Olgica Zaric1, Katja Pinker-Domenig2,3, Esau Poblador 1, Vadimir Mlynarik1, Thomas Helbich4, Siegfrid Trattnig1,5, and Wolfgang Bogner1
1High Field Magnetic Resonance Centre, Medical University of Vienna, Vienna, Austria, 2Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria, 3Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 5Christian Doppler Lab for Clinical Molecular MRI, Christian Doppler Forschungsgesellschaft, Vienna, Austria, Vienna, Austria
Synopsis
Proteoglycans content in malignant tumors may provide
information regarding the altered metabolism and neoplastic cell behavior.
The aim of this
study was to investigate the feasibility of gagCEST imaging in patients with
breast tumors at 7 Tesla. Eleven patients with 15 lesions were examined.
gagCEST imaging was performed with 1.7mm in-plane resolution and nine minutes
of measurement time. Results based on MTRasym showed excellent
differentation between malignant and benign lesions (CI=95%, p=0.001) and insignificant difference
between benign and healthy tissue (CI=95%, p=0.159). gagCEST has a great potential in breast
tumors evaluations providing substantially different information obtained with standard MRI techniques.Target Audience
Scientists
specializing in breast MRI
Introduction/Purpose
Our goal was to evaluate the feasibility of glycosaminoglycan (GAG) hydroxyl proton chemical exchange saturation transfer (gagCEST) imaging in detection and
characterization of breast lesions in human patients at 7 Tesla. gagCEST - MRI may provide biochemical information on tissue status via
altered proteoglycan content (1). This is supported by elevated proteoglycan
concentrations found in mammary tumors (2), indicating its involvement in
neoplastic cell behavior (3).
Subjects and Methods
Eleven female patients (age 60±16 years,
range 23-74 years) with 15 histologically verified breast lesions (nine
malignant and six benign) were examined. Institutional Review Board approval
and written informed consent were obtained prior to the measurements. The mean size
of malignant and benign lesions was 13±4 mm and 20±12 mm, respectively.
Patient measurements were performed on a 7.0 T MRI scanner (Siemens,
Erlangen, Germany) with a bilateral dual tuned
1H/
31P
phased array breast coil with patients in a prone position. For gagCEST imaging,
CEST
effects were induced by a train of Gaussian RF pulses followed by image
acquisition using a 3D turboFLASH sequence. The saturation pulse was applied at 17
saturation-offset frequencies (Δω) between ±3 ppm, with following characteristics: B1-CWAE (continuous wave amplitude equivalent) = 0.8 μT, pulse duration PD = 99 ms, interpulse
delay IPD = 100 ms, number of CEST pulses = 5. Selective fat saturation was
applied before readout. After gagCEST, contrast enhanced (CE)-MRI was performed
with the following imaging parameters: FOV=179x319mm
2, slice
thickness = 3 mm, TR/TE = 5 ms /2.2 ms, spatial resolution = 1.7×1.7 mm², flip
angle = 11°, total acquisition duration = 9:37 min. Z-spectra were calculated
for each pixel and were shifted for the water resonance to appear at 0 ppm.
MTRasym (∂) was calculated
as MTR(+∂)-MTR(-∂) integrated
over the offset range ∂
from
0.5 to 2 ppm, which corresponds to the resonance frequencies of exchangeable
hydroxyl protons of GAG. Regions of interests (ROI) were placed in the
tumors and statistical analysis was performed (Games-Howell test,
SPSS16; Chicago, IL, USA).
Results
In all carcinomas, the gagCEST maps showed
higher values compared to healthy tissue (Fig. 1). MTRasym measured in the healthy
glandular tissue (1.8±0.5%, range: 0.5-3.2%) was not significantly different from
that in benign lesions (CI=95%, p=0.159) (Fig.2). The mean measured MTRasym
value in breast carcinomas was (9.6±2.6% range: 6.6-13.3%), and was
significantly higher than in benign lesions (3.3±0.9% range: 1.5-5.3%, (CI=95%, p=0.001)
(Fig.3).
Discussion/Conclusion
Our preliminary data showed that gagCEST MRI has a
great potential in biochemical investigation of breast lesions
at 7 Tesla. In this pilot study we showed that the gagCEST effect in
malignant lesion is significantly higher than in benign ones, which can be explained
by the changed metabolism of the pathological tissue. However, the accuracy and reproducibility of this
technique need to be further evaluated. The measured quantitative values should
be compared with the content of proteoglycans found in tumors, using
histological techniques.
We believe that CEST MRI may become an attractive tool for the
investigation of breast tumors, because it provides substantially different
information than that obtained with established quantitative techniques.
Acknowledgements
This study was supported
by the Vienna Science and
Technology Fund (WWTF; Project LS14-096).References
1. Dula AN. et al. Optimization of 7-T Chemical
Exchange Saturation Transfer
Parameters for Validation of
Glycosaminoglycan and Amide
Proton Transfer of Fibroglandular
Breast Tissue. Radiology 2015;275(1):255-261.
2. Iozzo RV. Proteoglycans and neoplasia. Cancer
Metastasis Rev 1988;7(1):39–50.
3. Alini M, Losa GA. Partial characterization of
proteoglycans isolated from neoplastic and
nonneoplastic human breast tissues. Cancer
Res 1991;51(5):1443–1447.