Patent Description:
Determining and monitoring of the performance of the heart, in particular cardiac output, often relies on assessment of a single, key physiologic parameter that is taken as surrogate for the -inaccessible - cardiac output parameter of interest.

Typically, measurement of parameters for computing cardiac output (CO) rely on invasive catheters. Such catheters often contain either a fluid line that propagates the pressure inside the body to a sensor outside the body, or it consists of optical line that propagates a light signal from a measurement location inside the body to a sensor outside the body, or it contains an electric line that transports an analog signal from inside the body e.g. from a thermistor, to an analog-to-digital converter outside the body. The transmission of physical or analog signals from inside the body to a transducer outside the body is susceptible to mechanical or electrical noise; such catheters are often difficult and expensive to manufacture; their handling in clinical practice is laborious; the multiple connections (analog wires, fluids) and the external power supply and signal transfer lines that are needed for functionality render patient management more complex.

Future systems for cardiac output determination should therefore innovate in catheter designs to overcome these limitations.

Using a single parameter for determination of cardiac output, as is typically done with thermodilution or pulse contour analysis, has several disadvantages:.

In contrast, heart function determination methods that are based on combination of multiple biological signals have the potential to overcome weaknesses mentioned, in part by delivering more robust primary signals and by allowing control of confounding factors. One important practical limitation of current clinical practice when monitoring multiple vital parameters is that this leads to increased complexity of patient management, because each additional sensor typically comes with its own cable for power supply and sensor signal output, thereby increasing complexity and cost.

Thus, future systems for cardiac output determination should preferably have the capability of a) acquiring multiple signal modalities, with a minimum amount of equipment, in synchronous fashion, and b) analysing such multiple signal parameters in combination, and c) being applicable and reliable in patients that receive mechanical circulatory support.

This implies the need for innovation in cardiac monitor devices and algorithms to be used in conjunction with catheters/sheaths/shafts in this invention.

Most current state-of-the art monitoring catheters are capable of probing a single physical modality inside the body, that in typical scenarios is guided to the outside of the body where an external transducer converts the physical signal to an analog signal and the analog signal is converted in an additional stage to a digital signal, the typical example being current invasive pressure monitor catheters.

In addition, there exist medical pressure wires that can be placed in the body to measure a single signal that transduce pressure at the wire tip by converting it to an analog signal inside the body, and guide the analog signal to a catheter portion outside the body, with the device needing to be connected to a second device (the interface box) outside the body for analog to digital signal conversion and data transmission (Radi Patent <NUM>, patents. com/patents/<NUM>),(Volcano patent <NUM>, see http://patents. com/patent/<NUM>). There exist medical Doppler wires that allow to extract a single ultrasound Doppler signal from the body, by reading out not only low frequency pressure but also high frequency a pressure oscillation through a similar catheter; also in this case, an analog signal is guided from the catheter tip to a location outside the body where additional equipment is required for analog to digital conversion (Volcano patent <NUM>, see http://patents. com/patent/<NUM>). In addition, a limited number of multimodal sensing catheters for medicine exists, that typically have a an analog sensing element and a number of channels of fibers that guide a physical signal (pressure, light) out of the body to be transduced to an electrical signal outside the body. An example is the CCOmbo/SvO2 pulmonary artery catheter from Edwards Life Science. It combines an analog temperature sensing thermistor at its tip inside the body, contains fluid filled lumina that allow pressure determination outside the body an added external pressure transducers, and optical fibers that guide an optical spectrum to outside the body, whereby the actual optical sensors transduce the physical signal into a stream of digital information are located outside the body.

Prior Art in monitors for computing cardiac output, the main methods employed currently are the pulmonary artery catheter and in the PiCCO system and the pulmonary form the main body of prior art.

<CIT> describes a local power-delivery/data-reception unit installed within an insertion end of a sealed catheter. The local power-delivery/data-reception unit wirelessly powers a separately sealed sensor that is attached to the insertion end and configured for wirelessly sending a data signal to the local power-delivery/data-reception unit. The catheter may further feature a remote power-delivery/ data-reception unit disposed within the handle and configured for wirelessly communicating with the local power-delivery/data-reception unit and a controller for controlling the sensor.

Improvements in medical monitoring technology is desirable because they can lead to improved patient management.

Measuring multiple physical signals at a location inside the body has the potential to yield information that is suited as input to algorithms and systems that can exploit the complementary, redundant, and mutually dependent information content of signals, as described below.

By the expression "inside the body" any configuration is hereby encompassed wherein a medical invasive device is, in total or limitedly to just a body portion thereof, inserted into one of a blood vessel, a body cavity and a body tissue.

With Catheter, a hollow tube of a diameter less than a centimetre and more than hundred micrometer is meant that has a primary function to connect a body compartment, typically the intravascular compartment, with the outside of the body for with the goal of one of, infusion of therapeutic liquids, withdrawing blood, and measuring the hydrostatic pressure through a water column guided to the outside of the body.

With Sheath, a hollow tube of a diameter of less than a centimetre and more than <NUM> micrometers is meant that serves to contain in its main lumen an elongated inner object and guides it from the outside of the body to inside the body. Such a sheath may contain zero or more additional hollow lumina for other purposes, in addition to the object-carrying main lumen.

With Shaft, an elongated object with a diameter of less than a centimetre and more than <NUM> micrometers is meant that has the primary function to carry on its part inside the body a number of functional subsystems that includes at least one of, a pump, and a sensor array. C/S/S is here used for "catheters, sheaths, shafts".

Miniaturized digital sensor System-On-Chips (SoC) as described here combine, in integrated package having a diameter measured perpendicular to a device axis, not larger than the available space at target location inside the body, ( typically smaller than <NUM> square millimeters for catheters and shafts arranged for diagnostic purposes only, and typically smaller than <NUM> square millimetres for sheaths that are used in conjunction with heart pumps) , the necessary circuits to yield a digital encoding of a quantitative measurement of a physical modality, including at least the signal to analog transduction, analog-to-digital conversion, and digital transmission. The use of such miniaturized digital sensors has the following advantage a) the transmission of analog signals, which is prone to noise and bias, is eliminated, b) the number of noise sources is reduced because of integrated transducing and digitizing sensor elements, c) digital multiplexing of the output of multiple sensors allows minimizing the number of signal lines, d) the manufacture of the (C/S/S) is simplified because fewer electrical connections are needed, e) digital sensors with very low power requirements exist. The size limit of those sensors is important because clinically tolerable access size to blood vessels is limited and typically ranges up to from <NUM> to <NUM> millimeter device diameter for purely diagnostic use, up to <NUM> for shafts of circulation assist devices, and up to <NUM> for catheters used in extracorporeal circulation. Power requirements of sensors are important for clinical application and are preferably low, to simplify power supply and avoid excessive heating of the sensor that is clinically undesirable.

In connection with the invention the term "computer" can relate to any suitable computing system. In particular, the computer can be a desktop computer, a laptop computer, a tablet a smartphone or a similar device as well as an embedded computing system such as a microcontroller or any other single- or multi-processor embedded system.

Energy harvesting is used to designate a process whereby a device extracts electrical energy from a physical energy source in its surroundings without having a wired connection to the energy source. Energy harvesting technology is well known to a practitioner in the field. In the context of this patent, the term coil designates an electrical coil.

A heart pump is defined as a medical device that pumps blood from one compartment of the blood circulation to another compartment of the blood circulation. Typical pumps include a) extracorporeal pumps that have a mechanical pump part outside the body and b) catheter-based pumps that have the mechanical pump part inside the body and are mounted on the tip of a shaft that crosses the skin, and c) fully implantable pumps that have the mechanical pump part inside the body and no part except a power supply cable that crosses the skin.

In machine learning field, a deep neural network (DNN) is an artificial neural network (ANN) with multiple hidden layers of units between the input and output layers.

In machine learning field, a deep believe network is a type of a deep neural network, comprising multiple layers of latent variables with connections between the layers but not between units within each layer.

According to the present invention, the need for more precise measuring of signals which reflect the heart performance of a patient and allow the extraction of cardiac output parameters better representing the cardiac output is settled by a kit as defined by the features of the independent claim.

Preferred embodiments are subject of the dependent claims.

In particular, the present invention deals with an innovative configuration for medical invasive devices wherein, for instance, signal transduction, analog-to-digital signal conversion and digital signal transmission are moved into the portion of the catheter arranged to be located inside a vessel lumen, by using miniaturized digital sensor SoCs.

Accordingly, medical digital sensor SoC arrays are mounted on catheters, sheaths and shafts at their location inside the body.

The advantages deriving from such innovative configurations comprise <NUM>) reducing or eliminating the need for signal transducer modules outside of the body, thus simplifying industrial production, distribution and clinical use, and <NUM>) the elimination of hydrostatic columns for pressure propagation, of wires carrying sensitive analog signals and of optical lines for signal transmission. The proposed setup consists of devices in the shape of (C/S/S) that comprise miniaturized digital sensors at their tips performing the stages of physical signal sensing, signal transduction, analog-to-digital signal conversion and digital signal transmission, at a location positioned inside the body.

Moreover, a multitude of sensor SoCs that measure different, complementary physical signals, can be placed into a the portion of a medical (C/S/S) arranged to be positioned inside the body, according to the present invention.

Sensors to be used in connection with the present invention are described below more in detail. In line with the above innovative configuration, an arrangement of medical digital sensor SoC and SoC arrays is provided wherein the sensors are mounted at the portion of a medical invasive device that is located inside the body: Integrated multimodal sensor arrays for vital biosignal monitoring can be thus integrated in one of:.

A number of useful sensor combinations are possible and below given as nonlimiting examples.

The integration has the advantage of reducing the number of access cables to a patient to one per sensor array and leads to improved practicability in a clinical scenario.

In addition to that, in the following devices are described in the shape of a medical (C/S/S) comprising an arrangement of digital sensor SoCs with digital transmission at a location arranged to be positioned inside the body, that incorporate a digital interface at their part arranged to be located outside the body to allow to connect a connector cable for power supply and digital data transfer.

While the embodiments conceived according to the above aspect of the invention already simplify and improve medical monitoring, it is still desirable to also give up wired power supply and communication. For these reasons, further improvements are desirable.

According to another aspect of the present disclosure, wireless transmitting catheters and/or sheaths and/or shafts can be designed with integrated Medical Sensor SoCs and SoC arrays: Accordingly, an integrated multimodal biomedical sensor array may be driven by an integrated battery and read out by wireless data transmission.

Accordingly, a further aspect of the present disclosure consists of a medical (C/S/S) with an arrangement of miniaturized digital sensor SoCs at their portion arranged to be located inside the body in combination with a wireless communication chip and a miniaturized battery located at the portion arranged to be located outside the body in a single embodiment. This allows to eliminate the need for cables for power supply and communication and may greatly improve clinical practicability. It will also improve electrical safety because no metallic connection to the patient is needed.

According to a further possible embodiment of the present disclosure, a medical (C/S/S) can be designed with an arrangement of miniaturized digital sensors arranged to be located inside the body and a connector in combination with a pluggable module that comprises a small battery and electronics for wireless signal transmission.

This has the advantage that an empty battery can be replaced by plugging in a charged replacement module.

From the large spectrum of potential sensor modalities that can be used as elements for the sensor array according to the present invention, the following are preferred:.

While the above ameliorations over the prior art improve patient management, the elimination of the need for a battery is still desirable because it has the potential to simplify manufacture, to improve shelf life, to reduce cost, and to reduce the risk of battery leakage. Further innovations are therefore desirable.

In a further aspect of the present disclosure, a device in the shape of a medical (C/S/S) comprising an arrangement of digital sensor SoCs at their portion arranged to be located inside the body with a wireless transmission electronics in one of, their portion arranged to be located outside the body and a pluggable module, is additionally equipped with an energy transfer and harvesting mechanism that allows to eliminate the need for a power supply through battery or cable. A battery-free, energy harvesting medical sensor array, in combination with catheters, sheaths and carrying shafts, is described. Independence of batteries can lead to more compact designs and to improved practicability because battery discharge is not an issue any more.

Recent progress in wireless technology has made it possible to produce wireless sensors, which can be battery driven, thus reducing the need for cables.

Recent progress in energy harvesting has made it possible to harvest energy from environmental sources, like electromagnetic fields, sunlight, vibration, heat, etc..

The following energy harvesting mechanisms can be used: a) inductive energy transmission through electromagnetic fields, b) capacitive energy transmission, c) solar-cell based energy transmission, d) vibration based energy harvesting, d) thermoelectric energy transduction. A preferred version is the inductive energy transmission because larger energies can typically be transferred compared to other setups, but high voltages on the energy transmitter side are not required.

Furthermore, the present disclosure deals with algorithms for combining vital signals with technical control signals and motor parameters: It discloses a novel combination where multiparameter biosignal monitoring as known in the state of the art is combined with technical control signals and performance signals originating from a catheter-based or implantable circulatory pump, thus going beyond the state of the art. This has the practical advantage of rendering the biosignal analysis applicable to patients who have a catheter-based or implanted circulatory assist device.

The present disclosure also deals with methods to be used in conjunction with multiparameter signals that are suited for patients with and without heart assist devices.

One method combines a number of physiologic data sources with a number of parameters derived from a heart assist device and builds a non-linear mathematical model that correlates those data to targeted cardiac output values. The physiologic data vectors include one or more measurable or derivable parameters such as: systolic and diastolic pressure, pulse pressure, beat-to-beat interval, mean arterial pressure, maximal slope of the pressure rise during systole, the area under systolic part of the pulse pressure wave, gender (male or female), age, height, weight, and diagnostic class. The parameters derived from a heart assist device include one or more of the following: device blood flow, device type, device performance setting, motor current, rotation frequency, pressure inside device, pressure across device. The target cardiac output values are acquired using various methods, across a plurality of individuals. Multidimensional nonlinear optimization is then used to find a mathematical model which transforms the source data to the target CO data. The model is then applied to an individual by acquiring physiologic data for the individual and applying the model to the collected data.

A step consists of adding heart assist device parameters in addition to the physiological parameters for building a model. In contrast to what was done in prior art, this uses the joint information of biology and assist device to achieve a more robust result. Using setups described in prior art, assist device acted as confounders, while in the current disclosure the machine parameters are now sources of useful information. Practically, this will expand the patient spectrum to which such monitoring can be applied.

In another embodiment, measurements of the same biological parameter (preferably blood pressure and its time course) is performed at two different locations in the same compartment of the circulation. The advantage of this approach is that pulse wave propagation, that is a highly nonlinear biologic process, goes into the mathematical model as additional information and has thereby the potential to render the mathematical model more robust. In contrast, neglecting the pulse wave propagation as done in usual clinical practice renders wave propagation of the pulse wave a confounding factor for cardiac output analyses.

The present disclosure furthermore discloses a monitor designed for allowing the above described determination of a cardiac performance based on combinations of medical signals and motor control/performance signals; as well as:.

The medical invasive device according to the present invention, employed in connection with the method of computing cardiac output of a living subject, is described in more detail herein below by way of exemplary embodiments and with reference to the attached drawings, in which:.

Sensor catheter: In one embodiment of a (C/S/S) according to the present invention, a standalone monitoring catheter was constructed by polymer casting, having <NUM>" inner lumen (intended for a guide wire) and an outer diameter of <NUM>, smaller than the sheath of current pulmonary artery catheters. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of <NUM> and a length of <NUM> that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of <NUM>*<NUM>*<NUM> millimeters (STMicroelectronics, part Nr. LPS22HB ), and at the portion outside the body, the flexible electronics board carries a connector for wired readout.

Wireless sensor catheter: In one embodiment of a (C/S/S) according to the present invention, a standalone monitoring catheter was constructed by polymer casting, having <NUM>" inner lumen (intended for a guide wire) and an outer diameter of <NUM>, smaller than the sheath of current pulmonary artery catheters. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of <NUM> and a length of <NUM> that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of <NUM>*<NUM>*<NUM> millimeters (STMicroelectronics, part Nr. LPS22HB ), and at the portion outside the body, the flexible electronics board carries miniaturized chips comprising digital communication and wireless transmission (TI) and a small battery (type).

For successful energy harvesting, the energy harvested over time must be sufficient to drive the sensors at the desired measurement intervals (typically ranging between <NUM> milliseconds to <NUM> hours) and to drive wireless transmission at its desired transmission intervals (typically ranging between <NUM> milliseconds to <NUM> hours).

For inductive, wireless powering of the device, an external electromagnetic field needs to be built up. The requirements for this electromagnetic field include safety, capability for sufficient energy transfer, and compatibility with existing regulation. We have identified several design variants:.

In all options, higher frequencies typically facilitate the design of emitter and receive coils because the desired resonance frequencies can be achieved with lower inductances of coils and smaller capacitors.

Wireless energy transfer/harvesting: In a number of experiments, energy harvesting by coils integrated into our (C/S/S) was tested. To this end, a copper wire receive coil (<NUM> micrometer copper wire, <NUM> windings, coil diameter <NUM>, coil length <NUM>, inductance estimated by resonant tuning <NUM> microhenry) was integrated into a sheath, cast in PDMS. A resonant circuit was produced by connecting a <NUM> nanofarad capacitor parallel to the receive coil. Resonance in the receive circuit was observed at the frequency of <NUM>.

In addition, an energy transmit coil was built from <NUM> micrometer copper wire, <NUM> windings, coil diameter of <NUM> and coil length of <NUM>, having a measured inductance of <NUM> microhenry. The transmit coil was placed into the shaft of a catheter-based cardiac assist device. A resonant circuit was produced by connecting a capacitor of <NUM> nanofarad parallel to the emitter coil. Resonance in the emitter circuit was observed practically at the same resonance frequency (<NUM>) as in the receive circuit. The shaft was inserted into the sheath so that the emitter coil was positioned coaxially in respect to the receive coil. The emitter circuit connected in serial to a <NUM> Ohm current-limiting resistor was driven by a sinusoidal signal with frequency of <NUM> and amplitude of <NUM> V generated by a waveform generator Hewlett Packard 33120A. The receive circuit was connected in serial to a diode TS4148 used for rectification. The rectified signal was fed to a voltage regulator built based on LM3671 step-down DC-DC converter from Texas Instruments.

Successful energy transfer from the emitter circuit to the receiver circuit was documented as follows:
the voltage across a resistive load of <NUM> kOhm connected to the output of the voltage regulator was <NUM> V that corresponds to the current of <NUM> mA and the power of <NUM> mW. According to the specification of the pressure and temperature sensor LPS22HB and specification of Bluetooth Low Energy (LE) IC nrf52832 from Nordic Semiconductor this power is sufficient for acquisition of the pressure and temperature signals and transmission of the acquired data to a remote Bluetooth LE device.

These results confirm that sufficient energy can be transferred to the energy harvesting, sensor carrying catheter.

In one embodiment of a (C/S/S) according to the present invention, a copper wire receiver coil (<NUM> micrometer copper wire, <NUM> windings, coil diameter <NUM>, coil length <NUM>, inductance estimated by resonant tuning <NUM> microhenry) was integrated into a sheath, cast in PDMS. A resonant circuit was produced by connecting a <NUM> picofarad capacitor parallel to the receive coil. Resonance in the receive circuit was observed at the frequency of <NUM>. The emitter coil was separate from the catheter and was implemented with <NUM> micrometer copper wire, <NUM> windings, <NUM> coil diameter and coil length <NUM>, having a measured inductance of <NUM> microhenry. A resonant circuit was produced by connecting a <NUM> picofarad capacitor parallel to the emitter coil. Resonance in the emitter circuit was observed at <NUM>. The emitter circuit connected in serial to a <NUM> kOhm current-limiting resistor was driven by a sinusoidal signal with frequency of <NUM> and amplitude of <NUM> V generated by a waveform generator Hewlett Packard 33120A. An SMD1206 red LED was connected in parallel to the receive circuit. Successful energy transfer from the emitter circuit to the receiver circuit was documented as follows:
when the emitter coil was positioned in proximity of the receive coil (at a distance of <NUM>-<NUM>) the LED started to shine indicating availability of at least several hundred of microwatts of harvested electrical power according to LED specification.

Wireless, energy harvesting sensor catheter: In one embodiment of a (C/S/S) according to the present invention, an access sheath for a catheter-based cardiac assist device was constructed by polymer casting, having an inner open lumen of <NUM> and an outer diameter of <NUM>, corresponding to the size requirements for access sheaths of the cardiac assist device. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of <NUM> and a length of <NUM> that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of <NUM>*<NUM>*<NUM> millimeters (STMicroelectronics, part Nr. LPS22HB ), and at the portion outside the body, the flexible electronics board carries miniaturized chips comprising digital communication, wireless transmission and energy harvesting (TI).

Claim 1:
A kit comprising
- an outer element and
- an inner element,
wherein
- the outer element is a medical invasive device,
- the medical invasive device has a body portion arranged to be inserted into one of, a patient's blood vessel, a patient's body cavity and a patient's body tissue,
- the medical invasive device is equipped with an electronic circuit,
- the medical invasive device incorporates, in the body portion, a sensor arrangement and a digital data transmission arrangement,
- the medical invasive device is a sheath, the sheath being an elongated object arranged to guide the inner element, wherein the sheath covers at least a segment of the inner element, and
- the inner element is a shaft of a percutaneous heart pump, wherein the shaft comprises an integrated emitter coil circuit and wherein the sensor-equipped sheath is used to guide the shaft of the percutaneous heart pump into the body, thus assuring close proximity of emitting coil and sensor-equipped device and optimizing energy transfer.