Review Article
A Primer on Image-guided Radiation Therapy
for the Interventional Radiologist
Nishita Kothary, MD, Sonja Dieterich, PhD, DABR, John D. Louie, MD, Albert C. Koong, MD,
Lawrence Vincent Hofmann, MD, and Daniel Y. Sze, MD, PhD
The use of image-guided radiation therapy in thoracic and abdominal tumors is increasing. Herein, the authors review
the process of image-guided radiation therapy and describe techniques useful for optimal implantation of fiducial
markers.
J Vasc Interv Radiol 2009; 20:859 – 862
Abbreviation: DRR ⫽ digital deconstructed radiograph
IMAGE-GUIDED radiation therapy is
an emerging field integrating a highly
focused radiation therapy system with
two- and three-dimensional imaging
techniques to produce frameless spa-
tial registration, allowing for precise
localization and targeting of tumors.
Imaging guidance and the use of ra-
diographic landmarks eliminate the
need for rigid, stereotactic frame fixa-
tion. However, respiratory motion re-
mains a major source of error and un-
certainty for extracranial applications
of image-guided radiation therapy (1–
4). As image-guided radiation therapy
evolves into exploiting hypofraction-
ated courses of treatment by using
large doses of radiation per fraction,
the issue of precision becomes increas-
ingly more important to maximize
both treatment efficacy and safety. A
From the Departments of Interventional Radiology
(N.K., J.D.L., L.V.H., D.Y.S.) and Radiation Oncol-
ogy (S.D., A.C.K.), Stanford University Medical Cen-
ter, 300 Pasteur Dr, H3630, Stanford, CA 94305. Re-
ceived February 3, 2009; final revision received
March 24, 2009; accepted March 26, 2009. Address
correspondence to N.K.; E-mail: kothary@stanford.
edu
S.D. received an $8,000 research grant from Accuray,
Inc.
None of the authors have identified a conflict of
interest.
© SIR, 2009
DOI: 10.1016/j.jvir.2009.03.037
multitude of image-guided radiation
therapy systems are available, includ-
ing CyberKnife (Accuray, Sunnyvale,
California), Elekta XVI (Elekta, Stock-
holm, Sweden), and Novalis Tx (Var-
ian Medical Systems, Palo Alto, Cali-
fornia) among others. The following
paragraphs describe our experience
with one such system, the CyberKnife.
The CyberKnife uses orthogonal digi-
tal radiography (x-rays) and respirato-
ry-triggered software to track im-
planted fiducial markers in real time
(5,6). As image-guided radiation ther-
apy systems become more widely
available, interventionalists will in-
creasingly participate in the care of
these patients, placing fiducial mark-
ers or combining image-guided radia-
tion therapy with other conventional,
percutaneous, or catheter-based thera-
pies such as ablation and transhepatic
arterial chemoembolization. A thor-
ough understanding of the physics
and applications of image-guided ra-
diation therapy is becoming essential
to providing appropriate patient care.
COMPONENTS OF THE
CYBERKNIFE SYSTEM
The CyberKnife is a commercially
available image-guided radiation ther-
apy system that combines image guid-
ance, tracking technology, and robotics
to offer frameless precision stereotactic
radiation therapy. It consists of a light-
weight, 6-MV, linear accelerator specifi-
cally designed for radiation therapy that
is mounted on a highly maneuverable
robotic arm capable of precise position-
ing and aiming of the linear accelerator
with a total radial error of less than 0.6
mm (7). Radiographic landmarks, ob-
tained by two fixed x-ray sources ar-
ranged orthogonal to the patient, elimi-
nate the need for skeletal fixation by
correcting for patient movement during
treatment. In addition, to compensate
for respiratory motion, the CyberKnife
uses a continuous respiratory tracking
system called the Synchrony (Accuray).
Adjustments for respiratory variations
are made by correlating the motion of
radiopaque fiducial markers implanted
in and around the tumor with chest or
abdominal wall excursions. The fiducial
markers act as internal radiographic
landmarks, ideally maintaining a fixed
relationship within the tumor and with
each other. The location of the fiducial
markers on the orthogonal digital recon-
structed radiographs (DRRs) obtained
during the treatment indirectly specifies
the spatial position of the tumor during
all phases of respiration. Differences in
the three translational directions and
three rotational angles (six-dimensional)
are measured by using computer algo-
rithms (8). On the basis of these calcu-
lations, the robotic manipulator com-
pensates for the differences and
retargets the radiation beam, hence
maintaining targeting accuracy. This
859
860 • Percutaneous Implantation of Fiducial Markers for Image-guided Radiation Therapy
complete process of image acquisition,
registration, and compensation is au-
tomated and fast enough to provide
real-time localization for extracranial
applications (5,9).
TECHNIQUE FOR
PERCUTANEOUS PLACEMENT
OF FIDUCIAL MARKERS
At our institution, most percutane-
ous fiducial marker implantations are
performed by using computed tomo-
graphic (CT) guidance in a manner sim-
ilar to that of percutaneous biopsies. In
some applications, fiduical markers can
also be placed under fluoroscopic, ultra-
sonographic (US), bronchoscopic, or en-
doscopic guidance. Procedures are per-
formed with the patient under moderate
sedation (intravenous midazolam and
fentanyl) administered by a registered
radiology nurse. A preliminary unen-
hanced CT scan is obtained and an ap-
propriate needle trajectory determined.
The skin entry site is prepared in a ster-
ile fashion and local anesthesia (lido-
caine 1%) administered. We routinely
use a 19-gauge thin-wall coaxial intro-
ducer needle (Allegiance; Cardinal
Health, Dublin, Ohio) to implant the fi-
ducial markers. The coaxial needle is
advanced into the lesion under CT flu-
oroscopy guidance in a standard fash-
ion. A vertical or semivertical trajectory
is preferred so that gravity can help
“drop” the fiducial markers. We use cy-
lindrical gold fiducial markers measur-
ing 0.8 mm in diameter and 5 mm in
length (Alpha-Omega Services, Bell-
flower, California) for tumors in solid
organs and 2 ⫻ 3-mm VortX 0.018-inch
diamond-shaped platinum microcoils
(Boston Scientific, Natick, Massachu-
setts) for tumors in lung, where solid
gold fiducial markers have been found
to migrate (10) .
Sterile gold fiducial markers are best
picked up from the tray by using a
small, curved hemostat and are placed
in the hub of the 19-gauge coaxial intro-
ducer needle. With use of the trocar of
the 19-gauge introducer needle, the fi-
ducial marker is advanced through the
shaft of the introducer needle. Occasion-
ally, the fiducial marker may get
“stuck” in the hub of the needle, ob-
scured by blood; hence, it is crucial to
verify the deposition of each fiducial
marker with imaging. Fluoroscopy of-
fers the ability to monitor advancement
and deposition of the fiducial marker in
Figure 1. Schematic diagram of the CyberKnife shows two x-ray sources angled at 45°
oblique to the patient with the flat-panel detectors placed under the patient table. The two
marks indicate collinear fiducial markers. In order for the CyberKnife system to recognize
individual fiducial markers, they should not be collinear when viewed from 45° oblique
angulation.
real time and, hence, may offer an ad-
vantage over CT for tumors that are eas-
ily visible with fluoroscopy. When mi-
crocoils are used as fiducial markers, the
casing that houses the coil is placed
within the hub of the 19-gauge intro-
ducer needle and the coil is initially
pushed through the shaft of the intro-
ducer by using the coil pusher and then
the trocar. Alternatively, a smaller-
gauge needle, such as a 21-gauge coaxial
needle, can be used to allow for easy
deposition of the microcoils. Typically,
three to five fiducial markers are placed
(see below) by tilting and repositioning
the introducer needle to deposit the fi-
ducial markers in a non-collinear fash-
ion.
After all the fiducial markers are
placed, limited unenhanced CT is per-
formed to document the position of
the fiducial markers and evaluate for
immediate complications. Patients are
routinely monitored for 4 hours after
placement and then discharged home.
Because previous studies have shown
that gold fiducial markers can migrate
and settle for up to a week (11–13), we
allow a 1-week interval between the
placement of fiducial markers and
treatment-planning CT. In our past ex-
perience, migration of gold fiducial
markers was the most problematic for
thoracic tumors; since then we have
adopted the practice of placing micro-
coils because these appear to be rela-
July 2009 JVIR
tively more stable (14). To overcome
the problems of migration, alternative
methods of placement such as endo-
scopic US, electromagnetically navi-
gated bronchoscopy, and endovascu-
lar placement of fiducial markers have
been tried (15–17). In addition to gold
fiducial markers and microcoils, alter-
nate agents such as titanium clips (in
breast) have also been used; however,
experience with this is limited and
warrants further studies.
OPTIMAL PLACEMENT OF
FIDUCIAL MARKERS
To enable accurate detection of the
fiducial markers, the importance of
correct geometric positioning of the
markers cannot be overstated (18). The
orthogonal x-ray sources are mounted
on the ceiling while the imagers are
placed under the treatment table. The
orientation of the x-ray source is such
that the DRRs are obtained in the 45°
right and left posterior oblique views,
as demonstrated in Figure 1. Hence,
placement of the fiducial markers
should be such that no two markers lie
in the same line when viewed along
either of the 45° angles used for imag-
ing.
Typically, three to five fiducial
markers are implanted. Fewer then
three fiducial markers would result in
translational tracking only. For a full
Volume 20 Number 7 Kothary et al • 861

Figure 2. (a– d) Axial unenhanced CT

scans in a 60-year-old patient with a
large caudate mass with implanted fidu-
cial markers. (e) Corresponding DRR ob-
tained in the right posterior oblique angle
in the same patient at the time of treat-
ment. The images demonstrate four dis-
tinct well-placed fiducial markers (num-
bered 1– 4) that allow for a full six-di-
mensional translational and rotational
localization. A ⫽ anterior, Caud ⫽ caudal,
Cran ⫽ cranial, P ⫽ posterior.

Figure 3. (a,b) Axial unenhanced CT scans and (c) DRR in the left posterior oblique projection in a 55-year-old patient with
metachronous adenocarcinoma in the right and left lungs. Images demonstrate clustered fiducial markers (numbered 1– 4), with two
fiducial markers (numbered 3 and 4) in the same line, making the six-dimensional translational and rotational localization difficult.

six-dimensional translational and rota-
tional localization, at least three prop-
erly placed fiducial markers are need.
The fiducial markers should be placed
in a way that their movement corre-
sponds to the movement of the target.
Preferably all fiducial markers should
be placed within the tumor. In tumors
that are smaller than 2 cm, however,
this may obscure the tumor margins;
hence, one fiducial marker should be
placed within the tumor and the rest
along the perimeter of the tumor.
It is often inevitable that the final po-
sition of one or more fiducial markers is
not optimal; in these instances, we sug-
gest implanting additional fiducial
markers. Because fiducial markers can
cause artifacts and obscure adjacent
markers, adjacent markers should be
physically at least 1.5 cm (preferably 2
cm) apart and on the orthogonal views
should appear at least 1 cm apart. Given
these requirements, one possible algo-
rithm would be to imagine the tumor as
a tetrahedron and to place fiducial
markers in each corner. Another algo-
rithm would be to imagine a cube and
place two fiducial markers in the cranio-
caudal axes (one marker cranial and an-
other caudal) and the other two fiducial
markers in the anteroposterior axes (one
marker anterior and one marker poste-
862 • Percutaneous Implantation of Fiducial Markers for Image-guided Radiation Therapy
rior). Another placement algorithm
would be two fiducial markers in the
anterior-posterior axis (one marker an-
terior and another posterior) and two
fiducial markers to the left and right of
the midline such that none of the four
fiducial markers are collinear on the 45°
oblique views. If fluoroscopy is avail-
able at implantation, a simple technique
would be to rotate the C-arm 45° in both
right and left oblique views to visualize
where the fiducial markers would be
deposited before actually depositing
them. Patients with metallic hardware
need detailed planning because the
hardware can completely obscure the
fiducial markers. In such situations, not
only should the fiducial markers not be
in the same axial plane as the bulk of the
hardware (because the hardware will
cause substantial artifacts at CT) but
also the fiducial markers should not be
collinear with the hardware in the
oblique views. All fiducial markers
should be within 10 cm of each other to
accommodate for the field of view of the
imaging and targeting software.
Correlation of axial CT scans to DRRs
obtained at the time of CyberKnife use
is described in Figures 2 and 3. Axial
CT scans in Figure 2 demonstrate a
large caudate mass with implanted fi-
ducial markers. The DRR obtained in
the right posterior oblique in the same
patient a week later demonstrates four
distinct well-placed fiducial markers.
Conversely, the DRR in another pa-
tient (Fig 3) demonstrates the fiducial
markers clustered together. Two of the
fiducial markers are superimposed on
the same line and are hence indistin-
guishable.
In conclusion, the optimal placement
of fiducial markers for successful image-
guided radiation therapy can be chal-
lenging. A proper understanding of the
physics behind image-guided radiation
therapy and the methodology em-
ployed to visualize and target the tumor
is crucial to place the least number of
fiducial markers in the most beneficial
manner.
References
1. Ohara K, Okumura T, Akisada M, et al.
Irradiation synchronized with respira-
tion gate. Int J Radiat Oncol Biol Phys
1989; 17:853– 857.
2. Ross CS, Hussey DH, Pennington EC,
Stanford W, Doornbos JF. Analysis of
movement of intrathoracic neoplasms
using ultrafast computerized tomogra-
phy. Int J Radiat Oncol Biol Phys 1990;
18:671– 677.
3. Davies SC, Hill AL, Holmes RB, Halli-
well M, Jackson PC. Ultrasound quan-
titation of respiratory organ motion in
the upper abdomen. Br J Radiol 1994;
67:1096 –1102.
4. Bryan PJ, Custar S, Haaga JR, Balsara
V. Respiratory movement of the pan-
creas: an ultrasonic study. J Ultrasound
Med 1984; 3:317–320.
5. Adler JR Jr, Murphy MJ, Chang SD,
Hancock SL. Image-guided robotic
radiosurgery. Neurosurgery 1999; 44:
1299 –1306, discussion 1306 –1297.
6. Schweikard A, Shiomi H, Adler J.
Respiration tracking in radiosurgery.
Med Phys 2004; 31:2738 –2741.
7. Muacevic A, Staehler M, Drexler C,
Wowra B, Reiser M, Tonn JC. Technical
description, phantom accuracy, and clini-
cal feasibility for fiducial-free frameless re-
al-time image-guided spinal radiosurgery.
J Neurosurg Spine 2006; 5:303–312.
8. Fu D, Kuduvalli G. A fast, accurate,
and automatic 2D-3D image registra-
tion for image-guided cranial radiosur-
gery. Med Phys 2008; 35:2180 –2194.
9. Chang SD, Adler JR. Robotics and ra-
diosurgery: the cyberknife. Stereotact
Funct Neurosurg 2001; 76:204 –208.
10. Kothary N, Heit JJ, Louie JD, et al.
Safety and efficacy of percutaneous fi-
ducial marker implantation for image-
guided radiation therapy. J Vasc Interv
Radiol 2009; 20:235–239.
July 2009 JVIR
11. Imura M, Yamazaki K, Shirato H, et al.
Insertion and fixation of fiducial markers
for setup and tracking of lung tumors in
radiotherapy. Int J Radiat Oncol Biol
Phys 2005; 63:1442–1447.
12. Kitamura K, Shirato H, Shimizu S, et al.
Registration accuracy and possible mi-
gration of internal fiducial gold marker
implanted in prostate and liver treated
with real-time tumor-tracking radia-
tion therapy (RTRT). Radiother Oncol
2002; 62:275–281.
13. Shirato H, Harada T, Harabayashi T,
et al. Feasibility of insertion/implan-
tation of 2.0-mm-diameter gold inter-
nal fiducial markers for precise setup
and real-time tumor tracking in radio-
therapy. Int J Radiat Oncol Biol Phys
2003; 56:240 –247.
14. de Mey J, Van de Steene J, Vandenbro-
ucke F, et al. Percutaneous placement
of marking coils before stereotactic ra-
diation therapy of malignant lung le-
sions. J Vasc Interv Radiol 2005; 16:
51–56.
15. Pishvaian AC, Collins B, Gagnon G,
Ahlawat S, Haddad NG. EUS-guided
fiducial placement for CyberKnife ra-
diotherapy of mediastinal and abdom-
inal malignancies. Gastrointest Endosc
2006; 64:412– 417.
16. Anantham D, Feller-Kopman D, Shan-
mugham LN, et al. Electromagnetic
navigation bronchoscopy-guided fidu-
cial placement for robotic stereotactic
radiosurgery of lung tumors: a feasibil-
ity study. Chest 2007; 132:930 –935.
17. Prevost JB, Nuyttens JJ, Hoogeman
MS, Poll JJ, van Dijk LC, Pattynama
PM. Endovascular coils as lung tu-
mour markers in real-time tumour
tracking stereotactic radiotherapy: pre-
liminary results. Eur Radiol 2008; 18:
1569 –1576.
18. West JB, Fitzpatrick JM, Toms SA,
Maurer CR Jr, Maciunas RJ. Fiducial
point placement and the accuracy of
point-based, rigid body registration.
Neurosurgery 2001; 48:810 – 816, dis-
cussion 816 – 817.