Myocardial spectrometer probe and method for monitoring myocardium - Patent Application 20070122999

Abstract

The present invention relates to a myocardial spectrometer probe comprising at least two separate light guides (120A, 120B) insertable into tissue, wherein a first light guide (120A, 120B) is arranged to deliver light and a second light guide (120A, 120B) is arranged to collect light, and wherein the first light guide (120A, 120B) and the second light guide (120A, 120B) are arranged separately from each other.

Description

[Technical Field]

[0001] The present invention relates generally to the field of medical technology, and more particularly to a solution for monitoring the myocardium. [Background technology]

[0002] Open-heart surgery involves an incision in the chest. This surgery is performed on the large veins or aorta, which establish the inflow and outflow of blood to the heart, respectively, or on the heart itself, valves, arteries, shunts, muscle blockages, or other obstructions affecting the heart's normal function. In most cases, the pumping action of the heart must be stopped to allow surgery to be performed. When the heart is stopped, coronary blood flow to the myocardium must be interrupted, which inevitably causes ischemia in the heart. Currently, there are no means to measure cardiac oxygen availability and metabolism during aortic clamping. Instead, experience and general knowledge from previous practice are used. While this is often sufficient, it is not always the case. Approximately 20% of hearts fail after surgery due to intraoperative ischemia. This failure is caused by myocardial stunning, a reversible decrease in cardiac contractile function after reperfusion, and is not explained by tissue damage, reduced blood flow, or myocardial infarction. However, it may also result from irreversible myocardial damage caused by ischemia.

[0003] When operating on the coronary arteries of the heart, it is possible to perform the procedure while the heart is beating, i.e., without the aid of a cardiopulmonary bypass machine circuit. This is called off-pump surgery. In this procedure, the heart is displaced to properly establish the surgical field. In these cases, the heart becomes ischemic. Due to cardiac displacement, electrocardiogram measurements cannot reliably detect myocardial ischemia until the heart is repositioned. Currently, there is no direct and reliable method for measuring cardiac oxygenation during distal anastomosis in off-pump surgery to monitor cardiac ischemia.

[0004] Nearly all oxygen in the heart is consumed in the mitochondria by an enzyme called cytochrome c oxidase. This is the final enzyme in the electron transport chain that facilitates the production of ATP, the final fuel used by cells. Cells require a carrier molecule to deliver oxygen to cytochrome c oxidase. The carrier molecule in blood is hemoglobin, which delivers oxygen from long distances to cells and ultimately releases it to tissues with low oxygen tension. Within cells, myoglobin acts as a carrier, delivering oxygen across the cell to the mitochondria.

[0005] Reliable real-time measurement of cardiac oxygen availability and / or metabolic status would allow operating room staff to perform various maneuvers during surgery to improve cardiac oxygen delivery, reduce oxygen metabolism, and ultimately reduce the total ischemic load of the heart. Measurement of oxygen delivery via hemoglobin and myoglobin, as well as cytochrome c oxidase, would improve the safety of cardiac surgery and potentially improve the care of cardiac patients in general and reduce treatment costs.

[0006] When assessing cardiac oxygenation, it would clearly be beneficial to measure the reduction state and oxygen concentration of several other proteins with heme prosthetic groups, such as hemoglobin, myoglobin, and other heme proteins. Additionally, the ability to measure the concentrations of other molecules in the oxidative phosphorylation chain within mitochondria, including but not limited to cytochromes A, B, and C, which may be elevated in analyses of myocardial metabolism where the reduction state of enzymes is important, would be beneficial. Often, mitochondria exhibit damage very early during cellular stress, and the concentrations of enzymes that respond to mitochondrial stress are of interest. Because mitochondria generate large amounts of reactive oxygen species (ROS), enzymes involved in ROS catalysis, such as catalase, superoxide dismutase, and peroxidase, are also of interest.

[0007] Measuring molecular concentrations in the myocardium is important not only during surgery but also after surgery. During post-operative intensive care, patients often experience the period when left ventricular function is at its lowest. For example, U.S. Patent No. 5,629,999 discloses an oxygenation measurement system in which measurements are made by inserting a catheter device that contacts the tissue wall of interest. At least one drawback of the disclosed solution is that transcatheter measurements through the tissue wall are not very accurate or specific.

[0008] Therefore, there is a need to develop additional solutions applicable at least to open-heart surgery that accurately monitor intramyocardial molecular concentrations during open-heart surgery and, if possible, continue monitoring after the procedure. However, monitoring cardiac molecular concentrations would also be beneficial during any treatment where cardiac monitoring could provide additional knowledge to the patient's caregiver.

[0009] The following presents a simplified summary in order to provide a basic understanding of some aspects of various invention embodiments. The summary is not an extensive overview of the invention. It is not intended to identify key or critical elements of the invention, nor to delineate the scope of the invention. The following summary merely presents some concepts of the invention in a simplified form as a prelude to a more detailed description of example embodiments of the invention. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] US Patent Application Publication No. 2015 / 0282747(A1) Summary of the Invention [Problem to be solved by the invention]

[0011] SUMMARY OF THE INVENTION It is an object of the present invention to provide a medical device for monitoring tissue.

[0012] Another object of the present invention is to provide a medical device that can be used at least in part to provide information regarding the concentration of molecules in tissue and / or their oxygenation / oxidation ratios.

[0013] It is a further object of the present invention to provide a method for monitoring tissue.

[0014] The object of the invention is achieved by the apparatus and method defined by the respective independent claims. [Means for solving the problem]

[0015] According to a first aspect, a myocardial spectrometer probe is provided, the myocardial spectrometer comprising at least two separate light guides insertable into tissue, a first light guide arranged to deliver light and a second light guide arranged to collect light, the first light guide and the second light guide being at least partially separate from one another.

[0016] The first light guide and the second light guide can be positioned separately from one another such that, upon insertion into the tissue of interest, at least a portion of the intact tissue separates the first light guide from the second light guide.

[0017] By attaching the first light guide and the second light guide to a jig, the first light guide and the second light guide can be positioned separately from each other.

[0018] The tip of the light guide may be angled at 45 to 90 degrees, preferably 70 to 90 degrees, relative to the longitudinal axis of the light guide.

[0019] The first light guide and the second light guide may be realized by one of a single optical fiber, an optical fiber bundle, or a light tube.

[0020] For example, at least a portion of at least one of the light guides insertable into tissue may be coated with a steel tube.

[0021] The myocardial spectrometer probe may further include a pacing lead disposed to extend along at least one of the light guides, and the pacing lead may be electrically connected to a steel tube that coats at least a portion of at least one of the light guides.

[0022] For example, a first pacing lead may be electrically connected to the steel tube of the first light guide, and a second pacing lead may be electrically connected to the steel tube of the second light guide to form a bipolar pacing configuration including an anode and a cathode. The myocardial spectrometer probe may further include a stopper device for adjusting at least one of the insertion depth of at least one of the light guides within the tissue and the insertion angle of at least one of the light guides within the tissue. The stopper device may include, for example, a receiving portion for receiving at least the light guide and a light cover portion for at least partially preventing ambient light from entering the tissue. The receiving portion and the light cover portion of the stopper device may both be removably attached. For example, a fixation wire may be disposed to extend through the stopper device, with an end of the fixation wire being positioned to be anchored in the tissue to enable tensioning of the light guide by a fixed position of the fixation wire. The fixation wire may be a pacing lead. The fixation may be achieved by one of an inflatable balloon device, a fixation configuration including a second wire forming an anchor for the fixation wire, or an anchor device.

[0023] The myocardial spectrometer probe may further include an insertion assist device for penetrating the surface of tissue to insert the light guide into the tissue. The insertion assist device may include at least one tubular member having a light guide disposed therein. The light guide may be slidably disposed relative to the tubular member of the insertion assist device. The insertion assist device may also be configured to function as an electrode of a pacing lead coupled to the insertion assist device. An end of the tubular member of the insertion assist device facing the tissue may have a sharpened shape. The insertion assist device may be manufactured from one of stainless steel, ceramic, and composite materials.

[0024] Additionally, at least one of the light cover portion, the inflatable balloon device, the fixation device, and the fixation wire may be made of a biodegradable material.

[0025] The myocardial spectrometer probe may further comprise means for providing measurement data representative of tissue temperature.

[0026] The myocardial spectrometer probe may further include a removably attachable protective cover for protecting the first light guide and the second light guide.

[0027] The protective cover may be configured to serve as a calibration target for calibrating a measurement system that applies the myocardial spectrometer probe.

[0028] Myocardial spectrometer probes can be used, for example, to monitor tissue molecular concentrations in real time, for example, during and after open-heart surgery.

[0029] Methods for monitoring molecular concentrations in tissues of interest by spectroscopy typically include: - providing at least two separate light guides insertable into tissue, wherein a first light guide is positioned to deliver light and a second light guide is positioned to collect light; - inserting the light guide into the tissue of interest such that at least a portion of the intact tissue separates the first light guide from the second light guide, and such that light delivered by the first light guide passes through said intact tissue and reaches the second light guide; repeatedly delivering light from a first light guide and collecting the light delivered from the first light guide with a second light guide to form a plurality of signals corresponding to the collected light; - monitoring the signal thus obtained; Includes:

[0030] As used herein, the term "several" refers to any positive integer starting from 1 and up to, for example, 1, 2, or 3.

[0031] As used herein, the term "plurality" refers to any positive integer starting from 2 and up to, for example, 2, 3, or 4.

[0032] The various exemplary and non-limiting embodiments of the present invention, both as to structure and method of operation, together with additional objects and advantages thereof, will best be understood from the following description of specific exemplary and non-limiting embodiments, when read in conjunction with the accompanying drawings.

[0033] The verbs "comprise" and "include" are used in this specification as open limitations which neither exclude nor require the presence of features not recited. Features recited in dependent claims are mutually freely combinable unless expressly stated otherwise. Furthermore, it is to be understood that throughout this specification the use of "a" or "an", i.e. the singular, does not exclude the plural.

[0034] Embodiments are illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings. [Brief explanation of the drawings]

[0035] [Figure 1]1 is a schematic diagram of a monitoring system to which the present invention is applied; [Figure 2] 1 is a schematic diagram of a first example of a myocardial spectrometer probe, according to one embodiment of the present invention. [Figure 3] FIG. 2 is a schematic diagram of a second example of a myocardial spectrometer probe in a first state, according to an embodiment of the present invention. [Figure 4] FIG. 2 is a schematic diagram of a second example myocardial spectrometer probe in a second state, according to an embodiment of the present invention. [Figure 5] FIG. 10 is a schematic diagram of a third example myocardial spectrometer probe, according to an embodiment of the present invention. [Figure 6] FIG. 10 is a schematic diagram of a fourth example myocardial spectrometer probe, according to another embodiment of the present invention. [Figure 7A] 7 is a schematic diagram of a further example of a myocardial spectrometer probe according to another embodiment of the present invention, particularly the embodiment of FIG. 6. [Figure 7B] 7 is a schematic diagram of a further example of a myocardial spectrometer probe according to another embodiment of the present invention, particularly the embodiment of FIG. 6. [Figure 8] FIG. 10 is a schematic diagram of a further example of a myocardial spectrometer probe, according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0036] The specific examples provided in the following description should not be construed as limiting the scope and / or applicability of the appended claims. The lists and groups of examples provided in the following description are not exhaustive unless expressly stated otherwise.

[0037] At least some aspects of the present technology will now be described with reference to the embodiment of Figure 1. Figure 1 shows a schematic representation of a monitoring system for monitoring a subject, i.e., tissue such as the muscle of a heart 100. The operation of the system is based at least in part on optical spectroscopy, which makes it possible to determine the molecular concentrations and their oxygenation / oxidation ratios in the tissue under monitoring. Furthermore, the system shown schematically in Figure 1 can be applied to monitor the tissue in question in real time, making it possible to draw conclusions regarding the progression of the tissue's condition and thus aiding in the planning of treatment.

[0038] The monitoring system may include a controller 110 for controlling the operation of the system. Additionally, the monitoring system may include at least two separate light guides 120A, 120B having separate ends inserted into the tissue being monitored.

[0039] The desired distinction between the light guides 120A, 120B at the measuring end can be configured by feeding the light guides 120A, 120B through a fixture 130 that can fix the distance between the light guides 120A, 120B. Between the fixture 130 and the controller 110, the light guides 120A, 120B can extend, for example, with the same lead 140 or can be separate from each other. In accordance with operation of the monitoring system, the controller 110 can be configured to generate light in the first light guide 120A for delivery to the tissue under monitoring, e.g., the myocardium, while the second light guide 120B can be positioned to collect light from the tissue under monitoring, e.g., the myocardium, and return the light to the controller 110 for performing analysis based at least on the delivered and collected light. Additionally, the system can include additional elements and functions, such as configurations for providing cardiac pacing.

[0040] If the capability to provide cardiac pacing is integrated into the monitoring system, the controller 110 can include such functionality, and the pacing leads can be positioned on or at least alongside the same lead 140 as the light guides 120A, 120B, and a jig 130 can also be applied when introducing the pacing leads at least partially into the myocardium. Additionally, the monitoring system, and in particular the spectrometer probe, can include one or more features and / or devices for attaching the measuring end of the probe to the tissue being monitored, as well as one or more features and / or devices for improving the positioning of the light guides 120A, 120B within the tissue being monitored and for improving the signal-to-noise ratio of the measurements.

[0041] Various aspects of the present technology are discussed in the following description by way of non-limiting embodiments.

[0042] 2 shows, in cross section, a schematic illustration of an example of the measuring end of a myocardial spectrometer probe according to one embodiment of the present invention. The first light guide 120A and the second light guide 120B are positioned separately from each other by a jig 130. The structure of the jig 130 is machined such that the positions of the first light guide 120A and the second light guide 120B within the jig 130 define a mutual distance dm between the first light guide 120A and the second light guide 120B at the measuring end, i.e., the portion insertable into the tissue under monitoring.

[0043] In one embodiment, the mutual distance dm can be advantageously selected so that the second light guide 120B can collect enough light to ensure an adequate signal level to perform monitoring, but so that at least a portion of the intact tissue is between the first light guide 120A and the second light guide 120B when the myocardial spectrometer probe is positioned in the tissue being monitored.

[0044] In such a configuration, light has no other way to enter the second light guide 120B from the first light guide 120A other than by passing through the tissue between the light guides 120A and 120B.

[0045] In one embodiment, the majority of the light emitted from the first light guide and received by the second light guide passes through intact tissue, and less than 10%, particularly less than 5%, and preferably less than 1% of the light received by the second light guide passes through any superficial tissue.

[0046] In one embodiment, the mutual distance between the first light guide 120A and the second light guide 120B is between 0.1 mm and 5 mm, preferably between 1 mm and 2 mm. Furthermore, the insertion depth dt of at least one of the light guides 120A, 120B is advantageously considered in the application area. In the context of a myocardial spectrometer probe, an applicable insertion depth dt can be approximately 3 mm to 10 mm, preferably 4 mm to 6 mm, ensuring that the light guides 120A, 120B reach the myocardium through superficial layers such as the epicardium, endocardium, epicardial fat, fibrous tissue, scar, etc., to measure molecular concentrations in the tissue. In one embodiment, at least one of the light guides 120A, 120B is at the insertion depth.

[0047] In one embodiment, the myocardial spectrometer probe comprises at least two separate light guides 120A, 120B insertable into tissue to reach the myocardium through the superficial layer of the tissue, the first light guide 120A, 120B being arranged to deliver light and the second light guide 120A, 120B being arranged to collect light, and the first light guide 120A, 120B and the second light guide 120A, 120B being arranged at least partially separate from each other.

[0048] In one embodiment, the myocardial spectrometer probe comprises at least two separate light guides 120A, 120B insertable into tissue to an insertion depth of at least 3 mm, typically 3-10 mm, wherein a first light guide 120A, 120B is arranged to deliver light and a second light guide (120A, 120B) is arranged to collect light, and wherein the first light guide 120A, 120B and the second light guide 120A, 120B are arranged at least partially separate from each other.

[0049] In some embodiments, the light guides 120A, 120B may be coated in an applicable manner, for example, at the portion of the light guides 120A, 120B that enters the tissue, the coating may be made of a steel tube that provides protection and support to the light guides 120A, 120B.

[0050] Additionally, the portions of the light guides 120A, 120B exiting the fixture 130 toward the control device 110 may be coated with an applicable plastic material, such as an acrylic coating. Advantageously, the interface between the different coating materials is located inside the fixture 130 to maintain the coatings in place and provide structural support at the interface. The fixtures described herein provide support to hold the light guides at a predetermined distance from each other and can be of any material or shape that provides this function. The fixtures can be permanently affixed to the light guides or can be removable. Additionally, the coating of the light guides 120A, 120B, particularly on the side that enters the tissue being monitored, can be selected to harden the light guides 120A, 120B and support penetration of the surface and other layers of the target tissue.

[0051] In some embodiments, the light guides (120A, 120B) may be made of a biodegradable material.

[0052] In some embodiments, the light guide can be inserted during or after manufacture into a hole or holes in a solid block of material that protects the light guide during packaging, sterilization, shipping, and storage. If the block of material has suitable and known optical properties, it can also be used to calibrate the probe before measurements.

[0053] Furthermore, as can be derived from FIG. 2, the tips of the light guides 120A and 120B can be designed to optimize the transmission of light between the light guides 120A and 120B. This can be achieved by configuring the angle α of the tips of the light guides 120A and 120B relative to their longitudinal axes. According to the present invention, an advantageous angle α is between 45 and 90 degrees, preferably between 70 and 90 degrees. Additionally, the tips of the first and second light guides 120A and 120B can, in at least some embodiments, be positioned such that the openings of the light guides having angle α (i.e., inclined surfaces) face each other, as shown schematically in FIG. 2. The angle α can be introduced into the light guides 120A and 120B by, for example, cleaving, grinding, or polishing the light guides in question. Any material or lens that generates convergence, divergence, or diffusion of light can be used in front of the light guide head(s).

[0054] The first light guide 120A and the second light guide 120B can comprise one or more optical fibers (i.e., a single fiber or a fiber bundle) or can be realized by light tubes. Regardless of the physical realization of the light guides, the considerations regarding the applicable angles in the application area apply as discussed in the preceding description.

[0055] The thickness of the light guides 120A and 120B, ie, the material selected to fulfill the role of the light guides 120A and 120B, is preferably between 100 μm and 400 μm.

[0056] FIG. 3 schematically illustrates some further aspects according to some embodiments of the present invention. Specifically, as described above, the tip of at least one light guide 120A, 120B is brought into the tissue whose properties are to be measured. For example, with respect to entry into the myocardium, the light guides 120A, 120B penetrate multiple layers, which are inherently dense, before accessing the myocardium. To facilitate penetration of the light guides 120A, 120B through the aforementioned layer(s), the probe may be provided with an insertion assist device 310. The insertion assist device 310 is a device that protects the light guides 120A, 120B during insertion of the probe to the measurement location, but also has a structure and shape that allows penetration through layers and further helps maintain the mutual distance between the light guides 120A, 120B as designed. According to an exemplary embodiment, the insertion assist device 310 includes tubular members 320A, 320B through which the light guides can be inserted. The tubular members 320A, 320B preferably have sharpened ends facing the tissue in order to cut the tissue as they penetrate it. At their other ends, the tubular members 320A, 320B are attached to a support surface 330, which faces the jig 310 in one position, for example. As can be derived from FIG. 3 , the size of the insertion aid 310, and in particular the length of the tubular members 320A, 320B, is advantageously adjusted so as not to interfere with the light transmission between the light guides 120A, 120B. In one embodiment, the light guides 120A, 120B also protrude from the insertion aid tube so that the tube does not interfere with the light transmission between the light guides 120A, 120B when the light guides 120A, 120B are inserted to a predetermined depth.

[0057] According to some embodiments, the insertion assist device 310 can be configured to be at least partially movable relative to the light guides 120A and 120B. Therefore, the state shown in FIG. 3 can be considered to correspond to a situation in which the myocardial spectrometer probe is being inserted into tissue, i.e., the insertion phase. Meanwhile, FIG. 4 schematically illustrates an example in which the insertion assist device 310 is positioned so that the probe enters the tissue and the light guides 120A and 120B exit the tubular members 320A and 320B. In other words, the state shown in FIG. 4 is established when the probe is at a measurement position within the tissue. Therefore, for example, the insertion assist device 310 can be slidably positioned relative to the light guides 120A and 120B such that, in response to a support surface 330 facing the tissue, the insertion assist device 310 begins to slide along the light guides 120A and 120B until the support surface 330 reaches the jig 130. Of course, in that state, the light guides 120A, 120B slide out of the tubular members 320A, 320B for use in measurements.

[0058] The sliding mechanism described above can be achieved by adjusting the inner diameter of the tubular members 320A, 320B to the outer diameter of each light guide 120A, 120B, so that the total friction between the entities exceeds the force required to penetrate the tissue. Friction can also be adjusted by modifying the surfaces of the mentioned entities, such as by optimally roughening the surfaces. A suitable material for the insertion assist device 310 can be, for example, stainless steel (see, for example, a hypodermic needle). Furthermore, as mentioned above, the ends of the tubular members 320A, 320B facing the tissue are preferably sharp, or at least their profile is designed to ensure easy and safe insertion into the tissue.

[0059] FIG. 5 schematically illustrates an aspect of a further embodiment of the present invention. In this embodiment, a stopper device 510 is incorporated into a myocardial spectrometer probe. The stopper device 510 provides a method for adjusting at least the insertion depth of the light guides 120A, 120B into tissue as desired within the application area. Furthermore, the stopper device can also adjust the insertion angle by positioning the light guides 120A, 120B to exit the stopper device 510 toward the tissue at a desired angle. Thus, as shown, for example, in FIG. 2, the stopper device 510 facilitates adjustment of the probe's position within tissue compared to a probe without the stopper device 510. The stopper device 510 can comprise, for example, a receiving portion 520 and a light cover portion 530. The receiving portion 520 can include, for example, an adapter for receiving a fixture 130 that holds the light guides 120A, 120B. The angle at which the light guides 120A, 120B enter the tissue can be at least partially determined by designing the adapter at a desired angle.

[0060] In other words, in one embodiment, a channel is disposed within the stopper device 510 to provide a path for the light guides 120A, 120B through the stopper device 510. Additionally, the light cover portion 530 acts as a stopper against the tissue but also prevents ambient light from entering the tips of the light guides 120A, 120B, particularly the tips of the light guides positioned to collect light. This may be particularly important because myocardial spectrometer probes may be used during cardiac procedures where good illumination is required. This provides a significant amount of ambient light, which reduces the signal-to-noise ratio of optical measurements. Therefore, the light cover portion 530 may be important for reducing noise during measurements.

[0061] For example, the area of ​​the light cover portion can be 0.1 cm to 5 cm, preferably 0.5 cm to 2 cm. For example, the light cover portion and the entire stopper device 510 can be made of a biodegradable material, polymer, metal, or glass. Furthermore, the light cover portion 530 can be shaped to adhere well to the tissue being monitored or can include one or more holes used to suture the light cover portion 530 to the tissue. Furthermore, the light cover portion 530 can be shaped, for example, with anchors for gripping, to allow for easy removal before the chest is closed upon completion of open-heart surgery and when the post-operative phase begins. Furthermore, in some embodiments, the stopper device 510 can provide a counterforce to a fixation device used to secure the probe in a measurement position, as described below. The stopper device 510 can be used in conjunction with the insertion assist device 310, as described in the description of FIGS. 3 and 4.

[0062] FIG. 6 schematically illustrates a further exemplary embodiment. In FIG. 6, a myocardial spectrometer probe is attached to an organ, which in this case is the heart. In the embodiment of FIG. 6, a fixed wire 610 is brought into the myocardium along with light guides 120A, 120B. The fixed wire 610 may be coupled to the fixture 130 or, in embodiments where a stopper device 510 is applied, may be positioned in the same channel as the light guides 120A, 120B extending through the stopper device 510. The fixed wire 610 may be secured to a needle, such as that used in open-heart surgery, where the needle penetrates tissue, travels a predetermined distance within it, and places the tissue at a certain position (indicated by the letter "A" in FIG. 6). The needle may be removed after positioning the fixed wire 610 in the tissue by cutting the wire at the applicable location.

[0063] Advantageously, the end of the fixed wire 610 is fixed, preferably removably fixed, at the exit position. In this configuration, the fixed wire 610 can be used to secure the myocardial spectrometer probe within the tissue being monitored. Fixation can be achieved by tensioning the fixed wire 610 from the end of the stopper device 510 after the other end is anchored in the tissue at exit position A. As a result, the probe itself is rigidly attached to the tissue, the light guides 120A and 120B remain stationary in the measurement position, and artifacts caused by movement are at least partially eliminated. Fixation of the fixed wire can also be achieved with metallic or biodegradable surgical clips.

[0064] In some embodiments, as described, a pacing lead can be used as the fixed wire 610. The pacing lead allows for pacing of the myocardium, for example, during surgery and thereafter in any situation where this is required.

[0065] 7A and 7B schematically illustrate some non-limiting examples of applicable solutions for securing a fixation wire 610, such as a pacing lead, to the tissue of interest. For clarity, it is assumed herein that the fixation wire 610 is a pacing lead. FIG. 7A illustrates an example of fixation in an embodiment in which the pacing lead is positioned to extend within the myocardium (see FIG. 6). At the exit position, an inflatable balloon device 710 is attached to the end of the pacing lead where it exits the tissue. The inflatable balloon device 710 is a ring-shaped device secured around the pacing lead, which secures the pacing lead at the exit position and thus allows tensioning between the end of the pacing lead and the probe itself, as described in the context of FIG. 6. The inflatable balloon device 710 is attached to the end of the pacing lead when not inflated and is then inflated by a suitable inflation device. This is done, for example, during open-heart surgery. An advantage of the inflatable balloon device 710 is that if the pacing lead as well as the probe are left in the body after open-heart surgery, both the probe and the pacing lead can be removed remotely, i.e., percutaneously, from the body by pulling the probe outward after the balloon is remotely deflated. Deflation of the balloon device 710 allows the pacing lead to be pulled back through the myocardium.

[0066] A similar fixation method to that shown schematically in Figure 7A, in which an inflatable balloon device is applied, can be achieved using an anchoring device made from a material that has sufficient friction against the tissue surface, the anchoring device is placed on the tissue surface, and a fixation wire is then pulled through the tissue in the same manner as for the inflatable balloon device, but the fixation wire is attached to the anchoring device in some way.

[0067] For example, the anchoring device can have a hole or slot through which a fixation wire can be inserted. The mutual dimensions of the hole or slot and the diameter of the fixation wire are advantageously selected so that their mutual friction is sufficient to allow tensioning of the probe by pulling the fixation wire outward from the tissue at the probe end. However, in a preferred solution, the friction between the entities is configured so that pulling beyond a selected level causes the fixation wire to begin sliding through the hole or slot, allowing it to be removed from the tissue. For example, the anchoring device can be made of plastic or any other material applicable to operating in the described manner. Clamps can also be applied. In some embodiments, the anchoring device can be made of a biodegradable material that allows the anchoring device to remain in the body.

[0068] FIG. 7B schematically illustrates another example of anchoring a pacing lead within a heart, according to another embodiment of the present invention. Here, the pacing lead is positioned to extend over the myocardium, i.e., not passing through but passing over the light cover portion 530. Additionally, a wire 720 is positioned to pass through tissue, providing an anchoring configuration 730, such as a loop, at the location where the wire 720 exits the tissue. The pacing lead (see 610 in FIG. 7B ) can be anchored to the tissue by guiding it through the loop and tensioning the wire from the end of the probe to appropriately anchor the pacing lead. This type of anchoring may be configured during open-heart surgery. The anchoring according to the example of FIG. 7B also allows for remote removal by loosening the wire 720 and withdrawing the pacing lead. The wire can then be removed. In some embodiments of the present invention, anchoring of the pacing lead may be performed using the anchoring mechanism of FIG. 7B by placing a hole in the light cover portion 530 through which the wire and loop are placed on the surface of the light cover portion 530. Guiding the pacing lead through the loop provides tension against the surface of light cover portion 530, minimizing damage to the tissue in question. In some further embodiments, tissue damage can be avoided in the embodiment of FIG. 7B by placing, for example, a screen made from a biodegradable material under the pacing lead where wire 720 exits the tissue.

[0069] Additionally, the arrangement shown schematically in Figure 7B may be reversed such that the wire 720 of Figure 7B is achieved with a pacing lead having a loop at the end of the lead, with the wire positioned over the myocardium in a manner similar to the pacing lead of Figure 7B. Fixation can then be achieved by inserting the wire over the myocardium through the loop at the end of the pacing lead, thereby tensioning the pacing lead over the myocardium.

[0070] To enhance the ability to remove the pacing leads as well as the light guides 120A, 120B from the body, they may be encased in plastic or silicone tubing, either separately or together in some combination. The diameter of the tubing can be adapted to the diameter of the fixture 120 holding the light guides 120A, 120B, thus allowing for smooth removal of the detachable portion of the probe. The pacing leads themselves can be fabricated from a biocompatible material such as stainless steel. For example, the pacing leads can be 0.1 m to 10 m long, as needed.

[0071] Furthermore, in some embodiments, the light cover portion 530 may be configured to operate as an anode or a cathode (i.e., in the role of the other electrode) for achieving bipolar pacing, depending on the role of the end of the pacing lead. In such embodiments, at least a portion of the light cover portion 530 is made of a conductive material to which another pacing lead is connected. Correspondingly, in some further embodiments, the insertion assist device 310 can be used as an electrode for pacing. Depending on the embodiment, for example, one of the tubular members 320A, 320B may be connected to one of the pacing leads and advantageously insulated from the rest of the insertion assist device 310 to establish an electrode with the other electrode established at the end of the pacing lead. Furthermore, if the light guides 120A, 120B are coated with steel tubing, the pacing lead can be connected to at least one of the steel tubing, thereby establishing an electrode.

[0072] With respect to removal of the myocardial spectrometer probe, further care can be taken with the light cover portion 530. In some embodiments, the light cover portion 530 may remain in the heart after removal of the probe, at least in part due to its shape. In such embodiments, the light cover portion 530 and the receiving portion 520 of the probe may be removably coupled to one another. This coupling can be configured such that the force required to uncouple the light cover portion 530 is less than the force required to remove the light cover portion 530 from the tissue to which it is attached. Thus, pulling the probe outward results in the receiving portion 520 and the light cover portion 530 being uncoupled from one another, leaving the light cover portion 530 on the surface of the tissue in question. In such embodiments, the light cover portion 530 is advantageously made from a biodegradable material, such as an applicable polymer.

[0073] In another embodiment, the light cover portion 530 can be made at least partially from a foldable material, whereby when the probe is removed from the tissue and pulled outward from the body, the foldable light cover portion 530 is shaped such that the light cover portion 530, in its folded configuration, can fit through the hole along which the probe is removed from the body.

[0074] Additionally, in some embodiments, the light cover portion 530 of the probe may be attached to the tissue by suturing it with multiple sutures. In such embodiments, the light cover portion 530 may include one or more holes, for example, that are used for attachment by the sutures. Advantageously, the sutures release the light cover portion 530 from the tissue in response to a pulling force exceeding a predetermined value. The sutures may be made of a biodegradable material, or may be made of stainless steel or other biocompatible materials. In some embodiments, sutures made of a conductive material may be used as electrodes for cardiac pacing, with pacing leads coupled to such sutures.

[0075] FIG. 8 schematically illustrates a further exemplary embodiment of a probe according to the present invention. This exemplary embodiment is based on an embodiment in which at least some portions of the insertion assist device are integrated with the jig 130. In this embodiment, the tubular members are implemented as conductive tubes 810A, 810B, such as metal tubes, which are fixed to the jig 130 in an applicable manner, such as by gluing them to the jig 130. The conductive tubes 810A, 810B as tubular members provide a path for each light guide 120A, 120B to enter the tissue under monitoring. In other words, the conductive tubes 810A, 810B provide channels through the jig 130 for properly positioning the light guides 120A, 120B for monitoring. The conductive tubes 810A, 810B in the embodiment disclosed in FIG. 8 may be realized by applying a coating to the light guides 120A, 120B, as described above. According to an exemplary embodiment, each pacing lead 820A, 820B is positioned for each conductive tube 810A, 810B to establish an anode and cathode for providing bipolar pacing to the myocardium, as needed. Thus, the pacing leads 820A, 820B and the conductive tubes 810A, 810B are in electrical contact with each other and conduct electricity through the contact. The contact points can be configured within the fixture 130, for example, to position an adaptable connector to form a contact into which the pacing leads 820A, 820B can be inserted. Alternatively or additionally, the contact can be achieved by welding, soldering, or pressing. Furthermore, the fixture 130 is fabricated from a non-conductive material. A light protective cover can also be used with the exemplary embodiment shown in FIG. 8. The basic concept of FIG. 8 may also be applied in the context of separate insertion aids (see, e.g., the embodiments of FIGS. 3 and 4) by placing pacing leads 820A, 820B in each tubular member 320A, 320B, where the tubular members 320A, 320B are separated from each other by a non-conductive material (see, e.g., the material of the support surface 330).

[0076] Furthermore, in some exemplary embodiments, the myocardial spectrometer probe may further include a removably attachable protective cover to protect the first light guide 120A, 120B and the second light guide 120A, 120B when the probe is not in use, such as during storage or transportation of the probe. In some further embodiments, the protective cover is implemented to function as a calibration target for calibrating the measurement system to which the myocardial spectrometer probe is applied. To enable calibration, the properties of the protective cover may be appropriately selected. In exemplary embodiments, the material of the protective cover may be selected to have a constant and reasonably low absorption coefficient for light within the wavelength range of 600 to 900 nm used for measurement, such as less than 0.001 mm.

[0077] Furthermore, in one embodiment, the scattering coefficient of the material corresponds to the reduced scattering coefficient of the tissue being monitored, such as ∼1 mm-1. Furthermore, the size and shape of the protective cover are preferably designed so that the boundary area of ​​the material and the cavity into which the light guides are inserted do not cause background light to interfere with calibration. For example, it can be molded to extend at least 3 mm in each direction from the tips of the light guides 120A, 120B. Applicable materials can be, for example, transparent epoxy resin and titanium dioxide or optical PTFE.

[0078] Although the foregoing description provides an environment in which the first and second light guides 120A, 120B reach the same depth within tissue, the present invention is not limited to such implementation. That is, the insertion depth between the light guides 120A, 120B may vary as long as the collected light provides meaningful measurements of the monitored parameters. In some embodiments of the present invention, the other light guide 120A, 120B may be positioned on the surface of the tissue, or may be positioned such that its insertion depth penetrates only the epicardium while the other light guide 120A, 120B is embedded deeper in the tissue.

[0079] Generally speaking, myocardial spectrometer probes can be applied in real-time monitoring of molecular concentrations in tissues, for example, during and after open-heart surgery, using spectroscopic techniques such as diffuse optical spectroscopy, diffuse reflectance spectroscopy, Raman spectroscopy, Fourier transform spectroscopy, fluorescence spectroscopy, etc.

[0080] Thus, a method for monitoring molecular concentrations in a tissue of interest by spectroscopy includes providing at least two separate light guides, a first light guide positioned to deliver light and a second light guide positioned to collect light. The light guides are inserted into the tissue of interest, particularly the myocardium, such that at least a portion of intact tissue separates the first light guide from the second light guide. Thus, light delivered by the first light guide extends through the intact tissue and reaches the second light guide.

[0081] Furthermore, in this method, light is delivered (or emitted) from a first light guide, and the light delivered from the first light guide is received by a second light guide. Multiple pulses of light are delivered and received to form multiple signals corresponding to the collected light. The signals thus obtained are used to monitor the tissue of interest. Typically, 1 to 100 pulses per second, particularly 2 to 50 pulses, e.g., 5 to 20 pulses, or 8 to 15 pulses per second, are delivered and received.

[0082] In one embodiment, the measurement system disclosed in Figure 1 or in connection with any embodiment described herein generates clinically relevant information on cardiac metabolism measured simultaneously from intracellular organisms, extracellular molecule concentrations, and intravascular concentrations in the cytosol. In another embodiment, the system can measure the concentration of molecules in the oxidative phosphorylation chain in mitochondria during cardiac surgery.

[0083] In one embodiment, the myocardial spectrometer probe is used in a method for monitoring changes in enzyme concentrations in response to mitochondrial stress.

[0084] In one embodiment, the myocardial spectrometer probe is used to monitor the molecular concentrations of catalase, superoxide dismutase and peroxidase, and combinations thereof.

[0085] Furthermore, the myocardial spectrometer probe can be connected to an online monitor, for example, implemented in a control device, that displays relevant information about myocardial metabolism to medical personnel in real time, thereby enabling them to respond accordingly.

[0086] As can be derived from the above description, at least some essential features of the present invention are that the light guides 120A, 120B, at least one first light guide for capturing light and at least one second light guide for collecting light, are positioned separately from each other at a measurement location in the tissue under monitoring, such as the myocardium, to establish a reliable measurement setup in which at least a portion of the emitted light is transported through the tissue between the light guides 120A, 120B. The distance between the light-emitting light guides 120A, 120B and the light-collecting light guides 120A, 120B is predetermined.

[0087] Depending on the type of measurement, ie whether it is performed on a beating or resting heart, fixation of the light guides 120A, 120B to the tissue may be required.

[0088] The present invention also allows for the use of temporary pacing wires in open-heart surgery situations to support patients after surgery. Separately locating the light guide also offers the possibility of combining temporary cardiac pacing wires in the same structure in the manner described above, for example, by covering the light guide with metal or any other conductive material. Furthermore, the described structure allows for the performance of additional measurements from the tissue, such as measuring the temperature of the tissue by electrical or optical means. In other words, the light guide or insertion aid or other part of the probe can be equipped with an applicable tissue-penetrating sensor, from which measurement data can be acquired. Alternatively or additionally, the temperature can be determined from measurement data obtained using the light guide, i.e., optically.

[0089] The specific examples provided in the above description should not be construed as limiting the applicability and / or interpretation of the appended claims. The lists and groupings of examples provided in the above description are not exhaustive unless expressly stated otherwise.

Claims

1. A myocardial spectrometer probe comprising at least two separate light guides (120A, 120B) insertable into tissue, wherein a first light guide (120A, 120B) is arranged to deliver light and a second light guide (120A, 120B) is arranged to collect light, and the first light guide (120A, 120B) and the second light guide (120A, 120B) are arranged at least partially separate from each other; The tip of the light guide (120A, 120B) is angled at 70 to 90 degrees with respect to the longitudinal axis of the light guide (120A, 120B); A myocardial spectrometer probe, wherein the light guides (120A, 120B) are coated to harden the light guides (120A, 120B) and support penetration of the surface and other layers of target tissue.

2. 2. The myocardial spectrometer probe of claim 1, wherein the first light guide (120A, 120B) and the second light guide (120A, 120B) are positioned separately from each other such that, when inserted into the tissue of interest, at least a portion of intact tissue separates the first light guide from the second light guide.

3. 3. The myocardial spectrometer probe of claim 1, comprising at least two separate light guides (120A, 120B) insertable into tissue to reach the myocardium through the superficial layer of the tissue.

4. A myocardial spectrometer probe as described in any one of claims 1 to 3, wherein the first light guide (120A, 120B) and the second light guide (120A, 120B) are arranged separately from each other by attaching the first light guide (120A, 120B) and the second light guide (120A, 120B) to a jig (130).

5. The myocardial spectrometer probe of any one of claims 1 to 4, wherein the first light guide (120A, 120B) and the second light guide (120A, 120B) are realized by one of a single optical fiber, an optical fiber bundle, and a light tube.

6. The myocardial spectrometer probe according to any one of claims 1 to 5, wherein at least one of the light guides (120A, 120B) insertable into tissue is at least partially coated with a steel pipe.

7. The myocardial spectrometer probe of any one of claims 1 to 6, further comprising a pacing lead arranged to extend along at least one of the light guides (120A, 120B).

8. The myocardial spectrometer probe of claim 7 , wherein a pacing lead is electrically connected to a steel tube that coats at least a portion of at least one of the light guides (120A, 120B).

9. The myocardial spectrometer probe of any one of claims 6 to 8, wherein a first pacing lead is electrically connected to the steel tube of the first light guide (120A, 120B) and a second pacing lead is electrically connected to the steel tube of the second light guide (120A, 120B) to form a bipolar pacing configuration including an anode and a cathode.

10. A myocardial spectrometer probe as described in any one of claims 1 to 9, further comprising a stopper device (510) for adjusting at least one of the insertion depth of at least one of the light guides (120A, 120B) in tissue and the insertion angle of at least one of the light guides (120A, 120B) in tissue.

11. The myocardial spectrometer probe of claim 10, wherein the stopper device (510) comprises a receiving portion (520) for receiving at least the light guide (120A, 120B) and a light cover portion (530) for at least partially preventing ambient light from entering tissue.

12. The myocardial spectrometer probe of claim 11 , wherein the receiving portion (520) and the light cover portion (530) of the stopper device (510) are removably attached together.

13. A myocardial spectrometer probe as described in any one of claims 10 to 12, wherein a fixed wire (610) is arranged to extend through the stopper device (510), and an end of the fixed wire (610) is arranged to be fixed to tissue to enable tensioning of the light guide (120A, 120B) by a fixed position of the fixed wire (610).

14. 14. The myocardial spectrometer probe of claim 13 when dependent on claim 7, wherein the fixed wire (610) is the pacing lead.

15. The myocardial spectrometer probe of claim 13 or 14, wherein the fixation is configured by one of an inflatable balloon device (710), a fixation structure (720) configured to have a second wire (739) that forms an anchor for the fixation wire (610), and an anchor device.

16. The myocardial spectrometer probe of any one of claims 1 to 15, further comprising an insertion assisting device (310) for penetrating the surface of tissue to insert the light guides (120A, 120B) into the tissue.

17. 17. The myocardial spectrometer probe of claim 16, wherein the insertion assist device (310) comprises at least one tubular member (320A, 320B) in which the light guide (120A, 120B) is disposed.

18. The myocardial spectrometer probe of claim 17 , wherein the light guide (120A, 120B) is slidably disposed relative to the tubular member (320A, 320B) of the insertion assist device (310).

19. 19. The myocardial spectrometer probe according to any one of claims 16 to 18, when dependent on claim 7, wherein the insertion assist device (310) is arranged to operate as an electrode of the pacing lead coupled to the insertion assist device (310).

20. 20. The myocardial spectrometer probe according to claim 17 or claim 18 or 19 depending on claim 17, wherein the end of the tubular member (320A, 320B) of the insertion assist device (310) facing the tissue has a sharp shape.

21. The myocardial spectrometer probe of any one of claims 16 to 20, wherein the insertion assist device (310) is manufactured from one of stainless steel, ceramic, or composite materials, or a combination thereof.

22. 16. The myocardial spectrometer probe of claim 15, when dependent on claim 11, wherein at least one of the light cover portion (530), the inflatable balloon device (710), the fixation device (720), and the fixation wire (610) is made of a biodegradable material.

23. The myocardial spectrometer probe according to any one of claims 1 to 22, further comprising means for providing measurement data representative of tissue temperature.

24. The myocardial spectrometer probe of any one of claims 1 to 23, further comprising a removably attachable protective cover for protecting the first light guide (120A, 120B) and the second light guide (120A, 120B).

25. 25. The myocardial spectrometer probe of claim 24, wherein the protective cover is arranged to act as a calibration target for calibrating a measurement system to which the myocardial spectrometer probe is applied.

26. A myocardial spectrometer probe as described in any one of claims 1 to 25, wherein the first light guide (120A, 120B) and the second light guide (120A, 120B) are insertable into myocardial tissue between the epicardium and endocardium so that light provided by the first light passes through intact myocardial tissue and reaches the second light guide.

27. ​​A myocardial spectrometer probe as described in any one of claims 1 to 26 for use in monitoring molecular concentrations in tissue in real time during and after open heart surgery.

28. 28. The myocardial spectrometer probe of claim 27 for use in monitoring molecular concentrations in tissue, wherein said monitoring involves the application of diffuse optical spectroscopy, Raman spectroscopy, Fourier transform spectroscopy or fluorescence spectroscopy.

29. 1. A method of operating a medical device for monitoring molecular concentrations in a tissue of interest by spectroscopy, comprising: - providing at least two separate light guides insertable into tissue, a first light guide arranged to deliver light and a second light guide arranged to collect light; - positioning the light guides such that at least a portion of intact tissue separates the first light guide from the second light guide, and light delivered by the first light guide passes through the intact tissue and reaches the second light guide; repeatedly delivering light from the first light guide and collecting the light delivered from the first light guide with the second light guide to form a plurality of signals corresponding to the collected light; - monitoring the signal thus obtained; and A method for operating a medical device, including:

30. 30. A method of operating a medical device according to claim 29, comprising monitoring changes in enzyme concentration in response to mitochondrial stress.

31. 31. The method of operating a medical device of claim 30, comprising monitoring molecular concentrations of catalase, superoxide dismutase, and peroxidase, and combinations thereof.

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