor data from the plurality of axially spaced sensors, performing operations including noise reduction through digital filtering algorithms such as, for example; Kalman filtering, or Butterworth filters, signal normalization to account for sensor-to-sensor variation, and temporal alignment of signals received from different axial positions along the catheter length to ensure accurate differential measurements. This module can be configured to process sensor data at frequencies configured to balance temporal resolution with computational efficiency, and applies preprocessing algorithms to extract relevant features from the raw pressure or flow signals, including but not limited to moving averages, derivative calculations to detect rate of change in flow parameters, and frequency domain analysis to identify periodic fluctuations indicative of catheter occlusion or vascular pulsatility. Furthermore, the machine learning inference module 302 is operable to implement trained neural network models, decision tree ensembles, support vector machines, or other (initially) supervised (and later unsupervised) learning algorithms that have been previously trained on historical catheter flow data to classify current flow conditions, predict impending occlusion events, and identify abnormal flow patterns that may indicate catheter malposition, vessel spasm, or thrombus formation at the distal tip. In certain exemplaryimplementations, the inference module employs convolutional neural networks (CNNs) with onedimensional temporal convolution layers to process time-series sensor data, or recurrent neural networks (RNNs) including long short-term memory (LSTM) architectures to capture temporal dependencies in flow parameter evolution over the course of a therapeutic agent infusion procedure. The predictive modeling module 303 is configured to utilize the outputs from the inference module in combination with subject-specific anatomical data, catheter geometry parameters, and therapeutic agent viscosity characteristics to forecast future flow conditions over time horizons ranging from 10 seconds to 5 minutes, enabling proactive adjustment of infusion device parameters before problematic flow conditions develop. This module can be configured to implement regression models, probabilistic graphical models such as Bayesian networks, or physics-informed neural networks that incorporate fundamental fluid dynamics principles governing laminar flow through cylindrical conduits, including the Hagen-Poiseuille equation for pressure-driven flow and modifications thereof to account for non-Newtonian behavior of certain therapeutic agents such as drug-eluting microsphere suspensions or contrast media. The application programming interface (API) module 304 can be configured to provide standardized communication protocols, enabling the machine learning module 300 to exchange data with the CPM 130 (see e.g., FIG. 1), the infusion device control systems, and external data sources including hospital information systems, electronic medical records, or cloud-based data repositories containing aggregated procedural data from multiple institutions. The API implements RESTful web service architecture, WebSocket protocols for bidirectional real-time communication, or proprietary binary communication protocols optimized for low-latency data transfer, and includes authentication mechanisms to ensure secure data exchange in compliance with healthcare data privacy regulations. Through the API, the machine learning module can receive updated model parameters, access expanded Paining datasets for continuous learning and model refinement, and transmit procedural outcome data for post-hoc analysis and population-level statistical studies. The integration of these four submodules within the machine learning module enables the system to transition from purely reactive control based on instantaneous sensor measurements to anticipatory control that adjusts infusion parameters in advance of predicted flow disturbances, thereby improving the consistency and safety of therapeutic agent delivery to the target location within the subject's body.

[0034] In certain exemplary implementations, the plurality of sensors used are specifically pressure sensors, each comprising a pressure-sensitive element adapted, sized, and configured to measure, in real time, absolute pressure or differential pressure of the therapeutic agent within the catheter lumen at discrete axial locations. For example, each pressure sensor can comprise a micro-electromechanical systems (MEMS) pressure transducer with a pressure-sensitive diaphragm having a diameter ranging for example, between 0.5 millimeters and 3 millimeters, fabricated from silicon, silicon carbide, orbiocompatible polymer materials, and incorporating piezoresistive sensing elements, capacitive sensing elements, or optical sensing elements based on Fabry-Perot interferometry to convert mechanical diaphragm deflection into an electrical signal proportional to applied pressure. The pressure sensors can be distributed along a length of the catheter that is larger than eighty percent (80%) of the total catheter length, measured from the proximal end in communication with the infusion device, to the distal end adapted for insertion within the subject's body, ensuring comprehensive spatial coverage of pressure distribution throughout substantially the entire fluid path from the infusion device to the target location. For a catheter length of between about 100 cm., and about 150 cm., as employed for example, in in hepatic artery chemoembolization or other similar transcatheter procedures, the pressure sensors can be positioned at intervals of between about 5 cm., and about 20 cm., with at least two sensors and up to twenty sensors distributed along the catheter length to provide sufficient spatial resolution for accurate pressure gradient mapping, while maintaining catheter flexibility and structural integrity. The axial spacing between adjacent sensors can be selected based on the expected pressure drop per unit length for the specific therapeutic agent being administered, with higher viscosity agents such as drug-eluting bead suspensions requiring closer sensor spacing to detect localized pressure increases indicative of catheter obstruction, while lower viscosity agents such as liquid chemotherapy formulations may employ wider sensor spacing. The measurement of pressure differential along greater than eighty percent of the catheter length, as opposed to pressure measurement at only the proximal and distal ends, can further provide several technical advantages including early detection of flow restrictions occurring at intermediate axial positions within the catheter due to sharp bends in the catheter path through tortuous vasculature, partial occlusion of the catheter lumen by thrombus formation or air bubbles, cavitation, or external compression of the catheter where it passes through vascular bifurcations or crosses over bony structures. By comparing pressure measurements from multiple, axially distributed sensors, the CPM can localize the axial position of flow disturbances with spatial resolution equal to the inter-sensor spacing, enabling the system to distinguish between problems originating at the distal tip, such as distal vessel occlusion by previously administered embolic material, and problems occurring within the catheter itself, such as precipitation of incompatible pharmaceutical agents within the catheter lumen. The distributed pressure measurement also enables calculation of local pressure gradients between each pair of adjacent sensors, providing information about the spatial distribution of flow resistance along the catheter length and allowing the executable instructions to implement sophisticated control algorithms that account for the nonlinear relationship between infusion device output pressure and therapeutic agent flow rate through the catheter. In certain exemplary implementations, the pressure sensors are integrated into the catheter wall structure during catheter manufacturing through processes including embedding MEMS sensor chips into polymer catheter tubing during extrusion, adhering flexible printed circuit assemblies containingsensor elements to the interior or exterior catheter surface, or incorporating fiber optic pressure sensors within the catheter wall composite structure, with electrical or optical connections from each sensor routed proximally along the catheter length to interface with the central processing module at the proximal end.

[0035] In yet another exemplary implementation (see e.g., FIG. 2), at least one catheter used in the systems and methods disclosed, can be adapted, sized and configured as a coaxial catheter system comprising a first catheter defining a first lumen and having a first inner diameter and a first outer diameter, and a coaxial second catheter inserted therethrough, the second catheter defining a second lumen and having a second inner diameter smaller than the first inner diameter and a second outer diameter smaller than the first inner diameter such that the second catheter can be slidably inserted through the first lumen of the first catheter while maintaining an annular space between the first catheter inner wall and the second catheter outer wall. For example, the first catheter can have an outer diameter ranging between about 1.3 mm and about 2.3 mm, and an inner diameter ranging between about 0.89 mm and about 1.78 mm, while the second catheter has an outer diameter between about 0.8 mm, and about 1.7 millimeters, and an inner diameter ranging between about 0.53 millimeters and about 1.02, with dimensional tolerances maintained to within ±0.03 mm to ensure smooth coaxial movement while preventing excessive fluid leakage through the annular space. The plurality of sensors are disposed within both the first catheter and the second catheter, with each sensor axially spaced from adjacent sensors along the longitudinal axis defined by the catheter system, such that a first subset of sensors is integrated into or mounted upon the first catheter at first axial positions and a second subset of sensors is integrated into or mounted upon the second catheter at second axial positions. In preferred exemplary implementations, the first subset comprises three to ten pressure sensors distributed along the length of the first catheter with larger number of sensors having inter-sensor spacing that is wider than the second subset having lower number of sensors pressure sensors distributed along the length of the second catheter with shorter inter sensor spacing, and the first axial positions are offset from the second axial positions such that when the second catheter is fully inserted through the first catheter, the combined sensor array provides interleaved sensor positions along the catheter length with a shorter effective intersensor spacing, thereby achieving higher spatial resolution than would be possible with sensors on a single catheter alone. The coaxial configuration enables several operational modes, for example; a first mode where therapeutic agent flows through the second lumen of the second catheter with the plurality of sensors monitoring pressure distribution within and along the second catheter to guide selective delivery of embolic microspheres or chemotherapeutic agents to small-diameter target vessels, and a second mode where therapeutic agent flows through the annular space between the first and second catheters with the plurality of sensors monitoring pressure in both the annular space and the second lumen to enablesimultaneous or sequential delivery of different therapeutic agents or delivery of therapeutic agent through the annular space while using the second lumen for pressure monitoring, contrast injection, or guidewire passage. The independent axial positioning of the first and second catheters can enable an operator to selectably advance or retract the second catheter relative to the first catheter during a procedure, with the central processing module continuously tracking the relative axial position of the two catheters through position sensors, electrical continuity measurements, or imaging-based localization, while dynamically updating its pressure differential calculations to account for the changing spatial relationship between sensors on the first catheter and sensors on the second catheter. In certain exemplary implementations, sensors on the first catheter are electrically coupled to the CPM through wiring integrated into the first catheter wall that terminates at the proximal end of the first catheter in a first connector, while sensors on the second catheter are coupled through separate wiring integrated into the second catheter wall that terminates in a second connector that remains accessible at the proximal end of the second catheter even when the second catheter is inserted through the first catheter, with both connectors interfacing with the central processing module to provide simultaneous signal acquisition from all sensors in both catheters. The distributed placement of sensors across both coaxial catheters provides enhanced capability to detect flow disturbances occurring specifically within the second catheter lumen, specifically within the annular space, or affecting both flow paths simultaneously, enabling the executable instructions to implement differential control strategies that independently adjust flow parameters for therapeutic agents delivered through different lumens of the coaxial catheter system based on localized pressure measurements in each respective flow path.

[0036] The set of executable instructions, utilizing the computational capabilities of the machine learning module, is further configured, when executed by the at least one processor, to generate and display recommendations to a user through the display, included with the system, wherein said recommendations are derived from a database of pre-defined parameters that has been compiled from the subject’s own historical data, historical procedural data, clinical guidelines, device manufacturer specifications, and biomechanical models of therapeutic agent flow through catheter systems and vascular networks. The database can be configured to include, for example; structured data records that include catheter specification parameters such as catheter inner diameter, catheter length, catheter material composition, and maximum rated pressure for various catheter models. The therapeutic agent parameters included, can be, for example; viscosity, density, particle size distribution for embolic agents, chemical composition, temperature-dependent rheological properties, and recommended infusion rates for various chemotherapeutic formulations, contrast agents, and embolic materials; subject-specific anatomical parameters such as target vessel diameter, vessel tortuosity index, estimated blood flow rate in the target vessel, and vascular bed resistance; and procedural outcome parameters such as incidence of catheterocclusion, frequency of reflux of therapeutic agent into non-target vessels, rate of complete target lesion coverage, and occurrence of adverse events correlated with specific combinations of the aforementioned parameters. The pre-defined parameters are organized in relational database tables or document-oriented database structures with indexed fields enabling rapid querying based on current procedural conditions, and the database is periodically updated with accumulated data from completed procedures to continuously refine the parameter relationships and improve recommendation accuracy. During a given transcatheter procedure, the executable instructions can be configured to receive real-time flow parameter measurements from the plurality of sensors, retrieve subject-specific anatomical information from medical imaging data or user input, and query the database to identify historical cases or theoretical models with similar parameter profiles to the current procedure. Based on this comparative analysis, the executable instructions can generate recommendations that are displayed to the user on the display, such recommendations including optimal infusion rate recommendations that specify a target flow rate or infusion device pressure setting predicted to achieve complete target lesion coverage while minimizing risk of catheter occlusion or non-target embolization. Additionally, catheter position adjustment recommendations could suggest, for example; advancing or retracting the catheter distal tip by a specified distance to optimize the pressure gradient profile measured by the plurality of sensors. Likewise, therapeutic agent dilution recommendations could indicate increase in temperature, and / or addition of contrast medium or saline to reduce therapeutic agent viscosity when measured pressure differentials exceed threshold values associated with increased risk of catheter occlusion. Also, procedural endpoint recommendations could indicate when a sufficient therapeutic agent has been delivered to affect the therapeutic results sought, based on comparison of cumulative delivered volume and current pressure measurements to database parameters associated with successful procedural outcomes.

[0037] The recommendations can be displayed using graphical user interface elements including text notifications with color-coding to indicate urgency levels, graphical overlays on pressure trend plots that highlight regions of concern, suggested parameter values displayed adjacent to user- adjustable controls for infusion device settings, and procedural checklists that are automatically populated based on the current procedural phase as inferred from sensor data and database-defined procedural progression patterns. In certain exemplary implementations, the executable instructions implement a recommendation confidence scoring system that assigns numerical confidence values between 0 and 1 to each recommendation based on the quantity and quality of database records supporting the recommendation, the degree of similarity between current procedural parameters and database parameter profiles, and the statistical variance in outcomes for similar historical cases, with confidence scores displayed alongside recommendations to enable the user to assess the reliability of each suggested action. The database-driven recommendation system is configured to enhance procedural safety and efficacy by providing the userwith real-time, evidence-based guidance derived from aggregated clinical experience and theoretical modeling, while the user retains full control over whether to implement the recommendations, thereby combining the advantages of computational decision support with essential clinical judgment and procedural expertise.

[0038] The ML module may be further configured to furnish the operator with dynamic procedural guidance, real-time risk assessment, and adaptive subject-specific parameter adjustment. The system may analyze temporal evolution of sensed flow and pressure data to identify emerging risk signatures such as excessive perfusion pressure, flow stagnation, or thermal rise associated with embolic polymerization, and or metabolic changes. A probabilistic risk model may generate a dynamic safety index reflecting current procedural stability, while providing visual representation on the display through, for example; intuitive color-coded gradients or numerical thresholds. Simultaneously, the system may adjust computational models using patient-specific input such as vessel compliance, local hematocrit, and therapeutic agent viscosity, obtained from integrated sensors or pre-procedure (e.g., MRI, CT), or intraprocedure (e.g., ultrasound) imaging data. This enables personalization of infusion parameters, such as adaptive flow rate modulation, to reduce the likelihood of NTE. Implementation may also leverage embedded tensor computation units within the CPM to perform continuous data fusion at sampling rates exceeding 1 kHz for example. Alternative implementations of the systems disclosed, may transmit anonymized procedural data to a secure remote analytics server for post-procedure optimization and algorithm retraining.

[0039] In certain exemplary implementations, the operator guidance provided by the system involves multiple sensory modalities to provide effective communication of procedural information and alerts to the user under varying clinical conditions and user preferences, including, for example; visual pressure trend display that can be configured to render graphical representations of pressure measurements from the plurality of sensors as a function of time and / or axial position along the catheter, audio-visual alerts that can be configured to combine visual indicators displayed on the display with auditory signals, notifying the user of clinically significant events or conditions, haptic feedback that can be configured to provide tactile sensations to the user through vibration, force, or texture changes in interface devices, and / or or any guidance modality comprising one or more of the foregoing.

[0040] The visual pressure trend display can include time-domain plots depicting pressure values from each of the plurality of sensors on a common time axis spanning a historical time window of, for example 30 seconds to 10 minutes, with each sensor's pressure trace rendered in a distinct color or line style to enable visual differentiation, and with the vertical axis scaled automatically or manually to ensure that pressure variations are visually discernible across the expected pressure range of between about 0 mmHg, and about 300 mmHg for certain transcatheter procedures. Tire visual display can also includespatial pressure profile plots that depict pressure as a function of axial position along the catheter at the current moment in time, enabling the user to visualize the pressure gradient distribution and identify axial regions with abnormal pressure drops indicative of flow restrictions. The visual display can further incorporate annotations such as shaded regions that highlight time periods or axial positions where pressure values exceed or fall below threshold values, trend lines or curve fits that indicate the overall direction of pressure evolution, and reference markers that would indicate clinically significant events such as the start of infusion, changes in infusion rate, or the timing of fluoroscopic imaging acquisitions.

[0041] Audio- visual alerts can be configured to combine visual alert indicators such as, for example; flashing borders around the display, color changes in the display background, pop-up warning messages with text descriptions of the alert condition, or animated icons that appear on the display, with corresponding auditory signals such as beep tones with frequency, rhythm, or intensity that varies according to alert priority levels, spoken voice messages that verbally describe the alert condition and recommended actions, or continuous tones that persist until the alert condition is acknowledged or resolved by the user. The audio-visual alerts can be further categorized into priority levels, for example; high-priority alerts for conditions requiring immediate user response, such as pressure differentials exceeding maximum safe values indicating imminent catheter occlusion or vessel rupture: mediumpriority alerts for conditions requiring user attention within a period ranging for example between about 30 seconds and about 2 minutes, such as gradual upward trends in pressure suggesting progressive catheter obstruction; and low-priority alerts for informational notifications such as achievement of planned cumulative infused dose or completion of a procedural phase.

[0042] Haptic feedback can be provided through, for example; haptic actuators integrated into interface devices such as a handheld controller used to adjust infusion device parameters, a catheter shaft handle held by the user during catheter manipulation, or a wearable device such as a vibrating wristband or glove worn by the user. The haptic actuators can also include vibration motors that produce oscillating sensations with frequency ranging for example between about 50 Hz and about 300 Hz and amplitude adjustable for example between about 0 mm., and about 3 mm., electromechanical force feedback devices that apply resistive forces to catheter manipulation controls, or ultrasonic transducers that produce tactile sensations through acoustic radiation pressure on the user's skin. Haptic feedback patterns are designed to convey specific information, such as a continuous moderate-intensity vibration indicating that the system is actively monitoring and all parameters are within normal ranges, intermittent short-duration pulses with frequency increasing for example, between about 1 Hz and about 10 Hz, as a risk score approaches a threshold value, strong abrupt vibrations to indicate high-priority alert conditions, or directional force feedback that guides catheter movement by applying forces that indicate the recommended direction of catheter advancement or retraction.

[0043] The multi-modal approach to operator guidance accommodates diverse clinical environments where visual displays may be partially obscured by imaging equipment or sterile drapes, auditory alerts may be masked by ambient operating room noise or may be unsuitable in settings where multiple procedures occur simultaneously, and haptic feedback provides private notification to the primary operator without disturbing other clinical personnel. In certain embodiments. Accordingly, and in another exemplary implementation, the user can configure the operator guidance modalities through a settings interface, enabling or disabling specific modalities, adjusting alert thresholds for audio-visual alerts, customizing haptic feedback intensity, and selecting preferred visual display formats, with the user's preferences stored in the non-transitory memory device and automatically applied in subsequent procedures performed by the same user. The combination of visual, auditory, and haptic guidance modalities is configured to provide robust communication of (critical e.g.,) procedural information and enhances the user's ability to maintain situational awareness and respond appropriately to dynamic changes in flow parameters detected by the plurality of sensors throughout the transcatheter procedure.

[0044] In yet another exemplary implementation, the dynamic risk assessment functionality provided by the systems used in the methods disclosed, continuously evaluates procedural safety parameters throughout the transcatheter operation to provide actionable clinical decision support. The machine learning algorithms is configured to process vast amounts of clinical and radiological data to predict the likely outcomes of various interventions, enabling the system to calculate real-time complication probability by integrating multiple data streams including, for example; the measured flow parameters from the axially spaced sensors, historical complication databases, and current procedural conditions.

[0045] The real-time complication probability calculation can utilize, for example, probabilistic models that assess parameters such as. for example; reflux likelihood based on differential pressure measurements between sensor pairs, vessel wall stress indicators derived from localized, instantaneous flow rate changes, and embolic agent migration risk computed from flow velocity profiles, with the CPM continuously updating probability scores ranging from 0 to 100 percent and triggering graduated warning levels at user-defined, predetermined thresholds such as 25 percent for caution, 50 percent for heightened alert, and 75 percent for critical intervention recommendation.

[0046] Likewise, the optimal injection rate recommendation functionality can be used to analyze the measured difference in flow parameters between the axially spaced sensors to determine flow resistance characteristics of the vascular bed being treated, correlating these measurements with vessel caliber estimates, tortuosity indices, and downstream vascular resistance to calculate injection rates that maximize therapeutic agent delivery while minimizing risk of non-target embolization, with recommended rates ranging for example between about 0.1 mL / min, and about 5.0 mL / min depending oncatheter(s) inner diameter specifications, and target vessel characteristics. The end-point prediction component can be configured to analyze trend analysis of the flow parameter differential measurements over time and accordingly forecast procedural completion, employing for example - exponential decay models or polynomial regression to extrapolate when flow resistance will reach predetermined therapeutic endpoints such as, for example; cessation of antegrade flow, or achievement of specific flow reduction percentages (e.g., ranging from 70%-95%) reduction compared to baseline, thereby allowing the operator to anticipate procedure duration and therapeutic agent volume requirements.

[0047] The safety margin calculation can be configured to quantify the operational envelope between current procedural parameters and critical thresholds, by computing distances in multidimensional parameter space, wherein measured flow differentials, injection pressures inferred from flow resistance, and temporal rate-of-change values are compared against established danger zones derived from adverse events’ databases, with the CPM expressing safety margins as percentages or absolute units and can be further configured, either as user defined, or initially by the manufacturer of the system, to provide numerical displays and / or color-coded visual indicators transitioning from, for example; green for margins exceeding 40%, through yellow for margins between 20% and 40%, to red for margins below 20%, ensuring the operator maintains continuous awareness of how close current conditions approach potentially hazardous states.

[0048] Furthermore, as indicated and further provided herein, the subject-specific parameter provided by the system, and used in the methods disclosed, enables the system to tailor its monitoring, analysis, and guidance to the individual patient's unique physiological and anatomical characteristics, thereby enhancing both safety and efficacy compared to population-based protocols. In yet another exemplary implementation, establishing an individual procedure-specific baseline can take place during an initial calibration phase wherein the CPM receives signals from the plurality of axially spaced sensors during a preliminary injection of contrast agent, saline, or therapeutic agent at a standardized low flow rate, ranging for example from about 0.3mL / min., and about 0.5 mL / min for a duration ranging for example between about of 10 sec., and about 30 sec, allowing the system to characterize the patient's specific vascular resistance profile, flow dynamics, and sensor (linear or otherwise) response patterns under controlled conditions that serve as reference values against which all subsequent measurements are compared throughout the procedure. This baseline establishment captures parameters such as, for example; initial differential pressure measurements between sensor pairs that reflect native vascular impedance, baseline flow velocity profiles that characterize the patient's specific hemodynamic conditions, and catheter- specific response characteristics that account for individual catheter material variation, internal diameters, coaxial configuration, positioning within the patient's anatomy, and the like, with the CPM storing these baseline values in the non-transitory memory device and continuouslyinterrogating and referencing them to calculate relative changes rather than relying solely on absolute measurements that may vary significantly between patients due to anatomical variability.

[0049] The anatomical factor integration incorporates patient-specific morphological data obtained from pre-procedural imaging studies such as computed tomography angiography or magnetic resonance imaging angiography, with the CPM receiving, if necessary -fusing, and processing intra-operational digital imaging data that can determine and specify for example; vessel diameters at the target location and along the approach pathway, vessel tortuosity indices quantified as the ratio of actual vessel path length to straight-line distance with typical tortuosity (t) values ranging for example between about 1.0 for straight vessels and about 2.5 or higher for highly tortuous anatomy, branch vessel configurations including number, size, and angular orientation of vessels arising from the target treatment zone, and collateral circulation patterns that affect flow distribution and resistance characteristics within the target bed.

[0050] The pertinent personal historical data integration, is configured to provide access and utilize information the patient's previous procedures stored in an electronic medical record database or the system's own historical database, including, if existing, outcomes from prior embolization procedures performed on the same patient, which may indicate individual response patterns to specific therapeutic agents or injection protocols, complications encountered in previous interventions that may inform risk stratification such as prior episodes of non-target embolization or vasospasm, baseline laboratory values relevant to the current procedure including coagulation parameters with international normalized ratio values and platelet counts that affect embolization dynamics, and documented anatomical variants or pathological conditions such as arteriovenous malformations, aneurysms, or atherosclerotic disease that modify expected flow behaviors, with the machine learning module weighting these historical factors according to their temporal proximity and clinical relevance to generate patient-specific prediction models that demonstrate improved accuracy compared to population-derived algorithms.

[0051] In addition, the catheter-related parameter monitoring functionality is configured to address intrinsic technical factors specific to the catheter itself that can influence measurement accuracy and procedural safety, enabling the system to distinguish between true changes in therapeutic agent flow conditions and artifacts or effects attributable to the catheter's physical state or position. Catheter movement artifact detection and compensation addresses circumstances stemming from the fact that catheters are not rigidly fixed within the vasculature and may undergo displacement due to patient respiration, with axial translation ranging for example between about 2 mm., and about 15 mm., depending on anatomical location, cardiac pulsation (BPM) causing cyclical movements, patient gross body movement during conscious sedation, or active catheter manipulation by the operator (whether manual or motor-assisted) during positioning adjustments, all of which could generate spurious signals inthe plurality of axially spaced sensors. These may consequently be misinterpreted as changes in therapeutic agent flow parameters. The CPM can be configured to implement artifact detection algorithms that analyze the temporospatial characteristics of sensor signals to identify patterns consistent with motion artifact, such as, for (a non-limiting) example; simultaneous signal changes across all sensors in the plurality indicating bulk catheter movement rather than flow-related phenomena, high-frequency signal components ranging for example between about 1 Hz, and about 5 Hz - characteristic of cardiac pulsation, or low-frequency oscillations in the 0.2 to 0.4 Hz range consistent with respiratory cycles, applying signal processing techniques including digital filtering with band-pass or band-stop characteristics tuned to artifact frequency ranges, motion correlation algorithms that compare accelerometer data from integrated inertial measurement units within the catheter to flow sensor signals, and adaptive filtering methods that employ reference signals from motion sensors to subtract artifact components from flow measurements. Using these parameters allows the system to provide cleaned flow parameter signals that accurately represent therapeutic agent delivery conditions independent of catheter movement.

[0052] Pressure damping effects can arise for example, from the physical characteristics of the catheter system including the compliance of the catheter wall material, fabricated as indicated from thermoplastic polymers such as, for example; polyether block amide with durometer hardness values between 25 Shore D and 72 Shore D, the presence of air bubbles or particulate matter within the catheter lumen that can compress under pressure and absorb pressure transients, and the dynamic response characteristics of the sensors themselves which exhibit finite frequency response typically limited to DC through 50 Hz for microfabricated pressure sensors. The CPM can be configured to compensate for pressure damping by, for example; applying transfer function corrections derived from the known frequency response of the catheter- sensor system, implementing dynamic calibration routines that inject test signals or analyze the system's response to known flow transients to characterize damping coefficients which typically exhibit time constants ranging between about 0.05 sec., and about 0.3 sec., and employing predictive algorithms that anticipate actual distal conditions from proximal measurements by accounting for pressure wave propagation delays through the therapeutic agent column within the catheter lumen.

[0053] The parameter combinations allow the system to simultaneously address multiple catheter-related factors, taking into account that movement artifacts and pressure damping often occur concurrently and may interact in complex ways. In an exemplary implementation, the CPM can be configured to employ multi-variable correction algorithms that jointly estimate and compensate for both effects (e.g., pressure damping and movement) using techniques such as Kalman filtering that can recursively update estimates of true flow parameters based on, for example; noisy measurements corrupted by known and characterized error sources, or machine learning approaches including neural networks trained on datasets where ground-truth flow conditions were independently verified to learn thecomplex mapping between raw sensor signals affected by catheter-related parameters and the actual therapeutic agent flow conditions at the catheter distal end.

[0054] In an exemplary implementation, the embolizing agent that can be utilized in the methods implemented with the disclosed flow measurement and control system described, may be selected from several categories based on the therapeutic objective and target anatomy. These can be, for example; permanent embolizing agents that provide indefinite vascular occlusion, temporary embolizing agents composed of biodegradable materials that resorb over time allowing eventual recanalization (referring to the process of reopening the embolized passage in the body, to restore normal flow), liquid agents that transform from injectable fluids to solid implants in situ through various solidification mechanisms, particulate agents comprising microspheres or other sized particles, or embolizing agent compositions that combine one or more of these agent types to achieve specific clinical outcomes.[00055 J The permanent embolizing agents suitable for use with the system include but are not limited to: polyvinyl alcohol particles, tris-acryl gelatin microspheres, non-degradable polymeric microspheres having diameters ranging from approximately 40 micrometers to 1200 micrometers, metallic coils fabricated from platinum, stainless steel, or nitinol alloys with or without thrombogenic fiber coatings, detachable balloons formed from latex or silicone elastomers, vascular plugs constructed from braided nitinol mesh, and ethylene vinyl alcohol copolymer-based liquid embolics such as those dissolved in dimethyl sulfoxide carrier solvents that precipitate upon contact with aqueous blood to form cohesive embolic masses.

[0056] The temporary embolizing agents used can comprise resorbable materials, for example gelatin-based products such as gelatin sponge particles or pledgets that undergo enzymatic degradation and absorption within about two to six weeks, starch microspheres that degrade within hours to days through hydrolytic and enzymatic processes, and various biodegradable polymer compositions, for example; polylactic acid (PLA), polyglycolic acid (PGA), and their copolymers (PLGA) that provide controlled degradation rates ranging from weeks to months depending on molecular weight, fractional concentration of each polymer, and crystallinity.

[0057] Further, the liquid agents encompass both polymerizing and non-polymerizing formulations, with polymerizing liquid agents including N-butyl cyanoacrylate adhesives that can undergo anionic polymerization upon contact with blood to form solid implants, and non-polymerizing agents such as ethanol that induces immediate endothelial damage and subsequent thrombosis, or iodized oils that can remain liquid but cause vessel occlusion through inflammatory response and thrombus formation.

[0058] Moreover, the particulate agents comprise for example; calibrated microsphcrcs available in precise size ranges to enable selective embolization of vessels matching specific diameter criteria, withsizing categorized as small particles ranging from about 40 pm and about 200 pm for distal capillary bed embolization, medium particles ranging from about 200 pm and about 500 pm for intermediate arterial branches, large particles ranging from about 500 pm and about 900 pm for proximal arterial occlusion, and extra-large particles ranging from about 900 pm and about 1200 pm for very proximal vessel occlusion, where the particle size selection is configured to control the level of vascular occlusion and degree of ischemia induced in target tissues.

[0059] The particulate agents can also be drug-eluting beads (DEBs) that function both as embolic agents to occlude blood flow and as drug delivery vehicles for transarterial chemoembolization, wherein these drug-eluting beads comprise biocompatible polymeric microspheres such as polyvinyl alcohol (PVA), acrylic copolymers, or hydrogel-based materials that are pre-loaded with chemotherapeutic agents including doxorubicin, irinotecan, or other cytotoxic drugs through ionic interactions or physical entrapment within the bead matrix, enabling sustained local release of the therapeutic agent over periods ranging from hours to weeks while simultaneously achieving mechanical vascular occlusion, thereby increasing drug concentrations directly within target tumors while substantially reducing systemic drug exposure and associated toxicity compared to conventional chemoembolization techniques.

[0060] In certain exemplary implementations, the embolizing agent compositions can also combine multiple agent types, thereby providing synergistic benefits such as a slurry comprising particulate agents suspended in a liquid embolic carrier to achieve both immediate mechanical occlusion and sustained chemical or inflammatory-mediated thrombosis, or combinations of temporary and permanent agents to provide initial rapid occlusion followed by controlled recanalization while maintaining partial long-term flow reduction.

[0061] The flow measurement and control system of the disclosure enables real-time monitoring and adjustment of delivery parameters specific to each embolizing agent type, accounting for viscosity variations ranging from approximately 1 centipoise for low-viscosity liquid agents to over 100 centipoise for concentrated particulate suspensions, particle size distributions that affect flow resistance through catheter lumens having inner diameters ranging between about 0.3 mm. and about 2.7 mm., depending on catheter size, solidification kinetics that may occur within milliseconds for cyanoacrylate adhesives or over several minutes for EVA copolymer systems requiring controlled injection rates, and the tendency of certain agents to aggregate or settle during delivery necessitating continuous agitation or flow modulation to maintain homogeneous dispersion throughout the administration process.

[0062] As used herein, the target location, or tissue for embolization therapy using the disclosed flow measurement and control system encompasses a diverse range of anatomical sites and pathological conditions including blood vessels requiring occlusion such as arterial feeders supplying pathologicaltissue, organs with diseased regions requiring devascularization, tumors including both solid neoplastic masses and vascular malformations, fibroids referring to benign smooth muscle tumors, for example, uterine leiomyomas treated through embolization of supplying uterine arteries. Also included, are any abnormal cell mass requiring reduction in blood supply, aneurysms representing pathological dilations of blood vessel walls at risk of rupture (emphasizing the importance of real-time pressure monitoring throughout the process). Likewise, cancers of various histological types requiring palliative symptom control or pre-surgical devascularization, hypervascular malignant tumors characterized by excessive angiogenesis and prominent arterial blood supply such as renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, and certain metastatic lesions, hypervascular benign tumors including paragangliomas, hemangiomas, juvenile nasopharyngeal angiofibromas, and meningiomas that benefit from pre-operative embolization to reduce intraoperative blood loss. Furthermore, aortic aneurysms and particularly those unsuitable for conventional surgical repair can be addressed, as well as abdominal aortic aneurysms treated through endovascular aneurysm repair with or without adjunctive embolization of collateral vessels, peripheral aneurysms affecting arteries of the extremities such as popliteal, femoral, or splenic artery aneurysms.

[0063] Other sites can be sites of active hemostasis requiring emergent embolization to achieve hemodynamic stability, vascular lacerations resulting from trauma or iatrogenic injury, venous lacerations including portal venous injuries or variceal bleeding, or any tissue exhibiting a pathological condition that would benefit from controlled ischemia or flow modification.

[0064] Reference is now made to Fig. 1 , showing a simplified schematic illustration of an exemplary implementation of the flow measurement system for a transcatheter medical procedure. As illustrated in Fig. 1 catheter 100 is inserted into the vascular system of a subject. The catheter 100 is arranged a long a longitudinal axis 101 and has a proximal end 102 and a distal tip 104. The catheter 100 may be navigated and guided up to a location where the distal tip 104 thereof is disposed at the target location within the body of the subject. The navigation may be performed by means of a guide wire inserted into the catheter and may be controlled angiographically. It is seen that a syringe 110 is adapted, sized and configured to engage the proximal end 102 of the catheter 100 and can be configured for administering a therapeutic (e.g., embolizing) agent through the catheter 100 into the target location. It is noted that an unobstructed flow of therapeutic agent is adapted to be provided through the catheter 100. It is a particular feature of an exemplary implementation of the disclosure that a plurality of sensors 120 are incorporated into the wall of the catheter 100 and are operably associated with a processing unit (CPM) 130 (see also FIG. 3). In another exemplary implementation, plurality of sensors 120 are axially spaced from each other and configured for detection of at least one flow parameter of the unobstructed flow, such as the flow direction, pressure and pressure gradient inside the catheter 100 and for continuouslycommunicating this information to the CPM 130 in real time. Further, the plurality of sensors 120 are configured to measure a difference in the at least one flow parameter along the longitudinal extent of the catheter 100. Sensors 120 can be pressure sensors or flow sensors, for example, or may be any other suitable sensor. The sensors 120 can be embedded into the wall of the catheter 100 and made using, for example, piezoresistive, capacitive or fiber pressure sensors. The transcatheter embolization procedure can be performed using a micro-catheter, having a 3F or less outer diameter and inserted coaxially via larger catheter.

[0065] In yet another exemplary implementation, at least two sensors 120 are embedded into the wall of the catheter 100, the first sensor 120a may be located at or adjacent the distal tip 104 of the catheter and the second sensor 120b may be located adjacent the proximal end 102 of the catheter 100 or at any intermediate location along the longitudinal extent of the catheter 100. Additional sensors 120c -120e may be disposed between the first sensor 120a and the second sensor 120b. It is noted that alternatively or additionally, at least one sensor may be operably coupled to the catheter 100 and located externally to the proximal end of the catheter 100. The at least one sensor that is located externally to the proximal end of the catheter 100 is preferably configured to provide readings to the processing unit 130 and may be employed for controlling the injection rate of the therapeutic agent by providing a continuous indication of the injection rate to the user on a display.

[0066] Several sensors may be provided externally to the catheter 100 and pressure gradient between these several sensors may indicate the flow direction within the catheter 100. Based on the continuous readings the CPM 130 receives from the plurality of sensors 120, it is configured to detect a pressure gradient within the catheter 100, which is higher than a pre-defined pressure gradient threshold and to provide a corresponding indication to the user. The predefined gradients can be based on the lesion characteristics, patient blood pressure, type and viscosity of embolization materials used and any other relevant variable. In an exemplary implementation, based on the continuous readings the CPM 130 receives from the plurality of sensors 120, the flow direction within the catheter 100 is detected, particularly identification of reversal of flow direction, and providing a corresponding indication to the user via control system.

[0067] The detection of reversal of flow direction may indicate that the injection should be stopped and re- evaluated to prevent backflow of therapeutic agents potentially leading to NTE. It is a particular feature of an exemplary implementation of the disclosure that the intra-catheter pressure gradient detection can provide the following indications to the user: real time-controlled flow of the embolization material into target vessel and lesion; excessive pressure within the catheter during or with completion of the embolization process; detection of backflow during or with completion of the embolization process; blocking of the catheter by embolization material. It is noted that detection ofpressure gradient and / or flow direction within the catheter 100 using the plurality of sensors 120 enables reduction of radiation exposure to the patient and personnel, that is usually required in order to detect backflow.

[0068] Turning now to Fig. 2, showing a simplified schematic illustration of a flow measurement system for a transcatheter medical procedure, constructed and operable in accordance with another exemplary implementation. In accordance with this implementation, the micro- catheter 100 is inserted coaxially through a diagnostic catheter 140. The diagnostic catheter 140 can have a SF or 6F outer dimeter. Initially, diagnostic catheter 140 is advanced into the vessel until its distal tip is located as close as possible to the blood vessel branch that feeds the tumor or any other lesion to be embolized. Thereafter, micro-catheter 100 can be inserted via the diagnostic catheter 140 until its distal tip 104 is inside, or abuts the target vessel that feeds the tumor. As further illustrated in Fig. 2, some of the sensors 120 embedded into the wall of catheter 100 can be configured to measure the flow within the micro-catheter 100 and others of the sensors 120 can be configured to measure the flow around the micro- catheter 100 and around or within the diagnostic catheter 140. Alternatively, the plurality of sensors 120 are embedded into the wall of the micro-catheter 100 and a plurality of additional sensors 150 are embedded into the wall of the diagnostic catheter 14O.The readings from the sensors 120 measuring the flow around the catheter 100 may be utilized for detec ti ng flow direction, thus indicating to the user that the backflow occurred.[000691 The real time readings from the sensors measuring the flow within the catheter 100 may be utilized for detecting pressure gradient along the catheter 100, thus indicating to the user whether the injection rate should be adjusted or backflow occurred at the end of embolization process. The syringe used to inject the therapeutic agent through the catheter may be a standard mechanical syringe, whereby the user manually advances a plunger of the syringe in order to inject the therapeutic agent into the catheter 100. Alternatively, an automatic injector that is controlled by an algorithm may be employed. In another exemplary implementation, a third-party robotic system may be provided instead of the standard mechanical syringe, the robotic system can be configured to assist the user to perform the transcatheter embolization safely and efficiently. Specifically, the robotic system can comprise a customized pressure control injection sub-system and a flushing syringe adapted, sized and configured to maintain communication with CPM 130 via a specially designed flushing system. CPM 130 can be configured to receive signals from the plurality of sensors 120, to measure and display data such as pressure level within the catheter 100, flow direction and flow velocity in real-time.

[0070] Data processing can be based on an algorithm / algorithms, which employ a database of pre-defined parameters, such as the type of catheter, tumor characteristics (like tumor volume including necrotic tissues, CT density / MR features), number and dimensions of the vessels feeding the tumor, type and size of embolization particles, contrast media viscosity and more. The system is further configured toprovide real-time feedback on the pressure applied by the user and the flow velocity within the catheter 100. Moreover, the system is configured to detect backflow from the distal end of the micro-catheter 100 or the diagnostic catheter 140.

[0071] Accordingly and in an exemplary implementation, provided herein is a flow measurement and control system for transcatheter medical procedure adapted to administer a therapeutic agent to a target location within a body of a subject in need thereof by an infusion device, comprising: at least one catheter defining a longitudinal axis and having a proximal end in liquid communication with the infusion device comprising the therapeutic agent, providing an unobstructed flow of the therapeutic agent through the catheter, and a distal end adapted, sized and configured to be inserted within the body operable to administer the therapeutic agent to the target location; a plurality of sensors integrated within the catheter and axially spaced from each other, the plurality of sensors configured to sense at least one flow parameter of the unobstructed flow of the therapeutic agent: and a central processing module (CPM), the CPM being in communication with the infusion device, and each of the plurality of axially spaced sensors, the CPM further comprises at least on processor in communication with a non-transitory memory device storing thereon a computer-readable medium with a set of executable instructions, configured, when executed by the at least one processor, to cause the CPM to: receive a signal from each of the plurality of sensors; measure a difference in the at least one flow parameter between at least two axially spaced sensors; and based on the measured difference between the signals received from the at least two sensors control: flow parameter of the therapeutic agent, and / or a catheter-related parameter, wherein (i) the set of executable instructions further comprise a machine learning (ML) module (see e.g., FIG. 3) comprising: areal-time signal processing module; a machine learning inference module; a predictive modeling module; and an application programming interface, (ii) the system further comprising a user interface and a display, wherein (iii) the plurality of sensors are pressure sensors, adapted sized and configured to measure pressure differential along a length of the catheter that is larger than eighty (80) percent of the catheter length, (iv) wherein the at least one flow parameter is: flow rate; mass flow rate; and flow direction, (v) the at least one catheter further comprises a first catheter and a co-axial second catheter inserted therethrough, whereas the pl ural ity of sensors are each axially spaced and are disposed within both the first catheter and the second catheter, wherein (vi) the set of executable instructions using the ML module, is further configured when executed by the at least one processor, using the display, to provide recommendations to a user based on a database of pre-defined parameters, (vii) provide the user with: operator guidance, dynamic risk assessment, subject-specific parameters, or a combination comprising one or more of the foregoing, wherein (viii) operator guidance comprises: visual pressure trend display, audio- visual alert, haptic feedback, or a guidance comprising one or more of the forgoing, (ix) tire dynamic risk assessment comprises: real-time complication probability, optimal injection raterecommendation, end-point prediction, safety margin calculation, or a combination comprising one or more of the foregoing, (x) the subject-specific parameter comprises: establishment of an individual procedure- specific base-line, anatomical factor integration, pertinent historical data, wherein (xi) the catheter-related parameter is: catheter movement artifact, pressure damping effects, or a parameter combination comprising one or more of the foregoing.

[0072] In another exemplary implementation, provided herein is a method of delivering an embolizing agent to the target location, implemented using any of the flow measurement and control systems for transcatheter medical procedure disclosed herein, the method comprising: contacting the distal end of the catheter with the target location; and using the flow measurement and control system delivering the embolizing agent to the target location; and using the flow measurement and control system, determining the end point for the delivery of tire embolizing agent; and ending the delivery of the embolizing agent, wherein (xii), the embolizing agent is a permanent embolizing agent, a temporary embolizing agent, a liquid agent, a particulate agent, or an embolizing agent composition comprising one or more of the foregoing, (xiii) the permanent embolizing agent that is: a coil, or a plug, or an embolizing agent adapted, sized and configured to permanently block a vessel leading to the target location, (xiv) the temporary embolizing agent that is a gelatin foam, or an embolizing agent adapted, sized and configured to t block a vessel leading to the target location for a predetermined period, (xv) the liquid agent that is a biocompatible glue, onyx, ethanol, an N-butyl cyanoacrylate adhesive, an iodized oil, or a liquid embolizing composition adapted and configured to block a vessel leading to the target location, (xvi) the particulate agent that is poly(vinylalcohol) (PVA) particles, drug-eluting beads (DEB), or a particulate embolizing composition adapted, sized and configured to block a vessel leading to the target location, and wherein (xvii) the target location is: a blood vessel, an organ, tumor, a fibroid, a cell mass, an aneurysm, a cancer, a tumor, a hypervascular malignant tumor, a hypervascular benign tumor, an aneurysm, an aortic aneurysm, an abdominal aortic aneurysm, a peripheral aneurysm, a hemostasis, a vascular laceration, a venous laceration, or a tissue having a pathological condition.

[0073] While in the foregoing specification the systems and methods for flow measurement system and associated methods for controlled delivery of therapeutic agents to target locations within the body via catheter, have been described in relation to certain preferred exemplary implementations, and many details are set forth for purpose of illustration, it will be apparent to those skilled in the art that the disclosure of the systems and methods is susceptible to additional exemplary implementations and that certain of the details described in this specification and as are more fully delineated in the following claims can be varied considerably without departing from the basic principles of this disclosure.

Claims

What is claimed:

1. A flow measurement and control system for transcatheter medical procedure adapted to administer a therapeutic agent to a target location within a body of a subject in need thereof by an infusion device, comprising:a) at least one catheter defining a longitudinal axis and having a proximal end in liquid communication with the infusion device comprising the therapeutic agent, providing an unobstructed flow of the therapeutic agent through the catheter, and a distal end adapted, sized and configured to be inserted within the body operable to administer the therapeutic agent to the target location;b) a plurality of sensors integrated within the catheter and axially spaced from each other, the plurality of sensors configured to sense at least one flow parameter of the unobstructed flow of the therapeutic agent: andc) a central processing module (CPM), the CPM being in communication with the infusion device, and each of the plurality of axially spaced sensors, the CPM further comprises at least one processor in communication with a non-transitory memory device storing thereon a computer-readable medium with a set of executable instructions, configured, when executed by the at least one processor, to cause the CPM to:i. receive a signal from each of the plurality of sensors:ii. measure a difference in the at least one flow parameter between at least two axially spaced sensors; andiii. based on the measured difference between the signals received from the at least two sensors control: flow parameter of the therapeutic agent, and / or a catheter-related parameter.

2. The system of claim 1, wherein the set of executable instructions further comprise a machine learning (ML) module comprising:a) a real-time signal processing module;b) a machine learning inference module;c) a predictive modeling module; andd) an application programming interface.

3. The system of claim 1 , or 2, further comprising a user interface and a display.

4. The system of claim 3, wherein the plurality of sensors are pressure sensors, adapted sized and configured to measure pressure differential along a length of the catheter that is larger than eighty (80) percent of the catheter length.

5. The system of any one of claims 1-4, wherein the at least one flow parameter is: a) flow rate;b) mass flow rate; andc) flow direction.

6. The system of any one of claims 4 and 5, wherein the at least one catheter further comprises a first catheter and a co-axial second catheter inserted therethrough, whereas the plurality of sensors are each axially spaced and are disposed within both the first catheter and the second catheter.

7. The system of any one of claims 4-6, wherein the set of executable instructions using the ML module, is further configured, using the display, to provide recommendations to a user based on a database of pre-defined parameters.

8. The system of any one of claims 4-7, wherein the set of executable instructions using the ML module, is further configured, using the display, to provide the user with: operator guidance, dynamic risk assessment, subject-specific parameters, or a combination comprising one or more of the foregoing.

9. The system of claim 8, wherein operator guidance comprises: visual pressure trend display, audio-visual alert, haptic feedback, or a guidance comprising one or more of the foregoing.

10. The system of claim 8, wherein dynamic risk assessment comprises: real-time complication probability, optimal injection rate recommendation, end-point prediction, safety margin calculation, or a combination comprising one or more of the foregoing.

11. The system of claim 8, wherein subject-specific parameter comprises: establishment of an individual procedure- specific base-line, anatomical factor integration, pertinent historical data.

12. The system of claim 8, wherein the catheter-related parameter is: catheter movement artifact, pressure damping effects, or a parameter combination comprising one or more of the foregoing.

13. A method of delivering an embolizing agent to the target location, implemented using the flow measurement and control system for transcatheter medical procedure of any one of Claims 1-12, the method comprising:a) contacting the distal end of the catheter with the target location; and b) using the flow measurement and control system delivering the embolizing agent to the target location; andc) using the flow measurement and control system, determining the end point for the delivery of the embolizing agent; andd) ending the delivery of the embolizing agent.

14. The method of claim 13, wherein the embolizing agent is a permanent embolizing agent, a temporary embolizing agent, a liquid agent, a particulate agent, or an embolizing agent composition comprising one or more of the foregoing.

15. The method of claim 14, wherein the embolizing agent is the permanent embolizing agent that is: a coil, or a plug, or an embolizing agent adapted, sized and configured to permanently block a vessel leading to the target location.

16. The method of claim 14, wherein the embolizing agent is the temporary embolizing agent that is a gelatin foam, or an embolizing agent adapted, sized and configured to t block a vessel leading to the target location for a predetermined period.

17. The method of claim 14, wherein the embolizing agent is the liquid agent that is a biocompatible glue, onyx, ethanol, an N-butyl cyanoacrylate adhesive, an iodized oil, or a liquid embolizing composition adapted and configured to block a vessel leading to the target location.

18. The method of claim 14, wherein the embolizing agent is the particulate agent that is poly(vinylalcohol) (PVA) particles, drug-eluting beads (DEB), or a particulate embolizing composition adapted, sized and configured to block a vessel leading to the target location.

19. The method of claim 13, wherein the target location is: a blood vessel, an organ, tumor, a fibroid, a cell mass, an aneurysm, a cancer, a tumor, a hypervascular malignant tumor, a hypervascular benign tumor, an aneurysm, an aortic aneurysm, an abdominal aortic aneurysm, a peripheral aneurysm, a hemostasis, a vascular laceration, a venous laceration, or a tissue having a pathological condition.

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