gagCEST imaging in patients with breast tumors at 7 Tesla - preliminary results
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=179x319mm2, 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.

Figures

Fig.1. a) gagCEST map and b) CE-MRI in 45-years-old patient with invasive ductal carcinoma (IDC) in left breast. The gagCEST map shows higher values of MTRasym in tumor compared to healthy tissue.

Fig. 2. a) Color coded gagCEST map and b) T1w image of 50-years-old patient with fibroadenoma in right breast. The measured MTRasym values found in lesion were indistinguishable from those measured in healthy tissue.

Fig.3. Boxplot diagrams of MTRasym for malignant, benign tumors and a healthy tissue. There is a significant difference between malignant and benign lesions (CI=95%, p=0.001).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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