WO2019030395A2

WO2019030395A2 - Non invasive animal castration

Info

Publication number: WO2019030395A2
Application number: PCT/EP2018/071799
Authority: WO
Inventors: Henrik Norgreen; Hanne Willemoes MARIBO; Lotte SKADE
Original assignee: Norgri; Landbrug & Fødevarer F.M.B.A.
Priority date: 2017-08-11
Filing date: 2018-08-10
Publication date: 2019-02-14

Description

NON INVASIVE ANIMAL CASTRATION TECHNICAL FIELD

The present invention relates to non-invasive castration of animals, such as domestic animals. In particular, the present invention relates to castration carried out by interrupting the blood supply to the gonadal tissue, i. e. the testes or the ovaries.

BACKGROUND OF THE INVENTION

Domestic animals not intended for providing offspring are commonly sterilized or castrated, for instance in order to avoid undesired or uncontrolled reproduction/pregnancy or to reduce/prevent other manifestations of sexual behaviour (fighting between groups of a herd or between male individuals, mounting, attempts to escape fenced-in areas etc.) .

For instance, male horses and mules are often sterilized or castrated because the adult males are rather aggressive and troublesome. Male cattle are sterilized or castrated to improve fattening and docility in feedlots or for use as oxen.

Also, livestock may be sterilized or castrated when used for food in order to increase growth or weight or both of individual male animals and in certain cases because of undesirable taste and odour of the meat from sexually mature males; in particular, it is recognized that the taint, called boar taint, in meat from male pigs is primarily caused by androstenone and skatole concentrations stored in the fat and muscular tissues. In commercial meat production, male pigs are either castrated shortly after birth or slaughtered before they become sexually mature. In some cases, specially designed breeding programmes are followed to reduce boar taint in the animals, and resources are also allocated in

slaughterhouses to remove the animals that exhibit the distinct smell .

Also pets are often sterilized or castrated . This is done with a view to prevent overpopulation of the community by unwanted animals, and to reduce certain diseases such as prostate disease and testicular cancer in male dogs (oophorectomy in female pets is often called spaying) . Testicular cancer is rare in dogs, but prostate problems are somewhat common in unaltered male dogs when they get older. Neutered individuals have a much lower risk of developing prostate problems in comparison. Unaltered male cats are more likely to develop an obstruction in their urethra, preventing them from urinating to some degree; however, neutering does not seem to make much difference statistically because many neutered toms also have the problem . Methods of veterinary castration currently include instant surgical removal, the use of an elastrator tool to secure a band around the testicles that disrupts the blood supply, the use of a Burdizzo tool or emasculators to crush the spermatic cords and disrupt the blood supply, pharmacological injections ("chemical castration" using e.g . anti-androgen substances) and implants and immunological techniques to inoculate the animal against its own sexual hormones - one example is the immunocastration product Improvac®.

Fur animals like mink are not commonly castrated, mainly due to the risk of cannibalism when injured animals are present in a group of other carnivores.

Certain animals, like horses and male swine, are usually surgically treated with a scrotal castration (which can be done in horses with the animal standing while sedated and after local anesthetic has been applied) . Male piglets are usually castrated within 2-4 days post birth. However, there is a need to provide simple methods and means for castrating animals in a way which is highly automated and preferably painless to the animal, whereby animal welfare is considerably improved. SUMMARY OF THE INVENTION

The present inventors have realised that castration of animals can be accomplished in a painless and non-invasive manner by interrupting the blood supply to the gonads via application of radiation or pressure waves that can be focussed in the spermatic cords or the suspensory ligament of the ovaries containing the artery that supplies blood and nutrients to the gonads, as well as other vessels in the spermatic cords or the suspensory ligament of the ovaries that may in some cases supply blood and nutrients to the gonads. The interruption can be brought about by a number of effects: thrombus formation occasioned by blood coagulation and/or flocculation of protein and/or precipitation/denaturation of blood protein etc. (I. e. the interruption is occassioned by insoluble material formed in the lumen of the artery and other vessels), the artery and other vessels (in particular the arterial wall) itself becomes injured so as to become blocked, ruptured or completely severed .

Apart from the direct beneficial effect of reducing or eliminating pain in the animals, the present invention also allows an effective expansion of the possibility of castration of animals like mink, where traditional surgical methods are ruled out due to the risk of e.g.

cannibalism .

So in its most general embodiment of a first aspect, the invention relates to a method for non-invasive castration of a male or female animal, the method comprising selective interruption of the blood supply to the animal's gonadal tissue, wherein said selective interruption is sufficient to necrotize said gonadal tissue, and wherein the selective interruption is accomplished by delivering an effective dose of focused radiation or focused pressure waves to a selected region being the spermatic cords in the male animal, or being the suspensory ligament of the ovaries in the female animal.

DETAILED DESCRIPTION OF THE INVENTION Definitions

A number of terms and expressions are used herein and are explained in detail in the following : Sterilization is in the present context an intervention, which intentionally renders an animal (which in the present context normally is a mammal) incapable of reproduction. "Castration" is a form of sterilization, which achieves the goal of sterilization by rendering the gonads (testes or ovaries) non-functional. Unlike other forms of sterilization (such as tubal sterilization or vasectomy, castration shuts down a significant part, such as most or all biological functions of the gonads, including their production of hormones.

"Non-invasive" is a term intended to mean a procedure, which does not entail any trauma to the skin in the form of surgical wounds or any substantial application of mechanical force. Hence, non-invasive sterilization or castration is a procedure, which castrates an animal, but which does not entail mechanical intrusion into the body of the animal. "Selective interruption of blood supply to the animal's gonadal tissue" is an expression, which entails that the gonads are the only organs that are affected by the blood supply interruption to a degree that has a significant influence on the physiological function. In this context, it is noted that the location(s) of the interruption is/are selected so as to be as specific for gonadal tissue as possible. In some embodiments only blood vessels, such as the artery vessels supplying the gonadal tissue are affected by the selective interruption. Accordingly, in some embodiments, tissues such as the vas deferens, epididymis, testis, and/or scrotum is not directly affected by the delivering of an effective dose of focused radiation or focused pressure waves to the selected region of the procedure of the present invention.

"An effective dose" is in the present context the combination of 1) radiation or pressure wave intensity and 2) the application time at a location in the body, where the combination is sufficient to obliterate the gonadic artery (for instance by induction of an irreversible or long- lasting damage in the artery walls or by induction of a thrombus in the artery) for such a long time that the gonadal tissue will not survive the hypoxia following as a consequence of the interruption of the blood supply.

"Focused" is a term, which is used together with the terms radiation and pressure waves and implies that the energy density of the radiation or pressure waves has a local peak value at a position remote from the origin of the radiation or pressure waves. For instance, if pressure waves are generated travel in the direction of and are reflected by a parabolic surface, their energy will exhibit density maximum in the focal point of the parabolic surface, whereas the energy intensity will be considerably lower at points outside the focal point. This situation can be emulated by delivering the radiation or pressure waves form emitters arranged so as to allow the radiation or pressure waves generated to intersect at a focal point. Alternatively or in addition, the emitters may have their phases regulated so that interference between emission from each emitter/transducer minimises energy deposition in volumes outside the target area. In the present context, a "gonadal artery" is any arterial blood vessel that supplies or can supply the gonads with blood. In males, the only artery of relevance is the testicular artery. In females the main gonadal artery is the ovarian artery. However, the ovarian branch of the uterine artery communicates via anastomoses with the ovarian artery and it therefore cannot be excluded that exclusive obliteration of the ovarian artery proximal to the ovary could allow the ovaries to survive due to retrograde flow of blood delivered from the uterine artery.

As used herein, the spermatic cord is the cord-like structure in males formed by the vas deferens (ductus deferens) and surrounding tissue that runs from the deep inguinal ring down to each testicle containing arteries, such as the gonadal artery, vas deferens, as well as lymphatic vessels. As used herein, the suspensory ligament of the ovaries in the female animal is the ligament that extends out from the ovary to the wall of the pelvis surrounding the ovarian vessels including the ovarian artery.

In some embodiments, the terms "spermatic cords", "suspensory ligament of the ovaries", "gonadal artery", "testicular artery and other blood vessels", "ovarian artery" and other animal organ present as a pair of two in each subject animal, include both (two) tissue parts in each animal. Accordingly, a non-invasive castration of a male or female animal will typically be performed on each gonadal tissue of the pair of gonadal tissues in the subject animal. Detailed embodiments

In the first aspect, the invention provides a method for non-invasive castration of a male or female animal, the method comprising selective interruption of the blood supply to the animal's gonadal tissue, wherein said selective interruption is sufficient to necrotize said gonadal tissue, and wherein the selective interruption is accomplished by delivering an effective dose of focused radiation or focused pressure waves to a selected region being the spermatic cords in the male animal, or being the suspensory ligament of the ovaries in the female animal.

Embodiments of the first aspect of the invention provide a method which may be exercised by laymen, i. e. persons without any substantial educational background in the veterinary or medical sciences. Some embodiments allows castration of animals in a simple procedure where a handheld device is positioned on a surface area of an animal body - e.g. on the skin covering the scrotum - followed by a simple push of a button to trigger the handheld device to locates the selected area and subsequently obliterate it by means of electromagnetic or (preferably) pressure waves, thereby also obliterating the artery and other vessels in the selected region. In other words, the present invention can be implemented in the existing settings and under the essentially same conditions where e.g . piglets are normally castrated, but where the presently disclosed procedure provides for a painless and non-invasive method which is in contrast to the existing procedures. By delivering the effective dose to the selected region being the spermatic cords in the male animal, or being the suspensory ligament of the ovaries in the female animal, it may be ensured that no blood or nutrients are supplied to the gonads for an effective castration. This may be particularly suitable in animals where the gonadal artery and other arteries in the spermatic cords in the male animal or the suspensory ligament of the ovaries in the female animal are particularly difficult to locate. This may be the case in relatively young and/or small animals.

The inventors have further realised that other arteries than the gonadal artery in the spermatic chords in the male animal or in the suspensory ligament of the ovaries in the female animal have their blood flow redirected if the gonadal artery is disrupted . Moreover, these other blood vessels may normally supply other tissues - e.g., the vas deferens, the suspensory ligament of the ovary or the spermatic chord - under 'normal' conditions, while after disruption of the gonadal artery, blood may be redirected to the gonads via these other arteries. Accordingly, more effective and/or swift castration may be achieved by disrupting all blood vessels in the spermatic chords in the male animal or in the suspensory ligament of the ovaries in the female animal. In some embodiments, the selected region is the testicular artery and other blood vessels of the spermatic chords in the male animal, or the ovarian artery and other blood vessels of the suspensory ligament of the ovaries in the female animal.

This allows for disruption of the testicular artery and other blood vessels of the spermatic chords in the male animal or the ovarian artery and other blood vessels of the suspensory ligament of the ovaries in the female animal without necessarily disrupting the remaining vessels being, e.g., the vas deferens in the spermatic chord of the male animal. This may be particularly advantageous in animals where the individual vessels may be distinguished and may lead to further minimized pain for the animal, while still ensuring that all blood vessels in the spermatic chords in the male animal or in the suspensory ligament of the ovaries in the female animal are disrupted.

In some embodiments, the selected region is the testicular artery in the spermatic chords in the male animal, or the ovarian artery in the suspensory ligament of the ovaries in the female animal. This allows for disruption of the gonadal artery only, which may further minimize pain for the animal. It may be particularly useful when the gonadal artery can be clearly distinguished from the remaining vessels, and where the combined blood flow capacity of other blood vessels in the spermatic chords in the male animal or the ovarian artery are relatively small compared to the blood flow capacity of the gonadal artery. In some embodiments, at least the testicular artery in male animal ruptured or severed, or the ovarian artery in the female animal is ruptured or severed. This may increase the probability of achieving permanent disruption of the blood flow to the gonads and thereby increase the effectiveness of the castration method even further.

In some embodiments, the focused radiation or pressure waves is/are applied by means of an emission device, which is preferably handheld, and which comprises at least one means for emission of radiation or pressure waves.

The focused radiation or pressure waves is/are thus preferably applied by means of a (preferably hand-held) emission device comprising at least one means for emission (e.g. a transducer) of radiation or pressure waves. It will be understood that the provision of a handheld (preferably rechargeable and/or battery driven) device is by no means essential to the invention and that the method may be exercised by using a stationary device. However, for convenience purposes, it is contemplated that the use of a handheld device provides for the most flexible solution for e.g. a farmer who has to sterilize or castrate a larger number of animals.

In some embodiments, said emission device further comprises at least one means for detecting returned radiation or pressure waves. Again, this is not an essential feature, but may prove highly convenient and practical when and if it is difficult to determine the exact location of the selected area. In many male farm animals, the gonadal artery is embedded in the spermatic cord, which is relatively simple to identify, and in such cases it will for the more experienced user be unnecessary to rely on automated assistance in identifying an optimum location for the application of the inventive treatment. On the other hand, since the present invention aims at inflicting a minimum of damage to other tissues than the selected region (and secondarily to the gonads), the inclusion in the device of detection means for return radiation or pressure waves provides for the possibility of imaging the selected region and/or locating it and thereby enable subsequent control of the application of the effective dose to the optimum location in the animal's body. In some embodiments, said emission device further comprises data processing and storage means configured to compute the 3D location of the selected region, said 3D location being computed from data representing the radiation or pressure waves emitted by the emission device and data representing the returned radiation or pressure waves detected.

In some embodiments, said emission device includes means for qualitative or quantitative determination of arterial blood flow in the selected region and/or includes means for imaging the selected region.

Software and algorithms have been developed for similar purposes, and is e.g. used routinely when treating kidney stones with ultrasound pulses. According to the present invention, the device may therefore include means for qualitative or quantitative determination of arterial blood flow in the gonadal artery and/or includes means for imaging the selected region. This first option is typically used to verify that blood is flowing correctly in a blood vessel, but the detection of blood flow within a preselected region of a body also provides for the exact location of the pulsating vessel it is intended to destroy. One convenient way to identify a pulsating blood vessel is by Doppler analysis of the emitted signal (e.g. ultrasound) vs. the return signal, where a change in pitch (wavelength) unequivocally identifies moving objects. For instance, blood flow in the umbilical artery is routinely assessed by means of ultrasound Doppler analysis.

In some embodiments, the emission device is configured to deliver the effective dose of focused radiation or pressure waves to a target position within the 3D location of the selected region. Put in simpler terms, in present embodiments the device will emit the radiation or pressure wave dose in a controlled manner, where the measured and computed 3D position of the gonadal artery is used as input for a control function, which ensures that the effective dose is directed to and delivered within the region occupied by the gonadal vessel. In some embodiments:

- all of said at least one means for emission of radiation or pressure waves are configured to both deliver radiation at tissue non-injuring doses and to deliver the effective dose to the selected region, or

- at least one of said means for emission of radiation or pressure waves is configured to deliver radiation or pressure waves at tissue non-injuring doses and wherein at least one further means for emission of radiation or pressure waves is configured to deliver the effective dose to the selected region.

In the event the device is solely based on ultrasound generation and detection, it is envisaged that the transducers that deliver the tissue non-injuring waves provide the waves from a limited area so as to avoid problems with respect interpretation of the return waves - for instance by only emitting waves from one single transducer at a time. To increase accuracy, the device can deliver the tissue non-injuring waves in series of subsequent pulses from different single transducers, whereby the results obtained from measurements of the return waves can be integrated to define with high certainty the location of the artery. When the location has been established, the device then delivers the effective dose of the focussed wave to the location - this can conveniently be done by controlling the phase of the output from the transducers so as to direct the waves in the desired direction, but alternatively the device may include an adjustable parabolic reflector which allows that the focal point of the waves are adjusted according to the data gathered. In some embodiments, said emission device is configured to operate in the sequence of

1) a step of emission of a tissue non-injuring dose of radiation or pressure waves,

2) a step of receiving return radiation or pressure waves,

3) a step of computing the 3D location of the selected region from data representing the emitted and received radiation or pressure waves, and 4) a step of emission of focussed radiation or pressure waves to the selected region, where the focus of said focussed radiation is controlled on the bases of the computed 3D location. This allows for a user-friendly and reliable operation of the device.

In the most preferred embodiment, the sequence 1-4 is fully automated. When the device has been positioned correctly, a start signal is delivered, and the steps 1-4 will be carried out within a few seconds.

In many embodiments of the invention, the device used in the method will only use radiation (electromagnetic waves such as microwaves or IR) or only use pressure waves (typically ultrasound waves). But in some embodiments, it is possible to locate the selected region to be treated with either one of radiation and pressure waves and subsequently subject the selected region to the effective dose of the other of the radiation and the pressure waves. So, the method of the invention entails that the device comprises that

- the emissions in steps 1 and 4 described above are both of radiation or both of pressure waves,

- the emissions in steps 1 and 4 described above are of radiation and pressure waves, respectively, or

- the emissions in steps 1 and 4 described above are of pressure waves and radiation, respectively.

In some embodiments, the effective dose is delivered in the form of ultrasound waves. There are already hand-held ultrasound devices available on the market for various purposes meaning that the provision of a device adapted to provide the necessary energy intensity based on a location mechanism can be accomplished without any serious difficulty. It is believed however, that the hand-held ultrasound devices disclosed herein (see below) are inventive in their own right due to the inclusion of both detection/imaging technology and the effector technology for delivering the effective dose of ultrasound waves to the selected region.

One convenient and economical way of providing the necessary ultrasound pulses and waves is to have the at least one means for emission of pressure waves comprising piezoelectric elements capable of delivering ultrasound waves. In some embodiments, the effective dose is delivered in the form of electromagnetic waves. These embodiments can take various forms, but preferred electromagnetic waves are those in the microwave or infrared spectrum due to their ability to penetrate animal, such as human tissues and their non-ionizing nature. It will be understood from the above that the animals treated are normally not yet sexually mature and in the case of piglets, they are normally a maximum of 4 days old. On the other hand, animals, and in particular mammals of various relevant species and ages may be subjected to the present treatment. For instance the animal according to the present invention is typically a mammal selected from the group of humans, pigs, horses, cattle, sheep, goats, mink, dogs, cats, mink, and foxes (as well as other animals in the fur industry). The preferred animals are piglets, in male piglets or possibly female piglets. As will also appear from the above, the invention is typically practised on livestock animals in order to improve production of high quality products and improve animal welfare and the working environment. In some embodiments, the animal is non-human.

In some embodiments, the method is non-therapeutic and non-prophylactic.

In a second aspect, the invention provides the following numbered embodiments:

1. A method for non-invasive sterilization or castration of animals, the method comprising selective interruption of the blood supply to the animal's gonadal tissue, wherein said selective interruption is sufficient to necrotize said gonadal tissue, and wherein the selective interruption is accomplished by delivering an effective dose of focused radiation or focused pressure waves to the gonadal artery.

2. The method according to embodiment 1, wherein the focused radiation or pressure waves is/are applied by means of an emission device, which is preferably handheld, and which comprises at least one means for emission of radiation or pressure waves.

3. The method according to embodiment 2, wherein said emission device further comprises at least one means for detecting returned radiation or pressure waves.

4. The method according to embodiment 3, wherein said emission device further comprises data processing and storage means configured to compute the 3D location of said gonadal artery, said 3D location being computed from data representing the radiation or pressure waves emitted by the emission device and data representing the returned radiation or pressure waves detected.

5. The method according to embodiment 3 or 4, wherein said emission device includes means for qualitative or quantitative determination of arterial blood flow in the gonadal artery and/or includes means for imaging the gonadal artery. 6. The method according to embodiment 4-5, wherein the emission device is configured to deliver the effective dose of focused radiation or pressure waves to a target position within the 3D location of the gonadal artery.

7. The method according to any one of embodiments 2-6, wherein

- all of said at least one means for emission of radiation or pressure waves are configured to both deliver radiation at tissue non-injuring doses and to deliver the effective dose to the gonadal artery, or

- at least one of said means for emission of radiation or pressure waves is configured to deliver radiation or pressure waves at tissue non-injuring doses and wherein at least one further means for emission of radiation or pressure waves is configured to deliver the effective dose to the gonadal artery.

8. The method according to any one of embodiments 2-7, wherein said emission device is configured to operate in the sequence of

2) a step of receiving return radiation or pressure waves,

3) a step of computing the 3D location of a gonadal artery from data representing the emitted and received radiation or pressure waves, and

4) a step of emission of focussed radiation or pressure waves to said gonadal artery, where the focus of said focussed radiation is controlled on the bases of the computed 3D location. 9. The method according to embodiment 8, wherein

- the emissions in steps 1 and 4 are both of radiation or both of pressure waves,

- the emissions in steps 1 and 4 are of radiation and pressure waves, respectively, or

- the emissions in steps 1 and 4 are of pressure waves and radiation, respectively.

10. The method according to any one of the preceding numbered embodiments, wherein an effective dose of ultrasound waves is delivered to the gonadal artery.

11. The method according to any one of embodiment 2-10, insofar as embodiments 3-10 depend on claim 2, wherein said at least one means for emission of pressure waves comprises piezoelectric elements capable of delivering ultrasound waves.

12. The method according to any one of the embodiments 2-8, wherein an effective dose of electromagnetic waves is delivered to the gonadal artery. 13. The method according to any one of the preceding numbered embodiments, wherein the animal is male and the effective dose is delivered to the scrotal part of the testicular artery, preferably to the part of testicular artery present in the spermatic cord .

14. The method according to any one of embodiments 1-12, wherein the animal is female and wherein the effective dose is delivered to the ovarian artery, preferably to a position in the suspensory ligament of the ovary and in addition to a position just proximal to the regions where the ovarian artery anastomoses with the ovarian branch of the uterine artery.

15. The method according to any one of the preceding numbered embodiments, wherein the animal is not sexually mature. 16. The method according to any one of the preceding numbered embodiments, wherein the animal is selected from the group of pigs, horses, cattle, sheep, goats, dogs, cats, mink, and foxes.

17. The method according to any one of the preceding numbered embodiments, wherein the animal is a livestock animal. 18. The method according to any one of the preceding numbered embodiments, which is non-therapeutic and non-prophylactic.

Accordingly, embodiments of the second aspect of the invention provide a method which may be exercised by laymen, i. e. persons without any substantial educational background in the veterinary or medical sciences. Some embodiments allows sterilization or castration of animals in a simple procedure where a handheld device is positioned on a surface area of an animal body - e.g . on the skin covering the scrotum - followed by a simple push of a button to trigger the handheld device to locates the gonadal artery and subsequently obliterate it by means of electromagnetic or (preferably) pressure waves. In other words, the present invention can be implemented in the existing settings and under the essentially same conditions where e.g . piglets are normally castrated, but where the presently disclosed procedure provides for a painless and non-invasive method which is in contrast to the existing procedures.

In certain embodiments, such a (hand-held) device may further comprise at least one means for detecting returned radiation or pressure waves. Again, this is not an essential feature, but may prove highly convenient and practical when and if it is difficult to determine the exact location of the gonadal artery. In many male farm animals, the gonadal artery is embedded in the spermatic cord, which is relatively simple to identify, and in such cases it will for the more experienced user be unnecessary to rely on automated assistance in identifying an optimum location for the application of the inventive treatment. On the other hand, since the present invention aims at inflicting a minimum of damage to other tissues than the gonadic artery (and secondarily to the gonads), the inclusion in the device of detection means for return radiation or pressure waves provides for the possibility of imaging the artery and/or locating it and thereby enable subsequent control of the application of the effective dose to the optimum location in the animal's body. Therefore, the device may further comprise data processing and storage means configured to compute the 3D location of said gonadal artery, said 3D location being computed from data representing the radiation or pressure waves emitted by the hand-held device and data representing the returned radiation or pressure waves detected. Software and algorithms have been developed for similar purposes, and is e.g. used routinely when treating kidney stones with ultrasound pulses. According to the present invention, the device may therefore include means for qualitative or quantitative determination of arterial blood flow in the gonadal artery and/or includes means for imaging the gonadal artery. This first option is typically used to verify that blood is flowing correctly in a blood vessel, but the detection of blood flow within a preselected region of a body also provides for the exact location of the pulsating vessel it is intended to destroy. One convenient way to identify a pulsating blood vessel is by Doppler analysis of the emitted signal (e.g. ultrasound) vs. the return signal, where a change in pitch (wavelength) unequivocally identifies moving objects. For instance, blood flow in the umbilical artery is routinely assessed by means of ultrasound Doppler analysis. Also imaging is a well-known technology. For purposes of automation, the device used in the invention may e.g. include software enabling recognition of a gonadal artery. This is of particular relevance if the animal to be sterilized or castrated is female, since the gonadal artery (the ovarian artery) is located in the pelvic cavity and therefore not easily accessible. However, the exact course taken by the ovarian artery in the pelvis is highly characteristic and its formation of anastomoses with the ovarian branch of the uterine artery allows appropriate recognition software to distinguish the ovarian artery from other blood vessels in the pelvic cavity. This is all the more relevant because it may be of relevance to interrupt the ovarian artery at two distinct location: 1) proximal to the ovaries (e.g. in the suspensory ligament), which will interrupt blood supply to the ovaries from the ovarian artery, and 2) distal to the ovaries but proximal to the region where the ovarian artery anastomoses with the ovarian branch of the uterine artery - the latter will entail the effect that the ovaries cannot be supplied by blood from the uterine artery running in reverse direction from the anastomosis region through the ovarian artery.

It is preferred that the emission device is configured to deliver the effective dose of focused radiation or pressure waves to a target position within the (computed) 3D location of the gonadal artery. Put in simpler terms, the device will emit the radiation or pressure wave dose in a controlled manner, where the measured and computed 3D position of the gonadal artery is used as input for a control function, which ensures that the effective dose is directed to and delivered within the region occupied by the gonadal vessel.

In many embodiments of the invention, the device used in the method will comprise the means for emission (e.g. transducers) for both determining the presence of the blood vessel to interrupt and for delivering the effective dose. But it goes without saying that the device can instead include a dedicated subset of emission means for each purpose. So, the method of the invention entails that the device comprises that either

- all of said at least one means for emission of radiation or pressure waves are configured to both deliver radiation at tissue non-injuring doses and to deliver the above-discussed effective dose to the gonadal artery, or

- at least one of said means for emission of radiation or pressure waves is configured to deliver radiation or pressure waves at tissue non-injuring doses and wherein at least one further means for emission of radiation or pressure waves is configured to deliver the effective dose to the gonadal artery. In the event the device is solely based on ultrasound generation and detection, it is envisaged that the transducers that deliver the tissue non-injuring waves provide the waves from a limited area so as to avoid problems with respect interpretation of the return waves - for instance by only emitting waves from one single transducer at a time. To increase accuracy, the device can deliver the tissue non-injuring waves in series of subsequent pulses from different single transducers, whereby the results obtained from measurements of the return waves can be integrated to define with high certainty the location of the artery. When the location has been established, the device then delivers the effective dose of the focussed wave to the location - this can conveniently be done by controlling the phase of the output from the transducers so as to direct the waves in the desired direction, but alternatively the device may include an adjustable parabolic reflector which allows that the focal point of the waves are adjusted according to the data gathered. In the most automated - and thereby user-friendly - embodiments the device used in the inventive method is configured to operate in the sequence of

2) a step of receiving return radiation or pressure waves,

4) a step of emission of focussed radiation or pressure waves to said gonadal artery, where the focus of said focussed radiation is controlled on the bases of the computed 3D location.

In many embodiments of the invention, the device used in the method will only use radiation (electromagnetic waves such as microwaves or IR) or only use pressure waves (typically ultrasound waves). But in some embodiments, it is possible to locate the blood vessel to be treated with either one of radiation and pressure waves and subsequently subject the blood vessel to the effective dose of the other of the radiation and the pressure waves. So, the method of the invention entails that the device comprises that

The currently preferred method implies that an effective dose of ultrasound waves is delivered to the gonadal artery. There are already hand-held ultrasound devices available on the market for various purposes meaning that the provision of a device adapted to provide the necessary energy intensity based on a location mechanism can be accomplished without any serious difficulty. It is believed however, that the hand-held ultrasound devices disclosed herein (see below) are inventive in their own right due to the inclusion of both

detection/imaging technology and the effector technology for delivering the effective dose of ultrasound waves to the gonadal vessels.

One convenient and economical way of providing the necessary ultrasound pulses and waves is to have the at least one means for emission of pressure waves comprising piezoelectric elements capable of delivering ultrasound waves. Nevertheless, an alternative to ultrasound is to utilise an effective dose of electromagnetic waves, which is delivered to the gonadal artery. This embodiment can take various forms, but preferred electromagnetic waves are those in the microwave or infrared spectrum due to their ability to penetrate animal, such as human tissues and their non-ionizing nature. As noted above, the animals treated are typically male animals. In those embodiments the effective dose is preferably delivered to the scrotal part of the testicular artery, preferably to the part of testicular artery present in the spermatic cord in the scrotum. However, the animal may be female: one example is female piglets, which are used in the production of hams from adult pigs living in the wild (or at least in open-air environments) - in order to ensure high quality meat from these animals, it is preferable that the females do not become pregnant during their time in the wild. So, in some embodiments, the animal to be treated is female and the effective dose is delivered to the ovarian artery, preferably to a position in the suspensory ligament of the ovary and optionally also to position distal to the ovaries but proximal to the anastomosis with the ovarian branch of the uterine artery. It will be understood from the above that the animals treated are normally not yet sexually mature and in the case of piglets, they are normally a maximum of 4 days old. On the other hand, animals (mammals) of various relevant species and ages may be subjected to the present treatment. For instance the mammal is typically selected from the group of pigs, horses, cattle, sheep, goats, mink, dogs, cats, mink, and foxes (as well as other animals in the fur industry). The preferred animals are piglets, in particular male piglets. As will also appear from the above, the invention is typically practised on livestock animals in order to improve production of high quality products and improve animal welfare and the working environment.

The following neutralization process is one embodied example of the claimed method according to the first and second aspect of the invention, the procedure being intended for a male piglet.

Place the piglet in a fixture, which keeps the piglet at the same position with the testicles facing upward

Clean the testicles

- Apply Ultrasonic grease on testicles

Fix the Ultrasonic head (combined vision and heating) on the testicles

Push the Start button on the control unit

- The ultrasonic vision unit will identify the exact position of the arteries as first step, where after the ultrasonic heating unit will blockage the arteries. - After blockage, the ultrasonic vision unit will control stop of blood stream checking for no Doppler effect

- An visual and audible indication will be generated in case of successful / failed

neutralization

- The piglet can be removed from the fixture

Details pertaining to the device used in the present invention

It should be understood that the detailed description, while indicating specific embodiments, is provided by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

The method according to present invention is as pointed out above preferentially carried out by use of an ultrasonic device having an emission part and, according to some embodiments, also an imaging part or a sensor part. The emission part and the imaging/sensor part may be encompassed by a single housing, or alternatively by two housings with a first part comprising the emitters and sensors, and a second part comprising control electronics and a user interface, the user interface possibly comprising a graphical user interface for viewing images of a scanned area.

In the embodiments wherein the ultrasonic device has an imaging part, the imaging part preferentially comprises a commonly used image generating phased array system. The imaging system preferentially comprises a flat multi transducer element ultrasonic array with 55-70, preferentially 64, transducer elements. The multi transducer array preferentially forms a two dimensional surface oriented parallel to an animal engaging surface of the ultrasonic device. The size and dimensions of the animal engaging surface may vary depending on the animal being sterilized or castrated. The preferred driving frequency of the transducers of the imaging system lie in the range of 3-5 MHz, but may vary depending on the depth of imaging and desired resolution.

In embodiments of the present invention where an ultrasound emitting device is utilised, the "effector" part of the device can be provided in a number of configurations, so as to ensure transmission of the ultrasound from a larger area (where the energy density is relatively low) and focusing the ultrasound in the small target volume where the intensity reaches a relevant "destructive" level.

It is hence preferable that the ultrasound waves focuses energy delivery in a small volume without substantially injuring surrounding tissue. The emission part may preferentially comprise a transducer of a concave piezoelectric element arching above the skin engaging surface for generating a beam of ultrasound being relatively widely spread at the skin engaging surface of the ultrasonic device, while being directed towards a common focal point below the surface being, e.g., a part of the testicular or ovarian artery. Also, this effect can be attained if the piezoelectric crystals are arranged so as to transmit the ultrasound waves in the direction of a parabolic surface, which upon reflection of the waves will concentrate them in the focal point of the parabolic surface, said focal point being the target for the treatment. The piezoelectric crystals can thereby be (re)located and/or controlled via electric excitation in order for the sound pressure wave to focus in the target volume. It may be advantageous to employ more physical acoustic lenses.

To facilitate use of the emission part, a conductive paste is typically applied to the skin, after which the emission part (transducer) is placed on the paste treated surface. The concave piezoelectric element may as mentioned be formed by one single element or multiple elements, e.g., 2-16 separate piezoelectric elements arranged to form an overall concave shape, e.g. ellipsoid or elliptic. The widespread beam at the skin engaging surface enables non destructive intensities of the beam at the skin surface, while the focused beam below the skin surface enables tissue damage and/or blood coagulation, in particular at the focal point.

In one embodiment, the emission part further comprises a plurality of physical focusing lenses for focusing the ultrasonic waves from the concave piezoelectric element further. The size and dimensions of the animal engaging surface may vary depending on the animal being sterilized or castrated.

The driving frequency of the emission part transducer for interrupting blood flow

preferentially lies in the range of 20 kHz - 500 kHz. The lower part of the range is suitable for generation of high intensity ultrasonic Shockwaves directly causing tissue damage and abruption of blood flow. The higher part of the range is suitable for generation of ultrasonic waves eventually heating up the tissue. The heat is then primarily used for inducing blood coagulation and abruption of blood flow. Two transducer systems are often used: one for generating 3D data and one for providing the focused heat, but as pointed out above, it is possible to operate the same transducers for both purposes. It is to be noted that the frequencies selected for effecting the blood supply interruption are not critical - the skilled person will be able to select a suitable frequency, which will be able to deliver the necessary energy to the target artery. However, the selection of a suitable frequency is typically a choice incorporating the desired precision (resolution) of the treatment. Since the speed of sound (v) in most tissues is about 1480 m/s and since the relation between frequency (f) and wavelength (λ) is A=v/f, the wavelength of a 20 kHz ultrasound wave will be 7.4 cm. The imaging part of the device in one embodiment comprises a L10-22-RS transducer. Such a transducer is capable of wide-band, high frequency, linear array emission. The footprint of the part applied to the skin of the animal is 8.1 x 19.3 mm. The bandwidth of the transducer is 10-22MHZ. In one embodiment, ultrasonic radiation is delivered to the selected region for disruption of the blood flow with an electric power of 200 W. This may be particularly suitable for discretely producing an ablation zone without skin burn as desired. The maximal depth of the ultrasonic radiation may in this case be: 8-9 mm. In this case, an acoustic intensity of 1552 W/cm² and an acoustic energy of 1052 J is particularly suitable. Other relevant particularly useful embodied parameter values for the ultrasonic transducer at these embodied values are pulse length, 150 ms; intermission time between pulses, 150 ms; duty factor, 0.5; number of pulses per spot, 70; interval spacing between spots, 3 mm; and the distance between the skin surface and the focus, 5 mm.

Description of the figures Fig. 1 illustrates the working principles of an ultrasonic imaging part;

Fig. 2 illustrates working principles of an embodied ultrasonic device for ultrasonic emission; Fig. 3 illustrates a castration bench and an ultrasonic device.

In Fig. 1, the working principles of an embodied ultrasonic imaging device 1 having an emission part and a sensor part are illustrated. The emission part and the imaging/sensor part are encompassed by a single housing 3 in the illustrated embodiment. A second part (not illustrated) of the imaging device 1 comprises control electronics and a user interface, the user interface comprising a graphical user interface for viewing images of a scanned area.

The upper left corner of Fig. 1 illustrates ultrasonic waves 5 emitted from the emission part of the ultrasonic imaging device, and the reflected ultrasonic waves 7. In this case, the emitted waves 5 are reflected by a castration bench 9 as illustrated in Fig. 3. Accordingly, the emitted waves 5 are this case not reflected by any intervening entities, such as animal tissue. The diagram 11 in the lower left corner of Fig. 1 illustrates two peaks 13 corresponding to the detected waves reflected by the perimeter of the housing 3 and the castration bench 9. The horizontal axis of the diagram denotes time, and from the elapsed time 19 between the two peaks 13 and a known wave propagation speed of the waves, the distance D_c 20 between the housing 3 and the castration bench 9 can be calculated. The upper right corner of Fig. 1 illustrates a case where an entity 15 intersects the emission part and the castration bench 9. Again, the distance D_e 17 between the entity 15 and the housing 3 is derivable from the elapsed time 21 measured between the relevant peaks 13 of the diagram 11 in the lower right corner of Fig. 1. Fig. 2 illustrates working principles of an embodied ultrasonic device 2 for emission of an effective dose of focused ultrasonic radiation to a selected region being the spermatic cords in the male animal, or being the suspensory ligament of the ovaries in the female animal. The ultrasonic waves are emitted from an emitter 22, which is ellipsoidal so as to emit waves in a pattern that allows them to focus at the selected region 25. The focusing occurs in a focusing zone depth 23 extending between the emitter 22 and the selected region 25. The energy of the waves is at least substantially deposited in in the focal volume 27. The area 29 marks a region defined by the housing 3 between the emitter 22 and the skin surface 31 of the male or female animal being castrated. The effective dose is in one embodiment delivered in accordance with the following parameters: electric power of 175-225 W, such as around 200 W (focusing zone depth 23 of roughly 8-9 mm at 200 W); In this case, an acoustic intensity of 1490-1610 W/cm², such as around 1552 W/cm² and an acoustic energy of 995-1100 J, such as around 1052 J are particularly suitable. Other relevant particularly useful embodied parameter values for the ultrasonic emitter 22 at these embodied values are, e.g., pulse length, 140-170 ms, such as around 150 ms; e.g., intermission time between pulses, 140-170 , such as around 150 ms; e.g., duty factor, 0.4-0.6, such as around 0.5; e.g., number of pulses per spot, 65-75, such as around 70; e.g., interval spacing between spots, 2-4 mm, such as around 3 mm; and, e.g., the distance between the skin surface 31 and the focal volume, approximately 5 mm.

Fig. 3 illustrates a castration bench 9 and an ultrasonic device 1 for use in the embodied method.

According to one embodiment, the ultrasonic imaging device 1 of Fig. 1 and the embodied ultrasonic device 2 of Fig. 2 for emission of the effective dose are combined to form a single embodied ultrasonic imaging and emission device.

Study of blood flow disruption for castration A study of a surgical intervention to ligate the blood vessels, supplying the left testicle while the right testicle was untouched to serve as a control has been performed.

In four pigs (weight 26,2-46,2 kg), the blood supply for the left testicle and the spermatic duct with adjacent blood supply was exposed during surgery, and the blood supply was occluded by ligation. In two pigs (no. 1 and 4), the ligation was performed with a suture tied tightly around the blood supply for the left testicle. In the other two pigs (no. 2 and 3), the ligation was performed on both the blood supply for the left testicle and the spermatic duct with adjacent blood supply. 10 days later, all four pigs were killed for an autopsy. All the piglets' surgically treated testicles showed, by transection, signs of necrosis of the testicle tissue, characterized by light, and yellowish tissue with increased structure. Also, the epididymis was bumpy and reduced in size - except for the tail of the epididymis (cauda epididymis) in those two pigs, where only the blood supply - and not the spermatic duct and the adjacent blood supply - was ligated. Supposedly, the blood supply for the spermatic duct is supplying a part of the epididymis as well. The epididymis has no hormone production. It is not expected, but cannot either be excluded, that the blood supply for the spermatic duct is able to develop into a new blood supply to the testicle.

Conclusion: Occlusion of the blood supply to the testicle will result in necrosis of the testicle. It is confirmed with this study that occlusion of the blood supply e.g. with an ultrasound driven method will result in castration caused by necrosis of the testicle tissue.

Claims

1. A method for non-invasive castration of a male or female animal, the method comprising selective interruption of the blood supply to the animal's gonadal tissue, wherein said selective interruption is sufficient to necrotize said gonadal tissue, and wherein the selective interruption is accomplished by delivering an effective dose of focused radiation or focused pressure waves to a selected region being the spermatic cords in the male animal, or being the suspensory ligament of the ovaries in the female animal.

2. The method according to claim 1, wherein the selected region is the testicular artery and other blood vessels of the spermatic chords in the male animal, or the ovarian artery and other blood vessels of the suspensory ligament of the ovaries in the female animal.

3. The method according to claim 1 or 2, wherein the selected region is the testicular artery in the spermatic chords in the male animal, or the ovarian artery in the suspensory ligament of the ovaries in the female animal.

4. The method according to any of the preceding claims, wherein at least the testicular artery in male animal ruptured or severed, or the ovarian artery in the female animal is ruptured or severed.

5. The method according to any of the preceding claims, wherein the focused radiation or pressure waves is/are applied by means of an emission device, which is preferably handheld, and which comprises at least one means for emission of radiation or pressure waves.

6. The method according to claim 5, wherein said emission device further comprises at least one means for detecting returned radiation or pressure waves.

7. The method according to claim 6, wherein said emission device further comprises data processing and storage means configured to compute the 3D location of the selected region, said 3D location being computed from data representing the radiation or pressure waves emitted by the emission device and data representing the returned radiation or pressure waves detected.

8. The method according to claim 6 or 7, wherein said emission device includes means for qualitative or quantitative determination of arterial blood flow in the selected region and/or includes means for imaging the selected region.

9. The method according to claim 7 or 8, wherein the emission device is configured to deliver the effective dose of focused radiation or pressure waves to a target position within the 3D location of the selected region.

10. The method according to any one of claims 5-9, wherein

11. The method according to any one of claims 5-10, wherein said emission device is configured to operate in the sequence of

2) a step of receiving return radiation or pressure waves,

3) a step of computing the 3D location of the selected region from data representing the emitted and received radiation or pressure waves, and

4) a step of emission of focussed radiation or pressure waves to the selected region, where the focus of said focussed radiation is controlled on the bases of the computed 3D location.

12. The method according to claim 11, wherein

13. The method according to any one of the preceding claims, wherein the effective dose is delivered in the form of ultrasound waves.

14. The method according to any one of claims 1-12, wherein the effective dose is delivered in the form of electromagnetic waves.

15. The method according to any one of the preceding claims, wherein the male or female animal is not sexually mature.

16. The method according to any one of the preceding claims, wherein the male or female animal is selected from the group of pigs, horses, cattle, sheep, goats, dogs, cats, mink, and foxes.

17. The method according to any one of the preceding claims, wherein the male or female animal is a livestock animal.

18. The method according to any one of the preceding claims, which is non-therapeutic and non-prophylactic.