WO2003015864A2

WO2003015864A2 - Apparatus and method for locating implanted

Info

Publication number: WO2003015864A2
Application number: PCT/US2002/026248
Authority: WO
Inventors: Stephen Mcaleavey
Original assignee: University Of Rochester
Priority date: 2001-08-20
Filing date: 2002-08-19
Publication date: 2003-02-27
Also published as: AU2002326683A1; WO2003015864A3; WO2003015864B1

Abstract

A brachytherapy seed (100) includes a magnetized or magnetizable material (106). To locate seeds (100) which have been implanted into an organ, the organ is exposed to an oscillating magnetic field, which causes them to vibrate. Doppler ultrasound is used to detect the vibrating seeds (100).

Description

APPARATUS AND TECHNIQUE FOR DETECTION OF BRACHYTHERAPY

SEEDS AND SEED FOR USE WITH THE TECHNIQUE Field of the Invention

The present invention is directed to brachytherapy and more particularly to an apparatus and technique for detection of brachytherapy seeds which have been inserted into a patient's organ. The present invention is further directed to brachytherapy seeds for use with the technique. Description of Related Art

Prostate cancer is the most frequently diagnosed malignancy in America and the most prevalent cancer in the world. Numerous treatments exist, including radical prostatectomy, external-beam radiation, cryoablation, and brachytherapy, among others. Brachytherapy is highly favored for early stage cancers, both for its high success rate and the low risk of complications associated with it.

Brachytherapy involves the implantation of radioactive sources or "seeds" to apply a lethal dose of radiation to surrounding tissues. A typical seed 100, illustrated in Fig. 1, includes a titanium capsule 102 which is 0.8 mm in diameter and 4.5 mm in length. The capsule 102 contains a radioactive element 104, most commonly iodine (1-125) or palladium (Pd-103), and a radio-opaque marker 106 of gold, silver or lead, for identification in CT and X-ray images. The radiation energy of the seed is calculated to penetrate tissue up to ~1.3cm from the seed. The relatively small volume irradiated requires that seeds be placed accurately to ensure a uniform radiation dose. Transrectal ultrasound is often used to guide the percutaneous placement of the seeds for that reason.

Computed tomography (CT) is used postoperatively to map the location of the implanted seeds so that the radiation field may by estimated and additional seeds

I implanted if necessary. It would be beneficial in terms of cost and time if that map could be produced by 3D ultrasound at the time of seed implantation. However, that is not easily done, since the seeds are often hard to visualize in the ultrasound image. Though they are hard metal targets, their orientation and shape can cause them to produce a weaker echo than might be expected. Furthermore, the presence of other highly echogenic targets (e.g. air introduced by the brachytherapy needle, blood-tissue interfaces created by bleeding) suggests that simply making the target brighter is not necessarily a solution to the problem.

Summary of the Invention

It will be apparent from the above that a need exists in the art to improve the detection of seeds. It is therefore a primary object of the invention to provide an apparatus and technique for detection of seeds. It is a further object of the invention to provide an easily detected seed.

To achieve the above and other objects, the present invention is directed to a technique by which modified brachytherapy seeds may be identified and distinguished from other bright scatterers, or even within highly echogenic tissue. Brachytherapy seeds which have been magnetized or made magnetizable may be vibrated within an elastic medium by the application of an oscillating external magnetic field. Doppler ultrasound may be used to detect the vibration of the brachytherapy seeds. Even vibrations of minute amplitude (a small fraction of the ultrasound wavelength) are readily detectable, and the unique characteristics of Doppler signals arising from vibrating targets allow them to be distinguished from flow signals. The unique Doppler signature associated with the modified brachytherapy seeds in the oscillating field allow them to be readily distinguished from other bright scatterers in the prostate. An unmodified clinical scanner with Power Doppler facilities can highlight the vibrating seeds in a B-mode image and clearly distinguish them from surrounding bright echoes. Brief Description of the Drawings

A preferred embodiment of the present invention will be set forth in detail with respect to the drawings, in which:

Fig. 1 shows a cut-away view of a brachytherapy seed which can be modified for use in the preferred embodiment;

Fig. 2 shows a plot of current and torque as functions of time in a case in which an oscillating magnetic field is applied to a magnetizable object;

Fig. 3 shows an example of a Doppler spectrograph display in the case of a vibrating target; Fig. 4 shows a block diagram of an apparatus for Doppler imaging of ferrous targets;

Fig. 5 shows an agar phantom used in the imaging of ferrous arid non-ferrous targets;

Figs. 6A and 6B show Power Doppler scans of the phantom of Fig. 5 in cases in which an oscillating magnetic field is not applied and is applied, respectively;

Fig. 7 shows PW Dopper spectra for the ferrous and non-ferrous targets in the phantom of Fig. 5;

Figs. 8A and 8B show images of a seed in a liver tissue phantom in cases in which an oscillating magnetic field is not applied and is applied, respectively; and Fig. 9 shows a block diagram of an apparatus like that of Fig. 4, except adapted for use on a patient's prostate. Detailed Description of the Preferred Embodiment

A preferred embodiment of the present invention will now be set forth in detail with reference to the drawings.

A brachytherapy seed loaded with either a ferrous or magnetic component may be made to vibrate in the prostate under the influence of an external magnetic field and detected with Doppler ultrasound. Referring back to Fig. 1, a modified

brachytherapy seed 100' may be produced by replacing the gold, silver or lead marker

106 with a magnetized or magnetizable marker 106' made .of iron, a rare-earth magnet, or other suitable magnetic component. No external modification to the seed 100' is required, alleviating possible concerns about biological compatibility.

It is known in the art to form seeds in which the marker is not a single object, but instead a series of silver spheres. Of course, such seeds could be modified by replacing the silver spheres with spheres of iron or another suitable material.

However, a single, elongated magnetic object is preferable.

Once implanted, the seeds 100' can be imaged by applying an oscillating magnetic field to them to vibrate them. The vibration may be identified with the

Power Doppler mode of an ultrasound scanner, which highlights in color all vibrating targets within the image. Bright scatterers without any ferromagnetic component, such as air bubbles and tissue interfaces, do not vibrate under the influence of the field and are not illuminated by the Power Doppler display. Judicious selection of coil current and wall-filter cutoff frequencies allows for the rejection of low velocity flow and other Doppler sources. Alternatively, the PW Doppler range gate may be placed over a suspect echo to determine its nature. With the oscillating magnetic field in place, bands appear in the Doppler spectral display over a seed echo, while no bands are seen over other echo sources. The effect of the oscillating magnetic field on seeds containing magnetized and magnetizable materials will now be explained. An elongated, magnetizable particle in a magnetic field experiences a torque which tends to align it with the field. A magnetizable particle is one which is acted upon by a magnetic field but carries no significant permanent magnetic field of its own. That is observed, for instance, when iron filings are scattered on a paper placed atop a magnet; the filings, as magnetizable particles, align themselves with the field. The alignment occurs even though the particles themselves are not magnetized, so long as each particle has a discernable "long axis" (anisotropy). Magnetized particles, those possessing a permanent field, will tend to align their fields with an external magnetic field, just as a compass needle aligns itself with the Earth's field. The preferred orientation of the externally applied magnetic field lines is perpendicular to the orientation of the seed field.

Now consider magnetizable particles, in the form of small cylinders, embedded in an elastic medium. The particles have fixed rest positions, from which an external force may displace them, and to which they will return with the removal of the force. A periodic force applied to the particles causes them to vibrate about their rest positions. That periodic force may be applied to the particles by an oscillating magnetic field, generated, for instance, by an alternating current in a coil of wire. The field strength is proportional to the current flowing in the coil, and the torque on the particle is proportional to the square of the applied field. Because of the square law dependence of torque on current, the vibration of the particle is twice the frequency of the coil current, as illustrated in Fig. 2. The particle receives a torque in the same direction for each half cycle of the current. The preferred orientation of the externally applied magnetic field lines is 45 degrees to the magnetic long axis of the seed. A permanently magnetized particle responds . somewhat differently to an external field. Torques are applied with each half cycle of current. The direction of the torque, however, depends upon the direction of the current; reversing the flow of current reverses the torque. Here the torque is proportional to the applied field, and the vibration frequency is equal to the current frequency. That behavior is a consequence of the permanent magnetic field, which acts to match its poles with opposite poles of the external field. In contrast to the magnetizable particle case, the polarity of the external field determines in the direction of the torque.

Doppler ultrasound is routinely used to detect and quantify the motion of blood and other tissues in body; the art and technology of Doppler ultrasound are highly developed. Doppler systems are designed to measure motion of targets whose velocity is relatively constant on short time scales, on the order of hundreds of milliseconds. Most tissue motions, including the flow of blood under all but very turbulent conditions, fall into that category. Doppler echo data may be displayed either as a spectrograph, as in PW Doppler, or a color map over a grayscale image, as in Color Flow or Power Doppler.

Vibrating objects are not ordinarily the targets of Doppler scans, but even very slight vibrations are easily detectible with Doppler equipment. Vibrations with a frequency of more than a few Hertz produce Doppler signals with unique characteristics. That is most clearly seen in the Doppler spectrograph display, where vibrating targets result in bands in the spectrograph display at integer multiples of the vibration frequency. An example of a Doppler spectrograph display is shown in Fig. 3. Vibration amplitudes of even a fraction of the incident ultrasound wavelength produce bands in the PW Doppler display at the vibration frequency and its negative. Increased vibration amplitude shifts the bands to higher multiples of the vibration frequency.

The vibration-induced Doppler signals have features which readily distinguish them from flow-induced signals. Their spectral content is symmetric about zero frequency. The energy is confined to multiples of the vibration frequency, revealed as bands in a spectral Doppler display. Power Doppler produces color in areas of vibration, while Color Flow Doppler produces an incoherent color hash.

Apparatus for an in-vitro proof-of-concept study has been constructed and is illustrated in Fig. 4. The apparatus 400 includes a coil 402 having 150 turns of 22- gauge magnet wire 404 on a 10-cm diameter Lexan shell 406. The shell 406 could be replaced with a ferrous core. The coil 402 has a measured resistance of 3 ohms and an inductance of 3.3 millihenrys. The coil 402 is driven at 60Hz supplied by a variable transformer (variac) 408, which provides control over the current supplied to the coil 402. Phantoms placed within the coil 402 are coupled to the ultrasound transducer 410 by a water path. Scanning is performed with a GE Logiq 700MR ultrasound system. A 7MHz linear array transducer (L739) is used.

For use on a patient, an apparatus essentially like that of Fig. 4 could be used.

Only minor modifications would be required, such as proportioning and shaping the coil to apply the oscillating magnetic field to the organ to be imaged. One such apparatus is shown in Fig. 9. The orientation shown in Fig. 9 is correct for permanently magnetized seeds. Magnetizable (e.g., iron) seeds would require that the coils be tipped 45 degrees to the right in Fig. 9 for best performance.

As shown in Fig. 9, the apparatus 900 includes coils 902 and an ultrasound transducer 910. The coils 902, under control of a power source such as the trasnfoπner 408 of Fig. 4, produce field lines B in and around the patient^'s prostate-R. While the coils 902 are shown as air coils, an armature of highly magnetically permeable material could be used in shaping and strengthening the field. The tradeoff would be added weight and bulk.

Two phantoms were used in the experiments. An agar phantom was used to demonstrate the ability to discern ferrous from non-ferrous targets which are otherwise identical in appearance under ultrasound. Two populations of "seeds" were used, steel wire and copper wire, to provide the ferrous and non-ferrous targets. A bovine liver tissue phantom was used to provide a more echogenic and realistic tissue sample. Copper and steel seeds were again used. The agar phantom was formed according to the following procedure. A 3% by weight agar solution was mixed and heated in an autoclave for 1 hour to melt and degas the solution. A 1.5 cm layer was poured into an 8cm diameter mold and allowed to solidify. Copper (0.7mm diameter) and steel (0.5mm diameter) wire cut into 4.5 mm long sections was distributed on the surface of the solidified agar to simulate brachytherapy seeds, all oriented in the same direction. An additional centimeter of molten agar was poured atop the seeds and allowed to cool.

The phantom and the experimental setup used on it are shown in Fig. 5. The phantom 500 includes agar 502 in which the steel seeds 504 and the copper seeds 506 are suspended, as well as water for acoustic coupling with the ultrasonic transducer 410, whose scan plane is shown as SP.

A sample of fresh bovine liver tissue from a local butcher was used for a second phantom. Steel wire seeds were embedded in the liver at an angle of approximately 45 degrees to the plane of the excitation coil. The seeds were placed under ultrasound guidance using an 18-gauge hypodermic needle and stylus. The phantom was kept refrigerated but otherwise unpreserved. The agar phantom was centered in the coil (not shown in Fig. 5, but the same as that shown in Fig. 4) with the seed plane in the plane of the coil. A 2 cm water path coupled the ultrasound transducer to the phantom. The linear transducer was held in place above the phantom with a ring stand and clamp. Figs. 6A and 6B show a typical Power Doppler scan. The echo on the left is that of a steel wire, that on the right of a copper wire. With the coil off, as shown in Fig. 6A, the two are indistinguishable bright scatterers. With a current of -15 amps at 60Hz flowing in the coil, as shown in Fig. 6B, Power Doppler highlights the steel wire, while the copper wire echo is unchanged. Fig. 7 presents PW Doppler spectra for the same targets shown in Figs. 6A and

6B. A current of ~8 amps at 60Hz was pulsed through the coil approximately once every other second. With the range gate centered over the steel se d, the appearance

of ±120 Hz bands in the spectral display is noted when the current is switched on. With the range gate over the copper wire, no such bands are seen. The absence of bands in the spectral display at greater than unity multiples of the 120Hz fundamental

frequency means the amplitude of vibration is less than λ/10, or 5 microns at 7.5MHz,

where λ is the ultrasound frequency.

The detection by Doppler of vibration of the steel seed with alternating current applied to the coil and the absence of detectable vibration in the copper seed elucidates two important points. First, the vibration detected is not a microphonic effect. That is, vibrations from the coil are not coupling into phantom to a significant degree. Were that the case, one would expect to see vibration in both the copper and the steel seeds with the coil activated. Second, those images demonstrate that otherwise bright scatterers are distinguishable based on their magnetic properties. Images of the liver tissue sample with a seed in frame under Power Doppler are shown in Figs. 8A and 8B. With the coil off, as shown in Fig. 8A, it is difficult to distinguish the seed from the other echogenic targets in the liver, trapped air and connective tissue. With the coil switched on, as shown in Fig. 8B, a strong Doppler signal is detected and displayed about the seed. A secondary Doppler echo also appears behind the seed due to reverberation effects.

Of immediate concern when embedding magnetic materials in the body is whether or not the patient is rendered ineligible for magnetic resonance imaging. The growing role of MRI in many types of diagnosis makes that an important question indeed. Several authors have investigated the potential hazards and artifacts associated with MR imaging of embedded ferromagnetic materials. It appears that some discretion is involved in terms of the location magnetic material and the strength of displacement forces acting upon it. One such author has concluded that "MR imaging may be performed safely in patients with metallic implants, materials, or devices if the object is non-ferromagnetic or is only minimally attracted by the static magnetic field in relation to its in vivo application (i.e., the associated deflection force or attraction is insufficient to move or dislodge the implant or material in situ)." Thus, as a practical matter certain configurations, such as "open magnet" imaging of the shoulder or brain, may be possible in patients with implanted ferromagnetic brachytherapy seeds.

The effect of a strong alternating magnetic field on an ultrasound transducer and scanner is a concern. The potential exists to induce large currents in sensitive amplifiers of the scanner and cause damage. The tolerance of the scanner and transducer to large alternating fields must be established and could pose an upper bound on the strength of the field used to vibrate the seeds. π A technique for the ready identification of brachytherapy seeds under ultrasound has been presented. Doppler ultrasound is used to detect the vibration of modified seeds in an oscillating magnetic field. In vitro experiments with agar and liver-tissue phantoms using a clinical scanner and simple apparatus demonstrate that the technique is feasible. MRI compatibility has been identified as an important issue for any permanent-implant application.

While a preferred embodiment of the present invention has been set forth in detail above, those skilled in the art who have reviewed the present disclosure will readily appreciate that other embodiments can be realized within the scope of the present invention. For example, brachytherapy seed detection is not the only potential application of the present invention. Catheter tips and needles could be made ferrous and vibrated with an external field to make them more visible under ultrasound. Turning the MRI compatibility issue on its head, ultrasound-detected vibration of ferromagnetic structures could be used to determine if a patient may safely undergo MRI scans. The very low amplitude of vibration which may be detected means it is possible to detect movement of implants before damage is done to the surrounding tissue. Therefore, the present invention should be construed as limited only by the appended claims.

Claims

I claim:

1. A method for visualizing treatment of an organ, the method comprising:

(a) inserting a therapeutic object into the organ, the therapeutic object comprising a portion made of a magnetized or magnetizable substance; (b) vibrating the therapeutic object by applying a time-dependent magnetic field to the therapeutic object; and

(c) imaging the therapeutic object while the therapeutic object is being vibrated in step (b).

2. The method of claim 1, wherein the therapeutic object comprises a radioactive seed for brachytherapy.

3. The method of claim 2, wherein the organ is a prostate.

4. The method of claim 1, wherein step (c) is performed wilh ultrasound.

5. The method of claim 4, wherein the ultrasound comprises Doppler ultrasound.

6. The method of claim 1, wherein the time-dependent magnetic field is periodic.

7. The method of claim 6, wherein the time-dependent magnetic field is sinusoidal.

8. A seed for brachytherapy, the seed comprising: a capsule; a radioactive material in the capsule; and a magnetized or magnetizable material in the capsule.

9. The seed of claim 8, wherein the magnetized or magnetizable material comprises iron.

10. The seed of claim 8, wherein the magnetized or magnetizable material comprises a rare-earth magnet.

11. The seed of claim 8, wherein the radioactive material comprises iodine 125.

12. The seed of claim 8, wherein the radioactive material comprises palladium

103.

13. The seed of claim 8, wherein the capsule comprises titanium.

14. An apparatus for detecting a magnetized or magnetizable material in an organ, the apparatus comprising: at least one magnetic coil; a magnetic coil controller for controlling said at least one magnetic coil to apphj a time-dependent magnetic field to the organ to vibrate the magnetized or magnetizable material; and an imaging device for imaging the organ while the time-dependent magnetic field is vibrating the magnetized or magetizable material.

15. The apparatus of claim 14, wherein the imaging device comprises an ultrasound device.

16. The apparatus of claim 15, wherein the ultrasound device comprises a Doppler ultrasound device.

17. The apparatus of claim 14, wherein the magnetic coil controller controls said at least one magnetic coil such that the time-dependent magnetic field is periodic.

18. The apparatus of claim 17, wherein the magnetic coil controller controls said at least one magnetic coil such that the time-dependent magnetic field is sinusoidal.

19. A method for performing brachytherapy on an organ, the method comprising: providing a seed which comprises a capsule, a radioactive material in the capsule, and a magnetized or magnetizable material in the capsule; and inserting the seed into the organ.

20. The method of claim 19, wherein the organ is a prostate.

21. The method of claim 19, wherein the magnetized or magnetizable material comprises iron.

22. The method of claim 19, wherein the magnetized or magnetizable material comprises a rare-earth magnet.

23. The method of claim 19, wherein the radioactive material comprises iodine 125.

24. The method of claim 19, wherein the radioactive material comprises palladium 103.

25. The method of claim 19, wherein the capsule comprises titanium.

26. A method for detecting a magnetized or magnetizable material in an organ, the method comprising:

(a) vibrating the magnetized or magnetizable material by applying a time- dependent magnetic field to the organ; and (b) imaging the organ while the magnetized or magnetizable material is being vibrated in step (b).

27. The method of claim 26, wherein step (b) is performed with ultrasound.

28. The method of claim 27, wherein the ultrasound comprises Doppler ultrasound.

29. The method of claim 26, wherein the time-dependent magnetic field is

periodic.

30. The method of claim 29, wherein the time-dependent magnetic field is

sinusoidal.