The invention relates to sensor arrangements for an ultrasonic probe, wherein the sensor arrangement comprises emitters and receivers and wherein the emitters and receivers are arranged in rows and columns. In further aspects, the invention relates to a method for determining the difference in time of flight between two ultrasonic signals and to the use of the sensor arrangements.

Prior Art:

Osteoporosis is a disease, which often leads to an increased risk of bone fracture. It is a disease, which becomes more common with age and particularly women are af- fected. The increased risk of bone fracture is due to an increased weakness of the bone, which may lead to fractures which occur with minor stress or spontaneously.

In particular, it has been found that osteoporosis is due to a reduced bone mass and/or an increased bone loss. In order to assess whether or not a patient suffers from osteoporosis, X-ray absorption or ultrasound measurements can be carried out. Dual energy X-ray absorptiometry measurements are useful in order to meas- ure the areal bone mineral density (aBMD) and the osteoporotic fracture risk of a pa- tient. However, this method depends strongly on the bone mass and bone size, but does not provide any information about structural parameters and/or bone material properties. Other X-ray methods, such as High Resolution peripheral Quantitative Computer Tomography (HR-pQCT), are prone to motion artefacts and limited to pe- ripheral measurement sites, such as the distal radius or the distal tibia. In particular, the above-mentioned methods are not capable of segmenting structures in the im- age, which are smaller than 100 pm. A resolution in this range would, however, be required in order to differentiate healthy bone material from osteoporotic bone mate- rial. In an osteoporotic cortical bone material, the pore sizes vary between 7 and 400 pm, whereas in a healthy bone, the mean pore size is approximately 60 pm. Another disadvantage of X-ray methods is the radiation exposure of a patient which should be kept at a minimum.

With regard to ultrasound methods, the axial transmission technique is known, wherein the ultrasound velocity along the axis of long bones is measured. An exam- pie of a Jong bone" are the radius or the tibia. It has been found that the squared velocity of an ultrasonic signal in a bone correlates with the effective elastic modulus in the linear propagation regime. Therefore, said ultrasound velocity can be used to estimate the elasticity of bone material regions of interest. In the context of the pre- sent invention, it is preferred to use the terms“velocity of an ultrasonic signal” and “speed of sound” synonymously. Preferably, the abbreviation SOS is used for the term“speed of sound”.

It is known that the bone structure consists of essentially tubular, cortical and spongy, trabecular bone material. The cortical bone material forms the outer shell of the bone and is usually a strong and dense structure made of woven fibers. This outer shell surrounds the sponge-like trabecular bone material. In the state of the art, in particular quantitative ultrasound measurements have been carried out with regard to the trabecular bone material in order to assess the osteoporotic fracture risk of a patient. However, it has been found that cortical bone properties, i.e. prop- erties of the cortical bone material and structure, also contribute to the strength of a bone and influence the propagation speed of an ultrasonic signal through the corti- cal bone material. Examples of such fragility-relevant cortical bone properties are the porosity, mineralization or the thickness of the cortical region of the bone. How- ever, it has for example not been possible so far to discriminate between porosity and mineralization in a bone with a single measurement.

It is therefore the object of the present invention to provide sensor arrangements for an ultrasonic probe and a method for determining the difference in time of flight be- tween ultrasonic signals to overcome the shortcomings and disadvantages of the prior art. In particular, it is the object of the present invention to provide an ultrasonic device which is capable of measuring different fragility-relevant cortical bone proper- ties, such as the cortical porosity and the cortical thickness, with a single measure- ment and to reduce the radiation exposure for the patient. A person skilled in the art would appreciate if a device could be provided, which is capable of carrying out in vivo measurements of a number of fragility-relevant cortical bone properties, such as cortical porosity and cortical thickness. A further object of the present invention is to provide sensor arrangements and a method for determining the difference in time of flight between ultrasonic signals, which is well suited for the use in clinical set- tings. Description of the invention:

The object underlying the present invention is solved by the features of the inde- pendent claims. Preferred embodiments of the invention can be found in the de- pendent claims. According to the invention, a sensor arrangement for an ultrasonic probe is provided, wherein the sensor arrangement comprises emitters and receiv- ers and wherein the emitters and receivers are arranged in rows and columns. The sensor arrangement is characterized in that the sensors are arranged in rows of emitters and rows of receivers, wherein the columns are formed from upper emit- ters, upper receivers, lower receivers and lower emitters, wherein the sensor ar- rangement is configured to measure a velocity of an ultrasonic signal along a num- ber of different signal paths. In the context of the present invention, this sensor ar- rangement is preferably referred to as“proposed sensor arrangement” or“first sen- sor arrangement”.

For the proposed sensor arrangement, it is preferred that a central distance between the rows of sensors is in a range of 5 to 20 mm, preferably in a range of 10 to 15 mm and most preferably at 13 mm. In the context of the present invention, the term “central distance” preferably relates to the distance between the centers of the sen- sors. Preferably, the central distance between the columns of sensors is in a range of 5 to 15 mm, preferably in a range of 8 to 12 mm and most preferably at 10 mm.

When using the axial transmission technique, with which e.g. the cortical compart- ment of a long bone can be measured, at least one emitter and one receiver are placed on one side of the bone. The emitter is configured to excite an ultrasonic wave, which propagates through the coupling medium. In the context of the present invention, it is preferred to refer to the ultrasonic wave as ultrasonic signal. Prefera- bly, the coupling medium can be formed from soft tissue or water. It is preferred that the ultrasonic signal impinges on the specimen, e.g. a bone or a region of interest of a bone. The part of the ultrasonic signal, which impinges on the specimen under a critical angle, preferably travels along the surface of the specimen, wherein energy is preferably constantly emitted back into the coupling medium, e.g. the soft tissue surrounding the bone. This energy, which is emitted into the coupling medium, can be detected by a receiver or a receiving sensor. In the context of the present invention, it is preferred that there is a minimum dis- tance between the emitters and the receivers, which form the proposed sensor ar- rangement in order to receive the ultrasonic wave, which travels through the speci- men, before the ultrasonic wave passes through the coupling medium. It is preferred that two ultrasound signals are detected. Preferably, the first ultrasound signal is re- lated to a first receiver and the second ultrasound signal is related to a second re- ceiver, wherein both ultrasound signals preferably travel through the bone. In the context of the present invention, the period of time, which is needed by the first ultra- sonic signal and the second ultrasonic signal to travel through the bone and the soft tissue is preferably referred to as“time of flight” (TOF). The time difference between the detection of the first ultrasonic signal and the detection of the second ultrasonic signal is preferably referred to as“difference in time of flight” (ATOF). In the context of the present invention, it is preferred that the difference in time of flight is used in order to calculate the“speed of sound” (SOS), wherein the SOS preferably repre- sents the velocity of the ultrasonic signal propagating through the bone. In the con- text of the present invention, it is preferred to use the point in time, where the signal amplitude reaches 10 % of the first positive amplitude, to calculate the TOF. In order to determine the SOS, it is preferred to use the TOF, which is preferably defined as the point in time, where the amplitude of the first arriving signal reaches 10% of its maximum. In the context of the present invention, it is preferred to use the terms “first positive elongation” and the term“first arriving signal” synonymously. Other methods for the determination of the TOF can also be used in the context of the pre- sent invention. In one aspect, the invention relates to a method for determining the difference in time of flight between a first ultrasonic signal and a second ultrasonic signal. The dif ference in time of flight can preferably be used to assess the osteoporotic fracture risk of a material, in particular a bone material. Preferably, the method is configured to provide intermediate results, e.g. in order to evaluate the progress of the osteopo- rosis and/or the success of a treatment. In the context of the invention, it is preferred to further analyze the intermediate results preferably provided by the method, wherein the further analysis can e.g. be performed by means of information technol- ogy. It is preferred that the method can be carried out with the sensor arrangements as described in this document. In other words: the sensor arrangements described herein can be used in order to carry out the method described herein. The technical effects, definitions and advantages apply preferably analogously.

The proposed sensor arrangement is configured to measure a velocity of ultrasonic signals along a number of different signal paths. In particular, the sensor arrange- ment is configured to measure the velocity of at least one ultrasonic signal, prefera- bly more ultrasonic signals. Preferably, the number of different signal paths includes a subset of axial and tilted signals paths. As an example, the measurements along an axial signal path may include a first ultrasonic signal, which is preferably emitted by the left upper emitter and received by the left upper receiver. Preferably, the sec- ond ultrasonic signal may be emitted by the left upper emitter and received by the left lower receiver. The same applies analogously for the central and the right col- umn of the proposed sensor arrangement, preferably coinciding with the central and right axial signal path. For the tilted signal paths, it may e.g. be preferred that a first ultrasonic signal is emitted by the left upper emitter and received by the central up- per receiver and that a second ultrasonic signal is emitted by the left upper emitter and received by the right lower receiver. In another example describing a tilted sig- nal path, it may be preferred that a first ultrasonic signal is emitted by the right upper emitter and received by the central upper receiver and that a second ultrasonic sig nal is emitted by the right upper emitter and received by the left lower receiver. It is preferred that the first and second signals specified in these examples represent ul- trasonic signals forming the positive direction of the preferably bidirectionally meas- ured ultrasonic transmission, wherein the bidirectionality is explained further below in this document.

It is preferred that the difference in time of flight between the two ultrasonic signals is measured along a number of signal paths. Preferably, the number of signal paths can be 1 to 15, preferably 2 to 10 and more preferably 3 to 8, wherein all numbers between 1 to 15 may be preferred. It is most preferred that the differences in time of flight are measured along five different signal paths, wherein three signal paths pref- erably represent axial signal paths and the two remaining signal paths preferably represent tilted signal paths. Preferably, the measurements are carried out bidirec- tionally. In the context of the present invention, the term“bidirectional” preferably means that at least two measurements are carried out along each signal path, wherein the measurements are preferably referred to as“positive” and“negative” di- rection of the transmission of the ultrasound signal.

Preferably, the measurements performed along one signal path are carried out es- sentially in parallel. As an example, the measurements performed along an axial sig nal path may preferably only affect the receivers and emitters of said axial signal path. In other words, it is preferred that the measurements carried out along the ax- ial signal paths are carried out along the same column of receivers and emitters of the proposed sensor arrangement. This means preferably that the ultrasonic signals may by emitted by the upper and lower emitter of a column of the sensor arrange- ment and that the signals may be received and/or detected by the upper and lower receiver of the same column of the sensor arrangement. In particular, the positive transmission measurements may start at the left upper emitter, i.e. the ultrasonic signals are emitted by the left upper emitter, and the negative transmission meas- urements start at the left lower emitter, i.e. the ultrasonic signals are emitted by the left lower emitter.

It is preferred that the tilted signal paths are tilted by a tilting angle alpha compared to the axial signal path. As an example, the positive tilted signal path may comprise positive measurements, where the measurements start at the left upper emitter, i.e. the first and second ultrasonic signal are preferably emitted by the left upper emitter, wherein the corresponding negative measurements start at the right lower emitter, i.e. the first and the second ultrasonic signal are preferably emitted by the right lower emitter. The first positive ultrasonic signal is preferably detected by the central upper receiver. The second positive ultrasonic signal is preferably detected by the right lower receiver. The first negative ultrasonic signal is preferably detected by the cen- tral lower receiver and the second negative ultrasonic signal is preferably detected by the left upper receiver. The course of preferred signal paths and preferred posi- tions of the receivers and emitters are shown in more detail in the figures of this doc- ument.

Preferably, the columns preferably forming the proposed signal paths and/or the sig nal paths themselves comprise at least two receivers each, wherein the receivers are preferably configured to detect the ultrasonic signals emitted by the emitters. The use of at least two receivers within a signal path is particularly advantageous in order to eliminate the influence of the thickness of the coupling medium, e.g. the soft tissue. It is preferred that at least two receivers are arranged in line with at least one emitter, preferably two emitters, wherein the sensors preferably form part of the pro- posed sensor arrangement. It is particularly preferred that the receivers and the emitters form a signal path, along which the propagating ultrasound signal, in partic- ular its velocity, can be measured. The distance between the at least two receivers in one signal path is preferably referred to as distance s. The SOS, in particular the velocity of the ultrasonic signal propagating through the bone, can advantageously be calculated using the following equation:

SOS = s / ATOF.

In the context of the present invention, it is particularly preferred to use a bidirec tional axial transmission technique. The use of a bidirectional axial transmission technique is particularly advantageous in order to further improve the accuracy of the results of the measurement with regard to the often inconstant thickness of the coupling medium. In other words, using bidirectional axial transmission techniques advantageously helps to reduce the influence of the thickness of the coupling me- dium on the measurement and/or the quality of the measurement results. This is im- portant as the thickness of the soft tissue, preferably forming the coupling medium, often varies along the site of the measurement. Studies show that a maximum soft tissue thickness is in a range of 0 to 4 mm. In the context of the analysis of the axial transmission technique, it is preferred that the ultrasound wave as a whole is ana- lyzed and that the results are compared to theoretic models. For this analysis, it is preferred to plot the ultrasound signal, e.g. of a bone material, against the time.

It is particularly preferred to arrange a second emitter opposite of the first emitter within the columns preferably forming the proposed signal paths and/or within the signal paths, wherein the receivers and the emitters are preferably arranged in a line. Preferably, the SOS in preferably two directions can be measured making use of this preferred arrangement of sensors within a column of the proposed sensor ar- rangement. It is preferred that a first given direction can be referred to as“positive direction” or“+ direction”, and that a second direction, which preferably represents the opposite direction of the preferred bidirectional axial transmission technique, can be referred to as“negative direction” or“- direction”. The SOS values, which are ob- tained by the measurements in the positive and the negative direction, are prefera- bly referred to as“positive SOS” (SOS ⁺ ) and“negative SOS” (SOS ), respectively. Tests have shown that the harmonic mean of the two SOS values, in particular the harmonic mean of the positive SOS and the negative SOS, which can preferably be obtained by using the proposed sensor arrangement, is less susceptible to an incli- nation angel than each SOS value on its own. Preferably, the overall SOS can pref- erably be calculated using the following equation:

SOS = 2 / ( 1/SOS ⁺ + 1/SOS )

When developing the sensor arrangements according to the present invention, one particular challenge was that simulation studies indicated that the ultrasound velocity in tangential direction, i.e. perpendicular to the bone axis, is stronger influenced by deviations in porosity changes than the velocity in axial direction. The inventors therefore assumed that the squared ratio of the two velocities correlates with the po- rosity within the bone material of interest. This assumption led to the development of the proposed sensor arrangement, which is surprisingly capable of measuring the velocity, wherethrough the cortical porosity, e.g. of a human tibia, can advanta- geously be estimated in vivo. These advantageous effects are due to the advanta- geous arrangement of sensors of the ultrasonic probe. In the context of the present invention, the term“sensor” is preferably used for emitters and receivers, wherein the emitters are preferably configured to emit ultrasonic signals and wherein the re- ceivers are preferably configured to receive and/or detect preferably modified ultra- sonic signals. It is preferred that the modified ultrasonic signals are obtained after the propagation of the original ultrasonic signal through the bone region of interest. Preferably, the terms“ultrasound” and“ultrasonic” are used synonymously in the context of the present invention.

In the context of the present invention, it is most preferred that the method for deter- mining the difference in time of flight between a first ultrasonic signal and a second ultrasonic signal, i.e. the method for assessing the osteoporotic fracture risk of a ma- terial, in particular a bone material, most preferably a bone material of a patient, comprises the following steps:

a) Providing a sensor arrangement, e.g. as described in this document, b) Providing a first ultrasonic signal and a second ultrasonic signal, c) Determining a time of flight (TOF) of the first and the second ultrasonic sig nal,

d) Determining a difference in time of flight (ATOF) between the first and the second ultrasonic signal,

e) Using the ATOF in order to determine a speed of sound (SOS).

It is particularly preferred that the cortical porosity of the examined bone material can be derived from the SOS as determined according the proposed method. Addi- tionally, it is preferred that steps c) and d) can be repeated for a number of signal paths and/or in a positive and a negative direction. Preferably, the number of signal paths is five, including three axial and two tilted signals paths. Furthermore, it is pre- ferred that the positive and the negative direction contribute to form a bidirectional transmission measurement. In the context of the present invention, it is preferred that the method for determining the difference in time of flight between a first ultra- sonic signal and a second ultrasonic signal or the method for assessing the osteo- porotic fracture risk of a material can be carried out with the proposed sensor ar- rangements, as described in this document. This preferably means that the pro- posed sensor arrangements, as described herein, can be used to carry out the above-mentioned method. It is particularly preferred that the invention additionally refers to the use of the sensor arrangements according to the present invention in order to determine a speed of sound of an ultrasound signal within a bone material.

It is preferred that the sensor arrangement comprises emitters and receivers, which are preferably arranged in rows and columns to form a grid of sensors. Preferably, the ultrasonic signals are emitted by the emitters of the sensor arrangement. Addi- tionally, it is preferred that the arrival of the ultrasonic signals is detected by the re- ceivers, wherethrough the TOF of the ultrasound signals can advantageously be de- termined. This can preferably be done by using a personal computer and/or suited electronic systems, as will be described later. The TOF of the ultrasound signals can be used in order to determine a difference in time of flight (ATOF) between the TOF of the ultrasound signals, wherein the ATOF can preferably be used in order to de- termine a speed of sound (SOS) of the ultrasound signals within a material of inter- est, e.g. a bone material. Studies have shown that the curvature of the material of interest may influence the results of the SOS measurements, in particular the results of the tilted SOS meas- urements. In particular, the impact of the surface curvature of the bone material on the SOS measurements has been found to be direction-dependent. Therefore, it may be preferred that the analysis of the data obtained by the measurements may include a step of taking into account the curvature of the bone material. For this pur- pose, it is preferred to determine an estimated height h _est of the axial signal paths above the surface of the bone. This is preferably done by taking into account the ab- solute TOF measured by one axial emitter-receiver combination, an SOS value measured within this axial signal path via bidirectional transmission, an assumed SOS of the coupling medium and the distance between the emitter and the receiver. Preferably, the SOSCM of the coupling medium may be

SOSCM ⁼ 1478 m/s.

An estimated curvature elevation e _est can preferably be derived as the difference be- tween the estimated height h _est calculated with a TOF of one of the outer axial signal paths and the estimated height h _est calculated with the corresponding TOF of the central axial signal path. This determination can be repeated for all emitter-receiver- combinations and the calculated values for the curvature elevation can be averaged in order to obtain the estimated curvature elevation e _est . Preferably, the SOS values, which are obtained by measuring along the tilted signal paths, can be corrected with the curvature so determined. Improved results can be obtained, when the ultrasound probe is shifted and/or rotated with regard to the bone. The probe can also be tilted and/or lifted, wherein the results obtained can be averaged and/or compared.

In one preferred embodiment of the invention, it is preferred that the sensors are ar- ranged in rows of emitters and rows of receivers. In the context of the present inven- tion, it is particularly preferred that the sensor arrangement is formed from four rows of sensors, wherein a first row is formed from a row of upper emitters comprising three emitters, a second row is formed from a row of upper receivers comprising three receivers, a third row is formed from a row of lower receivers comprising three receivers and a fourth row is formed from a row of lower emitters comprising three emitters. In other words, the sensor arrangement comprises preferably six emitters and preferably six receivers, wherein three emitters form a row of upper emitters, where-in three receivers form a row of upper receivers, wherein three receivers form a row of lower receivers and wherein three emitters form a row of lower emitters. In a preferred embodiment of the invention, the rows of emitters and rows of receivers are arranged essentially equidistantly. In the context of the present invention, this preferably means that the distances between the sensor rows are essentially equal.

It is particularly preferred that the sensor arrangement comprises three columns, which preferably comprise an essentially identical built-up. In a preferred embodi- ment of the invention, the columns are arranged essentially equidistantly to each other, i.e. they have essentially identical distances. Preferably, the proposed sensor arrangement is formed from a sensor pattern comprising twelve sensors, wherein preferably three emitters are arranged in an upper row of emitters, the receivers are arranged in two subsequent rows of preferably three receivers, which are preferably referred to as upper row and lower row of receivers, and a fourth row of preferably three lower emitters.

Preferably, each column of the proposed sensor arrangement comprises one upper emitter, one upper receiver, one lower receiver and one lower emitter. It is preferred that the columns are arranged essentially in parallel to each other, wherein the two outer columns enclose the middle or central column. It is preferred to refer to the two outer columns as left column and right column. Thus, each of the preferably twelve sensors of the sensor arrangement can individually be addressed with an appropri- ate denotation, such as left upper emitter, central upper receiver or right lower emit- ter. The denotations can easily be understood in connection with the figures repre- senting the present invention. In connection with these figures, the person skilled in the art will easily understand terms, such as“right”,“left”,“upper” or“lower”, or indi- cations of direction, such as“below” or“above”, so that these terms are not unclear in the context of the present invention. Additionally, the term“essentially” is not un- clear for the person skilled in the art. The person skilled in the art knows that the terms“essentially parallel” or“essentially equidistant” are meant to mean that the corresponding elements are arranged in a parallel or an equidistant way, but that there may be small deviations in the range of some degrees ° or Millimeters (mm), for example due to the manufacture of the elements or the manufacture of the de- vice as a whole. Using the denotation described above, the first row of sensors preferably comprises the three upper emitters, i.e. a left upper emitter, a central upper emitter and a right upper emitter. The second row of sensors preferably comprises the three upper re- ceivers, i.e. the left upper receiver, the central upper receiver and a right upper re- ceiver. The third row of sensors preferably comprises the three lower receivers, i.e. the left lower receiver, the central lower receiver and a right lower receiver. The fourth row of sensors preferably comprises the three lower emitters, i.e. the left lower emitter, the central lower emitter and a right lower emitter.

These advantageous effects of the invention are particularly due to the measure- ment of the velocity of an ultrasonic signal along a number of different signal paths through the proposed sensor arrangement. In particular, the measurement along the preferably five signal paths enables for the estimation of the velocity in both the tan- gential and the axial direction, wherethrough the cortical porosity can advanta- geously be estimated in vivo. In a preferred embodiment of the invention, the num- ber of signal paths comprises axial signal paths and tilted signal paths, wherein it is particularly preferred that the measurements comprise three axial signal paths and two tilted signal paths.

Preferably, the columns of the sensor arrangement coincide with the axial signal paths. In the context of the present invention, this means preferably that one axial signal path runs along the left sensor column, wherein a second axial signal path runs along the central column of sensors and the third axial signal path runs along the right sensor column. The axial signal paths are preferably referred to as left axial signal path, central axial signal path and right axial signal path, respectively. In other words, it is preferred that the sensor arrangement comprises a first column, a sec- ond column and a third column, wherein the first column preferably coincides with a left outer axial signal path, the second column preferably coincides with a middle ax- ial signal path and wherein the third column preferably coincides with a right axial signal path.

As an example, the left axial signal path may comprise two ultrasound signals which are preferably emitted from the left upper emitter. The first ultrasound signal, which is emitted from the left upper emitter, is preferably detected by the left upper re- ceiver, whereas the second ultrasound signal, which is emitted from the left upper emitter, is preferably detected by the left lower receiver. In the context of the present invention, it is preferred to refer to these two ultrasound signals as“positive” or“+” direction of the left axial signal path.

The left axial signal path may further comprise two ultrasound signals, which are preferably emitted from the left lower emitter. The first ultrasound signal, which is emitted from the left lower emitter, is preferably detected by the left lower receiver, whereas the second ultrasound signal, which is emitted from the left lower emitter, is preferably detected by the left upper receiver. In the context of the present invention, it is preferred to refer to these two ultrasound signals as“negative” or direction of the left axial signal path. In the context of the present invention, it is preferred that the measurements carried out to form the positive direction and the negative direc- tion of the transmission measurement, represent the bidirectionality of the transmis- sion measurement.

Accordingly, the central axial signal path may comprise two ultrasound signals, which are preferably emitted from the central upper emitter. The first ultrasound sig nal, which is emitted from the central upper emitter, is preferably detected by the central upper receiver, whereas the second ultrasound signal, which is emitted from the central upper emitter, is preferably detected by the central lower receiver. These signals are preferably referred to as“positive” or“+” direction of the central axial sig nal path. The central axial signal path may further comprise two ultrasound signals which are preferably emitted from the central lower emitter. The first ultrasound sig nal, which is emitted from the central lower emitter, is preferably detected by the central lower receiver, whereas the second ultrasound signal, which is emitted from the central lower emitter, is preferably detected by the central upper receiver, where- in these latter signals are preferably referred to as“negative” or direction of the central axial signal path.

Accordingly, the right axial signal path may comprise two ultrasound signals, which are preferably emitted from the right upper emitter. The first ultrasound signal, which is emitted from the right upper emitter, is preferably detected by the right upper re- ceiver, whereas the second ultrasound signal, which is emitted from the right upper emitter, is preferably detected by the right lower receiver. These signals are prefera- bly referred to as“positive” or“+” direction of the right axial signal path. The right ax- ial signal path may further comprise two ultrasound signals, which are preferably emitted from the right lower emitter. The first ultrasound signal, which is emitted from the right lower emitter, is preferably detected by the right lower receiver, where- as the second ultrasound signal, which is emitted from the right lower emitter, is preferably detected by the right upper receiver, wherein these latter signals are pref- erably referred to as“negative” or direction of the right axial signal path. It is pre- ferred that the axial signal paths run essentially in parallel to each other.

Next to the axial signal paths, it is preferred that the number of signal paths addition- ally comprises two tilted signal paths. Preferably, the tilted signal paths are tilted compared to the axial signal paths at a +/- tilting angle alpha. The +/- tilting angle al pha can be determined as follows: A virtual straight line can be thought to run through the central sensor column. A tilted virtual straight line can for example be thought to run through the central upper receiver and the right upper emitter. At the central upper receiver, in particular on its right side seen from the virtual straight line, the two virtual straight lines enclose the tilting angle alpha. The orientation of this tilting angle alpha is preferably referred to as the“negative” tilted angle and the corresponding signal path is preferably referred to as“negative” tilted signal path.

The“positive” tilted signal paths can for example be obtained by virtually putting a virtual straight line through the central censor column and putting a tilted virtual straight line through, e.g., the central upper receiver and the left upper emitter. At the central upper receiver, in particular on its left side seen from the virtual straight line running through the central sensor column, the two virtual straight lines enclose the positive tilting angle alpha. The corresponding signal path is preferably referred to as“positive” tilted signal path.

In the context of the present invention, it is preferred that the distances of the rows and/or columns of the proposed sensor arrangement are arranged in way that the preferred +/- tilting angle alpha is arrived at. In particular, the emitters and receivers forming the proposed sensor arrangement are arranged so that the preferred +/- tilt ing angle alpha between the axial signal paths and the tilted signal paths is arrived at. In other words, it is preferred that the size of the tilting angle alpha can be used to determine the distances between the sensors of the proposed sensor arrange- ment. Preferably, the arrangement of the emitters and receivers depends from the choice of the size of tilting angle alpha.

In the context of the present invention, it is preferred that the negative tilted signal path comprises two ultrasound signals, which are preferably emitted from the right upper emitter. The first ultrasound signal, which is emitted from the right upper emit- ter, is preferably detected by the central upper receiver, whereas the second ultra- sound signal, which is emitted from the right upper emitter, is preferably detected by the left lower receiver. These signals are preferably referred to as“positive” or“+” direction of the negative tilted signal path. The negative tilted signal path may further comprise two ultrasound signals which are preferably emitted from the left lower emitter. The first ultrasound signal, which is emitted from the left lower emitter, is preferably detected by the right upper receiver, whereas the second ultrasound sig- nal, which is emitted from the left lower emitter, is preferably detected by the central lower receiver, wherein these latter signals are preferably referred to as“negative” or direction of the negative tilted signal path.

Accordingly, it is preferred that the positive tilted signal path comprises two ultra- sound signals, which are preferably emitted from the left upper emitter. The first ul- trasound signal, which is emitted from the left upper emitter, is preferably detected by the central upper receiver, whereas the second ultrasound signal, which is emit- ted from the left upper emitter, is preferably detected by the right lower receiver. These signals are preferably referred to as“positive” or“+” direction of the positive tilted signal path. The positive tilted signal path may further comprise two ultrasound signals which are preferably emitted from the right lower emitter. The first ultrasound signal, which is emitted from the right lower emitter, is preferably detected by the central lower receiver, whereas the second ultrasound signal, which is emitted from the right lower emitter, is preferably detected by the left upper receiver, wherein these latter signals are preferably referred to as“negative” or direction of the pos- itive tilted signal path. In the context of the present invention, it is preferred that the positive and negative direction measurements of the tilted signal paths are carried out essentially in paral- lel. Preferably, they are not carried out using identical emitters and receivers, as is preferably the case with regard to the axial signal paths. Preferably, the directions of the signal paths, which may be positive or negative, represent the bidirectional transmission pathways, which are used to measure the velocity of the ultrasonic sig nals, which are preferably emitted by the emitters and received and/or detected by the receivers of the proposed sensor arrangement.

It was challenging arriving at the proposed sensor arrangement, as it was found that a minimum transducer distance is required for axial ultrasonic measurements in or- der to receive the ultrasound wave propagating through the bone earlier than the ul- trasound wave propagating through the soft tissue only. The challenge particularly arises from the limited width of the human tibia, which makes is difficult to measure a bidirectional transmission in tangential direction. This is particularly due to the fact that not in all bones the minimal required transducer separation can be achieved. In order to overcome this challenge, the inventors propose to make use of the cosine behaviour of the propagation velocity of an ultrasound signal. As bone material pref- erably represents a transverse isotropic medium, the velocity profile preferably fol lows a cosine curve with its maximum in axial direction and its minimum in tangential direction. In order to obtain said cosine dependency, the SOS within a cortical bone material can be measured under different measuring angles and the results for the SOS can be plotted against the angles. It is particularly preferred to use the human tibia for these measurements. These findings lead to the proposed design of the sensor arrangement, wherein the proposed grid of sensors is surprisingly capable of measuring ultrasound velocities in preferably five different signal paths, wherein three axial signal paths preferably run in parallel to each other and two signal paths are preferably tilted compared to the axial signal paths.

In a preferred embodiment of the invention, the tilting angle alpha is in a range of 30 to 45 °, preferably in a range of 35 to 40 °, most preferably at 37.5 °. It came as a surprise that it is possible to estimate the ultrasonic signal velocity in tangential di- rection, when measuring the velocities under different angles, as preferably repre- sented by the number of different signal paths. Advantageously, the challenge cre- ated by the transverse isotropic nature of bone material with regard to the propaga- tion of ultrasonic signals through a bone can surprisingly be overcome with the pre- sent invention. The preferred sensor arrangements according to the present inven- tion surprisingly allow to obtain additional information about the bone material due to its transverse isotropic nature. Thus, the invention points in an opposite direction compared to the state of the art, where it is assumed that the transverse isotropic nature of the bone material represents an undesired source of errors.

In the context of the present invention, it is preferred to combine the results of the measurements for the axial velocity, which is preferably measured along the axis of the bone, with the results for the velocity in tangential direction in order to obtain an anisotropy index which advantageously correlates with the cortical porosity of a bone region of interest. It is preferred to obtain a calibration curve of this correlation on human tibia bone ex vivo. Surprisingly, tests have shown that an ultrasonic probe comprising the proposed sensor arrangement is less prone to additional error sour- ces, which may e.g. arise from variable curvature of the surface of a bone.

The most preferred size of the tilting angle alpha of 37.5 ° has been derived by the inventors by making use of the limited width of some human bones. In particular, the signal paths, which are preferably determined by the arrangement of the sensors, are chosen so that the preferably five signal paths arrive at measuring the bone es- sentially at the same time. Preferably, the measurement can be carried out without the need of moving the probe. Tests have shown that some bones have a width of only 20 mm. In particular for these bones, the most preferred size of the tilting angle alpha of 37.5 ° advantageously enables an essentially simultaneous measurement of the preferably five signal paths. This limited width of some bones advantageously led the inventors to arrange the left column of sensors and the right columns of sen- sor in a center distance of preferably 20 mm.

The most preferred size of the tilting angle alpha of 37.5 ° was also chosen as a compromise between the damping of the ultrasonic signals and the thickness of the soft tissue. In particular, the most preferred size of the tilting angle alpha of 37.5 ° has shown to be surprisingly well suited to be used in combination with the bidirec tional transmission technique, which is preferably used in the context of the present invention. Thus, the most preferred size of the tilting angle alpha of 37.5 ° is not cho- sen arbitrarily, but takes into account the circumstances and constraints of the SOS measurements to be carried out with the ultrasound probe. Other preferred angle sizes, which can advantageously be used for the SOS measurements, are 14.4 °,

21 ° or 60 °.

In another aspect of the invention, the sensor arrangement comprises additional rows of emitters and an additional row of receivers, whereby a modified sensor ar- rangement is preferably obtained. It is preferred that the present invention addition- ally relates to this modified sensor arrangement, which can also be used in connec- tion with an ultrasonic probe. It is preferred that the modified sensor arrangement comprises two additional rows of emitters, wherein these two rows of emitters are arranged outermost within the modified sensor arrangement. In other words, a first additional row of emitters is arranged above the row of upper emitters of the first sensor arrangement and the second additional row of emitters is arranged below the row of lower emitters of the first sensor arrangement. In other words, it is preferred that the additional rows of emitters are arranged as a row of additional upper emit- ters above the row of upper emitters of the first sensor arrangement and as a row of additional lower emitters below the row of lower emitters of the first sensor arrange- ment. It is preferred that the additional rows of emitters comprise three emitters, wherein the position of the three emitters corresponds to the left, central and right position of the sensors in the sensor rows of the proposed sensor arrangement. It is preferred that the denotations describing the sensor arrangement apply to the modi- fied sensor arrangement as well.

In the context of the present invention, it is preferred that the additional rows of emit- ters have a distance to the rows of emitters of the first sensor arrangement in a range of 3 to 15 mm, preferably 4 to 10 mm and most preferred at 6.5 mm. It is pre- ferred to indicate distances between sensor as the distance between the centers of the sensors. In other words: the first row of additional emitters is preferably arranged 3 to 15 mm, preferably 4 to 10 mm and most preferably 6.5 mm above the row of upper emitters of the first sensor arrangement and the second row of additional emitters is preferably arranged 3 to 15 , preferably 4 to 10 mm and most prefera- bly 6.5 mm below the row of lower emitters of the first sensor arrangement. These distances preferably represent center distances. If a center distance of preferably 6.5 mm is used between the outermost additional rows of emitters and the row of upper and lower emitters of the first sensor arrangement, the distance advantage- ously represents one half of the preferred center distance of 13 mm between the sensor rows of the first sensor arrangement. This arrangement facilitates the manu- facture of the ultrasound probe and the precision of the measurements.

The modified sensor arrangement preferably comprises an additional row of receiv- ers, wherein the additional row of receivers preferably comprises five receivers. The inventors have found that the SOS measurements can advantageously be improved and made more precise, if preferably one receiver is added to each of the preferably five signal paths. In particular, the presence of the additional receivers allows for measurements in cases, where the bone to be measured is surrounded by thick lay- ers of soft tissue. It is preferred that the additional row of receivers is arranged be- tween the existing rows of receivers of the first sensor arrangement. These prefera- bly five receivers are preferably referred to as additional receivers. It is preferred that the two outer additional receivers are arranged in line with the left and the right column of the proposed sensor arrangement. These additional receivers are prefer- ably referred to as left and right additional receiver, respectively. Preferably, the cen- tral of the preferably five additional receivers forming the additional row of receivers is in line with the central column of the proposed sensor arrangement. Two further additional receivers are preferably arranged on either side of the central receiver of the additional row of receivers. In particular, one additional receiver is arranged be- tween the left and the central additional receiver and one additional receiver is ar- ranged between the right and the central additional receiver. Preferably, these two further additional receivers are referred to as first and second further additional re- ceiver, respectively. It is preferred that the two further additional receivers are ar- ranged in the middle between the central additional receiver and the left and right additional receivers. In the context of the present invention, the term“being ar- ranged in the middle between two objects A and B” preferably means that the dis- tance to object A is essentially equal to the distance to object B. In other words: the object“in the middle” has preferably the same distance to object A and object B. In the context of the present invention, it is preferred that the center distance of the preferably two further additional receivers is 5 mm to the neighboring sensors, par- ticularly the neighboring additional receivers.

The modified sensor arrangement advantageously enables the in vivo measurement of human bone material. In particular, the cortical porosity and the cortical thickness of a bone material to be analyzed can be estimated. Tests have shown that the modified sensor arrangement is particularly useful for cases, where the bone mate- rial is covered by thick layers of soft tissue. Studies of the inventors show that this applies to about 50 % of the probands, who took part in the study. Thus, the use of the modified sensor arrangement enables for the first time that in vivo measure- ments can be carried out for a significant share of persons, whose osteoporotic bone fracture risk shall be determined. Tests of the inventors also show that the pre- cision of the SOS measurements can significantly be improved, when the modified sensor arrangement is used for the measurements. This is due to the additional sen- sors in the modified sensor arrangement, which particularly enable to detect the ul- trasound wave travelling through bone material not being superimposed by a wave travelling through soft tissue. Due to the advantageous discrimination between bone material and soft tissue, the measurement using the ultrasound probe with the modi- fied sensor arrangement can be carried out on living patients. In particular, the use of the modified sensor arrangement allows the measurement of ultrasound waves, which travel through a bone, even if overlying soft tissue is present. It is preferred that the modified sensor arrangement can be used to carry out the method for deter- mining the difference in time of flight between a first ultrasonic signal and a second ultrasonic signal and/or the method for assessing the osteoporotic fracture risk of a bone material.

Advantageously, a modified evaluation algorithm facilitates the in vivo measure- ments on the living patient, particularly if thick layers of soft tissue are present. Tests have shown that soft tissue layers, which may be up to 8 mm thick, can advanta- geously be measured with the modified sensor arrangement. Advantageously, the modified algorithm is extended compared to the evaluation algorithm for the pro- posed sensor arrangement in order to account for circumstances, which may be found in clinical settings, such as a varying velocity of the ultrasonic signal propagat- ing through the bone, positioning errors of the probe during the measurement, the presence of soft tissue and/or the bone geometry, such as the curvature of the bone.

When the ultrasound wave, in particular the ultrasonic signal, travels through the material to be analyzed, e.g. bone material, the ultrasonic signal may undergo a change. Changes may occur with regard to frequency and/or signal amplitude of the ultrasound signal. The person skilled in the art is familiar with the meaning of the terms“frequency” and“signal amplitude” in the context of ultrasound signals. The in- ventors have found that the frequency and/or signal amplitude advantageously im- prove the estimation of the cortical porosity and the cortical thickness of a material to be analyzed, otherwise preferably based on SOS-data. In particular, the modified sensor arrangement allows for the measurement of ultrasonic waves and/or signals within a bone material, even when overlying soft tissue is present. This is advanta- geously due to the incorporation of the parameters frequency and/or signal ampli- tude into the analysis. Additionally, the improvements achieved with the modified sensor arrangement are advantageously arrived at thanks to the additional sensors forming the modified sensor arrangement, i.e. the two additional rows of emitters and the additional row of preferably five receivers. It is noted that the specific ar- rangement of emitters and receivers forming the modified sensor arrangement can be understood in connection with the figures showing preferred embodiments of the invention.

It is preferred that the results of the axial SOS measurements can preferably be used in combination with the axial shift of the frequency of the ultrasound signals in order to determine the cortical porosity in the outer band of the cortex. In the context of the present invention, it is preferred that the outer band preferably relates to a surface up to a depth of 1 mm. Preferably, the term“axial SOS measurements” re- fers to the SOS measurements measured along the preferably three axial signal paths. Furthermore, it is preferred to use the results of the tilted SOS measurements in combination with the tilted shift of the frequency of the ultrasound signals in order to measure the cortical porosity in a deeper band, preferably starting at a depth of 1.5 mm going to the endost. Preferably, the term“tilted SOS measurements” refers to the SOS measurements measured along the preferably two tilted signal paths. Moreover, it is preferred to use the axial and/or tilted damping of the amplitude of the ultrasound signals in order to determine the cortical thickness of a bone.

In a preferred embodiment of the invention, it is preferred that the diameters of the emitters and/or receivers forming the modified sensor arrangement are smaller than the diameters of the emitters and/or receivers forming the proposed sensor arrange- ment. In particular, the modified sensor arrangement comprises emitters and receiv- ers with reduced diameter. It is particularly preferred that the diameters of the re- ceivers and emitters are in a range of 1 to 6 mm, preferably 1.3 to 3 mm, more pref- erably 1.5 to 2 mm and most preferably at 1.7 mm. The preferred diameter of 1.7 mm has shown to be particularly well suited to carry out the SOS measurements for patients with enhanced soft tissue thickness. Advantageously, the modified sensor arrangement allows for the measurement of additional signal paths and a larger vari- ety of signal paths. In particular, the additional signal paths can be measured under different angles with regard to the angle of the bone to be measured.

Preferably, the axial signal paths, which are used in connection with the modified sensor arrangement, coincide with the columns of the modified sensor arrangement, wherein the columns of the modified sensor arrangement comprise four emitters and three receivers. It is preferred that the emitters of the modified sensor arrangement are arranged in two upper rows and two lower rows and the receivers of the modi- fied sensor arrangement are arranged in three inner rows, wherein the central row of receivers is formed from additional receivers, preferably five additional receivers.

For the modified sensor arrangement, it is preferred that the axial signal paths coin- cide with the columns of the sensor arrangement. In particular, ultrasound signals are preferably emitted by the emitters of the first and second additional row of emit- ters and by the emitters of the row of upper and lower emitters. It is preferred that the ultrasound signals are sent from each emitter of one axial signal path to all re- ceivers of that same signal path. In the following example, this will be described as an example for the left column of sensors, which preferably coincides with the left axial signal path: Within the left axial signal path, the ultrasound signals, which are emitted by the emitter of the first additional row of emitters, are preferably received and/or detected by the receivers of the upper and lower receivers and by the additional left receiver. Furthermore, ultrasound signals are emitted by the emitter of the upper row of emit- ters, wherein these ultrasound signals are preferably received and/or detected by the receivers of the upper and lower receivers and by the additional left receiver. Additionally, ultrasound signals are emitted by the emitter of the lower row of emit- ters, wherein these ultrasound signals are preferably received and/or detected by the receivers of the upper and lower receivers and by the additional left receiver, too. Moreover, ultrasound signals are emitted by the emitter of the second additional row of emitters, wherein these ultrasound signals are preferably received and/or de- tected by the receivers of the upper and lower receivers and by the additional left re- ceiver. The exemplary description of the ultrasound signals preferably forming the left axial signal path can preferably be transferred to the central and right axial signal path.

For the modified sensor arrangement, it is preferred that the ultrasound signals pref- erably forming the tilted signal paths are emitted by the emitters of the row of upper and lower emitters preferably forming the first sensor arrangement, in particular by the left and right upper emitter and by the left and right lower emitter. It is preferred that the left upper emitter and the right lower emitter emit the ultrasound signals for the positive tilted signal path. Preferably, the ultrasound signals emitted by the left upper emitter are detected and/or received by the central upper receiver, the second further additional receiver and the right lower receiver. It is preferred that the ultra- sound signals emitted by the left upper emitter, which are preferably detected and/or received by the central upper receiver, the second further additional receiver and the right lower receiver, form the positive direction of the positive tilted signal path. The tilted signal path may be tilted with a most preferred tilting angle alpha of 37.5 °.

Additionally, the ultrasound signals emitted by the right lower emitter are detected and/or received by central lower receiver, the first further additional receiver and the left upper receiver. It is preferred that these ultrasound signals form the negative di- rection of the positive tilted signal path. The measurements along the tilted signal paths are preferably referred to as“quasi-bidirectional”, as the two measurement di- rections, i.e. the positive and the negative direction of the tilted signal paths, are not identical. Preferably, the positive and the negative direction of the tilted signal paths run essentially in parallel.

With regard to the negative tilted signal path, it is preferred that the ultrasound sig nals of the positive direction are emitted by the right upper emitter. Its ultrasound signals are preferably detected and/or received by the central upper receiver, the first further additional receiver and the left lower receiver. It is preferred that the ul- trasound signals of the negative direction are emitted by the left lower emitter, wherein its ultrasound signals are preferably detected and/or received by central lower receiver, the second further additional receiver and the right upper receiver. It is preferred that negative tilted signal path may be tilted with a most preferred tilting angle alpha of 37.5 ° compared to the axial signal paths. Preferably, the size of the tilting angle is determined by the arrangement of the sensors forming a particular signal path. In the context of the present invention, this preferably means that the distances between the sensors forming a particular signal path, particularly the tilted signal paths, are arranged so, that a desired preferred tilting angle is arrived at.

It is preferred that the ultrasonic probe comprising the proposed sensor arrangement or the modified sensor arrangement is part of a system further comprising a per- sonal computer (PC) and electronics specifically configured for the analysis of the data obtained with the proposed sensor arrangements. Preferably, the system rep- resents one further aspect of the present invention. In the context of the present in- vention, it is preferred that the electronics are configured to amplify the receiving sig nals and/or to digitalize the signals at a resolution of 14 bit and/or with a frequency of preferably 40 MHz. Preferably, the electronics itself does not comprise any filters.

The proposed sensor arrangement or the modified sensor arrangement are advan- tageously configured to measure the propagation of ultrasound signals along differ- ent signal paths. In the context of the present invention, it is preferred that the sys- tem comprises transducers which are preferably configured to transduce electrical power into mechanical pressure and vice versa. In the context of the present inven- tion, it is preferred that the transducers are configured to convert mechanical energy of the ultrasonic signals into electric energy, wherein the electric energy can be measured.

In the context of the present invention, it is particularly preferred to refer to the emit- ters and receivers of the proposed sensor arrangements as“transducers”. It is pre- ferred that the transducers have an essentially circular shape, wherein the essen- tially circular shape is preferably characterized by a diameter in a range of 1 to 10 mm, preferably 3 to 7 mm, most preferably of 5 mm. The preferred diameter sizes mentioned herein are particularly preferred for the first sensor arrangement. For the modified sensor arrangement, preferred diameter sizes may preferably be in range of 1 to 6 mm, preferably 1.3 to 3 mm, more preferably 1.5 to 2 mm and most prefer- ably at 1.7 mm. For some applications, it may be preferred that the sensors have the shape of an octagon or other shapes.

Preferably, the center distance between the first row of additional emitters and the row of upper emitters is in a range of 3 to 15 mm, preferably 4 to 10 mm and most preferred at 6.5 mm. It is preferred that the center distance between the second row of additional emitters and the row of lower emitters is also in a range of 3 to 15 mm, preferably 4 to 10 mm and most preferred at 6.5 mm. Additionally, it is preferred that the distance between the row of additional receivers and the row of upper and lower receivers is in a range of 3 to 15 mm, preferably 4 to 10 mm and most preferred at 6.5 mm. A center distance of 6.5 mm is most preferred in the context of the present invention. It is preferred that the central distance between the columns of sensors is in a range of 5 to 15 mm, preferably in a range of 8 to 12 mm and most preferably at 10 mm. Preferably, the transducers have a center frequency of 1 MegaHertz (MHz), wherein a 3 dB bandwidth preferably corresponds to 4 %. It is preferred that the re- ceivers are arranged at a central position of the sensor arrangement and/or in the middle of the ultrasonic probe. Preferably, the emitters are arranged on either side of the receivers, in other words in rows preferably arranged above and below the rows of receivers. It is preferred that an emitter section, preferably formed from the emitters or a group of emitters, is separated from a receiver section, preferably formed from the receivers or a group of receivers, by ditches, wherein the ditches are preferably configured to prevent ultrasound propagation through the ultrasonic probe itself. It is preferred that the system further comprises transducer pitches, wherein the transducer pitch in axial direction is in a range of 5 to 30 mm, preferably 10 to 18 mm and most preferably at 13 mm. Tests have shown that a transducer pitch in ax- ial direction of 13 mm is particularly suited to take into account the correlation be- tween the transducer distance and the thickness of the coupling medium, e.g. the soft tissue. In the tangential direction, a transducer pitch may be in a range of 1 to 50 mm, preferably 5 to 30 mm and most preferably at 10 mm. The value of 10 mm has shown to be particularly well suited for the tangential transducer pitch because of the limited width of the object to be measured, wherein the object will usually be a human bone, for example a tibia or a radius. Minimum widths of the object to be measured are found to be in a range of 20 mm. In the context of the present inven- tion, it is preferred that these values result in a pitch in a range of 10 to 25 mm, pref- erably 15 to 18 mm and most preferably at 16.4 mm in a 37.5 ° direction, i.e. when the tilted signal paths are tilted at a tilting angle of alpha = 37.5 ° compared to the axial signal paths.

It is preferred that the electronics of the system comprise six pulsers, wherein it is particularly preferred that each emitter is allocated one pulser. The signals can pref- erably be pre-amplified, amplified and/or multiplexed on the side of the receivers. This built-up is particularly preferred for the first sensor arrangement. For the modi- fied sensor arrangement, it can be preferred to use one pulser. Preferably, the exci- tation pulse is distributed by a multiplexer and in that way sent to the emitters. Pref- erably, one pre-amplifier is present for each receiver on the side of the receivers. Furthermore, it is preferred that the signals are multiplexed essentially directly after being pre-amplified. It may be preferred to amplify the signals subsequently, prefera- bly after the pre-amplifying and the multiplexing. Tests have shown that these built- ups and/or amplifying methods are particularly well suited to improve the usability of the ultrasound probe comprising the proposed sensor arrangements.

Preferably, the system further comprises six signal acquiring paths, wherein a signal acquiring path comprises a pre-amplifier and an amplifier. It is preferred that the gain of the amplifier is designed variable. It is preferred that the pre-amplifier is oper- ated at 26 dB. Preferably, the amplified signals can be multiplexed, digitized to 14 bit at a clock frequency of 40 MHz and/or transferred to the PC, which is preferably part of the system. In the context of the present invention, it is preferred that the emitters of the proposed sensor arrangement are excited once at a time with a +/- 100 V,

1 MHz square signal for one period. Preferably, 10 signals can be stored for each emitter-receiver-combination, wherein the average of these signals can be calcu- lated.

Preferably, the ultrasound probe comprising the proposed sensor arrangement or the modified sensor arrangement is configured to measure three bidirectional sig- nals paths and two quasi bidirectional signal paths. It is preferred that the bidirec- tional signals paths can also be referred to as axial signal paths and that the quasi bidirectional signal paths can also be referred to as tilted signal paths. In the context of the present invention, it is preferred that the axial signal paths are in alignment with the axis of the bone which is to be measured. Preferably, the bone to be meas- ured is a long bone, such as a human tibia or a human radius. In other words, the bidirectional signal paths are preferably in alignment with the long bone axis. The tilted signal paths are preferably referred to as“quasi” bidirectional signal paths, as they are configured to measure along ultrasound signal paths which are preferably essentially parallel, but not identical. In the context of the present invention, it is most preferred that the point in time, where the signal amplitude reaches 10 % of the first positive amplitude, is used to calculate the TOF of the ultrasonic signals. Advantageously, the SOS can be derived by way of calculation using the TOF of two ultrasound signals, in particular their difference in time of flight (ATOF). It is pre- ferred that the ultrasound probe comprising the sensor arrangement can be cali- brated on acrylic glass and polycarbonate in order to determine the distances be- tween the emitters and receivers.

In a further aspect, the invention relates to a method for determining a velocity of an ultrasonic signal, wherein the velocity of an ultrasonic signal is calculated from a time of flight of the ultrasonic signal, wherein the time of flight is calculated from a point in time when an amplitude of the ultrasonic signal reaches 10 % of the first positive amplitude. In order to obtain a SOS profile, the measurements can include a full rotation on the surface of the bone to be measured, wherein the measurement can be performed in steps of e.g. 15 °. As an example, three repositioning measure- ments can be carried out for each position, wherein each repositioning measure- ment may comprise 10 single measurements, wherethrough e.g. 100 averaged sig- nals for each emitter-receiver-combination are obtained. Advantageously, the elastic modulus E can be obtained using the relationship

SOS = £7 p ,

wherein p is the density of the measured material in the unit (kg/m ³ ). It is particularly preferred that the cortical porosity of the examined bone material can be derived from the SOS as determined according to the proposed method. The inventors as- sumed that a parameter, which is comparable to the anisotropy of the elastic coeffi- cients, can be obtained by determining the squared ratio of the SOS values in the axial and in the tilted signal paths, preferably measured when the axial signal paths are in alignment with the pores within the bone material. Advantageously, an anisot- ropy index (Al) can be calculated according to the following equation:

Al = (SOS _0° / SOS37.5 ) ² .

In this equation, the term“SOSo _° “ preferably refers to the mean of the preferably three SOS values measured with the axial signal paths, whereas the term“SOS37 _. 5 _° “ preferably refers to the mean of the preferably two SOS values measured with the tilted signal paths in the positive and negative 37.5° direction. It is preferred to deter- mine the cortical porosity by means of a linear regression of actual porosity and the Al values. In the context of the present invention, it is most preferred that the meth- ods described in this document can be carried out with the first sensor arrangement or with the modified sensor arrangement.

The invention is described by the following figures showing preferred embodiment of the invention.

Fig. 1 Preferred embodiment of the first sensor arrangement

Fig. 2 Preferred embodiment of the first sensor arrangement, in par- ticular the course of the signal paths

Fig. 3 Preferred embodiment of the first sensor arrangement, in par- ticular several potential positions of the tilting angle

Fig. 4 Preferred embodiment of the modified sensor arrangement Fig. 5 Preferred embodiment of the modified sensor arrangement, in particular the course of the signal paths

Fig. 6 Preferred embodiment of the modified sensor arrangement, in particular the course of the signal paths

Figure 1 shows a preferred embodiment of the first sensor arrangement (10). In par- ticular, figure 1 shows the rows of emitters (12) and receivers (14) forming a grid of sensors (12, 14), which represents an example of the first sensor arrangement (10) of the present invention. It is preferred that the emitters (12) are represented by dark circles and that the receivers (14) are represented by white circles. The preferred embodiment of the invention, which is shown in figure 1 , comprises a row of upper emitters (12u), a row of upper receivers (14u), a row of lower receivers (141) and a row of lower emitters (121). In the context of the present invention, it is preferred that the term“12u” refers both to the row of upper emitters and to the single emitters of that row. This preferably applies mutatis mutandis to the upper receivers (14u), the lower receivers (141) and the lower emitters (121). Preferably, the emitters (12) and receivers (14) are referred to as sensors (12, 14) in the context of the present inven- tion. In this example, it is also preferred that the distance between the rows is 13 mm. A preferred diameter of the sensors (12, 14) is 5 mm, but it may also be pre- ferred that the sensors (12, 14) have alternative diameters, such as 1 ,7 mm. The preferred embodiment of the invention shown in figure 1 comprises three sensors (12 or 14) per row and three columns (28, 30, 32) of sensors (12, 14). The first col- umn of the first sensor arrangement (10) is preferably referred to as left column (28) sensors (12, 14), the second column of the first sensor arrangement (10) is prefera- bly referred to as central column (30) of sensors (12, 14) and the third column of the first sensor arrangement (10) is preferably referred to as left column (32) of sensors (12, 14). Preferably, the distance between the columns (28, 30, 32) is 10 mm in the preferred embodiment of the invention shown in figure 1 .

It is preferred that the columns (28, 30, 32) coincide with ultrasonic signal paths (16), in particular the axial signal paths (16a), which are preferably used to carry out speed of sound (SOS) measurements within a bone material. It is preferred that the columns (28, 30, 32) of the first sensor arrangement (10) comprise one upper emit- ter (12u), one upper receiver (14u), one lower receiver (141) and one lower emitter (121). Preferably, the emitters (12u and 121) of a column (28, 30, 32) emit ultrasound signals and the ultrasound signals of the emitters (12u and 121) are received and/or detected by any of the receivers (14u and 141) of that column (28, 30, 32). As an ex- ample, the upper emitter (12u) of the right column (32) emits two ultrasound signals, which are received and/or detected by the upper receiver (14u) and the lower re- ceiver (141) of the right column (32).

As can be seen from figure 2, the part of the right axial signal path (16ar) comprising the ultrasound signals emitted by the upper emitter (12u) of the right column (32) is preferably referred to as the positive direction of bidirectional transmission measure- ment (34), wherein this allocation can be transferred to the left column (28) and the central column (30) of the sensor arrangement (10). The positive directions (34, 38) of the signal paths (16, 26) are indicated with solid lines in the figures 2 and 6. The negative directions (36, 40) of the signal paths (16, 26) are indicated with dashed lines in the figures 2 and 6. In the above-mentioned example of the right column (32), the negative direction of the axial bidirectional transmission measurement (36) is formed from the ultrasound signals emitted by the right lower emitter (121), which are preferably received and/or detected by the upper receiver (14u) and the lower receiver (141) of the right column (32).

The sensor arrangement (10) according to the present invention is configured to measure a velocity of ultrasonic signals within a bone material along signal paths (16). It is preferred that the signal paths (16) comprise axial signal paths (16a) and tilted signal paths (16t), wherein the tilted signal paths (16t) are tilted compared to the axial signal paths (16a) at a tilting +/- angle alpha (18). Figure 2 shows preferred courses of the signal paths (16) for the first sensor arrangement (10). Preferably, the preferably three axial signal paths (16a) can be referred to as left axial signal path (16al), central axial signal path (16ac) and right axial signal path (16ar). It is pre- ferred that the left axial signal path (16al) coincides with the left column (28) of the first sensor arrangement (10), that the central axial signal path (16ac) coincides with the central column (30) of the first sensor arrangement (10) and that the right axial signal path (16ar) coincides with the right column (32) of the first sensor arrange- ment (10).

Figure 3 shows several potential positions of the tilting angle alpha (18). The tilting angle alpha (18) is indicated with a dashed bow between two dashed legs. It is pre- ferred that the size of the tilting angle alpha (18) is determined by the positions and/or the arrangement of the sensors (12, 14) forming the sensor arrangements (10) proposed in this document. In particular, figure 3 shows examples of possible positions (18a, b, c), where the tilting angle alpha (18) can potentially be found within the proposed sensor arrangement (10). The virtual lines enclosing the tilting angle alpha (18) are indicated by dashed lines. A first central virtual line runs along and/or essentially in parallel with the central column (30), which preferably coincides with the central axial signal path (16ac). In particular, this first central virtual line runs through the central upper emitter (12u), the central upper receiver (14u), the central lower receiver (141) and the central lower emitter (121). A tilted virtual line starts at the central upper receiver (14u) and runs through the right upper emitter (12u), i.e. the upper emitter (12u) of the right column (32) of the first sensor arrangement (10). In the context of the present invention, it is preferred that three sensors (12, 14) of the sensor arrangement (10) enclose the tilting angle alpha (18).

The size of the tilting angle alpha (18) indicates how strong the tilted signal paths (16t) are tilted compared, for example, to the axial signal paths (16a). The tilting can preferably take place in a positive direction and in a negative direction. The prefera- bly two tilted signal paths (16t) are preferably referred to as positive tilted signal path (16t+) and negative tilted signal path (16t-), depending on the direction of the tilting, e.g. compared to the axial columns (28, 30, 32) of the sensor arrangement (10). Preferably, the signal path, which is preferably formed from the ultrasound signals emitted by the left upper emitter (12u) and the right lower emitter (121), is preferably referred to as positive tilted signal path (16t+). It is preferred that the signal path, which is preferably formed from the ultrasound signals emitted by the right upper emitter (12u) and the left lower emitter (121), is preferably referred to as negative tilted signal path (16t-). It is most preferred that the tilting angle alpha (18) is 37.5 °, but it may also be preferred for other applications that tilting angle (18) of 14.4 °, 21 ° and/or 60 ° are used.

In figure 3, three possible positions (18a, b, c) of the tilting angle alpha (18) are indi- cated as examples. The first example (18a) of the position of the tilting angle alpha (18) is preferably determined by the central upper emitter (12u), the central upper receiver (14u) and the right upper emitter (12u). It is preferred that these three sen- sors (12u, 14u) enclose the tilting angle alpha (18) and determine one possible posi- tion within the first sensor arrangement (10). The second example (18b) of the posi- tion of the tilting angle alpha (18) is preferably determined by the central upper re- ceiver (14u), the central lower receiver (141) and the left upper receiver (14u). The third example (18c) of the position of the tilting angle alpha (18) is preferably deter- mined by the central lower receiver (141), the central lower emitter (121) and the right lower emitter (121). The person skilled in the art understands that 18b and 18c are vertically opposed angles, which are equal in size.

Figure 4 shows a preferred embodiment of the modified sensor arrangement (20). Preferably, the modified sensor arrangement (20) can be regarded as the first sen- sor arrangement (10), as far as the positions of certain sensors (12, 14) are con- cerned, plus additional rows of emitters (22) and one additional row of receivers (24). In other words, the modified sensor arrangement (20) preferably comprises the row of upper emitters (12u), the row of upper receivers (14u), the row of lower re- ceivers (14I) and the row of lower emitters (12I), as described for the first sensor ar- rangement (10). These rows of sensors (12, 14) are preferably arranged as de- scribed for the first sensor arrangement (10), including the presence of a tilting angle alpha (18), which preferably indicates how strong the tilted signal paths (26t) are tilted compared to the axial signal paths (26a).

Additionally, the modified sensor arrangement (20) comprises additional upper emit- ters forming an uppermost row of emitters (22u). This uppermost row of emitters (22u) can preferably also be referred to as first row of additional emitters (22u). It is preferred that the first row of additional emitters (22u) is arranged above the row of upper emitters (12u) of the first sensor arrangement (10). Preferably, the distance between the centers of the additional emitters (22u) and the upper emitters (12u) is 6.5 mm. Furthermore, the modified sensor arrangement (20) comprises an addi- tional row of lower emitters (22I) forming a lowest row of emitters (22I). It is preferred that this lowest row of emitters (22I) is referred to as second row of additional emit- ters (22I). The additional emitters (22u, 22I) of the additional rows of emitters (22u, 22I) are indicated with a chessboard patter in figures 4 to 6. The modified sensor arrangement (20) further comprises an additional row of receiv- ers (24). In figures 4 to 6, the additional receivers (24) are indicated with hatched cir- cles. It is preferred that the additional row of receivers (24) is arranged between the row of upper receivers (14u) and the row of lower receivers (141). It is particularly preferred that the additional row of receivers (24) is arranged in the middle between the row of upper receivers (14u) and the row of lower receivers (141). In the context of the present invention, this preferably means that the additional row of receivers (24) has the same distance to the row of upper receivers (14u) and to the row of lower receivers (141). Preferably, this distance is 6.5 mm, which preferably repre- sents one half of the center distance of the rows of upper emitters (12u), upper re- ceivers (14u), lower receivers (141) and lower emitters (121) of the first sensor ar- rangement (10), which is preferably 13 mm. It is most preferred that the additional row of receivers (24) comprises five receivers, wherein the left additional receiver (24I) can preferably be regarded as part of the left column (28) of the sensor ar- rangement (20), i.e. of the left axial signal path (26al). Preferably, the central addi- tional receiver (24c) can preferably be regarded as part of the central column (30) of the sensor arrangement (20), i.e. of the central axial signal path (26ac). It is pre- ferred that the right additional receiver (24r) can preferably be regarded as part of the right column (32) of the sensor arrangement (20), i.e. of the right axial signal path (26ar).

It is preferred that the additional row of receivers (24) comprises two further addi- tional receivers (24a, 24b). Preferably, the first further additional receiver (24a) is ar- ranged between the left additional receiver (24I) and the central additional receiver (24c). It is particularly preferred that the first further additional receiver (24a) is ar- ranged in the middle between the left additional receiver (24I) and the central addi- tional receiver (24c), i.e. it is preferred that the distance between the first further ad- ditional receiver (24a) and the left additional receiver (24I) is essentially the same as the distance between the first further additional receiver (24a) and the central addi- tional receiver (24c). Preferably, the center distance between the two further addi- tional receivers (24a, 24b) and their neighboring receivers is 5 mm. Preferably, the second further additional receiver (24b) is arranged between the right additional re- ceiver (24r) and the central additional receiver (24c), wherein the second additional receiver (24b) is arranged in the middle between the right additional receiver (24r) and the central additional receiver (24c), i.e. it is preferred that the distance between the second further additional receiver (24b) and the right additional receiver (24r) is essentially the same as the distance between the second further additional receiver (24b) and the central additional receiver (24c). It is preferred that each additional re- ceiver (24) is part of one of the preferably five signal paths (26), which the modified sensor arrangement (20) is preferably capable of measuring along. It is particularly preferred that the modified sensor arrangement (20) is configured to measure the speed of sound (SOS) in different directions within a bone material, so that an oste- oporotic bone fracture risk can be determined from these intermediate results.

Exemplary courses of the signal paths (26) of the modified sensor arrangement (20) are shown in figures 5 and 6. Preferably, the modified sensor arrangement (20) is configured to measure the speed of sound (SOS) along five ultrasound signal paths (26), wherein there may be three axial signal paths (26a) and two tilted signal paths (26t) in the context of the modified sensor arrangement (20). The axial signal paths (26a) preferably coincide with the columns (28, 30, 32) of the sensor arrangement (20). It is particularly preferred that the left column (28) coincides with the left axial signal path (26al) of the modified sensor arrangement (20). Furthermore, it is pre- ferred that the central column (30) coincides with the central axial signal path (26ac) of the modified sensor arrangement (20) and that the right column (32) coincides with the right axial signal path (26ar) of the modified sensor arrangement (20). Pref- erably, the columns (28, 30, 32) and axial signal paths (26a) of the modified sensor arrangement (20) comprise seven sensors, specifically a first or upper additional emitter (22u), an upper emitter (12u), an upper receiver (14u), an additional receiver (24), a lower receiver (141), a lower emitter (121) and a second or lower additional emitter (221).

Preferably, the modified sensor arrangement (20) is also configured to measure the speed of sound (SOS) within a bone along two tilted signal paths (26t). These tilted signal paths (26t) are tilted by a tilting angle alpha (18) compared to the axial signal paths (26a). The most preferred size of the tilting angle alpha (18) is 37.5 °, but al- ternative sizes, such as 14.4 °, 21 ° or 60 °, are also conceivable. The tilted signal paths (26t) can be tilted in a positive direction or in a negative direction. It is pre- ferred to refer to the tilted signal path (26t), which is preferably tilted in a positive an- gel direction, as positive tilted signal path (26t+) and to refer to the tilted signal path (26t), which is preferably tilted in a negative angel direction, as negative tilted signal path (26t-). It is preferred that the positive tilted signal path (26t+) comprises the left upper emitter (12u), the left upper receiver (14u), the central upper receiver (14u), the two further additional receivers (24a, 24b), the central lower receiver (141), the right lower receiver (141) and the right lower emitter (121). Preferably, the negative tilted signal path (26t-) comprises the left lower emitter (121), the left lower receiver (121), the central upper receiver (14u), the two further additional receivers (24a,

24b), the central lower receiver (141), the right upper receiver (14u) and the right up- per emitter (12).

The SOS measurements carried out with the proposed sensor arrangements (10,

20) preferably make use of the bidirectional transmission technique. In the context of the bidirectional transmission technique, ultrasound signals are preferably emitted in two opposing directions within one signal path. Preferably, the two measuring direc- tions run in parallel - for example for the tilted signal paths (16t, 26t) - or are identi- cal - for example for the axial signal paths (16a, 26a). The measurements carried out along the tilted signal paths (16t, 26t) are preferably referred to as quasi-bidirec- tional, whereas the measurements carried out along the axial signal paths (16a,

26a) are preferably referred to as bidirectional. In figure 6, the positive directions (34, 38) of the (quasi-)bidirectional transmission measurements are indicated with solid lines and solid arrows, whereas the negative directions (36, 40) of the (quasi-)- bidirectional transmission measurements are indicated with dashed lines and/or ar- rows.

It is noted that in figure 6 only a choice of arrows representing ultrasound based SOS measurements is indicated with regard to the axial signal paths. This is done to provide a better overview. For example, for the left column (28) of the modified sen- sor arrangement (20), only the arrows from the four emitters (22u, 12u, 121 and 221) are indicated, which end at the upper left receiver (14u). In the context of the pre- sent invention, this preferably means that the four emitters (22u, 12u, 121 and 221) emit ultrasound signals, which are preferably received and/or detected by the upper left receiver (14u). Preferably, the four emitters (22u, 12u, 121 and 221) of the left col- umn (28) additionally emit ultrasound signals, which are received by the additional left receiver (241) and the left lower receiver (141). This can be seen, when taking into account the arrows plotted with regard to the central column (30) and the right column (32). Preferably, the graphic representation of the central column (30) shows those arrows, i.e. ultrasound signals, which are emitted by the four emitters (22u, 12u, 121 and 221) and which are received and/or detected by the additional central receiver (24c). It is preferred that the graphic representation of the right column (32) shows those arrows, i.e. ultrasound signals, which are emitted by the four emitters (22u, 12u, 121 and 221) and which are received and/or detected by the lower receiver (141). The person skilled in the art will understand from figure 6 that it is preferred in the context of the present invention that the ultrasound signals, which are emitted by the four emitters (22u, 12u, 121 and 221) of one column (28, 30 or 32) of the modified sensor arrangement (20), are preferably received and/or detected by all three re- ceivers (14u, 24, 141) of that column (28, 30 or 32). This will get particularly apparent from the overall view of the left part of figure 6 showing the axial signals paths (26a) of the modified sensor arrangement (20).

The right part of figure 6 preferably indicates exemplary courses for the tilted signal paths (26t) of the modified sensor arrangement (20). For the tilted signal paths (26t), all ultrasound signals taking part in the SOS measurements are indicated. It is pre- ferred that the ultrasound signals emitted by the left upper emitter (12u) are received and/or detected by the central upper receiver (14u), by the second additional re- ceiver (24b) and by the right lower receiver (141). Preferably, the ultrasound signals emitted by the right lower emitter (121) are received and/or detected by the central lower receiver (141), by the first additional receiver (24a) and by the left upper re- ceiver (14u). The measurements indicated by these six arrows preferably form the positive tilted signal path (26t+) for the modified sensor arrangement (20).

It is preferred that the ultrasound signals emitted by the right upper emitter (12u) are received and/or detected by the central upper receiver (14u), by the first additional receiver (24a) and by the left lower receiver (121). Preferably, the ultrasound signals emitted by the left lower emitter (121) are received and/or detected by the central lower receiver (141), by the second additional receiver (24b) and by the right upper receiver (14u). The measurements indicated by these six arrows preferably form the negative tilted signal path (26t-) for the modified sensor arrangement (20).

List of reference signs:

10 First sensor arrangement

12 emitters

12u upper emitters forming a row of upper emitters of the first sensor arrange- ment

12I lower emitters forming a row of lower emitters of the first sensor arrangement 14 receivers

14u upper receivers forming a row of upper receivers of the first sensor arrange- ment

14I lower receivers forming a row of lower receivers of the first sensor arrange- ment

16 signal paths

16a axial signal paths

16al left axial signal path

16ac central axial signal path

16ar right axial signal path

16t tilted signal paths

16t+ positive tilted signal path

16t- negative tilted signal path

18 tilting angle a/p/?a

18a potential exemplary position of the tilting angle alpha

18b potential exemplary position of the tilting angle

18c potential exemplary position of the tilting angle

20 modified sensor arrangement

22 additional emitters

22u additional upper emitters forming an uppermost row of emitters of the modi- fied sensor arrangement, first row of additional emitters 22I additional lower emitters forming a lowest row of emitters of the modified sensor arrangement, second row of additional emitters

24 additional receivers

24I left additional receiver

24c central additional receiver

24r right additional receiver

24a first further additional receiver

24b second further additional receiver

26 signal paths of the modified sensor arrangement

26a axial signal paths of the modified sensor arrangement

26al left axial signal path of the modified sensor arrangement

26ac central axial signal path of the modified sensor arrangement

26ar right axial signal path of the modified sensor arrangement

26t tilted signal paths of the modified sensor arrangement

26t+ positive tilted signal path of the modified sensor arrangement

26t- negative tilted signal path of the modified sensor arrangement

28 left column of sensors

30 central column of sensor

32 right column of sensors

34 positive direction of bidirectional transmission measurement

36 negative direction of bidirectional transmission measurement

38 positive direction of quasi-bidirectional transmission measurement 40 negative direction of quasi-bidirectional transmission measurement