Ablation catheter system for adrenal vein blood sampling and detection and method of use

Abstract

The present invention provides an ablation catheter system for adrenal vein blood sampling and detection, comprising: an imaging system, configured for imaging and / or positioning a blood vessel and surrounding tissues thereof, and guiding a catheter to enter the renal vein and the adrenal vein; a detection system, configured for entering the renal vein or the adrenal vein under the guidance of the imaging system, collecting a blood sample in a target region, and detecting a hormone concentration in the blood sample; and an ablation system, configured for performing, when the detection system determines that there is unilateral dominant secretion, ablation treatment on the adrenal gland or an adrenal tumor on the dominant secretion side to reduce or eliminate hormone secretion on the side. The present invention can simplify the workflow and integrate blood sampling, testing, and treatment.

Description

Adrenal vein blood sampling ablation catheter system and usage Technical Field

[0001] This invention relates to the field of medical devices, and in particular to an adrenal vein blood sampling and ablation catheter system and its method of use. Background Technology

[0002] Primary aldosteronism (PA) is a common endocrine disorder characterized by excessive secretion of aldosterone by the adrenal glands, leading to elevated blood pressure and hypokalemia. The incidence of PA is approximately 5-10% in patients with hypertension, and can reach over 20% in patients with refractory hypertension. PA not only increases the risk of cardiovascular events but may also lead to kidney damage. Therefore, accurate diagnosis and timely treatment of PA are crucial.

[0003] Current diagnostic and treatment processes often involve multiple and repeated visits, resulting in a very long and complex workflow that hinders patients from receiving rapid and effective diagnosis and treatment. As a result, on the one hand, it prolongs the time it takes for patients to receive the correct treatment, and sometimes, due to the excessive length of the process and the numerous departments and decisions involved, patients simply cannot receive the correct treatment at all. On the other hand, it leads to very high medical costs, increasing the burden on public health or further hindering patients from receiving effective treatment.

[0004] Currently, a typical workflow includes identification, screening, diagnosis, blood typing and collection, testing, and treatment.

[0005] In the process of blood collection based on blood type, the current method involves inserting a pre-designed angiography catheter into the inferior vena cava during interventional surgery. Referring to the approximate anatomical location, the catheter is repeatedly withdrawn until it springs into the vessel opening under tension. While there are many innovative designs, such as CN109820519B, CN217162119U, CN216603766U, CN219629632U, and CN219629633U, current industry understanding focuses solely on the specific tubing design to better suit the structure of the adrenal vessels. It fails to break free from the ingrained mindset of withdrawing the catheter and allowing it to slide into the vessel opening. Therefore, improvements to blood collection are marginal rather than qualitative, and certain blind spots still exist within the industry.

[0006] The current testing procedure involves placing a catheter in the target blood vessel (typically a Simmons catheter on the left and a Cobra catheter on the right), drawing blood, and measuring the concentrations of aldosterone and cortisol in the plasma using chemiluminescence immunoassay to determine whether aldosterone has a dominant distribution in different vessels, thus influencing treatment strategy. However, this method is currently very time-consuming, involving the transfer of blood samples between the operating room and the laboratory, as well as the time required for reagent elution and reaction, typically taking more than half a day. This means that doctors may not receive the test results for a long time after the surgery.

[0007] The current treatment approach involves surgically removing the lesion if blood tests indicate a dominant distribution; otherwise, lifelong medication is administered. The former approach requires readmission for general anesthesia, which is expensive and carries anesthetic risks. The latter approach raises concerns about medication complications and associated costs associated with lifelong medication.

[0008] The entire workflow is relatively fragmented. Blood typing and sampling are performed by interventional physicians in the catheterization lab, testing is done by sending blood samples to a testing laboratory, and treatment, especially surgical treatment, is performed by urologists in the operating room. The process is very complex, time-consuming, and uneconomical.

[0009] Therefore, designing a new, simplified workflow that combines blood collection, testing, and treatment becomes highly meaningful. This invention provides a system and related method for a one-stop procedure that integrates adrenal vein blood collection, testing, and ablation in a single interventional procedure. Summary of the Invention

[0010] The purpose of this invention is to provide an adrenal vein blood sampling and ablation catheter system to simplify the workflow by combining blood collection, testing and treatment, based on the above-mentioned problems.

[0011] To achieve this objective, the present invention provides an adrenal vein blood sampling and detection ablation catheter system, characterized by comprising: an imaging system for imaging and / or locating blood vessels and surrounding tissues, guiding the catheter into the renal vein and adrenal vein; a detection system, guided by the imaging system, entering the renal vein or adrenal vein, subsequently sampling blood in the target area and rapidly or in real-time detecting the hormone concentration in the blood sample; when the detection system indicates the presence of unilateral dominant secretion, the ablation system can perform ablation treatment on the adrenal gland or adrenal adenoma on the dominant secretion side, reducing or eliminating hormone secretion on that side.

[0012] Preferably, the imaging system includes a first catheter, a first imaging system, and a first channel; used to image blood vessels and surrounding tissues, as well as the detection system and ablation system, and to guide the detection and ablation systems into the target blood vessel; the first channel can accommodate at least a portion of the detection system and the ablation system; the first imaging system is preferably disposed on the first catheter.

[0013] The first catheter has at least one distal opening and one proximal opening. The first catheter includes a first channel connecting the distal opening and the proximal opening. At least a portion of the detection system or ablation system enters the target blood vessel via the first channel under the guidance of the first imaging system to perform subsequent operations. The first imaging system uses at least ultrasound imaging technology; the ultrasound imaging system can optionally be 2D imaging and is positioned distal to the distal opening of the first catheter, with one or a group of ultrasound transducer elements distributed axially. The imaging plane is a fan-shaped or similar fan-shaped surface parallel to the long axis of the first catheter, and the imaging plane is coplanar with the axis of the first channel, thereby detecting instruments entering and exiting within the first channel. The 2D ultrasound imaging system can also image the cross-section of the blood vessel by rotating a single ultrasound transducer, making the openings of the blood vessel branches more clearly visible; the ultrasound imaging system can also be configured for 3D imaging, that is, by generating multiple 2D ultrasound images in different orientations and stitching them together to form an image; the ultrasound imaging system can also be configured for real-time 3D imaging and is arranged at the distal end of the distal opening of the first catheter, with a set of ultrasound transducer element arrays distributed circumferentially, configured to perform 360° imaging of the cavity around the catheter system, facilitating rapid location of the target blood vessel.

[0014] Preferably, the imaging system images or locates the blood vessel and its surrounding tissues, and also images or locates a part of the detection system, so that a distal part of the detection system and the opening of the target blood vessel appear simultaneously in the imaging field of view.

[0015] Preferably, the detection system employs a homogeneous reaction system, comprising a donor bead microsphere on which an antibody or aptamer is modified. A acceptor bead microsphere is then designed, with another antibody or aptamer modified on its surface, forming a sandwich system. When the donor bead receives external excitation light, it emits oxygen free radicals, causing adjacent acceptor beads to emit light of different wavelengths. By capturing this specific wavelength of emitted light, the concentration of the analyte can be estimated by measuring the number of sandwich systems formed.

[0016] The detection system also employs a homogeneous reaction system, featuring a rotating disk containing one or more rotating axes. During rotation, centrifugal force is provided, effectively achieving stirring and separation. The disk performs plasma separation and measurement detection. After the blood sample is added to the disk, plasma separation is first achieved through centrifugation. Aldosterone and cortisol, being small molecules, are distributed in the supernatant, which is then extracted to another reaction chamber. By adjusting the centrifugal force, the reagents and supernatant are thoroughly mixed and reacted within the reaction chamber. The mixture is then introduced into the luminescence chamber via capillary action or active aspiration. The luminescence chamber is configured to accept a given light source with a wavelength range encompassing the designed wavelength range of the donor beads. Furthermore, the luminescence chamber is configured to allow the excitation light emitted by the acceptor beads to enter an optical probe. The optical probe measures the light flux, thereby measuring the concentration of the analyte. The light source is pulsed, and the optical probe collects the excitation light after a certain time delay to better avoid the influence of background noise on the results.

[0017] Preferably, the detection system includes a blood collection catheter and an in vitro detection module. The blood collection catheter is used to collect blood from a target blood vessel, and the collected blood sample is then dripped into the in vitro detection module to obtain the detection results. The diameter of the blood collection catheter is slightly larger than the target blood vessel size by 1-2 F, which facilitates its insertion into the target blood vessel and blocks the lumen opening, preventing blood from the upstream blood vessel from flowing into branches under negative pressure during the blood collection process and affecting the detection results. The blood collection catheter includes a first lumen, which allows for easier entry into the target blood vessel and / or blood aspiration sampling under the guidance of a guidewire. The blood collection catheter has a distal opening with a bevel design, and the distal end of the blood collection catheter includes at least one side hole. The blood collection catheter includes an occlusion balloon, which is preferably positioned 5-50 mm away from the distal opening of the blood collection catheter to isolate the target blood vessel from its upstream blood vessel, avoiding interference from blood in the upstream blood vessel with the detection results. The blood collection catheter includes an outer cannula and a central blood collection tube. The distal end of the central blood collection tube is provided with a blood collection groove. The central blood collection tube can be inserted only during blood collection or it can be placed in the outer cannula beforehand. When in use, the central blood collection tube is extended from the distal end of the outer cannula and exposed to the blood collection groove, allowing blood to fill the blood collection groove. Then, the central blood collection tube is retracted into the outer cannula, and the opening of the blood collection groove is blocked by the inner wall of the outer cannula, thereby preserving the blood sample.

[0018] Preferably, the ablation method for the ablation catheter can be alcohol ablation or steam ablation treatment.

[0019] The adrenal vein blood sampling and ablation catheter system also includes at least one display. The display can be integrated into or connected to the imaging system, detection system, and ablation system respectively, or it can be compatible with the above three systems at the same time, displaying the images and / or data required by the three systems simultaneously, making the data and information more intuitive and easier for the operator to operate.

[0020] The imaging system, detection system, and ablation system are configured on a single operating cart and share a single monitor. The in vitro detection module of the detection system is located at the bottom of the operating cart, while the imaging system is located at the top to avoid obstructing the operating area. The ablation system typically needs to be connected to the ablation instruments to provide ablation energy, but its operation is simpler than that of the imaging system, so it is located in the middle of the operating cart. When the three systems share the monitor, the screen is divided into three different areas to display the corresponding images, parameters, and other information for each system.

[0021] Another objective of this invention is to provide a method for using an adrenal vein blood sampling and ablation catheter. To achieve this objective, this invention provides a method for using an adrenal vein blood sampling and ablation catheter, the method comprising: coordinating a detection system with an imaging system; inserting a portion of the detection system into the left and right adrenal veins and / or their branches respectively, according to the method for entering the left or right adrenal vein; collecting blood samples from the adrenal vein and / or its branches and peripheral veins according to the in vitro hormone detection method for primary aldosteronism described above, and measuring the concentration and / or activity of the target hormone in vitro; or directly measuring the concentration and / or activity of the target hormone in the target blood vessel and peripheral veins in vivo according to the in vivo hormone detection method for primary aldosteronism described above; determining the subtype and treatment method according to the treatment strategy for primary aldosteronism, and performing ablation treatment according to the above ablation method.

[0022] The imaging system is positioned in the patient's inferior vena cava. Using the first imaging system mounted on the first catheter, the vascular opening conforming to the anatomical features of the renal vein is located. After determining the location and orientation of the renal vein, the instrument to be inserted into the target vessel is advanced along the first channel until the imaging system can simultaneously observe both the instrument and the renal vein opening. The first catheter is advanced into the renal vein via a sheath or by changing the guidewire, locating the opening of the left adrenal vein. Then, guided by the first imaging system, the detection system is advanced along the first channel into the adrenal vein. The blood collection catheter is then advanced to one of the target vessels through the first catheter. Blood is then collected from this vessel for real-time in-situ detection or external testing. If blood has been collected from all target vessels, the blood collection process ends, and the typing is determined based on the test results; otherwise, another target vessel is selected, and the above process is repeated.

[0023] The beneficial effects of this invention are that it integrates adrenal vein blood collection, detection, and ablation into a single interventional procedure, creating a one-stop surgical system and related methods. This effectively solves the problems of cumbersome, time-consuming, and costly workflows, eliminates delays in patient diagnosis and treatment, and offers the potential to provide better treatment options for both focal and diffuse lesions. Although blood collection, detection, and ablation may appear distinct in terms of instrument composition or surgical steps, they are actually organically coupled and indispensable for achieving the intended purpose of the invention, resulting in a synergistic effect greater than the sum of its parts (1+1+1>3).

[0024] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, preferred embodiments are described below in detail with reference to the accompanying drawings. Attached Figure Description

[0025] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0026] Figure 1 is a schematic diagram of the typical workflow for PA patients from identification to treatment;

[0027] Figure 2 is a schematic diagram of one implementation of the workflow from PA patient identification to treatment in this invention;

[0028] Figure 3 is a schematic diagram of the conventional catheter method for blood typing.

[0029] Figure 4 is a schematic diagram of the distribution of adrenal veins;

[0030] Figure 5 is a schematic diagram of focal lesions;

[0031] Figure 6 is a schematic diagram of diffuse lesions;

[0032] Figure 7 is a schematic diagram of the implementation methods of the imaging system and the detection system;

[0033] Figure 8 is a schematic diagram of the implementation method of the blood collection catheter;

[0034] Figure 9 is a schematic diagram of the implementation of the outer cannula and central blood collection tube of the blood collection catheter;

[0035] Figure 10 shows the method and schematic diagram for entering the left adrenal vein;

[0036] Figure 11 shows the method and schematic diagram for accessing the right adrenal vein;

[0037] Figure 12 is a schematic diagram of one embodiment of the blood collection method;

[0038] Figure 13 is a schematic diagram of an implementation method for the detection catheter;

[0039] Figure 14 is a schematic diagram of the implementation of the detection catheter and detection cannula;

[0040] Figure 15 is a schematic diagram of an implementation method for the in vitro detection module;

[0041] Figure 16 is a schematic diagram of an embodiment of traditional AVS classification decision-making;

[0042] Figure 17 is a schematic diagram of an embodiment of the superselective AVS classification decision-making method;

[0043] Figure 18 is a schematic diagram of an embodiment of the superselective AVS classification decision-making method;

[0044] Figure 19 is a schematic diagram of complete destruction of a unilateral adrenal gland in a focal lesion;

[0045] Figure 20 is a schematic diagram of complete destruction of a unilateral adrenal gland in a focal lesion;

[0046] Figure 21 is a schematic diagram of partial destruction of the entire adrenal gland in diffuse lesions;

[0047] Figure 22 is a schematic diagram of the lumen of the ablation catheter;

[0048] Figure 23 is a schematic diagram of the implementation of the ablation catheter and ablation guidewire;

[0049] Figure 24 is a schematic diagram of the tissue and vascular layers of the adrenal gland;

[0050] Figure 25 is a schematic diagram of the heat release method of steam ablation and the corresponding area;

[0051] Figure 26 is a schematic diagram of an implementation of the in vitro non-invasive ablation device;

[0052] Figure 27 is a schematic diagram of an implementation of the second catheter system;

[0053] Figure 28 is a schematic diagram of depth and direction indicators;

[0054] Figure 29 is a schematic diagram of the imaging system, detection system, and ablation system used together. Detailed Implementation

[0055] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0056] The following describes a systematic solution integrating blood collection, testing, and ablation. As a diagnostic and therapeutic system, it allows for the completion of blood typing, testing, and surgical treatment within a single interventional procedure—a one-stop procedure. This invention provides a system and related methods for a one-stop procedure that integrates adrenal vein blood collection, testing, and ablation into a single interventional procedure.

[0057] This system can be simply broken down into three functional modules: blood collection, detection, and ablation. Alternatively, this one-stop procedure can be broken down into three steps: blood collection, detection, and ablation. It is important to note that, within the scope of this invention, the different functional modules and steps are interconnected and require understanding and interpretation at the system level.

[0058] This invention discloses a simple, rapid, and stable catheter system and method for entering target blood vessels. As shown in Figure 7, its key feature is that it can utilize an imaging system to obtain real-time information on the orientation of the catheter or guidewire extending from the first channel relative to the blood vessel opening. This better guides the surgical procedure, avoiding the need for repeated attempts and processes without straight catheter guidance. It significantly reduces surgical difficulty, increases the success rate of blood vessel entry, and greatly shortens surgical time. Current blood retrieval catheter systems and methods typically take 1-2 hours to enter both adrenal veins; however, the catheter system and method used in this invention can reduce this time to less than 15 minutes.

[0059] As important hormones regulated by multiple factors, the secretion levels of aldosterone and cortisol fluctuate significantly over time. Therefore, to more accurately compare the concentrations of aldosterone and cortisol in different target blood vessels, the time delay between blood collection becomes crucial. The greatest benefit of this invention is a significantly reduced surgical time. Compared to current technologies, it substantially shortens the time delay between blood collection from different target blood vessels, maximizing detection accuracy and thus improving the detection module.

[0060] It is worth mentioning that this catheter system, in addition to delivering a detection catheter into the target blood vessel for blood sampling and testing, can also deliver an ablation catheter for ablation. In short, a convenient and easy-to-use delivery system is a prerequisite for simple, rapid, stable, and accurate blood sampling and testing, as well as for simple, rapid, stable, and accurate endovascular treatment. The catheter system and its method of use disclosed in this invention, which facilitates access to vascular branches, achieves these objectives.

[0061] This invention discloses various rapid detection methods for cortisol and aldosterone concentrations, characterized by: ① enabling point-of-care and even in vivo testing, eliminating the logistical costs of sending blood samples to a laboratory and the costs of interdepartmental coordination; ② utilizing efficient and rapid molecular techniques, avoiding limitations such as complex reagent elution and complex antigen-antibody immune reactions; and ③ providing clear and accurate information to physicians through an integrated device interface and user interface, rather than fragmented and complex reports, thus reducing the physician's understanding costs. Current testing equipment and methods typically take half a day, while the testing equipment and methods used in this invention can complete the test within 15 minutes.

[0062] Because the testing is extremely fast and well integrated into the surgical workflow, doctors can obtain test results during surgery and make immediate treatment decisions, enabling the patient to be treated in the same procedure—in other words, rapid testing systems and methods are a prerequisite for one-stop surgery. The rapid cortisol and aldosterone concentration detection system and method disclosed in this invention makes it possible to perform blood typing and interventional ablation in the same procedure. Patients no longer need to wait a long time for their next hospitalization, thus shortening the time it takes for patients to receive proper treatment and reducing related hospitalization costs.

[0063] This invention discloses an ablation system and method for interventional treatment of patients with primary aldosteronism, characterized by: ① using different ablation systems and methods for patients with different subtypes, or using the same ablation system and method but with different parameter configurations; ② for patients with focal lesions, inserting an ablation catheter into the blood vessel where aldosterone is predominant to completely destroy the focal lesion, while for patients with diffuse lesions, extensive partial destruction of the entire adrenal gland; ③ using methods such as steam, alcohol, electric field, and ultrasound, rather than surgical resection, preferably endovascular ablation therapy.

[0064] The advantages of ablation therapy are: ① It can be performed during interventional surgery, thus sharing the same operating table, equipment, and team with interventional blood sampling, rather than using two separate systems and personnel; ② It can be performed without general anesthesia, whereas traditional surgical resection requires pneumoperitoneum, necessitating general anesthesia, which increases costs and carries potential anesthetic risks; ③ For patients with focal lesions, endovascular treatment makes superselective treatment of adrenal lesions possible. Blood sampling is based on blood flow; if the lesion is located in the blood vessel basin, ablation of that basin can precisely damage the lesion without harming other healthy tissues. Blood can be drawn from the adrenal branch rather than the traditional main trunk. If aldosterone predominance is confirmed, the lesion can be identified as being located in the blood vessel basin of that specific branch. Superselective treatment of this specific branch, i.e., complete ablation of the adrenal tissue received by that branch, can preserve other ipsilateral kidneys outside that branch. Adrenal tissue, thereby achieving maximum destruction of lesions and maximum preservation of healthy tissue, that is, precision treatment—current surgical resection techniques are difficult to achieve based on the division of vascular flow domains because the contours of vascular flow domains cannot be distinguished during surgery, so such superselectivity is unrealistic and difficult to achieve; ④ For patients with diffuse lesions, both drug treatment and surgical treatment are valuable, but the current diagnostic classification results can only be obtained after the classification surgery. Therefore, when deciding whether to perform additional surgical treatment for these patients, the risk-benefit balance is more inclined towards lifelong medication, which leads to cost issues and potential drug side effects—if the classification results can be known during the operation, the risk-benefit balance will change, and low-risk ablation methods will become more valuable, or in other words, adrenal ablation treatment is worthwhile for these patients without increasing very limited additional costs and surgical risks, thus making it possible to cure patients with diffuse lesions.

[0065] The following describes the mechanism of primary aldosteronism (PA). Aldosterone is mainly secreted by the zona glomerulosa of the adrenal glands and is normally regulated by physiological feedback mechanisms. In PA, aldosterone secretion is highly autonomous and cannot be rationally suppressed by these mechanisms. This is a very complex endocrine disorder, not a single disease. The disease spectrum can be broadly divided into two categories: focal and diffuse lesions. Current treatment for the former is surgical removal of the lesion. The inventors believe that ablation therapy, which completely destroys the lesion, can achieve the same effect as surgery. The optimal treatment for the latter is drug therapy, which involves long-term medication to inhibit aldosterone activity. The inventors believe that either the current conventional treatment, namely drug therapy, can be adopted, or partial destruction of all adrenal glands can be considered to reduce adrenal function, which may achieve a complete or partial cure. In other words, no drug therapy is needed at all, or drug therapy is needed but at a smaller dose.

[0066] After being secreted by the zona glomerulosa of the adrenal gland, aldosterone enters the capillaries and flows back to the main adrenal vein through various venous branches (Figure 4). In the adrenal glands (PA), some adrenal tissues express excessive aldosterone synthase (CYP11B2), and its secretion can be unrestricted by endocrine regulation, spontaneously and excessively secreting excess aldosterone. These adrenal tissues are called lesions. Measuring aldosterone concentrations from blood samples taken from various veins can identify whether these lesions originate from a specific venous region or are diffusely distributed across all venous regions.

[0067] Focal lesions are characterized by one or more lesions expressing excessive aldosterone synthase, resulting in excessive aldosterone secretion at the lesion site, as shown in Figure 5. In these diseases, the spherical zone outside the lesion is relatively normal tissue and is inhibited, secreting only a small amount of aldosterone. Therefore, it exhibits a very obvious local characteristic, with some parts secreting excessive aldosterone and others secreting insufficient aldosterone. Usually, in patients with a single lesion, an excessively high aldosterone concentration can be detected in the adrenal vein on one side, while an inhibited aldosterone concentration can be detected in the adrenal vein on the contralateral side, thus identifying and locating the lesion side. In patients with multiple (more than one) lesions, bilateral lesions may occur, resulting in elevated aldosterone concentrations in the main trunks of both adrenal veins. However, when superselective adrenal vein branches are performed, inhibited aldosterone concentrations can be detected in some branches. In the case shown in Figure 5, there is a focal lesion 95 in the left adrenal gland 94a. If blood is drawn from the main adrenal veins on both sides, the main adrenal veins on one side will show an advantage over the main adrenal veins on the other side. If superselective blood is drawn from the various branches of the adrenal gland on this side, it can be found that branch 934a shows an advantage over branches 934b and 934c, and the lesion can be located more accurately in the basin of branch 934a.

[0068] Another characteristic of focal lesions is the suppression of aldosterone in non-lesion areas. When excessive aldosterone is secreted by glandular cells at the lesion site and reaches the whole body, the body inhibits further aldosterone secretion by the adrenal glands through physiological negative feedback regulation. The most typical signaling pathway is the RAAS system, but other regulatory mechanisms also exist. Glandular cells in non-lesion areas will be inhibited, thus reducing aldosterone secretion. If this inhibition is prolonged, it will also reduce the expression of CYP11B2, thereby weakening or even eliminating aldosterone secretion function. Therefore, the aldosterone concentration in non-lesion areas will be significantly lower than that at the lesion site, and may even be lower than the level in peripheral veins (such as the inferior vena cava).

[0069] Diffuse lesions, characterized by excessive expression of aldosterone synthase, are diffusely distributed throughout the zona glomerulosa of the adrenal glands, lacking distinct local features. The zona glomerulosa exhibits increased aldosterone synthesis capacity across the entire gland, with no apparent inhibition or significant local tissue secretion compared to other tissues, as shown in Figure 6. In these patients, a relatively consistent increase in aldosterone concentration can be detected in both main adrenal veins. Even after superselection of adrenal vein branches on one side, no particular vein shows a significantly suppressed aldosterone concentration.

[0070] The following will explain the focus and significance of the invention based on the inventor's understanding of the primary aldehyde mechanism and workflow. Currently, a typical workflow includes identification, screening, diagnosis, blood typing and sampling, and surgical treatment, as shown in Figure 1.

[0071] Identification: Patients may be identified as suspected PA patients during physical examinations, general practice visits, or other occasions. Typical characteristics include early onset, hypokalemia, hypertension, and insensitivity to antihypertensive medication.

[0072] Screening: For suspected PA patients, it is necessary to measure ARR level. ARR is the ratio of serum aldosterone concentration to serum renin concentration / activity. ARR screening is usually performed in cardiology or endocrinology outpatient clinics. Patients with high ARR levels are called PA screening positive patients.

[0073] Confirmation: For patients with positive PA screening results, a confirmatory test will be performed to determine whether aldosterone secretion can be suppressed. If not, PA can be formally diagnosed. There are four widely recognized confirmatory tests: saline test, captopril test, oral high-sodium diet test, and fludrocortisone test. The most commonly used test is the saline test. Confirmatory tests are usually performed in the endocrinology ward. If PA is diagnosed, the patient will be discharged and await the next hospitalization for AVS (see below). Currently, some researchers are exploring the possibility of other types of confirmatory tests.

[0074] Aldosterone (PA) typing is necessary for PA patients to determine treatment options (see below). There are three typing methods: adrenal vein sampling (AVS), CT / MRI imaging, and PET molecular imaging. AVS is the most accurate and widely accepted method, requiring an interventional vascular procedure to insert catheters into both adrenal veins to collect blood samples and measure aldosterone concentrations to complete the typing. Traditionally, only the main adrenal vein is measured; newer methods include measuring branches of the adrenal vein, called superselective AVS. AVS is usually performed in the interventional radiology department. Results are not available during the procedure and may take several hours or even a day. Patients requiring further surgery will be discharged and await their next hospitalization.

[0075] Surgical treatment: For patients with focal lesions, local lesion resection is required, usually performed endoscopically. Surgical treatment is typically performed in a urology ward. It is important to note that, as the inventors have stated, ablation therapy remains beneficial for both patients with focal and diffuse lesions.

[0076] In summary, patients often need to be transferred between multiple departments, undergo repeated hospitalizations, incurring high hospitalization costs, and experiencing significant delays from initial diagnosis to final treatment. Furthermore, some patients on long-term antihypertensive medication may need to discontinue their medication before examinations, leading to repeated medication interruptions and re-administration, exposing them to prolonged exposure to the risks of fluctuating blood pressure.

[0077] Adrenal vein sampling (AVS) is the gold standard for PA classification diagnosis. Its principle is to directly obtain blood samples from both adrenal veins, assess their secretory function to determine whether the patient has a focal or diffuse lesion, and identify the dominant secretory side within a focal lesion, thus guiding the choice of treatment. AVS measures the concentrations of aldosterone and cortisol in both adrenal veins and peripheral veins, and calculates the Selectivity Index (SI) and Lateralization Index (LI) to determine whether adrenal vein sampling was successful and whether aldosterone secretion was dominant, thereby deciding whether surgical resection or drug treatment is necessary. In recent years, with technological advancements, in addition to the traditional method of sampling from the main adrenal veins, there are also methods called selective or superselective adrenal vein sampling, which collect blood from branches of the adrenal veins in addition to the main trunks, to achieve more accurate diagnosis. However, current methods are not mature. Aldosterone and cortisol concentrations are affected by many factors, the most prominent being the time delay between blood collections (see below). The lack of sufficiently convenient, rapid, and reliable catheters leads to prolonged entry into target veins, resulting in significant delays and affecting blood collection accuracy. Making an accurate diagnosis based on inaccurate results is difficult and imprecise. Different people hold different classification decision-making strategies. For example, some choose the absolute value of aldosterone concentration as an indicator of aldosterone secretion function, while others believe that absolute aldosterone concentration itself is inaccurate and use the ratio of aldosterone to cortisol concentration as a relative concentration indicator. The inventors suggest using relative concentration, i.e., the ratio of aldosterone to cortisol concentration (A / C ratio), to evaluate aldosterone concentration. Unless otherwise specified in this invention, both absolute and relative concentration methods can be used to measure and represent aldosterone concentration, with relative concentration being the preferred option.

[0078] Current methods for AVS include sequential blood collection or bilateral simultaneous blood collection. Different people tend to use different methods, and there is no unified standard.

[0079] Sequential bilateral adrenal veno-venous (AVS) sampling refers to the procedure where blood is drawn from one adrenal vein first, followed by blood from the other. In practice, the right adrenal vein is usually sampled first because its anatomical location varies considerably, making sampling more difficult, while the left adrenal vein is relatively easier to access. While this method avoids simultaneous puncture of two sites, reducing the risk of venous thrombosis and puncture site complications, a long interval between sampling can lead to hormone concentration gradient errors due to pulsatile hormone secretion and the time difference in sampling time, especially when sampling from the right adrenal vein is difficult. Sometimes, ACTH stimulation can be added to sequential sampling. ACTH significantly stimulates the secretion of cortisol and aldosterone, thus smoothing out the natural fluctuations in cortisol and aldosterone levels and reducing errors. However, some have suggested that ACTH stimulation may cause side effects or lead to less accurate testing.

[0080] Simultaneous blood sampling refers to the simultaneous collection of blood from both adrenal veins using two catheters during adrenal vein sac osmosis (AVS). This method avoids errors caused by time differences in blood collection and improves the accuracy of test results. However, it requires simultaneous puncture at two sites, and the increased residence time of both catheters in the adrenal veins may increase the risk of venous thrombosis and puncture site complications. Furthermore, the use of two sets of puncture and blood collection instruments increases the cost of the procedure and the burden on the patient. Additionally, in superselective AVS, blood collection from more than two sites is required, making simultaneous blood sampling clearly impractical and impossible.

[0081] Simultaneous blood sampling is essentially a compromise, as current technology makes accessing the adrenal vein difficult. First, the adrenal vein needs to be located, currently achieved through venography. Venography is more challenging than arterography because, in arterial angiography, the contrast agent can flow with the blood into the arterial branches. However, in venography, the contrast agent must flow against the blood flow into the venous tributaries. Therefore, it often results in the contrast agent failing to reach the venous tributaries or receiving too little contrast agent to form an image, especially when the venous tributaries are small (the adrenal vein is only 1-2 mm in diameter), making it even more difficult to achieve ideal imaging. Secondly, the adrenal veins converge into veins with much larger diameters, making access extremely difficult. The left adrenal vein is approximately 1-2 mm in diameter, converging into the left renal vein, which is about 8-10 mm in diameter. The situation is even more pronounced on the right side, where the same 1-2 mm vein converges into the inferior vena cava, which is about 15-25 mm in diameter. Angularly, the opening of the adrenal vein occupies only a small portion of the wall of the converging vein, demanding extremely high precision. Because the adrenal veins are very small, only small-diameter catheters can be used, and these small-diameter catheters are difficult to maneuver effectively in large-diameter veins. In summary, due to current technological limitations, accessing the adrenal veins is very difficult, prone to failure, and time-consuming, hence the debate between sequential and simultaneous blood sampling. Clinically, a simple, convenient, and reliable method for accessing the adrenal veins is needed.

[0082] After the interventional blood sampling procedure, the blood sample needs to be sent to the laboratory for testing. As explained above, if the AVS results indicate localized dominant secretion and inhibition, the diagnosis is focal lesion; otherwise, the diagnosis is diffuse lesion. Due to current technological limitations and hospital management models, laboratory testing usually takes 3-24 hours, and patients can only receive a diagnosis after the procedure.

[0083] For patients with focal lesions confirmed by AVS, traditional treatment options include laparoscopic adrenalectomy and medication. While laparoscopic surgery is minimally invasive, it still carries surgical risks and the possibility of postoperative complications. Medication, while avoiding surgical risks, may present challenges in long-term adherence and drug side effects. Furthermore, for patients unwilling or unsuitable for surgery, medication may be the only option, but its efficacy may be inferior to surgical treatment.

[0084] In recent years, interventional ablation therapy for organs other than the adrenal glands, such as the heart, liver, or lungs, has emerged as a new treatment method, gaining attention due to its minimally invasive nature, repeatability, and good local therapeutic effects. Ablation therapy directly targets the diseased tissue using physical or chemical methods, reducing hormone secretion to achieve the therapeutic goal.

[0085] Regardless of the surgical method used, patients need to undergo two procedures: blood collection and treatment, which are quite invasive and involve a long waiting period.

[0086] In summary, existing AVS tests have certain limitations in accuracy, and performing blood tests and treatments in separate sessions still places a significant burden on patients.

[0087] Therefore, it is of great significance to find a way to quickly, conveniently, and economically achieve subtyping diagnosis and targeted treatment for PA patients.

[0088] To address the shortcomings of existing technologies, this invention aims to provide a one-stop catheter system for adrenal vein blood sampling, detection, and ablation, as well as its usage method. This catheter system integrates advanced catheter guidance technology, rapid / real-time detection technology, and ablation technology, enabling operators to perform rapid and accurate blood sampling, rapid / real-time intraoperative testing, and immediate ablation treatment based on intraoperative rapid test results, providing a safer, more effective, and more economical treatment option for PA patients.

[0089] This invention simplifies the workflow, enabling blood collection, testing, and ablation for primary aldosteronism patients to be completed in a single interventional procedure—a one-stop procedure, as shown in Figure 2. In addition to proposing this one-stop procedure concept, this invention will also introduce the specific design and related considerations of the catheter system required for performing this procedure, the method of using the catheter system, and decision-making methods for different intraoperative situations.

[0090] By integrating advanced catheter guidance, detection, and ablation technologies, it will be possible to significantly improve the workflow from classification to treatment of primary aldosteronism patients. The advantages are as follows: First, for patients, more accurate classification means more individualized treatment, allowing doctors to make more informed decisions and patients to receive higher-quality care. Second, for doctors, the workflow is simpler, easier to learn, and less prone to errors. Third, for hospitals, the collaborative process is simplified; what previously required two or even three hospitalizations is now combined into a single hospitalization; and what used to require patients to move between multiple departments and wards can now be completed within a single department and ward, shortening the diagnostic and treatment cycle and reducing personnel costs. Fourth, for payers (whether it's health insurance, patients, or co-payers), by reducing the number and duration of hospitalizations and the number of surgeries (from two surgeries for AVS+ treatment to one single surgery), hospitalization costs can be significantly reduced, resulting in significant health economic benefits.

[0091] It is worth mentioning that this invention applies ablation therapy to the treatment of both focal and diffuse lesions, rather than the traditional surgical adrenalectomy and drug therapy. This is because AVS classification requires interventional surgery, and the marginal cost of adding adrenal interventional ablation therapy to the same procedure is low, with minimal additional risk to the patient and minimal additional cost. Therefore, it disrupts the original risk-benefit balance, making the benefit more dominant in the risk-benefit decision-making process of ablation therapy. Furthermore, this invention is based on a fundamental understanding of focal and diffuse lesions. It recognizes that focal lesions require selective and complete destruction of the adrenal tumor while preserving other residual adrenal gland tissue, while diffuse lesions require non-selective, extensive, and incomplete destruction of both adrenal glands to broadly reduce adrenal secretory function without completely eradicating it. Therefore, a high-intensity ablation tool may be needed for focal lesions, while a low-intensity ablation tool may be needed for diffuse lesions, or the same ablation tool may be used for both, but the former has a larger dose and the latter has a smaller dose.

[0092] The following explanation, in conjunction with the accompanying drawings, details the method for adrenal vein blood sampling, detection, and ablation provided by this invention. For ease of explanation, the target vessel referred to herein is the target vessel for diagnosis or treatment involving adrenal vein blood sampling, detection, and ablation, typically the left and right adrenal veins. This may include the main adrenal vein, or its primary branches or higher-level branches. For some treatment methods, it may also refer to the adrenal artery, which may include one or more adrenal arteries, or their primary branches or higher-level branches. It should be noted that in anatomy, vein branches are usually called tributaries; however, for the sake of non-medical readers and because the inventors recognized the applicability of this technique in arteries, the term "branch" is used herein. In the section on detection, the term "test vessel" will be introduced because the interpretation of adrenal hormones includes both hormone concentrations in the adrenal veins and in peripheral blood vessels. Therefore, the test vessel refers to both the target vessel and peripheral blood vessels. The most commonly used and easiest site for blood sampling in peripheral blood vessels is the inferior vena cava, but this can also be extended to other peripheral blood vessels, such as the superior vena cava, femoral vein, axillary vein, brachial vein, aorta, and femoral artery.

[0093] This invention provides a one-stop catheter system for adrenal vein blood sampling, detection, and ablation, comprising: an imaging system 1, a detection system 2, and an ablation system 3. The imaging system images and / or locates the blood vessels and surrounding tissues, guiding the operator to locate and manipulate the catheter into the renal vein and adrenal vein. The detection system, guided by the imaging system, enters the renal vein or adrenal vein, then samples blood from the target area and rapidly or in real-time detects the hormone concentration in the blood sample. When the AVS result obtained by the detection system indicates unilateral dominant secretion, the ablation system can ablate the adrenal gland or adrenal adenoma on the dominant secretory side, reducing or eliminating hormone secretion on that side.

[0094] The imaging system includes a first catheter, a first imaging system, and a first channel; referring to the patent application number PCT / CN2024 / 113932, a catheter system and its method of use that facilitate access to a cavity branch are disclosed. The first imaging system can be any one or a combination of ultrasound, OCT, electro / magnetic positioning, optical endoscopy, etc., used to image blood vessels and surrounding tissues, as well as the detection system and ablation system, guiding the detection and ablation systems into the target blood vessel; the first channel can accommodate at least a portion of the detection system and the ablation system to pass through; the first imaging system is preferably disposed on the first catheter.

[0095] Preferably, the first catheter has at least one distal opening and one proximal opening, the first catheter includes the first channel, the first channel connects the distal opening and the proximal opening, and at least a portion of the detection system or ablation system enters the target blood vessel via the first channel under the guidance of the first imaging system to achieve subsequent operations.

[0096] Preferably, the first imaging system uses at least ultrasound imaging technology; the ultrasound imaging system may be 2D imaging and arranged at the distal end of the distal opening of the first catheter, with one or a group of ultrasound transducer elements distributed along the axial direction, the imaging plane being a fan-shaped or similar fan-shaped surface parallel to the long axis of the first catheter, and the imaging plane being coplanar with the axis of the first channel, thereby detecting instruments entering and exiting the first channel; the 2D ultrasound imaging system may also be able to image the cross-section of the blood vessel by rotating a single ultrasound transducer, making the openings of the blood vessel branches more clearly visible; the ultrasound imaging system may be 3D imaging, that is, generating multiple 2D ultrasound images in different orientations and stitching them together to form an image; the ultrasound imaging system may be real-time 3D (i.e., 4D) imaging and arranged at the distal end of the distal opening of the first catheter, with a group of ultrasound transducer element arrays distributed circumferentially, configured to perform 360° imaging of the cavities surrounding the catheter system, facilitating rapid location of target blood vessels.

[0097] The imaging frequency of the ultrasonic transducer is preferably 10-20MHz.

[0098] This invention also provides a method for accessing the left adrenal vein, the method comprising: positioning an imaging system in the patient's inferior vena cava and locating the opening of the left renal vein with the assistance of the first imaging system; inserting a guidewire or catheter to be inserted into the adrenal vein into the patient's body through a first channel of the imaging system; adjusting the orientation of the tip of the guidewire or catheter by observing the imaging field of the first imaging system to align it with the opening of the left renal vein; then inserting the guidewire or catheter into the left renal vein; subsequently slightly retracting the imaging system; and inserting the first catheter of the imaging system into the left renal vein along the guidewire or catheter already inserted into the left renal vein by using an additional adjustable curved sheath or directly adjusting the orientation of the first catheter; next, locating the opening of the left adrenal vein in the left renal vein with the assistance of the first imaging system; adjusting the orientation of the tip of the guidewire or catheter extending from the first channel by observing the imaging field of the first imaging system to align it with the opening of the left adrenal vein and inserting it; the process of locating, aligning, and inserting is similar to the aforementioned process for entering the left renal vein and will not be described in detail; in the above steps, other imaging methods can be combined to assist in adjustment or confirmation, such as X-ray angiography.

[0099] First, please refer to Figure 7. Imaging system 1 images or locates the blood vessel and its surrounding tissues, and simultaneously images or locates a portion of detection system 2. This ensures that a distal portion of the detection system and the opening of the target blood vessel appear simultaneously in the imaging field of view, guiding the surgeon to quickly locate the target blood vessel (such as the renal vein and / or adrenal vein) and manipulate detection system 2 or a portion thereof into the target blood vessel for subsequent operations. In the above embodiment, detection system 2 can be interchanged with ablation system 3; that is, ablation system 3 can also be used in conjunction with imaging system 1 to reduce the difficulty of the surgery.

[0100] Referring to patent application number PCT / CN2024 / 113932, in some embodiments, the imaging system 1 includes a first catheter 11, a first imaging system 12, and a first channel 13. In the embodiment shown in Figure 7, the first catheter 11 has a proximal opening 111 and a distal opening 112. The first channel 13 connects the proximal and distal openings. At least a portion of the detection system 2 or ablation system 3 enters the first channel 13 through the proximal opening 111 and extends from the distal opening 112, thereby entering the imaging field of the first imaging system 12 and further entering the target blood vessel. At least a portion of the first imaging system 12 can use any one or more combinations of technologies such as ultrasound, OCT, electro / magnetic positioning, and optical endoscopy. In a preferred embodiment, the first imaging system 12 employs ultrasound imaging technology, simultaneously presenting the position and / or orientation of the target blood vessel and the detection system 2 or ablation system 3 through 2D, 3D, or 4D (i.e., real-time 3D) images.

[0101] Referring to Figures 10(a) and (b), the imaging system 1 is first positioned in the patient's inferior vena cava 931. The first imaging system 12, mounted on the first catheter 11, locates the vascular opening conforming to the anatomical features of the left renal vein 932. After determining the position and orientation of the left renal vein 932, the instrument to be inserted into the target vessel is advanced into the vessel along the first channel 13 until the imaging system 1 can simultaneously observe both the instrument and the opening of the left renal vein. The instrument to be inserted into the target vessel in the figure is, for example, the detection system 2. This instrument can also be replaced by the catheter and / or guidewire in the ablation system 3 and the second catheter system 4, and is equally applicable to other subsequent methods. This will not be repeated hereafter. Under the guidance of the imaging system 1, the detection system 2 is advanced into the left renal vein 932. Then, referring to application number PCT / CN2024 / 11... Patent 3932 discloses a method for inserting a first catheter into a primary branch using a sheath or by changing the guidewire. The first catheter 11 is inserted into the left renal vein 932, and the opening of the left adrenal vein 934 is located. Then, guided by the first imaging system 12, the detection system 2 is inserted into the left adrenal vein 934 along the first channel 13, as shown in Figure 10(c). Furthermore, if the surgeon requires superselectivity, instruments can be directly inserted into the left adrenal vein branches 934a, 934b, and / or 934c using special techniques. Alternatively, the imaging system 1 can be inserted into the left adrenal vein 934 by repeating the above operations, and the instruments can be inserted into the branch under the guidance of the first imaging system 12. It is worth noting that in the above operations, other imaging methods, such as X-ray angiography, can be used to assist in confirming the position of the instruments, further improving the accuracy of the surgical procedure.

[0102] In addition to the above-described embodiments, other embodiments of the first imaging system, first catheter and first channel disclosed in the patent application number PCT / CN2024 / 113932 are applicable to the imaging system 1 of this patent. The cooperation between the detection system 2 or ablation system 3 of this patent and the imaging system 1 can also refer to the cooperation between "guidance system" and "first imaging system, first catheter and first channel" in the cited patent.

[0103] This invention also provides a method for accessing the right adrenal vein, the method comprising: positioning an imaging system in the patient's inferior vena cava and locating the opening of the right adrenal vein with the assistance of the first imaging system; inserting a guidewire or catheter to be inserted into the adrenal vein into the patient's body through a first channel of the imaging system; adjusting the orientation of the tip of the guidewire or catheter by observing the imaging field of the first imaging system to align it with the opening of the right adrenal vein; and inserting the guidewire or catheter into the right adrenal vein; in the above steps, other imaging methods can be combined to assist in adjustment or confirmation, such as X-ray angiography.

[0104] Referring to Figure 11, the imaging system 1 is first positioned in the patient's inferior vena cava 931. The first imaging system 12, mounted on the first catheter 11, locates the vascular opening that matches the anatomical features of the right adrenal vein 935. After determining the position and orientation of the right adrenal vein 935, the instrument to be inserted into the target vessel is advanced into the vessel along the first channel 13 until the imaging system 1 can simultaneously observe the instrument and the opening of the right adrenal vein. In the figure, the instrument to be inserted into the target vessel is the detection system 2. Under the guidance of the imaging system 1, the detection system 2 is advanced into the right adrenal vein 935. Furthermore, if the operator has a need for superselectivity, the instrument can be directly advanced into the branches 935a, 935b and / or 935c of the right adrenal vein using special techniques. Alternatively, the above operation can be repeated to advance the imaging system 1 into the right adrenal vein 935, and the instrument can be advanced into the branch under the guidance of the first imaging system 12.

[0105] Because adrenal veins typically bifurcate distally, the methods described above for accessing the left or right adrenal veins also include superselection of the adrenal veins. Superselection means that the surgeon can access different branches of the adrenal vein as needed. Note that the main adrenal vein usually receives 2 to 4 primary branches, mostly 3. Therefore, the following description uses 3 primary branches. However, it should be noted that depending on the patient's anatomical variations, there may be more or fewer primary branches than 3. In addition, veins in the human body can branch further within their branches. In clinical practice, it is often difficult and unnecessary to distinguish between primary and secondary branches. Therefore, although the branches of the adrenal vein mentioned in this article usually refer to primary branches, based on the knowledge of those skilled in the art or physicians in this field, it can be simply extended to secondary or even more subdivided branches. This invention provides a blood collection method, as shown in Figure 12. First, the blood collection catheter 21 is delivered to one of the vessels to be tested through the first catheter 11. Then, blood is collected from this vessel. Real-time in-situ detection can be performed, or the blood sample can be taken out of the body for detection, as detailed below. If blood collection has been completed for all blood vessels to be tested, the blood collection process ends, and the typing is determined based on the test results; otherwise, another blood vessel to be tested is selected, and the above process is repeated.

[0106] It is important to note that for the traditional AVS procedure, which does not involve superselection of the branches of the adrenal vein, the vessels to be tested include peripheral veins and the main trunks of the left and right adrenal veins; while for the superselective AVS procedure, which involves superselection of the branches of the adrenal vein, the vessels to be tested include peripheral veins, the main trunk of the left adrenal gland and its first-order branches, and the main trunk of the right adrenal gland and its first-order branches.

[0107] It should be noted that some patients may have previously undergone adrenalectomy or suffer from adrenal-related diseases, resulting in the absence of certain blood vessels. The system and method described in this invention are also applicable to these patients, but the manipulation of these missing blood vessels needs to be skipped.

[0108] Peripheral veins can include the inferior vena cava, superior vena cava, axillary vein, cubital vein, femoral vein, etc., and any one can be selected based on the convenience of the procedure. Because peripheral vein blood collection is relatively simple, blood can also be collected directly using the blood collection catheter 21 without the first catheter 11.

[0109] The following describes the invention of a detection system and method, including blood sample pretreatment and measurement. Current conventional detection technologies are too time-consuming. If a one-stop surgical procedure were used, it would require occupying an operating room and spending a very long time waiting for the results, making such a procedure impractical. Therefore, designing a rapid and accurate detection system and method is crucial. Preferably, the time from obtaining a blood sample to receiving the test result should be at least less than 20 minutes, the shorter the better, and less than 15 minutes is even more ideal.

[0110] According to the above method, the obtained blood sample is whole blood. However, the current mainstream detection methods will affect the detection performance when measuring whole blood, such as the limit of detection, specificity, sensitivity, and repeatability. This is because blood contains a large number of blood cells and a large number of proteins, which may lead to non-specific binding and affect the accuracy of the measurement. Some methods may also cause bioattachment.

[0111] Blood sample pretreatment methods include static agglutination and coagulant agglutination to obtain serum or centrifugation to obtain plasma; other methods include microfluidic methods, magnetic bead antibody binding methods, adsorption filtration membrane methods, lateral chromatography, or dialysis to achieve whole blood pretreatment for faster plasma acquisition. Simultaneously, blood samples can be concentrated using emulsification, extraction, dialysis, chromatography, and magnetic bead enrichment to increase the concentration of the analyte. If high measurement accuracy is not required, blood sample pretreatment may be omitted.

[0112] For the classification of PA patients, as mentioned earlier, the preferred measurement method is the relative concentration of aldosterone, which requires measuring the plasma concentrations of both aldosterone and cortisol. However, because the pathological characteristic of PA patients is the overexpression of CYP11B2, precursors of aldosterone, including 11-deoxycorticosterone, corticosterone, and 18-hydroxycorticosterone, are all diagnostically valuable, and the concentration of any of these precursors can be measured instead of the concentration of aldosterone. Similarly, the measurement of the cortisol precursor 11-deoxycortisol and the cortisol analog cortisone can also replace the measurement of aldosterone concentration. For ease of explanation, the following explanation will focus on the measurement of aldosterone and cortisol, but it should be noted that this can be extended to the measurement of their analogs.

[0113] It is important to note that cortisol, aldosterone, and other similar substances do not exist entirely in a free state in the blood, but rather in a form bound to related transport proteins in a certain proportion, such as albumin and cortisol-binding globulin. There are three processing methods: The first is to directly measure the concentration of the free component. Although the ratio of free to bound components varies slightly at different concentrations, this ratio is essentially constant and is a function of the total concentration. It can be easily measured through biochemical experiments, so the total concentration can be inferred from the measured free component concentration. The second method involves heating the blood sample. The binding force between transport proteins and cortisol and aldosterone decreases significantly with increasing temperature. Therefore, heating can rapidly release cortisol and aldosterone. Measuring the free component concentration at this point will yield a value close to the total concentration. The third method involves adding interfering substances to the blood sample, such as zinc ions, EDTA, acids, alkalis, and surfactants, to irreversibly damage the transport proteins, thereby releasing the bound cortisol and aldosterone. However, it should be noted that if the analyte is to undergo an immune-based binding reaction, such as an antigen-antibody reaction, these interfering substances may interfere with antibodies, aptamers, or other molecules. Therefore, before proceeding to the next step, it is necessary to ensure that the interfering substances have completely reacted, been removed, or neutralized from the supernatant.

[0114] Preferably, cortisol, aldosterone, and other similar substances belong to the steroid class of substances, which are more lipophilic than hydrophilic. Therefore, an emulsification process can be used to form an oil-in-water system in the blood sample. After filtering out the aqueous phase or extracting the oil phase to another container, a microsphere-breaking operation is performed to obtain a concentrated sample of cortisol, aldosterone, and other similar substances. Preferably, sodium dodecyl sulfate (SDS) or similar molecules can be used to form a long-chain hydrophilic end, serving as the interface for the aqueous phase in the microsphere interface. Its advantages include strong hydrophilicity, which accelerates the emulsification process; and because its groups are positively charged, an electric field can be applied during the microsphere-breaking process to orient them in the electric field, thereby releasing the cortisol, aldosterone, and other similar substances from the microspheres.

[0115] Preferably, three semi-permeable membranes with pore sizes of 300-500 / 150-300 / 50-150nm can be respectively provided to achieve the purpose of pretreatment in a reasonable manner.

[0116] One implementation of the detection module is to use mass spectrometry, such as liquid chromatography-tandem mass spectrometry (LC-MS / MS), high performance liquid chromatography-tandem mass spectrometry (HPLC-MS), isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC / MS / MS), or gas chromatography.

[0117] One implementation of the detection module uses an enzyme-linked electrochemical method. For example, an enzyme is designed to use aldosterone and / or cortisol as substrates. The concentration of aldosterone and / or cortisol is determined by measuring changes in the concentrations of the products, other substrates, or coenzymes in the enzymatic reaction. The aldosterone precursor 11-deoxycorticosterone can be converted to corticosterone under CYP11B2 catalysis. Corticosterone can then be converted to 18-hydroxycorticosterone under CYP11B2 catalysis, and 18-hydroxycorticosterone can then be converted back to aldosterone under CYP11B2 catalysis. These three enzymatic reactions have two properties: first, they are all reversible; second, they all require the coenzyme adrenodoxin. In the forward reactions of these three enzymatic reactions, adrenodoxin is converted from its reduced form to its oxidized form, and in the reverse reactions, it is converted from its oxidized form to its reduced form. When adrenodoxin changes from its reduced form to its oxidized form, it releases electrons; conversely, when it changes from its oxidized form to its reduced form, it accepts electrons. Therefore, this electrochemical reaction can be used to measure the rate at which adrenodoxin changes from its oxidized to its reduced form, thereby estimating the rate of the CYP11B2 enzymatic reaction and ultimately determining the concentration of aldosterone.

[0118] Specifically, adrenodoxin can be chemically modified to bind to the electrode, generating a current in the electrode when adrenodoxin gains or releases electrons. Since the plasma aldosterone concentration in PA patients is generally distributed in the range of 10 pM to 5 nM, the current generated by this method is very low. Preferably, chip technology can be used to amplify the current signal for more accurate measurement, such as using a current gain circuit.

[0119] Similarly, the cortisol precursor 11-deoxycortisol can be converted to cortisol under the catalysis of CYP11B1. This enzymatic reaction also exhibits two similar properties: it is reversible, and it requires the coenzyme Adrenodoxin. In the forward reaction, Adrenodoxin is converted from its reduced form to its oxidized form, while in the reverse reaction, it is converted from its oxidized form to its reduced form. Therefore, the rate of the CYP11B1 enzymatic reaction can be estimated by measuring the rate of Adrenodoxin conversion from its oxidized to its reduced form, thereby determining the concentration of aldosterone.

[0120] Another implementation method for the detection module is the immunoassay method, including radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, electrochemiluminescence immunoassay, and homogeneous photoexcitation immunoassay. These methods all require specific binding to cortisol and / or aldosterone, necessitating the design of antibodies, single-domain antibodies, aptamers, or other molecules that specifically bind to aldosterone and / or cortisol. It is important to note that sandwich methods, typically suitable for large molecules such as proteins and nucleic acids, may not be applicable to aldosterone and cortisol. In such cases, a competitive method may be necessary, or, in aptamer technology, a method using primary and secondary aptamers may be required (see PCT / US2017 / 035958).

[0121] Preferably, the detection module is implemented using a homogeneous reaction system, which has the advantage of eliminating the need for elution of the reaction system, thus maximizing the saving of reaction time. For example, a donor bead microsphere is designed, with an antibody or aptamer modified on its surface. A acceptor bead microsphere is then designed, with another antibody or aptamer modified on its surface, forming a sandwich system. When the donor bead receives external excitation light, it emits oxygen free radicals, causing the adjacent acceptor beads to emit light of different wavelengths. By capturing this specific wavelength of emitted light, the concentration of the analyte (aldosterone, cortisol, or similar substances) can be estimated by measuring the number of sandwich systems formed. Alternatively, one of the acceptor or donor bead microspheres can bind to the analyte instead of the antibody or aptamer, forming a competitive system. In this case, if it does not bind to the analyte, the donor and acceptor beads are adjacent in the system. When the analyte competes for the binding site, the analyte pre-loaded with the microsphere will detach, and the donor and acceptor beads will lose their adjacent relationship. Similarly, the concentration of the analyte can also be measured by capturing light of a specific wavelength emitted by the donor bead. The sandwich method has the advantage of a lower detection threshold and higher accuracy, while competing methods are easier to develop and less expensive. (Refer to Lucille Beaudet et al., AlphaLISA immunoassays: the no-wash alternative to ELISAs for research and drug discovery)

[0122] Preferably, the detection module is implemented using a homogeneous reaction system. Since the reaction process is wash-free, a rotating disk containing one or more rotating shafts can be used to provide centrifugal force during rotation, effectively achieving stirring and separation. Furthermore, this system can simultaneously perform plasma separation and measurement detection. After the blood sample is added to the rotating disk, plasma separation is first achieved under centrifugation. Aldosterone and cortisol, being small molecules, will be distributed in the supernatant. At this point, one or any combination of the following methods can be used: capillary effect, active aspiration, channel switching, sealing the connection between the supernatant and the precipitate, etc., to extract the supernatant to another reaction chamber. The reagent can bind with the supernatant in this reaction chamber, or it can bind with the supernatant when the blood sample is added. The reagent and supernatant can be thoroughly mixed and reacted in the reaction chamber by adjusting the centrifugal force. Then, the mixture can be introduced into the luminescent chamber using capillary effect or active aspiration. The luminescence chamber is configured to accept a given light source with a wavelength range encompassing the design wavelength range of the donor beads. The chamber is also configured to allow the excitation light emitted by the acceptor beads to enter an optical probe. The optical probe measures the light flux, thereby achieving the purpose of measuring the concentration of the analyte. Furthermore, the light source can be set to pulsed emission, with the optical probe collecting the excitation light after a certain time delay, to better avoid the influence of background noise on the results. (Refer to Yoon-Kyoung Cho et al., Exodisc for Rapid, Size-Selective, and Efficient Isolation and Analysis of Nanoscale Extracellular Vesicles from Biological Samples)

[0123] Another implementation method for measurement and detection is BioFET (Biofield-Effect Transistor) technology. Based on the immunoassay method, a sensor based on FET principles is designed. A bioFET architecture requires three key electrodes: Source, Drain, and Gate. The Source and Drain electrodes, made of highly conductive materials such as gold or platinum, are located at opposite ends of the semiconductor channel, responsible for carrier injection and collection, respectively. An aptamer or antibody that specifically binds to cortisol or aldosterone is designed and its surface modified near the channel. When the analyte binds to the aptamer or antibody, it causes a change in the surface charge distribution, thus affecting the current in the channel. The Gate electrode, located above or below the channel, typically consists of an insulating layer (such as SiO2) and a conductive layer (such as gold), used to modulate the electric field in the channel, thereby affecting the current flow. By measuring this current change, highly sensitive detection of cortisol or aldosterone can be achieved. (Refer to Jahyun Koo et al., A review of BioFET's basic principles and materials for biomedical applications)

[0124] It should be noted that some detection methods may not require specific binding, such as mass spectrometry-based methods.

[0125] After the hormone concentration (such as aldosterone, cortisol, etc.) is measured, the surgeon can compare the hormone levels secreted by the patient's bilateral adrenal glands. If there is unilateral dominant secretion, the surgeon can immediately perform adrenal interventional ablation in the same surgery using the ablation system 3 and its usage method described later, which is convenient and quick.

[0126] This invention also provides an in vitro hormone detection method for primary aldosteronism, the method comprising: inserting the blood collection catheter into the left or right adrenal vein to obtain blood samples from both adrenal veins respectively; it is worth noting that the blood samples from the adrenal veins can be blood samples from the main trunk of the adrenal vein without bifurcation, or blood samples from the branches of the adrenal vein used for superselection; positioning the blood collection catheter in a peripheral vein and obtaining blood samples from the peripheral vein; preferably using a liquid such as physiological saline, heparinized physiological saline, or iodine contrast agent for each blood sample collection. The blood samples are rinsed to avoid cross-contamination between blood samples from different sources, which could affect the test results. Alternatively, a brand-new blood collection catheter can be used to better avoid contamination. The collected blood samples are then sent to the in vitro detection module to measure the concentration and / or activity of cortisol and / or aldosterone in the blood vessel to be tested. The blood vessel to be tested can be the left adrenal vein, the right adrenal vein, or a peripheral vein (such as the inferior vena cava). Alternatively, branches of unilateral or bilateral adrenal veins can be superselected to better achieve accurate diagnosis of aldosterone secretion function in different segments of the adrenal gland.

[0127] This invention also provides an in vivo hormone detection method for primary aldosteronism, the method comprising: inserting a detection catheter or detection sheath loaded with the in vivo detection module into the blood vessels to be tested, and measuring the concentration and / or activity of cortisol and / or aldosterone in each vein; in conventional testing methods, the blood vessels to be tested typically include the left adrenal vein, the right adrenal vein, and peripheral veins (such as the inferior vena cava), and can also be further superselected from branches of unilateral or bilateral adrenal veins to better achieve accurate diagnosis of aldosterone secretion function in different segments of the adrenal gland; to avoid interference between different tests, after a single measurement, the sensor can be cleaned by methods such as liquid flushing, high-frequency vibration, back-and-forth scraping with a sheath, and applying an electric field repulsion to remove the analytes (i.e., aldosterone and / or cortisol) adhering to the sensor surface.

[0128] This invention also provides a detection module 22, which is optimally used for one-stop surgery for primary aldosteronism, including the in vivo detection module 221 and the in vitro detection module 222; it can also be used for other analytes, other diseases, and / or other application scenarios without additional effort by those skilled in the art. The module includes three modules: blood sample pretreatment, specific binding, and detection. These modules can be simplified through specialized design. The most commonly used technique is chemiluminescence immunoassay, which involves collecting whole blood from the patient, centrifuging to obtain plasma, sequentially adding a primary antibody, eluting, adding an enzyme-labeled secondary antibody (or an enzyme-labeled competitive ligand), eluting again, and adding magnetic beads for enrichment to improve efficiency and accuracy. Finally, a substrate is added, and under the enzymatic reaction linked to the secondary antibody (or competitive ligand), it is converted into an unstable luminescent product. The light intensity is calculated to infer the concentration of the analyte. These steps typically take several hours to complete. While automated devices exist to shorten the detection time, they are still not convenient for point-of-care testing in the operating room. To enable intraoperative bedside testing, a dedicated device system for measuring aldosterone and cortisol concentrations / activities can be designed, with some modules simplified. This allows for rapid intraoperative classification and diagnosis, enabling ablation treatment to be completed in the same procedure.

[0129] This invention provides an in vitro hormone detection method for primary aldosteronism. First, blood samples are collected from various target blood vessels via the blood collection catheter 21 (Figure 8 or Figure 9) or through a blood collection trough 20 or similar structure. Each time a blood vessel is changed for resampling, to avoid contamination of the newly collected blood sample by residual blood in the blood collection catheter 21, the blood collection catheter needs to be flushed with physiological saline, heparinized physiological saline, or iodine contrast agent, or a new blood collection catheter may be used. In addition, peripheral blood vessels can also be sampled and tested to facilitate subsequent subtyping diagnosis. The peripheral blood vessels are typically the inferior vena cava 931 (Figure 10). Then, the blood samples from each target blood vessel are sent to the in vitro detection module.

[0130] This invention provides an in vivo hormone detection method for primary aldosteronism. The detection catheter 23 or detection cannula 25, as shown in Figure 13 or Figure 14, equipped with the in vivo detection module 222, is directly inserted into each blood vessel to be tested and left for 10-120 seconds to allow the blood in the vessel to fully react with the in vivo detection module 222 until the reaction reaches equilibrium. The concentrations of cortisol and aldosterone in the blood vessel are then obtained using one or more of the aforementioned detection methods (such as BioFET, homogeneous immunoassay, etc.). After measuring the hormone concentration of one blood vessel, the in vivo detection module 222 needs to be eluted to avoid the pre-reaction affecting subsequent test results.

[0131] Preferably, to prevent the reaction reagents from escaping into the blood vessel and causing the reagent concentration to decrease over time, a semipermeable membrane can be used on the catheter surface. This membrane is configured to selectively permeate aldosterone and cortisol, but not antibodies, aptamers, microspheres, and / or competitive antigens in the reagents. The semipermeability of the membrane can be provided by pore size, electrostatic properties, and hydrophilicity / hydrophobicity. Preferably, a three-layer semipermeable membrane with pore sizes of 300-500 / 150-300 / 50-150 nm can be respectively configured to reasonably achieve the above-mentioned objectives.

[0132] Preferably, the detection system includes a blood collection catheter and an in vitro detection module. The blood collection catheter is used to collect blood from a target blood vessel, and then the collected blood sample is dripped into the in vitro detection module to obtain the detection result.

[0133] Optionally, the blood collection catheter is 1-7F in size, and can directly drain or aspirate venous blood from the target area out of the body;

[0134] Optionally, the diameter of the blood collection catheter is slightly larger than the target blood vessel size by 1-2F, so that it can be easily inserted into the target blood vessel and block the lumen opening, preventing blood from the main trunk (i.e., the blood vessel above the target blood vessel) from flowing into the branches under negative pressure during the blood collection process and affecting the test results.

[0135] Preferably, the blood collection catheter includes a first lumen, which can be more conveniently inserted into the target blood vessel and / or aspirated to sample blood from the target blood vessel under the guidance of a guidewire;

[0136] Preferably, the distal opening of the blood collection catheter is designed with a bevel to increase the aspiration area, shorten the blood collection time, and improve surgical efficiency;

[0137] Preferably, the distal end of the blood collection catheter includes at least one side hole, which can be circular, elliptical, elongated, etc., to increase the aspiration area.

[0138] Preferably, the blood collection catheter includes an occlusion balloon, which is preferably positioned 5-50 mm from the distal opening of the blood collection catheter to isolate the target blood vessel from its upstream blood vessel, thereby avoiding interference from blood in the upstream blood vessel on the test results, improving the accuracy of the test results, shortening the blood collection time, and improving the efficiency of the operation.

[0139] Optionally, the blood collection catheter includes an outer cannula and a central blood collection tube; the distal end of the central blood collection tube is provided with a blood collection groove, which can hold 5-50 μl ml of blood; the central blood collection tube can be inserted only during blood collection, or it can be placed in the outer cannula beforehand. When in use, the central blood collection tube is extended from the distal end of the outer cannula and exposed to the blood collection groove, allowing blood to fill the blood collection groove. Then, the central blood collection tube is retracted into the outer cannula, and the opening of the blood collection groove is blocked by the inner wall of the outer cannula, thereby preserving the blood sample.

[0140] The blood collection groove can be a completely open recess or a deep groove with side wall openings.

[0141] Referring to Figure 8, in some embodiments, the detection system 2 includes a blood collection catheter 21 and an in vitro detection module 221. The blood collection catheter 21 has a first inner lumen 211, which facilitates the aspiration or drainage of blood from the target blood vessel. The first inner lumen 211 can also accommodate a guidewire, allowing the blood collection catheter 21 to enter the target blood vessel more easily under the guidance of the guidewire. As shown in Figure 8, the distal end of the blood collection catheter 21 can be designed with a bevel or curved surface. It can also have one or more side holes 215 of circular, elliptical, or elongated shapes, as shown in Figures 8(c)-(e), thereby increasing the effective cross-sectional area during blood aspiration, improving the aspiration rate, and reducing surgical waiting time. Figure 8(a) shows a more common blood collection catheter design. In this embodiment, the size of the blood collection catheter 211 can be slightly larger than the diameter of the target blood vessel by 1-2F, making it easier to hold more securely in the target blood vessel and preventing blood from the main trunk (i.e., the upstream vessel of the target blood vessel) from flowing into branches under negative pressure during blood aspiration, thus affecting the detection results.

[0142] In a preferred embodiment, as shown in Figure 8(b), to better avoid interference from the main blood vessel and more accurately obtain the hormone concentration in the target blood vessel, a occlusion balloon 212 is also provided at the distal end of the blood collection catheter 21 to isolate the target blood vessel from its upstream blood vessel. The distance between the occlusion balloon 212 and the distal opening of the blood collection catheter 21 depends on the length of the target blood vessel. For most patients, 10-30 mm from the tip is a better choice. When the balloon is inflated to a size of 2-12F, it can effectively occlude the target blood vessel and reduce damage to the blood vessel caused by excessive expansion.

[0143] As shown in Figure 9, the blood collection catheter 21 can also be a combination of a central blood collection tube 214 and an outer tube 213. In these embodiments, the distal end of the central blood collection tube 214 is provided with a blood collection groove 20 with a volume of 5-50 μL. The blood collection groove 20 can be a completely open groove as shown in Figure 9(a), or a deep groove with only one side wall opening as shown in Figure 9(b). Referring to Figure 9(c), when blood needs to be collected, the central blood collection tube 214 is sent out through the internal channel of the outer tube 213, so that the opening of the blood collection groove 20 is exposed in the target blood vessel. After the blood naturally fills the blood collection groove, the central blood collection tube is retracted, and the opening of the blood collection groove 20 is closed by the tube wall of the outer tube 213, thereby preserving the blood sample for subsequent testing.

[0144] In some embodiments, the blood collection catheter 21 can also be directly connected to the in vitro detection module 221 at its tail end through a structure such as a piston, Luer connector, or threaded port. Blood samples from the blood vessels can be drawn into the in vitro detection module 221 through the first inner lumen 211 of the blood collection catheter using a syringe or other negative pressure aspiration design. Referring to Figure 15, this eliminates the step of blood sample transfer and reduces the risk of blood sample contamination.

[0145] This invention proposes a classification strategy for adrenal glands. From a functional and operational perspective, the inventors provide an example of the relationship between diagnostic and treatment decisions. The most typical pathological classification of focal lesions is APA (Aldosterone-Producing Adenoma), and the most typical pathological classification of diffuse lesions is IHA (Idiopathic hyperaldosteronism). It is important to note that the pathological classification of PA is not mutually exclusive, but rather resembles a disease spectrum. In addition to focal and diffuse lesions, there are pathological classifications such as APM and APCC, which, according to different scholars, fall between typical APA and typical IHA in terms of pathological manifestations, while their functional manifestations are focal or diffuse. For clinicians, only functional information is available; pathological information is unavailable. Therefore, when interpreting AVS results, the A / C ratio is calculated for each target vessel, which is the ratio of aldosterone concentration to cortisol concentration measured in that vessel. Thus, measuring n target vessels should result in n A / C ratios. The lowest value, A / C_min, is found. For the remaining n-1 vessels, the ratio of their A / C value to A / C_min is calculated. If the ratio is higher than a certain set threshold T_Dominant, the vessel is considered to have an aldosterone concentration advantage; otherwise, it is considered not to. If at least one of these n-1 vessels shows an aldosterone concentration advantage, the patient is considered to have a focal lesion; conversely, if none of the vessels show an aldosterone concentration advantage, the patient is considered to have a diffuse lesion. It is important to note that when calculating the A / C ratio, aldosterone concentration is usually expressed in pg / ml, while cortisol concentration is expressed in ng / ml, or aldosterone concentration in pmol / L, while cortisol concentration is expressed in nmol / L. However, since the numerical value of the A / C ratio itself is not important, what is important is the ratio between the A / C ratios of different blood vessels, logically speaking, the concentration units of aldosterone and cortisol can be chosen arbitrarily. It is only necessary to note that all aldosterone concentrations use the same unit, and all cortisol concentrations use the same unit.

[0146] Preferably, when interpreting the AVS results, the A / C ratio at peripheral blood vessels (such as the vena cava, axillary vein, cubital vein, femoral vein) can also be measured and calculated (this value is called A / C_peripheral). After calculating the A / C ratio of n target blood vessels, for these n blood vessels, calculate the ratio of their A / C value to A / C_peripheral. If it is lower than a set threshold T_inhibition, it is considered that this blood vessel or its corresponding tissue is inhibited; otherwise, it is considered that the aldosterone concentration of this blood vessel or its corresponding tissue is not inhibited. If all blood vessels are not inhibited, it supports the diagnosis of diffuse lesions in the patient. If at least one blood vessel is inhibited, it can be decided whether to take measures to protect this blood vessel according to the actual situation, such as not ablating this blood vessel, or avoiding this blood vessel during ablation, or reducing the dose when ablating near this blood vessel (especially in the embodiment of energy ablation).

[0147] An embodiment of the typing judgment decision for the adrenal gland is proposed in the present invention. If the traditional AVS typing method is adopted, that is, the method of not performing super-selection on the branches of the adrenal vein, refer to FIG. 16. First, calculate the aldosterone and cortisol concentrations measured for each blood vessel to be tested respectively, that is, divide the aldosterone concentration by the cortisol concentration to obtain the A / C ratio. Next, for the target blood vessels, that is, the left adrenal vein and the right adrenal vein, compare their A / C ratios to find the larger and smaller ones. Calculate the dominance index LI, that is, divide the larger A / C value by the smaller A / C value. Compare LI with T_Dominant. If LI < T_Dominant, it is considered that there is no dominant distribution of blood vessels, and the patient has diffuse lesions. Otherwise, if LI ≥ T_Dominant, it is considered that there is a dominant distribution in the blood vessel where the larger A / C value is located, and the patient has focal lesions, and the watershed of this blood vessel can be located.

[0148] Furthermore, the inhibition index CSI can be obtained by dividing the smaller A / C value by the A / C ratio of the peripheral blood vessel. Compare CSI with T_inhibition. If CSI < T_inhibition, it can be more surely determined that the blood vessel where the larger A / C value is located is the blood vessel where the focal lesion is located. Otherwise, if CSI ≥ T_inhibition, although it is inclined to think that the patient has focal lesions, it indicates that the patient's condition is not a typical manifestation of focal lesions. At this time, the doctor can combine the clinical situation, that is, the patient's imaging manifestations, clinical manifestations, laboratory tests, medical history characteristics, etc., and comprehensively analyze and judge. The steps of this paragraph can be omitted.

[0149] Another embodiment of the typing judgment decision for the adrenal gland is proposed in the present invention. If the super-selective AVS typing technique is adopted, that is, the super-selective technique for the branches of the adrenal vein, reference can be made to FIG. 17. First, the aldosterone and cortisol concentrations measured for each vessel to be measured are calculated respectively, that is, the aldosterone concentration is divided by the cortisol concentration to obtain the A / C ratio. Next, for the target vessels, that is, the main trunk of the left adrenal vein and its branches, and the main trunk of the right adrenal vein and its branches, the A / C ratios of all vessels are compared to find the maximum and minimum values. The dominance index LI is calculated for each vessel, that is, the A / C of this vessel is divided by the minimum A / C. Each LI is compared with T_Dominant. If all LIs < T_Dominant, it is considered that there is no dominant distribution of vessels, and the patient has diffuse lesions. On the contrary, if at least one LI ≥ T_Dominant, it is considered that there is a dominant distribution in the vessel corresponding to this LI value, and the patient has focal lesions, and the lesion can be localized to the basin of this vessel.

[0150] Further, the A / C ratio of each target vessel other than the undetected dominant distribution can be divided by the A / C ratio of the peripheral vessels to obtain the suppression index CSI respectively. Each CSI is compared with T_inhibition. If at least one CSI < T_inhibition, it can be more surely determined that the vessel with the larger A / C is the vessel where the focal lesion is located. On the contrary, if all CSIs ≥ T_inhibition, although it is inclined to think that the patient has focal lesions, it indicates that the patient's condition is not a typical manifestation of focal lesions. At this time, the doctor can combine the clinical situation, that is, the patient's imaging manifestations, clinical manifestations, laboratory tests, historical characteristics, etc., for comprehensive analysis and judgment. The steps of this paragraph can be omitted.

[0151] Another embodiment of the typing judgment decision for the adrenal gland is proposed in the present invention. As shown in FIG. 18, for all target vessels, a threshold T_aldosterone is set. Instead of calculating the A / C value, and even without measuring the cortisol concentration, the aldosterone concentration [A] is directly compared with T_aldosterone. If the aldosterone concentration [A] of this target vessel > T_aldosterone, it is considered that there is a dominant distribution in this vessel, there are focal lesions, and the lesion is located within the basin of this vessel. If the aldosterone concentration [A] of all target vessels < T_aldosterone, it is considered that there is no dominant distribution in all these vessels, and the patient has diffuse lesions.

[0152] Preferably, for the traditional AVS, that is, the technique of only measuring the main trunk of the adrenal vein, the threshold T_Dominant is preferably 2 - 8.

[0153] Preferably, for superselective AVS, i.e., the procedure that also measures the adrenal vein branches, the threshold T_Dominant is preferably 4 to 20.

[0154] Preferably, the threshold T_inhibition is 0.8 to 1.2.

[0155] Preferably, when using ACTH stimulation, the threshold T_aldosterone is preferably 140 ng / ml, but can also be extended to 80-200 ng / ml; when not using ACTH stimulation, the threshold T_aldosterone is preferably 40-140 ng / ml.

[0156] Preferably, for patients with focal lesions, complete destruction of the lesion can be performed locally. Of course, conventional treatment methods, such as surgical resection, can also be used.

[0157] Preferably, for patients with diffuse lesions, partial destruction of all adrenal glands can be performed. Of course, conventional treatment methods, such as drug therapy, can also be used.

[0158] For focal lesions, because the lesion distribution is very localized, the glandular cells at the lesion site and those outside the lesion site do not share the same veins. In veins receiving cells from the lesion site, an excess of aldosterone can be detected, while in veins receiving cells from outside the lesion site, a deficiency (suppressed) aldosterone can be detected. In this case, the veins receiving cells from the lesion site can be called the dominant veins, or aldosterone secretion dominance can be detected in these veins, or the side of the adrenal gland where the lesion is located can be called the dominant side. For example, if the lesion is located in the left adrenal gland, an excess of aldosterone can be detected in the main trunk of the left adrenal vein, while a suppressed aldosterone concentration can be detected in the main trunk of the right adrenal vein. As another example, if the lesion is located on the lateral side of the left adrenal gland, an excess of aldosterone can be detected in the lateral branches of the left adrenal vein, while a suppressed aldosterone concentration can be detected in the upper-middle and upper-lateral branches of the left adrenal gland. This confirms that the lesion is received by the lateral branches of the left adrenal gland.

[0159] The inventors have proposed a technical solution that involves measuring the main trunks of the bilateral adrenal veins, and even measuring the branches of multiple adrenal veins. When one or more veins are identified as having aldosterone secretion dominance, meaning that one or more veins receive aldosterone from the lesion, endovascular ablation should be performed in one or more of these veins to achieve excellent therapeutic results.

[0160] One method involves injecting alcohol or spraying water vapor into one or more veins (hereinafter referred to as the veins to be ablated), directing it against the direction of blood flow towards the arteries and into the capillary network and even arterioles. This allows the lesion to be reached, and through chemical or thermal damage, the lesion is completely destroyed, achieving ablation with results comparable to surgical resection. In this method, because the alcohol or water vapor is injected or sprayed only into the veins to be ablated, its reversible blood flow reaches an area exhibiting a "watershed characteristic," much like traveling upstream in a river—one can only reach the watershed of that river and cannot reach the watershed of another adjacent river. The inventors call this characteristic blood flow selectivity, and its advantages are obvious: it can most accurately destroy the tissue that needs to be destroyed and preserve the tissue that needs to be preserved based on the results of AVS functional analysis. Through conventional AVS or superselective AVS, the aldosterone concentration of each vein can be measured. Those areas that show a predominance of aldosterone concentration are the "water areas" where lesions exist. These "water areas" can be completely destroyed using this method. On the other hand, those areas that show suppressed aldosterone concentration are the relatively healthy "water areas" without lesions. These "water areas" can be protected using this method, even if they are very close in location.

[0161] Another approach involves applying energy, such as radiofrequency energy, microwave energy, pulsed high-voltage electric field energy, ultrasound energy, or cryotherapy energy, to the vein to be ablated to destroy the lesion. The advantage of this method is that the energy attenuates with distance, allowing for distance-selective killing of adjacent tissues.

[0162] Preferably, by combining superselective absorptiometry (AVS) with multiple branches of the adrenal vein, the location of lesions can be identified precisely down to the branch level. In this way, endovascular treatment of the vein to be ablated (including injection of alcohol, spraying of water vapor, and application of energy) can achieve more precise ablation, destroying the lesion as much as possible while protecting non-lesions.

[0163] Preferably, based on the embodiment of injecting alcohol or spraying water vapor, a balloon can be placed at the proximal end of the distal opening of the ablation catheter lumen. The balloon is inflated before or at the same time as the alcohol or water vapor needs to be injected to prevent the alcohol or water vapor from flowing proximally and instead direct it to flow in the direction of capillary-artery, so as to better ensure blood flow selectivity.

[0164] In typical diffuse lesions, the distribution of lesions is diffuse, with lesions and non-lesions intermingling and indistinguishable. Therefore, AVS results show that aldosterone concentrations are relatively uniform in all adrenal veins, while avascular lesions show a significant advantage. In this case, all adrenal glands secrete excessive aldosterone.

[0165] The inventors propose a technical solution whereby, by measuring the main trunks of the bilateral adrenal veins, and even the branches of multiple adrenal veins, when no single vein or multiple veins exhibit aldosterone-dominant secretion (i.e., the lesion distribution is diffuse), all adrenal tissue should be partially destroyed. Partial destruction refers to adjusting the dosage to avoid both ineffectiveness due to excessively low doses and complete destruction of the adrenal tissue due to excessively high doses.

[0166] Specifically, this involves completely destroying the focal lesion. For example, if blood sampling confirms that the lesion is located in the left adrenal gland 94a (Figure 19(a)), the ablation catheter 31 can be placed in the main trunk 934 of the left adrenal vein (Figure 19(b)) to ablate the entire left adrenal gland 94a (Figure 19(c)). Alternatively, if superselective blood sampling confirms that the lesion is located in a branch 934a of the left adrenal gland (Figure 20(a)), and aldosterone secretion is dominant in the left adrenal vein branch 934a, the ablation catheter 31 can be placed in the left adrenal vein branch 934a (Figure 20(b)) to selectively ablate the entire basin of the left adrenal vein branch 934a (Figure 20(c)) while preserving other healthy tissue of the left adrenal gland 94a.

[0167] For patients with diffuse lesions, comprehensive partial destruction can be achieved by using a treatment method similar to that for focal lesions, such as injecting alcohol or spraying water vapor into the vein to be ablated, but using a lower dose to kill some rather than all cells. Similarly, energy can be applied to the vein to be ablated, such as radiofrequency energy, microwave energy, pulsed high-voltage electric field energy, ultrasound energy, cryotherapy energy, etc., but using a lower dose to kill some rather than all cells.

[0168] Specifically, this involves partially destroying the entire adrenal gland in patients with diffuse lesions. For example, if blood sampling confirms a diffuse distribution of lesions, meaning no blood vessel shows aldosterone secretion dominance (Figure 21(a)), then partial destruction of the left and right adrenal glands can be performed separately, without order; the procedure is similar, and the left side will be used as an example below. The ablation catheter 31 can be placed in the main trunk 934 of the left adrenal vein (Figure 21(b)) to ablate the entire left adrenal gland 94a (Figure 21(c)). It is important to note that the ablation intensity should be lower than that for patients with focal lesions to ensure that the adrenal tissue is not completely destroyed, but only partially destroyed. This can be achieved by using different ablation methods, or the same ablation method but with a lower dose, duration, or power.

[0169] Preferably, regardless of whether conventional AVS or superselective AVS is used for blood collection and testing, when treating patients with diffuse disease, treatment is performed within the main bilateral adrenal veins without entering the branches, in order to simplify the procedure.

[0170] This invention also provides a one-stop diagnostic and treatment method for the classification and diagnosis of primary aldosteronism and ablation therapy for unilateral adrenal dominant secretion. The method includes: coordinating a detection system with an imaging system; inserting a portion of the detection system into the left and right adrenal veins and / or their branches according to the method described for entering the left or right adrenal veins; collecting blood samples from the adrenal veins and / or their branches, as well as peripheral veins, according to the in vitro hormone detection method for primary aldosteronism, and measuring the concentration and / or activity of the target hormone in vitro; or directly measuring the concentration and / or activity of the target hormone in the target blood vessels and peripheral veins in vivo according to the in vivo hormone detection method for primary aldosteronism; determining the classification and treatment method according to the treatment strategy for primary aldosteronism, and performing ablation therapy according to the above-described ablation method.

[0171] It is worth noting that in the above method, there is no requirement for the order of blood collection or hormone measurement of each blood vessel to be tested (such as the main trunk, branches and peripheral veins of the adrenal vein).

[0172] The goal of treating adrenal lesions is to improve or completely eliminate the effects of PA. Specifically, this involves two factors: clinical outcome and biological outcome. The ideal treatment result is partial or even complete clinical and biological remission.

[0173] Clinical outcome refers to the effect on blood pressure; PA (painful antihypertensive therapy) leads to elevated blood pressure. A complete clinical remission is defined as the complete return of blood pressure to normal (i.e., blood pressure drops below 140 / 90 mmHg, or even below 130 / 80 mmHg) after treatment without the need for additional antihypertensive medication. A partial clinical remission is defined as a reduction in blood pressure (systolic, diastolic, or mean blood pressure) of at least 5 mmHg after treatment (without increasing the dosage or type of existing antihypertensive medication), or a return to pre-treatment levels after reducing the dosage or type of existing medication. Otherwise, it is considered a no-response.

[0174] Biological outcome refers to the endocrine effect. PA leads to decreased serum potassium and an increased aldosterone-renin ratio (ARR). A complete biological response is defined as no hypokalemia after treatment (i.e., serum potassium ≥ 3.5 mmol / L) and an ARR within the normal range. A partial biological response is defined as no hypokalemia after treatment (i.e., serum potassium ≥ 3.5 mmol / L), an ARR higher than the normal range, but a 50% reduction in plasma aldosterone levels compared to pre-treatment levels, or an improvement in diagnostic test results compared to pre-treatment levels. Otherwise, it is defined as no response.

[0175] Therefore, it can be summarized that the goal of adrenal lesion treatment, and indeed the entire system and method of one-stop treatment, is to improve hypertension (if present) and hypokalemia (if present) in PA patients, and to reduce ARR in PA patients.

[0176] The following describes the ablation system and method for the adrenal glands of this invention.

[0177] Optionally, the ablation system includes an ablation catheter;

[0178] The ablation catheter preferably includes a third lumen to facilitate entry into the target blood vessel under guidewire guidance, injection of fluid into the target blood vessel, or blood aspiration when necessary;

[0179] Optionally, the ablation catheter includes a third lumen and a fourth lumen, such that the guidewire lumen and the fluid lumen are independent of each other;

[0180] The ablation method of the ablation catheter can be alcohol ablation, which involves directly injecting anhydrous ethanol into the target blood vessel through the second or fourth lumen;

[0181] Optionally, the ablation catheter includes a catheter ablation element, at least a portion of which is disposed at the distal end of the ablation catheter 0-30 mm from the tip.

[0182] The catheter ablation element includes at least a microwave antenna radiation unit, which performs tissue ablation via microwaves;

[0183] The catheter ablation element includes at least electrodes and can perform tissue ablation via radio frequency (RF), pulsed electric field ablation (PFA), or other methods.

[0184] The catheter ablation element includes at least a heating element, which can rapidly heat the saline solution injected through the third lumen to generate a large amount of steam and use the steam for ablation treatment.

[0185] The catheter ablation element includes at least an ultrasonic transducer, which utilizes principles such as high-intensity focused ultrasound (HIFU) and histotripsy to achieve tissue ablation.

[0186] The catheter ablation element includes at least an optical fiber, from which a laser is emitted to achieve tissue ablation;

[0187] The catheter ablation element includes at least an ablation balloon, which uses liquid nitrogen freezing or argon-helium freezing principles to perform cryoablation on the target blood vessel and surrounding tissue.

[0188] Optionally, the ablation system includes an ablation guidewire, which preferably includes a guidewire ablation element, at least a portion of which is arranged at the distal end of the ablation guidewire 0-30 mm from the tip.

[0189] The guide wire ablation element includes at least a microwave antenna radiation unit, which performs tissue ablation via microwaves;

[0190] The guidewire ablation element includes at least electrodes and can perform tissue ablation via radio frequency (RF), pulsed electric field ablation (PFA), or other methods.

[0191] The guidewire ablation element includes at least an ultrasonic transducer, which utilizes principles such as high-intensity focused ultrasound (HIFU) and histotripsy to achieve tissue ablation.

[0192] The guidewire ablation element includes at least an optical fiber, from which a laser is emitted to achieve tissue ablation.

[0193] Optionally, the ablation system includes a non-invasive ablation device, which preferably performs ablation treatment on the adrenal gland outside the body using methods such as high-intensity focused ultrasound (HIFU) or histotripsy.

[0194] The adrenal gland is divided into the cortex and medulla, with the cortex on the outside and the medulla on the inside. The adrenal arteries enter from the outer surface of the adrenal gland, transitioning to the outer surface of the cortex. Branches of the adrenal arteries penetrate the cortex, branching and merging into a capillary network, which then converges to form branches (tributaries) of the adrenal veins. These branches are finally received by the main trunk of the adrenal veins located within the medulla. The adrenal veins transition within the adrenal medulla and then leave the adrenal gland. The adrenal cortex is divided from the outside in into the zona glomerulosa, zona fasciculata, and zona reticularis. Although the exact boundary between the zona glomerulosa and zona fasciculata is still debated academically, it can generally be understood that the zona glomerulosa is the part of the adrenal gland responsible for aldosterone secretion, and lesions of adrenal aldosterone (PA) are also distributed within the zona glomerulosa.

[0195] Based on the above description of the structure and function of the adrenal gland, this invention proposes that effective ablation therapy can be achieved.

[0196] Figure 22 illustrates some embodiments of the ablation system 3 performing ablation operations via the ablation catheter 31. In these embodiments, the ablation catheter 31 includes an inner lumen, which can be used at least to inject fluids such as anhydrous ethanol, allowing the alcohol to diffuse along the blood vessel to distal branches, thereby achieving tissue ablation through chemical means. The ablation catheter 31 shown in Figure 22(a) only includes a third inner lumen 312, which can be used to accommodate the guidewire for easy entry into the target blood vessel, and also for aspiration or injection of fluid; while the ablation catheter 31 shown in Figure 22(b) includes two inner lumens, namely the third inner lumen 312 and the fourth inner lumen 313, making the guidewire lumen and the fluid lumen independent of each other, reducing mutual interference between different operations.

[0197] The adrenal vein ablation system provided by this invention involves alcohol entering the vein to be ablated. The alcohol distributes and moves along the vein lumen, penetrating into the adjacent tissues innervated by the vein. Through chemical reactions of biomolecules, particularly oxidation-reduction and dehydration, alcohol damages the tissue. To achieve sufficient tissue destruction, the injected alcohol concentration should be between 75% and 100%. For immediate visualization during the procedure to clearly define the ablation area, a mixture of iodine-containing contrast agent and alcohol can be injected to visualize the alcohol penetration area under X-ray, or a mixture of ultrasound contrast agent and alcohol can be injected to visualize the alcohol penetration area under ultrasound. To simplify operation and better quantify the injection dosage, the cavity can have only a distal outlet and no proximal inlet; that is, the cavity has a blind end proximally. Alcohol is pre-stored on the blind end side, and the alcohol is discharged from the distal end of the cavity by hydraulic pressure, deformation compression, or a piston.

[0198] Referring next to Figures 23(a) and (b), in some embodiments, the distal end of the ablation catheter 31 is provided with a catheter ablation element 311.

[0199] In a preferred embodiment, the catheter ablation element 311 is a heating element, such as an electrode or a resistance wire, which rapidly heats only the saline solution or other liquid that is about to be ejected from the distal end of the third inner lumen 312 to obtain steam. The steam is used to ablate the tissue, and the steam can quickly diffuse with the blood to the distal end of the blood vessel and enter more small branches, resulting in a wider ablation range. At the same time, it avoids damage to other healthy tissues that need to be preserved during the heat transfer process due to excessively high local temperature. In the steam ablation embodiment, in order to simplify the structure of the ablation catheter 31 itself, the steam generator can also be placed outside the body to directly inject high-temperature steam into the third inner lumen 312.

[0200] The adrenal vein ablation system provided by this invention allows steam to enter the vein to be ablated, distribute along the vein lumen, and penetrate into the adjacent tissues innervated by the vein. By releasing heat, steam causes chemical reactions in biomolecules, such as protein denaturation, enzyme inactivation, and eschar formation, thereby damaging the tissue. After entering the body, the steam releases sensible and latent heat during cooling and phase transition.

[0201] Q = Q_sensible heat + Q_latent heat

[0202] Q_sensible heat = m_water vapor × c_water × ΔT

[0203] Q_latent heat = m_water vapor × l_water

[0204] m_water vapor = ρ_water vapor × V_water vapor = ρ_water vapor × S_cavity opening × v_jet × t_duration

[0205] As shown in Figure 25(a), after the ablation catheter sprays high-temperature, high-pressure water vapor, different physical phenomena will occur depending on the depth. In the initial region immediately after leaving the ablation catheter, the system is mainly in the gas phase, and this region is called the gas phase region. As the pressure and temperature of the water vapor gradually decrease, and significant turbulence is generated with the fluid in the blood vessel, this region is called the liquid-gas mixing region. As the pressure and temperature of the water vapor further decrease, the water vapor almost reverts to liquid, and this region is called the liquid phase region.

[0206] When water vapor releases heat, it can do so through both sensible and latent heat. In the gas and liquid phases, where the phase change of water vapor is not significant, the heat released is primarily sensible. However, in the liquid-gas mixing zone, the heat released is primarily latent heat. Since the latent heat released during water vapor liquefaction is significantly higher than the sensible heat, the heat released is greatest in the liquid-gas mixing zone.

[0207] Preferably, the ablation system is configured such that the zona glomerulosa is covered by a liquid-gas mixing zone, as shown in Figure 25(b), thus ensuring maximum thermal damage to lesions within the zona glomerulosa. It should be noted that different vessel diameters and courses affect the specific extent of the three zones mentioned above. Generally, vapor travels at higher speeds in the main trunk and primary branches of the adrenal vein, resulting in a larger vapor phase zone, while the relative speed is slower when vapor travels retrogradely into secondary branches within the primary branches. The depth of the zona glomerulosa to the main trunk or primary branches of the adrenal vein is determined based on anatomical considerations.

[0208] The therapeutic dose of water vapor introduced into the body can be adjusted by regulating the pressure of the water vapor leaving the cavity, the cross-sectional area of ​​the cavity opening, the jetting speed, and the jetting duration. Adjusting the temperature of the water vapor as it leaves the cavity can further regulate the degree of tissue damage by affecting the sensible heat energy. Energy loss during water vapor movement within the cavity can be reduced by improving the thermal insulation design of the ablation catheter and shortening the cavity length.

[0209] The advantages of using water vapor are as follows: First, the latent heat released by water vapor in the body far exceeds the sensible heat: the specific heat capacity of water is approximately 4.2 kJ / kg / K, while that of water vapor is approximately 1.6–2.1 kJ / kg / K. The latent heat energy of the liquid-gas phase is 2265 kJ / kg, therefore, a unit mass of water vapor can release a very high amount of energy. Second, after water vapor is injected into the bloodstream, it does not liquefy immediately. Instead, it travels a certain distance retrogradely along the veins before liquefying. This liquefaction process is the stage where latent heat is released. Therefore, energy is released to damage tissues only in the latent heat zone. By configuring the relevant parameters of the steam, the location of the latent heat zone can be relatively optimized, such as making the liquid-gas mixing zone partially overlap with or even completely encompass the zona glomerulosa region of the adrenal gland, thus achieving a sufficient effect of killing lesions in the zona glomerulosa of the adrenal gland. Third, water vapor converts into water without producing additional substances, exhibiting good biocompatibility.

[0210] To achieve sufficient tissue-killing effect, the steam temperature should be greater than 120°C, and the steam velocity ejected from the distal end of the catheter should be between 100 m / s and 340 m / s to ensure sufficient depth. For a catheter with an outer diameter of approximately 1 mm, the steam treatment time should be between 3 and 15 minutes. Increasing the outer diameter of the catheter can reduce the duration of the steam treatment.

[0211] Furthermore, referring to Figure 23(c), the distal end of the ablation catheter 31 may also be provided with an occlusion balloon 212, which makes the ablation catheter more firmly fixed in the target blood vessel and prevents it from slipping out, and also prevents the backflow of steam or blood heated by steam into the next level blood vessel.

[0212] In other embodiments, the ablation element 311 shown in FIG23(a) may also be a part of a microwave antenna radiating unit, an electrode, a part of an optical fiber, an ultrasonic transducer, or a combination of other elements, so that the ablation catheter 31 can achieve tissue ablation by means of radio frequency (RF), pulsed electric field ablation (PFA), high intensity focused ultrasound (HIFU), histotripsy, laser ablation, etc.

[0213] In addition, the ablation catheter 31 can also be designed to perform cryoablation of the target blood vessel and surrounding tissues by means of liquid nitrogen freezing or argon-helium freezing, as shown in Figure 23(b). In this embodiment, the ablation element 311 is an ablation balloon design.

[0214] Figure 23(d) illustrates an implementation of the ablation guidewire 32. The ablation guidewire 32 can be used alone as an ablation system 3. Its distal end is provided with a guidewire ablation element 321, which can be a part of a microwave antenna radiation unit, an electrode, a part of an optical fiber, an ultrasonic transducer, or a combination of elements, so that the ablation guidewire 32 can achieve tissue ablation through radio frequency (RF), pulsed electric field ablation (PFA), high intensity focused ultrasound (HIFU), histotripsy, laser ablation, and other methods.

[0215] Furthermore, referring to Figure 23(e), the ablation system 3 can be used in conjunction with the ablation catheter 31 and the ablation guidewire 32 to cover a wider ablation area. For example, the ablation catheter 31 can be used to ablate nearby blood vessels and surrounding tissues, while the ablation guidewire 32 can be extended further to ablate deeper tissues and blood vessels.

[0216] In the embodiment shown in Figure 26, the ablation system 3 uses a non-invasive ablation device 33 to perform adrenal gland ablation. The preferred ablation method is high-intensity focused ultrasound (HIFU) or histotripsy. The non-invasive ablation device 33 can integrate an ultrasound transducer array and adjust the ultrasound focusing area by setting parameters to achieve precise tissue ablation.

[0217] The above-mentioned methods of ablation by applying energy to the vein to be ablated, such as radiofrequency energy, microwave energy, pulsed high-voltage electric field energy, ultrasound energy, and cryo-energy, have the advantage that these energies attenuate with distance, thus selectively killing adjacent tissues through distance selectivity.

[0218] Specifically, the detection system may also include a detection catheter and an in vivo detection module. The detection catheter delivers the in vivo detection module into the target blood vessel and directly measures the hormone concentration in real time within the blood vessel, reducing operational steps and improving surgical efficiency.

[0219] The detection catheter may be hollow, containing a second lumen, for delivering a guidewire or performing other procedures; the detection catheter may also be solid, such as a guidewire.

[0220] Preferably, the in vivo detection module is disposed at the distal end of the detection catheter;

[0221] Optionally, the detection system includes a detection catheter, an in vivo detection module, and a detection cannula;

[0222] Optionally, the detection cannula is first inserted into the target blood vessel under the guidance of the imaging system. The detection catheter can be placed inside the detection cannula beforehand but without exposing the in vivo detection module. Alternatively, the detection catheter loaded with the in vivo detection module can be inserted into the body through the cavity of the detection cannula only when detection is required, so as to avoid the in vivo detection module coming into contact with blood in non-target areas and affecting the accuracy of the detection results.

[0223] Optionally, the in vivo detection module is disposed inside the detection cannula, and the distal end of the detection catheter is provided with a blood sampling groove. The blood sampling groove can be a completely open groove or a deep groove with side wall openings. The blood sampling groove can hold 5-50 μl of blood. The detection catheter is preferably placed inside the detection cannula beforehand. In use, the detection catheter is extended from the distal end of the detection cannula and exposed to the blood sampling groove, so that the blood of the target blood vessel fills the blood sampling groove. Then, the detection catheter is retracted into the detection cannula until the opening of the blood sampling groove is aligned with the in vivo detection module, so that the blood in the blood sampling groove comes into contact with the sensor of the in vivo detection module, thereby realizing real-time blood detection in the blood vessel and obtaining the detection results.

[0224] Preferably, the in vivo detection module may include structures such as semi-permeable membranes, filter membranes, adsorption columns, and dialysis columns that can selectively allow or block substances, reducing or avoiding direct contact between substances in the in vivo detection module and blood participating in human circulation, thus significantly reducing biocompatibility-related risks; at the same time, the structure can also filter out large molecules in the blood, reducing interference from impurities on the detection module.

[0225] The detection catheter 23 and the in vivo detection module 222 work together to enable the surgeon to obtain the target hormone concentration in real time within the target blood vessel, further optimizing the surgical procedure. Referring first to Figure 13, the in vivo detection module 222 is positioned at the distal end of the detection catheter 23. In this embodiment, the sensor of the in vivo detection module 222 is configured to preferentially contact the blood outside the detection catheter 23. The detection catheter 23 can be a hollow catheter with a second lumen 231, as shown in Figure 13(a). The second lumen 231 can be used for operations such as guidewire delivery, blood aspiration, and contrast agent spraying. Therefore, in the embodiment shown in Figure 13(a), the in vivo detection module 222 can also be configured to preferentially contact the blood aspirated into the second lumen 231, preventing the detection catheter 23 from contacting blood in a non-target area before being properly positioned, thus avoiding interference with the hormone concentration detection results. The detection catheter 23 can also be a solid catheter, as shown in Figure 13(b), which can directly possess properties similar to a guidewire, thereby reducing the size of the detection catheter, saving space, and providing better delivery performance.

[0226] To better prevent the collected blood sample from being infected or contaminated by blood from other blood vessels, the detection system 2 may also include a detection sleeve 25, as shown in Figure 14. In the embodiment shown in Figure 14(a), the detection cannula 25 first enters the target blood vessel under the guidance of the imaging system 1. After ensuring that the position is correct, the detection catheter 23 is then inserted into the target blood vessel through the inside of the detection cannula 25, exposing the in vivo detection module 222 at its distal end to the blood for detection. Further, as shown in the embodiments in Figures 14(b) and (c), the distal end of the detection catheter 23 is provided with a blood sampling groove 20, which is similar in function and structure to the blood sampling groove of the blood collection catheter 21 in Figure 9, and is used to collect and store blood samples from the target blood vessel for subsequent hormone concentration detection. Referring to Figures 14(b)-(d), in these embodiments, the in vivo detection module 222 is configured inside the detection cannula 25, and the sensor inside is designed to communicate with the inside of the detection cannula. When the blood sampling groove 20 shown in Figure 14(d) collects enough blood samples, the detection catheter 23 is pulled back and the opening of the blood sampling groove 20 is aligned with the in vivo detection module 222 to trigger real-time detection.

[0227] In a preferred embodiment, the area of ​​the in vivo detection module 222 that comes into contact with the outside world is also provided with a semi-permeable membrane 223, which only allows specific small molecules to enter and exit, avoiding direct contact between the sensors and other components of the in vivo detection module and the blood that still circulates in the blood vessels, thus greatly improving the safety of real-time detection of hormones in vivo, as shown in Figures 14(d) and (e).

[0228] In the above embodiments, in order to further improve the accuracy of detection, the detection catheter 23 and the detection cannula 25 may also be provided with a blocking balloon 212 at the distal end as shown in Figure 8(b), so that the detection system 2 can be better fixed in the target blood vessel to avoid slipping out, and to avoid interference from the blood in the upstream blood vessel of the target blood vessel, see Figures 14(f)-(g).

[0229] Since some embodiments of the detection system 2 and the ablation system 3 have similar features and structures, the catheter system mentioned in this invention also provides a second catheter system 4, in which both the detection system and the ablation system are configured. It is worth noting that when the second catheter system 4 is used in place of the detection system and the ablation system, the second catheter system 4 can also replace the detection system 2 in Figure 7 and be used in conjunction with the imaging system 1.

[0230] Optionally, the second catheter system includes a blood collection catheter, an in vitro detection module, and an ablation system. The ablation system can be used to perform alcohol or vapor ablation directly through the blood collection catheter, or the catheter ablation element can be placed at the distal end of the blood collection catheter (i.e., the blood collection catheter is also used as an ablation catheter). It can also include an ablation guidewire and a guidewire ablation module so that the ablation guidewire can be directly inserted through the channel inside the blood collection catheter for subsequent ablation operations.

[0231] Preferably, the second catheter system includes a detection catheter equipped with an in vivo detection module and an ablation system. The ablation system can be configured to directly utilize the second lumen of the detection catheter for alcohol or vapor ablation, or the catheter ablation element can be arranged at the distal end of the detection catheter (i.e., the detection catheter is also used as an ablation catheter). It can also include an ablation guidewire and a guidewire ablation module, so that the ablation guidewire can be directly inserted through the channel inside the detection catheter for subsequent ablation operations.

[0232] Figure 27 shows a typical implementation of part of the second imaging system 4.

[0233] Referring to Figure 27(a), one embodiment of the second catheter 4 is a combination of a blood collection catheter 21, an in vitro detection module 221, and an ablation system 3. In this embodiment, the first lumen 211 of the blood collection catheter 21 can also be used as the third or fourth lumen in the ablation system 3, and alcohol ablation can be performed using the first lumen 211. Furthermore, the catheter ablation element 311 can be arranged at the distal end of the blood collection catheter 21, which is consistent with directly using the third lumen 312 of the detection catheter 31 shown in Figure 23(a) for blood collection. In addition, referring to Figure 27(b), a blood sample can be obtained through the blood collection catheter 21 and the hormone concentration in the blood sample can be obtained using the in vitro detection module 221. If ablation is required, the ablation guidewire 32 can be directly inserted through the first lumen 211 of the blood collection catheter 21, and tissue ablation can be performed using the guidewire ablation element 321 integrated at the distal end of the ablation guidewire.

[0234] Referring to Figure 27(c), another typical implementation of the second catheter system 4 is to use a detector 23 with a blood collection groove 20, a detector cannula 25 with an in vivo detection module 222, and a catheter ablation element 311 disposed at the distal end of the detector cannula 25; wherein the catheter ablation element is preferably disposed at the distal end of the in vivo detection module 222, that is, closer to the opening of the detector catheter 25, so that the catheter ablation element 311 is closer to the adrenal gland and the ablation area is more precise.

[0235] In addition to the above-described embodiments, the second catheter system 4 can also directly utilize the shape of the balloon catheter in Figure 8(b) or Figure 23(b), injecting fluid into the balloon when detection is needed to make it only serve a sealing function, and then injecting liquid nitrogen or other substances into the balloon to perform cryoablation when ablation is needed.

[0236] To further improve the operator's control over the catheter system provided by this invention, the catheter system may also be provided with a depth indicator 91 and a direction indicator 92 as shown in FIG28(a), indicating to the operator the depth and orientation of the imaging system entering the human body, as well as the relative position and orientation of the detection system, ablation system, second catheter system and the imaging system.

[0237] The depth indicator is preferably set in the form of a scale on at least a part of the imaging system, ablation system, detection system, and second catheter system, especially the part of the catheter that does not enter the human body, so as to facilitate the operator's observation; the depth indicator 91 on the imaging system 1 indicates the depth of the imaging system entering the human body, so as to facilitate the operator's prediction of the position of the first catheter in the imaging system; if the depth indicator 91 is set on the catheter or guidewire of the detection system, ablation system, or second imaging system, it can be used to indicate the depth of these catheters or guidewires entering the first channel and whether they have entered the imaging range of the imaging system; in addition, when the depth indicator 91 does not surround the first catheter and is only a line segment of fixed length as shown in FIG28(a), the depth indicator 91 itself can also serve as a direction indicator 92 to indicate the orientation of the first imaging system and / or the first channel to the operator.

[0238] The direction indication includes at least a direction mark, which is disposed on at least a portion of the imaging system, ablation system, detection system, and second imaging system, indicating the orientation of each component itself and the relative orientation between instruments;

[0239] The directional indicator includes at least an operating handle, which may include a tee, a tail fin, or other non-axisymmetric design, so that the operating handle can provide directional indication while facilitating the operator's grip and manipulation of the catheter or guidewire.

[0240] The direction indicator 92 can be implemented in various ways. It can exist as a direction mark 921 on the imaging system 1 in Figure 28, with its center or axis coplanar with the first channel. The direction mark 921 can be set on the catheter body or on the catheter handle. When the catheter tip in the detection system, ablation system, or second catheter system has a certain curvature, the direction mark 921 can be set on the catheter body and / or handle to indicate the orientation of the catheter tip opening. Furthermore, the catheter system can also realize the direction indicator function through the operating handle 922. Referring to Figures 28(a) and (b), a protruding tail can be set on the operating handle 922 to facilitate gripping and manipulating the catheter. At the same time, the direction of the tail can also indicate the orientation of the catheter and / or guidewire, so that the operator can more intuitively and quickly insert the catheter and / or guidewire into the target blood vessel. In some embodiments, the function of the tail of the above-mentioned operating handle 922 can also be realized through features such as the side branch of the three-way handle or the catheter label.

[0241] It is worth noting that the tubular instruments that enter the human body in the one-stop catheter system mentioned in this invention, such as the first catheter 11, blood collection catheter 21, detection catheter 23, detection sheath 25, ablation catheter 31, and ablation guidewire 32, can all be designed with a fixed or adjustable bend structure that is more in line with the vascular course and easier to implant, based on the anatomical structure of the blood vessels in the patient's body, without requiring creative labor.

[0242] Preferably, the imaging system 1 further includes an imaging host 14, which provides the necessary power supply, ultrasonic energy, light source, and image acquisition capabilities to the first imaging system 12 according to its design.

[0243] Preferably, the detection system 2 further includes a detection host 24, which can acquire relevant data from the in vivo detection module 222 and calculate hormone concentration, and can also be used as an in vitro detection module 221, and can also display the measurement results of hormone concentration;

[0244] Preferably, the ablation system 3 further includes an ablation host 34, which provides at least the energy required for ablation of the ablation catheter, ablation guidewire, and non-invasive ablation device, such as emitting ultrasound, emitting alternating current, or providing steam.

[0245] Furthermore, the one-stop catheter system provided by the present invention also includes at least one display 95. The display can be integrated or connected to the imaging host 14, the detection host 24, and the ablation host 34 respectively, and can also be compatible with the above three hosts at the same time, displaying the screen and / or data required by the three hosts simultaneously, making the data and information more intuitive and convenient for the operator to operate.

[0246] The images may include those generated by the first imaging system 12, such as ultrasound, OCT, or endoscopic images. The data may include the A / C ratio of each blood vessel, and may also include indicators such as aldosterone concentration, cortisol concentration, L1, and CSI. The data may also include parameters of the ablation system 3, which may vary depending on the embodiment, such as ablation power, ablation time, temperature, gas pressure, liquid pressure, flow rate, voltage, resistance, impedance, and frequency.

[0247] Referring to Figure 15(a), when the detection host 24 is used independently, the host is equipped with an in vitro detection module 222 and a display 95 for use by the detection system 2. After receiving the blood sample through the in vitro detection module, the detection host 24 analyzes the data and displays the obtained values ​​and even the judgment results on the display 95.

[0248] In some implementations, to achieve higher integration of the catheter system, the imaging host 14, detection host 24, and ablation host 34 can be configured on a single operating cart, as shown in Figure 29, with all three hosts sharing a single display 95. Taking the implementation shown in the figure as an example, considering the operator's convenience, the external detection module 222 of the detection host 24 does not need to be connected to the catheter or guidewire entering the body, and is therefore positioned at the bottom of the operating cart. The imaging host 14 requires frequent operation to adjust the imaging screen, and is therefore positioned at the top to avoid obstructing the operating area. The ablation host 34 typically needs to be connected to the ablation device to provide ablation energy, but its operation is simpler than that of the imaging system, and is therefore positioned in the middle of the operating cart. When the three hosts share a display, the screen of the display 95 can be divided into three different areas, as shown in Figure 29, to display the screen, parameters, and other information corresponding to each host. It can also be further designed to selectively zoom in and switch between the data screens corresponding to each host.

[0249] Although embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. It can be applied to various fields suitable for the present invention. Other modifications can be readily implemented by those skilled in the art. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

Claims

1. An adrenal vein blood sampling and ablation catheter system, characterized in that... include: The imaging system images and / or locates blood vessels and surrounding tissues, guiding the catheter into the renal vein and adrenal vein; the detection system, guided by the imaging system, enters the renal vein or adrenal vein, then collects blood in the target area and performs rapid or real-time detection of hormone concentration in the blood sample; when the detection system determines that there is unilateral dominant secretion, the ablation system can perform ablation treatment on the adrenal gland or adrenal adenoma on the dominant secretion side to reduce or eliminate hormone secretion on that side.

2. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The imaging system includes a first catheter, a first imaging system, and a first channel; it is used to image blood vessels and surrounding tissues, as well as the detection system and ablation system, and to guide the detection and ablation systems into the target blood vessel; the first channel can accommodate at least a portion of the detection system and the ablation system; the first imaging system is preferably disposed on the first catheter.

3. The adrenal vein blood sampling and ablation catheter system as described in claim 2, characterized in that... The first catheter has at least one distal opening and one proximal opening. The first catheter includes a first channel that connects the distal opening and the proximal opening. At least a portion of the detection system or ablation system enters the target blood vessel via the first channel under the guidance of the first imaging system to perform subsequent operations.

4. The adrenal vein blood sampling and ablation catheter system as described in claim 3, characterized in that... The first imaging system uses at least ultrasound imaging technology; the ultrasound imaging system employs 2D imaging and is arranged at the distal end of the distal opening of the first catheter, with one or a group of ultrasound transducer elements distributed along the axial direction, the imaging plane being a fan-shaped surface or a similar fan-shaped surface parallel to the long axis of the first catheter, and the imaging plane being coplanar with the axis of the first channel, thereby detecting instruments entering and exiting the first channel.

5. The adrenal vein blood sampling and ablation catheter system as described in claim 4, characterized in that... The 2D ultrasound imaging system also images the cross-section of the blood vessel by rotating a single ultrasound transducer, making the openings of the blood vessel branches more clearly visible. The ultrasound imaging system uses 3D imaging, that is, it generates multiple 2D ultrasound images in different orientations and stitches them together to form an image. The ultrasound imaging system uses real-time 3D imaging and is arranged at the distal end of the distal opening of the first catheter. A set of ultrasound transducer element arrays is distributed circumferentially and configured to perform 360° imaging of the cavity around the catheter system, which facilitates the rapid location of the target blood vessel.

6. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The imaging system images or locates the blood vessel and its surrounding tissues, and also images or locates a part of the detection system, so that a distal part of the detection system and the opening of the target blood vessel appear in the imaging field of view at the same time.

7. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The detection system adopts a homogeneous reaction system, with a donor bead microsphere on which antibodies or aptamers are modified. Design another receptor bead microsphere and modify its surface with another antibody or aptamer to form a sandwich system; When a donor bead receives external excitation light, it can emit oxygen free radicals, causing adjacent acceptor beads to emit light of different wavelengths. By capturing the emitted light of this specific wavelength, the concentration of the analyte can be estimated by measuring how many sandwich systems are formed.

8. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The detection system adopts a homogeneous reaction system and is equipped with a turntable containing one or more rotating shafts. When rotating, the turntable provides centrifugal force, thereby effectively realizing the functions of stirring and separation.

9. The adrenal vein blood sampling and ablation catheter system as described in claim 8, characterized in that... The rotating disc performs plasma separation and measurement detection functions. After the blood sample is added to the disc, it first undergoes plasma separation under centrifugation. Aldosterone and cortisol, being small molecules, are distributed in the supernatant. The supernatant is then extracted to another reaction chamber. By adjusting the centrifugal force, the reagents and supernatant are thoroughly mixed and reacted in the reaction chamber. Subsequently, the mixture is introduced into the luminescence chamber via capillary effect or active aspiration. The luminescence chamber is configured to accept a given light source with a wavelength range that includes the design wavelength range of the donor beads. The luminescence chamber is also configured to allow the excitation light emitted by the acceptor beads to enter the optical probe. The optical probe measures the light flux, thereby achieving the purpose of measuring the concentration of the analyte.

10. The adrenal vein blood sampling and ablation catheter system as described in claim 9, characterized in that... The light source is pulsed, and the optical probe collects the excitation light after a certain time delay to better avoid the influence of background noise on the results.

11. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The detection system includes a blood collection catheter and an in vitro detection module. The blood collection catheter is used to collect blood from the target blood vessel, and then the collected blood sample is dripped into the in vitro detection module to obtain the detection results.

12. The adrenal vein blood sampling and ablation catheter system as described in claim 11, characterized in that... The diameter of the blood collection catheter is 1-2 F larger than the target blood vessel size, which makes it easier to be inserted into the target blood vessel and block the lumen opening, preventing blood from the upstream blood vessel of the target blood vessel from flowing into the branch under negative pressure during the blood collection process and affecting the test results.

13. The adrenal vein blood sampling and ablation catheter system as described in claim 11, characterized in that... The blood collection catheter includes a first lumen, which allows for easier entry into the target blood vessel and / or aspiration of blood from the target blood vessel under the guidance of a guidewire.

14. The adrenal vein blood sampling and ablation catheter system as described in claim 11, characterized in that... The blood collection catheter has a beveled distal opening and at least one side hole at the distal end.

15. The adrenal vein blood sampling and ablation catheter system as described in claim 11, characterized in that... The blood collection catheter includes an occlusion balloon, which is preferably positioned 5-50 mm from the distal opening of the blood collection catheter to isolate the target blood vessel from its upstream blood vessel and avoid interference from blood in the upstream blood vessel with the test results.

16. The adrenal vein blood sampling and ablation catheter system as described in claim 11, characterized in that... The blood collection catheter includes an outer tube and a central blood collection tube. The distal end of the central blood collection tube is provided with a blood collection groove. The central blood collection tube can be inserted only during blood collection, or it can be placed in the outer tube beforehand. When in use, the central blood collection tube is extended from the distal end of the outer tube and exposed to the blood collection groove, allowing blood to fill the blood collection groove. Then, the central blood collection tube is retracted into the outer tube, and the opening of the blood collection groove is blocked by the inner wall of the outer tube, thereby preserving the blood sample.

17. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The ablation method using the ablation catheter involves ablation with alcohol or steam.

18. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... It also includes at least one display, which can be integrated or connected to the imaging system, detection system, and ablation system respectively, or can be compatible with the above three systems at the same time, displaying the images and / or data required by the three systems simultaneously, making the data and information more intuitive and easier for the operator to operate.

19. The adrenal vein blood sampling and ablation catheter system as described in claim 1, characterized in that... The imaging system, detection system, and ablation system are all located on one surgical cart and share a single monitor. The in vitro detection module of the detection system is located at the bottom of the surgical cart, while the imaging system is located at the top to avoid obstructing the operating area. The ablation system usually needs to be connected to the ablation instrument to provide ablation energy, but its operation is simpler than that of the imaging system, so it is located in the middle area of ​​the operating cart; when the three systems share a monitor, the monitor screen is divided into three different areas to display the screen, parameters and other information of each system respectively.

20. Method for using an adrenal vein blood sampling ablation catheter, characterized in that... The procedure includes the following steps: The detection system is integrated with an imaging system; a portion of the detection system is inserted into the left and right adrenal veins and / or their branches, respectively, according to the method described for entering the left or right adrenal veins; blood samples are collected from the adrenal veins and / or their branches, as well as peripheral veins, according to the in vitro hormone detection method for primary aldosteronism described above, and the concentration and / or activity of the target hormone are measured in vitro; or the concentration and / or activity of the target hormone in the target blood vessels and peripheral veins are directly measured in vivo according to the in vivo hormone detection method for primary aldosteronism described above; the subtype and treatment method are determined according to the treatment strategy for primary aldosteronism, and ablation treatment is performed according to the ablation method described above.

21. The method of using the adrenal vein blood sampling and ablation catheter as described in claim 21, characterized in that... The steps for cooperating with the detection system and the imaging system include: positioning the imaging system in the patient's inferior vena cava; using the first imaging system mounted on the first catheter to locate the vascular opening that conforms to the anatomical characteristics of the renal vein; determining the location and orientation of the renal vein; and then inserting the instrument that needs to enter the target blood vessel into the blood vessel along the first channel until the imaging system can simultaneously observe the instrument and the renal vein opening.

22. The method of using the adrenal vein blood sampling and ablation catheter as described in claim 21, characterized in that... The method further includes: inserting the first catheter into a primary branch via a sheath or by replacing the guidewire, inserting the first catheter into the renal vein and locating the opening of the adrenal vein, and then, under the guidance of the first imaging system, inserting the detection system into the adrenal vein along the first channel.

23. The method of using the adrenal vein blood sampling and ablation catheter as described in claim 21, characterized in that... The method further includes: delivering a blood collection catheter to one of the blood vessels to be tested through a first catheter; then completing the blood collection action on this blood vessel, which can be used for real-time in-situ detection or the blood sample can be taken outside the body for detection; if blood collection has been completed for all blood vessels to be tested, the blood collection step is ended; the typing is determined based on the test results; otherwise, another blood vessel to be tested is selected and the above process is repeated.

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