AJR 2005; 185:257-264
© American Roentgen Ray Society
Urethral Bulking Agents: Imaging Review
Mellena D. Bridges1,
Steven P. Petrou2 and
Deborah J. Lightner3
1 Department of Radiology, Mayo Clinic Jacksonville, 4500 San Pablo Rd.,
Jacksonville, FL 32224.
2 Department of Urology, Mayo Clinic Jacksonville, Jacksonville, FL.
3 Department of Urology, Mayo Clinic, Rochester, MN.
Received October 2, 2004;
accepted after revision October 21, 2004.
Address correspondence to M. D. Bridges
(bridges.mellena{at}mayo.edu).
Abstract
OBJECTIVE. At imaging, injectable bulking materials used for urinary
incontinence have the potential to mimic urethral and periurethral pathology.
This article elucidates the appearance of the most commonly used agents in
multiple techniques and helps the practicing radiologist avoid potential
diagnostic pitfalls.
CONCLUSION. Carbon-coated microbeads (Durasphere) and cross-linked
bovine collagen (Contigen) have fairly characteristic imaging appearances and
can in most cases be differentiated from true pathology.
Introduction
Over the years, many materials have been used in attempts to provide
minimally invasive therapy for stress urinary incontinence. These include
polytetrafluoroethylene (Teflon, DuPont), silicone, autologous fat, purified
bovine dermal glutaraldehyde cross-linked collagen, and pyrolytic
carbon-coated zirconium oxide beads
[1]. Recent advances in
materials technology have produced new synthetic agents with acceptable safety
profiles and improved efficacy. Of these, cross-linked bovine collagen
(Contigen, Bard) and carbon-coated beads (Durasphere, Carbon Medical
Technologies) have rapidly become the most commonly used agents in the United
States. Recently, the Durasphere formulation was changed from a carbon to a
graphite coating with a smaller bead (Durasphere EXP), resulting in
alterations in imaging characteristics. As clinical use of these materials
continues to expand, the radiologist will be expected to recognize their image
features in multiple modalities, most important to avoid diagnostic pitfalls.
This pictorial essay illustrates the radiographic, CT, and MRI appearance of
collagen and the two Durasphere formulations.
Indications for Urethral Bulking Therapy
Traditionally, the primary indication for injectable therapy has been
urinary incontinence caused by urethral intrinsic sphincter deficiency,
although its use with symptomatic urethral hypermobility has been described
[2]. The bulking agent is
intended to increase periurethral volume and firmness and is administered
transurethrally or periurethrally. An effective injection coapts the urethral
mucosae, increasing resistance to urine loss with increase in abdominal
pressure.
In addition, although urinary incontinence is much more prevalent among
women, men who experience postprostatectomy urinary incontinence also have
been treated with periurethral bulking agents
[3].
Injection Technique
Under the appropriate anesthesia, the patient is placed in the dorsal
lithotomy position and routine cystourethroscopy is performed. Next,
submucosal injection of the agent is done with a dedicated injection needle
using a transurethral or periurethral approach based on surgeon preference.
Multiple sites can be injected to optimize therapeutic efficacy (Figs.
1A,
1B, and
1C).
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Fig. 1B —Series of fluoroscopic spot radiographs of pelvis obtained
during course of urethral bulking procedure. Image obtained during injection
shows accumulation of radiodense material (Durasphere, Carbon Medical
Technologies) around lower urethra and to right of upper urethra
(arrows). Notice urethral catheter with its retention balloon and
opacification of bladder.
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Fig. 1C —Series of fluoroscopic spot radiographs of pelvis obtained
during course of urethral bulking procedure. Postprocedure image with bulking
material that is now also to left of upper urethra, near bladder base. Note
small foci of venous or lymphatic intravasation (arrows).
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Imaging Findings
Cross-Linked Bovine Collagen
Reported outcomes for collagen therapy vary, with symptomatic improvement
in 17-94% of cases [4]. More
than one injection treatment session often is required to achieve satisfactory
primary results, and because bovine collagen is biodegraded and resorbed over
time, incontinence may recur within 2 years. The primary potential side effect
of this agent is local tissue hypersensitivity.
Because the density of collagen is in the soft-tissue range (Figs.
2A,
2B, and
2C), it is poorly detectable on
conventional radiography. In addition, collagen is avascular; thus, its CT
appearance will vary depending on the relative density of the adjacent tissues
[5], becoming more discernible
as the periurethral tissues enhance (Figs.
3A,
3B, and
3C).
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Fig. 2A —Comparative CT densities of bulking agents in vitro. Scout
image from CT shows three syringes containing, from left to right, new
Durasphere (Carbot Medical Technologies) formulation (arrowhead),
collagen (asterisk), and old Durasphere formulation
(arrow).
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Fig. 2C —Comparative CT densities of bulking agents in vitro. Axial CT
image of same three syringes using bone settings. Greater density of older
Durasphere formulation is more obvious on bone window settings.
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Fig. 3A —CT appearance in 68-year-old woman of periurethral collagen
injected approximately 6 months previously. Unenhanced axial CT image obtained
during triphasic examination of abdomen and pelvis. Collagen deposits are
difficult to discern.
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Fig. 3B —CT appearance in 68-year-old woman of periurethral collagen
injected approximately 6 months previously. Avascular collagen
(arrow) is more readily seen during arterial phase after
administration of contrast agent as adjacent tissues begin to enhance.
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MRI characteristics of collagen can be variable. Because the commercial
product consists of collagen suspended in an aqueous medium, its appearance
largely depends on the degree of water resorption and the level of degradation
of the collagen itself. When freshly injected, the collagen suspension is
T2-hyperintense, becoming isointense to hypointense with time on T1- and
T2-weighted images (Figs. 4A,
4B, and
4C).
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Fig. 4A —Variable MRI appearance of collagen. T2-weighted image shows
collection of hyperintense collagen (black arrow), which was recently
injected into a tissue phantom. Compare with signal intensity of cerebrospinal
fluid (CSF) (white arrow).
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Fig. 4B —Variable MRI appearance of collagen. Coronal T2-weighted
HASTE image in 72-year-old woman shows bulky urethra and elevated urethral
neck (arrow). Here, collagen is isointense with urethral tissue.
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Fig. 4C —Variable MRI appearance of collagen. Axial fat-suppressed
T2-weighted image in same patient. Relative signal intensity scale has shifted
so that periurethral collagen (arrows) is now hypointense to
urethra.
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Because of its poorly predictable appearance on T2-weighted images,
injected periurethral collagen can mimic true pathology. For example, in its
isointense guise, it can appear similar to a solid mass, such as a urethral
leiomyoma (Figs. 5A, and
5B). In this case,
gadolinium-enhanced T1-weighted images can clarify the collagen because the
injected material should not enhance (Figs.
6A,
6B,
6C, and
6D). In addition, when
T2-hyperintense, the material can be mistaken for a urethral diverticulum.
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Fig. 5A —MRI was requested to evaluate 63-year-old woman for urethral
diverticulum who had history of recurrent urinary tract infections and firm
urethral mass on physical examination. On postoperative histopathology, this
proved to be urethral leiomyoma. Axial T2-weighted turbo spin-echo image
through the level of urethra shows fairly homogeneous, isointense mass
(arrow), which displaces vagina posteriorly and is indistinguishable
from urethra.
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Fig. 5B —MRI was requested to evaluate 63-year-old woman for urethral
diverticulum who had history of recurrent urinary tract infections and firm
urethral mass on physical examination. On postoperative histopathology, this
proved to be urethral leiomyoma. Axial volumetric gradient-echo T1-weighted
image of mass (arrow) at same level obtained immediately after IV
administration of gadolinium. Faint, but unmistakable enhancement proves this
is neither bulking agent nor urethral diverticulum. Compare with
Figure 6D.
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Fig. 6A —MRI of 74-year-old woman with history of urethral collagen
injection 4 years previously for urinary incontinence. Physical examination
revealed small, firm urethral mass, and MRI was requested to exclude urethral
neoplasm. Axial T2-weighted turbo spin-echo image shows symmetric enlargement
of urethra (arrow). Signal intensity is isointense to other perineal
soft tissues, with mild heterogeneity.
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Fig. 6B —MRI of 74-year-old woman with history of urethral collagen
injection 4 years previously for urinary incontinence. Physical examination
revealed small, firm urethral mass, and MRI was requested to exclude urethral
neoplasm. Axial image at same level from fat-suppressed volumetric
gradient-echo T1-weighted (VIBE) sequence shows isointense enlargement of
urethra (arrow).
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Fig. 6C —MRI of 74-year-old woman with history of urethral collagen
injection 4 years previously for urinary incontinence. Physical examination
revealed small, firm urethral mass, and MRI was requested to exclude urethral
neoplasm. Coronal HASTE image shows to better advantage smooth enlargement of
urethra (arrow) and its isointensity.
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Fig. 6D —MRI of 74-year-old woman with history of urethral collagen
injection 4 years previously for urinary incontinence. Physical examination
revealed small, firm urethral mass, and MRI was requested to exclude urethral
neoplasm. Gadolinium-enhanced axial VIBE image clearly shows bilateral,
nonenhancing pockets of collagen flanking urethral mucosa (arrow).
Note signal intensity of unenhanced images excludes possibility of urethral
diverticulum, which also would fail to enhance.
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Carbon-Coated Microbeads
The Durasphere injectable agent has been approved for therapy of urinary
incontinence in the United States since 1999. In early trials, some
improvement was noted in 80% of cases
[6]. The material also may have
less immunogenic potential than does collagen.
With CT density measurements ranging between 1,500 and 2,000 H, the
microbead agent appears at least as dense as cortical bone on both radiography
and CT, whether in vitro (Figs.
2A,
2B, and
2C) or in vivo (Figs.
7,
8A,
8B, and
8C). As a consequence, the
material may be mistaken for deposits of calcium or even metal. In addition,
local beam hardening and aliasing artifacts can interfere with optimal
visualization of the immediately adjacent tissue. Use of window-level settings
appropriate for bone allows for better delineation of the individual injection
sites. An appreciation for the volume of the injection can be improved with
coronal reconstructions (Fig.
8C).
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Fig. 7 —Pelvic radiograph in 81-year-old woman several months after
Durasphere (Carbon Medical Technologies) injection. Note very dense
periurethral collections and small streaks of material in vicinity,
representing intravasation (arrows).
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Fig. 8A. —43-year-old woman with severe urinary incontinence after
pelvic trauma. Axial images from CT urography examination. Four Durasphere
(Carbon Medical Technologies) administrations during previous year failed to
relieve symptoms. Durasphere therapy represented as clump of extremely dense
periurethral material. Note aliasing and beam-hardening artifact in the
vicinity (arrows). Density measurements averaged 1,800 H.
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Fig. 8B. —43-year-old woman with severe urinary incontinence after
pelvic trauma. Axial images from CT urography examination. Four Durasphere
(Carbon Medical Technologies) administrations during previous year failed to
relieve symptoms. Bone window settings provide more accurate depiction of
actual extent of material.
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Fig. 8C. —43-year-old woman with severe urinary incontinence after
pelvic trauma. Axial images from CT urography examination. Four Durasphere
(Carbon Medical Technologies) administrations during previous year failed to
relieve symptoms. Oblique coronal maximum-intensity-projection reconstruction
image shows vertical extent of material and clearly shows bilateral
intravasation into pelvic vessels (arrows).
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Although attention is given to minimizing injection pressure during the
procedure, the viscosity of the agent and the need to apply sufficient force
to be therapeutic often lead to a degree of intravasation or extravasation
into adjacent tissues. This is easily appreciated both fluoroscopically and on
CT (Figs. 7,
8A,
8B, and
8C).
On MRI, Durasphere consistently appears quite hypointense on T1- and
T2-weighted images (Figs. 9A,
9B, and
9C). Also, as expected, the
material fails to enhance after gadolinium administration
(Fig. 10). Given these
characteristics, misdiagnosis should not be an issue.
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Fig. 9A —MRI of pelvis of 58-year-old woman to evaluate pelvic floor
dysfunction. Durasphere (Carbon Medical Technologies) injection is represented
on T2-weighted turbo spin-echo (TSE) axial image by a small, extremely
hypointense focus (arrow) in the muscular wall of urethra. Rectal
tube (arrowhead) had been placed to facilitate injection of rectal
gel.
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Fig. 9B —MRI of pelvis of 58-year-old woman to evaluate pelvic floor
dysfunction. Fat-suppressed T2-weighted TSE image at same level. Note how
change in signal intensity range increases conspicuity of injected material
(arrow).
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Fig. 9C —MRI of pelvis of 58-year-old woman to evaluate pelvic floor
dysfunction. Coronal single-shot T2-weighted image shows bulked-up,
low-signal-intensity urethra bulging upward into bladder base
(arrow).
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Fig. 10 —Axial gadolinium-enhanced volumetric gradient-echo
T1-weighted image in 77-year-old woman clearly shows periurethral pocket of
nonenhancing microbead bulking material (arrow) adjacent to and
slightly displacing urethra (arrowhead).
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Graphite-Coated Microbeads
The recent reformulation of Durasphere, with its smaller particles and new
graphite coating, was designed to improve ease of administration. Because the
new material, like the old, lacks mobile protons, its MRI appearance has not
changed. On the other hand, its density is significantly less, leading to a
change in radiographic and CT scan behavior (Figs.
2A,
2B, and
2C). Although occult on
conventional radiography, it is obvious on CT scan because its density is
approximately that of medullary bone (Figs.
11A,
11B, and
11C). The diminished density
results in a reduction of the beam-hardening and aliasing artifacts associated
with the carbon-coated material.
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Fig. 11A —54-year-old woman with stress urinary incontinence treated
with periurethral injection of new Durasphere (Carbon Medical Technologies)
formulation. Because of its diminished density, new agent is indiscernible on
conventional pelvic radiography.
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Fig. 11B —54-year-old woman with stress urinary incontinence treated
with periurethral injection of new Durasphere (Carbon Medical Technologies)
formulation. Axial image from CT scan obtained same day clearly shows
Durasphere (arrow) as hyperdense periurethral collection. Material
extends into, or immediately adjacent to, wall of left bladder base,
suggesting overzealous injection technique. Note reduced beam-hardening
artifact compared with artifact in Fig.
8A.
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Fig. 11C —54-year-old woman with stress urinary incontinence treated
with periurethral injection of new Durasphere (Carbon Medical Technologies)
formulation. Same CT slice displayed at bone settings. Injected material
(arrow) appears to be approximately same density as medullary bone.
Compare with Fig. 8B.
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Abstract
Introduction
