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Description  |
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BACKGROUND OF THE INVENTION
Proton nuclear magnetic resonance (NMR) tomography has become an important
tool in biomedical research and medical diagnosis. The image contrast
mechanisms of NMR are different from X-ray imaging, and provide
substantial contrast between certain soft tissues that are nearly
identical using radiological techniques. Further, conventional
radiological imaging techniques involve the use of high energy
electromagnetic radiation associated with potential cancer induction,
whereas the low energy radio waves associated with NMR poses no such risk.
However, while some soft tissues provide substantial contrast using NMR
techniques, others, particularly those involving the gastrointestinal
tract, yield a relatively low level of contrast in proton NMR imaging.
This has prompted the development of suitable NMR contrast agents. While
numerous substances, such as vegetable oils and paramagnetic metal salt
solutions, such as ferric chloride solutions and solutions of gadolinium
oxide, have been used to visualize the lumen of the stomach and intestines
in NMR tomography, none have the coating and filling characteristics which
have made barium sulfate so useful in radiological applications. Moreover,
many paramagnetic metal ion containing solutions e.g. those of Cu.sup.2+,
Cr.sup.3+, Fe.sup.3+ and Mn.sup.2+, are generally toxic at concentrations
which sufficiently shorten the spin relaxation times, T.sub.1 and T.sub.2,
of the solution environment to render such solutions useful NMR contrast
agents. Runge et al., Radiology, Vol. 147, pp. 789-791 (1983).
Further, since conventionally available proton NMR tomography equipment is
complex in terms of operator selectable paramaters, there is a need for
storage stable materials especially in the form of a collection or array,
which substantially mimics the range of proton density values,
spin-lattice or longitudinal relaxation (T.sub.1) values, and spin-spin or
traverse relaxation (T.sub.2) values, associated with various animal
tissue, for tuning such selectable parameters. Appropriate tuning of the
operator selectable parameters enables the operator to optimize the
desired contrast characteristics associated with NMR tomographic images,
including, for example, inversion recovering images, partial saturation
images, density images, spin echo images, and the like. See in general,
Wehrli et al., Magnetic Resonance Imaging, Vol. 2, pp. 3-16 (1984).
It has now been surprisingly discovered that synthetic substantially
non-degradable cross-linked water-swellable hydrogel materials, having in
the swollen state between about 5 to about 95% water and containing
functional groups which interact with water, possess nuclear magnetic
resonance spin density values, and T.sub.1 and T.sub.2 values sufficiently
analogous to the spectrum of values associated with mammalian tissue, such
that the aqueous swollen materials are highly useful in proton NMR
tomographic imaging techniques, and overcome many of the disadvantages
associated with known materials and techniques.
It has been further unexpectedly discovered that those hydrogels having
T.sub.1 and T.sub.2 values substantially shorter than that of
gastro-intestinal viscera are highly useful as proton NMR image contrast
agents.
Thus, it is an object of the instant invention to provide a method of
contrasting a proton NMR tomograph of the gastro-instestinal tract, or a
portion thereof, by administering to a mammal, including man, an effective
image contrasting amount of a physiologically tolerable, synthetic
substantially non-degradable cross-linked hydrogel having, in the aqueous
swollen state, spin-lattice or spin-spin relaxation values substantially
shorter than the surrounding gastro-intestinal tissue environment.
It is a further object of the instant invention to provide an aqueous
coating suspension or slurry of particulate swollen synthetic
substantially non-degradable cross-linked hydrogel, said hydrogel having
spin-lattice or spin-spin relaxation values substantially shorter than the
respective spin-lattice or spin-spin average relaxation values of
gastro-intestinal viscera, for use as proton NMR contrast agents.
It is yet a further object of the instant invention to provide a collection
or array of storage stable swollen cross-linked hydrogel materials
possessing a range of nuclear magnetic resonance spin density values,
spin-lattice relaxation values and spin-spin relaxation values, embracing
at least a portion of the spectrum of such values possessed by distinct
anatomic mammalian tissue, and suitable for use in NMR imaging equipment
for proton NMR image contrast determinations.
These and other objects of the invention are apparent from the following
disclosure.
DETAILED DISCLOSURE OF THE INVENTION
One embodiment of the instant invention relates to a method of contrasting
a proton NMR tomograph of the gastro-intestinal tract of a mammal, by
administering to the mammal an effective image contrasting amount of a
physiologically tolerable cross-linked synthetic substantially
non-degradable hydrogel in particulate form, said hydrogel having, in the
aqueous swollen state, spin-lattice or spin-spin relaxation times
substantially shorter than the surrounding gastro-intestinal tissue
environment, and subjecting the mammal to said proton NMR tomography.
The hydrogel particulate may be administered to the gastro-intestinal tract
orally or rectally.
Conveniently, the hydrogel is administered as an aqueous suspension or
slurry of particulate swollen cross-linked hydrogel. The size of the
hydrogel particles can vary over a wide range, depending upon the desired
resolution of the image desired, and the like. In general, the hydrogel
particulate can range, in average diameter between about 100 and about 100
mm, preferably between about 1 mm and about 10 mm, and most preferably
between about 2 mm and about 10 mm. The particulate hydrogel material may
be in the form of beads, powders or granulates. Because of the crosslinked
nature of hydrogels, they are substantially insoluble, but
water-swellable, in aqueous media. Thus, the hydrogels are not absorbed
through the gastro-intestinal walls upon administration. Accordingly, the
image contrasting cross-linked hydrogels are generally well tolerated and
avoid the toxic aspects associated with many paramagnetic metal ion
solutions, due to the substantially non-degradable, i.e. non-digestible,
nature of the hydrogel material.
In order for the aqueous swollen particulate cross-linked hydrogel material
to exert an effective contrasting effect in proton NMR tomography of the
gastro-intestinal tract, the hydrogen material chosen should, in the fully
swollen state, exhibit relaxation time constants, T.sub.1 and T.sub.2,
substantially less than that of gastro-intestinal viscera. In general,
suitable hydrogels exhibit, at a proton resonance frequency of about 10
megahertz (MHZ), a T.sub.1 relaxation time of between about 10 to about
200 milliseconds (msec), preferably between about 10 to about 150 msec,
and most preferably between about 20 to about 120 msec, and a T.sub.2
relaxation time of between about 1 to about 60 msec, preferably between
about 1 to about 50 msec, most preferably between about 2 and about 50
msec. At about 10 megahertz, the T.sub.1 value of gastro-intestinal
viscera characteristically is between about 150-700, and the T.sub.2 value
is between about 20-100, msec.
As the proton resonance frequency is decreased, the respective T.sub.1 and
T.sub.2 values of suitable image contrasting hydrogel materials likewise
decrease, as do the T.sub.1 and T.sub.2 average values of
gastro-intestinal viscera.
Similarly, as the proton resonance frequency of the NMR is increased,
T.sub.1 and T.sub.2 values of suitable image contrasting hydrogel
materials likewise increase, as do the average T.sub.1 and T.sub.2 values
for the gastro-intestinal tract. The instant image contrasting materials
are generally suitable throughout the conventional range of chosen proton
resonance frequencies characteristically used in NMR tomography, e.g.
between about 2 to about 30 MHZ.
Eligible cross-linked hydrogel materials suitable for use as contrast
agents in NMR tomography of the gstro-intestinal tract are easily
determined by simple comparison of sample swollen cross-linked hydrogel
T.sub.1 and T.sub.2 values with the corresponding average value of
gastro-intestinal tissue at a chosen proton resonance frequency. Such
tests can be conducted in vitro, using representative actual or phantom
tissue samples, or in vivo, using live test animals.
Typical hydrogels found to be suitable as NMR gastro-intestinal contrast
agents characteristically contain between about 5% to about 80% water,
more preferably between about 10% to about 75% water. The hydrogel is
advantageously swollen with a saline solution for in vitro comparative
purposes in order to mimic the environment of the gastro-intestinal tract.
Moreover, suitable synthetic substantially non-degradable hydrogel
materials contain as part of the cross-linked, three dimensional matrix,
hydrophilic functional groups which interact with water. As is well known,
these functional groups are to a large extent responsible for the
hydrophilic aqueous swelling ability of the hydrogels. Representative
hydrophilic groups include hydroxyl, keto, amino, amido, ether, carboxy,
sulfoxy, sulfonyl, and the like.
In general, the T.sub.1 and T.sub.2 relaxation times for a given hydrogel
material will be proportional to the aqueous swelling ability of the
material. Since the aqueous swellability can be decreased by increasing
the amount of crosslinking of the hydrogel, the T.sub.1 and T.sub.2 values
of the fully swollen hydrogel can be decreased by increasing the amount of
crosslinking agent incorporated into the hydrogel material. It is believed
that the T.sub.1 and T.sub.2 values are decreased as cross-linking is
increased because the average compartment size for the absorbed water is
reduced, thereby increasing the interaction between the water molecules
and the hydrophilic components of the hydrogel matrix. Further, increasing
the number of hydrophilic groups present in the hydrogel likewise tends to
decrease the T.sub.1 and T.sub.2 relaxation times as the degree of
interaction of absorbed water is dependent upon the amount and nature of
such hydrophilic groups.
Suitable synthetic substantially non-degradable hydrogel materials include
the known classes of pharmaceutically acceptable crosslinked hydrogel
materials employed in the fields of soft contact lenses and pharmaceutical
medicament diffusion carriers, including without limitation, those
crosslinked hydrogel materials described in Wichterle et al. U.S. Pat.
Nos. 2,976,576 and 3,220,960; Mueller et al. 4,136,250, 4,192,827 and
4,224,427; Siederman 3,639,524, 3,721,657 and 3,767,731; Ewell 3,647,736;
O'Driscoll et al. 3,700,761, 3,822,196, 3,816,571 and 3,841,985; Steckler
3,532,679; Stamberger 3,758,448 and 3,772,235; Neefe 3,803,093; Tanaka et
al. 3,813,447; Blank 3,728,317, Isen 3,488,111; and Ohkada et al.
4,347,198, the disclosures of which incorporated by reference herein, in
toto.
Such hydrogels are generally prepared by polymerizing a monomer or mixture
of monomers, either in the presence of a cross-linking agent to crosslink
the polymer, or in the absence of a cross-linking agent to form a
pre-crosslinked intermediate which is subsequently crosslinked with a
crosslinking agent. Also in the polymerization step there may be present,
in addition to a monomer or mixture of monomers, a polymer or prepolymer
substrate upon which the monomers may be grafted, by polymerization, for
example. Where mixtures of monomers are employed, the resulting copolymer
may be random, alternating, block or graft copolymers depending upon the
polymerization techniques, sequence of monomer addition, reaction
conditions, nature and reactivity of the monomers employed, and the like.
Generally the monomer employed is hydrophilic in nature. However, mixtures
of hydrophilic and hydrophobic monomers, preferably containing less than
50 mole percent hydrophobic constituents, may be employed. Alternatively,
a hydrophobic monomer may be polymerized and subsequently converted to a
hydrophilic species, for example as is well known in the polymerization
and subsequent hydrolysis of vinyl acetate to form polyvinyl alcohol,
which may then be cross-linked with glyoxal, diglycidyl ether or the like.
Suitable hydrophilic monomers commonly employed in the preparation of
crosslinked hydrogels useful in the instant invention include, without
limitation, acrylic and/or methacrylic acid and the water-soluble
derivatives thereof such as the epoxy or hydroxy substituted lower alkyl
esters thereof including e.g. the 2-hydroxyethyl, glycidyl,
3-hydroxypropyl, or 2,3-dihydroxypropyl esters thereof; the ethoxylated
and polyethoxylated hydroxy substituted lower alkyl esters thereof; the
di-(lower alkyl) aminoloweralkyl acrylates or methacrylates, such as the
2-(dimethylamino)ethyl acrylate, or the 2-(diethylamino)ethyl
methacrylate; the water soluble amides thereof, such as the unsubstituted
amides and amides substituted by one or two hydroxyloweralkyl groups, such
as N-(2-hydroxyethyl)-methacrylamide; water soluble heterocyclic nitrogen
containing monomers, such as N-vinylpyrolidone, N-vinyl-succinimide,
N-vinyl-pyrrole, 2- and 4-vinylpyridine, 4-vinyl-quinoline,
4-acrylylmorpholine and the like, mono-olefinic sulfonic acids and their
pharmaceutically acceptable salts, such as sodium ethylene sulfonate,
sodium styrene sulfonate and the like; hydroxyloweralkyl maleates,
fumarates and vinyl ethers, such as 2-hydroxyethyl monomaleate,
di(2-hydroxyethyl) maleate, 2-hydroxyethyl vinyl ether, 4-hydroxybutyl
vinyl ether and the like.
Preferably, for patient administration the crosslinked hydrogels are
substantially free of strongly ionic groups, such as sulfonates, free
amine groups and the like, which may adversely interact with
gastro-intestinal fluids and upset the electrolytic balance.
Suitable hydrophobic monomers which may be employed include, without
limitation, C.sub.1-18 alkyl acrylates or methacrylates; vinyl acetate;
C.sub.1-18 alkenes which are unsubstituted or substituted by halo;
acrylonitrile; styrene; di-lower alkyl-acrylamides and -methacrylamides,
vinyl C.sub.l-5 alkyl ethers, such as propyl vinyl ether, and the like.
Suitable crosslinking agents include, without limitation, divinyl benzene,
ethylene glycol dimethacrylate, polyethyleneglycol dimethacrylate,
glyoxal, diglycidyl ether, and macromer cross-linking agents such as
polytetramethylene oxide having a molecular weight of about 1500 which is
capped at both ends by isophorone diisocyanate or 2,4-toluene diisocyanate
and subsequently terminated by 2-hydroxyethylmethacrylate, e.g. as
described in U.S. Pat. No. 4,277,582, or a polysiloxane having a molecular
weight of about 400 to about 8500 capped at both ends with 2,4-toluene
diisocyanate or isophorone diisocyanate and subsequently terminated by
2-hydroxymethacrylate, e.g. as described in U.S. Pat. No. 4,136,250.
If desired, the hydrogel materials may be formulated in the presence of a
radio-opaque substance, such as particulate barium sulfate, iobenzamic
acid, iocarmic acid, iocetamic acid, iodamide, iodipamide and
pharmaceutically acceptable salts thereof. Alternately, the hydrogels may
be prepared in the presence of tomographic inhancing aids such as ferric
(Fe.sup.+3) and/or manganese (Mn.sup.+5) salts to increase the contrast of
the hydrogel material in comparison with the surrounding tissues. A
preferred method of preparing hydrogel beads by suspension polymerization
is described in U.S. Pat. No. 4,224,427. In such process one may
incorporate the aforementioned adjuvant ingredients, e.g. for rendering
such beads radio-opaque or for enhancing NMR contrast, simply by adding
the adjuvant to the suspension polymerization medium. The amount of
adjuvant present will vary, dependent upon the nature thereof. Preferably,
no more than 10 percent by weight of hydrogel consists of such adjuvant.
The hydrogel material generally is administered to the patient orally or
rectally as an aqueous slurry or suspension. As the hydrogel material is
soft, flexible and substantially inert, the slurry or suspension is
generally very well tolerated by the patient.
Also, a collection or array of diverse hydrogel samples, possessing varying
T.sub.1 and T.sub.2 constants, preferably exhibiting T.sub.1 and T.sub.2
constants embracing at least a substantial portion of the spectrum of such
constants exhibited by diverse mamalian tissues may be employed as tissue
phantom kits for adjusting tomography equipment. Generally, at least three
such samples are employed in such kits.
The following examples are presented for the purpose of illustration only
and are not to be construed to limit the nature or scope of the invention
in any manner whatsoever. All parts are by weight unless otherwise
specified.
EXAMPLE 1
In accordance with the procedure set forth in Example 1 of U.S. Pat. No.
4,224,427, 48 parts by weight of a macromer, 20 parts N-vinyl pyrrolidone
and 32 parts of 2-hydroxyethyl methacrylate were polymerized using 0.2
parts of tert-butyl peroctoate as a free radical initiator. The macromer
consists of poly(tetramethylene oxide) glycol having an average molecular
weight of approximately 2000 endcapped with isophorone diisocyanate in an
amount of two moles per mole of said glycol, and terminated with 1 mole of
2-hydroxyethyl methacrylate per mole of said diisocyanate, reacted for 72
hours at room temperature. The reaction mixture of macromer and monomers
with initiator are combined in about 240 parts of an aqueous suspension of
magnesium hydroxide (prepared by combining about 180 parts of a 20% by
weight aqueous sodium chloride solution with about 12 parts of magnesium
chloride hexahydrate with stirring at about 80.degree. C. and adding
dropwise about 60 parts of a 1-normal sodium hydroxide solution) with
stirring at 150 rpm under a nitrogen blanket at 80.degree. C., the
macromermonomer mixture allowed to polymerize for 3 hours, and the
temperature raised to 100.degree. C. for one hour, after which the
reaction medium is cooled to room temperature, the magnesium hydroxide
suspending agent neutralized with concentrated hydrochloric acid and the
reaction mixture beads isolated by filtration and washed with water to
remove any residual monomer. The resulting polymer spherical beads
(diameter approx. 1 mm) have a water content of approximately 56% by
weight, based upon the weight of swollen crosslinked hydrogel polymer
beads. Upon subjecting the swollen crosslinked polymer beads to NMR
imaging at 6.4 MHz the following T values were obtained:
T.sub.1 =320.+-.34 ms
T.sub.2 =52.+-.3 ms.
EXAMPLE 2
Following the method of Example 1 a crosslinked hydrogel in the form of
beads having a diameter of approx. 1 mm and containing 30% by weight of
the macromer of Example 1 and 70% by weight 2-hydroxyethyl methacrylate
are prepared. The resulting aqueous swollen beads contain approximately
25% by weight water and when subjected to NMR imaging at 6.4 MHz exhibit
the following T values:
T.sub.1 =1330.+-.400
T.sub.2 =294.+-.55.
EXAMPLE 3
Following the method of Example 1, crosslinked hydrogel beads containing
12% by weight of the macromer of Example 1, 40% by weight n-octyl
methacrylate, 27% by weight hydroxyethyl methacrylate are prepared. The
resulting aqueous swollen beads contain approximately 27% by weight water
and when subjected to NMR imaging at 6.4 MHz exhibit the following T
values:
T.sub.1 =390.+-.120
T.sub.2 =44.+-.16.
EXAMPLE 4
Following the method of Example 1, crosslinked hydrogel beads containing
12% of the macromer of Example 1, 21% 2-hydroxyethylmethacrylate, 21%
N-vinyl pyrrolidone, 27.5% methyl methacrylate and 27.5%
.alpha.-ethylhexyl acrylate are prepared. The resulting aqueous swollen
beads contain about 10% water and when subjected to NMR imaging at 6.4 MHz
exhibit the following T values:
T.sub.1 =1800.+-.220
T.sub.2 =340.+-.80.
EXAMPLE 5
Following the method of Example 1, crosslinked hydrogel beads containing
30% of the macromer of Example 1, 20% 2-hydroxyethyl methacrylate and 50%
methyl methacrylate are prepared. The resulting aqueous swollen beads
contain approximately 9.9% water and when subjected to NMR imaging at 6.4
MHz exhibit the following T values:
T.sub.1 =1670.+-.400
T.sub.2 =294.+-.92.
EXAMPLE 6
Crosslinked hydrogel buttons having a diameter of about 20 mm and a height
of about 10 mm are prepared by placing in a mold a mixture of 50 parts by
weight 2-hydroxyethyl methacrylate, 50 parts by weight dimethyl acrylamide
and 0.5 parts ethyleneglycol dimethacrylate in the presence of about 0.1
part benzoin methyl ether as initiator and polymerizing the reaction
mixture under ambient conditions in the presence of an ultraviolet light
source for about 8 hours. Upon swelling the crosslinked hydrogel with
water, the equilibrated swollen material contained 79.8% water by weight,
and when subjected to NMR imaging at 6.4 MHz exhibits the following T
values:
T.sub.1 =1470.+-.300 ms
T.sub.2 =174.+-.30 ms.
Alternatively, the aforementioned monomer mixture is polymerized in a mold
to form substantially spherical beads of crosslinked hydrogel having an
average diameter of about 2 mm, which upon equilibration with water under
ambient conditions contains approximately 80% water by weight.
EXAMPLE 7
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a monomer mixture containing 75 parts 2-hydroxyethyl
methacrylate, 25 parts dimethylacrylamide, 0.5 parts ethyleneglycol
dimethacrylate as crosslinker and about 0.1 part benzoin methyl ether as
polymerization initiator. The products, upon equilibration with water,
contain approximately 59 weight percent water and having the following T
values at 6.4 MHz:
T.sub.1 =250 .+-.60
T.sub.2 =56 .+-.10.
EXAMPLE 8
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 100 parts 2-hydroxyethyl methacrylate, 0.5
parts ethyleneglycol dimethacrylate and about 0.1 parts benzoin methyl
ether. The products, upon equilibration with water, contain 39.3% water, a
T.sub.1 value of 1850.+-.300 and a T.sub.2 value of 224.+-.100 (at 6.4
MHz).
EXAMPLE 9
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 75 parts 2-hydroxyethyl methacrylate, 25
parts methylmethacrylate, 0.5 parts ethyleneglycol dimethacrylate and 0.1
part benzoin methyl ether. The products upon equilibration with water,
possess a water content of 22.7% by weight, a T.sub.1 value of about 1050
and a T.sub.2 value of 248.+-.90 (at 6.4 MHz).
EXAMPLE 10
Using the methods of Example 6, buttons and sperical beads, respectively,
are prepared from a mixture of 80 parts methylmethacrylate, 20 parts
dimethylacrylamide, 0.5 parts ethyleneglycol dimethacrylate and about 0.1
part benzoin methyl ether. The products, upon equilibration with water,
had a water content of 12.5% by weight and, at 6.4 MHz, a T.sub.1 value of
1440.+-.700 and a T.sub.2 value of 234.+-.100.
EXAMPLE 11
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 30 parts 2-hydroxyethyl methacrylate, 40
parts methyl methacrylate, 30 parts dimethylacrylamide, 0.5 parts
ethyleneglycol dimethacrylate and about 0.1 part benzoin methyl ether. The
products, upon equilibration with water, have a water content of 27.6% by
weight and at 6.4 MHz exhibit a T.sub.1 of 220.+-.110 and a T.sub.2 of
40.+-.19.
EXAMPLE 12
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 70 parts methyl methacrylate, 30 parts
dimethyl acrylamide, 0.5 parts ethyleneglycol dimethacrylate, and 0.1 part
benzoin methyl ether. The products produced posess upon equilibration with
water, a water content of 22.8% and, at 6.4 MHz, a T.sub.2 value of
38.+-.50.
EXAMPLE 13
Upon the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 50 parts of a fluorinated methacrylate
ester of the formula
R.sub.f --CH.sub.2 CH.sub.2 --SCONHCH.sub.2 CH.sub.2 OCO--C(CH.sub.3)
=CH.sub.2
wherein R.sub.f is a 1:1 mixture of n-C.sub.8 F.sub.17 and n-C.sub.10
F.sub.21, 30 parts methyl methacrylate and 20 parts dimethyl acrylamide,
with 0.2 parts ethyleneglycol dimethacrylate and about 0.1 part benzoin
methyl ether. The fluorinated methacrylate is prepared by combining one
mole of perfluoroalkylthiol of the formula R.sub.f CH.sub.2 CH.sub.2 SH
per mole of 2-isocyanatoethyl methacrylate, adding to the reaction mixture
0.005 mole triethylamine per mole of thiol with mixing under ambient
conditions to promote the reaction, reacting the resulting mixture at
about 30.degree. C. for 6 hours, and washing the resulting product with
ethanol to remove unreacted material.
The crosslinked hydrogel, upon equilibration in water, had a water content
of 11.6%, and, at 6.4 MHz, a T.sub.1 value of 730.+-.300 and a T.sub.2
value of 172.+-.105.
EXAMPLE 14
Using the methods of Example 6, buttons and spherical beads, respectively,
are prepared from a mixture of 50 parts methyl methacrylate, 50 parts
hydroxyethyl methacrylate, 0.5 parts ethylene glycol dimethacrylate, and
about 0.1 part benzoin methyl ether. The resulting crosslinked hyrogel
upon equilibration exhibits a water content of 13.9%, a T.sub.1 value of
300.+-.200 and a T.sub.2 value of about 64 at 6.4 MHz.
EXAMPLE 15
A siloxane macromer is prepared according to Example 8 of U.S. Pat. No.
4,136,250. A mixture of 30 parts of the siloxane macromer, consisting of
polydimethyl siloxane triol (Dow Corning 1248) having a molecular | | |
