Method for non-invasively obtaining information on the intracranial pressure of a patient

Abstract

In a method for non-invasively obtaining information on the intracranial pressure of a patient, during a first interval a plurality of facial veins of the patient, leading from a region surrounding the orbital socket are obstructed by applying external pressure on each of the plurality of facial veins. During the first interval, an external pressure is applied on a designated vein (17) connected to an intracranial vessel, at a location in the region, upstream the obstructions of the plurality of facial veins. A change of geometry of the designated vein (17) is observed, caused by the external pressure to obtain at least one first value related to a venous pressure in the designated vein (17). The at least one first value is processed to obtain the information on the intracranial pressure. The method enables the measurement of a pressure value that is closely related to an intracranial pressure without having to perform the measurement in the intracranial volume. Instead, the obstruction creates a direct communication of pressure between an intracranial vessel and the designated vein on the outside of the head that may be easily examined.

Description

[0001] Method for non-invasively obtaining information on the intracranial pressure of a patient

[0002] Technical Field

[0003] The invention relates to a method and a system for non-invasively obtaining information on the intracranial pressure of a patient.

[0004] Background Art

[0005] Intracranial pressure (ICP) is the pressure generated by the contents of the cranial cavity (in particular the cerebrospinal fluid) on the wall of the cranial cavity and on brain tissue. Normal ICP in supine adults is 5 to 15 mm Hg, acceptable values go up to about 20 - 25 mm Hg. The ICP exceeding these values (i.e. intracranial hypertension), e. g. due to a traumatic event, indicates a medical emergency as the increased pressure causes inter alia headache, ataxia, confusion, drowsiness, coma and death. Accordingly, treatment is required to reduce the ICP.

[0006] Reliably, the ICP can only be measured invasively by inserting a pressure probe through a drill hole in the skull or by puncturing the cerebrospinal fluid space in the dural sac, so- called lumbar puncture.

[0007] Several approaches for measuring the ICP non-invasively have been proposed, cf. S. J. Muller et al.: "Non-lnvasive Intracranial Pressure Monitoring", J. Clin. Med. 2023, 12, 2209. One of these approaches is discussed inter alia in US 9,585,578 B2 (Third Eye Diagnostics, Inc.) and WO 2004 / 100770 A2 (Caritas St. Elizabeth's Medical Center of Boston, Inc.), based on applying an external force on the eye and imaging the central retinal vein, e. g. by Doppler ultrasound techniques. The occlusion of the collapsed vein, stopping the blood flow, is visible from the Doppler signal. Whereas these approaches allow performing the examination through the closed eyelid, Doppler ultrasound examinations are associated with a high impact on the delicate tissue of the eye and its surrounding region. This is why acoustic output exposure levels are severely limited for ophthalmic use and usual Doppler techniques cannot just be applied to the ocular region. Furthermore, in order to obtain the ICP the value of the external pressure applied for occluding the central retinal vein needs to be adjusted to account for the intraocular pressure (IOP). This poses further problems and makes the process more complicated.

[0008] Summary of the invention

[0009] It is the object of the invention to create a method for obtaining information on the intracranial pressure of a patient that is non-invasive, reliable and has minimum impact on the patient.

[0010] The solution of the invention is specified by the features of claim 1. According to the invention, the method comprises the steps of a) during a first interval obstructing a plurality of facial veins of the patient, leading from a region surrounding the orbital socket by applying external pressure on each of the plurality of facial veins; b) during the first interval applying an external pressure on a designated vein connected to an intracranial vessel, at a location in the region, upstream the obstructions of the plurality of facial veins; c) observing a change of geometry of the designated vein caused by the external pressure to obtain at least one first value related to a venous pressure in the designated vein; d) processing the at least one first value to obtain the information on the intracranial pressure. Obstructing the facial veins prevents blood overflow out of the orbital socket and pressure equalization from the region. Therefore, obstruction relates to a state where blood overflow and pressure equalization are prevented, complete occlusion of the corresponding vessel is not required, but reduction of the cross-section by 80% or more, in particular 90% or more, may be sufficient. As the venous vessels within the region communicate with intracranial vessels such as e. g. the cavernous sinus that have an interior pressure that is directly affected by the ICP, a substantially closed system is obtained after obstruction. The closed system includes the intracranial vessels and the veins in the region that can be easily examined from the outside. This is in contrast to intracranial vessels such as the cavernous sinus, the central retinal vein or similar.

[0011] When obstructing the facial veins, it is not required to obstruct the totality of vessels that lead from the region. Vessels having only a very small cross-section will not significantly contribute to overflow or pressure equalization, so they do not need to be obstructed for creating the substantially closed system.

[0012] Measurements on healthy volunteers have shown that the relevant vessels may be obstructed by applying an external pressure of merely 20 mm Hg. Considering that the ICP will not exceed 50 mm Hg, applying an external pressure of about 55 mm Hg or more, in particular 55-70 mm Hg, is sufficient to ensure obstruction. Such a pressure has been found to be well tolerated by the healthy volunteers und it is assumed that it will be tolerated by most patients as well.

[0013] A system for non-invasively obtaining information on the intracranial pressure of a patient comprises a) an applicator for obstructing a plurality of facial veins of the patient, leading from a region surrounding the orbital socket by applying external pressure on each of the plurality of facial veins; b) an imaging probe for observing a change of geometry of a designated vein connected to an intracranial vessel, at a location in the region, upstream the obstructions of the plurality of facial veins, caused by an external pressure applied on the designated vein; and c) a processor for processing at least one first value related to a venous pressure in the designated vein, obtained from the observed change of geometry to obtain the information on the intracranial pressure.

[0014] The applicator has the purpose of simultaneously blocking blood flow in the plurality of facial veins. For this purpose, suitable pressures between the applicator and the patient's skin are in the range of 60 - 100 mmHg. They ensure that the relevant facial veins are obstructed even at high ICP values of about 50 mmHg. At the same time, such application pressures are well tolerated by the patients.

[0015] In some embodiments the applicator can have the additional function of guiding and / or supporting the imaging probe. This facilitates the measurement procedure for the operator and improves the consistency of the positioning of the imaging probe if the designated vein shall be examined at the mentioned location repeatedly. The applicator and / or the probe may have guiding elements or guiding surfaces that are designed to interact with each other to provide a reliable guidance or positioning of the probe relative to the applicator.

[0016] The processor runs software instructing the system to carry out the inventive method. The corresponding software is a further subject of the present invention. The software may be run on the imaging probe, a separate unit connected to the imaging probe by a wired or wireless connection and / or on a remote server. In general, the software controls the imaging probe to generate images of the designated vein and the surrounding tissue, processes the images (e. g. to enhance contrast or detect edges), processes further sensor data such as data of a pressure sensor for indicating the external pressure applied on the designated vein, and processing the at least one first value to obtain the information on the intracranial pressure.

[0017] Allowing for a non-invasive measurement of ICP or related quantities, the invention reduces the risk for complications, such as infections, hemorrhage or damage to the brain tissue or spinal cord.

[0018] Furthermore, compared to other non-invasive approaches, the invention enables the measurement of a pressure value that is closely related to an intracranial pressure without having to perform the measurement in the intracranial volume. Instead, the obstruction creates a direct communication of pressure between an intracranial vessel and the designated vein on the outside of the head that may be easily examined. The obstruction prevents an overflow of blood or a pressure equalization through other vessels of the venous system, which is particularly critical if the ICP is increased over normal levels. Thus, an examination outside of the intracranial volume can be carried out much more easily. In addition, the burden on the patient is reduced, e.g. by not affecting sensitive intracranial structures (such as the central retinal nerve) by the imaging process. Due to the fact that such structures are not affected, limits on imaging parameters such as energies or frequencies are less strict, which allows for imaging with better resolution and / or contrast, thus improving the precision and reliability of the measurements. Another advantage is the small distance between the skin and the designated vein, which means that the required penetration depth of the imaging modality is small and negative impacts of layers between the probe and the vein are minimized.

[0019] The inventive system and method are suitable for long-term monitoring of ICP for a period of weeks to months. The resulting information on disease development and patient rehabilitation improves patient care. In addition, due to its non-invasive nature and simplicity, the inventive system and method improve accessibility to ICP monitoring. The invention may be implemented in pre-hospital setups, allowing for more efficient patient screening and faster clinical decision making. In a preferred embodiment, during a second interval, prior and / or after the first interval, an external pressure on the designated vein at the location is applied and a change of geometry of the designated vein caused by the external pressure is observed to obtain at least one second value related to the venous pressure, i. e. the at least one first value is obtained in a scenario where the plurality of facial veins are obstructed, and the at least one second value is obtained in a scenario where the plurality of facial veins are not obstructed. Therefore, the at least one second value provides a reference value for the situation where there is no closed system including the designated vein at the measuring location and the intracranial vessel.

[0020] Again, removing the obstruction does not require to completely remove the external pressure exerted on each of the plurality of facial veins by the applicator, but the available cross-section has to be restored to e. g. at least 80% or more, in particular 90% or more of the free cross-section.

[0021] In this preferred embodiment, both the at least one first value and the at least one second value are used to obtain the information on the intracranial pressure.

[0022] In a preferred embodiment, an intracranial pressure (ICP) value is obtained from a difference between the at least one first value (pobs) and the at least one second value (Pnonobs), in particular from a set of first values and a set of second values obtained in a series of near-time measurements. This is based on the assumption that the at least one second value represents a reference value of the "open" system, whereas the higher pressure according to the at least one first value is caused by the intracranial pressure, effectively increasing the basic pressure by the effect of the ICP in the now closed system.

[0023] In this embodiment, the intracranial value (ICP) may e. g. be calculated as

[0024] ICP = k - p, where Ap denotes the veno-venous pressure difference Ap: where pnonobsdesignates the occlusion pressure without the obstruction and pobsdenotes the occlusion pressure with the obstruction of the facial veins.

[0025] Because intracranial vessel (e. g. the cavernous sinus) is under the influence of the cerebrospinal fluid and thus the ICP, the higher the intracranial pressure, the higher the pressure difference between the two states. However, even if the ICP were zero, there would be an increase in pressure because the cross-sectional area of the venous vessels was reduced. Therefore, the empirical factor k additionally comes into play. It has to be determined by experiments and may differ in particular depending on the choice of designated vein. First experiments have shown that the value of k might be close to 1, at least if the designated vein is the naso-facial vein or a sideward branch thereof (in particular close to the junction with the naso-facial vein) and if the location of the measurement is at a root of the nose (see below).

[0026] Instead of multiplication by a constant k, a more complicated function may be used to determine the ICP from the veno-venous pressure difference. Calculating the ICP from the veno-venous pressure difference has the further advantage that a constant pressure offset that is dependent from the zero-reference point for the measurement of the external pressure affects both the first and the second value in the same way and cancels out when the pressure difference is calculated.

[0027] In clinical practice, measurement of the ICP is usually zeroed to atmospheric pressure and leveled to the external auditory meatus in the supine position of the patient and to the glabella (midline between the eyebrows) in a strict lateral position, corresponding to the level of the foramen of Monro (cf. P. Reinstrup et al.: "Best zero level for external ICP transducer", Acta Neurochirurgica (2019) 161 :635).

[0028] If only a single pressure value (for the closed system) is used in the inventive method, a zero level compensation may be required to obtain an absolute ICP value relating to the specified zero-reference, allowing for comparison with values in the literature. If e. g. the zero-reference is at the brain center and if the measurements performed at the patient being in a supine position, an offset value depending on the vertical distance between the measuring location and the level defined by the brain center (phlebostatic axis). Typically, the vertical distance of the brain center from the root of the nose is about 45- 48% of the vertical distance between the forehead and the back of the head. The latter distance h may be measured, and the offset value pOffSmay be determined e. g. as

[0029] PIof Jfs5= 0-465 ■ h ■ 0.074^ mm^, based on an average distance of 46.5% and converting the vertical distance to mmHg. The offset may be entered into a user interface of the ultrasound system.

[0030] Typical values of h are 60 mm, accordingly, a typical value for pOffSmay be 4.4 mmHg. Similar offset values may be calculated in an analogous fashion for other zero-reference levels and / or head orientations during the measurements.

[0031] Positioning of the patient in a true supine position or in a true lateral position may be supported by a laser projector projecting a horizontal and / or vertical line onto the face of the patient. The line may then be aligned with facial features such as the bridge of the nose, the chin, etc. Alternatively, or in addition, visual markers, transducers or sensors may be arranged on designated facial features, and the vertical distance between the measuring location and the phlebostatic axis may be automatically determined based on (video) images of the patient including the markers or based on signals from the transducers or sensors.

[0032] Measurements on healthy subjects in the supine and in the lateral position have shown excellent correlation between the pressure values corrected for a given zero level. Instead of performing a zero-level compensation, the first value may be re-referenced to the second value or to an estimate of central venous pressure, such as supine peripheral venous pressure in the forearm or at the level of the jugular vein.

[0033] Further measured values may be taken into account for obtaining the information on the intracranial pressure, such as a venous pressure measured outside the region surrounding the orbital socket. When taking and / or processing the measurements, the pulse or the point in time within the cardiac cycle may be taken into account.

[0034] In alternative embodiments, a machine learning approach is used to obtain the ICP value from the veno-venous pressure difference, pressure values relating to the open and / or closed state and / or further measured values. The machine learning approach may be based e. g. on a trained multi-layer artificial neural network.

[0035] In some embodiments, the information on the intracranial pressure is obtained from the at least one first value and a duration measured from an onset of obstruction to a point in time of obtaining the at least one first value.

[0036] In particular, the information is based on the duration until a stable elevated pressure is established. With healthy individuals, this duration is usually about 5-6 s. An increased duration points to delayed pressure equalization in the intracranial volume and may be an indication of elevated ICP and / or onset of an impending increase of the ICP.

[0037] In these embodiments, it is not required to determine an absolute value of the ICP. The duration may be obtained directly from the analysis of several measurements of the first value over time.

[0038] In preferred embodiments, the geometry of the designated vein is observed based on ultrasound images of the designated vein.

[0039] Therefore, in these embodiments the imaging probe is an ultrasonic probe. Ultrasound is particularly well suited for the examination of blood vessels embedded in tissue close to the skin surface. Corresponding probes are compact, cost-effective and allow for an intuitive way of examining the designated vein.

[0040] Ultrasound frequencies in the range of 10-60 MHz, preferably 15-50 MHz, most preferably 20-30 MHz, have been turned out to provide good results. They provide a good resolution, and the depth of penetration allows for imaging all relevant blood vessels. During the measurement process, the ultrasound frequency may be tuned in order to ensure sufficient depth of penetration in an identification phase of the designated vein, and sufficient resolution in the phase of observing the designated vein's geometry.

[0041] Preferably, the external pressure is exerted on the designated vein by a front surface of an ultrasound probe.

[0042] In particular, the ultrasound probe features a pressure sensor for measuring the external pressure exerted by the ultrasound probe at the location of the measurements. Such probes have already been proposed, see EP 3 716 842 A1 (Veinpress GmbH).

[0043] The pressure sensor may be arranged in front of the ultrasound array, e. g. comprising a liquid-filled cavity delimited at the front face by a flexible membrane, and the pressure of the fluid may be measured by a sensor arranged inside the cavity or connected to the cavity by a fluid line. In other embodiments, the pressure sensor may be (completely) arranged beside the ultrasound array or behind the ultrasound array. In the latter case, e. g. a strain gauge may be arranged behind the array.

[0044] There are alternatives to ultrasound imaging. The geometry of the designated vein may be observed based on A-mode ultrasound. A hybrid approach is possible, where the location of the vein is identified in B mode ultrasound images. Subsequently, the geometry of the vein is monitored in A mode, using a single element of the ultrasound array. A further alternative to ultrasound is near-infrared imaging. In principle, different approaches may be used, in a first phase of identifying the designated vein and in a second phase of observing the vein's geometry. Nevertheless, using an imaging process throughout the method ensures that the relevant vessel and position may be tracked without any interruption, reducing the risk of inadvertent shifts of position or vessel.

[0045] Advantageously, the information on the venous pressure is an external pressure value corresponding to an onset of occlusion of the designated vein.

[0046] Occlusion may be determined from a distinct reduction of the diameter or cross-section of the vein and / or from the lack of blood flow in Doppler ultrasound pictures. Alternatively, or in addition, the stopping of the blood flow may be identified from acoustic measurements, based on the noise generated by the flowing / non-flowing blood in the vein.

[0047] The measured occlusion pressures closely correspond with the pressure within the vein: In healthy subjects with experimentally induced venous hypertension with a wide range of pressure values, a strong correlation (r= 0.95, p= 0.001) between non- invasive and invasive peripheral pressure at the forearm was shown. High interobserver agreement with an interclass correlation index of 0.988 showed excellent reliability of the system. Best results were achieved when a superficial vein was compressed against underlying bone (Ch. Thalhammer et al.: Noninvasive central venous pressure measurement by controlled compression sonography at the forearm, J Am Coll Cardiol. 2007 Oct 16;50(16):1584-9).

[0048] David Martin stated in 2016: "In this technique, a bladder filled with an ultrasound- translucent mixture of water and glycerin and connected to a manometer is attached to the head of a linear array ultrasound probe. The ultrasound probe / bladder is then slowly pressed against the skin overlying a vein of interest until the vein is compressed to the point of closure as visualized on the ultrasound screen. In accordance with Laplace's law, the pressure which is applied to compress the vein is assumed to equal the pressure within the vein." (D. S. Martin et al: Internal jugular pressure increases during parabolic flight, Physiol Rep. 2016 Dec; 4(24): e13068).

[0049] In a preferred embodiment, a plurality of ultrasound image frames are stored with assigned values of external pressure and the external pressure corresponding to the outset of occlusion is determined retroactively based on the plurality of ultrasound image frames and the assigned values of external pressure.

[0050] This retroactive determination may be automatic, e. g. by an image analysis algorithm. Alternatively, the determination is made manually, based on a displayed video representing the image frames. The video may be replayed at different replay speeds, and the replay speed may be adjusted by the operator.

[0051] Instead or in addition, the processing of the imaging data may be supported by an automated vein tracking and occlusion detection algorithm. Such a vision-based algorithm is designed to identify and track veins within ultrasound images during measurements performed by the healthcare professional, maintaining stability despite minor probe movements. In addition, the algorithm may provide visual assistance in identifying veins within ultrasound images, thereby enhancing visibility; guide optimal probe positioning; and / or offer visual confirmation of vein occlusion, observing changes in the vein's expansion and shape under obstruction.

[0052] The probe may include a mechanism for the controlled application of external pressure (i.e., compression and decompression), mimicking the process of gradually increasing external pressure until vein collapse to acquire average occlusion pressure.

[0053] A unit for measuring position and / or orientation may be integrated to the imaging probe, such as a 6 degrees of freedom inertial measurement unit comprising an accelerometer and gyroscope. Such a unit provides accurate data on the positioning, tilting, and movements of the probe, guiding the user for optimal probe positioning during measurement and / or providing data for the improved processing of the measured data.

[0054] Instead of occlusion, the external pressure value may correspond to a certain reduction in diameter and / or cross-section of the observed vein, wherein the relevant quantities may be defined in such a way that the external pressure does not correspond to complete occlusion of the respective vein. A progression of pairs of external pressure values and specific dimensions obtained from the corresponding images may be modelled by a fitting function, and the external pressure value corresponding to said reduction may be obtained from the fitting function.

[0055] In general, the designated vein and the location shall fulfil the following criteria: the vein shall be close to the skin surface, this allows for reliable compression when observing the change of geometry and facilitates the imaging of the vein; at the location, a bone should be directly behind the designated vein; again, this ensures reliable compression and prevents the vein from migration when applying external pressure.

[0056] In first preferred embodiments, the designated vein is the naso-facial vein or a sideward branch thereof (in particular close to the junction with the naso-facial vein) and the location is at a root of the nose.

[0057] The naso-facial vein (including sideward branches in a region at the root of the nose) and the mentioned location fulfil the above criteria. At the lower outer rim of the orbital socket, this vein crosses over the flat cheek bone. Thanks to its superficial location, it can be displayed with high-resolution ultrasound, making it an ideal candidate for measuring venous occlusion pressure using compression sonography. Furthermore, the location is easily accessible and performing measurements there is not particularly uncomfortable for the patient.

[0058] In second preferred embodiments, the designated vein is the frontal vein (vena frontalis, also vena supratrochlearis) and the location is on the forehead, above the eyebrow and approximately vertically above the inner corner of the eye. In particular, the location is within a region 3-6 cm above the inner corner of the eye and having a horizontal distance from that inner corner of less than 2 cm. The frontal vein may be easily found, wherein the visibility may be even enhanced by the patient performing a Valsava manoeuver. At the mentioned region, the frontal vein has a superficial location, lying close to the frontal bone (os frontale), a hard and smooth base. Therefore, this vein is easy to compress, with few potential error sources, until it is occluded. Furthermore, the measuring location is on the central axis of the patient's face, which means that no zero level compensation is required if the measurements are taken in the patient's lateral position or that zero level compensation is rather simple if the the measurements are taken in the patient's supine position.

[0059] In order to facilitate the compression of the frontal vein and the imaging thereof, the frame of the applicator preferably features a central frontal extension, exposing and surrounding a region above the nose and the inner corners of the eyes, including the location mentioned above. The horizontal width of the extension (parallel to the line connecting the centers of the eyes) may be preferably about 4-9 cm, in particular 5-7 cm. The vertical extension of the region exposed by the extension may be preferably about 2-6 cm, in particular 3-5 cm. This ensures easy accessibility of the location where the frontal vein shall be compressed and monitored and at the same time safe obstruction of the plurality of facial veins.

[0060] In other embodiments, the information on intracranial pressure is obtained at a first point in time, the information on intracranial pressure is obtained at a second point in time and a measure for a progression of intracranial pressure is obtained from a comparison of the information obtained at the two points in time.

[0061] An increase of pressure values obtained in the course of the measurements over time is a sign of an increase in intracranial pressure. This holds true even if no absolute intracranial pressure value is determined. Therefore, even if no absolute pressure values are deemed to represent physiological quantities relating to the patient the inventive method provides meaningful results.

[0062] In preferred embodiments of the inventive system, the applicator has an elongated shape adapted to reach pressure application points of all of the plurality of facial veins, the applicator being formed in particular to at least partially surround the orbital socket when applied to a face of the patient. This allows for leaving out an aperture in the eye region(s), which on the one hand improves patient comfort and on the other hand allows easy access to the designated vein with the imaging probe.

[0063] In general, the applicator should fulfil the following criteria:

[0064] It is adaptable to different head shapes.

[0065] It applies the load periorbital to the scalp evenly.

[0066] They may be switched quickly between the two states (load, no load).

[0067] They may be fixed in such a way that their position does not shift during the measurements.

[0068] In a first group of preferred embodiments, a shape of a contact surface of the applicator to contact a face of the patient is adaptable prior to starting the obstruction, wherein an adapted shape may be fixedly set prior to applying pressure to the face of the patient.

[0069] This allows for specifically adapting the shape of the applicator to the shape of the patient's face, thus ensuring at the same time complete obstruction of the relevant facial veins and the patient's comfort. Several solutions are available: a) The applicator may comprise elements featuring cavities delimited at least by a flexible airtight material and accommodating a number of small objects (e. g. small spheres made from polystyrene). In a configuration where the elements contact the patient's skin and where the cavities comprise air the objects will be distributed in the cavities in such a way that the elements' outer shape corresponds to the shape of the contacted regions of the face. If the air is evacuated, the position of the objects and thus the outer shape of the elements is fixed. b) Contact elements of the applicator are made from an elastic material that can be hardened in short time. c) The applicator features mechanical hinges and / or guides, wherein an angle position of extension may be fixed by appropriate means, e. g. screw or clamping elements.

[0070] In more simple embodiments, an elastic material is used that adjusts itself to the geometry of the contacted surface, e. g. a foam rubber material.

[0071] In other embodiments, the applicator comprises at least two support regions and at least one contact pressure region, wherein a variable length spacer is arranged between each of the at least two support regions and the at least one contact pressure region in such a way that a distance between a first contact surface of the at least two support regions and a second contact surface of the at least one contact pressure region, in a direction perpendicular to a main extension of the applicator is adjustable.

[0072] This allows for changing the applicator between the non-obstructing and obstructing configuration without affecting the positioning of an imaging probe, e. g. an ultrasound probe. Accordingly, it is ensured that the geometry of the same vessel will be measured at the same time in both configurations.

[0073] The positioning of the spacers, i. e. the location of the support regions will be chosen in such a way that the spacers act on facial regions where no relevant facial veins are obstructed due to the forces exerted by the spacers. For example, the spacers may be supported on the cheekbones and in suitable regions of the forehead bone, in the regions of the eyebrows.

[0074] Advantageously, the variable length spacers comprise pneumatic elements that may be actuated by an air pump

[0075] The pneumatic elements may be pneumatic bellows that may be filled or emptied by ambient air using the air pump and a switchable outlet valve. In the filled state, the pneumatic elements will lift off the contact pressure region(s) from the face of the patient, such that the plurality of the facial veins of the patient are not obstructed and blood may freely flow in these veins. When the pneumatic elements are emptied, their extension in the direction perpendicular to the main extension of the applicator is reduced and the contact pressure region(s) contact the corresponding regions of the patient's face. An external pressure applied onto the applicator is thus transmitted to the face and leads to obstructing the facial veins.

[0076] The air pump may be a manual pump. It is preferably equipped with a manometer for measuring the pressure in a cavity of the pneumatic elements. Instead, an electric pump may be used.

[0077] In alternative solutions, the changing the applicator between the non-obstructing and obstructing configuration is achieved by selectively pulling on a retaining element that is attached to the applicator and allows for retracting the applicator in the direction of the patient's face. The required force may be produced e. g. by a pneumatic cylinder.

[0078] In a second group of preferred embodiments, the applicator comprises a substantially rigid frame, a retaining device for attaching the frame to the patient's face and at least one pneumatic bladder attached to the frame, a contact surface of the applicator being formed by the bladder. Using the retaining device, the frame is attached to the patient's face, and subsequently, by inflating the bladder, a contact pressure between the contact surface and the face is built up, and at the same time, the contact surface assumes the shape of the facial region it is interacting with. Therefore, using just a single action, namely inflating the bladder, allows for selectively activating the obstruction and at the same time adapting the shape of the applicator to the specific shape of the patient's face.

[0079] In preferred embodiments, the pneumatic bladder includes sections having different cross sections. This allows for taking into account different requirements in different regions of the patient's face. Preferably, a second cross section in a temple section of the pneumatic bladder is larger than a first cross section in a frontal section of the pneumatic bladder. In particular, the second cross section is at least 130%, in particular at least 150%, of the first cross section.

[0080] In a particularly preferred embodiment, the retaining device comprises a section interacting with the back of the patient's head and at least one further pneumatic bladder arranged in this section. The further pneumatic bladder may be inflated simultaneously with the pneumatic bladder attached to the frame. This minimizes the movement of the frame when activating or deactivating the obstruction and thus avoids negative impact on the positioning of the probe, in particular in cases where the operator rests his hand on the frame. To achieve this, the volume and geometry of the (front) pneumatic bladder interacting with the patient's face should be appropriately matched to the volume and geometry of the (back) pneumatic bladder.

[0081] The section may be constituted at a strap that is connected with its ends to the left and right end of the frame. Alternatively, the section may be constituted by two brackets, each of the brackets being connected to one end of the frame and partially embracing the patient's head on the respective side.

[0082] Alternatively, the pressure on the applicator is generated exclusively from the front and no retaining device is required that interacts with the back of the patient's head. This is advantageous or even required in cases of skull injuries. Contact surfaces of the at least one pneumatic bladder and or the retaining device may be coated by a peelable adhesive and / or a substance that increases friction between the contact surface and the patient's head. This reduces the risk of slipping and thus shifts of the applicator.

[0083] The applicator, in particular the frame and / or the retaining device including the respective bladder(s) may be single-use objects. This ensures reliable function, in particular of the bladders, and improves hygiene.

[0084] In preferred embodiments, the ultrasonic probe has a head piece, a contact portion of the head piece having a generally circular footprint and accommodating an ultrasound transparent fluid.

[0085] The ultrasound transparent fluid is a liquid that has a low evaporation, in particular a natural oil. The circular footprint is optimal for the present application, and the head piece is preferably formed in such a way that a rear part matches the elongated shape of the ultrasound array whereas the front part has the circular shape. The shape is designed such that the ultrasound radiation, at least ultrasound radiation emanating from a central part of the ultrasound array, is not negatively affected on its path between the front surface of the head and the ultrasonic array.

[0086] For the examination of the naso-facial vein, a diameter of the contact portion of 12-30 mm, in particular 15-25 mm, has turned out to be optimal. It is small enough that the measuring location can be reached and large enough that the external pressure is evenly distributed in the head and from the head to the facial surface the probe is acting on.

[0087] Preferably, the head piece features a constricted section, the constricted section being arranged between a front surface of the head piece and an interface region to connect the head piece to a base body of the ultrasound probe The front surface of the head piece forms the contact surface to the skin of the patient. It is made from a flexible and ultrasound transparent material, in particular a silicone rubber material, having a thickness of 0.01 -0.5 mm. A jacket of the head may be made from a stiffer material, e. g. from the same silicone material with a larger thickness or from another material having a larger stiffness than silicone.

[0088] Preferably, a front surface of the ultrasound array is embedded in the cavity defined by the head piece, containing the ultrasound transparent fluid. This reduces the number of interface surfaces between the array and the patient's skin by one and thus improves the overall image quality.

[0089] The distance between the array and the front surface of the head is chosen in such a way that reverberations in the visible image region are avoided.

[0090] In a variant, the inventive method comprises the further step of illuminating the designated vein using a visible light source placed in an intracranial cavity, in particular in the oral-pharyngeal cavity. This approach is known as diaphanoscopy and is applied in various areas such as supporting endoscopy-assisted percutaneous puncture of organs in gastroenterology or endoscopic fluoroscopy of the trachea, illumination of paranasal sinuses, fluoroscopy of the scrotum or finger joints or in ophthalmology.

[0091] The tissues separating the oral-phyryngeal cavity from some of suitable facial veins, e. g. the naso-facial vein, are rather thin and translucent. With many patients, using e. g. a white LED light source with a luminous flux of about 500-1000 Im, placed in the oral- phyryngeal cavity is sufficient to illuminate the naso-facial vein and its surroundings in such a way that the vein is clearly discernible from the outside, having a darker appearance than the surrounding tissue. The effect is strongly enhanced when the plurality of facial veins are obstructed as foreseen in the inventive method.

[0092] Illuminating the vein from behind facilitates the identification of the location of the vein and provides information on the stage of obstruction of the facial veins. In addition a video imaging device may be used to produce high-resolution images of the illuminated designated vein. This allows for monitoring the changes caused by the obstruction and / or the external pressure exerted onto the designated vein. The imaging device may be part of the imaging probe and provide the primary imaging data to be processed further in order to obtain the first value. Alternatively, the imaging device provides further data that is processed together with the data obtained by the imaging probe.

[0093] Preferably, the light source is part of a device having an external housing made from materials that are suitable for medical use and disinfection. The emitted light should include the wavelength range of 600-900 nm, ensuring optimal visualization of venous structures. The illumination intensity may be adjustable in order to suit different patient physiologies and skin types. A diffuser may be foreseen to ensure uniform distribution of light. As mentioned, an LED light source is suitable as it minimizes the heat produced and thus potential discomfort to the patient.

[0094] Other advantageous embodiments and combinations of features come out from the detailed description below and the entirety of the claims.

[0095] Brief description of the drawings

[0096] The drawings used to explain the embodiments show:

[0097] Fig. 1 a representation of the blood vessels in the region of the orbit and the cavernous sinus;

[0098] Fig. 2A, 2B the arrangement of veins in the orbital region and locations where facial veins may be squeezed to prevent overflow from the orbital region;

[0099] Fig. 3A, 3B the situation during a measurement in the obstructed state of the facial veins in a front and in a lateral view; Fig. 4A, 4B an oblique view and a top view of an applicator that may be used in the context of the inventive system;

[0100] Fig. 5 a side view of an embodiment of an ultrasonic probe that may be used in the context of the inventive system;

[0101] Fig. 6A, 6B an oblique view and a cross section of the head of the probe;

[0102] Fig. 7A, 7B views of the user interface of the ultrasound system during measurements according to the inventive method;

[0103] Fig. 8 the temporal progression of the measured occlusion pressures in four series of measurements, taken on the two subjects;

[0104] Fig. 9 the increase of the occlusion pressure due to obstruction of the facial veins;

[0105] Fig. 10 a frontal view on a further embodiment of an applicator that may be used in the context of the inventive system;

[0106] Fig. 11 the situation during a measurement in the obstructed state of the facial veins using the further embodiment in a front view;

[0107] Fig. 12A-C the temporal progression of the measured occlusion pressures in three further series of measurements;

[0108] Fig. 13 an oblique view of yet a further embodiment of an applicator that may be used in the context of the inventive system; and

[0109] Fig. 14 an oblique view of an alternative embodiment of a rear bladder for the applicator.

[0110] In the figures, the same components are given the same reference symbols. Preferred embodiments

[0111] The Figure 1 is a representation of the blood vessels in the region of the orbit and the cavernous sinus, including connecting intracranial veins. The ophthalmic veins 12.1, 12.2, drain the blood from the eye socket in direction to the inside of the skull, to the cavernous sinus (CS) 11. They include the superior ophthalmic vein 12.1 that joins the CS 11 after passing through the supraophthalmic fissura. They further include the inferior ophthalmic vein 12.2 that can either join the CS 1 1 separately or join the superior ophthalmic vein 12.1 before the CS 1 1.

[0112] The cavernous sinus 11 is a paired dural venous sinus in the middle of the cranial fossa on either side of the sella turcica of the sphenoidal bone.The cavernous sinus 11 itself is in direct contact to the intracranial sinus and intracranial veins. A characteristic feature of the CS 1 1 is its anatomical division into smaller compartments. It is approximately 1 x 2 cm in size in a human adult. Physiologically, it has many inflows because of connections with the surrounding venous network including the ophthalmic veins 12.1, 12.2, sphenoparietal sinus, superficial middle cerebral vein (Sylvian vein) and pterygoid plexus 13 located in the infratemporal fossa. The superior and inferior petrosal sinuses are continuations of the CS, changing during their further course into the transverse sinus and internal jugular vein.

[0113] The CS 11 contacts on one hand the bone, on the other hand it is covered by a connective tissue membrane (approx. 50%) that is directly affected by the intracranial pressure (ICP). Accordingly, an increase in ICP will lead to a constriction of the CS 11, thus inhibiting venous return from the ophthalmic veins 12.1, 12.2 with a corresponding increase in pressure. Furthermore, the CS 11 is in direct contact to intracranial sinuses and veins. There are no valves in intracranial veins. Therefore, the ICP is directly transmitted to the intracranial veins and the CS. Similarly, no valves are in the veins of the orbital socket. For this reason, it is assumed that the ICP is transmitted directly to the veins in the orbital socket.

[0114] The superior ophthalmic vein 12.1 is formed by the union of the angular vein 14 and the supraorbital vein 15. The supraorbital vein (SOV) 15 is the largest vein of the orbital socket. The SOV 15 provides the main venous drainage of the orbit, originating in the supranasal quadrant of the orbit and extending posteriorly through the medial part of the superior orbital fissure into the cavernous sinus 11. There are no valves in the respective intracranial vein nor in the orbital veins.

[0115] In 1971 SOHAN SINGH HAYREH AND JOHN EDWARDS from the Department of Experimental Ophthalmology, University of London published a paper on the effect of acute intracranial hypertension on ophthalmic arterial and venous pressures (Brit. J. Ophthal. (1971) 55, 649). In 27 rhesus monkeys, the normal systemic and ophthalmic venous pressures and superior sagittal sinus pressure were recorded after cannulation. In summary they stated, "The ophthalmic venous pressure and superior sagittal sinus pressure showed a significant correlation with each other and with the rise in the cerebrospinal fluid pressure". Therefore, a direct correlation between the (artificially augmented) ICP and the ophthalmic vein pressure was shown.

[0116] Furthermore, case studies have observed that pressure from the cavernous sinus can be transmitted through the emissary veins to the periorbital area, causing bruising in patients with high ICP (S. Hadjikoutis, C. Carroll, and G. T. Plant, "Raised intracranial pressure presenting with spontaneous periorbital bruising: two case reports.", J Neurol Neurosurg Psychiatry, vol. 75, no. 8, pp. 1192-3, Aug. 2004). This supports the existence of a measurable correlation between ICP and emissary venous diameter or pressure.

[0117] The diameter of the SOV 15 can be radiolog ica lly recorded in CT and MRI. However, local resolution of ultrasound imaging is much higher than of CT or MRI. Ultrasound at 24 MHz allows for a resolution of about 0.2 mm. The Doppler ultrasound examination allows the determination of the flow direction and velocity.

[0118] Enlargement of the supraorbital vein 15 and elevated intracranial pressure (ICP) are related to each other. Studies suggest that an increased ICP impairs the pressure gradient for venous return from the extracranial SOV 15 to the intracranial cavernous sinus 11 (Kiyotaka Kuroda et al.: Does the superior ophthalmic vein dilate in acute intracranial hypertension due to hemorrhagic stroke?, Radiology Case Reports Vol. 18, Issue 7, July 2023, p. 2522).

[0119] In a further study (Jing-Feng Lirng. et al.: Diameter of the Superior Ophthalmic Vein in Relation to Intracranial Pressure, AJNR Am J Neuroradiol., Apr 2003, 24(4):700), 69 patients (32 male, 37 female; mean age, 46 years + / - 19) were included. The average diameters of the SOV and the ICP were positively correlated (r = 0.58, P <.001), if an SOV diameter of < 1 mm was treated as 0.5 mm for calculations. In patients with increased ICP (CSF pressure >200 mm H(2)O), SOV diameters were larger than those of patients with a normal CSF pressure (3.0 vs 1.6 mm, P <.001). Frequencies of increased ICP were 3% among patients with an average SOV diameter of 0.5-1 mm, 15% for 1.5-2 mm, and 58% for 2.5-5 mm (P <.001).

[0120] Based on the available evidence, there seems to be a correlation between elevated ICP and orbital vein dilatation, specifically the diameter of the superior ophthalmic vein. However, not all studies have found consistent results. Some studies came to the conclusion that SOVs do not consistently dilate with increased ICP.

[0121] The present invention is based on the assumption that the pressure in the SOV 15 is limited to a certain maximum value due to the fact that orbital veins act as emissary veins having an outflow to the facial veins. Thus, an overflow out of orbital pocket is possible and the pressure in the SOV 15 can maximally reach the venous pressure in the facial veins. A higher pressure is relieved via the facial veins by overflow. Therefore, no expansion of the SOV 15 needs to be visible on MRI or CT despite elevated ICP. In addition, there might be (irregular) flaps in the SOV 15, influencing pressure transmission.

[0122] The invention proposes to overcome this limitation by preventing the overflow to the facial veins and thus getting direct access to the pressure in the cavernous sinus 11 and thus the ICP by outside measurements. In order to prevent the undesired overflow, the relevant facial veins are squeezed in a region where they lie close to the skin surface and are backed by bone tissue. The squeezing is effected by applying pressure on the skin using a suitable applicator.

[0123] The Figure 2A represents the arrangement of veins in the orbital region. In addition to the superior ophthalmic vein 12.1, the inferior ophthalmic vein 12.2, the angular vein 14 and the supraorbital vein 15 mentioned above these veins include for example the superior palpebral vein 16.1 and the inferior palpebral vein 16.2 draining the upper eyelid.

[0124] In Figure 2B, locations 21.1...5 where the relevant facial veins may be squeezed to prevent overflow from the orbital region are indicated by arrows. The goal is to temporarily obstruct all larger blood vessels that could enable an overflow from the system constituted by the facial veins downstream to the respective obstruction and the ophthalmic veins 12.1, 12.2 that are directly connected to the cavernous sinus 11. It is not critical, if smaller venous vessels having a substantially smaller cross-section are not obstructed, as they could not significantly contribute to overflow from the system.

[0125] Figure 3A, 3B show the situation during a measurement in the obstructed state of the facial veins in a front and in a lateral view. The relevant facial veins are obstructed using the applicator 30, which will be described in more detail below. In Figure 3A, only the contact surface of the applicator 30, in its activated configuration, is indicated by the dashed surface. The location 22 at the root of the nose, above the nostrils, where the naso-facial vein 17 (or a sideward branch thereof) is compressed and its occlusion is monitored by ultrasound is indicated by an arrow. The same location 22 is shown in Figure 3B as well. The naso-facial vein 17 here lies superficially directly under the skin on the bone of the nasal insertion. It can easily be compressed.

[0126] The applicator compresses the periorbital region in selected regions and with it the veins in the skin. If the compressing pressure is sufficient, outflow of blood out of the orbital socket into the veins of the face is stopped. The result is a funnel-shaped measuring system that is closed to the outside. Thus, venous blood flow in the orbital socket is diverted to the cavernous sinus 11. A communicating system of vessels is formed. The venous pressure in the orbit increases to the outflow pressure in the cavernous sinus 11.

[0127] The Figure 4A is an oblique view of an embodiment of an applicator that may be used in the context of the inventive system. The Figure 4B shows a top view of the applicator.

[0128] The applicator 30 features a mask 31 and a strap 34. The mask 31 comprises a C-shaped frame 32, wherein the open legs of the frame 32 are connected by a nose bow 33. The frame 32 and the nose bow are made from a rigid plastic material. In the frame 32 vertical grooves 32a are formed on both the upper leg and the open legs, symmetric to the central symmetry axis, the upper groove of one side being aligned with the lower groove of the same side. The grooves 32a improve the flexibility of the mask 31 with respect to its curvature about the symmetry axis. The geometry of the frame 32 and the nose bow 33 is adapted to the geometry of the human face such that the mask 31 may be applied to the face in such a way that the frame 32 encloses both orbital regions, whereas the nose bow 33 runs around the wearer's nose. In both its outer regions, the frame 32 features a group of three fastening holes 32a. At a central location of the upper part, an attachment hook 32b is arranged.

[0129] The strap 34 is made from an inelastic textile material. At both ends, it features an adjustment mechanism 34a and a hook 34b. Using the hooks 34b and the fastening holes 32a, the strap may be removably attached to the frame 32 of the mask 31. This allows for securing the mask 31 to the wearer's head. Selecting different fastening holes 32a allows for selecting a different load distribution of the strap 34 to the upper and lower rim of the mask 31. A further strap (not shown) may be attached to the attachment hook 32b of the mask 32 and the rear portion of the strap 34 in order to further secure the mask 31 on the head and to avoid the strap 34 slipping downwards. In an alternative embodiment, described in connection with Figure 13 below, the strap includes cooperating Velcro elements and runs through lugs arranged on both sides of the frame. This replaces the hooks and fastening holes as well as the length adjustment mechanism shown in the Figures. Further variants of the adjustment mechanism are possible, e. g. using systems employing rotary knobs as known from the BOA Fit System offered by Boa Technology, Inc., or drawstring stoppers. The adjustment mechanism(s) may be arranged at the lateral or rear portion of the strap or on the mask.

[0130] The applicator 30 further comprises a pneumatic system. This system features a C-shaped bladder 35 that is attached to the back surface of the C-shaped frame 32 of the mask 31. It further features a rear bladder 36 supported by the inside surface of a load shield 37 which itself is attached to the inner side of the strap 34. Both the C-shaped bladder 35 and the rear bladder 36 are connected to a common pressure source 38 by respective tubing. The pressure source 38 features a hand pump 38a, a release vent 38b and a manometer 38c. In order to enhance the extendibility of the bladders 35, 36, some or all of them may feature several stacked chambers and / or bellows. To match the shape of different faces, applicators with different sizes and / or curvatures may be provided.

[0131] The Figure 5 is a side view of an embodiment of an ultrasonic probe that may be used in the context of the inventive system. The Figure 6A shows an oblique view of the head of the probe, and Figure 6B shows a cross section of the head.

[0132] The ultrasonic probe 40 features a housing 41 accommodating electronics 42 for controlling the device and processing measurements. A linear ultrasonic array 43 with 32 elements is accommodated in a front portion of the housing 41. A frequency of 24 MHz is used for the imaging of the tissues in the region of interest. The ultrasonic probe 40 delivers B-mode images with 256 gray shades, having a resolution of 0.07-0.10 mm.

[0133] Alternatively, ultrasonic arrays with more elements, e. g. 128 elements, may be used. The number of active elements may be dynamically reduced by the control software as soon as the region to be observed is identified. In parallel, the ultrasound frequency may be varied and assume values that are higher or lower than 24 MHz.

[0134] The head 44 of the ultrasonic probe 40 is constituted by an attachment part 45 formed from a unitary piece of shore 40 A silicone material. The attachment part 45 features a base part 45a with an oval footprint (main axes 28 mm I 14 mm) that may be attached on a corresponding counterpart section of the housing 41 of the ultrasonic probe 40. Attached to the oval base part is a circular front part 45b (diameter 20 mm) made from the same material but with a smaller wall strength. The maximum wall strength in the base part 45a is about 1.5 mm. The wall strength is minimal (about 0.3 mm) at a substantially planar front surface 45c of the front part 45b.

[0135] Between the attachment part 45 and wall structures inside the housing 41, a closed cavity is formed. The cavity is filled with an ultrasound-transparent liquid, e. g. a natural oil with low viscosity. The liquid surrounds the ultrasonic array 43. A pressure sensor 46 communicates through a thin tube with the cavity and allows for measuring the interior pressure in the cavity. The sensor allows for a measurement rate of at least 20 Hz and has a resolution of 0.1 mbar. A corresponding solution is described in WO 2023 / 104390 A1 (Compremium AG).

[0136] Using the applicator 30 and the ultrasonic probe 40, measurements according to the inventive method may be taken. The Figures 7A, 7B are views of the user interface of the ultrasound system during such measurements. An exemplary sequence of steps in a measuring process may be as follows, wherein the healthcare professional is guided to perform these steps by the user interface of the ultrasound system:

[0137] 1. The patient is made to lie down in a supine position, on a 4° inclined surface, where the head is positioned lower than the feet. This ensures complete filling of the veins. Other measures ensuring complete filling of the veins may be taken, e. g. further increasing the height of the patient's legs, positioning the patient in a sitting portion with the head tilted forward or positioning the patient on the side.

[0138] 2. The healthcare professional measures the distance from the orbital socket measuring point to the external auditory canal (meatus acusticus). This will later be used for hydrostatic correction. The value is entered using the system's user interface.

[0139] 3. An applicator 30 is selected from several available sizes, based on the geometric properties of the patient's head. In particular, the applicator is chosen based on the frontal width. The applicator 30 is attached to the patient's head. For this purpose, the strap is shortened using the adjustment mechanisms 34a until it rests snugly against the head, without exerting forces on the mask 31. The bladders 35, 36 are non-inflated and the release vent 38b is open. Already, the mask 31 is positioned such that its frame 32 lies on the final position that will be used in a subsequent step to obstruct the facial veins.

[0140] 4. Next, first measurements of the occlusion pressure of the naso-facial vein are taken.

[0141] First, the integrated pressure sensor is calibrated, and the value of the measured pressure is set to zero. In addition, the user may specify parameters relating to the linear ultrasound array of the probe, such as depth, gain, focus and frequency. Next, the operator grasps the ultrasonic probe 40 and orients it in such a way that the head points downwards. In this orientation, the pressure sensor of the probe is calibrated to 0 mmHg.

[0142] Next, the well-gelled head of the ultrasonic probe 40 is placed in such a way that its center contacts the skin covering the naso-facial vein itself or a sideward branch thereof, close to the junction with the naso-facial vein and that the respective vein is clearly visible in the ultrasound image. (Optionally, this step is supported by illuminating the vein and the surrounding tissue from behind, using a light source placed in the oral-pharyngeal cavity as described above.) The probe is oriented in such a way that its array points vertically in the direction of the nasal root of the respective half of the patient's face. In most cases it should be possible to find the facial vein at a distance of about 2 cm below the lower eyelid. During the examination, the guiding hand of the operator rests on the patient's head at at least one point, and the probe is rotated and aligned until the cross-section of the target vessel appears as a round contour. Vessels may be squeezed at low external pressures at or below 5 mmHg. Thus, to find a suitable vessel, the specimen should be searched by pumping movements for a contour that collapses under load. The lower load should fall well below 5mmHg.

[0143] The Figure 7A shows an ultrasound image, where the uncompressed vessel is clearly visible (item 1). Its width is about 2.8 mm and the height is 1.6 mm. The contours are sharp. Now, the external pressure between the head of the ultrasonic probe and the skin is increased until the vessel collapses. The corresponding picture, just prior to collapse, is shown in Figure 7B, item 2. The corresponding value for the required external pressure is noted (item 3). Preferably, this procedure is repeated several times and an average pressure value is considered to be a first value for the occlusion pressure of the naso-facial vein. 5. Now, the bladders 35, 36 are inflated by closing the release vent 38b and pumping using the hand pump 38a until an interior pressure of at least 60-100 mm Hg, in particular 60 mm Hg, is obtained. The pressure may be monitored using the manometer 38c. Inflating the bladders leads to the buildup of pressure between the C-shaped bladder 35 and the patient's face without substantial movement of the frame 32 of the mask 31. This is achieved because the force required to support the patient's head as well as to obstruct the facial veins is basically provided by the rear bladder 36, whereas the front bladder 35 has the main purpose of adapting the inner shape of the mask 31 to the patient's face. This is supported by the grooves 32a, enhancing the mask's flexibility.

[0144] As described above, obstructing the facial veins, overflow out of the orbital socket into those veins is prevented. Thus, a closed venous measuring system of communicating vessels is formed only opening to the cavernous sinus. The pressure in the orbital veins rises to the pressure in the CS.

[0145] Due to the obstruction of the facial veins the vessel should expand in the ultrasound image. Furthermore, it was observed by ultrasound imaging that the obstruction leads to a change of shape of the naso-facial vein coming with a reduction of the ratio between width and height of about 15%. These are important indicators to ensure that the vessels around the eye are fully squeezed on load. Without load change with venous blood stasis, in many cases no meaningful ICP-related information may be obtained

[0146] During inflation and thus obstruction of the facial veins, the ultrasonic probe 40 is held in its position and the vessel is observed without interruption. This ensures that the same vein will be measured at the same position in subsequent measurements.

[0147] 6. After reaching the required pressure in the bladders and after a delay of at least 10 s to ensure pressure equalization in the now closed system of facial veins and cavernous sinus, second measurements of the occlusion pressure of the naso-facial vein are taken, at the same location as the first measurements. The protocol is the same as for the first measurements. This leads to a second value for the occlusion pressure of the naso-facial vein.

[0148] The described steps 4-6 may be repeated several times in order to further reduce the statistical errors and / or to monitor the progression of the occlusion pressures or derived quantities over time. Based on repeated measurements, covering several minutes to several hours, a progression curve may be established. Based on the curve, in particular on a study of its gradients, statements on the health condition of the patient may be derived.

[0149] The measurements may be taken on both the right hand as well as on the left hand side of the patient's face. Substantial differences in the measured pressures may be a valuable indication of certain conditions affecting the blood flow on one side but not on the other, such as ocular tumors, certain eye injuries, thrombosis, etc. Furthermore, taking measurements on both sides ensures that potential systematic errors are identified and affected values are not used as a basis for decision by the responsible persons.

[0150] The inventive method has been tested in experiments. Measurements on healthy volunteers confirmed the increase of venous pressure when obstructing the facial veins. The venous pressure was rising regularly within at most 15 s after obstructing the facial veins. It is this increase in pressure in the orbital veins that is the veno-venous pressure difference Ap:

[0151] Ap Pobs Pnonobsi where pnonobsdesignates the occlusion pressure without the obstruction and pobsdenotes the occlusion pressure with the obstruction of the facial veins. Stability of the value of Ap after the initial period of 15 s was observed in all measurements on test subjects, regardless of head position (up to -15° in the supine position, as well as in the lateral position) and over time (up to 15 min). 208 individual measurements were performed on two subjects using a preliminary embodiment of the applicator, obtained from obtaining swimming goggles. The inclination of the support surface of the subjects was -3.6°. The impact of this embodiment on the facial veins was comparable to that of the applicator described above.

[0152] The Figure 8 shows the temporal progression of the measured occlusion pressures in four series of measurements, taken on the two subjects. The horizontal axis denotes time, the vertical axis is the measured pressure including phases of unobstructed facial veins and phases where the veins were obstructed. The four curves represent the following:

[0153] The deviation at the end of curve 53 shows that it is crucial to track the vessel and measuring location throughout the entire series of measurements.

[0154] Usually, after inflating the bladder to obstruction pressure, the new pressure balance at the higher pressure level is reached within 5-6 s.

[0155] Taking into account further measurements, an average increase of the occlusion pressure by 8.4mmHg was observed, measured on the right eye of both subjects and by three investigators using the protocol described above. Figure 9 summarizes the results. In the first section, the bars represent the values for the occlusion pressure of the naso-facial vein when the facial veins are unobstructed obtained from four different series of measurements. In the second section, the bars represent the corresponding occlusion pressures of the naso-facial vein, when the facial veins are obstructed. The further two sections show the value of the veno-venous pressure difference Ap obtained from averaged values (third section) and from the single values, Ap' (fourth section). Obviously, the values are the same, however, the scatter is slightly smaller for the results obtained from the single values (3.5 mmHg compared to 3.7 mmHg). As discussed above, the value of Ap is a good starting point to obtain information on the ICP, and at least its development over time is deemed to provide physiologically relevant information on the state of the patient's ICP.

[0156] Several potential sources for systematic errors were examined. Firstly, the impact of the pressured applied by the applicator to the skin was examined in experiments. In a first experiment, the superficial skin displacement (stretch) caused by the load change on the applicator was measured. The load of the applicator pulled down the skin by approx. 0.5mm. Next, two series of measurements of the occlusion pressure of the naso-facial vein have been taken. In the first series, apart from the region contacted by the ultrasonic probe, the skin was free from external influence. In the second series, the skin was stretched downwards by more than 0.5mm by applying adhesive tape. However, no significant influence could be observed when comparing the results of the two series. Accordingly, it may be assumed that the tightening of the skin caused by the applicator has no influence on the measurement results.

[0157] Comparative measurements in the supine and lateral position of the patient have shown that the occlusion pressures differed by a value corresponding to the difference in vertical position of the measurement site between the two positions. The value of Ap showed no significant difference.

[0158] Furthermore, MRI examinations on two subjects over 30 minutes each, with the applied and pressurized activator, showed no effects on the intracranial veins. This is an indication that effects of the measurement on the value of the ICP are likely very small. It was also observed whether there was an effect on the measured pressure in the obstructed state due to outflow over the pterygoid plexus as there may be venous connections to the extracranial pterygoid sinus and as there might be an overflow in these vessels. These vessels have a much smaller cross-section than the obstructed facial veins, and therefore, it would be expected that overflow into the pterygoid plexus would be observable only after a certain time. However, measurements have shown that there was no pressure drop within at least 15 minutes after applying the applicator. This is a clear sign that there is no significant influence by this potential bypass. It is assumed that the cross-sections of the vessels of the pteryogoid sinus are that small that no relevant overflow happens. It has to be noted that in principle, in the context of the present invention, it is possible to obstruct the pterygoid plexus as well, if it turns out that this is necessary, using e. g. check pads exerting a pressure onto the patient's cheek. However, the mentioned results indicate that it is unlikely that such pads will be needed.

[0159] The Figure 10 is a frontal view on a further embodiment of an applicator that may be used in the context of the inventive system. In particular, this further embodiment is adapted to perform measurements on the frontal vein, in a location on the forehead, above the eyebrow and approximately vertically above the inner corner of the eye (cf. Figure 11 showing the situation during a measurement in the obstructed state of the facial veins using the further embodiment in a front view).

[0160] The applicator 130 features a mask 131 and a strap 134. The mask 131 is similar to the mask 31 described in connection with Figures 4A, 4B. The main difference is a central frontal extension that exposes a region of the forehead above the nose and the inner corners of the eyes when the mask 131 is attached to the patient's face. Therefore, the mask 131 comprises a C-shaped frame 132, wherein the open legs of the frame 132 are connected by a nose bow 133. In an upper section, opposite the nose bow 133, the frame 132 forms a convex extension 139, running substantially in the main plane of the frame 132, increasing the region surrounded by the frame 132. The shape of the extension is roughly semi-circular. The width of the surface surrounded by the extension 139, parallel to the plane defined by the strap 134, is about half the width of the surface surrounded by the frame, whereas the height of the surrounded surface, perpendicular to said width, is about 2 / 3 of the height of the total surface surrounded by the frame 132.

[0161] The frame 132 and the nose bow 133 are made from a rigid plastic material. The geometry of the frame 132 and the nose bow 133 is adapted to the geometry of the human face such that the mask 131 may be applied to the face in such a way that the frame 132 encloses both orbital regions and a central lower portion of the forehead, whereas the nose bow 133 runs around the wearer's nose. In both its outer regions, the frame 132 features a group of three fastening holes 132a. At a central location of the upper part, an attachment hook 132b is arranged.

[0162] The strap 134 and its functioning are identical to that of the first embodiment described above.

[0163] The applicator 130 further comprises a pneumatic system. This system features a frontal bladder 135 matching the extension and geometry of the frame 132. The frontal bladder 135 is attached to the back surface of the frame 132 of the mask 131. It further features a rear bladder 136 supported by the inside surface of a load shield 137 which itself is attached to the inner side of the strap 134. Again, both the frontal bladder 135 and the rear bladder 136 are connected to a common pressure source featuring a hand pump and a manometer. To match the shape of different faces, applicators with different sizes and / or curvatures may be provided.

[0164] The relevant facial veins are obstructed using the applicator 130. In Figure 11, the contact surface of the applicator 130, in its activated configuration, is indicated by the dashed surface. The location 122 at the root of the nose, above the nostrils, where the frontal vein 118 is compressed and its occlusion is monitored by ultrasound is indicated by an arrow. The frontal vein 1 18 here lies superficially directly under the skin on the frontal bone. It can easily be compressed. Apart from using a different applicator and performing the measurements on another dedicated vein, the steps of the measuring process correspond to those of the process described above, in connection with the first embodiment of the applicator.

[0165] It has to be noted that the measurements required in the inventive method may only be taken on intact skin. Furthermore, diseases in the orbit that influence venous flow, e.g. Graves disease, tumors and cavernosus syndrome (cavernous thrombosis), are contraindications.

[0166] The Figures 12A-C show the temporal progression of the measured occlusion pressures in three further series of measurements, taken using the further embodiment of the applicator, based on examination of the frontal vein.

[0167] The horizontal axis denotes time, the vertical axis is the measured pressure. The Figures respresent the following:

[0168] Fig. 12A The applicator is attached to the face of the patient, but not inflated. The pressure applied by the applicator is therefore negligible. Five successive cycles of increasing and decreasing the external pressure exerted by the probe are ran. In each cycle, the pressure is increased over the occlusion pressure. Accordingly, five values of occlusion pressure result, taken at about 3, 9, 14, 18 and 23 s after the beginning of the examination. The resulting average occlusion pressure is 9.0 mmHg with a standard deviation of 0.6 mmHg.

[0169] Fig. 12B The applicator is now inflated and exerts a pressure of about 60 mmHg along its contact surface with the patient's face. Six successive cycles of increasing and decreasing the external pressure exerted by the probe are ran. In each cycle, the pressure is increased over the occlusion pressure. Accordingly, six values of occlusion pressure result, taken at about 3, 8, 13, 18, 23 and 26 s after the beginning of the examination. The resulting average occlusion pressure is 14.2 mmHg with a standard deviation of 2.0 mmHg.

[0170] Fig. 12C The applicator is still inflated, exerts a pressure of about 60 mmHg along its contact surface with the patient's face. In a first phase, four successive cycles of increasing and decreasing the external pressure exerted by the probe are ran. In each cycle, the pressure is increased over the occlusion pressure. Accordingly, four values of occlusion pressure result, taken at about 4, 7, 10 and 14 s after the beginning of the examination. The resulting average occlusion pressure in this first phase is 12.5 mmHg with a standard deviation of 1.5 mmHg. In a second phase, six further successive cycles of increasing and decreasing the external pressure exerted by the probe are ran. In each cycle, the pressure is increased over the occlusion pressure. During the entire second phase, the patient carries out a Valsalva manoeuver. Six values of occlusion pressure result, taken at about 22, 26, 30, 34, 38 and 42 s after the beginning of the examination. The resulting average occlusion pressure in this second phase is 28.3 mmHg with a standard deviation of 3.0 mmHg.

[0171] The results of these further measurements confirm the findings summarized above. In particular, the Valsalva manoeuver is an established practice to simulate an increased intracranial pressure, cf. e. g. F. P. Tiecks, A. M. Lam, B. F. Matta, S. Strebel, C. Douville, and D. W. Newell, "Effects of the valsalva maneuver on cerebral circulation in healthy adults. A transcranial Doppler Study," Stroke 26(8), 1386-1392 (1995). The effects of the increased ICP are clearly visible in the third measurement series represented by Fig. 12C, confirming that an increase in ICP manifests itself in an increase of the occlusion pressure of the frontal vein if the facial veins that could allow for pressure equalization are obstructed.

[0172] The Figure 13 is an oblique view of yet a further embodiment of an applicator that may be used in the context of the inventive system. Similar to the embodiment described in connection with Figs. 10, 11, this further embodiment is adapted to perform measurements on the frontal vein, in a location on the forehead, above the eyebrow and approximately vertically above the inner corner of the eye.

[0173] The applicator 230 features a mask 231 and a strap 234. The mask 231 is similar to the mask 131 described in connection with Figure 10. The main differences relate to the shape of the mask 231 in the region of the forehead as well as to the fastening mechanism of the strap 234. The mask 231 comprises a C-shaped frame 232, wherein the open legs of the frame 232 are connected by a nose bow 233. Compared with the applicator described in connection with Figure 10, instead of having a central frontal extension exposing a central region of the forehead above the nose, the extension of the mask in the region of the forehead is generally larger exposing not only a central portion of the forehead but a larger region of the forehead extending further to the left and the right. This increases the available space for taking measurements of facial veins within the obstructed region.

[0174] The frame 232 and the nose bow 233 are made from a rigid plastic material. The geometry of the frame 232 and the nose bow 233 is adapted to the geometry of the human face such that the mask 231 may be applied to the face in such a way that the frame 232 encloses both orbital regions and a lower portion of the forehead, whereas the nose bow 233 runs around the wearer's nose. In both its outer regions, the frame 232 features a buckle 232a, 232b. Both end portions of the strap 234 are guided through the respective buckle 232a, 232b and connected to the respective adjacent portion of the strap 234 with a Velcro fastener. This allows for easily adjusting the length of the strap 234 as well as buckling and unbuckling the strap 234.

[0175] The applicator 230 further comprises a pneumatic system. This system features a frontal bladder 235 matching the extension and geometry of the frame 232. The frontal bladder 235 is attached to the back surface of the frame 232 of the mask 231. It further features a rear bladder 236 which itself is attached to the inner side of a rear section of the strap 234, in which the width of the strap 234 is enlarged. Both the frontal bladder 235 as well as the rear bladder 236 are made from a fiber-mesh reinforced plastic foil. Again, both the frontal bladder 235 and the rear bladder 236 are connected to a common pressure source featuring a hand pump and a manometer. To match the shape of different faces, applicators with different sizes and / or curvatures may be provided.

[0176] The steps of obstructing the relevant facial veins and performing the measurements are the same as described above in connection with Figure 11.

[0177] The Figure 14 is an oblique view of an alternative embodiment of a rear bladder for the applicator. The rear bladder 336 has a toroidal shape ("donut") and is directly attached to the strap 334, without needing a load shield. This improves the comfort for the patient. Due to its shape, the rear bladder 336 stabilizes the position of the applicator on the patient's head. Additionally, if the patient is in a supine position, the shape of the rear bladder 136 further stabilizes the head position on the supporting surface.

[0178] The invention is not restricted to the disclosed embodiments. First of all, features of the hardware components may differ. For example, instead of a hand pump, an automated pump may be used for inflating the bladders of the applicator and details of the applicator and the ultrasonic probe may be different from the described embodiments.

[0179] Further measures may be taken to further improve the quality of the measurements, e. g. the use of Doppler ultrasound data or image processing, e. g. edge detection. The obstruction force may be measured directly and / or the obstruction of the facial veins may be monitored, e. g. by further (Doppler) ultrasound measurements.

[0180] Instead or in addition to the determination of the veno-venous pressure and / or an ICP value, the progression of the pressure values measured on the closed system and / or of the veno-venous pressure values may be monitored, and conclusions may be drawn from this monitoring. In summary, it is to be noted that the invention creates a method and a system for obtaining information on the intracranial pressure of a patient that is non-invasive, reliable and has minimum impact on the patient.

Claims

Claims1. A method for non-invasively obtaining information on the intracranial pressure of a patient, comprising the steps of : a) during a first interval obstructing a plurality of facial veins of the patient, leading from a region surrounding the orbital socket by applying external pressure on each of the plurality of facial veins; b) during the first interval applying an external pressure on a designated vein connected to an intracranial vessel, at a location in the region, upstream the obstructions of the plurality of facial veins; c) observing a change of geometry of the designated vein caused by the external pressure to obtain at least one first value related to a venous pressure in the designated vein; d) processing the at least one first value to obtain the information on the intracranial pressure.

2. The method as recited in claim 1, characterised by the steps of: during a second interval, prior and / or after the first interval, applying an external pressure on the designated vein at the location and observing a change of geometry of the designated vein caused by the external pressure to obtain at least one second value related to the venous pressure; using the at least one first value and the at least one second value to obtain the information on the intracranial pressure.

3. The method as recited in claim 2, characterised in that an intracranial pressure value is obtained from a difference between the at least one first value and the at least one second value.

4. The method as recited in claim 1, characterised in that the information on the intracranial pressure is obtained from the at least one first value and a duration measured from an onset of obstruction to a point in time of obtaining the at least one first value.

5. The method as recited in one of claims 1 to 4, characterised in that the geometry of the designated vein is observed based on ultrasound images of the designated vein.

6. The method as recited in claim 5, characterised in that the external pressure is exerted on the designated vein by a front surface of an ultrasound probe.

7. The method as recited in one of claims 1 to 6, characterised in that the change of geometry caused by the external pressure is observed to determine an onset of occlusion of the designated vein and in that the information on the venous pressure is an external pressure value corresponding to an onset of occlusion of the designated vein.

8. The method as recited in claim 7 and in claim 5 or 6, characterised in that a plurality of ultrasound image frames are stored with assigned values of external pressure and in that the external pressure corresponding to the outset of occlusion is determined retroactively based on the plurality of ultrasound image frames and the assigned values of external pressure.

9. The method as recited in one of claims 1 to 8, characterised in that the designated vein is the naso-facial vein or a sideward branch thereof and in that the location is at a root of the nose.

10. The method as recited in one of claims 1 to 8, characterised in that the designated vein is the frontal vein and in that the location is on the forehead.

11. The method as recited in one of claims 1 to 10, characterised in that the information on intracranial pressure is obtained at a first point in time, that the information onintracranial pressure is obtained at a second point in time and in that a measure for a progression of intracranial pressure is obtained from a comparison of the information obtained at the two points in time.

12. The method as recited in one of claims 1 to 11, comprising the further step of illuminating the designated vein using a visible light source placed in an intracranial cavity, in particular in the oral-pharyngeal cavity.

13. A system for non-invasively obtaining information on the intracranial pressure of a patient, comprising: a) an applicator for obstructing a plurality of facial veins of the patient, leading from a region surrounding the orbital socket by applying external pressure on each of the plurality of facial veins: b) an imaging probe for observing a change of geometry of a designated vein connected to an intracranial vessel, at a location in the region, upstream the obstructions of the plurality of facial veins, caused by an external pressure applied on the designated vein; c) a processor for processing at least one first value related to a venous pressure in the designated vein, obtained from the observed change of geometry to obtain the information on the intracranial pressure.

14. The system as recited in claim 13, characterised in that the applicator has an elongated shape adapted to reach pressure application points of all of the plurality of facial veins, the applicator being formed in particular to at least partially surround the orbital socket when applied to a face of the patient.

15. The system as recited in claim 14, characterised in that a shape of a contact surface of the applicator to contact a face of the patient is adaptable prior to starting the obstruction, wherein an adapted shape may be fixedly set prior to applying pressure to the face of the patient.

16. The system as recited in one of claims 13 to 15, characterised in that the applicator comprises at least two support regions and at least one contact pressure region, wherein a variable length spacer is arranged between each of the at least two support regions and the at least one contact pressure region in such a way that a distance between a first contact surface of the at least two support regions and a second contact surface of the at least one contact pressure region, in a direction perpendicular to a main extension of the applicator is adjustable.

17. The system as recited in one of claims 13 to 15, characterised in that the applicator comprises a substantially rigid frame, a retaining device for attaching the frame to the patient's face and at least one pneumatic bladder attached to the frame, a contact surface of the applicator being formed by the bladder.

18. The system as recited in claim 17, characterised in that the frame features a central frontal extension exposing and surrounding a region above the nose and the inner corners of the eyes when attached to the patient's face.

19. The system as recited in one of claims 13 to 18, characterised in that the imaging probe is an ultrasonic probe.

20. The system as recited in claim 19, characterised in that the ultrasonic probe has a head piece, the contact portion of the head piece having a generally circular footprint and accommodating an ultrasound transparent fluid.

21. The system as recited in claim 20, characterised in that the head piece features a constricted section, the constricted section being arranged between a front surface of the head piece and an interface region to connect the head piece to a base body of the ultrasound probe.

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