DOI:10.2214/AJR.07.2610
AJR 2008; 190:W234-W236
© American Roentgen Ray Society
Microcalcifications of Breast Tissue: Appearance on Synchrotron Radiation Imaging with 6-µm Resolution
Keiko Imamura1,
Norishige Ehara1,
Yoichi Inada2,
Yoshihide Kanemaki1,
Joji Okamoto3,
Ichiro Maeda4,
Keiko Miyamoto3,
Haruki Ogata3,
Hisanori Kawamoto3,
Yasuo Nakajima1,
Mamoru Fukuda3,
Keiji Umetani5 and
Kentarou Uesugi5
1 Department of Radiology, St. Marianna University School of Medicine, 2-16-1
Sugao, Miyamae-ward, Kawasaki, Kanagawa 216-8511, Japan.
2 Department of Physics, St. Marianna University School of Medicine, Kawasaki,
Japan.
3 Department of Breast Surgery, St. Marianna University School of Medicine,
Kawasaki, Japan.
4 Department of Pathology, St. Marianna University School of Medicine, Kawasaki,
Japan.
5 Japan Synchrotron Radiation Research Institute, Kouto, Hyogo 679-5198,
Japan.
Received May 11, 2007;
accepted after revision November 9, 2007.
Address correspondence to K. Imamura
(keiko401{at}marianna-u.ac.jp).
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Abstract
OBJECTIVE. The purpose of this study was to use synchrotron
radiation imaging with 6-µm resolution to evaluate amorphous and
pleomorphic breast tissue microcalcifications.
CONCLUSION. Synchrotron radiation imaging depicted
microcalcifications as small as 24 µm. Imaging with this technique revealed
that most amorphous and pleomorphic calcifications on conventional mammograms
are clusters of fine specks and that in addition to the shape or density of a
speck, the distribution density of clustered specks is a factor determining
the apparent shape.
Keywords: breast imaging • mammogram • microcalcification • morphology • synchrotron radiation imaging
Introduction
The shape and distribution of individual microcalcifications are important
in classification of benign or malignant behavior on conventional mammograms.
Studies [1,
2] of the diagnostic role of
microcalcifications have shown the superior effectiveness of the distribution
factor over the shape factor in differentiating benign and malignant lesions.
The fuzzy nature of the morphologic features of microcalcifications on
conventional mammograms partially explains the poor reliability of the shape
of microcalcifications in predicting the presence of malignancy.
Synchrotron radiation imaging has had promising results in imaging of
specimens of human breast tissue
[3]. The greater visibility
with synchrotron radiation imaging is due to refraction enhancement in the
experimental setup of a long sample-to-detector distance
[4,
5] and the development of
electronic detectors with small pixels that enable high-resolution imaging
[6]. Using contrast enhancement
by X-ray refraction for small (< 150 µm) specks, we attained a minimum
detectable speck size of 24 µm in breast specimens (Imamura K, et al.,
presented at the 2004 Nuclear Science Symposium and Medical Imaging Conference
of the Institute of Electrical and Electronics Engineers). We can therefore
expect further improvement in the visibility of calcifications with
synchrotron radiation imaging. The purposes of this study were to evaluate the
feasibility of synchrotron radiation imaging with refraction enhancement for
visualization of microcalcification details in breast tissue and to assess
fuzzy morphologic findings on conventional mammograms.
Materials and Methods
Breast specimens fixed in wax blocks were examined with both conventional
mammography and radiography performed with a synchrotron radiation source.
Materials
The specimens were from 107 patients with pathologically proven breast
lesions (53 benign, 54 malignant). Wax blocks had been originally prepared for
pathologic examination (131 blocks; 62 benign and 69 malignant; size, 25
x 35 x 8 mm). Patient consent was obtained in a written format
approved by the institutional review board of our institution.
Conventional Imaging
Conventional mammograms were acquired with a dedicated mammographic X-ray
unit (MGU 100B, Toshiba; Mo target, Mo filter; tube voltage, 22 kV; screen
film, MinR-EV, Kodak).
Synchrotron Radiation Imaging with Refraction Enhancement
Synchrotron radiation imaging was performed at a synchrotron radiation
facility in Harima, Japan. The experimental parameters were as follows: beam
line, 20B2; monochromatic 20-keV X-rays; sample-to-detector distance, 11 m; 6
x 6 µm pixel charged-coupled device camera (C4742-95-12HR, Hamamatsu
Photonics); exposure time, 200 seconds.
Image Analysis
Two qualified mammogram reviewers assessed the morphologic features of the
microcalcifications on the conventional mammograms according to BI-RADS. The
two readers evaluated the images independently; in cases of disagreement,
classification was determined by discussion. Microcalcifications with
amorphous and pleo morphic morphologic features were subjected to further
analysis on the synchrotron radiation images. The smaller specks detected
solely on the synchrotron radiation images were counted visually. Speck size
was measured on the synchrotron radiation images with image-processing
software (IPLab, Scanalytics).
Results
The detection limit of the conventional technique and the multiple
characteristics of microcalcifications on conventional mammograms were
assessed by comparing them with the high-resolution synchrotron radiation
images. Regarding the detection power of the conventional technique, all
specks larger than 300 µm were recognizable, and those smaller than 180
µm were barely visible. Specks in the range of 180–300 µm were
partly detectable depending on the density or thickness of the specks.
Synchrotron radiation imaging, which had a detectability of 24 µm, showed
12,141 fine specks that were not visible on the conventional mammograms of 131
blocks. This finding suggests the feasibility of this imaging technique for
exploring the detailed features of calcifications within breast tissue.
Synchrotron radiation imaging showed that amorphous or pleomorphic
microcalcifications on conventional mammograms were not necessarily solitary
specks but frequently occurred as clusters of multiple fine specks with
various degrees of compactness. Synchrotron radiation images and conventional
mammograms are compared in Figures
1A,
1B,
2A, and
2B, which show a specimen with
clusters of small microcalcifications (Figs.
1A and
1B) and one with bordering or
separate moderate-sized microcalcifications (Figs.
2A and
2B).
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Fig. 1A —55-year-old woman with intraductal calcification with no
malignancy found. Synchrotron radiation image shows two clusters of specks.
Compact cluster of 1.4 x 2.1 mm on left is composed of numerous specks;
1.3 x 3.5-mm cluster on right is less compact. Image size is 6.8 x
6.8 mm.
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Fig. 1B —55-year-old woman with intraductal calcification with no
malignancy found. Conventional mammogram shows 10 microcalcifications (five
pleomorphic, five amorphous) in group on left and 18 microcalcifications (two
pleomorphic, 16 amorphous) in group on right. Image size is 6.8 x 6.8
mm.
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Fig. 2A —79-year-old woman with mastopathy. Synchrotron radiation with
refraction mode image of biopsy specimen shows seven separate round specks
measuring 260–310 µm within region measuring 1.6 x 0.7 mm.
Image size is 4.8 x 3.9 mm.
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Fig. 2B —79-year-old woman with mastopathy. Conventional mammogram of
biopsy specimen shows three microcalcifications (one pleomorphic
[arrow], two amorphous). Five closely distributed specks in A
are not resolved but were interpreted as irregularly shaped pleomorphic
microcalcification (arrow). Two others are individually categorized
as having amorphous shape. Image size is 4.8 x 3.9 mm.
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Most microcalcifications of moderate size that were well-separated from
neighboring calcifications on conventional mammograms were identified in
approximately one-to-one correspondence with specks on the synchro tron
radiation images. Despite similarities in the shapes of individual specks,
radiographic density appeared to affect morphologic classification on
mammograms. Brighter radiographic densities corresponded to a pleomorphic
shape, whereas moderate or weak radiographic densities corresponded to an
amorphous or indistinct shape (not shown).
On the conventional mammogram in Figure
1B, the pleomorphic-to-amorphous ratio is 5 to 5 in the left
cluster and 2 to 16 in the right cluster. The synchrotron radiation image
(Fig. 1A) shows that all of the
microcalcifications on the conventional mammogram
(Fig. 1B) correspond to
clusters or coagulations of multiple fine specks on the synchrotron radiation
image and that a compact cluster of specks tends to have a pleomorphic
appearance on the conventional mammogram. The five clustered specks on the
synchrotron radiation image in Figure
2A were depicted together as one microcalcification and defined as
an irregularly shaped pleomorphic structure on the conventional mammogram
(Fig. 2B, arrow). In contrast,
the other two specks on the synchrotron radiation image
(Fig. 2A) were visibly separate
and defined as amorphous microcalcifications on the conventional mammogram
(Fig. 2B).
The statistics are shown in Table
1. In benign cases, 77.6% of amorphous specks and 87.7% of
pleomorphic specks were clusters of multiple specks (chi-square result, 5.39;
p < 0.025). In malignant cases, 81.4% of amorphous findings and
86.4% of pleomorphic findings were clusters of multiple specks (no statistical
difference). For the benign and malignant cases combined, pleomorphic mor
phologic features had a higher ratio of clustering than did amorphous
morphologic features: 87.0% (260/299) versus 79.9% (819/1,025) (chisquare
result, 7.18; p < 0.01). The radiation dose in this experimental
setup was measured as 5.9 mGy/s with a dosimetric chamber.
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TABLE 1: Number of Microcalcifications in Wax Blocks Containing Breast Specimens
Detected on Conventional Mammograms and Synchrotron Radiation Images with
Refraction Enhancement
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Discussion
Morphologic features and distribution pattern characterize the benign or
malignant nature of microcalcifications on conventional mammograms; however,
it is sometimes a fuzzy process to determine the morphologic features of
microcalcifications. It has been thought that the morphologic features of a
microcalcification are determined by the shape, size, and radiographic density
of an individual speck. This study with high-resolution synchrotron radiation
imaging showed that on conventional mammograms, in addition to factors
inherent in individual specks, the effects of neighboring specks influence
visualization of morphologic features because of the limited resolution of the
technique. Despite the similarity of the intrinsic characteristics of
individual specks, some specks are classified as pleomorphic and some as
amorphous or indistinct depending on radiographic density, the distribution
density of fine specks in the cluster (Figs.
1A and
1B), and the presence or
absence of bordering specks (Figs.
2A and
2B).
It appears, therefore, that there is not always an essential difference
between amorphous and pleomorphic morphologic features. It is also evident
that most microcalcifications with amorphous and pleomorphic morphologic
features on conventional mammograms are clusters of multiple specks. Most of
the microcalcifications with pleomorphic features were found to be clusters of
specks (87.0%). The difference compared with the ratio of amorphous clusters
found was statistically significant (p < 0.01). There was little
difference in incidence between benign and malignant cases.
Imaging with various exposure times has shown that a 24-µm speck, the
smallest on a 200-second image, is visible on a 10-second image. The radiation
dose of a 10-second exposure is estimated to be 59 mGy, which is accordingly
high for detector resolution. Limited distribution of synchrotron radiation
systems and the high dose of 6-µm imaging are issues for clinical
utility.
In conclusion, this study showed that amorphous or indistinct and
pleomorphic microcalcifications on conventional mammograms actually have only
a fuzzy difference. This finding should enhance understanding of
characteristics of microcalcifications hidden on clinical mammograms.
Acknowledgments
The authors thank Drs. Nobuteru Nariayam and Junichiro Tada of Japan
Synchrotron Radiation Research Institute for radiation dose measurement.
References
- Leichter I, Lederman R, Buchbinder SS, Bamberger P, Novak B, Fields
S. Computerized evaluation of mammographic lesions: what diagnostic role does
the shape of the individual microcalcifications play compared with the
geometry of the cluster? AJR 2004;182
: 705-712[Abstract/Free Full Text]
- Sakka E, Prentza A, Koutsouris D. Classification algorithms for
microcalcifications in mammograms. Oncol Rep2006; 15:1049
-1055[Medline]
- Yu Q, Takeda T, Umetani K, et al. First experiment by
two-dimensional digital mammography with synchrotron radiation. J
Synchrotron Rad 1999; 6:1148
-1152[CrossRef]
- Umetani K, Yagi N, Suzuki Y, et al. X-ray refraction-contrast
imaging using synchrotron radiation at Spring-8. Physics of medical
imaging: proceedings of SPIE medical imaging 1999, vol.3659
. Bellingham, WA: SPIE, 1999:560
-571
- Yagi N, Suzuki Y, Umetani K, et al. Refraction-enhanced X-ray
imaging of mouse lung using synchrotron radiation source. Med
Phys 1999; 26:2190
-2193[CrossRef][Medline]
- Imamura K, Ehara N, Umetani K, et al. Sensitive detection of voids
in solid materials by refraction-enhanced synchrotron radiation imaging.
App Phys Lett 2002;81
: 2559-2560[CrossRef]
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Abstract
Introduction
