A molecular laser ablation system and method for post-ba interventional therapy restenosis of biliary atresia

Abstract

The present application relates to the technical field of vascular interventional treatment instruments, and discloses a system and method for the selective laser ablation of restenosis after the treatment of Budd-Chiari syndrome, comprising a controller, a pulse emission module and a reference element built into a catheter, the system is based on the reference element for periodic self-calibration, collects and processes the associated photoacoustic signals to identify the tissue type, and then realizes the selective ablation of the diseased tissue and the boundary self-stop when the healthy tissue is touched. The present application converts the traditional open-loop energy delivery into a closed-loop self-control process with real-time information interaction capability, so that the ablation operation end can in-situ perceive the tissue boundary and realize autonomous stop, thereby avoiding the problem of damaging the healthy tissue due to uncontrollable energy application, improving the safety of the operation, and having the advantages of high precision, few complications, repeatable treatment and the like.

Description

Technical Field

[0001] This invention relates to an excimer laser ablation system and method for restenosis after interventional treatment of Budd-Chiari syndrome, belonging to the field of vascular interventional therapy device technology. Background Technology

[0002] Interventional therapy has gained widespread recognition both domestically and internationally as the preferred clinical treatment for Budd-Chiari syndrome. A review of domestic literature since 1990 reveals over 110 articles on interventional treatment of Budd-Chiari syndrome in my country, involving more than 12,600 cases. The level of interventional treatment for Budd-Chiari syndrome in China has reached an internationally leading level. With the increase in the number of Budd-Chiari syndrome cases treated with intervention, prolonged patient survival, and increased awareness of quality of life, clinical findings show that the restenosis rate after interventional treatment for Budd-Chiari syndrome has exceeded 21%.

[0003] Restenosis following interventional treatment for Budd-Chiari syndrome can manifest as acute restenosis, chronic restenosis, recurrent restenosis, and iatrogenic restenosis caused by stent implantation. The mechanism of restenosis remains unclear. Vascular elastic recoil, local tissue damage and repair due to balloon dilation, persistent underlying causes, diaphragmatic reformation, stent-induced local tissue hyperplasia, and differences in operator skill levels all contribute to restenosis. Strengthening research on the basics, equipment, drugs, and predictive biological models for restenosis after interventional treatment of Budd-Chiari syndrome is a crucial clinical challenge.

[0004] Restenosis following interventional treatment of hepatic vein and inferior vena cava obstruction, especially recurrent restenosis, not only increases the psychological and economic burden on patients but also has unsatisfactory long-term outcomes. The reasons for this phenomenon are multifaceted. The etiology and pathogenesis of Budd-Chiari syndrome remain unclear, and the persistent underlying causes cannot be eliminated simply by using balloons and stents.

[0005] Strengthening research on restenosis after interventional treatment for Budd-Chiari syndrome is an important clinical issue. Minimizing restenosis after interventional treatment for Budd-Chiari syndrome is crucial to further highlighting the advantages of interventional therapy and benefiting patients. Clinical research on interventional treatment for Budd-Chiari syndrome has made significant progress, relieving the suffering of tens of thousands of patients. However, further research on restenosis after interventional treatment for Budd-Chiari syndrome remains a challenging task.

[0006] In the field of vascular interventional therapy, ablation of restenosis lesions within blood vessels using energy catheters is a technique for restoring patency. However, when such energy catheters are used in human blood vessels, the separation between the energy application process and the tissue state perception process is a significant challenge. Existing procedures typically involve an open-loop energy delivery process, where the catheter tip applies preset energy to the target tissue, but it lacks the ability to identify the physical characteristics of the tissue below the point of application in real time. This asynchrony between energy delivery and information acquisition means that precise control of the procedure relies on the operator's judgment based on external medical images, such as digital subtraction angiography (DSA). However, these images have information delays, making it difficult to precisely match the energy release with the boundary of the lesion tissue, and collateral damage to adjacent healthy tissues is unavoidable.

[0007] To address this issue, one approach is to integrate the ablation catheter with intravascular real-time imaging technologies, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). However, in engineering practice, this approach requires the system to handle a series of issues, including multimodal information fusion, image registration, and signal synchronization, increasing system complexity and operating costs. Furthermore, the instantaneous correspondence between imaging information and the energy application point still presents positioning errors in dynamic blood flow environments. This approach adds an external observation end in addition to the execution end, without solving the problem of missing information perception at the execution end itself.

[0008] Specifically, existing technologies have the following limitations: 1. The energy application end effector lacks the inherent function of real-time differentiation of the physical characteristics of the target tissue; 2. The ablation process is an open-loop control, and its safety and accuracy are limited by external, non-real-time information sources and the operator's personal experience. Therefore, how to construct an ablation system in which the end effector itself possesses the ability to in-situ sense and distinguish the physical characteristics of tissue, and based on the sensing results, performs closed-loop adaptive control of the energy release process, especially enabling autonomous stopping of the operation when it is determined that the ablation has reached the boundary of healthy tissue, is the technical problem to be solved by this invention. Summary of the Invention

[0009] This invention provides an excimer laser ablation system and method for restenosis after interventional treatment of Budd-Chiari syndrome. Its main purpose is to solve the problem that in existing ablation techniques, the energy application tip does not have the ability to sense the in-situ physical characteristics of tissues, resulting in an open-loop control process that makes it difficult to avoid collateral damage to healthy tissues.

[0010] To achieve the above objectives, the present invention provides an excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome, comprising:

[0011] A pulse transmission module is configured to transmit diagnostic pulses and therapeutic pulses according to a preset timing sequence;

[0012] A reference element located at the end of the conduit has a preset photoacoustic response characteristic;

[0013] A photoacoustic signal acquisition module is configured to synchronously acquire photoacoustic signals generated when a diagnostic or therapeutic pulse interacts with biological tissue or when a calibration pulse interacts with a reference element.

[0014] A pulse infusion module linked to a pulse emission module is configured to inject fluid during the interval between the emission of a treatment pulse;

[0015] A controller module is configured to: generate a calibration factor based on the difference between a reference photoacoustic signal generated by a reference element and a pre-stored reference signal, and use the calibration factor to correct subsequent photoacoustic signals acquired from biological tissue; extract tissue type features based on the corrected photoacoustic signal and after subtracting a periodically updated background noise baseline; authorize the pulse emission module to apply a treatment pulse at the current position only when the tissue type features meet the preset ablation target area conditions; and automatically stop applying the treatment pulse at the current position when the ablation has reached the tissue boundary based on the re-extracted tissue type features after applying the treatment pulse.

[0016] Preferably, the controller module is further configured to: after applying a treatment pulse, instruct the pulse emission module to emit a diagnostic pulse and instruct the photoacoustic signal acquisition module to acquire photoacoustic signals to extract tissue type features for determining whether ablation has reached the tissue boundary.

[0017] Preferably, the controller module is configured to update the background noise baseline by instructing the photoacoustic signal acquisition module to continuously acquire signals within a preset time window before transmitting the diagnostic pulse, in order to establish a background noise baseline characterizing the current blood flow or cardiac state.

[0018] Preferably, the pulse perfusion module is configured to inject fluid through a nozzle at the end of the catheter during the time window from the end of one treatment pulse emission to the start of the next diagnostic pulse emission, in order to remove ablation products and restore the acquisition window for photoacoustic signals.

[0019] Preferably, the controller module is configured to generate the calibration factor by: the instruction pulse transmission module transmitting a calibration pulse to the reference element and comparing the amplitude of the acquired reference photoacoustic signal with the amplitude of the pre-stored reference signal to calculate the calibration factor.

[0020] Preferably, the controller module is further configured to: lock the pulse emission module, stop emitting treatment pulses and enter a safe standby state when the extracted tissue type features do not meet the ablation target area conditions within a period exceeding a preset number of consecutive cycles.

[0021] Preferably, the single-pulse energy of the diagnostic pulse is set to be within the range of 0.5% to 10% of the single-pulse energy of the treatment pulse, and the pulse width of the diagnostic pulse is smaller than the pulse width of the treatment pulse.

[0022] Preferably, the organization type feature is a feature vector containing at least two parameters extracted from the photoacoustic signal, selected from the group consisting of: signal amplitude, peak frequency of the spectrum, bandwidth, or signal envelope attenuation time constant.

[0023] Preferably, the transducer portion of the pulse emission module, the photoacoustic signal acquisition module, the reference element, and the fluid nozzle of the pulse perfusion module are integrated into the distal end of a flexible catheter. The controller module determines the condition that ablation has reached the tissue boundary based on the following relationship: the rate of change between the characteristic parameters satisfies the following equation: ,in, These are the characteristic parameters of the photoacoustic signal acquired before applying a treatment pulse at the current location. The characteristic parameters of the photoacoustic signal acquired after the application of the treatment pulse, and This is a preset threshold for determining whether an tissue type has changed from a restenotic tissue to a healthy tissue.

[0024] A method for excimer laser ablation of restenosis after interventional treatment of Budd-Chiari syndrome includes the following steps:

[0025] Based on the difference between the reference photoacoustic signal generated by the system's reference element and a pre-stored reference signal, a calibration factor is generated, and the calibration factor is used to correct subsequent photoacoustic signals acquired from biological tissue.

[0026] Based on the corrected photoacoustic signal, and after subtracting a periodically updated background noise baseline, tissue type features are extracted;

[0027] A treatment pulse is applied to the current location only when the tissue type characteristics meet a preset ablation target area condition;

[0028] During the interval between treatment pulses, fluid is injected;

[0029] After applying the treatment pulse, the tissue type features are extracted again, and when it is determined that the ablation has reached the tissue boundary, the application of the treatment pulse at the current location is stopped.

[0030] Compared with the prior art, the beneficial effects of the present invention are:

[0031] 1. By transmitting diagnostic and therapeutic pulse sequences in a time-division manner, and using the accompanying photoacoustic signals generated by tissue in response to different pulses as the basis for decision-making, the ablation operation is transformed from a unidirectional energy application process into a closed-loop operation process with an inherent logical sequence of probing, identification and confirmation, targeted execution, and immediate verification. The establishment of this process means that the control of the ablation boundary no longer depends on the lag feedback of external imaging equipment or the operator's subjective experience, but is based on the comparison of physical signals obtained from the point of application itself before and after each energy application, thereby forming an immediate safety limit at the smallest unit level of the operation.

[0032] 2. By employing a multi-mechanism collaborative approach, the system addresses the practical challenge of precise operation in a dynamic and complex living vascular environment. Before initiating the ablation task, the controller is configured to first acquire and analyze background noise generated by blood flow, heartbeat, etc., to establish a dynamic signal baseline. In subsequent signal acquisition and feature extraction, this baseline is used to process the raw signal in real time, thereby separating the characteristic signals that characterize tissue state from strong environmental interference. Simultaneously, the pulse perfusion module synchronously injects fluid during the intervals between treatment pulses to actively remove ablation products. This removal action, on the one hand, avoids interference from ablation products on the subsequent photoacoustic signal transmission path, providing a physical window for the acquisition of characteristic signals; on the other hand, it directly removes potential microemboli, which itself constitutes a safety guarantee. The collaborative operation of these two mechanisms provides a stable operating foundation for the core workflow in the surgical environment.

[0033] 3. This invention also includes a periodic self-calibration mechanism for the system's own measurement link to address measurement reference drift caused by factors such as hardware aging, changes in fiber coupling efficiency, or manufacturing tolerances of disposable consumables. The reference element set at the end of the catheter has a stable and predictable physical characteristic. The controller is configured to instruct the pulse emission module to emit calibration pulses to the reference element at specific working nodes and collect the generated reference photoacoustic signal. By comparing this measured reference signal with the theoretical reference signal stored in the system, the controller generates a calibration factor in real time and applies this factor to correct all subsequent photoacoustic signals collected from biological tissue. This process changes the reliability of the entire measurement system from relying on factory consistency to relying on real-time calibration before each use. This makes the accuracy of tissue identification and boundary determination promised by this invention reproducible and consistent across different equipment, different batches of consumables, and different life cycle stages of the equipment. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of the closed-loop ablation control process based on photoacoustic signal feedback according to the present invention;

[0035] Figure 2 This is a diagram showing the optimal selection relationship of the therapeutic pulse energy parameters of the present invention;

[0036] Figure 3 This is a timing diagram of tissue ablation treatment based on photoacoustic signal feedback according to the present invention;

[0037] Figure 4 This is a diagram of the human body and catheter structure of the present invention;

[0038] Figure 5 This is a general diagram of the laser mechanism of the present invention. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in further detail below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0040] like Figure 4 , Figure 5 As shown, the present invention discloses an excimer laser ablation system and method for restenosis after interventional treatment of Budd-Chiari syndrome, comprising: a controller module, a pulse emission module, a photoacoustic signal acquisition module, a pulse perfusion module, and a reference element disposed at the end of a catheter. The controller module coordinates the sequential operation of other modules and performs signal processing and decision-making. The transducer parts of the pulse emission module and the photoacoustic signal acquisition module, the fluid nozzle of the pulse perfusion module, and the reference element are integrated into the distal part of a flexible catheter, which together constitute an end effector for performing operations in the blood vessel. The working process of the system is to transform the unidirectional energy delivery process into a closed-loop self-control process based on information feedback. By analyzing the accompanying photoacoustic signal generated when the laser pulse interacts with biological tissue, selective action on the ablation target area is achieved and autonomous stopping is achieved when the healthy tissue boundary is reached.

[0041] In a specific application scenario, such as treating long-segment diffuse fibrotic restenosis lesions of the hepatic vein or inferior vena cava, the operator pushes a flexible catheter integrating the aforementioned functional modules through the vascular pathway to the lesion location. Before initiating the ablation procedure, considering that hardware aging, changes in fiber optic coupling efficiency, or individual tolerances of disposable catheter consumables may introduce measurement reference drift, the system is configured to first perform a periodic self-calibration based on a built-in reference element. Specifically, the controller module instructs the pulse emission module to emit a calibration pulse to the reference element located at the catheter tip. This reference element is made of a material with stable photoacoustic response characteristics (e.g., a specific metal film) and generates a predictable reference photoacoustic signal upon receiving the calibration pulse. The photoacoustic signal acquisition module synchronously acquires this reference photoacoustic signal, and the controller module compares its amplitude with the amplitude of a pre-stored reference signal within the system to generate a calibration factor. For example, if the pre-stored reference signal amplitude is... The unit is the amplitude of the currently measured reference photoacoustic signal. If the unit is specified, the controller module calculates and generates a calibration factor of: In subsequent operations, the controller module will use this calibration factor to perform real-time correction on the raw photoacoustic signal acquired from the biological tissue. This ensures that the system's criteria for tissue identification remain consistent across different devices or batches of consumables.

[0042] After the system completes self-calibration, considering the background noise interference generated by physiological activities such as heartbeat and blood flow within living blood vessels, the controller module executes a dynamic update procedure for the background noise baseline before transmitting the working pulse. The controller module instructs the photoacoustic signal acquisition module to perform this update within a preset time window (e.g., The system continuously acquires signals within milliseconds. During this time, the pulse emission module is in a silent state, and the acquired signal is the background noise that characterizes the current physiological state. The controller module processes this signal to establish a dynamic background noise baseline. In the subsequent tissue identification process, this background noise baseline is subtracted from the photoacoustic signal after calibration factor correction, thereby separating the signal that can characterize the physical properties of the tissue from environmental interference.

[0043] To address the non-stationary, time-varying characteristics of hemodynamic noise at different physiological states and lesion locations, the controller module incorporates an adaptive noise cancellation procedure before performing background noise baseline subtraction. This procedure uses the mixed signal acquired by the transducer of the photoacoustic signal acquisition module as the main input. Simultaneously, a signal containing only background physiological noise, acquired by the same transducer during the laser pulse emission interval, is used as a reference input. A finite impulse response filter is iteratively updated using a least mean square (LMS) algorithm. The weighting coefficients are used to generate a predicted noise signal that is highly correlated with the noise components in the mixed signal. The mathematical expression for this process is: ,in, Using the reference input signal vector, the controller module then subtracts the predicted noise signal from the main input signal to obtain an error signal. ,Right now The error signal is the photoacoustic signal with improved signal-to-noise ratio after noise cancellation processing, and it is used as input data for subsequent tissue type feature extraction.

[0044] Subsequently, the system executes its core workflow using a time-division multiplexed pulse sequence. First, the controller module instructs the pulse transmission module to transmit a low-energy diagnostic pulse to the current point of application. The single-pulse energy of this diagnostic pulse is set as the single-pulse energy of the subsequent treatment pulse. to Within the specified range, and with a pulse width smaller than that of the treatment pulse, a photoacoustic signal is excited without producing a tissue ablation effect. The photoacoustic signal acquisition module simultaneously acquires the accompanying photoacoustic signal generated by the interaction between the diagnostic pulse and the tissue at the point of action, and transmits the calibrated and background noise-subtracted signal to the controller module. The controller module extracts a feature vector characterizing the tissue type from the signal. This feature vector contains at least two parameters selected from signal amplitude, peak frequency, bandwidth, or signal envelope decay time constant. Because restenotic fibrotic tissue differs from healthy vascular wall tissue in physical properties, these differences are reflected in the feature parameters of the photoacoustic signal. The controller module compares the extracted feature vector with the preset ablation target area conditions. Only when the tissue type characteristics of the current point of action meet the conditions is the pulse emission module authorized to apply a high-energy treatment pulse at the current location to perform ablation.

[0045] After applying a treatment pulse, to immediately verify the ablation effect and determine whether the tissue boundary has been reached, the system immediately repeats the detection and identification steps. The controller module instructs the pulse emission module to emit a diagnostic pulse again, acquires and processes the corresponding photoacoustic signals, and extracts the tissue type characteristics after ablation. The controller module determines whether ablation has reached the tissue boundary using a judgment condition. This judgment is based on the rate of change of photoacoustic signal characteristic parameters before and after the application of the treatment pulse, and its relationship can be expressed as: In the formula, These are the characteristic parameters of the photoacoustic signal acquired before applying a treatment pulse at the current location. The characteristic parameters of the photoacoustic signal acquired after the application of the treatment pulse, and A preset threshold is set to indicate whether the tissue type has changed from restenosis to healthy tissue. If the calculated rate of change is not less than this threshold, the controller determines that ablation is not yet complete; if the rate of change is less than the threshold... The controller then determines that the ablation has reached the tissue boundary and automatically stops applying any subsequent treatment pulses at the current location, thereby achieving tissue-selective self-stopping.

[0046] like Figure 4 As shown, to further ensure the stability of the operation process, the system also integrates a pulse perfusion module. This module is linked with the pulse emission module and is configured to inject fluid (such as saline) through the nozzle at the end of the catheter within the time window from the end of one treatment pulse emission to the start of the next diagnostic pulse emission. This action can remove tiny debris or bubbles generated by ablation, restore a clear photoacoustic signal acquisition window, and directly remove potential microemboli from the treatment area. In addition, the controller module is also equipped with a safety lock function. When the tissue type characteristics extracted by the controller module do not meet the preset ablation target area conditions within a preset number of consecutive cycles, such as when the catheter tip has moved out of the lesion area, the system determines that the current state is not suitable for continuing ablation and automatically locks the pulse emission module, causing it to stop emitting treatment pulses and enter a safe standby state until the operator reconfirms the target area position.

[0047] Example 1: In a specific application for treating fibrotic restenosis lesions adjacent to the openings of important branch vessels, the technical solution disclosed in this invention operates as follows: This scenario poses a technical challenge for traditional interventional methods, namely, when applying mechanical force sufficient to dilate the stenotic segment of the main vessel, it is difficult to avoid the uncontrollable axial displacement or radial tearing of the openings of adjacent branch vessels caused by this force, which may lead to branch vessel occlusion; When a flexible catheter with an integrated end effector is placed at the lesion, given the complexity of the blood flow state near the branch vessel opening, the physiological background noise at this location is more variable than that of a straight vessel segment. At this time, the background noise baseline dynamic update procedure, as described in the specific implementation, is executed; Before transmitting a pulse, the controller module instructs the photoacoustic signal acquisition module to acquire a signal in an unexcited state to establish a background noise baseline that reflects the current local blood flow state. This step enables the accompanying photoacoustic signal carrying tissue information, which is subsequently excited by the diagnostic pulse, to be separated from environmental interference.

[0048] Based on this, the system executes a workflow centered on time-division multiplexing pulse sequences. The controller module emits low-energy diagnostic pulses to probe the tissue at the edge of the branch vessel opening. Because fibrotic restenosis tissue differs in physical properties from healthy vessel wall tissue, their photoacoustic signal feature vectors are also different. The controller module analyzes these feature vectors to establish a real-time feature distribution of the tissue type below the point of action. This information acquisition process transforms the energy application decision from a judgment dependent on external images and subject to spatial and temporal delays into an instantaneous decision based on in-situ physical feedback from the point of action. Furthermore, when the controller module confirms, based on the feedback from the diagnostic pulses, that the catheter tip is aligned with the fibrotic tissue, it authorizes the application of therapeutic pulses for ablation. After each therapeutic pulse is emitted, the system immediately emits another diagnostic pulse, according to the relationship described in the specific implementation. This system determines whether the ablation has reached the tissue boundary; this closed-loop control logic, which performs real-time verification after each energy application unit, enables the ablation process to selectively stop on its own; as the ablation area gradually approaches and reaches the healthy tissue edge of the branch vessel opening, the rate of change of the characteristic parameters will be less than the preset judgment threshold. The controller module automatically stops applying treatment pulses when it reaches the boundary, thus removing the obstruction in the main channel while preserving the structural integrity of the branch vessel openings.

[0049] The operation of this technical solution does not directly address the inherent mechanical control problem in traditional mechanical expansion methods. Instead, it transforms the problem to be solved from how to apply controllable mechanical force without damaging adjacent structures to how to identify and selectively remove target tissue. By coupling energy action with information perception in time and space, the boundary of the operation is no longer limited by the physical size of the instrument or the resolution of external images, but is defined by the difference in physical characteristics between the target tissue and healthy tissue.

[0050] Example 2: To objectively verify the effectiveness of the system of the present invention in distinguishing different tissue types and achieving boundary self-stopping, an experiment was conducted. This experiment aimed to quantitatively verify whether the closed-loop control logic of the system based on photoacoustic signal feedback could autonomously terminate energy application at the tissue interface when ablating simulated restenosis tissue, so as to avoid damage to the underlying simulated healthy blood vessel wall. The experiment used an ex vivo tissue model, with freshly obtained porcine aortic tissue samples as the subjects, on which a layer of glutaraldehyde-treated bovine pericardial patch was fixed to simulate fibrotic restenosis tissue. A physical interface was formed between the pericardial patch and the aortic tissue. The entire experimental device was placed at 37°C. The experiment was conducted in a constant-temperature heparinized saline environment to simulate in vivo physiological conditions. The system included a photoacoustic signal acquisition module with a transducer bandwidth covering 10-50MHz, connected to a data acquisition unit with a sampling rate of no less than 250MSa / s. During the experiment, a preset threshold was used in the controller module to determine whether ablation had reached the tissue boundary. The value was set to 0.5. This setting was based on the preliminary photoacoustic property calibration of the two material samples. The results showed that healthy aortic tissue and sclerotic pericardial tissue had distinguishable differences in photoacoustic signal amplitude and spectral characteristics. The value is set in the region that can distinguish between the two feature vectors.

[0051] The experiment included an experimental group employing the complete technical solution of this invention and a control group with the photoacoustic signal feedback loop disabled. In the experimental group, a flexible catheter integrated with an end effector was first placed on the surface of simulated restenosis tissue (bovine pericardial patch). After system startup, the system operated according to the specific implementation procedure. At each location point, the controller module sequentially performed operations such as emitting diagnostic pulses, acquiring and processing photoacoustic signals, extracting tissue type characteristics, deciding whether to apply a treatment pulse, and re-probing after application to determine whether to stop. The catheter moved at a constant speed from the pericardial patch area to the healthy aortic area, and the decision-making process of the controller module was recorded in real time. Table 1 shows the data recorded by the controller module at several key test points when crossing tissue boundaries in the experimental group. Referring to Table 1, when the test point was located in the pericardial patch area (test points 1-4), the photoacoustic signal characteristic parameters extracted by the system were... (Taking signal amplitude as an example) Maintaining at a high level (0.82-0.85V), the controller decides to continuously apply treatment pulses; when the test point moves to the tissue boundary (test point 5), a single treatment pulse penetrates the remaining thin pericardial film, and subsequent diagnostic pulses detect the underlying healthy aortic tissue, leading to... The amplitude drops to 0.39V. At this point, the rate of change calculated according to the relationship is... This value is not less than the threshold. The system will perform ablation again at that point; at the next test point (test point 6). This represents the previously detected healthy tissue signal (0.39V), and the signal detected this time... The signal is still from healthy tissue (0.38V), and the calculated rate of change... This value is less than the threshold. Correspondingly, the controller decision shifts to stop, and even if the catheter continues to move to the healthy aortic region (test point 7-8), the system no longer applies treatment pulses because the stop condition is continuously met; this process shows that changes in tissue type characteristics are converted into actions that the controller stops executing through quantitative calculation of the decision conditions.

[0052] Table 1: Data table of the decision-making process of the test group controller.

[0053]

[0054] In the control group experiment, the system was set to open-loop operation, i.e., continuously emitting a preset number of treatment pulses without acquiring or processing photoacoustic signals. After the experiment, the tissue samples were examined. The results showed that in the experimental group, the bovine pericardial smear was removed, and the surface of the underlying porcine aortic tissue was intact, with no energy damage observed. In the control group, the bovine pericardial smear was also removed, but visible pits and thermal damage areas appeared on the surface of the underlying porcine aortic tissue. The experimental results indicate that the system integrating real-time photoacoustic signal feedback and closed-loop control logic can make decisions based on the differences in the physical characteristics of different tissues and terminate the ablation operation when the tissue boundary is reached, thereby removing the target tissue while preserving non-target tissue.

[0055] To further verify from the opposite perspective the technical necessity of the closed-loop control logic described in this invention in avoiding damage to healthy tissues, the following comparative example is provided.

[0056] Comparative Example 1: This comparative example aims to simulate a scenario in which a person skilled in the art would perform laser ablation using a conventional open-loop control approach. Therefore, the laser ablation system, experimental environment, and ex vivo tissue model composed of fresh porcine aortic tissue samples and bovine pericardial slices were identical to those used in the experimental group of Example 2. The essential difference was that the closed-loop control function based on photoacoustic signal feedback in the controller module, including tissue type determination and ablation boundary determination logic, was disabled. The system was set to a conventional open-loop operating mode, meaning that at each test point, the operator manually triggered the emission of a treatment pulse sequence with a preset energy and number of pulses. Based on the thickness and ablation threshold of the simulated restenosis tissue (bovine pericardial slice) in Example 2, to ensure complete removal, the preset treatment pulse sequence was set to emit 5 pulses at each test point, with the energy density of the treatment pulses remaining consistent with Example 2. During the experiment, a flexible catheter integrated with an end effector moved at the same speed as in Example 2 from the simulated restenosis tissue area to the healthy aortic tissue area. After the experiment, the tissue samples were visually examined and histologically analyzed, and the results are recorded in Table 2.

[0057] Table 2: Comparative Example 1 Controller Decision Process Data Table.

[0058] Test point number Tissue type below the point of action Execute operation Histological examination results after the experiment 1 Simulated restenosis tissue Fire 5 healing pulses The target tissue has been removed, exposing the tissue underneath. 2 Simulated restenosis tissue Fire 5 healing pulses The target tissue has been removed, exposing the tissue underneath. 3 Simulated restenosis tissue Fire 5 healing pulses The target tissue has been removed, exposing the tissue underneath. 4 Simulated restenosis tissue Fire 5 healing pulses The target tissue has been removed, exposing the tissue underneath. 5 Organizational Boundaries Fire 5 healing pulses A pit with a depth of approximately 85µm was observed, and thermal damage was observed at the bottom and edge of the pit. 6 Healthy aortic tissue Fire 5 healing pulses A distinct pit with a depth of approximately 160 µm was observed, and the width of the thermal damage zone was approximately 95 µm. 7 Healthy aortic tissue Fire 5 healing pulses The pit depth exceeds 150µm, the thermal damage zone width is approximately 105µm, and the internal elastic layer structure is damaged. 8 Healthy aortic tissue Fire 5 healing pulses The pit depth is approximately 175µm, the width of the thermal damage area is approximately 110µm, and there is necrosis of the smooth muscle cells in the tunica media.

[0059] The experimental results show that when using the open-loop control method, because the system does not have the ability to sense changes in tissue type in situ and stop applying energy autonomously, although it successfully removed the target tissue at test points 1-4, the preset treatment pulse sequence was still executed after the catheter tip moved to the tissue boundary and healthy tissue area (test points 5-8), which caused severe and irreversible energy damage to the healthy aorta, which is a non-target tissue, forming obvious pits and thermal damage areas.

[0060] Example 3: This example combines Figures 1 to 3 This document describes an excimer laser ablation system and method for restenosis following interventional treatment of Budd-Chiari syndrome. Figure 1 As shown, the process begins by placing a flexible catheter with an integrated end effector at the lesion site. The system uses time-division multiplexing to emit low-energy diagnostic pulses to probe tissue and generate photoacoustic signals. These accompanying signals are then acquired and sent to the controller module for signal processing. To ensure signal accuracy, the processing employs a calibration factor generated by a periodic self-calibration mechanism to address measurement reference drift caused by factors such as hardware aging or consumable tolerances. This calibration factor originates from a reference photoacoustic signal generated by a reference element. Simultaneously, the processing subtracts a periodically updated background noise baseline, which is updated by a multi-mechanism collaborative protection module designed to isolate environmental interference caused by blood flow and heartbeat. This collaborative protection module also includes a... The pulse perfusion module is used to clear ablation products and restore the acquisition window during the treatment interval. The controller module extracts tissue features based on the processed signal and determines the tissue type to see if the current features meet the preset ablation target area conditions. If not, or if the signal quality is too low, the system enters a safe standby state. If it meets the conditions, it authorizes the emission of a high-energy treatment pulse to perform selective ablation. After the treatment pulse is applied, the system immediately emits a diagnostic pulse to verify the tissue state after ablation and to determine the ablation boundary to see if the healthy tissue boundary has been reached. If not, it returns to the step of emitting the diagnostic pulse and performs cyclic ablation. If so, it executes boundary self-stop and automatically stops applying treatment pulses at the current position.

[0061] like Figure 2 As shown, the horizontal axis represents energy density, with units of... The vertical axis represents the ablation depth, indicated by solid-lined squares, in units of... / pulse, and the width of the thermal damage zone, indicated by a dashed triangle, in units of The curve shows that as the energy density increases from 20... Increase to 100 Both the ablation depth and the width of the thermal damage zone increase accordingly. Specifically, the ablation depth increases when the energy density reaches approximately 60... The growth rate then slows down and plateaus, while the width of the thermal damage zone continues to increase approximately linearly. This relationship curve allows us to find a working window that balances ablation efficiency and safety; for example, selecting 60... The energy density of the treatment pulse is used to control the width of the associated thermal damage zone within a specific threshold while achieving high ablation efficiency.

[0062] like Figure 3 As shown, the process begins with the controller module. After confirming that the current point of action is the ablation target area, it first records the tissue characteristic parameters before treatment. Subsequently, a command to emit a treatment pulse is sent to the pulse emission module. Upon receiving the command, the pulse emission module emits a high-energy treatment pulse towards the biological tissue, thereby achieving tissue ablation. Immediately afterwards, the controller module sends a command to initiate perfusion ablation to the pulse perfusion module. This module then injects saline solution into the ablation area to remove ablation products and air bubbles, and sends a perfusion completion signal back to the controller module upon completion of the task. Upon receiving this signal, the controller module instructs the pulse emission module to emit a low-energy diagnostic pulse to the same point of action. This pulse interacts with the biological tissue, generating a verification photoacoustic signal. This signal is captured by the photoacoustic signal acquisition module and transmitted to the controller module. Finally, based on the received signal, the controller module extracts post-treatment characteristic parameters. The ablation effect is assessed by calculating the characteristic change rate to decide whether to continue applying energy at the current location.

[0063] Example 4: To establish ablation target area conditions capable of addressing the heterogeneity of restenosis tissue, the system executes a multi-dimensional feature space modeling procedure during the offline calibration phase. This procedure first constructs a standardized photoacoustic property database using a set of ex vivo tissue samples containing various pathological types such as fibrosis, calcification, and lipid cores. Subsequently, for the photoacoustic signals acquired from each sample in the database, a feature space model is extracted based on the peak amplitude of the signal. Spectrum centroid frequency and the signal envelope energy decay time constant The constructed three-dimensional feature vector Finally, Linear Discriminant Analysis (LDA) is used to process the feature vectors corresponding to all samples in the database, calculating a hyperplane that optimally separates the feature vector clusters of restenosis tissue from those of healthy tissue. The equation of this hyperplane is then embedded in the controller module, serving as a quantitative basis for determining whether the tissue type corresponding to the currently acquired signal meets the ablation target area conditions. To determine the tissue type identification logic and boundary judgment threshold built into the controller module of this invention, a standardized offline calibration procedure needs to be executed. This procedure aims to systematically measure the photoacoustic characteristics of tissue samples of known types to... The controller module establishes a quantitative feature parameter model that can be used to distinguish simulated restenosis tissue from healthy tissue. The initial conditions of this calibration procedure are two sets of ex vivo tissue samples with different physical properties. The first set is bovine pericardial slices treated with glutaraldehyde to simulate fibrotic restenosis tissue, and the second set is fresh porcine aortic tissue to simulate healthy blood vessel walls. Each set contains no fewer than 20 samples. The procedure relies on a calibration platform that operates in data acquisition mode, identical to the system of this invention. This platform can accurately position the catheter tip on the surface of each tissue sample and record the photoacoustic signal waveform generated after being excited by a diagnostic pulse.

[0064] At the start of the procedure, the system sequentially acquires data from each tissue sample, emitting diagnostic pulses to multiple different locations on each sample and recording the time-domain waveform of the returned photoacoustic signal. Subsequently, the controller module's software algorithm performs feature extraction on each acquired waveform data. This process is algorithmically structured as follows: First, the peak-to-peak value of the waveform signal in the time domain is calculated and defined as the signal amplitude. Second, a Fast Fourier Transform is performed on the time-domain waveform, and the frequency point with the highest energy in the resulting spectrum is identified and defined as the peak frequency. By processing the data from all samples, the system obtains two sets of multidimensional feature vector datasets, corresponding to simulated restenosis tissue and healthy tissue, respectively, containing both signal amplitude and peak frequency. Next, the procedure performs statistical analysis on these two datasets to establish an identification model. The analysis results show that the average signal amplitude and peak frequency of the simulated restenosis tissue dataset are higher than those of the healthy aortic tissue dataset. Based on this, an ablation target area condition can be determined. A two-dimensional judgment boundary is set between the statistical distributions of the two datasets. Any feature vector falling within one side of this boundary is identified by the system as an ablation target area. Simultaneously, a preset judgment threshold is established. The value is also determined based on this statistical result. This threshold needs to be greater than the normal fluctuation of characteristic parameters within the two types of tissues, but less than the step change in characteristic parameters that occurs when one type of tissue completely transforms into the other. If the mean values ​​of the simulated restenosis tissue and healthy tissue in terms of signal amplitude are respectively V and V, then the normalized difference between the two is approximately To establish a stable discrimination window during this change, The value can be set to 0.5. By executing this calibration procedure, the tissue identification model and judgment threshold that originally relied on preset values ​​are transformed into a set of engineering parameters that can be reproduced through standardized experimental procedures. These parameters are then embedded into the controller module of the mass production system, thereby providing a data foundation for the system to perform reliable tissue identification and boundary judgment.

[0065] Example 5: In the production stage of the system of the present invention, in order to establish a pre-stored reference signal with consistency and traceability, a master reference calibration procedure is executed. The procedure uses a standard reference phantom and a reference conduit. Under a controlled environment, a calibration pulse is emitted to the reference element at the end of the reference conduit and the reference photoacoustic signal generated therefrom is collected. The waveform of the signal and the signal amplitude and decay time constant extracted from it are digitized. The obtained data is defined as a pre-stored reference signal and is solidified into the controller module of the mass production equipment, so that different equipment refer to the same reference for correction when performing periodic self-calibration.

[0066] During system operation, the controller module is also configured to execute a signal quality monitoring process to handle signal quality degradation caused by factors such as poor contact between the catheter tip and tissue or transient interference. Before the controller module extracts tissue type features, this process calculates the signal-to-noise ratio (SNR) of the acquired photoacoustic signal after background noise baseline subtraction. The controller module has a built-in minimum acceptable SNR threshold determined in the offline calibration procedure. If the calculated SNR is lower than this threshold for several consecutive diagnostic cycles, the controller module determines that the current signal does not meet the preset conditions for tissue type identification, and then suspends authorized transmission of treatment pulses and prompts the operator until the signal SNR recovers to above the threshold.

[0067] Example 6: To calibrate the operating parameters of the pulse perfusion module and pulse emission module in the system of this invention, so as to avoid collateral damage to non-target tissues while achieving effective ablation and cleaning effects, a parameter optimization and verification procedure needs to be performed. This procedure aims to determine a set of operating parameters for the controller module that balance efficiency and safety, including the fluid pressure and duration of pulse perfusion, as well as the energy density of diagnostic and therapeutic pulses. The procedure first calibrates the pulse perfusion parameters using isolated porcine aortic tissue samples and sets multiple different combinations of perfusion parameters, wherein the fluid pressure is increased in 5 kPa increments within the range of 5 kPa to 50 kPa. The perfusion duration was adjusted in 10-ms increments within the range of 10-ms to 100-ms. Under each set of parameters, the system performed a single-point ablation pulse on the tissue sample and immediately triggered a pulse perfusion. Subsequently, the clearance of micro-debris around the ablation point was recorded by high-speed imaging, and the tissue sample after perfusion was subjected to histological examination to assess the degree of damage to vascular endothelial cells. By analyzing all data sets, a pressure-duration combination that could clear more than 95% of visible debris without causing structural damage to the endothelial cell layer was identified. A pressure of 20 kPa and a duration of 30 ms were set as the system's default perfusion parameters.

[0068] After determining the perfusion parameters, the procedure further calibrated the energy density of the laser pulses. The experiment used glutaraldehyde-treated bovine pericardial slices as the target ablation material, and set up multiple sets of treatment pulses with increasing energy density. to ,by The gradient is used; at each energy density, a fixed number of pulses are applied to the target, and the ablation efficiency per unit pulse is calculated by measuring the depth of the ablation pit. Simultaneously, the width of the thermal damage zone at the edge of the ablation pit is measured using histological sections. The calibration results aim to find a balance point, namely, ensuring that the ablation efficiency is not lower than a preset value while keeping the width of the thermal damage zone below a safe threshold of 50µm. If it is found that... At a given energy density, the ablation efficiency reaches a plateau, and the width of the thermal damage zone is 45µm. This energy density is then selected as the operating parameter for the treatment pulse. Subsequently, the energy density of the diagnostic pulse is tested within the range of 0.5% to 10% of its energy relative to the treatment pulse to identify the lowest energy density that can stably achieve a signal-to-noise ratio above the minimum acceptable threshold. Through this procedure, key process control parameters in the system are defined with clear experimental data sources and engineering trade-offs. These optimized parameters are written into the configuration file of the controller module, ensuring that every operation of the system is performed within a validated working window that balances efficiency and safety.

[0069] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. An excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome, characterized in that, include: A pulse transmission module is configured to transmit diagnostic pulses and therapeutic pulses according to a preset timing sequence; A reference element located at the end of the conduit has a preset photoacoustic response characteristic; A photoacoustic signal acquisition module is configured to synchronously acquire photoacoustic signals generated when a diagnostic or therapeutic pulse interacts with biological tissue or when a calibration pulse interacts with a reference element. A pulse infusion module linked to a pulse emission module is configured to inject fluid during the interval between the emission of a treatment pulse; A controller module is configured to: generate a calibration factor based on the difference between a reference photoacoustic signal generated by a reference element and a pre-stored reference signal, and use the calibration factor to correct subsequent photoacoustic signals acquired from biological tissue; and extract tissue type features based on the corrected photoacoustic signal and after subtracting a periodically updated background noise baseline. The pulse emission module is authorized to apply a treatment pulse at the current location only when the tissue type characteristics meet the preset ablation target area conditions; after the treatment pulse is applied, the application of the treatment pulse at the current location is automatically stopped when it is determined that the ablation has reached the tissue boundary based on the re-extracted tissue type characteristics. The controller module is also configured to: after applying a treatment pulse, instruct the pulse emission module to emit a diagnostic pulse and instruct the photoacoustic signal acquisition module to acquire the photoacoustic signal; The controller module is configured to update the background noise baseline by instructing the photoacoustic signal acquisition module to continuously acquire signals within a preset time window before transmitting the diagnostic pulse; The pulse perfusion module is configured to inject fluid through a nozzle at the end of the catheter during the time window from the end of one treatment pulse to the start of the next diagnostic pulse, thereby clearing ablation products and restoring the acquisition window for photoacoustic signals. The transducer sections of the pulse emission module and photoacoustic signal acquisition module, the reference element, and the fluid nozzle of the pulse perfusion module are integrated into the distal end of a flexible catheter. The controller module determines that ablation has reached the tissue boundary based on the following condition: the rate of change between the characteristic parameters satisfies the following relationship: ,in, These are the characteristic parameters of the photoacoustic signal acquired before applying a treatment pulse at the current location. The characteristic parameters of the photoacoustic signal acquired after the application of the treatment pulse, and a preset threshold for determining whether the tissue type has changed from restenosis to healthy tissue.

2. The excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome according to claim 1, characterized in that, The controller module is configured to generate calibration factors by instructing the pulse transmission module to transmit calibration pulses to the reference element and comparing the amplitude of the acquired reference photoacoustic signal with the amplitude of the pre-stored reference signal.

3. The excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome according to claim 1, characterized in that, The controller module is also configured to lock the pulse emission module, stop emitting treatment pulses, and enter a safe standby state when the extracted tissue type features do not meet the ablation target area conditions within a preset number of consecutive cycles.

4. The excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome according to claim 1, characterized in that, The single-pulse energy of the diagnostic pulse is set to be between 0.5% and 10% of the single-pulse energy of the treatment pulse, and the pulse width of the diagnostic pulse is smaller than that of the treatment pulse.

5. The excimer laser ablation system for restenosis after interventional treatment of Budd-Chiari syndrome according to claim 1, characterized in that, The organization type feature is a feature vector containing at least two parameters extracted from the photoacoustic signal, selected from the group consisting of: signal amplitude, peak frequency of the spectrum, bandwidth, or signal envelope decay time constant.

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