Monitoring of renal denervation ablation using perfusion angiography

Abstract

A device is provided for providing patient selection and treatment guidance for ablation procedures (particularly renal denervation procedures). This device is adapted to derive two dynamic measures from two time series of diagnostic images indicating two states of the patient to determine at least one indicator indicating the relative difference between a first state and a second state. Based on at least one indicator, it is possible to track the progress of the ablation procedure and determine whether the ablation procedure has been completed. Furthermore, the indicator can be used to select potential responders for the ablation procedure.

Description

Technical Field

[0001] This invention relates to apparatus, corresponding methods, and corresponding computer programs for providing treatment guidance for ablation procedures. Specifically, this invention relates to apparatus and methods for providing treatment guidance and patient selection for renal denervation procedures involving ablation of nerves in the wall of the renal artery. Background Technology

[0002] Hypertension (HTN) (commonly known as hypertension) is a long-term medical condition and a major risk factor for coronary artery disease, heart failure, peripheral artery disease, and more. Therefore, it is crucial to manage hypertension appropriately to reduce the risk of patients developing the diseases it causes.

[0003] Typically, hypertension is managed by controlling blood pressure with appropriate antihypertensive medications, often accompanied by necessary lifestyle modifications. However, in cases of refractory hypertension, blood pressure remains above a target level despite medication treatment. In such cases, alternative management options should be considered.

[0004] One such alternative is renal sympathetic denervation (RSDN), also known as renal denervation (RDN). RDN is a catheter-based, minimally invasive endovascular procedure that employs ablation techniques such as radiofrequency ablation, ultrasound ablation, and alcohol ablation. This ablation procedure ablates the nerves in the wall of the renal artery. This results in a reduction of sympathetic afferent and efferent activity to the kidney. This treatment takes into account the fact that systemic vascular impedance is regulated, among other things, by the renin-angiotensin system (RAS). Stimulation of efferent activity causes increased RAS activity, renal sodium reabsorption, and reduced renal flow, while stimulation of afferent activity causes increased renal sympathetic outflow to peripheral organs such as the kidney, heart, and / or peripheral vascular system. Afferent renal sympathetic activity can be regulated by efferent renal sympathetic nerves via norepinephrine as a neurotransmitter. Thus, efferent renal sympathetic nerves activate α1- and α2-adrenergic receptors (sometimes commonly referred to as α receptors) on afferent renal nerves, which can increase and decrease afferent renal nerve activity, respectively. As a result, reducing this activity can lower blood pressure.

[0005] However, the blood pressure response to RDN varies from patient to patient. That is, in some cases, patients have shown a very positive response by exhibiting a significant decrease in blood pressure, while in others, patients have shown an actual increase in blood pressure in response to RDN treatment. Therefore, the success of RDN treatment depends heavily on appropriate patient selection.

[0006] Furthermore, the success of RDN treatment depends on the extent of nerve ablation in the renal artery wall, i.e., on the completeness of the ablation procedure. Currently, treatment guidance for ablation procedures is often unavailable. Therefore, users performing the ablation procedure (such as physicians) cannot track the progress of the ablation process and know when it is complete.

[0007] US2016 / 0113699 discloses an apparatus and method for kidney denervation, and discloses the ability to assess treatment effectiveness by comparing responses to stimuli before and after denervation.

[0008] WO2018 / 204284 discloses a comparison of blood perfusion levels before and after ablation to provide a measure of ablation progress. Summary of the Invention

[0009] Therefore, the object of the present invention is to provide an apparatus and a corresponding method for providing treatment guidance for an ablation procedure performed on the renal vessel wall of a patient.

[0010] Another object of the present invention is to provide an apparatus and method for monitoring an ablation procedure and for determining when the ablation procedure has been completed. More specifically, the object of the present invention is to provide an apparatus and corresponding method for monitoring the progress of an ablation procedure during treatment by making appropriate patient selections and for providing treatment guidance to a user performing a renal denervation (RDN) procedure by indicating that the ablation procedure has been completed in order to terminate the treatment.

[0011] This objective is achieved by an apparatus for providing treatment guidance for ablation procedures, the apparatus comprising: an input unit adapted to receive a first time series of diagnostic images of a region of interest (ROI) of a patient's vascular system and a second time series of diagnostic images of the ROI of the patient's vascular system, the first time series representing a first state and the second time series representing a second state; a processing unit adapted to derive from the first time series of the diagnostic images a first dynamic measure indicating the dynamics of contrast agent passing through the ROI over time for the first state, derive from the second time series of the diagnostic images a second dynamic measure indicating the dynamics of contrast agent passing through the ROI over time for the second state, and determine at least one index indicating a relative difference between the first state and the second state based on the first dynamic measure and the second dynamic measure; and an output unit adapted to output the at least one index to a user.

[0012] Devices used to provide treatment guidance utilize the fact that the physiology of the vascular system changes during the ablation process. Specifically, when ablation is performed on a nerve located in the wall of the artery being treated, microvascular resistance decreases. This allows fluid (typically blood) to flow through the artery more rapidly. This means that the progress of the ablation treatment can be tracked by following the flow of fluid through the vascular system. Since measuring blood flow velocity is quite difficult in itself, this tracking is performed by introducing a trackable fluid (such as a contrast agent) into the artery and tracking the trackable fluid using a non-invasive imaging modality that allows visualization of the trackable fluid.

[0013] In this context, terminology guidance can specifically refer to providing information about the extent of ablation performed by an ongoing ablation procedure (i.e., the progress of the ablation procedure), whether the ablation procedure has been completed, and whether the patient is a likely responder to the ablation procedure. This allows for improvements in the treatment process by being able to determine its progress, its endpoints—and therefore its success—and by improving patient selection, such as avoiding unnecessary treatment of patients who are unlikely to respond to the procedure anyway.

[0014] Furthermore, the terms "first time series of diagnostic images" and "second time series of diagnostic images" can specifically refer to multiple diagnostic images obtained using a specific imaging modality that allows visualization of contrast agents within a region of interest. Thus, each diagnostic image in the time series corresponds to a specific point in the measurement time. This allows for tracking dynamic processes, such as the evolution of contrast agents through the vascular system presented in the diagnostic images.

[0015] In this context, the term diagnostic image can specifically refer to an image representing a region of interest within a patient's vascular system. Thus, the term vascular system can refer to a vascular tree or a single vessel. In some embodiments, the diagnostic image may represent a vessel of interest that is part of the renal artery. That is, the region of interest for a first time series of diagnostic images and / or a second time series of diagnostic images is placed on the patient's kidney.

[0016] In some embodiments, a first time series of diagnostic images and / or a second time series of diagnostic images can be obtained using a diagnostic imaging modality that allows visualization of contrast agents in the artery. Suitable diagnostic imaging modalities may in particular include X-ray imaging modalities.

[0017] Diagnostic imaging modalities can be specifically gated. Thus, gated diagnostic imaging modalities can typically employ gated reconstruction, where the acquisition of diagnostic images is performed in parallel with the acquisition of data providing information within the cardiac cycle, such as electrocardiogram (ECG) or photoplethysmography (PPG) data. This data can then be used to gate image acquisition and reconstruction using appropriately selected phase points within the cardiac cycle.

[0018] The first and second time series of diagnostic images can represent the first and second states of the ablation procedure, respectively. Thus, the first and second states can specifically correspond to states indicating the progress of the ablation procedure and corresponding reference states. The reference states correspond to states indicating the expected / desired outcome of the ablation procedure.

[0019] Specifically, in some embodiments, the first state may correspond to a patient-specific state. The second state may correspond to a reference state that provides a reference for determining the effectiveness of the (potential) ablation treatment.

[0020] Therefore, patient-specific states and reference states can be specifically selected based on the type of treatment guidance desired. Consequently, different combinations of patient-specific states and reference states are possible.

[0021] In some embodiments, where the desired treatment guidance involves appropriate patient selection, the patient-specific status may correspond to the patient’s “as is” status prior to ablation treatment, i.e., a baseline acquisition of the microvascular function of the renal artery of that particular patient before any drug administration and / or ablation treatment has been performed.

[0022] In these embodiments, the reference state may specifically correspond to a state derived from clinical studies. In some embodiments, the state derived from clinical studies specifically represents the expected outcome of the ablation treatment. In this case, the reference state may correspond to a general reference state for all patients or for a specific patient group (such as those of the same age, sex, etc.). In these embodiments, the reference state may also correspond to the state of a patient who has been administered an alpha blocker, i.e., a patient who has received a drug that blocks alpha receptor stimulation and thus blocks vasoconstriction. This state is typically also derived prior to the ablation treatment. The use of drug administration allows for the provision of a reference state indicating the effect that ablation of the nerves in the renal artery will have on that particular patient. Therefore, the reference state does not correspond to a general reference state for all patients, but rather to a reference state derived for each individual patient.

[0023] In these embodiments (where the first state corresponds to the baseline state and the second state corresponds to the state providing a reference for the expected outcome of the ablation process), if the difference between a first dynamic measure for the first state and a second dynamic measure for the second state is large (this can be specifically expressed by corresponding indicators indicating the difference), the patient can be determined to be suitable for ablation treatment for the purpose of renal denervation. This means that the effect of renal denervation will also be significant, resulting in a significant reduction in microvascular impedance in the event of successful treatment, and therefore a reduction in hypertension for the patient.

[0024] In some embodiments (where the desired treatment guidance involves appropriate patient selection), it can also be a patient-specific (first) state corresponding to the patient's state after administration of the alpha blocker, while the reference state can be a general reference state derived from clinical studies. As indicated here above, administration of a drug that blocks alpha receptors mimics the effect of ablation of nerves in the renal artery. Therefore, patients can also be selected by determining a first dynamic measure of the first state, including drug administration, and comparing it with a second dynamic measure of a second state, indicating the desired outcome to be achieved through the ablation procedure, i.e., a state indicating that microvascular impedance has been appropriately reduced.

[0025] In such cases, with small differences indicated by the indicators, the patient can be considered suitable for ablation treatment. This means that the patient will indeed be susceptible to the effects of nerve ablation, leading to a decrease in microvascular impedance.

[0026] In cases where treatment guidance involves tracking the progress of an ablation procedure and / or determining whether the ablation procedure has been completed, the patient-specific state may specifically correspond to the patient's state before and / or during and / or after the ablation procedure. That is, in the case of treatment guidance for an ongoing ablation procedure, the patient-specific (first) state may correspond to the current state of the patient undergoing the ablation procedure. In these cases, the reference state may again correspond to a state derived from a clinical study. In some embodiments, the state derived from a clinical study may specifically represent the state of the expected outcome of the ablation procedure. In some embodiments, multiple first time series of diagnostic images may be obtained during the ongoing ablation procedure, such as to derive multiple first dynamic measures, each used to iteratively provide an indication of the patient's (new) current state. The progress of the ablation procedure can be tracked by comparing the thus determined current first dynamic measure with a dynamic measure of the reference state from the clinical study.

[0027] In some embodiments, the reference state may also correspond to the state of a patient who has been administered an alpha blocker, i.e., a patient who has received a drug that blocks the vasoconstrictive effect of alpha receptor stimulation. In this case, the reference state also indicates the expected outcome of the ablation procedure. That is, the progress of the ablation procedure can be tracked in a similar manner by comparing a second dynamic measure for the thus defined reference state with a first dynamic measure for the first state that is iteratively updated during the ablation procedure.

[0028] In other words, in the above embodiment where the reference state corresponds to the state indicating the desired outcome of the ablation treatment, a first dynamic measure of the first state should approach a second dynamic measure of the reference state during the ablation treatment. Once the difference between the first and second dynamic measures becomes minimal (i.e., the states become very similar), the treatment can be considered successful and can be terminated. Therefore, by tracking the progress of the treatment, it is also possible to determine when the ablation treatment is completed.

[0029] Furthermore, in some embodiments (where treatment guidance involves tracking the progress of the ablation treatment and / or determining whether the ablation treatment has been completed), the first state used for the first assessment can be used as a reference state for subsequent assessments. More specifically, in some embodiments, a first time series and a second time series for deriving a first dynamic measure and a second dynamic measure can be repeatedly acquired, particularly at predefined intervals, during the ablation treatment. As an example, a second time series of diagnostic images can be acquired before the ablation treatment, and a first time series of diagnostic images can be acquired after some (predefined) time period following the start of the ablation treatment. The first dynamic measure and the second dynamic measure derived for these time series are then compared to each other, resulting in an index indicating the relative difference between the first dynamic measure and the second dynamic measure—and thus between the first state and the second state—having a specific value. Subsequently, another first time series of diagnostic images can be acquired after another interval based on the predefined time period, i.e., for example, after twice the time period following the start of the ablation treatment. Another first dynamic measure can be derived from this first time series. For subsequent comparisons, the dynamic measure derived from the previously determined first time series (i.e., the time series acquired a period after the start of the ablation procedure) is considered to correspond to the second dynamic measure; that is, the state derived from the previously determined first time series is considered the reference state. The first and second dynamic measures (from the first dynamic measure of the previous round) are then compared, and an index indicating the relative difference between the first and second states is again determined. In the case of procedure progress, this index should differ from the previously determined index. This process can be repeated until the difference between the current index and the previously determined index is minimal or nonexistent, i.e., until there is no change between the current first state and the previous first state (used as a reference). As indicated above, the first time series of diagnostic images can be used to derive a first dynamic measure indicating the contrast agent dynamics through the region of interest for the first state. The second time series of diagnostic images can be used to derive a second dynamic measure indicating the contrast agent dynamics through the same region of interest for the second state. Thus, both the first and second dynamic measures represent the flow dynamics through the artery treated by the ablation procedure and the vascular system behind it, and thus for physiological and, in particular, (micro)vascular impedance.

[0030] Both the first and second dynamic measures are thus derived over time. This allows both the first and second dynamic measures for the first and second states to be defined as functions of time. This can be achieved, in particular, by determining the value of the first dynamic measure for each diagnostic image of the first time series and the value of the second dynamic measure for each diagnostic image of the second time series. These values, as determined for the first and second dynamic measures respectively, can then be analyzed as functions of time. This analysis allows for a better understanding of contrast agent dynamics, and therefore a better understanding of the flow dynamics through the treated artery and the vascular system in its periphery.

[0031] A first dynamic measure and a second dynamic measure can be used to determine at least one indicator that indicates the relative difference between a first state and a second state. In some embodiments, the at least one indicator may be specifically provided, such as to indicate the difference between the state of the vascular system (e.g., the treated artery) before treatment and the state of the vascular system after treatment. In some embodiments, the at least one indicator may be provided, such as to indicate the difference between the state of the vascular system during treatment and the state of the vascular system after treatment or the state of the vascular system before treatment. In some embodiments, the at least one indicator may also be used to indicate the difference between the state of the vascular system at the start of a predefined interval and at the end of a predefined interval during ablation treatment, thereby allowing the indicator to be iteratively re-determined.

[0032] Alternatively or additionally, at least one dynamic indicator may be provided, such as to allow assessment of the post-treatment status of the vascular system, regardless of the pre-treatment status.

[0033] At least one indicator should be provided to the user (such as a physician) to allow the user to visually assess the progress of the ablation procedure. This allows the user to draw conclusions about the progress of the procedure and / or identify the endpoint of the procedure. In some embodiments, the endpoint may be considered to correspond to the point at which the ablation procedure is considered complete. In some embodiments, this point at which the ablation procedure is considered complete can be determined by comparing at least one indicator to a predefined threshold.

[0034] In some embodiments (where the second (reference) state corresponds to a state indicating the desired outcome of the ablation treatment, such as derived from clinical studies or based on drug administration, particularly the administration of alpha-blockers), the treatment can be considered complete if at least one indicator indicating the relative difference between the first and second states becomes minimal. In the case where at least one indicator is between 0 and 1, this means that at least one indicator will approach 0. In this case, the predefined threshold could be approximately 0.1, more specifically approximately 0.05, or even more specifically approximately 0.02 relative difference. If at least one indicator falls below these thresholds, the treatment will be considered complete.

[0035] In some embodiments (where the second (reference) state corresponds to a condition indicating the patient's condition prior to ablation, such as derived, for example, from a time series of diagnostic images acquired prior to ablation), the procedure can be considered complete if at least one indicator becomes maximum. In the case where at least one indicator is between 0 and 1, this means that at least one indicator will approach 1. In this case, a predefined threshold could be approximately 0.9, more specifically approximately 0.95, or even more specifically approximately 0.98 relative difference. If at least one indicator will exceed these thresholds, the procedure will be considered complete.

[0036] That is, in some embodiments, the ablation procedure can be determined to be complete if the indicator is below or above a given threshold. In some embodiments, the endpoint can also be determined based on the determination that the ablation was not successful. That is, in some cases, if no significant change in contrast agent dynamics is recorded after a predetermined amount of time, the procedure should be considered unsuccessful and should be terminated accordingly. In some embodiments, the termination of the procedure can be performed manually by the user. In some embodiments, the termination of the procedure can be performed automatically in response to a corresponding indication generated and output when the indicator is compared with a threshold and it is determined accordingly that the ablation procedure can be considered complete.

[0037] In some embodiments, a first time series of diagnostic images and / or a second time series of diagnostic images are acquired using X-ray angiography. In some embodiments, the ablation procedure corresponds to renal denervation (RDN) treatment.

[0038] X-ray angiography is a diagnostic imaging technique particularly well-suited for visualizing blood vessels within the human body. X-ray angiography is typically performed by injecting a contrast agent into a blood vessel and subsequently irradiating the body portion containing the contrast-filled vessel with X-ray radiation to obtain a clearly visible two-dimensional image of the contrast-filled vessel. Therefore, a first time-series diagnostic image and / or a second time-series diagnostic image can correspond to an X-ray angiography image representing a region of interest within the patient's vascular system. Thus, the use of X-ray perfusion angiography is particularly well-suited for obtaining first and second time-series diagnostic images.

[0039] In some embodiments, digital subtraction angiography (DSA) may be employed to determine first and second time series of diagnostic images. DSA is a technique employing a subtraction method that subtracts a diagnostic image obtained before the injection of the contrast agent (a so-called mask) from a diagnostic image acquired once the contrast agent has entered the blood vessel. This allows for reduction of the influence of bone and soft tissue surrounding the blood vessels, and thus enhances the visibility of the vessels. These highly visible vessels can then be removed to focus on the region of interest. Consequently, a classifier already trained with appropriate standard data can be used to perform the DSA method, as well as the subsequent removal of vessels other than those in the region of interest. In some embodiments, the classifier may specifically include a deep neural network.

[0040] Devices for providing treatment guidance for ablation procedures can be specifically used to provide treatment guidance for radiofrequency ablation or ultrasound ablation aimed at treating refractory hypertension. In some embodiments, they can also provide treatment guidance for newly developed techniques, such as alcohol ablation, cryoablation, and / or microwave ablation, which can also be used to treat refractory hypertension.

[0041] Ablation-based hypertension treatment is based on the idea that the sympathetic nervous system induces its effects on the renal arteries by stimulating alpha receptors that cause vasoconstriction. Ableasing nerves in the wall of the renal arteries using, for example, radiofrequency pulses or ultrasound (or any other ablation method) that allows for nerve ablation leads to a reduction in renal sympathetic afferent and efferent activity, thereby releasing vasoconstriction. This can result in a decrease in blood pressure.

[0042] Therefore, the use of X-ray perfusion angiography can, for example, allow visualization of the time-density curve of contrast agent in a region of interest. This region of interest can thus be located on the kidney (i.e., the renal vascular system) and / or above the renal artery. This then allows for monitoring the flow of contrast agent through the renal vascular system and / or renal artery over time during ablation. Now, if the ablation of the renal artery is successful, the flow of contrast agent will exhibit a different behavior than before the procedure, because the vasoconstriction release induced by denervation implies reduced impedance. However, peripheral vascular impedance affects the flow of fluids (such as blood or contrast agent) through the renal vascular system and / or renal artery. That is, the effect of denervation can be tracked by analyzing the dynamic behavior of contrast agent flow over time. As another benefit, since the time-series acquisition of diagnostic images typically covers the entire kidney, where the region of interest is located over the entire kidney or its sub-regions, this allows for analysis of the dynamic behavior of contrast agent in different regions, such as the renal cortex compared to the renal medulla.

[0043] In some embodiments, the apparatus further includes a comparison unit, wherein the comparison unit is adapted to determine that the ablation treatment has been completed by comparing at least one indicator with a predefined threshold.

[0044] Terminating ablation once sufficient treatment has been achieved can be beneficial, such as preventing unnecessary patient exposure. To determine the endpoint of the treatment—the point in time when ablation has been completed—a threshold can be established. This threshold can then be compared to the value of at least one metric. Therefore, it should be understood that the threshold depends on the metric used. That is, a suitable threshold can be selected for each individual metric.

[0045] In some embodiments, the device includes a comparison unit adapted to compare the value of a corresponding indicator with a threshold defined thereon. Thus, the comparison unit can derive whether the indicator value is below or above a given threshold, and depending on how the threshold has been selected, can indicate that the ablation procedure has been completed and can be terminated, or has not yet been completed and should continue. The corresponding indication can be specifically output to a user (such as a physician) to prompt the user to respond accordingly.

[0046] In some embodiments, the first state corresponds to the state during treatment, and the second state corresponds to a reference state. In some embodiments, the reference state is achieved by administering the drug to the patient.

[0047] Adequate tracking of treatment progress and patient selection can be achieved using indicators that differentiate a patient's state from a corresponding reference state. Therefore, in some embodiments, the first state of a first time series of acquired diagnostic images corresponds to the patient's patient-specific state during treatment. In this context, the term "during treatment" can specifically refer to any stage of the treatment. That is, the patient-specific state can be the patient's state at the start of treatment, during ongoing treatment, and / or after treatment. It should be understood that this patient-specific state can change with each iteration of the first time series of acquired diagnostic images during its duration. This is due to treatment progress. Changes in the first state during treatment are what allow for tracking treatment progress and / or determining the endpoint of treatment. Furthermore, by considering the pre-treatment state as the first state, potential responders to the desired ablation treatment can be identified.

[0048] The second state can specifically correspond to a reference state. That is, the second time series of the diagnostic image indicates a reference. The reference can specifically correspond to a reference to the expected / desired outcome of the ablation treatment, i.e., what the diagnostic image should look like upon successful treatment. In some embodiments, the reference can also correspond to a reference to the initial disease state, i.e., what the diagnostic image should no longer look like upon successful treatment. Other references are conceivable.

[0049] In some embodiments, a second time series of diagnostic images indicating a second reference state can be derived from clinical studies. In these cases, the second time series may in particular be a pre-stored patient-nonspecific time series from which a second dynamic measure indicating the reference state can be derived.

[0050] In some embodiments, the at least one metric is determined as the normalized root mean square error (NRMSE) of a first dynamic measure and a second dynamic measure. In some embodiments, the normalized root mean square error is determined as:

[0051]

[0052] in, Corresponding to the first dynamic measure, Corresponding to the second dynamic measure, where i = 1,…,n, and This corresponds to the maximum value of the dynamic metric that can be derived for either the first or second state.

[0053] To provide an objective comparison, the values ​​of the first and second dynamic measures can be compared by defining the normalized root mean square error (NRMSE) as at least one metric. NRSME provides a measure of the correspondence between the first and second dynamic measures. The smaller the NRMSE, the closer the values ​​of the first and second dynamic measures are. Therefore, the magnitude of the NRMSE can be used as a measure of the completion / progression of the ablation procedure.

[0054] In other words, when the second (reference) state corresponds to the state indicating the expected result of the ablation procedure, a reduced NRMSE will indicate the continued (successful) progress of the ablation procedure, and a minimum NRMSE will indicate the completed ablation procedure.

[0055] On the other hand, when the second (reference) state corresponds to the patient's initial state before treatment, an increase in NRMSE will indicate continued (successful) progress of the ablation treatment, and a maximum NRMSE will indicate the completion of the ablation treatment. Therefore, to determine the completion of the ablation treatment, it can be determined that the NRMSE will decrease beyond or increase beyond a certain threshold.

[0056] It should be mentioned that NRMSE can also be used as at least one indicator when appropriate patient selection is performed. Thus, NRMSE can be determined specifically for a first state corresponding to the patient's "as is" state before ablation treatment (i.e., a baseline acquisition indicating the microvascular function of the renal artery in that particular patient before any drug administration and / or ablation treatment has been performed). A second (reference) state can then correspond to a state derived from clinical studies and representing the expected outcome of the ablation treatment, or to a state in which an alpha blocker has been administered, thus indicating the effect that ablation of the nerves surrounding the renal artery will have on that particular patient. In both cases, if the determined NRMSE is large, the patient can be considered suitable for ablation treatment.

[0057] Returning to the exemplary embodiment for renal denervation described above, it can be achieved by... Set as the time density curve representing the post-treatment state as the first state and set as The NRMSE is determined exemplarily by setting a time density curve representing a reference state as the second state. Furthermore, The maximum value of the time-density curve corresponding to the first or second state. The NRMSE calculation provides a dynamic index representing the correspondence between the time-density curves. Ablation is considered complete if this index falls below a predefined threshold.

[0058] Therefore, it should be understood that due to the specific shape of the curve, NRMSE can typically have a maximum value of about 0.5. Thus, values ​​of about 0.3 or even 0.2 can still be considered large NRMSE values, and thus indicate the need for continued ablation treatment until the NRMSE becomes even smaller.

[0059] Alternatively or additionally, in renal denervation, it can be achieved by... Set as a time density curve representing the situation after treatment and The NRMSE was determined by setting up a time-density curve representing the effect of α-blocker treatment. This again corresponds to the maximum value of the time-density curve. In this case, if the NRSME, as a dynamic indicator, is close to 0, the ablation can also be considered complete.

[0060] Although NRSME has been used as an indicator of the difference between the first and second states in the above example, it should be understood that alternatively or additionally, at least one indicator may also represent parameters such as the time to peak of the perfusion time curve, the upper stroke time of the perfusion time curve, peak density, or any combination of other time density curve parameters.

[0061] In some embodiments, a second time series of diagnostic images can indicate a second reference state that can be obtained by administering a drug to the patient and, subsequently, by acquiring the second time series of diagnostic images. This allows for the determination of a second dynamic measure indicative of the second reference state, as the administration of certain drugs (such as alpha blockers) to the patient causes a reduction in vasoconstriction in the vascular system, thereby—again—providing a reference to the situation intended to be achieved through the ablation procedure.

[0062] In some embodiments, this means injecting an alpha blocker into the patient. Thus, the administration of the alpha blocker can be performed before and / or after the treatment. Subsequently, a second time series of diagnostic images is acquired for the patient under the influence of the just-administered drug. The second state represented by the second time series of the thus acquired diagnostic images indicates the desired outcome of the ablation treatment.

[0063] In some embodiments, a first time series of diagnostic images of the region of interest can be acquired for a patient after treatment without drug therapy.

[0064] First and second dynamic measures are then derived from the first and second time series of the diagnostic images, respectively, and corresponding indices are determined based on the first and second dynamic measures. These indices can then be compared with thresholds to determine whether the ablation treatment has reached its endpoint. Thus, completed ablation can be identified by the absence of a (significant) difference between the second dynamic measure, which indicates inhibition of vasoconstriction by means of an alpha blocker, and the first dynamic measure, which indicates the absence of such inhibition.

[0065] In some embodiments, a first time series of diagnostic images of the region of interest may also be acquired for patients prior to treatment in the absence of medication.

[0066] In this context, the first and second dynamic measures can then be derived from the first and second time series of diagnostic images, respectively, to determine the corresponding indices. These indices can then be evaluated to determine whether the patient is suitable for successful ablation treatment. Typically, if the patient is susceptible to treatment, the deviation between the pre-treatment state without medication and the state with medication will be large, resulting in large indices (such as NRMSE). In some embodiments, the indices thus determined can then be compared with indices derived from clinical studies—such as NRMSE—which indicate pre-treatment indices for patients who have undergone successful renal denervation treatment. This can guide users (such as physicians) in determining, for example, whether a patient under consideration is suitable for denervation treatment.

[0067] For specific cases of renal denervation, the method may specifically include intrarenal administration of an alpha blocker to block the sympathetic nervous system and a second time series of diagnostic images of the region of interest on the kidney before and / or after treatment for the drug-treated patient. Additionally, a first time series of diagnostic images of the region of interest on the kidney may be acquired after treatment. Indicators representing the difference between the first and second states (and thus the progression of the renal denervation process) can then be determined by comparing perfusion time curves obtained as a second dynamic measure for patients under drug treatment with perfusion time curves obtained as a first dynamic measure for patients without drug treatment but after ablation. Denervation is thus considered complete if the change between the first and second dynamic measures (i.e., between the two perfusion time curves) is minimal.

[0068] In some embodiments, the region of interest is subdivided into a first sub-region of interest and a second sub-region of interest, wherein a first time series of a diagnostic image is obtained for the first state and for the first sub-region of interest, and a second time series of a diagnostic image is obtained for the second state and for the first sub-region of interest, and a third time series of a diagnostic image is obtained for the first state and for the second sub-region of interest, and a fourth time series of a diagnostic image is obtained for the second state and for the second sub-region of interest, wherein the processing unit is further adapted to: derive a first dynamic measure from the first time series of the diagnostic image, the first dynamic measure indicating the time-varying performance of the image over the first state through the first sub-region of interest. The contrast agent dynamics of the region; deriving a second dynamic measure from the second time series of the diagnostic image, the second dynamic measure indicating the contrast agent dynamics over time through the first sub-region of interest for the second state; deriving a first dynamic measure from the third time series of the diagnostic image, the first dynamic measure indicating the contrast agent dynamics over time through the second sub-region of interest for the first state; deriving a second dynamic measure from the fourth time series of the diagnostic image, the second dynamic measure indicating the contrast agent dynamics over time through the second sub-region of interest for the second state; and determining at least one index indicating the relative difference between the first state and the second state based on the first dynamic measure and the second dynamic measure.

[0069] In some embodiments, at least one metric indicating the difference between a first state and a second state can be derived by determining dynamic measures at different locations within the region of interest. For this purpose, the region of interest can be subdivided into a first sub-region and a second sub-region. A first time series of diagnostic images can be acquired for the first state and for the first sub-region, and a third time series of diagnostic images can be acquired for the second sub-region in the first state. It should be understood that the first and third time series may correspond to a single time series acquired at a specific time, thereby subdividing a time series of diagnostic images according to the subdivision of the region of interest. That is, the first time series corresponds to the first sub-region, and the third time series corresponds to the second sub-region. In some embodiments, the first state may correspond to a post-treatment state.

[0070] Furthermore, a second time series of diagnostic images can be acquired for the first region in the second state, and a fourth time series of diagnostic images can be acquired for the second sub-region in the second state. Here, it should be understood that the second and fourth time series may also correspond to a time series acquired at a specific time, thereby subdividing a time series of diagnostic images according to the subdivision of the region of interest. That is, the first time series corresponds to the first sub-region, and the fourth time series corresponds to the second sub-region. In some embodiments, the second state may specifically correspond to the patient's pre-treatment state, and the first state may correspond to the patient's post-treatment state.

[0071] Then, the first and third time series of the diagnostic images can be analyzed to derive a first dynamic measure for a first state in the first and second sub-regions, respectively. The second and fourth time series of the diagnostic images can be analyzed to derive a second dynamic measure for a second state in the first and second sub-regions, respectively.

[0072] Therefore, the determined first and second dynamic measures (for the first and second sub-regions) can then be used to determine an indicator indicating the difference between the first and second states. For this purpose, the first dynamic measure derived for the first sub-region and the first dynamic parameter derived for the second sub-region can be used to determine the state 1 indicator. The second dynamic measure for the first and second sub-regions can be used to determine the state 2 indicator. Thus, since the second state corresponds to the pre-treatment state, the state 2 indicator indicates the patient's pre-treatment state. Similarly, since the first state corresponds to the post-treatment state, the state 1 indicator indicates the post-treatment dynamic condition. At least one indicator indicating the difference between the first and second states can then be determined as the difference between the state 2 indicator and the state 1 indicator.

[0073] In some embodiments, the state 2 metric may specifically correspond to the pre-treatment state determined for the first sub-region and the second sub-region using a first dynamic metric for the first sub-region and a first dynamic metric for the second sub-region, respectively. Furthermore, the State 1 indicator can specifically correspond to the post-treatment determined for the first and second sub-regions using the second dynamic measure of the first sub-region and the second dynamic measure of the second sub-region. .

[0074] Subsequently, at least one index indicating the difference between the first state and the second state can be determined specifically according to the following formula:

[0075] .

[0076] Furthermore, in this case, NRSME can be compared with a predefined threshold, and if NRSME drops below the predefined threshold, the process is considered complete.

[0077] In some embodiments, at least one indicator may again be specifically used to provide treatment guidance for renal denervation. In this case, a first dynamic measure for a first subregion may correspond to a time-intensity curve of the renal cortex, which is the first region, and a first dynamic measure for a second subregion may correspond to a time-intensity curve of the renal medulla, which is the second region. The first dynamic measure may indicate a first state, which is a post-treatment state.

[0078] Similarly, the second dynamic measure for the first subregion can correspond to the time-intensity curve of the renal cortex, and the second dynamic measure for the second subregion can correspond to the time-intensity curve of the renal medulla. Since the sympathetic nervous system primarily affects renal perfusion of the cortex, in this case, successful ablation can be determined by considering the changes in the tissue intensity curves of the medulla and renal cortex compared to the baseline RDN (i.e., the measurement performed prior to the ablation procedure).

[0079] In some embodiments, one or more predetermined acquisition settings are used to acquire a first time series and / or a second time series.

[0080] Improving the reproducibility of methods used to provide treatment guidance can be beneficial. One possibility for achieving this is to standardize the intensity used by acquiring first and / or second time series of diagnostic images using multiple predetermined acquisition settings. In some embodiments, these predetermined acquisition settings may specifically relate to contrast agent concentration, contrast agent injection rate, velocity, pressure, etc. By pre-determining these settings, in cases where the diagnostic images of the first and second time series correspond to X-ray perfusion images, the first and second dynamic measures can be standardized, and thus possible perfusion parameters derived therefrom are possible.

[0081] In some embodiments, the input unit is also adapted to receive additional patient data, and wherein the processing unit is adapted to determine the at least one indicator based at least in part on the additional patient data.

[0082] In some embodiments, information derived from the first and second time series and / or the third and fourth time series can be combined with additional currently or previously collected patient data, such as blood pressure, body temperature, blood oxygenation, hematocrit, glomerular filtration rate, creatine levels, drug details (such as dose, concentration, administration), and other patient details (such as age, sex, etc.). Since all these factors influence renal sympathetic activity, this additional information can help improve the accuracy of treatment guidance.

[0083] In some embodiments, the processing unit is further adapted to derive the first dynamic measure for the first state and / or the second dynamic measure for the second state by: for each time point, deriving the value of the first dynamic measure and / or the second dynamic measure, and representing the value of the first dynamic measure and / or the second dynamic measure as a function of time.

[0084] In some embodiments, the first and second dynamic measures correspond to time-related curves of measurements that can be derived from first and second time series of diagnostic images. That is, the first dynamic measure may correspond to a first time-related curve for a first state, such as a time-intensity curve, and the second dynamic measure may correspond to a second time-related curve for a second state, such as a time-intensity curve. These curves can be plotted by deriving specific values ​​as a function of measurement time for each diagnostic image in the time series—or a subset thereof—whereby the measurement time indicates the time point at which the corresponding diagnostic image was acquired. In some embodiments, the specific value may correspond to an intensity value indicating the intensity of contrast agent passing through the vascular system in the region of interest. In other embodiments, the value may correspond to the relative intensity of the contrast-filled vessel compared to the entire region of interest. Other values ​​are conceivable.

[0085] In some embodiments, determining at least one metric includes analyzing one or more of the following for the first state and the second state based on the first dynamic measure and the second dynamic measure, respectively:

[0086] -Time of arrival of the contrast agent

[0087] - Washing rate of contrast agent,

[0088] - Washout rate of contrast agent

[0089] - The peak time of the first dynamic measure and / or the second dynamic measure.

[0090] - The duration of the peak of the first dynamic measure and / or the second dynamic measure.

[0091] - The peak value of the first dynamic measure and / or the second dynamic measure,

[0092] -The average peak value of the first dynamic measure and / or the second dynamic measure, and / or

[0093] - The area under the curve representing the values ​​of the first dynamic measure and / or the second dynamic measure as a function of time.

[0094] In some embodiments, individual parameters may be analyzed to provide treatment guidance. These parameters may specifically relate to time of arrival, infusion rate, elution rate, time to peak, peak duration, peak value, average peak value, and / or area under a curve (such as a time-intensity curve or a perfusion time curve).

[0095] Any one of these parameters, or a linear combination thereof, can be used to assess the completeness of the ablation procedure. Therefore, all these parameters can be measured either once or over different selected time intervals.

[0096] To determine the relative difference between the first state and the second state respectively, i.e., to compare the first state and the second state, the index is determined according to the following formula:

[0097] ,

[0098] in, This corresponds to a value of one of the parameters that can be used to provide disposal guidance in the first state, and This corresponds to the value of the same parameter in the second state.

[0099] It should be understood that although some specific embodiments of the invention have been outlined above, the invention is not limited thereto. In particular, it is possible to use different metrics as indicators of the difference between the first and second states. One possible metric is the normalized root mean square error (NRMSE) as discussed above. Furthermore, cross-correlation or the Kolmogorov-Smirnoff test can be used to compare the relative differences between the first and second states.

[0100] In the most general sense, an index indicating the relative difference between the first state and the second state can be defined as:

[0101] ,

[0102] in, This corresponds to the value of one of the parameters in the first state, and Corresponding to the value of the same parameter in the second state, and a, b, c and d This corresponds to variables that can be selected based on the parameters chosen for determining the indicator. By using this general formula, it is possible to determine indicators such as the following:

[0103] ,

[0104] Furthermore, an index is determined by dividing the difference in the corresponding parameter values ​​by the average parameter values, that is, by using variables... a, b, c and d Select as:

[0105] , , .

[0106] In some embodiments, the output unit includes an indication unit adapted to generate visual, auditory, tactile, and / or audiovisual indications that the ablation treatment has been completed, and to output the indications to the user.

[0107] According to some embodiments, the device is also provided with an indication unit, such as a speaker and / or display and / or vibration device, which allows the device to provide a identifiable output to the user if it is determined that the ablation procedure has been completed. That is, if the device determines that the ablation procedure has been successfully completed by comparing at least one dynamic indicator with a predefined threshold, the indication unit can output an indication confirming this, such as prompting the user to terminate the procedure. This arrangement avoids unnecessaryly long procedure times.

[0108] According to another aspect, a method for providing treatment guidance for ablation procedures includes the following steps: receiving a first time series of diagnostic images of a region of interest (ROI) of a patient's vascular system, the first time series representing a first state; receiving a second time series of diagnostic images of the ROI of the patient's vascular system, the second time series representing a second state; deriving at least one first dynamic measure from the first time series of the diagnostic images, the at least one first dynamic measure indicating contrast agent dynamics over time through the ROI for the first state; deriving at least one second dynamic measure from the second time series of the diagnostic images, the at least one second dynamic measure indicating contrast agent dynamics over time through the ROI for the second state; and determining at least one index indicating a relative difference between the first state and the second state based on the at least one first dynamic measure and the at least one second dynamic measure; and outputting the at least one index to a user.

[0109] The method may be a computer-implemented method. The input may be part of a controller or processing unit. The controller or processing unit may be part of a computer and / or a device.

[0110] In another aspect, a computer program for controlling an apparatus according to the invention is provided, the computer program being adapted, when run by a processing unit, to perform the method steps according to the invention. According to yet another aspect, a computer-readable medium having a computer program stored thereon is provided.

[0111] It should be understood that the claimed apparatus, method, computer program, and computer-readable medium have similar and / or identical preferred embodiments.

[0112] These and other aspects of the invention will become apparent and will be described with reference to the embodiments described below. Attached Figure Description

[0113] In the following figures:

[0114] Figure 1 The diagram schematically illustrates an apparatus for providing treatment guidance for ablation treatment according to a first embodiment.

[0115] Figure 2 A first dynamic measure indicating a first state and a second dynamic measure indicating a second state are shown according to an embodiment.

[0116] Figure 3 An exemplary method for providing treatment guidance for ablation treatment according to a first embodiment is illustrated.

[0117] Figure 4 An exemplary method for providing treatment guidance for ablation treatment according to a second embodiment is illustrated.

[0118] Figure 5 An exemplary method for providing treatment guidance for ablation treatment, modified according to a second embodiment, is illustrated.

[0119] Figure 6A The figure illustrates a set of time series curves obtained for two sub-regions of the region of interest in the first state.

[0120] Figure 6B The figure illustrates a set of time series curves obtained for two sub-regions of the region of interest in the second state. Detailed Implementation

[0121] The illustrations in the accompanying drawings are schematic. In different drawings, similar or identical elements are provided with the same reference numerals.

[0122] Figure 1 An exemplary embodiment of the apparatus 1 for providing treatment guidance for ablation is schematically illustrated. Figure 1 In an exemplary embodiment, an ablation procedure is performed for the purpose of denervating the kidney. That is, an ablation procedure is performed on the wall of the renal artery.

[0123] Device 1 includes an input unit 100, a processing unit 200, a comparison unit 300, and an output unit 400. The output unit 400 includes an indicator unit 401 and is communicatively coupled to a user interface 500, which includes a display unit 501 and an input unit 502.

[0124] Input unit 100 receives a first time series 10 representing a diagnostic image of a first state and a second time series 20 representing a diagnostic image of a second state. According to... Figure 1 In an exemplary embodiment, the first time series 10 of the diagnostic images includes multiple X-ray perfusion images 10a, 10b, and 10c acquired after renal denervation for a region of interest on the patient's kidney. That is, the first state corresponds to a patient-specific post-treatment state.

[0125] The second time series 20 of the diagnostic images includes multiple X-ray perfusion images 20a, 20b, and 20c representing a second reference state for the same region of interest on the patient's kidney. For the purpose of representing an appropriate reference, the multiple X-ray perfusion images 20a, 20b, and 20c may be obtained from clinical studies or may correspond to the time series 20 of diagnostic images already acquired for a drug-induced reference state. This drug-induced reference state can be achieved by administering an alpha blocker (such as toprazole or phentolamine) into the patient's kidney. The alpha blocker causes the blocking of alpha receptors that induce vasoconstriction, resulting in sympathetic nerve block in the renal artery, thereby causing the renal artery to enter a state of reduced microvascular impedance. Following administration, the second time series 20 of the diagnostic images can then be acquired.

[0126] In some embodiments, the reference state may also correspond to a pre-treatment state determined for a specific patient. That is, in some embodiments, the second time series 20 of the diagnostic images may have already been acquired for a specific patient before treatment. This allows the patient's initial state to be derived prior to the ablation treatment, and thus also allows the progress of the ablation treatment to be determined based on other factors, such as during or after the treatment.

[0127] After being received at input unit 100, the first time series 10 and the second time series 20 are provided to processing unit 200. Processing unit 200 derives a first dynamic measure from the first time series 10 of the diagnostic image, indicating the contrast agent dynamics over time through the region of interest in a first post-treatment state, and derives a second dynamic measure from the second time series 20 of the diagnostic image, indicating the contrast agent dynamics over time through the region of interest in a second reference state.

[0128] According to Figure 1 In a specific embodiment, the region of interest is on the kidney. Figure 2 Schematic representation based on Figure 1The apparatus 1 of the embodiment derives a first dynamic measure and a second dynamic measure. Thus, the first dynamic measure corresponds to the time-intensity curve 31 for the renal artery after renal denervation (i.e., in the post-treatment state). The second dynamic measure corresponds to the time-intensity curve 32 for the renal artery in a reference state (i.e., a reference for successful renal denervation treatment).

[0129] Then, the processor 200 uses a first dynamic metric and a second dynamic metric to determine at least one indicator that indicates the relative difference between the time-intensity curve 31 representing the first state and the time-intensity curve 32 representing the second state. This indicator indicates the progress (and success) of the ablation treatment.

[0130] According to Figure 1 In an exemplary embodiment, this means that the processor 200 determines the normalized root mean square error (NRMSE) between the perfusion in the first post-treatment state and the perfusion in the second reference state. Therefore, the processor 200 derives a quantitative measure of the similarity between the two perfusion curves according to the following formula:

[0131] ,

[0132] in, Corresponding to the perfusion curve in the region of interest for the first state, and The perfusion curve corresponds to the region of interest for the second state, where i = 1, ..., n. This corresponds to the maximum value of the perfusion curve within the region of interest.

[0133] Processing unit 200 determines the NRMSE metric and provides it to comparison unit 300. Comparison unit 300 derives a predefined threshold for the metric and compares the received metric with the derived threshold. Figure 1 In an exemplary embodiment, the comparison unit 300 includes a memory 301, in which a threshold is stored, and the threshold is derived by reading the threshold from the memory 301. Thus, if a comparison with the threshold shows an index lower than the predefined threshold, particularly lower than 0.1, more preferably lower than 0.05, the comparison unit 300 determines that renal denervation has been (successfully) completed. Figure 1 In an exemplary embodiment, the threshold indicating completed kidney denervation is indeed close to 0.0, because the drug-induced reference state corresponds to successful ablation.

[0134] Then, comparison unit 300 is configured to provide an indicator (optionally along with the comparison result) to output unit 400. Output unit 400 is configured to output the indicator to the user. Figure 1In a particular embodiment, this means that the output unit 400 provides indicators to a user interface 500, which includes a display unit 501 and an input unit 502. The display unit 501 may be configured to generate a graphical representation of the indicators and optionally display them to the user along with at least one diagnostic image of the region of interest.

[0135] According to Figure 1 In a particular embodiment, the output unit 400 includes an indication unit 401. If a comparison result is provided to the output unit 400 and if the comparison result indicates that renal denervation has been completed, the indication unit 401 may generate an (additional) indication that renal denervation has been completed and provide said indication to the user. In an exemplary embodiment, the indication is an auditory indication, and the indication unit 401 outputs the auditory indication. However, it should be understood that the indication may also be a visual, tactile, or audiovisual indication, and the indication unit 401 may output the indication directly or through the user interface 500 (particularly the display unit 501).

[0136] Upon receiving a completion instruction, the user (usually a physician) may be prompted to terminate the renal denervation procedure, or, if the procedure has already been terminated, receive confirmation of the procedure's success.

[0137] Figure 3 An exemplary embodiment of a method 1000 for providing treatment guidance for ablation procedures (particularly renal denervation procedures) according to a first embodiment is illustrated. According to this first embodiment, the method 1000 for providing treatment guidance is used to identify potential responders to renal denervation procedures, such as those who can be identified by... Figure 1 The apparatus 1 is implemented by way of example.

[0138] The method begins at step S101, wherein a first time series 10 of a diagnostic image is received, whereby the first time series 10 of the diagnostic image represents a first state. Based on... Figure 3 In a specific embodiment (wherein method 1000 is used to identify potential responders to treatment), the first state corresponds to the pre-treatment state of the patient to be considered (i.e., a patient suspected of sympathetic overdrive).

[0139] In step S102, a second time series 20 representing a diagnostic image of a second state is received. According to... Figure 3 In this embodiment, the second state corresponds to the reference state, representing a non-sympathetic overdrive state. According to... Figure 3 In a specific embodiment, the second time series 20 of the diagnostic images is thus obtained from clinical studies and exported from a storage device for further evaluation. Although according to Figure 3In this embodiment, the reference state is derived from clinical studies; however, it is understood that, alternatively or additionally, the reference state can also be obtained by administering an alpha blocker to the patient's kidney and subsequently performing actual X-ray perfusion measurements on the patient during drug treatment. Other methods for obtaining a second time series 20 representing the reference state may also be considered. The defining characteristic of the reference state is that it represents a state achievable with successful renal denervation.

[0140] In step S201, a first dynamic measure is derived from the first time series 10 of the diagnostic image. The first dynamic measure indicates the contrast agent dynamics over time through the region of interest in the first pretreatment state. Based on... Figure 3 In a specific embodiment, the first dynamic measure corresponds to the time-intensity curve of the renal vascular system and / or renal artery for a specific patient suspected of sympathetic overdrive and therefore considered for renal denervation.

[0141] In step S202, a second dynamic measure is derived from the second time series 20 of the diagnostic image. This second dynamic measure indicates the contrast agent dynamics over time through the region of interest in a second reference state. This second dynamic measure also corresponds to a time-intensity curve for the renal vascular system and / or renal arteries, which is derived from clinical studies and thus represents a non-sympathetic overdrive condition.

[0142] In step S203, at least one index indicating the relative difference between the first state and the second state is determined. Based on... Figure 3 In an exemplary embodiment, the normalized root mean square error (NRMSE) between the first and second time-intensity curves is determined in step S203. Then, in step S501, the NRMSE indicator is provided for output (specifically, presented) to the user. Based on this indicator, the user can then determine whether the patient is a potential responder to renal denervation treatment. Optionally, the display of the indicator in step S501 may thus be accompanied by the presentation of treatment recommendations. In this case, the device may have already optionally determined whether the patient is a potential responder based on a comparison of the determined indicator with a predetermined threshold, and may also output this indication to the user in addition to the indicator.

[0143] Figure 4 An exemplary embodiment of a method 2000 for providing treatment guidance for ablation procedures (particularly renal denervation) according to a second embodiment is illustrated schematically. According to this second embodiment, the method 2000 for providing treatment guidance is used to monitor the progress of the treatment during an ablation procedure, particularly for the purpose of renal denervation. The method 2000 for monitoring treatment progress can also be based on... Figure 1 The device 1 is implemented.

[0144] Steps S101 and S102 are in accordance with the provisions of Figure 3 The procedure is performed in a manner similar to that explained in the first embodiment. That is, in step S101, a first time series 10 of the diagnostic image is received, whereby the first time series 10 of the diagnostic image represents a first state. According to... Figure 4 In an exemplary embodiment, the first state corresponds to the patient's current state during the ongoing ablation procedure. That is, when the method 2000 is first initialized, the first time series 10 of the diagnostic images may specifically correspond to the patient's pre-treatment state, i.e., the patient's state before the ablation procedure to be monitored.

[0145] Furthermore, in step S102, a second time series 20 representing the second state of the diagnostic image is received. Thus, it is possible, as already stated regarding... Figure 3 The second time series 20 of the diagnostic images is obtained as described in the first embodiment. Furthermore, prior to the start of the ablation procedure, as per [the previous sentence]... Figure 3 Steps S201, S202, and S203 are performed as described. That is, a first dynamic measure is determined based on the first time series 10, and a second dynamic measure is determined based on the second time series 20. The first and second dynamic measures are used to determine at least one indicator indicating the relative difference between the first and second states. In step S501, this indicator may optionally be presented to the user along with a treatment recommendation.

[0146] In step S601, the ablation process then begins. After some time has elapsed, steps S101, S201, S203, and S501 are repeated. The repeated steps... Figure 4 The middle part is marked with a dashed line.

[0147] That is, in step S101, an additional first time series 10 of diagnostic images representing the patient's first current state is obtained. During repetitions some time after the start of the ablation treatment, if the patient responds to the ablation treatment, the patient's current state should have changed. Therefore, the indices calculated in step S203 also change. The change in indices can be presented in step S501.

[0148] Optionally, the method 2000 for providing ablation monitoring may further include steps S301 to S402. In step S301, a predefined threshold for an indicator is derived. Subsequently, in step S302, the indicator derived in step S203 for the patient's current state is compared with the predefined threshold, and a corresponding comparison result is generated. In step S401, the comparison result may be evaluated by a corresponding processor. In some embodiments, the evaluation may be based on... Figure 1The processing unit 200 and / or comparison unit 300 and / or output unit 400 of the device 1 perform the operation. In some embodiments, a dedicated evaluation unit may be provided for this purpose. Based on the evaluation of the comparison results, it can be determined whether the ablation treatment (i.e., renal denervation treatment) has been completed. This determination may be based specifically on whether the comparison results indicate that the index calculated in step S203 is below a predetermined threshold. If this is the case, the treatment is considered complete. If not, the treatment continues.

[0149] In step S402, a corresponding indication of the evaluation of the comparison results is generated and optionally displayed to the user in step S501. In some embodiments, additional indications may be output to the user, such as prompting the user to stop the treatment when it is considered complete. In some embodiments, the indication may also be used to signal the treatment device used for ablation treatment to automatically terminate the treatment when it is considered complete.

[0150] According to Figure 4 In an exemplary embodiment, steps S101, S201, S203, and S301 to S601 are repeated until it is determined that the ablation procedure has been completed and / or the patient does not respond to the ablation procedure. This allows for frequent monitoring of the procedure's progress.

[0151] Figure 5 The diagram illustrates the following: Figure 4 Method 2000 is a modification of Method 2000'. That is, Method 2000' is also used to perform treatment monitoring during ablation treatment. Typically, it is used in accordance with... Figure 4 Monitoring is performed in a similar manner to the embodiments described above. To avoid repetition, only monitoring based on... Figure 4 Implementation examples and according to Figure 5 The differences between the modifications.

[0152] In steps S101' and S102', a first time series 10 representing a first state and a second time series 20 representing a second state of diagnostic images are obtained again, respectively, whereby both the first and second time series are acquired from patients suspected of sympathetic overdrive. Thus, the second time series 20 representing a second reference state for the patient is obtained before the ablation procedure, and the first time series 10 representing a first current state is obtained some time after the ablation procedure has begun. That is, the first time series 10 represents the patient's state during the ablation procedure, while the second time series 20 represents the patient's state before the ablation procedure, whereby the state before the ablation procedure is considered the reference state.

[0153] In steps S201 and S202, the corresponding first dynamic metric value and second dynamic metric value are obtained and used for the index calculation in step S203, as described above. Figure 4 As described. In step S501, the determined index is displayed in a known manner. This process is repeated, as per [the previous sentence]. Figure 4 As described. Specifically, as previously stated, the performance indicators are compared with predetermined thresholds and corresponding indications are output to track the progress of the treatment. Therefore, it should be mentioned that, due to the... Figure 5 The indicators are different; they are patient-specific indicators that show the relative difference between the patient's pre-treatment state and their current (during treatment) state. Therefore, the threshold derived in step S301 is different from... Figure 4 The thresholds used are also different from those used in the previous section. That is, a specific threshold must be selected for each metric to determine when the treatment is complete.

[0154] In some embodiments, treatment monitoring can also be performed using drug administration (particularly alpha blocker administration) to obtain a reference. That is, in such embodiments, the user (i.e., the physician) can—based on experience or based on a specific time frame—consider that the ablation treatment has been completed. After (considering) the ablation treatment is complete, the physician can then optionally administer an alpha blocker into the patient's kidney, and can then collect a second time series 10 of the patient's diagnostic images (such as an X-ray perfusion time series) as a reference state. Based on this second time series 10, a second dynamic measure can be determined in a known manner. Furthermore, in the absence of any alpha blocker, a first time series 10 of the patient's diagnostic images can be obtained after (considering) the ablation treatment is complete. Based on this first time series 10, a first dynamic measure can be derived. The first and second dynamic measures can then be used to calculate an index in a known manner. If the index indicates a minimal or non-existent relative difference between the first and second states, the completion of the ablation treatment can be assumed.

[0155] In some modifications to the embodiments defined above, additional measurement data, particularly additional parameters related to renal denervation, may be considered to determine appropriate reference status and / or a more accurate assessment of the progress of treatment. In this context, particularly useful measurement data may include, for example, measurements such as blood pressure (systolic, diastolic, etc., obtained at different locations on the patient's body), body temperature, blood oxygen saturation, red blood cell count, glomerular filtration rate, creatinine levels, drug details (such as dosage, concentration, administration), or other patient details (such as age, sex, etc.). All these parameters allow conclusions to be drawn regarding the achieved renal sympathetic activity—remaining, decreased, increased, specific renal filtration, perfusion in renal regions, and / or left and / or right renal activity—thereby increasing the accuracy of the determination and / or assessment of reference status.

[0156] Figure 6A and Figure 6BTwo sets of time-intensity curves, used as corresponding dynamic measures, are schematically illustrated according to another embodiment. In accordance with... Figure 6A and 6B In this embodiment, ablation is performed for the purpose of kidney denervation. Thus, the region of interest corresponds to the kidney. Consequently, the region of interest has been subdivided into a first sub-region of interest and a second sub-region of interest. According to... Figure 6A and 6B In a specific embodiment, the first sub-region of interest corresponds to the renal cortex, and the second sub-region of interest corresponds to the renal medulla.

[0157] Figure 6A This illustrates the time-intensity curve 33 for the first sub-region (i.e., the renal cortex), where the time-intensity curve 33 has been presented as shown in the figure. Figure 1 The method of description is derived from the first time series 10 obtained for the first sub-region of interest in the first state. Furthermore, Figure 6A The figure illustrates time-intensity curve 34 for the second sub-region (i.e., the renal medulla), which has been derived from a third time series obtained for the second sub-region of interest in the first state. Based on... Figure 6A In a specific embodiment, the first state here specifically corresponds to the post-treatment state, that is, the state of the renal cortex and renal medulla after renal denervation treatment.

[0158] Figure 6B The illustration shows time-intensity curves 35 for a first sub-region and 36 for a second sub-region. Time-intensity curve 35 is derived from a second time series 20 obtained for the first sub-region of interest in the second state, and time-intensity curve 36 is derived from a fourth time series of a diagnostic image obtained for the second sub-region of interest in the second state. Based on... Figure 6B In a specific embodiment, the second state corresponds to the pre-treatment state, that is, the state of the renal cortex and renal medulla before the renal denervation treatment.

[0159] According to Figure 6A and 6B In a specific embodiment, indices are determined by comparing time-intensity curves 33 and 34 for the first state with time-intensity curves 35 and 36 for the second state. Since the sympathetic nervous system primarily affects renal perfusion in the cortex, successful ablation can be determined by changes in the time-intensity curves of the medulla and renal cortex compared to baseline measurements prior to the ablation procedure for renal denervation, for example, by determining the normalized root mean square error or by considering changes in specific parameters describing the effects of renal denervation on the renal cortex and medulla.

[0160] In this case, a possible indicator of the relative difference between the first and second states could be determined, for example:

[0161] ,

[0162] in, These are the parameters of the first sub-region in the first state (such as the values ​​representing the time intensity curve). These are the parameters of the second sub-region in the first state. It is the parameter of the first sub-region in the second state, and It is the parameter of the second sub-region in the second state.

[0163] Another possible metric that can be used in this case is a comparison of the normalized root mean square error determined for the two regions relative to the baseline RDN of the first and second states, respectively, according to the following formula:

[0164] ,

[0165] Therefore, the NRSME for the two states can be calculated using the following formula:

[0166] ,

[0167] in, The time intensity curves of the first time series corresponding to the two states, and The time intensity curves corresponding to the second time series under the two states. Thus, i = 1,…,n, and This corresponds to the maximum value of the derivative time-intensity curve.

[0168] Although diagnostic images have been acquired using X-ray perfusion angiography for tracking contrast agents in the above embodiments, it should be understood that other imaging modalities and other fluids can also be used, provided that both the imaging modality and the fluid are selected to enable the use of the imaging modality to track fluids through the vascular system.

[0169] Furthermore, it should be understood that although X-ray imaging has been performed with single energy, dual-energy X-ray measurements can also be used to quantify dynamic measurements because these measurements allow for more accurate quantification of iodine concentration in the contrast agent. Additionally, background subtraction to remove overlapping and interfering anatomical structures can be achieved.

[0170] Furthermore, although the treatment guidance described in the above embodiments pertains to renal denervation, it should be understood that the treatment guidance process can also be adapted to other ablation-based treatments that rely on changes in fluid flow dynamics due to the ablation process.

[0171] Although the normalized root mean square error (NRMSE) has been used as at least one dynamic metric in the above embodiments, it should be understood that other metrics can also be used, as long as they indicate the relationship between the first dynamic metric and the second dynamic metric.

[0172] Furthermore, although in the above embodiments the device itself derives the first and second dynamic measures from the first and second time series, it should be understood that the term "derive" is to be interpreted broadly and may also cover the import of the first dynamic measure and / or the second dynamic measure from other measurement modalities to determine dynamic indices.

[0173] Those skilled in the art, through studying the accompanying drawings, the disclosure, and the claims, can understand and implement other variations of the disclosed embodiments when practicing the claimed invention.

[0174] In the claims, the word "comprising" does not exclude other elements or steps, and the words "a" or "an" do not exclude a plurality.

[0175] A single unit or device may perform the functions of several items recited in the claims. Although some measures are recited in different dependent claims, this does not mean that combinations of these measures cannot be used advantageously.

[0176] Processes such as deriving a first dynamic measurement value and / or a second dynamic measurement value, determining at least one indicator indicating the relative difference between a first state and a second state, comparing at least one indicator with a predefined threshold, and generating an indication that ablation treatment has been completed, which are performed by one or more units or devices, can be performed by any other number of units or devices. These processes according to the invention can therefore be implemented as program code modules of a computer program and / or as dedicated hardware.

[0177] Computer programs can be stored / distributed on suitable media, such as optical storage media or solid-state media provided together with or as part of other hardware, but computer programs can also be distributed in other forms, such as via the Internet or other wired or wireless telecommunications systems.

[0178] Any reference numerals in the claims should not be construed as limiting the scope.

[0179] This invention relates to an apparatus for providing treatment guidance for ablation procedures, comprising: an input unit adapted to receive a first time series of diagnostic images of a region of interest (ROI) of a patient's vascular system and a second time series of diagnostic images of the ROI of the patient's vascular system, the first time series representing a first state and the second time series representing a second state; a processing unit adapted to derive from the first time series of the diagnostic images a first dynamic measure indicating the dynamics of contrast agent passing through the ROI over time for the first state, derive from the second time series of the diagnostic images a second dynamic measure indicating the dynamics of contrast agent passing through the ROI over time for the second state, and determine at least one index indicating a relative difference between the first state and the second state based on the first dynamic measure and the second dynamic measure; and an output unit adapted to output the at least one index to a user.

Claims

1. An apparatus for providing treatment guidance for ablation treatment, comprising: Input unit (100), adapted to receive: A first time series (10) of diagnostic images of the region of interest of the patient's vascular system, the first time series representing a first state, wherein the first state corresponds to a post-treatment state specific to the patient; and A second time series (20) of diagnostic images of the region of interest of the patient's vascular system, the second time series representing a second state, wherein the second state includes a reference state for successful renal denervation achieved by administering a drug to block α-receptor stimulation; Processing unit (200), which is adapted to: A first dynamic measure is derived from the first time series (10) of the diagnostic images, the first dynamic measure indicating the contrast agent dynamics over time through the region of interest for the first state; A second dynamic measure is derived from the second time series (20) of the diagnostic images, the second dynamic measure indicating the contrast agent dynamics over time through the region of interest for the second state; and Based on the first dynamic measure and the second dynamic measure, at least one indicator is determined to indicate the relative difference between the first state and the second state; and An output unit (400) is adapted to output the at least one indicator to a user.

2. The apparatus according to claim 1, wherein, The first time series of the diagnostic images and / or the second time series of the diagnostic images were acquired using X-ray angiography.

3. The apparatus according to claim 1, wherein, The ablation procedure corresponds to renal denervation (RDN) procedure.

4. The apparatus according to claim 1, wherein, The first time series of the diagnostic images and / or the second time series of the diagnostic images were acquired using X-ray angiography, and wherein the ablation treatment corresponds to a renal denervation (RDN) treatment.

5. The apparatus according to any one of claims 1-4, further comprising a comparison unit (300), wherein, The comparison unit is adapted to determine that the ablation treatment has been completed by comparing the at least one indicator with a predefined threshold.

6. The apparatus according to any one of claims 1-4, wherein, The region of interest is subdivided into a first sub-region of interest and a second sub-region of interest, wherein, for the first state, a first time series of the diagnostic image is obtained for the first sub-region of interest, and for the second state, a second time series of the diagnostic image is obtained for the first sub-region of interest; and The processing unit is further adapted to: obtain a third time series of diagnostic images for the second sub-region of interest in relation to the first state, and obtain a fourth time series of diagnostic images for the second sub-region of interest in relation to the second state, wherein the processing unit is further adapted to: A first dynamic measure is derived from the first time series of the diagnostic images, the first dynamic measure indicating the contrast agent dynamics over time through the first sub-region of interest for the first state. A second dynamic measure is derived from the second time series of the diagnostic images, the second dynamic measure indicating the contrast agent dynamics over time through the first sub-region of interest for the second state; A first dynamic measure is derived from the third time series of the diagnostic images, the first dynamic measure indicating the contrast agent dynamics over time through the second sub-region of interest for the first state. A second dynamic measure is derived from the fourth time series of the diagnostic images, the second dynamic measure indicating the contrast agent dynamics over time through the second sub-region of interest for the second state; and The at least one indicator that indicates the relative difference between the first state and the second state is determined based on the first dynamic measure and the second dynamic measure.

7. The apparatus according to any one of claims 1-4, wherein, The first time series and / or the second time series were acquired using one or more predetermined acquisition settings.

8. The apparatus according to any one of claims 1-4, wherein, The input unit (100) is also adapted to receive additional patient data, and wherein the processing unit (200) is adapted to determine the at least one indicator based at least in part on the additional patient data.

9. The apparatus according to any one of claims 1-4, wherein the processing unit (200) is further adapted to derive the first dynamic measure based on the first time series of the diagnostic images and / or derive the second dynamic measure based on the second time series of the diagnostic images by: For each time point, derive the values ​​of the first dynamic metric and / or the second dynamic metric; and The values ​​of the first dynamic measure and / or the second dynamic measure are expressed as functions of time.

10. The apparatus according to any one of claims 1-4, wherein, The determination of the at least one indicator includes: analyzing one or more of the following based on the first dynamic measure and the second dynamic measure for the first state and the second state, respectively: - The arrival time of the contrast agent; - Washing rate of contrast agent, - Washout rate of contrast agent - The peak time of the first dynamic measure and / or the second dynamic measure. - The duration of the peak of the first dynamic measure and / or the second dynamic measure. - The peak value of the first dynamic measure and / or the second dynamic measure, -The average peak value of the first dynamic measure and / or the second dynamic measure, and / or - The area under the curve representing the values ​​of the first dynamic measure and / or the second dynamic measure as a function of time.

11. The apparatus according to any one of claims 1-4, wherein, The output unit (400) includes an indicator unit (401), the indicator unit being adapted to: Generate visual, auditory, tactile, and / or audiovisual indications that the ablation treatment has been completed; and The instruction is output to the user.

12. A method for providing treatment guidance for ablation treatment, comprising the following steps: (S101) Receive a first time series (10) of diagnostic images of the region of interest of the patient's vascular system, the first time series representing a first state, wherein the first state corresponds to a post-treatment state specific to the patient; (S102) Receive a second time series (20) of diagnostic images of the region of interest of the patient's vascular system, the second time series representing a second state, wherein the second state includes a reference state for successful renal denervation achieved by administering a drug to the patient to block α-receptor stimulation; (S201) Derive at least one first dynamic measure based on the first time series (10) of the diagnostic image, the at least one first dynamic measure indicating the contrast agent dynamics over time through the region of interest for the first state; (S202) Derive at least one second dynamic measure based on the second time series (20) of the diagnostic image, the at least one second dynamic measure indicating the contrast agent dynamics over time through the region of interest for the second state; (S203) Determine at least one index indicating the relative difference between the first state and the second state based on the at least one first dynamic measure and the at least one second dynamic measure; and (S501) Output the at least one indicator to the user.

13. A computer program product comprising a computer program for controlling an apparatus according to any one of claims 1 to 11, the computer program being adapted to perform the method according to claim 12 when run by a processing unit.

14. A computer-readable medium having stored thereon a computer program for controlling an apparatus according to any one of claims 1 to 11, the computer program being adapted to perform the method according to claim 12 when run by a processing unit.

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