U.S. patent application number 10/702942 was filed with the patent office on 2004-05-20 for products and methods for brachytherapy.
Invention is credited to Bacon, Edward, Black, Christopher, Cooney, Geraldine, Cornacoff, Joel, Eriksen, Morten, Gates, Virginia Ann, Mclntire, Gregory, Snow, Robert, Tornes, Auden.
Application Number | 20040097779 10/702942 |
Document ID | / |
Family ID | 30773278 |
Filed Date | 2004-05-20 |
United States Patent
Application |
20040097779 |
Kind Code |
A1 |
Mclntire, Gregory ; et
al. |
May 20, 2004 |
Products and methods for brachytherapy
Abstract
Radioactive sources, preferably radioactive seeds, for use in
brachytherapy comprising a radioisotope within a sealed
biocompatible container, wherein at least one part of a surface of
the container is roughened, shaped or otherwise treated so that it
is no longer smooth. The surface treatment may enhance the
ultrasound visibility of the source and/or reduce the tendency of
the source to migrate once implanted in a patient's body. Preferred
radioisotopes are palladium-103 and iodine-125.
Inventors: |
Mclntire, Gregory; (West
Chester, PA) ; Snow, Robert; (West Chester, PA)
; Bacon, Edward; (Audubon, PA) ; Eriksen,
Morten; (Oslo, NO) ; Tornes, Auden; (Oslo,
NO) ; Cooney, Geraldine; (Gilbertsville, PA) ;
Gates, Virginia Ann; (Collegeville, PA) ; Cornacoff,
Joel; (Audubon, PA) ; Black, Christopher;
(Rockville, MD) |
Correspondence
Address: |
AMERSHAM HEALTH
IP DEPARTMENT
101 CARNEGIE CENTER
PRINCETON
NJ
08540-6231
US
|
Family ID: |
30773278 |
Appl. No.: |
10/702942 |
Filed: |
November 6, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10702942 |
Nov 6, 2003 |
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09831229 |
Jul 23, 2001 |
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6689043 |
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09831229 |
Jul 23, 2001 |
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PCT/GB99/03668 |
Nov 5, 1999 |
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60107406 |
Nov 6, 1998 |
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Current U.S.
Class: |
600/1 ;
600/3 |
Current CPC
Class: |
G21G 4/08 20130101; A61N
2005/1024 20130101; A61B 2090/3925 20160201; A61N 5/1027
20130101 |
Class at
Publication: |
600/001 ;
600/003 |
International
Class: |
A61N 005/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 27, 1998 |
GB |
9826121.7 |
Claims
1. A radioactive source for use in brachytherapy comprising a
radioisotope within a sealed biocompatible container, wherein at
least one part of a surface of the container is roughened, shaped
or otherwise treated so that it is no longer smooth.
2. A radioactive source as claimed in claim 1 wherein the
roughened, shaped or otherwise treated surface is the outer surface
of the container.
3. A radioactive source as claimed in claim 1 or claim 2 where the
roughened, shaped or otherwise treated surface is effective to
enhance ultrasound visibility.
4. A radioactive source as claimed in any of claims 1 to 3 wherein
the container comprises gold, titanium, platinum or stainless
steel.
5. A radioactive source as claimed in any of claims 1 to 4 wherein
the roughened, shaped or otherwise treated surface comprises
grooves, scratches, abrasions or depressions.
6. A radioactive source as claimed in claim 5 wherein the grooves,
scratches, abrasions or depressions are arranged randomly on the
surface.
7. A radioactive source as claimed in claim 5 wherein the grooves,
scratches, abrasions or depressions are arranged in a regular
pattern.
8. A radioactive source as claimed in any of claims 1 to 7 wherein
the roughened, shaped or otherwise treated surface comprises
ridges, bumps, undulations or serrations upstanding from the
surface.
9. A radioactive source as claimed in any of claims 1 to 8 wherein
the radioisotope is palladium-103 or iodine-125.
10. A method for the preparation of a radioactive source as claimed
in any of claims 1 to 9 which comprises roughening, shaping or
otherwise treating an exterior surface or part of an exterior
surface of the biocompatible container to thereby provide
irregularities or discontinuities of dimensions in the exterior
surface.
11. A method for the preparation of a radioactive source as claimed
in any of claims 1 to 9 which comprises: (i) roughening, shaping or
otherwise treating a surface or part of a surface of a
biocompatible container material to provide irregularities or
discontinuities of dimensions; (ii) loading a radioisotope into the
biocompatible container material of step (i); and (iii) sealing the
biocompatible container.
12. A method as claimed in claim 10 or claim 11 where the surface
roughening or shaping is achieved by forcing through a ridged or
serrated die, or a threading device, milling, roughening by
mechanical friction, etching, crimping, or wet or dry blasting.
13. A method as claimed in claim 10 or claim 11 where the surface
roughening or shaping involves selective dissolution of one
component of a composite biocompatible material.
14. A method as claimed in claim 13 wherein the composite material
is a ceramic composite, a polymer blend, or a polymeric or ceramic
material with soluble materials entrained therein.
15. A method as claimed in any of claims 11 to 14 where the surface
roughening or shaping is applied to the exterior surface of the
biocompatible container material.
16. A method of treatment of a condition which is responsive to
radiation therapy, which comprises the temporary or permanent
placement of a radioactive source comprising a radioisotope within
a sealed biocompatible container, wherein at least one part of a
surface of the container is roughened, shaped or otherwise treated
to thereby provide irregularities or discontinuities of dimensions,
at the site to be treated within a patient for a sufficient period
of time to deliver a therapeutically effective dose.
17. A method of treatment as claimed in claim 16 wherein the
condition to be treated is cancer, arthritis or restenosis.
18. A method of treatment as claimed in claim 16 or claim 19
wherein the condition is prostate cancer.
19. A method of treatment as claimed in any of claims 16 to 18
whereby the irregularities or discontinuities enhance the
ultrasound visibility of the source.
20. A composition which comprises a multiplicity of radioactive
sources as claimed in any of claims 1 to 9 within a substantially
linear, biodegradable material.
21. A composition as claimed in claim 20 where the biodegradable
material is semi-rigid.
Description
[0001] This invention relates to radiotherapy. More particularly,
it relates to radioactive sources for use in brachytherapy, and in
particular to radioactive sources with improved ultrasound imaging
visibility.
[0002] Brachytherapy is a general term covering medical treatment
which involves placement of a radioactive source near a diseased
tissue and may involve the temporary or permanent implantation or
insertion of a radioactive source into the body of a patient. The
radioactive source is thereby located in proximity to the area of
the body which is being treated. This has the advantage that a high
dose of radiation may be delivered to the treatment site with
relatively low dosages of radiation to surrounding or intervening
healthy tissue.
[0003] Brachytherapy has been proposed for use in the treatment of
a variety of conditions, including arthritis and cancer, for
example breast, brain, liver and ovarian cancer and especially
prostate cancer in men (see for example J. C. Blasko et al., The
Urological Clinics of North America, 23, 633-650 (1996), and H.
Ragde et al., Cancer, 80, 442-453 (1997)). Prostate cancer is the
most common form of malignancy in men in the USA, with more than
44,000 deaths in 1995 alone. Treatment may involve the temporary
implantation of a radioactive source for a calculated period,
followed by its subsequent removal. Alternatively, the radioactive
source may be permanently implanted in the patient and left to
decay to an inert state over a predictable time. The use of
temporary or permanent implantation depends on the isotope selected
and the duration and intensity of treatment required.
[0004] Permanent implants for prostate treatment comprise
radioisotopes with relatively short half lives and lower energies
relative to temporary sources. Examples of permanently implantable
sources include iodine-125 or palladium-103 as the radioisotope.
The radioisotope is generally encapsulated in a titanium casing to
form a "seed" which is then implanted. Temporary implants for the
treatment of prostate cancer may involve iridium-192 as the
radioisotope.
[0005] Recently, brachytherapy has also been proposed for the
treatment of restenosis (for reviews see R. Waksman, Vascular
Radiotherapy Monitor, 1998, 1, 10-18, and MedPro Month, January
1998, pages 26-32). Restenosis is a renarrowing of the blood
vessels after initial treatment of coronary artery disease.
[0006] Coronary artery disease is a condition resulting from the
narrowing or blockage of the coronary arteries, known as stenosis,
which can be due to many factors including the formation of
atherosclerotic plaques within the arteries. Such blockages or
narrowing may be treated by mechanical removal of the plaque or by
insertion of stents to hold the artery open. One of the most common
forms of treatment is percutaneous transluminal coronary
angioplasty (PTCA)--also known as balloon angioplasty. At present,
over half a million PTCA procedures are performed annually in the
USA alone. In PTCA, a catheter having an inflatable balloon at its
distal end is inserted into the coronary artery and positioned at
the site of the blockage or narrowing. The balloon is then inflated
which leads to flattening of the plaque against the artery wall and
stretching of the artery wall, resulting in enlargement of the
intraluminal passage way and hence increased blood flow.
[0007] PTCA has a high initial success rate but 30-50% of patients
present themselves with stenotic recurrence of the disease, i.e.
restenosis, within 6 months. One treatment for restenosis which has
been proposed is the use of intraluminal radiation therapy. Various
isotopes including iridium-192, strontium-90, yttrium-90,
phosphorous-32, rhenium-186 and rhenium-188 have been proposed for
use in treating restenosis.
[0008] Conventional radioactive sources for use in brachytherapy
include so-called seeds, which are smooth sealed containers or
capsules of a biocompatible material, for example of metals such as
titanium or stainless steel, containing a radioisotope within a
sealed chamber but permitting radiation to exit through the
container/chamber walls (U.S. Pat. No. 4,323,055 and U.S. Pat. No.
3,351,049). Such seeds are only suitable for use with radioisotopes
which emit radiation which can penetrate the chamber/container
walls. Therefore, such seeds are generally used with radioisotopes
which emit .gamma.-radiation or low-energy X-rays, rather than with
.beta.-emitting radioisotopes.
[0009] In brachytherapy, it is vital to the therapeutic outcome for
the medical personnel administering the treatment to know the
relative position of the radioactive source in relation to the
tissue to be treated, to ensure that the radiation is delivered to
the correct tissue and that no localized over or under dosing
occurs. Current seeds therefore typically incorporate a marker for
X-ray imaging such as a radiopaque metal (e.g. silver, gold or
lead). Location of the implanted seed is then achieved via X-ray
imaging, which exposes the patient to an additional radiation dose.
Such radiopaque markers are typically shaped so that imaging gives
information on the orientation as well as location of the seed in
the body, since both are necessary for accurate radiation dosimetry
calculations.
[0010] Permanent implantation of brachytherapy radioactive sources
for the treatment of, for example, prostate cancer may be done
using an open laparotomy technique with direct visual observation
of the radioactive sources and the tissue. However, the procedure
is relatively invasive and often leads to undesirable side effects
in the patient. An improved procedure comprising the insertion of
radioactive sources transperineally into predetermined regions of
the diseased prostate gland using an external template route to
establish a reference point for implantation has been proposed (see
for example Grimm, P. D., et al., Atlas of the Urological Clinics
of North America, Vol. 2, No. 2, 113-125 (1994)). Commonly, these
radioactive sources, for example seeds, are inserted by means of a
needle device while an external depth gauge is employed with the
patient in the dorsal lithotomy position. For prostate cancer
treatment, typically 50 to 120 seeds are administered per patient
in a 3-dimensional array derived from multiple needle insertions of
linear, spaced seeds. The dose calculation is based on this complex
3-D array, plus data on the tumour volume plus prostate volume
etc.
[0011] Preferably, the insertion or implantation of a radioactive
source for brachytherapy is carried out using minimally-invasive
techniques such as, for example, techniques involving needles
and/or catheters. It is possible to calculate a location for each
radioactive source which will give the desired radiation dose
profile. This can be done using knowledge of the radioisotope
content of each source, the dimensions of the source, an accurate
knowledge of the dimensions of the tissue or tissues in relation to
which the source is to be placed, plus a knowledge of the position
of said tissue relative to a reference point. The dimensions of
tissues and organs within the body for use in such dosage
calculations may be obtained prior to placement of the radioactive
source by using conventional diagnostic imaging techniques
including X-ray imaging, magnetic resonance imaging (MRI) and
ultrasound imaging. However, difficulties may arise during the
radioactive source placement procedure which may adversely affect
the accuracy of the placement of the source if only pre-placement
images are used to guide the source placement. For example, tissue
volume may change as a result of swelling or draining of fluid to
and from the tissue. Tissue position and orientation can change in
the patient's body relative to a selected internal or external
reference point as a result of for example manipulation during
surgical procedures, movement of the patient or changes in the
volume of adjacent tissue. Thus, it is difficult to achieve
accurate placement of sources to achieve a desired dosage profile
in brachytherapy using only knowledge of tissue anatomy and
position that was obtained prior to the placement procedure.
Therefore, it is advantageous if real-time visualisation of both
the tissue and the radioactive source can be provided. A
particularly preferred imaging method due to its safety, ease of
use and low cost, is ultrasound imaging.
[0012] During the placement of the radioactive sources into
position, a surgeon can monitor the position of tissues such as the
prostate gland using, for example, transrectal ultrasound
pulse-echo imaging techniques which offer the advantage of low risk
and convenience to both patient and surgeon. The surgeon can also
monitor the position of the relatively large needle used in
implantation procedures using ultrasound. During the implantation
or insertion procedure, the location of the source may be inferred
to be proximal to the tip of the needle or other device used for
the procedure. However, the relative location of each separate
radioactive source should be evaluated subsequent to the
implantation procedure to determine if it is in a desired or
undesired location and to assess the uniformity of the therapeutic
dose of radiation to the tissue. Radioactive sources may migrate
within the tissue following implantation. However, the relatively
small size of current brachytherapy radioactive sources and the
specular reflection properties of their surfaces makes them very
difficult to detect by ultrasound imaging techniques, especially
when they are orientated in directions other than substantially
orthogonal to the incident ultrasound beam. Even very small
deviations from 90.degree. relative to the incident ultrasound beam
cause substantial reductions in the intensity of the echo
signal.
[0013] The ultrasound visibility of conventional radioactive seeds
is highly dependent upon the angular orientation of the seed axis
with respect to the ultrasound inducer used for imaging. A smooth
flat surface will generally act as a mirror, reflecting ultrasound
waves in the wrong direction unless the angle between the sound and
the surface is 90.degree.. A smooth cylindrical structure such as a
conventional radioactive seed will reflect waves in a fan shaped
conical pattern spanning a considerable spatial angle but will only
give strong ultrasound reflections when imaged at an angle very
close to 90.degree.. One way of improving the ultrasound visibility
of conventional radioactive seeds is therefore to reduce the
angular dependence of the reflected ultrasound.
[0014] There is therefore a need for radioactive sources for use in
brachytherapy with improved ultrasound imaging visibility, and in
particular for sources where the dependence of visibility on the
angular orientation of the axis of the source with respect to the
ultrasound transducer is reduced.
[0015] Ultrasound reflections may be either specular (mirror-like)
or scattered (diffuse). Biological tissue typically reflects
ultrasound in a scattered manner, whilst metallic devices tend to
be effective reflectors of ultrasound. Relatively large smooth
surfaces such as those of needles used in medical procedures
reflect sound waves in a specular manner.
[0016] Efforts have been made to enhance the ultrasound visibility
of relatively large surgical apparatus, such as surgical needles,
solid stylets and cannulae by suitable treatment of their surfaces
such as roughening, scoring or etching. Thus, U.S. Pat. No.
4,401,124 discloses a surgical instrument (a hollow needle device)
that has a diffraction grating inscribed on the surface to enhance
the reflection coefficient of the surface. Sound waves that strike
the grooves are diffracted or scattered as secondary wave fronts in
many directions, and a percentage of those waves are detected by
the ultrasound transducer. The diffraction grating is provided for
use at the leading edge of a surgical instrument for insertion
within a body or for use along a surface of an object the position
of which is to be monitored while in the body.
[0017] U.S. Pat. No. 4,869,259 discloses a medical needle device
that has a portion of its surface particle-blasted to produce a
uniformly roughened surface that scatters incident ultrasound such
that a portion of the scattered waves is detected by an ultrasound
transducer.
[0018] U.S. Pat. No. 5,081,997 discloses surgical instruments with
sound reflective particles imbedded in a portion of the surface.
The particles scatter incident sound, and a portion is detected by
an ultrasound transducer.
[0019] U.S. Pat. No. 4,977,897 discloses a tubular cannula device
comprising a needle and an inner stylet in which one or more holes
are cross-drilled perpendicular to the axis of the needle to
improve ultrasound visibility. The solid inner stylet may be
roughened or scored to enhance the sonographic visibility of the
needle/stylet combination.
[0020] WO 98/27888 describes a echogenically enhanced medical
device in which a print pattern mask of non-conductive
epoxy-containing ink is transfer-coated to the surface of the
device, flash dried, and then thermally crosslinked. Portions of
the needle not protected by the mask are removed by etching in an
electropolishing step to leave a pattern of substantially square
depressions in the bare metal, and the ink masked is removed with a
solvent and mechanical scrubbing. The depressions provide the
device with enhanced echogenicity under ultrasound.
[0021] U.S. Pat. No. 4,805,628 discloses a device which is inserted
or implanted for long-term residence in the body, which device is
made more visible to ultrasound by providing a space in the device
which has a substantially gas impermeable wall, such space being
filled with a gas or mixture of gases. The invention is directed to
IUD's (intrauterine devices), prosthetic devices, pacemakers, and
the like.
[0022] McGahan, J. P., in "Laboratory assessment of ultrasonic
needle and catheter visualization." JOURNAL OF ULTRASOUND IN
MEDICINE, 5(7), 373-7, (July 1986) evaluated seven different
catheter materials for their sonographic visualisation in vitro.
While five of the seven catheter materials had good to excellent
sonographic detection, nylon and polyethylene catheters were poorly
visualised. Additionally, various methods of improved needle
visualisation were tested. Sonographic needle visualisation was
aided by a variety of methods including either roughening or
scoring the outer needle or inner stylet and placement of a guide
wire through the needle.
[0023] However, none of the above-mentioned prior art discloses or
suggests methods for improving the ultrasound visibility of
radioactive sources for use in brachytherapy, including the
relatively much smaller radioactive sources or seeds for use in
permanent implants, nor the need to provide improved ultrasound
visibility of such sources. Indeed, there is a bias in the
brachytherpay field against changing the seed capsule design, since
it has been essentially unchanged and has continued to be
commercially successful for over 20 years, together with the fact
that any such change may have Regulatory or nuclear safety
implications, and would hence typically be avoided. In addition,
any such change could be viewed as increasing the liklihood of
problems with the seeds `sticking` in needles etc., i.e. it is
viewed as highly desirable that the seeds move smoothly within
needles, cannulae etc. "Sticking" of seeds within loading devices
is a known problem for clinicians and can present a safety risk.
Thus, if undue pressure is applied to move a stuck seed, it is
known that the seed capsule may rupture with consequent radioactive
release, contamination etc. Hence, there is a bias in the art
towards making seeds smoother (or at least having less friction)
rather than seemingly the other way round.
[0024] Once implanted, seeds are intended to remain permanently at
the site of implantation. However, individual seeds may on rare
occasions migrate within a patient's body away from the initial
site of implantation or insertion. This is highly undesirable from
a clinical perspective, for example as it may lead to underdosing
of a tumour or other diseased tissue and/or exposure of healthy
tissue to radiation. There is therefore also a need for radioactive
sources for use in brachytherapy which show a reduced tendency to
migrate within a patient's body when compared to conventional
brachytherapy seeds.
[0025] According to one aspect of the present invention there is
therefore provided a radioactive source for use in brachytherapy
comprising a radioisotope within a sealed biocompatible container,
wherein at least one part of a surface of the container is
roughened, shaped or otherwise treated such that it is no longer
smooth. The surface treatment may enhance the ultrasound visibility
of the source and/or reduce the tendency of the source to migrate
once implanted in a patient's body.
[0026] Suitable radioisotopes for use in the radioactive
brachytherapy sources of the invention are known in the art.
Particularly preferred radioisotopes include palladium-103 and
iodine-125.
[0027] Suitable carriers for the radioisotope within the
biocompatible container may comprise materials such as plastics,
graphite, zeolites, ceramics, glasses, metals, polymer matrices,
ion-exchange resins or other, preferably porous materials.
Alternatively, the carrier may be made of metal, e.g. silver or may
comprise a layer of metal plated onto a suitable substrate.
Suitable substrate materials include a second metal such as gold,
copper or iron, or solid plastics such as polypropylene,
polystyrene, polyurethane, polyvinylalcohol, polycarbonate,
TeflonT.TM., nylon, delrin and Kevlar.TM.. Suitable plating methods
are known in the art and include chemical deposition, sputtering,
ion plating techniques, electrodeless plating and
electrodeposition.
[0028] The carrier material may be in the form of a bead, wire,
filament or rod. Such carrier materials may be encapsulated in a
hollow sealed container, for example a metal container, to provide
a sealed source or "seed", or the carrier may be coated with an
electroplated shell, for example a layer of a metal such as silver
or nickel. The radioisotope may be physically trapped in or on the
carrier, for example by adsorption, or may be chemically attached
to it in some way. Alternatively, the source may comprise a hollow
sealed container directly encapsulating the radioisotope without
the need for a carrier.
[0029] Suitable biocompatible container materials include metals or
metal alloys such as titanium, gold, platinum and stainless steel;
plastics such as polyesters and vinyl polymers, and polymers of
polyurethane, polyethylene and poly(vinyl acetate), the plastics
being coated with a layer of a biocompatible metal; composites such
as composites of graphite, and glass such as matrices comprising
silicon oxide. The container may also be plated on the outside with
a biocompatible metal, for example gold or platinum. Titanium and
stainless steel are preferred metals for such containers,
especially titanium.
[0030] The radioisotope may also be incorporated into a polymer
matrix, or a plastic or ceramic composite, and/or may form part of
a container wall. For example, if a metal alloy is used to form a
container, then a component of the alloy may be a suitable
radioisotope. If a container is made from a composite material, a
component of the composite may be a suitable radioisotope.
[0031] The source should be of an overall size and dimensions
suitable for its intended use. For example, the overall dimensions
are preferably such that the source can be delivered to the
treatment site using conventional techniques, for example using a
hollow needle or a catheter. Seeds for use in the treatment of
prostate cancer are, for example, typically substantially
cylindrical in shape and approximately 4.5 mm long with a diameter
of approximately 0.8 mm, such that they may be delivered to the
treatment site using a hypodermic needle. For use in the treatment
of restenosis, a source should be of suitable dimensions to be
inserted inside a coronary artery, for example with a length of
about 10 mm and a diameter of about 1 mm, preferably a length of
about 5 mm and a diameter of about 0.8 mm, and most preferably with
a length of about 3 mm and a diameter of about 0.6 mm. Sources for
use in the treatment of restenosis are typically delivered to the
treatment site using conventional catheter methodology. The sources
of the invention may also be substantially spherical in shape.
[0032] The sources of the invention may be used as permanent
implants or for temporary insertion into a patient. The choice of
radioisotope and type of source, plus the method of treatment used,
depends in part on the condition to be treated.
[0033] As used herein, the term "roughened, shaped or otherwise
treated" means a surface or part surface which is not smooth and
polished as in regular or conventional brachytherapy sources but
which comprises irregularities or discontinuities of some kind. The
irregularities or discontinuities may be arranged in a regular
pattern or may be random, or there may be present a mixture of
random and regular regions. The irregularities or discontinuities
may take the form of grooves, scratches, abrasions, depressions or
the like incised, pressed, stamped, etched or otherwise scored into
a surface. The irregularities or discontinuities may also take the
form of ridges, bumps, undulations or the like upstanding from a
surface.
[0034] If a source with improved ultrasound visibility is required,
the roughening, shaping or other treatment should be over a
sufficient portion of the surface of the container that the
scattering of ultrasound by the source is substantially
omnidirectional. The roughening, shaping or other treatment may
occur over substantially the entire surface of the container, at
one or both ends, in the centre or over any other portion of the
surface. Preferably, the roughening, shaping or other treatment is
such that the source will be visible to ultrasound in substantially
all orientations relative to the incident beam.
[0035] For improved ultrasound visibility, the size of the
irregularities or discontinuities on the surface of the containers
(such as rods, spheroids, canisters, seeds and the like) should be
such that the ultrasound imaging visibility of the sources is
improved over that of a similar source with a smooth surface.
Preferably, each individual irregularity reflects and/or scatters
ultrasound in an omnidirectional manner. Typically, the
irregularities will be of an amplitude up to approximately one
quarter of a wavelength of the ultrasound involved in water. At an
ultrasound frequency of 7.5 MHz, this is about 50 .mu.m for example
40-60 .mu.m. Depending on the frequency of the ultrasound,
amplitudes of about 30 to about 90 .mu.m may be suitable. Within
this size range, larger irregularities are preferred due to an
increase in reflected energy. Lower amplitudes, for example below
about 20 .mu.m, may not provide significant enhancement of
ultrasound visibility.
[0036] The roughening, shaping or other treatment may take the form
of production of grooves, depressions, scratches or the like on a
surface of the container. The grooves etc may be arranged randomly
on the surface or in more regular patterns, for example in
geometric shapes and patterns such as squares and circles, or as
lines running substantially parallel or perpendicular to an axis of
the source, or in a helical arrangement. Preferably, the grooves
etc are not arranged in a highly repeating pattern with more than 1
repeat per quarter wavelength as such patterns may act as optical
gratings and lead to a loss of omnidirectionality in the echo
return. Suitable roughening, shaping or other treatment will depend
in part on the exact size and shape of the radioactive source
concerned, and can be readily determined using trial and error
experiments.
[0037] Preferably, the irregularities or discontinuities are in the
form of a helical groove (e.g. with a sinusoidal profile) on the
surface of the container. The pitch of the helix may be chosen to
give first order maxima in the intensity of the reflected
ultrasound at certain specific angles with respect to the
orthogonal orientation. For example, for a conventional radioactive
seed 4.5 mm long and 0.8 mm in diameter, a pitch of about 0.6 mm
will give a maximum at 10.degree. from orthogonal with 7.5 MHz
ultrasound, whilst a pitch of about 0.3 mm will give a maximum at
20.degree. from orthogonal. For such a seed the depth of the groove
from peak to bottom should be approximately 40 to 60 .mu.m. The
spacing of repetitive grooves along a source's axis should not be
too close, otherwise a minimum of ultrasound scattering may occur
at angles close to 90.degree. (i.e. orthogonal).
[0038] Preferably, the source will comprise a radiopaque substance,
for example silver or another metal, such that the sources may be
visualised using X-ray imaging techniques in addition to ultrasound
imaging.
[0039] Preferred sources of the invention are sources comprising a
metal container or capsule encapsulating a radioisotope, with or
without a carrier, which can be visualised by both ultrasound and
X-ray imaging techniques.
[0040] One advantage of using the sources of the invention in
brachytherapy is that the ultrasound signal and image may be read,
measured and analysed by suitable computer software sufficiently
quickly to allow a physician to plan real-time dosimetry. This is
advantageous from a clinical view point for both patient and
medical personnel. However, the sources of the invention may be
used in processes involving any type of dosimetry mapping that uses
information obtained due to the ultrasound visibility of the
sources.
[0041] In addition, a physician may use the same imaging technique,
i.e. ultrasound, already in place during surgery to confirm both
organ (e.g. prostate) position and size, and source placement. This
could enable a physician to calculate if additional sources need to
be inserted, for example in situations where the dose pattern needs
to be recalculated based on the "real" position of the seeds.
[0042] The radioactive sources of the invention may be supplied
within a substantially linear biodegradable material, for example
as in the product RAPIDStrand.TM. available from Medi-Physics, Inc.
of Illinois, U.S.A. Preferably the sources are evenly spaced (e.g.
10 mm apart in RAPIDStrand.TM.) to permit more even/uniform
radiation dosimetry and the dimensions of the array are such that
the whole can be loaded into a needle for administration to a
patient. The biodegradable material may be a suture or a suitable
biocompatible polymer.
[0043] The roughened, shaped or otherwise treated surface of a
source of the invention may be produced by a variety of different
methods. In a further aspect of the invention, there is provided a
method for increasing the ultrasound visibility of a radioactive
source for use in brachytherapy comprising a radioisotope and a
sealed biocompatible container, the method comprising roughening,
shaping or otherwise treating a surface or part of a surface of the
container to thereby provide irregularities or discontinuities of
dimensions and arrangement effective to enhance reflection of
ultrasound to facilitate detection thereof.
[0044] For example, if the source comprises a radioisotope
encapsulated in an essentially cylindrical container or an
encapsulating material, then the outer surface of the container or
encapsulating material may be roughened or shaped by forcing the
source through a ridged or serrated dye or a threading device to
impart grooves on the surface. A similar effect may be produced by
milling. The surface may also be roughened as a result of
mechanical friction, for example by use of a wire brush or a file,
or a suitable grade of sandpaper, e.g. a coarse grade. The outer
surface may also be etched, for example using a laser or water-jet
cutter, or by electrolytic etching. Blasting, for example sand
blasting, may also be used. Blasting may be done dry, or wet as in
water-jet blasting.
[0045] If the source comprises an electroplated support, the
electroplating process itself may lead to a sufficiently roughened
surface for the purpose of the invention.
[0046] Manufacture of radioactive seeds comprising a radioisotope
inside a sealed metal or metal alloy container usually involves the
provision of a suitable metal tube, one end of which is sealed for
example by welding to form a canister. The radioisotope is then
introduced into the canister and the other end also sealed by for
example welding to provide a sealed source or seed. Alternatively,
a container or canister may be formed by stamping in a press from a
core of metal or by casting, moulding or forming a core of molten
metal, or by machining or drilling a solid core stock of metal, or
by melting and reforming and solidifying metal stock or by
fastening a cap to the end of a tube by means such as welding or
threading, or by use of heat to expand and then contract the cap on
cooling. The outer surface of the container may be roughened,
shaped or otherwise treated at any stage of the manufacturing
process. For ease of manufacture, the roughening, shaping or other
treatment process preferably occurs before loading of the container
with the radioisotope, more preferably on the non-radioactive metal
tube before sealing of either end, and most preferably on a long
section of metal tubing before it is cut into short segments
suitable for use in forming canisters. The roughening, shaping or
other treatment process should not be such that the integrity of
the container is compromised. Preferably, the thickness of the
container wall is maintained whilst the overall shape after the
treatment process is such that the surface is no longer smooth.
[0047] In a still further aspect of the invention, there is
provided a method for the preparation of a radioactive source
comprising a radioisotope and a biocompatible sealed container at
least one part of the surface of which is roughened, shaped or
otherwise treated so that it is no longer smooth, the method
comprising roughening, shaping or otherwise treating an exterior
surface or part of an exterior surface of the biocompatible
container of the source to thereby provide irregularities or
discontinuities in the exterior surface.
[0048] In a still further aspect of the invention, there is
provided a further method for the preparation of a radioactive
source comprising a radioisotope and a sealed biocompatible
container at least one part of the surface of which is roughened,
shaped or otherwise treated so that it is no longer smooth, the
method comprising
[0049] (i) roughening, shaping or otherwise treating a surface or
part of a surface of a biocompatible container material to provide
irregularities or discontinuities of dimensions;
[0050] (ii) loading a radioisotope into the biocompatible container
material of step (i); and
[0051] (iii) sealing the biocompatible container.
[0052] For example, a suitable thin-walled metal tube such as a
titanium metal tube may be mechanically deformed before insertion
of the radioactive material and welding of the ends to form a
sealed source. A smooth helical groove may be produced on both the
inner and outer surfaces of the tube without affecting the
thickness of the wall by use of a suitable crimping process. A
support tool of cylindrical shape and with outer threads of a
suitable pitch and depth may first be inserted into the metal tube.
The support tool should fit tightly within the tube. A crimping
tool may then be applied forcefully to the outer surface of the
tube. The shape of the crimping tool should match that of the
support tool. The crimping tool may consist of two or more parts,
each part covering a different sector of the tube's surface.
Following the crimping operation, the support tool may be removed
by simply twisting due to its helical threaded shape.
[0053] One or more helical grooves may also be produced by gently
pressing a sharp metal edge to the surface of a container while the
container is rolled over a solid surface at a slight angle, either
before or after the container is sealed to form a radioactive
source.
[0054] If improved ultrasound visibility of a source is desired,
alternatively or additionally to roughening, shaping or treatment
of the outer surface, the inner surface of the container may be
roughened, shaped or otherwise treated prior to introduction of the
radioisotope. For example, a non-uniform or roughened surface
inside a container may be introduced by means of a tap to create
helical or screw threads on the inside of the container. The tap
may gouge, score or auger out a thread pattern as it is turned into
the container. The spacing of the threads on the inside of a
container may be set at any desired dimension obtainable by tapping
the inside of the container. The tapping may be done before one end
is sealed (i.e. on a tubular precursor to the container) or after
one end is sealed (i.e. on a can). Preferably, the tubing is scored
before it is sealed at one end.
[0055] If the inner surface of a container is roughened, shaped or
otherwise treated, the overall thickness of the container wall
should not be so great that no ultrasound penetrates to the
interior of the container and is reflected therefrom. Suitable
thicknesses may be readily determined by experimentation. A
thickness of the container wall of up to about 0.1 mm is
suitable.
[0056] The thickness of the wall of a container encapsulating a
radioisotope is dependent upon at least the energy of the
radioisotope and the nature of the carrier. For example,
conventional .sup.125I sources use 50 .mu.m thick titanium
cylinders for containment which are sufficient to block beta
particles emitted by the .sup.125I while letting enough gamma rays
and low energy X-rays through for therapeutic impact. However, if
an aluminum container were used, the wall thickness would need to
change in order to adequately capture any beta particles emitted.
Correspondingly, if a polymeric container were used, it would need
to be coated, for example with a titanium oxide "paint" or be
plated with a metal to modify or block beta particle emissions if
the plastic itself did not capture them. Higher energy sources may
be used with thicker carriers than lower energy sources.
[0057] The number of helical or spiral ridges, threads, grooves or
the like on an inner or outer surface of a container may be, for
example, in the range from about 1 to about 100 per mm of length of
the container body.
[0058] The tube or container may be incised with at least one
ridge, thread or groove pattern and optionally with more than one
such pattern of different advancing spiral or helical threads which
may be in the same or opposite sense of handedness. The thickness
or depth of each such ridge, thread or groove may vary from about 1
.mu.m to about half the thickness of the container wall if desired.
Two or more ridges, threads or grooves of different spacings,
different handedness, and/or different thicknesses or depths may be
tapped into the container to give a wide variety of scoring
patterns on the inside surface thereof or incised onto the outer
surface of the container to give a wide variety of scoring patterns
on the outside thereof.
[0059] The thickness of the container wall may preferably be within
the specifications set for conventional brachytherapy radioactive
sources and seeds, or it may be selected as the optimum useful in
brachytherapy by clinical experimentation. Optionally, the
container wall may be thicker than finally desired at the start of
the roughening, shaping or other treatment procedure, and excess
thickness may be removed during the procedure, for example during
tapping of the inside of the container.
[0060] The roughening or shaping on the outer surface of a
container according to the invention may take the form of
serrations on the surface. The serrations may be in the form of
teeth, steps, notches or projections on the surface of the
container. Such serrations may be grouped on part of the surface to
form a cluster, and/or may be set in rows on part of the surface. A
serrated tooth has one edge subtended from the surface that is
longer than a second edge that is also subtended from the surface,
the two such edges meeting at a common point or peak. The direction
of the serrated tooth is defined as the direction in the plane of
the shorter edge. In another aspect, the edges of the teeth may be
of similar length, and the teeth may be substantially symmetrical
in two-dimensions. In another aspect, the teeth may be conical,
pyramidal or trigonal or of other geometric shape wherein a point
is achieved. The teeth may be of uniform or non-uniform size, and
the teeth may comprise more than one serrate. When more than one
set of serrations is present, they should be spaced apart on the
surface of the source and should not all run in the same direction.
Preferably, there will be two sets of serrations on opposite sides
of a source, and more preferably running in opposite
directions.
[0061] The roughening, shaping or other treatment of an outer
surface of the source of the invention may reduce the tendency of
the sources to migrate or move once implanted inside a patient when
compared to conventional smooth seeds. Serrations on two or more
portions of the surface of a source are particularly suitable in
this respect. Such serrations may also lacerate tissue during
implantation, resulting in the formation of scar tissue which may
also help serve to keep the implanted source in place. Preferably,
the roughening, shaping or other treatment is sufficient to reduce
the tendency of a source to migrate but is not such that the
sources cannot be delivered to the treatment site using
conventional methodology and handling techniques. A suitable degree
of roughening etc. may be found by trial and error
experimentation.
[0062] If the source comprises a container comprising a composite
material, then the outer surface of the container may be roughened
by exploiting differences in the physical properties of the
materials comprised in the composite. For example, if the composite
comprises a blend of polymers that are phase separated in the blend
and have different solubility properties in a particular solvent,
then the surface may be roughened by exposing it to that solvent
and thereby causing part of the blend to dissolve. Alternatively,
if the composite comprises a polymer and a salt, then exposure to a
suitable solvent may dissolve the salt but not the polymer and
thereby cause roughening of the surface.
[0063] A container comprising a polymeric or ceramic could be
rendered "rough" by entraining particles of water soluble materials
within the material of the container. For example, particles of
sodium chloride which are substantially insoluble in most polymer
melts could be entrained in a polymeric container. Upon exposure to
water or simply by placement within the tissue of interest, the
sodium chloride particles may dissolve leaving a "rough" surface to
the container. The resulting hyperosmotic effect around the source
may also elicit a physiological response, which might help serve to
anchor the source to a greater degree than normal and so avoid
subsequent movement of the source.
[0064] A ceramic composite container could be prepared from two or
more different but compatible ceramic materials such that exposure
of the container to acid or base could selectively dissolve one or
more of the carrier components so leading to a suitably roughened
surface. For example, a combination of aluminum oxide and titanium
oxide could afford selective dissolution in strongly basic
solutions as aluminum is soluble at very high pH whilst titanium
passivates and does not dissolve in such media.
[0065] Alternatively, a container may be exposed to a corrosive
solution such that the surface is corroded in an uneven way to lead
to a suitably roughened surface. For example, stainless steel is
susceptible to crevice corrosion by action of chloride ion in an
oxidizing environment at lower pH values.
[0066] Any conventional brachytherapy sources may be roughened,
shaped or otherwise treated using the method of the invention to
improve their ultrasound imaging visibility. For example, the
ultrasound visibility of the radioactive seeds disclosed in U.S.
Pat. No. 5,404,309, U.S. Pat. No. 4,784,116 and U.S. Pat. No.
4,702,228 could be improved. These seeds comprise a capsule and two
radioactive pellets separated by a radiopaque marker within the
capsule. The opaque marker imparts detectability by X-ray imaging
of the seeds. Roughening of the surface of such capsules could be
achieved for example by abrasive filing or scratching of the
surface. Furthermore, abrasive roughening could be done exclusively
in the region of the capsule proximal to the opaque marker in each
design to thereby impart enhanced ultrasound detectability to the
capsule in addition to detectability by X-ray imaging. The region
of the capsule that is proximal to the radioactive pellets may not
be roughened, so that the thickness of the wall of the capsule
remains substantially uniform around the radioactive pellets. The
dose of radiation received from such partially roughened capsule
when implanted in a patient may therefore be substantially
unchanged from the dose of radiation from a completely unroughened
conventional capsule. Calculation and administration of the dose of
radiation may then be independent of the depth or extent of the
surface roughening in the region of the opaque marker. Likewise,
roughening in the region of the marker may be done in depths and to
degrees which may change the thickness of the capsule wall without
substantially altering the profile of radiation dose received by
the patient.
[0067] In a further aspect, the invention also provides a method of
treatment of a condition which is responsive to radiation therapy,
for example cancer, arthritis or restenosis, which comprises the
temporary or permanent placement of a radioactive source comprising
a radioisotope within a sealed biocompatible container, wherein at
least one part of a surface of the container is roughened, shaped
or otherwise treated to thereby provide irregularities or
discontinuities, at the site to be treated within a patient for a
sufficient period of time to deliver a therapeutically effective
dose.
[0068] The invention will be further illustrated, by way of
example, with reference to the following Drawings:
[0069] FIG. 1 illustrates one embodiment of a radioactive source
according to the invention;
[0070] FIG. 2 illustrates another embodiment of a radioactive
source according to the invention;
[0071] FIG. 3 illustrates a metal tube suitable for use in the
production of one embodiment of a radioactive source according to
the invention;
[0072] FIG. 4 illustrates a cross-sectional view of the metal tube
of FIG. 3 during the crimping operation;
[0073] FIGS. 5 and 6A to D are ultrasound images of a metal wire
and metal tubes roughened using embodiments of the methods of the
invention.
[0074] FIG. 7A is a picture of a conventional titanium seed casing
and FIGS. 7B and 7C are pictures of similar seed casings roughened
using embodiments of the method of the invention. FIG. 7D shows in
graphical form the backscattered intensity as a fucntion of the
angle of the seed axis in relation to the ultrasound beam for the
seed casings of FIGS. 7A to C.
[0075] FIG. 8 shows in graphical form the backscattered intensity
as a function of the angle of the seed axis in relation to the
ultrasound beam for a conventional seed casing and two seed casings
modified according to the invention.
[0076] FIG. 1 is a schematic illustration of part of a source 1
with serrated edges 2, the serrations running in opposite
directions on opposite edges.
[0077] FIG. 2 is a schematic illustration of a sealed source 3
according to one embodiment of the invention. The source comprises
a metal, for example titanium, container 4 sealed at both ends 5.
The inside and/or outside on the container has a screw thread 6
etched thereon. The container contains a silver rod 7 coated with a
layer of .sup.125I-containing silver iodide. The silver rod 7 is
detectable by X-ray imaging techniques.
[0078] FIG. 3 illustrates a metal (e.g. titanium) tube 8 which has
been subjected to a crimping operation to form helical groves 9 on
the outside and inside thereof. Such a tube is suitable for use in
the production of a sealed radioactive source according to the
invention.
[0079] FIG. 4 illustrates in schematic form a cross section through
the metal tube 8 of FIG. 3 during the crimping operation. The tube
is crimped between a support tool 10 and a crimping tool 11, made
up of four different segments.
[0080] FIGS. 5 and 6A to D are ultrasound images which are
discussed in more detail in the following Examples.
[0081] FIGS. 7A to D and 8 will also be discussed in more detail in
the Examples.
[0082] The invention will be further illustrated with reference to
the following non-limiting Examples:
EXAMPLES
Example 1
[0083] A 12 mm long section of a 0.8 mm diameter copper wire was
mechanically roughened using pliers with a serrated jaw, but no
material was removed form the wire. The ultrasound visibility
compared with that of a smooth, unroughened portion of the same
wire. The results are shown in FIG. 5, which is a sample B-mode
ultrasound image of the wire in a water tank obtained using a
Vingmed CFM-750 scanner at 5 MHz.
[0084] In FIG. 5, 12 is the 12 mm long roughened portion of the
wire; 13 is the bottom edge of the water tank used in the
experiment; 14 is a smooth portion of the wire and 15 is a specular
reflection from the smooth wire section at a 90.degree. angle to
the incident ultrasound. The brightest region of the wire in the
ultrasound image is the roughened portion, illustrating that the
roughening of the invention greatly increases ultrasound
visibility.
[0085] Similar results are obtained if the surface of a
conventional titanium seed canister is roughened in the same
way.
Example 2
[0086] A straight, thin (0.1 mm diameter) monofilament nylon wire
was mounted in a water bath, and imaged with a Vingmed CFM-750
ultrasound scanner at 7.5 MHz. The wire was arranged to run
diagonally across the image, at an angle of 45.degree. with respect
to the soundbeam direction in the centre of the image sector. This
wire served as a support for pieces of titanium tubing that could
be moved in and out of the central image field. The titanium tubes
were those used to form conventional canisters for production of
brachytherapy seeds (length 5 mm, diameter 0.8 mm, wall thickness
0.05 mm), but without welded ends and the radioactive insert.
Images of pieces of tubing with different surface modifications
were made in the exact same location, and without changing the
geometry or the scanner instrument settings. A common feature of
all imaged tube segments are diffraction artefacts at the unclosed
ends. Valid comparisons of performance can thus only be made by
studying the central regions of the tubes. Also, a bright halo was
seen in the images behind the tubes, most probably caused by
acoustic reverberations inside the tube structure.
[0087] The following surface modifications were made: a) fine
abrasive grinding, b) rough abrasive grinding, c) rough deformation
with no loss of material, and d) no modifications to the original
surface.
[0088] FIG. 6A to D shows the resulting ultrasound images. All
modifications resulted in an improved visibility of the central
portion of the seeds when compared to the non-modified case d).
Best performance was observed with fine grinding, a).
Example 3
[0089] Measurement Set-Up
[0090] A wide band 7.5 MHz transducer (Panametrics V320) was
mounted in the measurement chamber wall. With a transducer diameter
of 13 mm and a focal distance of 50 mm this transducer has an
acoustic field similar to a typical phased array transducer used in
clinical TRUS applications.
[0091] A brachytherapy seed was mounted on a holder which could be
rotated to defined angles in relation to the direction of the
ultrasound beam. The seed was glued on to the tip of a needle
protruding from the specimen holder with cyanoacrylate glue so that
the seed's centre of gravity coincided with the rotational axis of
the holder. The angular rotation could be set with half a degree
accuracy, which is of great importance given the high angular
dependency of the US backscatter. The holder could also be adjusted
by translation to position the seed in the focal point of the
transducer and fixed throughout the experiments.
[0092] The transducer was excited with a wide band pulse from a
Panametrics 5800 pulser-receiver. The received signal was acquired
with a LeCroy 9310 oscilloscope and digitised. The sampled radio
frequency (RF) signal (fs=50 MHz) was then transferred to a
computer for further processing.
[0093] Three different seeds were tested; an unmodified seed and
two different modified seeds. The unmodified seed (A) was identical
to a standard seed except that it has not loaded with radioactive
iodine. The dimensions of the seed were 0.8.times.4.2 mm and the
wall thickness of the titanium tube was 50 microns. Two similar
seeds were modified by gently pressing a sharp metal edge to the
seed surface while the seed was rolled over a solid surface at a
slight angle. The resulting deformation was one or more helical
grooves running along the full length of the seed. One of the
modified seeds (B) was placed on very fine sandpaper for friction
during the deformation and a helical groove of 0.058 mm depth, 0.1
mm width and about 0.54 mm pitch was produced. The other modified
seed (C) was placed on a thin rubber sheet during the deformation
and the result was several finer helical grooves with about 0.03 mm
depth and 0.2 mm groove spacing. FIGS. 7A, 7B and 7C show magnified
views of the seeds A, B and C respectively. The images were
transferred to an image analysis program (Optimas) for measurements
of the deformations. The image processing program was calibrated
using the undistorted length of the seed as a reference and several
measurements of groove thickness, width and pitch were averaged for
a representative characterisation of the seed surface
distortion.
[0094] A series of measurements mapping the ultrasound backscatter
of each of the seeds throughout the full range of incidence angles
(-65 to 65 degrees) were performed. After accurate positioning at
the desired angle, 10 ultrasound pulses were transmitted at a PRF
of is 10 Hz and the received echoes were digitised and stored. The
10 pulses were averaged coherently before further processing. Three
different methods were tested for estimation of the backscattered
echo intensities; a) the square of the peak amplitude, b) the
integral of the signal in a 0.5 microsecond gate around the peak
amplitude, and c) the integral of a bandpass filtered (5-9 MHz)
version of the signal in a 1 microsecond timegate centred as in b).
Method a) best represents the "brightness" of the seed in an
ultrasound image, while methods b) and c) more nearly represent the
overall backscattered energy. The three methods yielded very
similar results for all seeds and angles and the results of method
a) are used herein. Further, images of envelope detected individual
scanlines at different angles were made for visualisation. These
images directly represent what a small section of the image
containing the seed would look like on a normal B-mode image.
[0095] The numeric results of the backscattered intensity are
presented in graphical form in FIG. 7D. The intensity at normal
incidence (i.e with the seed axis orthogonal to the ultrasound
beam) was very similar between the different samples. For the
unmodified seed A, the backscattered intensity dropped off very
quickly with increasing angle away from the normal. At 10 degrees
angle in either direction, the intensity had reached a minimum
about 23 dB below the level of normal incidence (0 degrees).
Judging from those measurements, the seed would be dramatically
less visible, if visible at all, at angles exceeding .+-.2.5
degrees from normal incidence. The backscattered intensity
increased again as the incidence angle approached 60 degrees since
the tip of the seed entered the ultrasound beam and sound was
reflected off the rounded seed tip.
[0096] The modified seeds B and C had a much less pronounced
reduction in backscattered intensity with increasing incidence
angle. The intensity did not drop more than about 10 dB for either
of the two modified seeds within +60 degrees of the incidence
angle, and the seeds are therefore expected to be visible at a much
larger angular range than the unmodified seed. For lower angles,
variations in intensities caused by constructive and destructive
interference of the sound reflected on the groves could be
observed. This was more pronounced for seed B as the helical
pattern here was deeper and more defined than for seed C. The
dispersion of scattered energy through larger angles for the
modified seeds compared to the unmodified seed did not
significantly effect the backscattered intensity at normal
incidence.
Example 4
[0097] The ultrasound visibility of three types of seed in a
prostate phantom was investigated. The prostate phantom was a
commercially available phantom and seeds were inserted in the
phantom using the clinical set-up for seed implantation: i.e.,
B&K Panther ultrasound machine using 7.5 MHz transrectal
ultrasound transducer; MMS treatment planning software; B&K
hardware for seed implantation; standard 18 gauge seed-implantation
needles.
[0098] Three different seed types were investigated. The reference
seeds (ref) were dummy (i.e non-radioactive) seeds corresponding to
the seeds commercially available from Medi-Physics, Inc. under
model number 6711. Seeds A corresponded to the reference seed
modified by the addition of five longitudinally spaced grooves
around the central portion of each seed and seeds AC were prepared
in a manner analogous to seed B of Example 3.
[0099] The seeds were implanted at a range of angles relative to
the ultrasound beam (with 0.degree. corresponding to the long axis
of the seed being orthogonal to the ultrasound beam) and the
ultrasound visibility of the implanted seeds was measured.
[0100] FIG. 8 shows the results for the three different types of
seed. When the ultrasound beam struck a seed within the phantom
with a deviation of 0.degree..+-.2.degree. (i.e.: at exactly
90.degree. to the seed's long axis) there was little difference
between the reference and the modified seeds of the invention.
However, when the seeds were implanted at an angle to the
ultrasound beam, the modified seeds retained their echogenicity to
a much greater extent than did the reference seeds.
* * * * *