Key words breast - sonography - mammary gland tumor
Schlüsselwörter Mamma - Mammakarzinom - Ultraschall - Brustdrüsentumor
Introduction
Breast cancer is the most common cancer among women in all industrialized countries.
Screening mammography can detect cancer at an early stage and help to initiate immediate
treatment; however, the sensitivity of digital mammography for detecting breast cancer
is strongly dependent on breast density and declines to 48% for patients with the
densest breasts [1 ]. This group of patients requires individual clarification since it is known that
a dense breast is an independent risk factor for breast cancer [2 ], [3 ], [4 ].
B-mode ultrasound is not influenced by breast density, is commonly available, and
has the advantage of not exposing the patient to radiation. Furthermore, supplemental
breast ultrasound as an adjunct to mammography helps to increase the cancer detection
rate by 5.3 per 1000 women [5 ], [6 ]. However, performing a handheld ultrasound (HHUS) of both breasts, including history
taking and clinical examination, takes approximately 20 – 30 minutes and the physician
must be present continuously. Automated breast ultrasound (ABUS) systems seem to be
promising tools for overcoming the time-consuming process of HHUS whilst also possessing
the same benefits that B-mode imaging has in the diagnosis of breast lesions in dense
breasts. The first ABUS system was introduced almost 50 years ago [7 ], and several manufacturers have developed devices where patients are examined in
the supine position [8 ], [9 ], [10 ]. The examination box of the ultrasound device, which contains the approximately
10-cm wide ultrasound probe, is positioned on the breast and automatically moves in
one direction. The ultrasound probe is attached to the breasts via a flexible membrane
on the underside of the examination box and easily adapts to the breast contour. The
scanned raw data is subsequently reconstructed in a workstation to a 3D dataset, which
allows analysis of the breast in all planes, in a manner similar to tomography.
Although it achieves a fairly high sensitivity, one major problem of the ABUS is the
reported high recall rate due to artifacts or incomplete breast imaging, which results
in reduced specificity [11 ]. In HHUS, an artifact can often be easily distinguished from a suspicious lesion
by changes in the contact pressure of the ultrasound probe on the skin or by changes
in the angle of the probe.
This pilot study used the newly introduced ABUS system, named SOFIA, where patients
lie in the prone position during the examination. The idea of using the prone position
is not new as the first system named Octoson was introduced more than 40 years ago
[12 ]. In that first setting using the Octoson the breast was positioned in a water tank
without any compression and eight ultrasound scanners were used to generate an ultrasound
image. However, the diagnostic approach of the newly developed SOFIA system is different.
Here, the breast is not positioned in a water tank, but is compressed by the patientʼs
body weight, which forces the breast against the surface of the SOFIA bed. The rationale
behind this examination position is that the breast is flattened by contact with the
lying surface and the resulting compression of the tissue allows a more homogeneous
ultrasound echo frequency pattern than in the supine position. The exact positioning
of the patient is explained in detail in the Material and Methods section.
To the best of the authorsʼ knowledge, this is the first study to focus on the use
of this new SOFIA device. The aims of this pilot study were to check whether the new
ABUS system could recognize all lesions that could be seen in HHUS and to communicate
the initial experiences for the examination procedure and the possible limitations
of this imaging method.
Materials and Methods
This prospective pilot study was conducted according to the protocol of the latest
World Medical Association Declaration of Helsinki Ethical Principles for Medical Research
Involving Human Subjects and was approved by the local ethics committee.
Patient cohort
The study recruited 63 patients with a mean age of 57.95 years (range: 35 – 81 years)
who attended the outpatient service from May 2016 to June 2016. All patients were
scheduled for a conventional B-mode ultrasound at the breast center for special diagnostic
queries such as palpable lumps, ultrasound imaging in high-risk situations, suspected
cancer, or benign lesions. B-mode ultrasound was initially performed as planned, and
the image was classified according to the American College of Radiology Breast Imaging
Reporting and Data System (BI-RADS) [13 ]. The patient was positioned in the supine position for HHUS. All grayscale ultrasound
examinations were performed by examiner one (F. S.), who had over 15 years of experience
in breast ultrasounds, using the Philips EPIQ 7 ultrasound device equipped with the
L12-5 transducer (range: 5 – 12 MHz) (Philips Medical Systems DMC GmbH, Hamburg, Germany).
All B-mode pictures were digitally stored. The patient was asked to participate in
the pilot study if the final HHUS assessment revealed an unambiguously benign lesion
(BI-RADS 2), a malignant lesion (BI-RADS 5), or no lesion (BI-RADS 1). In this study,
the final BI-RADS category assessed by the B-mode ultrasound was used as the gold
standard to which the diagnostic accuracy of the new ABUS system was compared.
SOFIA examination procedure
The SOFIA scan was performed after written informed consent was obtained. All SOFIA
images were acquired using the Hitachi automated whole breast ultrasound system with
a 92 mm high-resolution ultrasound probe and a frequency of 5 – 10 MHz (Hitachi Medical
Systems GmbH, Wiesbaden, Germany). This device consists of three different parts,
the first of which is the SOFIA bed ([Fig. 1 ]) on which the patient lies in the prone position. The bed has a small recess in
which the ultrasound probe is located ([Fig. 2 ]). The probe is sealed by a layer of glass on which the ultrasound gel is applied.
The patient is positioned in such a way that the breast comes to rest in the recess.
The breast flattens out as it touches the glass with the applied ultrasound gel. The
SOFIA bed with the integrated 92 mm ultrasound probe is connected to the ultrasound
device Noblus (Hitachi Medical Systems GmbH), which works as a transient raw data
storage device. The automated breast scan is started using a touch screen located
on the SOFIA bed when the patient is positioned correctly with the nipple in the center
of the ultrasound area.
Fig. 1 SOFIA bed. The SOFIA bed with a recess at the top end. The ultrasound device, Noblus,
functions as an intermediate raw data storage and is positioned on the right side
of the bed.
Fig. 2 Ultrasound scanning area. Magnification of the ultrasound recess in the SOFIA bed
in which the breast is positioned in. The nipple should be placed in the center of
the recess so that the breast is evenly distributed in the field of view of the ultrasound
probe (white arrow) during the scanning procedure.
The ultrasound probe moves in a clockwise direction in a circular motion until a full
360° scan of the breast is completed. The reason for the circular scanning technique
is the possibility to scan the entire breast with only one scan and thus save time.
We would like to emphasize that the aim of this approach is not to enable ductal echography.
A scan of one breast takes 35 seconds. The trapezoid linear probe extends the field
of view to more than 10 cm, and it can scan breast tissue up to a depth of 6 cm. As
with conventional probes, there are additional features, such as HI Definition Tissue
Harmonic Imaging and HI Compound Imaging, implemented into the system to improve the
SOFIA image quality. After the scan is finished, raw data from the ultrasound device
is sent to the SOFIA workstation, which consists of a personal computer with a hard
drive and a software solution which enables the examiner to view the 3D reconstructed
images in all planes (e.g. sagittal, transversal, coronal, and radial) and make measurements.
The steps from patient positioning and data acquisition to data transfer were carried
out by medical assistants and a physician did not need to be present during this procedure.
Image evaluation
All data sent to the workstation were digitally stored and evaluated by examiner two
(A. F.) who had 13 years of experience in breast ultrasound. Examiner two had no information
on the history of the patient and was only aware that BI-RADS 1, 2, and 5 findings
were included in the study while BI-RADS 3 and 4 lesions were not. Examiner two had
software tools that enabled them to scroll through the reconstructed 3D picture of
the breast, change the angle or plane of the scan, and perform measurements. The standard
procedure in this study was to scan the coronal plane from the skin to the chest wall.
When a suspicious region was seen in the coronal plane, the axial and sagittal planes
were used to confirm a lesion in at least two planes. Finally, examiner two decided
the BI-RADS category for the SOFIA image. The examiner knew that there were no BI-RADS 0,
3, and 4 lesions in this study, therefore they were only allowed to use BI-RADS 1,
2, and 5 for categorization. If the examiner asked for a second-look HHUS due to ambiguous
findings or possible suspicious artifacts, this was rated as BI-RADS 0. If a second-look
HHUS was requested for a scan without a proven lesion, the SOFIA reading was rated
as false positive. Conversely, if a second-look HHUS was requested for an actual malignant
lesion, the SOFIA reading was rated as true positive.
Statistical analysis
The descriptive statistics were initially calculated for the acquired data. The sensitivity,
specificity, and accuracy with the respective 95% confidence intervals were subsequently
analyzed. Finally, the interobserver agreement between the rating of examiner one
using HHUS and examiner two using SOFIA was calculated using Cohenʼs kappa. According
to Landis and Koch, κ values of 0.81 – 1 were regarded as almost perfect agreement,
0.61 – 0.80 as substantial, 0.41 – 0.60 as moderate, 0.21 – 0.40 as fair, 0.00 – 0.20
as slight, and < 0 as no agreement.
SPSS (V 14.0, SPSS, Inc, Chicago, IL) statistical software was used for all calculation,
and p < 0.05 was regarded as statistically significant.
Results
The experimental setting using the SOFIA system reached a sensitivity of 100% (95%
CI: 83.89 – 100%), a specificity of 83.33% (95% CI: 68.64 – 98.03%), and a diagnostic
accuracy of 88.89% ([Table 1 ]).
Table 1 Sensitivity, specificity, and accuracy of the respective imaging method.
SOFIA
95% CI
CI: confidence interval
Sensitivity
100%
83.89 – 100%
Specificity
83,33%
68,64 – 98.03%
Accuracy
88,89%
78.44 – 95.41%
Distribution of BI-RADS categories for HHUS and SOFIA
[Table 2 ] shows the distribution of the BI-RADS rating of a lesion using HHUS and SOFIA. Using
HHUS as the gold standard for analyzing breast lesions, there were 22 BI-RADS 1 lesions,
20 BI-RADS 2 lesions, and 21 BI-RADS 5 lesions. For the 41 BI-RADS 2 and 5 lesions,
the lesion size was measured with HHUS and a mean lesion size of 17.98 mm (range:
5 – 48 mm; SD: 10.92) was reported. All 21 tumors rated as BI-RADS 5 by HHUS were
detected with SOFIA. In 14 cases, the primary assessment as BI-RADS 5 by HHUS was
the same as with SOFIA. In 7 cases, the examination by SOFIA was rated as BI-RADS 0,
therefore a second-look ultrasound assessment was induced and none of the lesions
were missed. In two of these cases, the recall was explained by shadowing artifacts
which did not allow a final assessment. The remaining five cases were suspicious and
examiner two was not able to make a final assessment as to the BI-RADS category by
the SOFIA images provided. Therefore the examiner requested a second-look ultrasound
in these five cases.
Table 2 Distribution of BI-RADS categorization for the respective imaging method (n). Recall
rate for a second-look HHUS (%).
HHUS
BI-RADS 1
BI-RADS 2
BI-RADS 5
Total (n)
SOFIA
BI-RADS 1
19
4
0
23
BI-RADS 2
0
12
0
12
BI-RADS 5
0
0
14
14
BI-RADS 0
3
4
7
14
Total (n)
22
20
21
63
Recall rate
13.64%
20.00%
100.00%
Of the 20 BI-RADS 2 lesions, 12 were correctly rated as BI-RADS 2 using SOFIA; however,
four lesions were rated as BI-RADS 1 meaning that these four benign lesions were not
detected by SOFIA. The remaining four BI-RADS 2 lesions were rated as BI-RADS 0 by
SOFIA and resulted in unnecessary second-look ultrasounds. Artifacts were identified
in two cases which prevented a final assessment, and incomplete images of the breast
were produced in another two cases. Both incomplete images were acquired from a D-cup
breast.
SOFIA correctly classified 19 of the 22 breast scans rated as BI-RADS 1; however,
three BI-RADS 1 scans in which no lesion was detectable were rated as BI-RADS 0, one
because of artifacts and two because of incomplete breast images. Again, these two
incomplete images were acquired from D-cup breasts.
Recall rate
In summary, in addition to the 21 second-look ultrasounds requested by SOFIA for the
BI-RADS 5 lesions, an additional seven lesions were rated as false positive and therefore
resulted in an unnecessary second-look ultrasound. This equaled 13.64% of second-look
ultrasound requests for BI-RADS 1 lesions where no lesion was present and 20.00% of
second-look ultrasound requests for BI-RADS 2 lesions. In total, an additional recall
rate of 16.67% was noted for SOFIA.
Interobserver agreement
The Cohenʼs kappa value was calculated to estimate the interobserver agreement. Examiner
one performed HHUS and had access to clinical history and clinical examination as
additional information. Examiner two had the SOFIA scans and the age of the patients
but did not have any additional information. The Cohenʼs kappa value (κ) = 0.769,
indicating substantial agreement between examiner one and two.
Examination procedure
The examination duration was measured for all cases. The mean duration for HHUS was
24.21 minutes (range: 14 – 32 minutes; SD: 3.96), which included the clinical examination,
the whole breast HHUS, and the final assessment of the images. The examination duration
for SOFIA included the whole breast ultrasound, image evaluation, and the final assessment.
Clinical examination was not part of the SOFIA procedure as the physician did not
see the patient but only analyzed the 3D volume data on the workstation. The mean
duration of the SOFIA examination was 12.94 minutes (range: 8 – 19 minutes; SD: 2.16),
which amounted to 53.45% of the duration of the HHUS. The SOFIA image acquisition
time, beginning with getting the patient ready for positioning and acquiring the scans
of both breasts but not including the evaluation of the images, had a mean duration
of 3.84 minutes (range: 2 – 10 minutes; SD: 1.67). For D-cup breasts, it was difficult
to position the breast centrally in the scanning area. Four times this resulted in
not all the breast tissue being scanned and therefore a final assessment was not possible.
Discussion
Modern ABUS systems from several manufacturers have emerged on the market in the last
10 years. They have numerous areas of application, such as monitoring the response
to chemotherapy or preoperative planning of the resection volume using the coronal
plane as the so-called surgical view [14 ], [15 ]. However, one main topic is the use of ABUS devices as an adjunct to mammography
in very dense breasts. Mammography is known to have a diagnostic gap and decreased
sensitivity for very dense breasts and thus cancers may not be recognized [1 ]. Recently published studies have highlighted the ability of this method to detect
additional cancers in very dense breasts. A study evaluating 1668 asymptomatic women
with dense breasts found an additional 2.4 cancers per 1000 women when using ABUS
in addition to mammography [16 ]. The study showed that an increase in sensitivity of up to 36.4% in this setting
is possible in comparison to mammography alone; however, an increase in the recall
rate for a second-look ultrasound due to artifacts or incomplete imaging has to be
taken into account, thus resulting in a decrease in specificity [17 ].
Most ABUS devices on the market are supine-type scanners. The scanner is positioned
on the breast with a soft pad assuring good contact with the skin. A large ultrasound
probe then moves in one direction to scan the breast. All raw images are transferred
to a workstation where the 3D dataset is reconstructed for analysis in all planes.
However, this poses a problem for larger breasts as the ultrasound probe has to be
repositioned three or four times to get a full scan of the entire breast [18 ] and this process is time-consuming.
The newly introduced ABUS device, SOFIA, uses a different approach. The patient lies
on the SOFIA bed in the prone position and the breast rests in a small recess. The
prone position ensures good contact with the glass layer directly above the ultrasound
probe due to the compression caused by the patientʼs body weight. This results in
evenly-flattened breast tissue and causes homogenous echogenicity. Furthermore, one
entire scan of the breast takes 35 seconds and the patient does not have to adjust
their position nor does the ultrasound have to be realigned. This results in a mean
examination duration of 3.84 minutes, which is shorter than that of supine ABUS systems
[19 ].
In this experimental setting, in which HHUS was used as the gold standard to which
SOFIA was compared, no cancer was overlooked. This resulted in a sensitivity of 100%;
however, it should be noted that two of the BI-RADS 5 lesions were recalled for a
second-look ultrasound, not because a suspicious lesion was seen on the SOFIA 3D images
but because of artifacts that did not allow a final assessment. The overall specificity
reached 83.33%. In a similar study design for a preliminary study on a supine ABUS
system, the specificity reached 52.8% [11 ]. The higher specificity in the current study was attributed to the fact that the
coupling of the breast tissue to the glass surface in front of the ultrasound probe
appears more even and the breast tissue flattens due to the weight of the patient
lying in the prone position. Therefore this method generated fewer artifacts, which
normally make images harder to interpret. As mentioned earlier, one limitation of
this system is the size of the breast. We noticed that D-cup sized breasts were difficult
to position correctly in the ultrasound area due to the size of the breast exceeding
the scanning area ([Fig. 3 ]). This problem occurred four times throughout the study and resulted in an incomplete
assessment and a request for a second-look HHUS. Furthermore, a limitation that all
ABUS devices have in common is their inability to assess unclear structures by changing
the amount of applied pressure, changing the angle of the ultrasound probe, or using
Doppler or elasticity imaging to differentiate lesions from artifacts. [Fig. 4 ] shows a SOFIA scan from a breast with two lesions that was rated BI-RADS 0; however,
in a conventional B-mode ultrasound these potential lesions were dissolved immediately
when the amount of pressure was increased and the angle of the probe was altered.
The images provided ([Figs. 3 ] and [4 ]) indicate pitfalls of this new method that have to be addressed. On the other hand,
none of the malignant lesions was overlooked.
Fig. 3 Incomplete scan of a D-cup sized breast. A 3D image of a D-cup sized breast. Arrow
1: The shadowing artifact because of the space in between the right and left breast.
Arrow 2: The right breast is displayed approximately 75%. Arrow 3: The left breast
is displayed accidentally because the positioning of the breast was insufficient.
Fig. 4 False positive findings with SOFIA. Axial view of the breast with two suspicious
areas that lead to the request for a recall for a second-look ultrasound. The image
shows two hypoechoic lesions with indistinct margins and posterior shadowing (white
circles). In B-mode ultrasound, no lesions were found.
It was expected that reviewing the data using SOFIA would lead to a total recall of
21 cases, as there were 21 BI-RADS 5 lesions seen with HHUS. In this study, an additional
recall rate of 16.67% was noted for SOFIA. The situation would have been clarified
in the assessment; however, the waiting time until clarification would have generated
a psychological burden and uncertainty for the patient, which was avoidable.
Limitations
The study population was small and therefore does not represent the overall population.
Thus these initial findings should only be understood as a trend within a feasibility
study that must be further evaluated in larger prospective studies. Furthermore, the
circular scanning technique used by the SOFIA system reminds one of the ductal echography
approach. However, we noticed during this study that the complete imaging of a duct
is limited due to compression and angulation of the ducts which moves them out of
the scanning plane. This led to the evaluation protocol used in this study in which
we focused on the coronal plane and then adding the axial or sagittal plane in a second
step.
Conclusion
The new SOFIA device that places a patient in the prone position during the examination
did not miss any cancer in the preselected study population, and the specificity of
this method was higher than preliminary studies using an ABUS system where patients
were in the supine position. The examination time was approximately half as long as
for HHUS. Furthermore, once the patient was positioned for the scan, no readjustments
needed to be made. In addition, it took approximately 35 seconds for one scan to be
completed and the whole breast digitalized for further evaluation. However, problems
occur with larger breasts with a D cup as these exceed the ultrasound area, make it
hard to position the breast centrally, and result in an incomplete image of the breast.
One advantage of the prone position is that it results in good contact with the ultrasound
area and the subsequent flattening of the breast creates a homogeneous echo pattern
and makes it easier to analyze the images. Based on this feasibility study, it seems
reasonable and promising to prepare a larger prospective study that examines this
new method outside of a preselected patient population.
