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27 Magnetic Advances in Cancer Surgery
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469
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2013;22:321–8.
Ultrasound Fusion (SPECT/US)
https://t.me/med1917
Martin Freesmeyer and Thomas Winkens
2 8
Contents
28.1 Introduction 471
28.2 Technical Foundations 472
28.2.1 fhSPECT 472
28.2.2 Navigated US 472
28.2.3 Fusion Imaging: Examination Protocol 474
28.3 fhSPECT/US Fusion for Breast Cancer
and Melanoma SLN Examination 475
28.4 fhSPECT/US Fusion Imaging in
Thyroid Disease Diagnostics 476
28.5 Summary 478
References 479
Abstract
This chapter is about initial experiences regarding the feasibility and applicability of quasiintegrated freehand (fh) single-photon
emission computed tomography (SPECT)/
ultrasonography (US) fusion imaging in
patients undergoing sentinel lymph node
(SLN) imaging or in patients with thyroid disease. The principles of radioguided surgery
can be applied to this technology. The successful and emerging concept of hybrid imaging is
applied to US imaging, resulting in a tool that
combines the delivery of functional information (SLN, thyroid tissue) with excellent visualization of morphology. The medium-term
goal of fhSPECT/US fusion imaging is to
enhance diagnostic accuracy; however, further
improvements are necessary to overcome technical limitations regarding the quality of coregistration and fhSPECT resolution.
28.1 Introduction
M. Freesmeyer (*) • T. Winkens
Clinic of Nuclear Medicine, Jena University Hospital ,
Bachstraße 18 , Jena 07743 , Germany
martin.freesmeyer@med.uni-jena.de;
e-mail:
thomas.winkens@med.uni-jena.de
© Springer International Publishing Switzerland 2016
K. Herrmann et al. (eds.), Radioguided Surgery: Current Applications and Innovative
Directions in Clinical Practice, DOI 10.1007/978-3-319-26051-8_28
Radioguided surgery is a surgical methodology
which involves the administration of a radionuclide and the subsequent intraoperative identifi cation and surgical removal of resultant
radiolabeled structures. Radioguided surgery
involves the use of hand held gamma detection
probes, as well as may incorporate the use of
471
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M. Freesmeyer and T. Winkens
portable gamma cameras for optimizing intraoperative detection. Recently, it has become
possible not only to identify a radiolabeled
structure in the body during radioguided surgery, but also to perform intraoperative crosssectional imaging combined with visualization
and display of the radioactivity distribution on
a monitor screen – based on the freehand
SPECT (fhSPECT) system, as previously
described in the literature [ 1 – 4 ]. Therefore, the
incorporation of intraoperative cross-sectional
imaging (which can be performed in a multimodal approach) into the standard radioguided
surgery methodology can potentially provide
additional valuable intraoperative information
for optimizing the surgical outcome for patients.
This is the subject of the current chapter.
Multimodal cross-sectional diagnostics fusion
imaging has gained importance over the past
10 years [ 5 – 8 ]. The use of PET/CT and SPECT/
CT has spread rapidly as these hybrid techniques
offer advantages over separately undertaken
diagnostic procedures (e.g., PET and CT). The
benefi ts of PET/MR are currently being assessed
in clinical studies. In addition, technical prerequisites have been addressed with a view to integrating ultrasound (US) into hybrid imaging
strategies and enabling its combination with
existing cross-sectional image datasets (PET,
SPECT, CT, MR) [ 9 – 12 ]. This will permit the
advantages of US, in particular its superior soft
tissue contrast and high spatial resolution, to be
utilized in a hybrid imaging setting.
The technique of combining fhSPECT with US
has the potential to become an accurate and useful
method to improve preoperative surgical planning.
For example, in breast cancer, a sentinel lymph
node (SLN) can be accurately identifi ed prior to
axillary lymph node dissection after injecting a
specifi c radiopharmaceutical. The fhSPECT/US
fusion technique can then be used both to target
the appropriate radiolabeled lymph node and subsequently allow examination using US.
Furthermore, in addition to its preoperative
use, fhSPECT/US can exclusively be employed
in a diagnostic capacity to combine information
from any nuclear medicine imaging examination
with US data. This instantaneous combination of
data would be desirable especially for thyroid
diagnostics, as standard and separate diagnostic
examination with
99m
TcO 4 and thyroid US can
occasionally yield ambiguous results [ 13 ].
The medium-term goals of the fusion concept
presented in this chapter are, on the one hand, to
improve diagnostic accuracy and, on the other, to
optimize patient selection for therapeutic procedures and better plan interventions.
28.2 Technical Foundations
28.2.1 fhSPECT
Freehand SPECT is a three-dimensional crosssectional imaging technique that is based on measurement of the radioactivity distribution of a
radionuclide with a gamma detection probe [ 1 ].
After administration of a radiopharmaceutical, the
gamma detection probe, with its attached localization markers, is moved in different planes around
the examination region in a meandering fashion
(around the axilla in the case of a breast SLN
examination and around the neck in the case of a
thyroid examination) and measures the radiation
emitted (Fig. 28.1a–c ). Using a video camera and
an optical positioning system that are mounted
above the patient, the position of the gamma detection probe is registered, and the activity distribution is spatially allocated. In addition, the patient is
marked with localization markers (shared sensor)
to minimize the infl uence of patient movements on
registration accuracy (Fig.
28.1a ). After data
acquisition, a three-dimensional SPECT crosssectional image dataset is reconstructed in DICOM
format and subsequently displayed on a monitor
screen (Fig. 28.1c ).
28.2.2 Navigated US
Navigated US is based on the positioning of the
two-dimensional US images within a virtual
three-dimensional space. For this purpose, two
positioning markers are attached to the US probe,
which are detected using a magnetic fi eld generated by an electromagnetic transmitter next to the
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a
c
b
Fig. 28.1 ( a ) fhSPECT examination setup. The radiation
that is emitted from the body (here the thyroid gland) is
measured using a gamma detection probe ( blue arrow ).
The position of the gamma detection probe is recorded
with optical markers ( white spheres ) and an optical track-
ing system ( green ), which is mounted above the patient. In
addition, the patient is monitored with an optical tracker
( orange arrow ), to register and correct minor patient
movements and enable US data fusion in the second
examination step. The activity distribution is projected
onto a video image of the patient that is captured by a
camera ( gray circle ) mounted above the patient and is ini-
tially displayed on a screen. ( b ) Depiction of the gamma
detection probe. The gamma detection probe has three
optical markers attached at defi ned distances, which allow
precise spatial localization. ( c ) Video recording of an
fhSPECT examination of an SLN. The scanned region is
represented in color within a virtual space ( cube ). The
handheld gamma detection probe ( blue arrow ) traces
around the respective region (here the left axilla)
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M. Freesmeyer and T. Winkens
a
b
Fig. 28.2 ( a ) Setup of fhSPECT/US fusion imaging during
US examination. The position of the US probe within the
magnetic fi eld that is generated by the transmitter ( yellow ) is
detected using the attached markers ( red ). This enables iden-
tifi cation of the plane of the US image and superimposition
of it onto the previously recorded fhSPECT dataset. The
fhSPECT/US fusion images are displayed in nearly real time
on the screen of the US device, both in the semitransparent
overlay mode (screen left) and as the SPECT image on its
own (screen right). The optical tracker of the patient ( orange
arrow ) is equipped with an additional electromagnetic sensor
that allows detection within the magnetic fi eld. This tracker
is connected to the US device. When moving the US probe,
the movement can be traced in the US image as well as in the
fhSPECT dataset. ( b ) Freehand SPECT/US examination.
The image shows the US probe ( red arrow ) with two red
localization markers and the electromagnetic transmitter
( yellow arrow ). Nearly real-time visualization of fusion
imaging is depicted on the screen of the US device ( b : From
Freesmeyer et al. [
14 ]. Image Courtesy: Schattauer Verlag )
patient’s bed (Fig. 28.2a, b ) [ 15 ]. The allocation
of these markers allows the US image to be
mapped to a given plane within the virtual threedimensional space.
28.2.3 Fusion Imaging: Examination
Protocol
The fusion of fhSPECT and US is carried out via
a complex but manageable (within the clinical
routine) sequence of steps, as explained below.
1 . Acquisition of fhSPECT data
First, the activity distribution is measured, as
described above. It is important that the patient
does not move at this stage, if possible. To
reduce the infl uence of minor patient movements, the gamma detection probe and the
patient are marked with optical position markers, which allow unequivocal mapping of the
activity distribution in space, and the automatic
correction of data obtained during minor involuntary changes in patient position. To ensure
precise matching between the US (performed
later) and fhSPECT examination data, the
patient’s optical position marker for fhSPECT
is equipped with an additional electromagnetic
sensor that allows detection within the magnetic fi eld during the entire fhSPECT/US procedure (Fig. 28.1a , Fig. 28.2b ).
2 . Reconstruction of fhSPECT data
Data reconstruction is carried out with a modifi ed iterative algorithm (maximum likelihood
expectation maximization) for nonuniform
limited-angle projections and can be either
projected as a maximum intensity projection
onto a video image of the patient or visualized
as a three-dimensional cross- sectional dataset
in DICOM format (Fig.
3 . Transfer of fhSPECT data to the US
instrument
The fhSPECT dataset is transferred to the US
instrument using a USB stick. The subsequent
processing and fusion is carried out “online”
(live) on the US device.
4 . Image fusion on the US device
The fhSPECT dataset is opened on the US system and can be viewed on its computer screen.
As soon as the navigation software of the
instrument is turned on, the US image within
the electromagnetic fi eld is displayed simultaneously with the corresponding sectional plane
of the fhSPECT data in split- screen mode.
28.1c , Fig. 28.2a ) [ 1 ].
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The registration of both datasets is achieved
using the shared patient sensor, which serves
as a reference point for both examination
modes, as described above (Fig. 28.2a ). Apart
from the side-by-side display of both datasets
(split-screen mode), it is also possible to overlay both imaging modalities in a semitransparent fashion, which allows exact localization of
radiolabeled structures with the corresponding
anatomical correlates (Fig. 28.2a ). When the
US probe is moved within the electromagnetic
fi eld, a congruent shift of the fhSPECT image
occurs, which results in a “live” overlay of
fhSPECT and US data. Throughout the US,
examination of the corresponding sectional
plane of the fhSPECT is simultaneously
shown, making it possible to precisely overlay
activity distribution onto the anatomical
structure.
5 . Data storage
As with conventional US images, the splitscreen and overlay images can be saved as
screenshots and as such permanently archived.
In addition, it is possible to record moving
images as image stacks (loops) that allow subsequent inspection of the entire region captured by fhSPECT/US.
28.3 fhSPECT/US Fusion
for Breast Cancer
and Melanoma SLN
Examination
Just as preoperative lymphoscintigraphy and portable intraoperative gamma cameras play an
important role in the identifi cation and removal
of SLNs, preoperative US plays an important role
in the diagnostics of breast cancer and melanoma
[ 16 , 17 ]. Preoperative diagnostic ultrasound is
useful in the identifi cation of anatomically abnormal lymph nodes within lymph node basins
draining the region of a tumour, thus signifying
possible metastatic lymph node involvement.
However, the information provided by preoperative lymphoscintigraphy and diagnostic US tends
to be separate and disconnected. On the one hand,
conventional diagnostic US examination can
only assess the morphology of all visible lymph
nodes; yet it cannot identify the exact SLN into
which the primary lymph drainage from the
tumor will occur. On the other hand, preoperative
lymphoscintigraphy can be used to identify the
SLNs with confi dence, but morphological assessment of those lymph nodes is not possible. Thus,
the combined information from both examination
methods would allow for targeted SLN-specifi c
sonographic characterization and would help
optimize the surgical management of the lymph
nodes.
We undertook a pilot study in our clinic to evaluate the feasibility and applicability of fhSPECT/
US fusion imaging in patients with breast cancer and melanoma [
SLNs were identifi ed through planar lymphoscintigraphy of the lymphatic- draining region.
Immediately afterward, an fhSPECT examination of the same region was carried out. Patients
with breast cancer who presented axillary SLNs
were examined in the lateral body position with
the arm elevated. Patients with melanoma were
examined in a position depending on the localization of the lymph-draining region, such that the
respective lymph nodes were easily accessible
for US examination. The subsequent fhSPECT
examination was carried out in accordance with
the previously described protocol (Fig. 28.3 ).
In this pilot study [ 14 ], the following points
were also considered: (1) the resolution and the
quality of the three-dimensional fhSPECT reconstruction, (2) the accuracy of the signal registration (did the focal accumulation in the fhSPECT
image correspond to a lymph node in the US
image?), (3) a thorough examination of criteria
for malignancy in the respective lymph node, and
(4) retrospective comparison of the US result
with the histological diagnosis.
All examinations in this pilot study [
technically successful. Artifacts that led to limited visualization of the SLN were observed in
approximately 33 % of cases. These were caused
by a superimposed injection site, insuffi cient resolution of two foci in close proximity, or central
void areas in the activity distribution within focal
maxima. In approximately 70 % of cases, we
observed a good correlation between the two
14 ]. Initially, one or more
14 ] were
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M. Freesmeyer and T. Winkens
abcde
Fig. 28.3 Example of an fhSPECT/US examination of an
SLN in a patient with malignant melanoma on the left
lower leg. ( a ) Planar scintigram after injection of 100 MBq
Nanocoll, showing the SLN and the respective draining
lymph vessel ( white arrow ). ( b ) The fhSPECT reconstruc-
tion and overlay with the video image of the patient shows
focal activity accumulation in the left inguinal region in
the projection. ( c – e ) fhSPECT/US fusion imaging with
datasets, with a spatial deviation of <1 cm.
According to US criteria, one lymph node in a
total of 18 patients was classifi ed as potentially
malignant. In total, lymph node metastases were
detected in 5/18 patients by histopathology.
However, these were not suspicious in the preoperative fhSPECT/US examination.
Thus, it can be concluded that for preoperative
SLN visualization, fhSPECT/US can be successfully
performed at a technical level and, with reasonable
organizational effort, can be integrated into the clinical routine. In individual cases, the concept might
also aid in preoperative planning. In this pilot study
[ 14 ], we performed the method in a small patient
group, but could not demonstrate its clinical benefi t.
There is further potential to optimize the registration accuracy of both imaging modalities.
Furthermore, additional steps are necessary to
improve the three-dimensional reconstruction
quality of fhSPECT data, as well as the spatial
resolution.
28.4 fhSPECT/US Fusion Imaging
in Thyroid Disease
Diagnostics
In addition to measuring thyroid hormones in
blood, US and thyroid scintigraphy play key roles
in thyroid diagnostics [ 18 ]. The radiopharmaceuti-
cal of choice is
via the sodium-iodide integral membrane protein
symporter. Following administration of the radio-
99m
TcO 4 , which enters thyroid cells
fhSPECT ( c ), semitransparent overlay of fhSPECT and
US (fhSPECT/US) ( d ), and US ( e ). A lymph node with no
signs of malignancy can be seen in the ultrasound image
at the location of highest activity ( white arrows ; e ). Both
datasets are almost exactly aligned and show no spatial
incongruence (From Freesmeyer et al. [
tesy: Schattauer Verlag )
14 ]. Image cour-
pharmaceutical, subsequent planar thyroid scintigraphy shows functional thyroid tissue. Due to
image capture using the summation technique,
abnormal regions that are completely surrounded
by normal tissue or those located at the organ
periphery may escape reliable detection. Likewise,
when several thyroid nodules in close proximity
are detected by US, it becomes diffi cult to match
them with the correct functional state. In particular, in the case of thyroid carcinomas that present
exclusively as hypofunctional tissue, accurate
matching between the functional state and morphology is essential for diagnosis (Fig. 28.4 ) [ 19 ].
The second component of thyroid diagnostics
in any patient with suspected thyroid disease is
US [ 18 ]. Special attention is paid to thyroid vol-
ume and the existence of thyroid nodules.
However, analogous to the preoperative US examination of the axillary lymph nodes in breast cancer, the information from radiopharmaceutical
imaging is missing. US alone cannot reveal
whether a thyroid nodule represents hypofunctional, normal, or hyperfunctional tissue. This distinction is essential to determine the subsequent
therapeutic approach. Hypoactive thyroid nodules
need to be monitored, punctured, or removed.
Thyroid nodules with normal tissue activity usually do not require therapeutic intervention,
whereas hyperfunctional thyroid nodules need
either radioiodine therapy or removal. In particular, when planning a fi ne-needle aspiration biopsy
of several thyroid nodules in close proximity, the
accurate allocation of functional state to morphol-
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a
477
b
c
d
e
Fig. 28.4 Example of US fusion imaging in a patient with
thyroid cancer. Small papillary thyroid cancer allocated laterally in the right thyroid lobe. Thyroid scintigraphy ( a )
does not show a clear focal abnormality, B-mode ultrasonography ( b , e ) revealed an irregular hypoechoic area ( red
arrows ), and color Doppler sonography ( c , f ) showed partial
hyperperfusion ( yellow arrows ) within a regular-size right
lobe (5 mL). The lesion consisted of two differently confi gured areas: ventrally, a hypoechoic part with a distinct mar-
ogy is essential for selection of the correct puncture sites.
The almost simultaneous performance of
fhSPECT and US examination assists in overcoming the uncertainties in correlating scintigraphic data with US information since it allows:
(1) three-dimensional visualization of the activity
distribution, (2) free of superimposition artifacts,
and (3) unambiguous colocalization with a specifi c anatomical structure as detected by US.
In the diagnostic thyroid imaging setting, a thyroid fhSPECT/US examination can be performed
99m
as based upon the same does of
TcO4 that is
given for the performance of the standard of care
recommendation for thyroid scintigraphy. Thus,
such a combined examination approach of standard thyroid scintigraphy and thyroid fhSPECT/
US examination adds no additional radiation exposure to the patient as compared to standard thyroid scintigraphy alone. Therefore, the fhSPECT
examination can be carried out immediately after
standard thyroid scintigraphy in planar imaging mode. The gamma detection probe is moved
around the patient’s neck in a meandering fashion
in order to capture the activity distribution in three
dimensions. The positioning of the gamma detection probe/camera is analogous to the technique
f
gin, and dorsally, a more hypoechoic, probably necrotic part
with an irregular margin. Magnetic sensor-navigated
PET/US fusion ( d , g ) confi rmed that the sonographic fi nd-
ing was clearly
(From Freesmeyer et al. [
lism in a very similar way as
124
I is superior to
resolution. 124I was chosen in this example to demonstrate
the usefulness of fusion imaging with ultrasound
124
I-negative (hypofunctional, blue arrows )
99m
TcO4 SPECT imaging regarding spatial
g
124
19 ]).
I depicts thyroid metabo-
99m
TcO4 does. As a PET-tracer,
124
I-
described for SLN visualization. A further important aspect of thyroid examination is the positioning of the patient. We have found it advantageous
to position the neck as freely as possible, in order to
be able to measure the radioactivity emitted from
the thyroid gland from as many angles and directions as possible. Analogous to the SLN fhSPECT/
US examination, the following steps are required:
acquisition of the raw data, reconstruction, data
transfer to the US device, and image fusion on the
screen of the US system (Fig.
28.5 ).
The fhSPECT/US examination of the thyroid
gland was evaluated in a proof-of-concept study
[ 20 ]. Its technical feasibility was demonstrated in
all the examinations carried out. The registration
accuracy was always <1 cm. However, artifacts
appeared in the thyroid fhSPECT that prevented
the correct assignment of the functional state to
the matching morphological correlate. In one case,
apparent radiotracer uptake outside the thyroid
tissue was observed; in another case, two focal
maxima were reconstructed even though planar
thyroid scintigraphy only showed one maximum.
Furthermore, the marginal areas of the thyroid
gland were sometimes insuffi ciently depicted.
In summary, we conclude that fhSPECT/US
examination of the thyroid gland is applicable
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M. Freesmeyer and T. Winkens
ab c
Fig. 28.5 Example of an fhSPECT/US examination of
the thyroid gland. ( a ) Planar thyroid scintigram depicting
an autonomous adenoma in the right thyroid lobe ( white
arrow ). The surrounding thyroid tissue is almost completely suppressed. (b) The fhSPECT reconstruction and
overlay with the video image of the patient shows focal
activity accumulation in the right neck region in the projection. ( c – e ) fhSPECT/US fusion imaging with fhSPECT,
and feasible. Moreover, it can be integrated with
moderate effort into the clinical routine. It is also
important to emphasize that patients are not
exposed to additional radiation.
28.5 Summary
Freehand SPECT/US is technically feasible and
easily executable. Our pilot studies have demonstrated the applicability of the method in small
groups of patients [ 14 , 20 ]. Proof of clinical bene-
fi t of the method is a topic for further needed studies that should, in particular, focus on its possible
role in clinical care and its potential contribution in
improving therapeutic decision-making.
The fact that the fhSPECT component of
fhSPECT/US is carried out immediately before the
US examination, within one examination session
and with the patient in the same position, signifi cantly reduces the negative infl uence that different
patient positioning in two separate examinations
has on registration accuracy. Therefore, fhSPECT/
US is a one-time, albeit sequential, examination
procedure comparable to hybrid imaging such as
SPECT/CT, PET/CT, and PET/MRI.
The fhSPECT/US method presented here fi ts in
with similar hybrid imaging approaches that
include US. Initially, CT and MRI datasets were
fused with US data for prostate and liver examinations [
15 , 21 – 24 ]. Later, PET data were added for
d
( c ) semitransparent overlay of fhSPECT and US
(fhSPECT/US) ( d ), and US ( e ). At the location of the
focal activity, there is a hypoechoic, partially cystic nodule with a halo, without signs of malignancy, which sonographically matches an adenoma. As can be seen in d , the
two datasets are almost exactly superimposed (From
Freesmeyer et al. [
Radiological Society of North America )
20 ]. Image courtesy: Radiology;
e
fusion imaging, a topic that has been described
extensively by Ewertsen et al. and has been further
evaluated by several subsequent studies related to
nuclear medicine [
10 , 25 – 28 ]. Galdames et al.
fused previously recorded and segmented DMSA
SPECT datasets of the kidney “offl ine” with separately collected US datasets on a dedicated workstation [ 11 ]. In a further development of this
approach, Bucki et al. fused SPECT with US datasets using optical markers that were attached to the
patient’s bed during both examinations [ 9 ]. This
concept already included “live” visualization of
both datasets on the screen of the US instrument.
However, the fhSPECT/US concept does have
several limitations that need to be taken into
account:
1 . Slight to moderate inaccuracy of data registra-
tion : Although fhSPECT and US are carried out
in immediate succession, some inaccuracies can
still occur due to minor patient movements.
This limitation is why fhSPECT/US imaging
can only be classifi ed as nearly real-time and
not simply as real-time. This effect can be
amplifi ed by the fact that the fhSPECT exami-
nation is carried out without direct skin contact,
while US examination requires gentle pressure
on the skin. This can lead to slight tissue dis-
placement in the axillary region (SLN) and in
the soft tissue in the neck region (thyroid gland),
which also contributes to the inaccuracies.
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