Devices, systems, and methods for measurement of flow, pressure, and resistance

Abstract

Methods and systems for determining a stenosis indicator in a thoracic duct or other bodily lumen. A catheter assembly is inserted into the bodily lumen, and an occlusion device disposed near a distal end of the catheter is actuated to at least partially occlude the duct. A bolus of fluid is then delivered into the bodily lumen at a controlled rate and volume to induce a transient hemodynamic response. First pressure measurements are obtained in the bodily lumen during and after the bolus delivery, while a second pressure measurement is obtained in a downstream bodily luminal structure as a reference pressure. A stenosis indicator is calculated from the pressure differential and / or a decay characteristic of the pressure response relative to the reference pressure. The stenosis indicator is displayed.

Description

DEVICES, SYSTEMS, AND METHODS FOR MEASUREMENT OF FLOW, PRESSURE, AND RESISTANCEBACKGROUND

[0001] Currently, there are several existing methods used for the assessment of general lymphatic health as described above. The most typical approach is the use of various methods of lymphangiography, in which a contrast solution is injected into the lymphatic system and visualized with magnetic resonance imaging (MRI), x-ray, or computed tomography (CT) scans. Another common method is lymphoscintigraphy, utilizing an injected radioactive tracer to assist in generating an image of the lymphatic system. Although these imaging methods are common, there are no quantitative, real-time point of care diagnostic tools specifically for Central Conducting Lymphatic Anamoly (CCLA). For example, there is currently no method to assess the severity of Complex Lymphatic Anaomalies (CLA) or CCLA (specifically, the degree of lymph flow resistance in the thoracic duct (TD)).

[0002] There are two clinical methods to measure flow on a guidewire: 1) Thermodilution method to measure flow ratio, and 2) Doppler method for measurement of flow velocity. The thermodilution method requires a thermistor on the guidewire in conjunction with saline injection to provide a flow ratio (maximal flow with adenosine relative to baseline) rather than absolute flow. The principle of thermodilution is based on the injection of a quantity of cold saline and measurement of its dilution by the blood by recording the changes in the blood temperature downstream from the point of injection. This method is known to be qualitative and lacks precision as thermodilution injections are often made repeatedly to obtain reproducible results.

[0003] The doppler method uses ultrasound doppler shift and can only measure velocity accurately if the doppler sensor < 60° angle to the centerline of the vessel axis. The principle of doppler method relies on detection of the shift and frequency of ultrasound signal reflected from moving fluid. Since the angle is important for measurement accuracy, this method lacks precision for tortuous vessels where the angle requirement cannot be met. Furthermore, velocity measurement is not as meaningful as volumetric flow for assessment of organ function since the velocity remains relatively constant under a wide range of conditions whereas volumetric flow dictates perfusion of the organ or clearance of fluid in the case of lymphatics. Both thermodilution and doppler methods have been implemented on a guidewire and used to measure coronary flow reserve (ratio of flowrather than absolute flow). Neither method is clinically used widely due to inaccuracies in the measurements and because they do not provide absolute volumetric flow. Neither method is appropriate for the TD lymph flow since absolute lymph flow is required to understand the hemodynamics of the lymphatic system.

[0004] Medical imaging techniques (angiography, MRI, CT, etc.) have been used to quantify volumetric flow based on first pass principles of contrast agents. Basically, the velocity (length over time) of a contrast agent is measured over temporal images and then the velocity is multiplied by the cross-sectional area of the vessel to calculate the volumetric flow rate (i .e., conservation of mass provides that Q=UA where Q, U and A represent volumetric flow, flow velocity and lumen area, respectively).

[0005] In a similar but alternative approach, phase-matched subtracted images are used to quantify regional coronary blood flow using a video densitometry technique.

[0006] A dynamic contrast-enhanced CT lymphangiography method has been used for quantification of lymphatic flow rate in the thoracic duct (TD) in a swine model. Lymphatic flow rate was measured with two techniques: A first-pass analysis technique based on a single compartment model and a thresholding technique distinguishing between opacified and nonopacified voxels within the TD.

[0007] These methods are limited as they require identification of region of interest (ROI) of the blood vessel of interest on each medical image and analysis of temporal series of images that are subject to image artifacts.

[0008] Accordingly, it is desirable to provide systems and methods that enable objective, digital, real-time measurement of volumetric flow, pressure, resistance, and / or related vessel characteristics, without requiring subjective interpretation. Desirably, such systems and methods are configured to integrate seamlessly within existing interventional procedures so that no additional time, devices, or training are required of the clinician. Furthermore, other desirable features and characteristics of the present invention will be apparent from the subsequent detailed description and the appended claims, taken in conjunction with the accompanying drawings and the foregoing technical field and background.SUMMARY

[0009] The current diagnosis of lymphatic system is based on medical imaging (e.g., lymphangiography) to obtain a “road map” of the large lymphatic vessels. There is substantial variation in lymphatic structure including the thoracic duct (TD) and the lympho-venous junction. Hence, there is substantial need to quantify the structure (lumen cross-sectional area) and function (flow, pressure and resistance) systematically to understand the hemodynamic principles of the TD organ. The disclosure of the present application provides various devices, systems, and methods for measuring flow, pressure, resistance and / or other vessel characteristics that addresses this need.

[0010] Although imaging has been used to measure flow velocity, this does not necessarily correlate with flow rate, since lymphatic vessels can expand or contract their cross-sectional area to accommodate fluid when necessary. This allows flow velocity to remain relatively constant while flow rate fluctuates and dictates lymph flow discharge into the vein. Therefore, it is advantageous to assess volumetric flow rate, as is done with embodiments of the devices, systems and methods of the present disclosure, over fluid velocity, since fluid velocity is less likely to be impacted when attempting to diagnose CCLA in its early stages.

[0011] Additionally, the devices, systems and methods of the present disclosure can be integrated into current interventional workflow, which is not possible with intravascular ultrasound (IVUS), and will greatly improve diagnosis and allow evidence-based medicine where lesion severity is quantitatively and objectively assessed, and therapeutic interventions are qualified. The devices, systems, and methods of the present disclosure can be configured in the form of a guidewire and microcatheter assembly suitable for accessing target vessels in a manner consistent with current interventional practices. In certain embodiments, the assembly integrates novel components such as a miniature pressure sensor and balloon within a single device, thereby maintaining compatibility with clinical workflow while also providing new diagnostic capabilities. The routine acquisition of quantitative lesion geometry and implications on flow without added devices, interpretation, or analysis will streamline TD interventions and make practice more efficient and cost effective.

[0012] Furthermore, the objective real-time measurements (which is currently not possible with imaging) of the devices, systems and methods of the present disclosure, which do not require subjective interpretation, can provide routine diagnostic records of the procedure to ensure evidence-based treatment. This practice is in the theme of precision medicine to tailor the procedure to the patient based on quantitative, objective, accurate and reproducible measurements.Moreover, the present technology is non-ionizing and does not require fluoroscopy which exposes the clinicians and patients to x-ray radiation.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The disclosed embodiments and other features, advantages, and disclosures contained herein, and the matter of attaining them, will become apparent and the present disclosure will be better understood by reference to the following description of various exemplary embodiments of the present disclosure taken in conjunction with the accompanying drawings.

[0014] It should be appreciated that not all of the features of the components of the figures are necessarily described and some of these non-discussed features (as well as discussed features) are inherent from the figures themselves. Other non-discussed features may be inherent in component geometry and / or configuration. Furthermore, wherever feasible and convenient, like reference numerals are used in the figures and the description to refer to the same or like parts or steps. The figures are in a simplified form and not to precise scale.

[0015] Figure lAis a graphical representation illustrating arterial flow and pressure characteristics relative to stenosis severity in accordance with embodiments of the present disclosure.

[0016] Figure IB is an electrical circuit analog illustrating the relationship between arterial and venous pressures, resistances, and flow in accordance with embodiments of the present disclosure.

[0017] Figure 2 is a schematic representation of venous stenosis and related pressure-flow dynamics in accordance with embodiments of the present disclosure.

[0018] Figure 3 is a block diagram illustrating an exemplary system concept for thoracic duct flow and pressure measurement in accordance with embodiments of the present disclosure.

[0019] Figure 4 is a schematic illustration of a guidewire and microcatheter system for obtaining pressure and flow measurements during a saline challenge in accordance with embodiments of the present disclosure.

[0020] Figure 5A is a graph showing thoracic duct pressure-diameter relationships in accordance with embodiments of the present disclosure.

[0021] Figure 5B is a graph illustrating representative pressure-flow relationships during a saline challenge in accordance with embodiments of the present disclosure.

[0022] Figure 6 is a schematic of a bench-top experimental model used to simulate thoracic duct flow and stenosis in accordance with embodiments of the present disclosure.

[0023] Figure 7 is a set of representative pressure curves illustrating pressure dynamics during a saline challenge under different stenosis conditions in accordance with embodiments of the present disclosure.

[0024] Figures 8A to 8C show an illustration of a microcatheter assembly in various views configured for measurement of cross-sectional area, flow, pressure, and resistance in accordance with embodiments of the present disclosure.

[0025] Figure 9 is a system-level block diagram illustrating interaction between a user or clinician block, a console block, a pressure sensor block, a power injector block, a balloon block, and a patient block in accordance with embodiments of the present disclosure.

[0026] Figure 10 is a flowchart illustrating an exemplary method of operation of the system from a procedural perspective in accordance with embodiments of the present disclosure.DETAILED DESCRIPTIONAssessment of Functional Significance of Stenosis

[0027] Figure 1 A illustrates representative pressure-flow relationships associated with arterial stenosis. The left vertical axis represents percent maximum flow or pressure differential (AP) expressed as a percentage, ranging from 0 to 100. The top horizontal axis represents percent stenosis, ranging from 0 to 100, while the bottom horizontal axis represents the inside vessel radius in centimeters from 0.5 cm to 0.0 cm. Flow in cubic centimeters per second is indicated along the lower portion of the graph from 0 to 5. An adjacent vertical axis on the right provides a scale for AP in millimeters of mercury (mmHg) from 0 to 30.

[0028] As shown, the solid line represents flow and the dashed line represents AP. At larger vessel radii, corresponding to less than about 60% stenosis, the solid flow line remains near its maximum value and the dashed AP line remains close to zero, indicating that volumetric flow is relatively unaffected by narrowing in this range. As stenosis progresses beyond this threshold, however, the flow line decreases sharply while the AP line rises, reflecting the critical inflection point at which volumetric flow is compromised and pressure differential across the lesion increases. The crossover of these two curves highlights the transition from hemodynamically insignificant narrowing to functionally significant stenosis.

[0029] The systems, methods, and devices of the present disclosure are configured to provide real-time, objective measurement of these same parameters in vivo. By using integrated electrodes, sensors, and microcatheter assemblies to quantify both volumetric flow and pressure differential across a lesion, the disclosed technology enables clinicians to identify when a vessel stenosis reaches the critical range depicted in Figure 1A. In this way, the graphical relationship of Figure 1 A provides a theoretical basis for the diagnostic value of the disclosed measurements, and demonstrates the need for simultaneous acquisition of pressure and flow data that is not achievable with conventional imaging alone.

[0030] Arterial Stenosis. Percentage area stenosis (% stenosis) is the standard in assessing severity in arterial lesions. A clinician may wish to know if the stenosis is below or above a critical threshold to dictate treatment. Distal perfusion pressure remains largely unaffected until “critical” stenosis threshold is reached (Figure 1A). At the critical stenosis, there is a sudden drop in volume flow and pressure which will cause ischemia in the perfused territory. Flow and pressure drop are proportionally related through Poiseuille equation for a given flow resistance. For most arteries of clinical interest, the critical threshold centers around -70% ±10% area stenosis. There is some variation of the “critical” threshold due to differences in regional resistance and flow. The critical threshold as an empirical fact is well known, but the underlying reason for this phenomenon lies in the microvasculature.

[0031] The non-linear flow-stenosis curves are due to autoregulation of the peripheral circulation. When there is increasing stenosis of the regional artery, there is corresponding compensatory relaxation of peripheral arterioles which lowers peripheral resistance. This compensatory mechanism offsets the effects of proximal stenosis keeping flow across the stenosis relatively constant. This distal vasodilation is ‘maxed out’ at the critical threshold, i.e., the resistance of the stenosis approaches that of distal vasculature. Further increase of the stenosis results in flow loss and parallel pressure fall across the stenosis. It is important to remember that the pressure loss at issue is downstream of the stenosis affecting the perfused tissue. There is of course pressure change upstream, but they are buffered by baroceptor and other reflexes.

[0032] Figure IB illustrates an electrical circuit analog used to conceptualize the hemodynamic impact of a stenosis. In this representation, Pa corresponds to arterial pressure upstream of the stenosis, Pv corresponds to venous pressure downstream of the stenosis, Rs represents theresistance attributable to the stenosis itself, and Rp represents the resistance of the downstream peripheral vasculature. The circuit analogy demonstrates that total flow Q is given by the pressure difference divided by the sum of the two resistances, i.e., Q = (Pa - Pv) / (Rs + Rp). When Rs is much smaller than Rp, changes in stenosis severity do not materially affect overall flow. However, as Rs approaches or exceeds Rp, the total resistance increases significantly, resulting in a sharp reduction in flow, which corresponds to the critical stenosis threshold observed in Figure 1A.

[0033] A simple way to understand the origin of the critical threshold is to view peripheral vascular resistance as a stenosis in aggregate. The reduction in mean arterial pressure from 100mm Hg to 30 mmHg across the peripheral arterioles (AP of 70%) represents a terminal stenosis of 70% in the artery. Any proximal tandem stenosis in the artery will have to be greater than 70% to diminish perfusion further. The phenomenon of critical threshold can be represented mathematically by classical electrical theory analog as shown in Figure IB, where Paand Pvrepresent arterial and venous pressures, respectively, whereas Rsand Rprepresent stenosis and peripheral arteriolar resistances, respectively. Ohm’s law (electrical analog) or Poiseuille’s relation can be expressed Pa- Pv = Q (Rs + Rp) where Q represents volumetric flow. Normally, Rs« RPand hence any changes in Rsfor %stenosis < 70% do not affect the sum of the two resistors since one term is much larger than the other. At the point at which Rsbecomes similar to Rp, then the sum of the two resistors can be changed by further increases in Rsand hence can lead to a reduction in Q since Q = (Pa- Pv) / (Rs + RP).

[0034] Venous Stenosis. Iliac vein stenosis (e.g., May Thumer syndrome) is used here as a specific example, but the general principles described have broad application to most outflow pathways. The major difference between arterial and venous stenosis is of course the flow direction is reversed. The point of interest is still the peripheral circulation. Flow and pressure upstream of a venous stenosis are the salient elements. In chronic venous stenosis, flow is generally not compromised as venous collaterals are more abundant than in arteries. Venous pressure is more important in venous pathology. For example, peripheral venous hypertension is the basis of chronic venous disease (CVD) manifestations in Iliac vein stenosis. A 50 or 70% stenosis is commonly used as a significant lesion with therapeutic implications in venous disease. This is not a valid concept as there is no evidence for autoregulation related to stenotic lesions in the venous outflow. There is a continuous gradual pressure increase upstream of venous stenosis in experimentalvenous models. The curve is non-linear without a clear inflection point, i.e., there is no ‘critical’ venous stenosis such as seen in Figure 1A. In the electrical circuit analog (Figure IB), the proximal and distal resistance are similar and hence even a small stenosis can have a physiological impact on pressure (as opposed to arteries where the stenosis resistance must approach that of peripheral circulation to be significant). Peripheral venous pressure in the lower limb is influenced by many factors other than iliac stenosis, even though the latter is the dominant influence when present.

[0035] Many clinicians use stenotic diameter (venogram), or area measured by intravascular ultrasound (IVUS) to calculate %stenosis using adjacent “normal” lumen as a comparator. The problem with this approach is that there is no assurance that the “normal” lumen is indeed normal. Long diffuse stenosis without focal clues (Rokitanski stenosis) is a unique feature of iliac venous stenosis. The venographic appearance of such lesions can be deceptively normal, the presence of severe long stenosis comes to light only on IVUS planimetry. A more dependable method is to calculate %area stenosis based on expected normal lumen size. Such an ‘optimal’ lumen size for the various iliac-femoral vein segments can be calculated from flow equations using known normal values for flow and pressure. Calculated optimal areas closely correspond to IVUS-observed areas in non-stenotic normal iliac segments and comply with Young’s scaling rule. The ‘optimal’ segmental areas are the minimum caliber necessary to maintain normal venous pressure. Any reduction in caliber associated with obstructive symptoms is significant. In large clinical trials, median caliber reduction is in the range of 60-70%, but milder venous lesions occur at 10-15% stenosis. This is because factors such as lesion length and poor compliance of the venous bed contribute to venous hypertension in addition to stenosis caliber. Most iliac vein stenoses are asymptomatic because of compensatory mechanisms such as collateralization, increase in lymph flow, venodilatation and other factors.

[0036] Thoracic duct (TD) Stenosis. Like veins, the lymphatic system is a low-pressure system where pressure ratio such as fractional flow reserve (FFR) cannot discern the functional significance of TD stenosis. Given the low pressure / flow, a saline challenge is necessary analogous vasodilation in the coronary system that overcomes autoregulation and increases flow. The theoretical basis of the principle is described below. With the devices, systems and methods of the present disclosure, one can quantify not only lymph flow during intervention in real-time but also the functional degree of the stenosis to decide whether to treat or not. Flow rate outsideof normal values can be considered a biomarker for CCLA, since it relates to complications (e.g., obstructions or leakage) within the central lymphatics. Also, the rate of recovery of the pressure curve after the saline injection challenge will determine the severity of the stenosis (i.e., quick recovery denotes a normal lymphatic system, and slow recovery is a result of low flow or obstruction).

[0037] The present disclosure is particularly concerned with determining the functional significance of a stenosis in the thoracic duct by quantifying a pressure differential between the downstream vein and the upstream thoracic duct. However, the principles of the present disclosure are not limited to the thoracic duct and can be applied more generally in analogous diagnostic settings. For example, the disclosed systems and methods may be used to assess arterial stenosis, such as in the coronary or peripheral arteries, by correlating flow and pressure measurements to determine when a narrowing has reached hemodynamic significance. Similarly, the technology may be applied to venous outflow obstructions, including iliac vein stenosis or arteriovenous access stenosis, where objective assessment of resistance and pressure gradient can guide therapeutic decision-making. Other applications include evaluation of pulmonary vein stenosis, dialysis graft function, and lymphatic outflow disorders beyond the thoracic duct. In each case, the ability to obtain objective, real-time measurements of flow, pressure, and resistance provides a valuable diagnostic tool that is not achievable through imaging alone.

[0038] An exemplary embodiment of a microcatheter assembly 12 of the present disclosure is illustrated in Figures 8Ato 8C. The microcatheter assembly 12 comprises a catheter 10, a balloon 14, and a pressure sensor 16 disposed near the distal working end. The catheter assembly 12 is adapted for use with a 0.014 inch guidewire (not shown), consistent with common interventional practice. Since interventional procedures, including lymphatic interventions, typically require the use of such a guidewire and a 3 Fr. microcatheter that can be used for therapy (for example, for microembolization of lymphatic vessels), the catheter assembly 12 provides added diagnostic functionality while remaining compatible with established clinical workflow. In particular, the catheter 10, balloon 14, and pressure sensor 16 cooperate to enable measurement of cross-sectional area, pressure, flow, and resistance in real time, in addition to providing therapeutic access. This multiple functions-in-one approach maintains compatibility with current interventional practice while adding precision and vital information to aid in diagnosis and therapy assessment.

[0039] The guidewire (not shown) should mechanically perform like a standard device delivery rail. A guidewire typically consists of a solid core stainless steel material that can transmit force from the proximal end of the guidewire, whether manipulated directly by the hand of the interventionalist or by a robotic drive system, to the distal end of the core inside the body. By way of example only, the peripheral sizing guidewire may have a stainless-steel core, an atraumatic tip, and a body length of approximately 190 cm with a diameter of about 0.014 inch. The guidewire may include electrical wires (for example, approximately 0.001 inch in diameter) that run along its length and connect to two outer radiopaque electrodes and two inner opaque electrodes positioned at the distal end of the guidewire. The two outer electrodes can deliver a very low, safe, and non-stimulating voltage current (for example, about 125 pA peak-to-peak at 10 kHz) into the vessel lumen, while the two inner electrodes receive voltage drop measurements. Vessel sizing can be enabled with a transient displacement of fluid using a manual or automated saline injection (for example, about 3 ml over 2 to 3 seconds). The performance of the guidewire hinges on the ability to provide good pushability (no dissipation of the force), torqueability (1-to-l transmission without energy storage in the guidewire), and trackability (navigation through tortuous paths). The guidewire of the present device may alternatively be a hypo-tube rather than a solid core, which can facilitate transmission of multiple impedance wires as well as a pressure sensor wire through the center of the guidewire or hypotube.

[0040] The TD guidewire requires only a simple, sterile hook-up to a console via a connector cable attached to its proximal end. It is important to note that the TD guidewire does not require calibration during usage and can be disconnected and reconnected to the connector cable at any time, allowing the clinician to easily exchange devices over the wire.

[0041] Figure 2 illustrates torque transmission characteristics that are desirable in guidewires suitable for use with the present disclosure. The vertical axis shows output rotation in degrees, ranging from 0 to 2000, while the horizontal axis shows input rotation in degrees, also from 0 to 2000. The solid line corresponds to a comparative guidewire (CGW) that demonstrates an essentially linear 1 : 1 relationship between input and output rotations, such that a 1000 degree input results in nearly a 1000 degree output. The dashed line corresponds to a Wholey guidewire (Wholey GW), which exhibits significant hysteresis, such that a 1000 degree input may result in only about 700 to 800 degrees of output.

[0042] From these characteristics it can be appreciated that a guidewire used in the disclosed systems should demonstrate torque transmission ratios of at least about 90%, and preferably approaching 100%, across the operating range, with minimal lag or hysteresis. These properties facilitate accurate navigation through tortuous anatomy and allow precise positioning of electrodes, sensors, and balloons at the target site. In the context of the present disclosure, Figure 2 therefore provides an illustration of the type of mechanical performance characteristics desirable in a guidewire (not shown) that may be used with the catheter assembly 12 and console 50 described herein.

[0043] As shown in Figure 9, a console 50 provides the primary data acquisition, processing, and user interface functionality of the system. The console 50 may be implemented as a dedicated touch-screen unit or as a general -purpose computing device such as a laptop, tablet, or workstation operating appropriate software. The console 50 is configured to receive input signals from one or more interface devices, including but not limited to electrodes on a guidewire (not shown), a pressure sensor 16 on the catheter 10, and signals associated with inflation of the balloon 14 and operation of the power injector. From these signals, the console 50 determines vessel pressure values at upstream and downstream locations, and from these readings calculates differential pressure across the vessel segment of interest.

[0044] The console 50 is further configured to generate a constant current, measure the resulting voltage drop across electrodes, and apply modified Ohm’s law to compute vessel cross-sectional area or diameter. Additional algorithms executed by the console 50 may include resistance calculations, flow calculations based on pressure-flow relations, decay or recovery curve analysis following a saline challenge, and determination of parameters such as half-life or recovery time of the pressure curve.

[0045] The outputs of the console 50 may include real-time numerical values of vessel diameter, cross-sectional area, flow rate, pressure differential, and resistance. Graphical displays may be generated, such as pressure versus time curves, flow-pressure plots, or visual indicators of stenosis severity. The console 50 may also provide diagnostic outputs such as a percent stenosis value, a classification of whether a stenosis is hemodynamically significant, or raw and processed data available for export to external hospital information systems. In some embodiments, the console 50 may record and store patient-specific baseline data, facilitate comparison of pre- and postintervention measurements, and generate reports for documentation of the procedure.

[0046] Although a dedicated integrated console 50 may be preferred to streamline workflow, improve regulatory compliance, and facilitate reproducibility, the functionality described herein may also be distributed across multiple devices, such as an external data acquisition module coupled with a laptop computer or bedside monitor. Accordingly, the present disclosure encompasses any computing platform capable of executing the described acquisition, calculation, and display functions. The microcatheter, e.g., a 3 Fr., 40 cm long dual lumen microcatheter, will have one lumen for injection of saline and another for inflation of a balloon. The microcatheter will have a stiff proximal part and flexible distal part (5-10 cm). Apressure sensor will be mounted on the tip of the microcatheter for lymph pressure measurements. A thermistor as a component of the pressure sensor is used to automate the measurement process such that, when the bolus injection of saline is made at room temperature, the system detects the drop in temperature (from body temperature to saline temperature) and records the CSA / diameter without any manual intervention.

[0047] The catheter 10 may further comprise a balloon 14 located near its distal end. In certain embodiments, the balloon 14 may be a “smart” balloon configured with one or more electrodes to enable measurement of the balloon diameter in real time during inflation. Such a configuration allows the console 50 to confirm balloon apposition to the vessel wall and to correlate measured balloon expansion with vessel cross-sectional area. In other embodiments, the balloon 14 may be a conventional compliant or semi-compliant balloon without integrated electrodes, in which case balloon diameter may be inferred from known pressure-volume characteristics of the balloon material, from calibration curves, or from radiopaque markers. The balloon 14 may be sized according to the vessel being evaluated, for example ranging from about 2 Fr. to about 6 Fr., and may be configured in different shapes (for example, cylindrical or tapered) depending on clinical requirements.

[0048] The functionality of the balloon 14 within the disclosed methods may include temporary occlusion of the vessel to direct fluid flow during a saline challenge, ensuring antegrade delivery of saline without reflux. Inflation of the balloon 14 may also be used to create controlled pressure conditions for assessing pressure differentials across a stenosis, to evaluate vessel compliance, or to secure stable positioning of the catheter 10 during measurement. In certain embodiments, inflation and deflation of the balloon 14 may be automated and coordinated by the console 50, while in other embodiments manual inflation may be used. The balloon 14 may therefore serveboth a mechanical role in directing or stabilizing flow and, when configured with electrodes, a diagnostic role in providing vessel dimension data in real time.

[0049] A simple flow diagram of the system concept is shown in Figure 3 (TD - Thoracic duct, CC - Cistema chyli; P - Pressure; Giymph - Electrical conductivity of lymph; Qc and Rc - Flow and resistance during saline challenge, respectively; G - Electrical conductance, Dti / 2 - Half-life of pressure discharge’ DtR - Time to recovery of discharge pressure to baseline; Gp - Parallel conductance; S / F - Structure / function). The flush of saline both in the microcatheter and during saline challenge are automatically recorded by the thermistor. All calculations are done automatically internal to the console and displayed in real-time.

[0050] Theory of Flow Measurements. Ohm’s analog law for hemodynamics that relates pressure, flow and resistance has the form:DP = QR [1]

[0001] For a thoracic duct (TD)-venous system: DP, Q and R represent the pressure difference between the TD and the vein at the lympho-venous junction where the lymph drains, the lymph flow and the TD resistance, respectively. In measuring the pressure difference (TD guidewire pressure sensor in the vein and microcatheter pressure in the TD as shown in Figure 4, wherein PTD and Pv are the pressures in the thoracic duct and vein, respectively and RFC is the resistance to flow during the flow challenge and Q is the lymph flow), Equation 1 still has two unknowns (Q and R). To determine R, a saline challenge is introduced at flows substantially higher (e.g., 0.5 ml / s) than baseline lymph flow (0.05 ml / s) for several seconds (e.g., 5-10 seconds). The saline challenge is introduced through the microcatheter through a standard power injector (Figure 4). Prior to the saline injection, the balloon on the microcatheter is inflated to ensure that the saline flow through the TD is fully antegrade (i.e., prevents retrograde flow). The saline injection accomplishes two goals: 1) Determines R as the ratio of measured DP divided by the given Q (Equation 1); and 2) The time of recovery of the pressure curve (i.e., half-life or Dti / 2 or time to recovery of pressure curve DtR) determines the severity of the occlusion. Each of these goals is elaborated in turn.

[0052] To further understand the theory behind the first goal, one must appreciate the pressure / flow relation as dictated by Poiseuille’s law for a low flow, steady state system with Newtonian fluid given by:DP = Q (128pml / D4) R]

[0053] where 1 and D represent the length and diameter of the TD, respectively; and m is viscosity of lymphatic fluid. Poiseuille’s law for laminar flow steady state flow has the same form as Equation 1 where R = 128pl / D4. The question is whether the resistance R is constant or not. Since 1 is a given length of TD, R is constant if the diameter D of TD and the viscosity of lymph fluid are constant. Experiments have shown the pressure-diameter relation for the TD is relatively constant, i.e., the TD becomes rigid (does not change diameter) at relatively low pressure (> 5 mmHg, see Figure 5A). The viscosity of lymphatic fluid is constant (i.e., does not contain any red blood cells) and is like serum (1.1 centi -poise, slightly higher than water due to presence of protein and fat). Since both D and m are constant, R must be constant and can be determined during the flow challenge as R = RFC = DP / QFC (FC represents saline fluid challenge) or as the slope of the P-Q relation (Figure 5B). In essence, the flow challenge allows us to calibrate the TD-vein system to determine the resistance to flow. Once RFC = R is determined during the saline challenge, Q can be determined as Q = DP / RFC.

[0054] The rationale for the second goal is that the rate of discharge of a saline bolus injection challenge will depend on the resistance to flow which is determined by the degree of obstruction or resistance in the system. The rate of discharge can be quantified by either the half-life of the pressure curve or the duration for the spiked pressure curve during the injection to recover to baseline. To provide proof of concept for this rationale, a bench study has been performed to mimic the TD system as shown in Figure 6. Briefly, a container filled with saline at a pressure head that mimics the lymphatic TD pressure and flow allowed the discharge of saline through a tube with similar diameter as the TD (3-4 mm). A side arm syringe allowed a saline challenge over several seconds and the pressure was recorded (Figure 6). The dynamics of the pressure rise and fall during and after the saline injections were recorded at various degrees of tube stenosis relative to baseline (no stenosis). The flow rate was measured by the collection method (volume collected divided by period of collection).

[0055] Figure 7 shows representative pressure curves during the saline challenge at baseline (no stenosis of tube) and under different degrees of tube stenoses. As expected, both the pressure rise and fall curves are different under stenosis as compared to baseline. Since the rise pressure curve may be influenced by the rate of injection etc. (albeit this can be standardized with a power injector where the rate of flow and duration can be specified), the fall or discharge curve where the injection is completed is more indicative of the system response. Consider both the half-life of the pressure curve, Dti / 2 (i.e., time required for the pressure to equal to half the value from the peak pressure value to baseline) as well as the time required for the peak pressure to restore (R) to baseline, DtR. Some representative data of the relation between Dt and degree of stenosis are shown in Figure 7. Several observations can be made from this in vitro study. First, when inflow stenosis (Si) is < 59.7%, the Dt remains -0.07 s regardless of outflow stenosis. Second, the Dt remains -0.07 s when outflow stenosis increased from 0% to 62.6% if the stenosis (Si) was > 59.74%. Finally, a linear relation between Dt and outflow stenosis are observed when outflow stenosis increased from 62.6% to 100%. On the bench, DTR appears superior to Dti / 2 in terms of sensitivity (i.e., much broader range; 20-fold difference in range vs. 3 -fold difference for Dti / 2).

[0056] Theory of TD Lumen Cross-Sectional Area Measurements. The method of vessel sizing is based on the principle of electrical impedance based on a modified Ohm’s law as follows:G= EV = (CSA G) / L + GP[3] where G = measured electrical conductance; I = known electrical current injected; V = measured voltage drop; CSA = cross sectional area; o = fluid conductivity; L= distance between inner electrodes in a tetrapolar electrode arrangement where outer electrodes excite an alternating current (AC); and Gp= Parallel conductance. When a small and safe electric field is created inside the vessel, Ohm’s Law allows vessel cross-sectional area (CSA) to be determined by measurement of total measured conductance (G). Equation [3] has three unknowns: G, CSA and GpI is a known injected current and G is measured conductance). Equation [3] can be expressed as two equations in the TD in the presence of lymph and saline as:GlymPh (CSA OlymPh) / L + Gp[3 a]Gsaline (CSA Osaline) / L + Gp [3b]Since Osaiine is known, Eqs. [3a-b] can reduce to two equations and two unknowns to determine the patient-specific oiymph. This can be done using Equation [3] for lymph inside of the TD microcatheter (i.e., lymph will be withdrawn into the microcatheter when the TD guidewire is in the catheter prior to advancement to TD site of interest), to obtain (Gp= 0 since microcatheter is electrically insulative or non-conductive) and Eq. [3] becomes Ohm’s law:Giymph = I / V = CSA*oiymPh / L inside microcatheter [4a]

[0057] If saline is used to flush the lymph from the catheter, Eq. [4a] can be expressed as (CSA of catheter and electrode spacing L do not change and hence cancel out):Gsaiine / Glymph = Osaiine / ciymph inside microcatheter [4b]

[0058] Rearranging Equation [4b] and solving for the patient-specific lymph conductivity in the microcatheter as:Olymph = (G]ymph / Gsaime)oSaiine inside microcatheter [4c]

[0059] The patient-specific lymph conductivity can be determined since all other parameters are known / measured. It should be noted that devices and method presented herein represent the first ever in vivo lymph conductor meter that will determine each patient’s lymph conductivity which reflects the constitution of the lymphatic fluid (i.e., fat, protein, immune cells, etc. all have different conductive properties). Lymph conductivity may become a biomarker of various disease conditions.

[0060] Since the patient-specific Givmph will be calculated, this allows us to reduce Equations [3a- b] to two equations / two unknowns which can be solved as:CSATD — L (GQ.9% - Giymph) / ( D 0.9% “ Olymph) inside TD [5a]Gp (^saline Glymph " Glymph Gsaline) / (Osaline " Glymph) inSide TD [5b]

[0061] The parallel conductance Gpis a measure of conductivity of the surrounding tissue to the TD and is sensitive to edema. If the TD is assumed to be cylindrical or circular cross-section, the diameter D of TD can be given as:DTD = (4LDG / pDC)'2[6]

[0062] where D is the change in quantity between saline and lymph. Hence, measurement of Giymph at the location of interest in TD prior to the saline injection allows to compute the lumen CSA with single injection of saline as desired. This is a novel method that allows determination of patientspecific lymph conductivity, diameter and parallel conductance using single injection. This is an advancement over prior methods developed that used dual injections (0.9% normal saline and 0.45% half normal saline) to size blood vessels.

[0063] A schematic flow diagram of an exemplary method 300 is illustrated in Figure 3, delineating a systematic workflow for accessing the lymphatic system, performing conductance and pressure measurements, and deriving quantitative parameters such as flow, resistance, and cross-sectional area (CSA) in real time. This method is optimized for thoracic duct (TD) assessment, particularly for diagnosing conditions such as Central Conducting Lymphatic Anomaly (CCLA), but its underlying principles-based on electrical impedance (via Ohm's law analogs) and hemodynamic modeling (via Poiseuille's law)-are adaptable to other low-pressure vascular or conduit systems, including venous pathways (e.g., iliac veins), cerebrospinal fluid conduits, or dialysis access grafts, where precise measurement of pressure gradients, flow rates, resistance, or stenosis severity is clinically essential. The method 300 integrates previously described components, including a microcatheter assembly 12 (equipped with a balloon 14 or other occlusive element and a pressure sensor 16 or equivalent transducer), a guidewire with electrodes (e.g., in a tetrapolar configuration as depicted in Figures 8A-8C), a power injector or other fluiddelivery device for saline challenges, and a console 50 or processing unit that processes and displays data. This seamless integration aligns with existing interventional workflows, eliminating additional training or procedural time, and complements imaging-based techniques by providing functional data without ionizing radiation.

[0064] The procedure initiates at step 302 with access to a peripheral lymph node using a hookshaped needle (e.g., a HOOK needle or similar specialized access device), selected for its precision in penetrating superficial lymphatic structures under ultrasound or other imaging guidance while minimizing tissue trauma. At step 304, a contrast agent such as lipiodol (or alternatives like indocyanine green for fluorescence imaging or other radiopaque or fluorescent tracers) is injected to visualize the lymphatic system (LS), generating a roadmap to identify anatomical variations such as tortuosity or collateral channels, analogous to the stenosis mapping in Figure 1A. At step 306, the cistema chyli (CC) is accessed with a curved-tip needle (e g., a CURVE needle or other ergonomic navigation tool), designed for safe traversal through the retroperitoneal space or similar anatomical regions. At step 308, a guidewire with radiopaque markers or electrodes and a shapeable atraumatic tip (as shown in Figure 8) is inserted over the needle, functioning dually as a delivery rail and a sensor for impedance-based CSA measurements. At step 310, the microcatheter 10 or similar delivery catheter is advanced over the guidewire to the TD, where the pressure sensor 16 records intraluminal pressure P_TD, establishing a baseline for detecting upstream hypertension associated with obstructions.

[0065] In step 312, the guidewire is retracted into the lumen of the microcatheter, drawing lymph fluid into the catheter via aspiration or other fluid displacement methods, and the console 50 records conductance G lymph using electrodes (e.g., in a tetrapolar configuration) to minimize edge effects and ensure accurate voltage measurements (per the relation G = (CSA x sigma) / L + G_p [3]). At step 316, the microcatheter is flushed with saline or another known conductivity fluid, and the console records conductance G saline. At step 318, the console calculates the electrical conductivity of lymph sigma ymph using the approximation sigmajymph = (G lymph / G_saline) x sigma_saline [4c], where calibration factors may be applied to account for electrode geometry, boundary conditions, or fluid viscosity variations. This sigmajymph measurement serves as a novel biomarker of lymph composition (e.g., protein or lipid content), offering diagnostic insights into conditions like lymphedema or chylothorax.

[0066] At step 320, the guidewire is advanced to the lympho-venous junction or equivalent drainage site, and the pressure sensor 16 records venous pressure P_vein(t), providing the downstream reference for calculating the pressure differential delta P = P TD - P vein, a key parameter for assessing TD function. At step 322, a saline challenge is initiated using the power injector or similar device at a controlled flow rate (e.g., 0.1-0.5 ml / s for 5-10 seconds, exceeding baseline lymph flow of -0.05 ml / s), optionally with inflation of the balloon 14 or other occlusive mechanism to prevent reflux (as illustrated in Figure 4). A thermistor, conductivity sensor, or other suitable detector (e.g., optical or impedance-based) detects the saline bolus, enabling automatic synchronization of data capture. At step 324, the console 50 derives flow Q_C and resistance R_C using the relation delta P = Q x R [1], where R_C = delta P / Q_C is based on the known injector flow rate. Additional parameters, including delta_t_l / 2 (half-life of pressure decay) and delta t R (time to recovery of baseline pressure), are calculated from the pressure curve's decay profde, with bench models (Figure 7) demonstrating their sensitivity to stenosis severity (e.g., delta_t_R increases with obstruction). At step 326, continuous flow Q(t) is computed as Q = delta_P / R, with resistance R calibrated from the challenge (R FC), facilitating real-time monitoring critical for assessing TD hemodynamics.

[0067] At step 328, the console 50 records conductance G(t) following the saline flush and calculates the time-varying cross-sectional area CSA(t) using the relation CSA_TD = L x (G_saline - G_lymph) / (sigma_saline - sigma_lymph) [5a], where L is the electrode spacing or detection distance. Parallel conductance G_p is also determined, providing insight into surrounding tissue conductivity (e.g., elevated G_p may indicate edema or fluid overload). At step 330, the console 50 displays the structure-function (S / F) relationship in real time, where outputs- such as P_vein(t), P_TD(t), Q_TD(t), CSA(t), R, delta_t_l / 2, delta t R, sigma lymph, and G_p- may be provided individually or in any combination based on clinical needs, rather than requiring all parameters simultaneously. Among these, delta P, Q(t), CSA(t), R, and delta t R are particularly relevant to the overarching goal of quantifying TD structure and function, enabling objective assessment of flow resistance and stenosis severity for evidence-based interventions in CCLA. These outputs may be presented as numerical values, graphical plots (e.g., pressure-time curves per Figure 4 or flow-pressure relationships per Figure 5B), or diagnostic indices (e.g., percent stenosis calculated as (1 - (CSA_lesion / CSA_normal)) x 100, with thresholds informedby Figure 1 A). Optional visualizations include color-coded severity maps, overlays of pre- and post-intervention data, or automated reports integrated into hospital information systems.

[0068] Not all steps or outputs of method 300 are required in every embodiment. Certain steps, such as conductivity measurements (312-318) or balloon inflation (322), may be omitted if clinically unnecessary or if anatomical constraints preclude their use. Clinicians may select specific outputs based on the clinical context-e.g., relying solely on delta_P for rapid assessment or reviewing detailed CSA(t) data for lesion characterization. Alternative embodiments enhance flexibility: (1) Access Variations: Inguinal, transhepatic, or other percutaneous approaches may replace peripheral lymph node access for patients with inaccessible nodes or varying anatomies. (2) Injectate Options: Hypertonic saline, conductive dyes, or therapeutic agents (e.g., sclerosants) may be used for enhanced signal contrast or dual diagnostic / therapeutic effects. (3) System Configurations: The console 50 may incorporate wireless data transmission, distributed processing units, or Al-driven predictive models (e.g., forecasting post-stenting outcomes). (4) Multi-Site Analysis: Repositioning the guidewire enables segmental resistance profiling along the TD or other conduits. (5) Extended Applications: The method may be adapted for venous stenosis (reversing flow direction per Figure IB), dialysis access graft patency, or cerebrospinal fluid dynamics, with scaled devices for pediatric or small-vessel use. These variations underscore the method's adaptability, delivering objective, quantitative vessel function data across diverse clinical scenarios.

[0069] Figure 4, generally referenced by numeral 400, illustrates an exemplary implementation of the disclosed system for assessing thoracic duct (TD) function through integrated pressure and conductance measurements in conjunction with a saline challenge. The system comprises the catheter assembly 12 including catheter 10, balloon 14 or another occlusive element, and a distal pressure transducer 16 that is carried on a dedicated pressure-sensing wire (not shown) routed within the catheter 10. A separate bioimpedance guidewire (not shown) provides electrodes for conductance measurements and vessel sizing. A power injector 24 (or other controlled fluid delivery device) delivers a defined bolus, and a console 50 (or processing unit) performs data acquisition, analysis, and output generation.

[0070]

[0069] Figure 4, generally referenced by numeral 400, illustrates an exemplary implementation of the disclosed system for assessing thoracic duct (TD) function through integrated pressure and conductance measurements in conjunction with a saline challenge. Thesystem comprises the catheter assembly 12 including catheter 10, balloon 14 or another occlusive element, and the distal pressure transducer 16 that is carried on a dedicated pressure-sensing wire (not shown) routed within the catheter 10. A separate bioimpedance guidewire (not shown) provides electrodes for conductance measurements and vessel sizing. A power injector 24 (or other controlled fluid delivery device) delivers a defined bolus, and a console 50 includes a processor configured for data acquisition, signal processing, analysis, and output generation. The combination of these components allows objective, real-time quantification of TD hemodynamics and provides a functional alternative to imaging-only techniques, thereby supporting precision diagnosis of conditions such as central conducting lymphatic anomaly (CCLA) and other lymphatic or venous outflow disorders.

[0071] A method block 410 represents placement of the pressure-sensing wire in the subclavian vein to record venous pressure P_v. Because venous flow is substantially greater than TD flow, P_v may be considered substantially constant over the time scale of the challenge and thus can be acquired either before or after the saline bolus without materially affecting accuracy. The signal from the pressure transducer 16 is communicated to the processor of console 50, which receives, digitizes, and stores the venous pressure value for later use in calculating pressure gradients. Block 412 illustrates determination of TD cross-sectional area (CSA) by bioimpedance using electrodes on the bioimpedance guidewire. Conductance signals generated by the electrodes are transmitted to the processor, which applies calibration factors to convert conductance into CSA values. Block 414 depicts recording of intraluminal TD pressure P_TD via the distal pressure transducer 16, with the resulting signal again received by the processor for comparison with P_v. Balloon 14 may be inflated during the challenge to prevent retrograde reflux of inj ectate and ensure antegrade flow into the venous system, with balloon control optionally synchronized by console 50.

[0072] Anatomical schematic 420 shows catheter 10 advanced into the TD, with balloon 14 and the distal tip of pressure-sensing wire positioned to capture P_TD and maintain directional flow during the maneuver. The power injector 24 delivers a saline bolus at a controlled rate and duration (for example, about 0.1-0.5 ml / s for several seconds) to create a reproducible hemodynamic perturbation against which TD pressure, resistance, and flow can be quantified. Timing and volume signals from injector 24 may be communicated to console 50 so that the processor can synchronize known bolus delivery with sensor data, thereby enabling accurate real-time calculations of AP, Q, and R.

[0073] Several representative outputs may be generated by the processor of console 50. Plot 418 shows flow Q versus time during the saline challenge, with the processor deriving Q from pressure responses and known injector inputs, typically demonstrating a baseline, a step increase to a plateau, and a return to baseline as the bolus dissipates. Plot 422 shows pressure differential AP versus time; the processor computes AP as P_TD - P_v and plots the decay profde, where a solid line represents normal recovery and dashed lines illustrate progressively delayed recoveries indicative of obstruction or severe obstruction. Plot 424 shows CSA versus time; here, the processor converts bioimpedance signals into CSA values and displays their dynamic changes, with abnormal recovery curves reflecting impaired duct compliance. Scatter graph 426 plots AP against Q; the processor calculates both AP and Q, performs regression analysis, and generates a line of best fit representing functional resistance R FC (consistent with the relation AP = Q x R). Functional resistance, calculated as the ratio of pressure differential to flow (R FC = delta P / Q_C) [1], is a useful parameter in diagnostics, providing an objective measure of thoracic duct (TD) obstruction severity that guides evidence-based interventions for conditions like Central Conducting Lymphatic Anomaly (CCLA). Plot 428 provides a detailed view of Q versus time, including bolus entry, peak flow, and return to baseline. Console 50 may be configured such that its processor generates all, some, or only a subset of these outputs, and the clinician may select which plots or parameters are displayed for a given case.

[0074] Collectively, the outputs 418-428 illustrate how the disclosed system, through its processor, converts raw pressure and conductance signals into clinically actionable parameters. The processor executes algorithms to calculate indices such as resistance curves (R_FC), decay times (At R, At 1 / 2), and CSA recovery profiles. These calculations provide objective markers of hemodynamic significance that can be tailored to different diagnostic needs. Not all processor- derived outputs are required in every procedure: for rapid stenosis assessment, a AP-versus-time trace may suffice; for more detailed evaluation of duct mechanics, CSA-versus-time or resistance analysis may be preferred. Outputs generated by the processor may be displayed in real time on console 50, stored for post-procedural review, or exported to hospital information systems. The ability of the processor to (i) receive venous reference pressure P_v from the pressure sensing wire, (ii) receive TD pressure P_TD from the same wire, (iii) receive conductance signals from guidewire to estimate CSA, and (iv) integrate injector 24 timing signals to impose a controlledperturbation enables quantitative, procedure-integrated assessment of stenosis severity, resistance, and compliance.

[0075] In certain embodiments, the order of operations may be varied without departing from the method. For example, P_v can be acquired before or after the saline challenge; CS A measurements may be taken pre- and post-challenge to assess dynamic lumen behavior; and balloon 14 inflation may be omitted in anatomies where reflux risk is low. The processor of console 50 accommodates these variations by adjusting the sequence in which signals are received, synchronized, and analyzed. The pressure-sensing wire and the bioimpedance guidewire may also be exchanged or repositioned between steps to map segmental variations in resistance or compliance along the TD, with the processor updating calculations accordingly.

[0076] Signal processing performed by the processor of console 50 may include filtering of pressure and conductance waveforms, synchronization of injector 24 timing signals with acquired data, calibration of conductance-to-CSA relations (including electrode spacing and boundarycondition factors), and derivation of AP, Q(t), R, R FC, At_R, and At_l / 2. Optional visualizations may be generated by the processor, including color-coded severity indicators, comparative pre- / post-intervention overlays, or automated summaries suitable for integration into procedural records or hospital information systems.

[0077] Although Figure 4 is described in the context of the thoracic duct, the same configuration — using a pressure-sensing wire 30 distinct from the bioimpedance guidewire, together with balloon- assisted flow control, a controlled fluid challenge, and processor-driven signal analysis — may be applied to other vessels or conduits where objective assessment of pressure gradients, flow, resistance, or stenosis is desired. These include venous outflow pathways, dialysis access grafts, or cerebrospinal fluid conduits. In each case, the processor of console 50 may be configured with vessel-specific algorithms so that the same system architecture delivers tailored, clinically relevant outputs.

[0078] Figures 5A and 5B disclose additional potential outputs generated by the disclosed system, illustrating relationships derived from the method 300 that enhance the quantitative assessment of thoracic duct (TD) function. Figure 5A plots diameter (in millimeters, ranging from 1 to 5 mm) against pressure differential delta P (in cmH20, ranging from 2 to 10 cmH20), demonstrating the TD’s pressure-diameter response under varying hemodynamic conditions. Figure 5B plots delta P (in cmFhO, ranging from 0 to 10 cmFFO) against flow Q (in ml / min, ranging from 0 to 25 ml / min),reflecting the flow-resistance characteristics during a saline challenge. These outputs, produced by the console 50 through data acquired via the pressure sensor 16 and guidewire electrodes (as described in steps 310 and 324 of method 300), complement the system’s real-time monitoring capabilities. The diameter versus delta P relationship in Figure 5A, measured via bioimpedance (block 412), reveals the TD’s rigidity or compliance, with a relatively constant diameter above 5 mmHg, indicating that diameter changes are minimal under physiological pressures, which is clinically relevant for assessing structural integrity in conditions like CCLA where vessel compliance may be impaired. The delta P versus Q relationship in Figure 5B, derived from the saline challenge (step 322) and calculated using delta P = Q x R [1], provides a direct measure of functional resistance R FC, with the slope of the best-fit line (e.g., scatter graph 426 in Figure 4) offering a quantitative indicator of flow obstruction. Clinically, these outputs are significant for diagnosing TD stenosis severity, as a reduced diameter range or steeper delta_P-Q slope may signal significant resistance or patency issues, guiding therapeutic decisions such as stenting or embolization, and supporting the system’s goal of enabling evidence-based, precision medicine for CCLA management.

[0079] Figure 6 illustrates an exemplary bench model embodiment of the disclosed system configured to simulate thoracic duct (TD) hemodynamics for validating the saline challenge method (e.g., step 322 of method 300) and assessing the impact of stenosis on pressure decay profiles. This in vitro setup provides proof-of-concept data supporting the system's ability to quantify flow resistance and stenosis severity through parameters such as delta_t_l / 2 and delta t R, as derived from console 50 processing of pressure sensor data during fluid challenges. The model mimics the low-pressure, low-flow characteristics of the TD-vein system, enabling controlled testing of the devices and methods described herein without in vivo risks, and can be implemented using standard laboratory components for research, training, or calibration purposes. While this section focuses on the benchtop embodiment, the features, values, and teachings presented are applicable to the other embodiments described herein, including in vivo implementations, ensuring consistency across clinical and experimental contexts.

[0080] The bench model comprises a raised flask or reservoir filled with saline or a lymphatic fluid analog (e.g., serum-like solution with viscosity of approximately 1.1 centipoise) positioned at a height equivalent to 8 mmHg (practically ranging from 5-15 mmHg to simulate physiological TD pressure heads), serving as a constant pressure source to drive baseline flow. Connected to thereservoir is a tubing segment with an inner diameter of 2.6 mm (practically ranging from 2-4 mm to approximate TD dimensions) and length of 690 mm (practically ranging from 500-1000 mm for scalable simulation), through which saline discharges at a baseline flow rate Q of 3.528 ml / min (practically ranging from 1-5 ml / min, consistent with TD lymph flow estimates). Variable stenosis elements S_i (inflow stenosis) and S_o (outflow stenosis) are incorporated along the tubing, allowing adjustment of outflow stenosis from 0% (no stenosis) to 95% (severe stenosis), or practically up to 100% for complete occlusion studies, to evaluate resistance effects as per Poiseuille's law [2], These ranges and configurations are representative of both benchtop and in vivo TD conditions, facilitating direct translation of findings.

[0081] A catheter assembly 12, including catheter 10 (e.g., a microcatheter with at least two lumens for fluid delivery and pressure sensing), is integrated into the tubing pathway, with fluid efflux depicted at the distal end of catheter 10 to simulate antegrade discharge into a venous analog. A pressure wire 30 (analogous to the guidewire's pressure capabilities in Figure 8) is positioned within the tubing to record dynamic pressure changes. A side-arm syringe or injector is connected for delivering a saline challenge bolus, labeled with a pressure peak of approximately 30 mmHg (practically ranging from 20-50 mmHg to exceed baseline while remaining safe for device integrity), enabling simulation of the flow challenge described in step 322 of method 300. These components and their operational parameters are consistent with those used in the in vivo embodiments, ensuring applicability across settings.

[0082] In operation, the bench model replicates the TD system by allowing baseline saline discharge through the tubing, with the syringe introducing a transient high-flow challenge (e.g., 0.5 ml / s for several seconds) to spike pressure and assess discharge dynamics. The pressure wire 30 captures the rise and fall of induced pressure, generating data for calculating delta_t_l / 2 and delta_t_R as functions of stenosis degree, validating that prolonged recovery times (e.g., as shown in Figure 7) indicate higher resistance or obstruction. This embodiment ties directly to the disclosed systems and methods by demonstrating how components like the catheter assembly 12, pressure wire, and console 50 (for automated analysis) can be adapted for ex vivo testing, ensuring reproducibility and calibration of in vivo measurements for CCLA diagnostics. Practically, variations may include adjustable flask heights (5-20 mmHg), tubing materials (e.g., silicone or PVC for compliance simulation), or automated injectors for precise challenge replication,broadening its utility for method optimization and clinician training, with these adaptations equally applicable to clinical embodiments.

[0083] Figure 7 illustrates bench-derived validation data demonstrating how the disclosed system can quantify functional stenosis severity using discharge dynamics of a saline challenge. The figure contains three related plots: pressure versus time (A), AtiA versus percentage outflow stenosis So (B), and At_R versus So (C).

[0084] Plot A shows representative pressure-time curves obtained during bolus injections under different stenosis conditions. A first injection at baseline (Si = 59.7%, So = 0%) produces a steep, rapidly decaying pressure spike, with a half-life Ati / 2 of approximately 0.032 seconds and a recovery time At_R of 0.07 seconds. A second injection under increased outflow stenosis (Si = 59.7%, So = 95%) produces a broader, slower-decaying curve, with corresponding values of 1.17 seconds and 0.096 seconds. These paired traces demonstrate that increasing outflow obstruction prolongs the time constants of pressure decay, reflecting impaired duct clearance.

[0085] Plot B aggregates measurements of Ati / 2 across varying So values. The data indicate that when inflow stenosis (Si) is less than approximately 59.7%, Ati / 2 remains stable around 0.07 seconds regardless of outflow stenosis, suggesting limited sensitivity of this metric in early disease. However, at higher So values approaching 100%, Ati / 2 increases, displaying a roughly threefold dynamic range.

[0086] Plot C depicts At_R versus So. Unlike Ati / 2, At_R shows a linear and broader response range as outflow stenosis increases, with approximately twentyfold sensitivity between baseline and severe obstruction. This makes At_R particularly valuable as a biomarker of functional stenosis severity.

[0087] In the context of the disclosed system, these plots are generated by the console processor, which receives raw pressure signals from the intraductal pressure sensor and synchronizes them with injector timing data. The processor computes decay constants (Ati / 2, At_R) by curve fitting and exponential regression, then relates them to calibrated stenosis indices.

[0088] For clinicians, the practical meaning of Figure 7 is that different discharge parameters provide complementary information: Ati / 2 may serve as a rapid screening tool, while At_R provides finer discrimination of obstruction severity. Together, these outputs transform transient pressure spikes into objective, quantitative markers of thoracic duct resistance and compliance, guiding decisions about whether intervention is warranted.

[0089] Figures 8A-8C respectively illustrate a side view, a cross-sectional view, and a detail view of an exemplary catheter assembly 12 in accordance with embodiments of the present disclosure. The catheter assembly 12 includes an elongated catheter shaft 10 having a proximal end and a distal end, with balloon 14 or other occlusive element disposed adjacent the distal end. At the proximal end, the assembly incorporates three connectors: an electrical connector 18, a guidewire connector 20, and a balloon inflation connector 22. The electrical connector 18 establishes a signal pathway from the distal pressure sensor 16 to console 50 for data acquisition and processing, enabling real-time transmission of pressure measurements. The guidewire connector 20 permits insertion, exchange, or manipulation of a guidewire for advancing the catheter through tortuous vasculature or lymphatic pathways, such as the thoracic duct. The balloon inflation connector 22 communicates with balloon 14 through a dedicated inflation lumen, allowing the balloon to be selectively inflated or deflated to occlude flow during diagnostic maneuvers such as the saline challenge, ensuring antegrade flow for accurate resistance calibration.

[0090] The catheter 10 incorporates multiple internal lumens to support these functions. These include a balloon inflation lumen 42 for fluid delivery to the balloon, a sensor wire lumen 44 for routing electrical conductors from the pressure sensor, and a guidewire lumen 46 for accommodating the guidewire. The guidewire lumen 46 is sized to accommodate a guidewire of 0.014 inches in diameter or larger (approximately 0.36 millimeters or more), permitting compatibility with standard interventional guidewires while maintaining navigability in small vessels, with practical ranges from 0.014 to 0.035 inches (0.36 to 0.89 millimeters) to suit various anatomical constraints. The catheter 10 has an overall outer diameter of approximately 3 French (about 1 millimeter), or practically ranging from 2 to 4 French (0.67 to 1.33 millimeters), balancing functional capacity with the need for atraumatic navigation in small-caliber ducts such as the thoracic duct. Given these dimensional constraints and the limited real estate available for miniature catheters that can access the thoracic channels, integration of a pressure sensor requires the use of very small-scale technology to ensure compatibility without compromising device performance, with sensor dimensions typically under f millimeter in any axis to fit within the catheter's profile.[009 f] In one embodiment, the pressure sensor 16 may comprise a miniature absolute pressure sensor dimensioned to fit within a 1-French hypo tube, such as a disposable catheter tip sensor. The sensing component of such a device is based on a micro-electro-mechanical system (MEMS)die incorporating a thin, pressure-sensitive silicon diaphragm. The diaphragm is formed over a sealed reference cavity held at vacuum. When exposed to in vivo fluid pressure, the diaphragm deflects by a minute amount, altering the resistance of piezoresistive elements configured in a Wheatstone bridge on the die. The bridge output voltage is directly proportional to the applied pressure, with sensitivity on the order of several microvolts per volt per mmHg. By comparing the in vivo pressure against the vacuum cavity, the sensor provides an absolute pressure measurement rather than a relative or gauge value.

[0092] The MEMS die and associated micro-scale electronics are fully encapsulated for in vivo use without external gels or encapsulants, and may be pre-attached to insulated micro-conductors (for example, a trifilar three-strand cable) for simplified integration. Typical sensor dimensions are on the order of 750 micrometers x 220 micrometersx75 micrometers, with an operating range of about -300 mmHg to +500 mmHg (460 to 1260 mmHg absolute). The device exhibits low drift (e.g., <2 mmHg per 24 hours in 37 °C saline) and compliance with applicable AAMI / ANSI BP22 standards, making it well suited for acute procedures.

[0093] Alternative miniature sensing technologies may also be used, including capacitive MEMS diaphragms, optical fiber Bragg grating transducers, or piezoelectric thin-film sensors, particularly in embodiments where catheter dimensions differ or where longer-term monitoring is required. Larger pressure sensors, which may not rely on MEMS fabrication, can also be employed in applications involving larger vessels or conduits where spatial constraints are less stringent. Alternative miniature pressure sensors may also be employed, including fiber-optic micro-sensors (e.g., those utilizing Fabry-Perot interferometry for high-resolution measurements), MEMS piezoresistive devices (e.g., silicon-based chips with integrated strain gauges), or capacitive diaphragm sensors (e.g., those detecting membrane deflection via capacitance changes), provided they can be miniaturized to dimensions suitable for use in a <3 French catheter while maintaining biocompatibility and stability in saline environments. While miniature devices are preferred for accessing thoracic channels due to anatomical constraints, larger pressure sensors may be used in applications where catheter size is less constrained, such as central venous pressure monitoring, dialysis graft assessment, or other large-caliber conduits like arteries or cerebrospinal fluid pathways, allowing for sensors with enhanced features like multi -parameter sensing or wireless transmission.

[0094] The working end of catheter 10 includes balloon 14, which may have a length of about 10 millimeters (practically ranging from 5-20 millimeters) and an inflated diameter of about 5 millimeters (practically ranging from 3-10 millimeters), with dimensions selected based on the target anatomy to achieve effective occlusion without vessel trauma. The catheter 10 extends distally beyond balloon 14 to position pressure sensor 16 either at the extreme distal tip or slightly proximal thereto, ensuring accurate intraluminal pressure capture downstream of the occlusion during challenges. In certain embodiments, the pressure sensor 16 may protrude distally beyond the catheter shaft to ensure direct exposure to the intraluminal environment outside the confines of the catheter lumens, minimizing artifacts from lumen confinement. In other embodiments, the pressure sensor 16 may be flush-mounted at the distal tip or positioned just proximal to it, provided fluid communication with the intraluminal space is maintained through apertures or open lumens, allowing for design flexibility in balancing sensor protection and measurement fidelity.

[0095] Marker bands 46 are incorporated into catheter 10 to assist with visualization under fluoroscopy, ultrasound, or other imaging modalities. At least one band marks the proximal end of balloon 14, a second band marks the distal end of balloon 14, and a third band marks the distal tip of catheter 10. These radiopaque or echogenic markers facilitate precise positioning of the balloon and sensor within the target anatomy, ensuring that pressure and conductance measurements are obtained at the intended location while minimizing procedural time and radiation exposure.

[0096] Figure 9, generally referenced by numeral 500, illustrates a functional and hardware diagram of the complete system in accordance with embodiments of the present disclosure. The diagram depicts the integration of user 502, catheter assembly 12 (including pressure sensor 16 and balloon 14), bioimpedance guidewire (not explicitly shown but implied through data flow), power injector 540 for saline challenges, console 50, and patient 542 as the anatomical target. This architecture 500 ties back to previously described components, such as the catheter assembly in Figures 8A-8C, pressure sensor details in the IntraSense embodiment, and method steps in Figure 3, while illustrating hardware interconnections (e.g., electrical, fluidic, and data pathways) and functional data flows (e.g., inputs, processing, and outputs) that enable quantitative assessment of thoracic duct (TD) or other vessel stenosis, flow, pressure, and resistance.

[0097] User 502 interacts with the system by providing commands through console 50, initiating steps such as taking initial lymphatic pressure measurement 504 via pressure sensor 16 positioned in the TD, taking venous pressure measurement 506 via the pressure sensor 16 placed in thesubclavian vein, inflating balloon catheter 508 to occlude retrograde flow, and dispensing X volume saline challenge 510 via power injector 540. These actions may be manual (e.g., user- triggered via buttons or touchscreen) or semi / fully-automated (e.g., console-guided sequences), with console 50 providing feedback on readiness and completion.

[0098] Console 50 serves as the central processing hub, receiving inputs 512 including user commands (e.g., start challenge, inflate balloon), pressure signals from pressure sensor 16, "Complete" flag from power injector 540 indicating bolus delivery finish, and status flag from balloon catheter 12 confirming inflation / deflation state.

[0099] Console 50 incorporates memory 520, which may comprise any non-transitory computer- readable medium such as random access memory (RAM), read-only memory (ROM), flash memory, optical storage, magnetic storage, or solid-state drives, for storing software modules 526, calibration data 532, and baseline measurements. Processor 522, which may include one or more microprocessors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or central processing units (CPUs), executes software modules 526 comprising computer programming instructions in languages such as C, C++, Java, Python, or assembly, to perform processing 516 tasks including storage of initial lymphatic pressure baseline, "RC" decay calculation algorithms (e.g., exponential fitting to derive delta_t_l / 2 and delta t R from pressure decay curves post-challenge), and stenosis calculation algorithms (e.g., using delta_P, Q, and CSA to compute percent stenosis via (1 - (CSA_lesion / CSA normal)) x 100). Outputs 518 from console 50 include control commands to saline injector, sensor, and balloon, transmitted via a 3-pin connector 526 (or alternatives such as USB, Ethernet, wireless Bluetooth, or proprietary interfaces) that handles trigger signals out and data in, ensuring bidirectional communication. The graphical user interface (GUI) 524 displays results, which may include delta_P, percent stenosis, raw data (e.g., pressure waveforms), or diagnostic summaries (e.g., "normal," "obstruction," "severe obstruction" based on thresholds), presented numerically, graphically (e.g., curves per Figure 4), or as alerts, with options for export to hospital information systems.

[0100] In embodiments where console 50 is implemented on a general -purpose computing platform (e.g., laptop, desktop, tablet, or smartphone), it runs under operating systems such as Windows, Linux, macOS, iOS, or Android, with software modules 526 as applications or apps. Alternatively, console 50 may be a dedicated device without a general -purpose OS, usingembedded firmware or RTOS (e g., FreeRTOS, VxWorks) for real-time processing, with GUI 524 as a touchscreen, LCD display, or LED indicators integrated into the hardware. Calibration data 532, such as factory-set coefficients or in situ adjustments, is stored in memory 520 and tracked via unique device IDs, timestamps, or blockchain-like logs for traceability, ensuring compliance with medical standards.

[0101] Pressure sensor 528 is integrated into the distal region of the catheter assembly 12 and functions to capture intraluminal pressure signals during diagnostic or interventional procedures. In some embodiments, the pressure sensor 528 is dimensioned for compatibility with small-lumen guidewire systems, for example catheters designed to accept 0.014-inch guidewires (approximately 0.36 mm in diameter). In other embodiments, sensors may be scaled for use with larger lumens, such as those designed for 0.018-inch or 0.035-inch guidewires (approximately 0.46 mm and 0.89 mm, respectively), depending on the target anatomy and clinical workflow.

[0102] The sensor is configured to measure pressure within the thoracic duct or other vessel with a defined tolerance and resolution. For example, the device may operate with a tolerance in the range of about 5-10% of the measured value and an absolute accuracy of about ±5 to ±10 mmHg across a clinically relevant pressure range (for example, 0-50 mmHg). The resolution of the sensor may be on the order of ±2 mmHg or finer, enabling the system to detect small changes in intraluminal pressure that are critical for accurate calculation of differential pressure (AP) between upstream and downstream sites. This fine resolution also supports reliable derivation of cross- sectional area (CSA) when conductance measurements are combined with pressure readings.

[0103] Communication between the pressure sensor 528 and the console 50 occurs through a dedicated electrical connection, illustrated as a three-pin connector 526 (reference numeral 18 in figure 8A). This connection allows bidirectional communication: the console 50 may transmit control signals to trigger a measurement sequence, perform calibration checks, or adjust sensor gain, while the sensor transmits raw or pre-calibrated pressure signals back to the console in real time. The received signals are processed by the console’s processor 522, which filters the waveforms, applies calibration data 532, and integrates the pressure information with other inputs such as venous reference pressure, conductance-based CSA, and saline injection timing.

[0104] By integrating these functions, the pressure sensor 528 provides high-fidelity input that enables the processor of console 50 to compute clinically actionable outputs such as AP versus time, resistance values, decay constants (At_l / 2, At_R), and percent stenosis. In larger-vesselapplications, where more physical space is available, pressure sensors with larger membranes or housings may be used to increase durability, while in small-vessel or thoracic duct applications, miniature MEMS-based sensors or fiber-optic transducers may be preferred to minimize catheter profile while maintaining resolution.

[0105] Balloon 546 (reference number 14 in figure 8A) receives inputs 548 from console 50 or manual controls, where balloon fill is managed by console commands (automated using pneumatic pumps or solenoid valves) or manual syringe (for user-controlled inflation), with outputs 550 including inflate / deflate balloon to occlude / restore flow, controlled by fluid (e.g., saline, air) through lumen 42 and balloon inflation connector 22, leveraging catheter 10's inflation lumen.

[0106] Power injector 540 (reference numeral 24 in figure 4), or equivalent fluid delivery device, receives dispense command 538 from console 50 and acts only if a "Ready" flag is active (e.g., balloon inflated, patient positioned). It accepts commands for dispensing X volume (e g., 3-10 ml) at rate Y (e.g., 0.1—0.5 ml / s), or variables adjusted for patient anatomy (e.g., reduced rate for high- pressure faults or reduced volume to clear lymph baseline), and may perform an initial flush to displace lymph for baseline conductance (G lymph [3]) before the main challenge. Outputs 536 include dispensing X at Y, sending "Complete / Ready" flag to console 50, and status signals for synchronization; the injector may incorporate pressure limits (e.g., 20-50 mmHg fault threshold) or adaptive modes (e.g., closed-loop adjustment based on real-time delta P feedback to reduce rate or abort). Notes on reduced flow rate or initial flush are addressed through variable X / Y and console-triggered flush protocols, with injector 540 capable of open-loop (fixed parameters) or closed-loop operation (e.g., modulating Q if pressure exceeds limits or lymph is detected via thermistor).

[0107] Balloon 546 receives inputs 548 from console 50 or manual controls, where balloon fill is managed by console commands (automated using pneumatic pumps or solenoid valves) or manual syringe (for user-controlled inflation), with outputs 550 including inflate / deflate balloon to occlude / restore flow, controlled by fluid (e.g., saline, air) through lumen 42 and balloon inflation connector 22, leveraging catheter 10's inflation lumen. The balloon 546 may be controlled manually by a syringe for fine adjustments or automatically by a console-linked pump for synchronized timing with the saline challenge, with balloon inflation synchronized to console commands, or may be left under manual user control. Balloon inflation may be automated based on console commands synchronized to the saline challenge, or may be left under manual usercontrol, with console 50 or manual syringe alternatives including pneumatic pumps, solenoid valves, or manual syringes for balloon fill, and pressure sensor 528 providing feedback on balloon status for synchronization.

[0108] In certain embodiments, the saline challenge is delivered through the guidewire lumen 46 of catheter 10. The guidewire lumen 46, which is dimensioned to accommodate a guidewire of at least 0.014 inch (approximately 0.36 mm) diameter, provides a direct fluid pathway to the distal end of the catheter assembly 12. During a procedure, the bioimpedance guidewire 22 may be retracted proximally within or removed from the lumen, after which the power injector 24 or another controlled infusion device is coupled to the proximal hub of lumen 46 to deliver the saline bolus. This arrangement allows the same lumen to serve both as a navigation channel during catheter placement and as an infusion channel for the diagnostic challenge once the catheter is positioned.

[0109] In other embodiments, particularly in larger catheters where additional lumens can be accommodated, a dedicated infusion lumen may be provided for saline delivery. Such a lumen may terminate either at the distal tip or in proximity to balloon 14 to facilitate localized infusion into the thoracic duct. This configuration allows simultaneous presence of a guidewire in lumen 46 while infusion is performed through a separate channel. In either arrangement, the proximal end of the lumen is adapted to couple with standard fluid delivery systems, such as Luer-lock connectors, permitting integration with manual syringes, automated syringe pumps, or high- precision power injectors.

[0110] Power injector 540, or equivalent fluid delivery device, receives dispense command 538 from console 50 and acts only if a "Ready" flag is active (e.g., balloon inflated, patient positioned). It accepts commands for dispensing X volume (e.g., 3-10 ml) at rate Y (e.g., 0.1-0.5 ml / s), or variables adjusted for patient anatomy (e.g., reduced rate for high-pressure faults or reduced volume to clear lymph baseline), and may perform an initial flush to displace lymph for baseline conductance (G lymph [3]) before the main challenge. Outputs 536 include dispensing X at Y, sending "Complete / Ready" flag to console 50, and status signals for synchronization; the injector may incorporate pressure limits (e.g., 20-50 mmHg fault threshold) or adaptive modes (e.g., closed-loop adjustment based on real-time delta P feedback to reduce rate or abort). Notes on reduced flow rate or initial flush are addressed through variable X / Y and console-triggered flushprotocols, with injector 540 capable of open-loop (fixed parameters) or closed-loop operation (e.g., modulating Q if pressure exceeds limits or lymph is detected via thermistor or conductivity sensor).

[0111] The patient 542 represents the anatomical target (e.g., TD or other vessel) in which measurements are made, with the system's components interacting with patient anatomy to acquire physiological signals that are processed by console 50. The pressure sensor 16, balloon 14, and bioimpedance guidewire interact with patient anatomy to acquire physiological signals that are processed by console 50. The pressure sensor 16, balloon 14, and bioimpedance guidewire (previously described in Figure 8) interact with patient anatomy to acquire physiological signals that are processed by console 50, with console commands controlling balloon inflation and saline delivery to the patient, and injector outputs used to time-stamp pressure and conductance data for alignment.

[0112] The overall method supported by the system of Figure 9 may be described in an ordered sequence as follows: (i) positioning the catheter assembly 12 within the thoracic duct or target vessel, as guided by marker bands 46 in Figures 8A-8C; (ii) obtaining an initial lymphatic pressure baseline using pressure sensor 16 in the TD (method block 504); (iii) recording a venous reference pressure P_v in the subclavian vein or equivalent drainage site (method block 506); (iv) inflating balloon 14 to occlude retrograde flow if required (method block 508, automated or manual); (v) commanding injector 540 to dispense a defined saline bolus (method block 510, automated with variable X / Y or manual flush options); (vi) receiving sensor outputs from pressure sensor 16 and bioimpedance guidewire; (vii) executing processor algorithms to calculate RC decay (e.g., exponential fitting to derive delta_t_l / 2 and delta_t_R from pressure decay curves), delta_P, CSA, and stenosis severity (e.g., using (1 - (CSA lesion / CSA normal)) x 100 [5a]); (viii) storing and optionally calibrating data in memory 520 (e.g., via factory calibration or in situ routines from calibration data 532, tracked by device IDs or logs); and (ix) displaying results on GUI 524 for review by the user 502 (e.g., delta_P, percent stenosis, raw waveforms, or diagnostic indices like "normal" or "obstruction"). Each of these steps may be automated, semi-automated, or manually initiated, with the console 50 processor coordinating timing, data synchronization with power injector 540 (e.g., t_0 start-of-injection, t_l end-of-inj ection timestamps for calibration window), and processing to derive outputs like delta P, Q(t), CSA(t), R, and delta t R, key for CCLA diagnostics. This ordered method description supports potential method claims by outlining the workflow without necessitating a separate flowchart.

[0113] [Accordingly, Figure 9 illustrates a complete system architecture 500 integrating hardware, software, injector synchronization, and functional processes for objective, real-time measurement of vessel pressure, conductance, flow, resistance, and stenosis severity. By showing both interconnections and workflows, the figure provides support for system and method claims, without the need for a separate method flowchart.

[0114] While the foregoing description illustrates various embodiments of the present disclosure, it should be understood that these embodiments are presented by way of example only and are not intended to limit the scope of the invention. Numerous modifications, variations, and alternative arrangements will be apparent to persons skilled in the art in view of the teachings contained herein, including substitutions of equivalent elements, reordering of steps, or use of different materials, components, or configurations to achieve similar functional results. All such modifications and equivalents are considered to be within the scope of the present disclosure as defined by the appended claims.

Claims

CLAIMS1. A catheter assembly, comprising: a catheter comprising a plurality of lumens; a wire including a pressure sensor disposed at a distal end for placement in a pressure sensor lumen of the plurality of lumens; an occlusion ballon disposed adjacent a distal end of the catheter, wherein the pressure sensor is locatable distally of the balloon; and a connector for liquid delivery through one of the plurality of lumens.

2. The catheter assembly of claim 1, comprising a guidewire for placement in one of the plurality of lumens.

3. The catheter assembly of claim 2, wherein the one of the lumens for placement of the guidewire is useable as the one of the plurality of lumens for liquid delivery.

4. The catheter assembly of claim 1, wherein the catheter has an outside diameter in the range of 2 to 4 French.

5. The catheter assembly of claim 1, wherein the pressure sensor fits within an envelope having a diameter of 1.5 French or less.

6. The catheter assembly of claim 5, wherein the pressure sensor fits within an envelope having a diameter of 1 French or less.

7. The catheter assembly of claim 1 , wherein the pressure sensor has a resolution of ±2 mmHg or better within a range of 0-50 mmHg.

8. The catheter assembly of claim 1, wherein the pressure sensor comprises a micro-electro- mechanical system (MEMS) die including a silicon diaphragm formed over a sealed reference cavity to provide an absolute pressure reference.

9. The catheter assembly of claim 8, wherein the pressure sensor comprises a plurality of piezoresistive elements disposed on the diaphragm and interconnected in a Wheatstone bridge configuration to produce an electrical output signal proportional to diaphragm deflection.

10. A system, comprising: a catheter assembly, comprising: a catheter comprising a plurality of lumens;a wire including a pressure sensor disposed at a distal end for placement in a pressure sensor lumen of the plurality of lumens; an occlusion device disposed adjacent a distal end of the catheter, wherein the pressure sensor is locatable distally of the occlusion device; at least one processor; and memory storing computer programming instructions that, when executed by the at least one processor, cause the system to: obtain a first pressure measurement at a first location in a bodily lumen of a patient; obtain a second pressure measurement at a second location in the bodily lumen of the patient; calculate a stenosis indicator for the bodily lumen; and output the stenosis indicator to a display device.

11. The system of claim 10, comprising a power injector fluidly coupled to one of the plurality of lumens for delivering a bolus of liquid, wherein the computer programming instructions are configured to cause the processor to control the power injector to deliver the bolus.

12. The system of claim 10, wherein the stenosis indicator comprises a pressure differential AP between the first pressure measurement and the second pressure measurement.

13. The system of claim 10, wherein the stenosis indicator is determined based at least in part on a decay curve of pressure measured in the bodily lumen following cessation of a fluid bolus, the decay curve comprising one or more parameters including a half-life Ati / 2 of pressure discharge and a recovery time Atrto baseline.

14. The system of claim 11, wherein the computer programming instructions are further configured to cause the processor to synchronize delivery of the bolus by the power injector with timing of pressure measurements at the first location.

15. The system of claim 10, wherein the first location is in a relatively small bodily lumen and the second location is in an adjacent relatively larger bodily lumen.

16. The system of claim 15, wherein the first location is in the thoracic duct and the second location is in a venous structure downstream of the thoracic duct.

17. The system of claim 10, further comprising a display device configured to display the stenosis indicator as at least one of a numeric value, a graphical plot, or a diagnostic index.

18. The system of claim 10, wherein the instructions are configured to cause the processor to calculate the stenosis indicator by: determining a pressure differential using the second pressure measurement as a reference and a plurality of first pressure measurements at the first location; and determining a decay characteristic of the pressure differential over time, the decay characteristic comprising at least one of a half-life, a recovery time, or a time constant obtained by fitting the pressure differential to a decay model.

19. The system of claim 10, wherein the computer programming instructions are further configured to automate one or more of: actuating or de-actuating the occlusion device, controlling timing of a bolus delivery, time recording pressure measurements, storing results in memory, or exporting results to an external information system.

20. A method of determining a stenosis indicator, comprising: inserting a catheter assembly into a thoracic duct of a patient; actuating an occlusion device disposed adjacent a distal end of a catheter of the catheter assembly to at least partially occlude the thoracic duct; delivering a bolus of fluid into the thoracic duct through the catheter assembly at a controlled rate and volume; taking first pressure measurements over time in the thoracic duct after the bolus delivery using a pressure sensor disposed in one of the lumens of the catheter assembly; taking a second pressure measurement in a venous structure downstream of the thoracic duct using the pressure sensor;calculating a stenosis indicator for the thoracic duct using the first pressure measurements and the second pressure measurement, including a pressure differential or a decay characteristic derived from the bolus response; and displaying, on a display device, the stenosis indicator.

Images