Amide proton transfer imaging of the breast at 3 T: Establishing reproducibility and possible feasibility assessing chemotherapy response

Abstract

Chemical Exchange Saturation Transfer (CEST) imaging can generate contrast that is sensitive to amide protons associated with proteins and peptides (termed amide proton transfer, APT). In breast cancer, APT contrast may report on underlying changes in microstructural tissue composition. However, to date, there have been no developments or applications of APT CEST to breast cancer. As a result, the aims of this study were to i) experimentally explore optimal scan parameters for breast CEST near the amide resonance at 3 T, ii) establish the reliability of APT imaging of healthy fibroglandular tissue, and iii) demonstrate preliminary results on APT changes in locally advanced breast cancer observed during the course of neoadjuvant chemotherapy. CEST measurements were experimentally optimized on cross-linked bovine serum albumin phantoms and the reliability of APT imaging was assessed in ten women with no history of breast disease. The mean difference between test-retest APT values was not significantly different from zero, and the individual difference values were not dependent upon the average APT value. The 95% confidence interval limits were ± 0.70% (α = 0.05) and the repeatability was 1.91. APT measurements were also performed in three women before and after one cycle of chemotherapy. Following therapy, APT increased in the one patient with progressive disease and decreased in the two patients with a partial or complete response. Together, these results suggest that APT imaging may report on treatment response in these patients.

Optimization of 7-T Chemical Exchange Saturation Transfer Parameters for Validation of Glycosaminoglycan and Amide Proton Transfer of Fibroglandular Breast Tissue

“…The healthy fibroglandular (FG) tissue was isolated using a semi-automated segmentation as previously described (4). The signal intensities ( S (Δ ω )) from images acquired with saturation far off resonance were defined as S 0 = S (Δ ω = 80 ppm).…”

“…This results in signal enhancement and allows the presence of low-concentration solutes to be examined indirectly. CEST has been used to examine cancer in brain (3) and breast (4–6), detecting increased APT in tumor due to differences in pH and protein content inside cells. This sensitivity to intracellular protein content provides valuable information regarding the viability and health of fibroglandular tissue.…”

Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma

“…The APTw signals are mainly related to cell density and endogenous mobile proteins and peptides [15–18]. APTw imaging has emerged as a valuable tool for grading brain tumors[18–20] and other cancers that occur in the prostate [21], breast [22; 23] and neck [24; 25]; for distinguishing tumor recurrence from radiation necrosis [26], distinguishing pseudo-progression from true progression in gliomas [27], and differentiating between primary central nervous system lymphomas and glioma [15]; and for characterizing cerebral ischemia [28–30]and Parkinson’s disease [31]. However, this technique has not been used to compare SBMs and GBMs.…”

Balanced Steady-State Free Precession (bSSFP) from an effective field perspective: Application to the detection of chemical exchange (bSSFPX)

“…Thus, if the simplest asymmetry analysis is used, chemical shift difference should be limited to less than 0.5/TR. In the future, more sophisticated analysis methods could be adopted similar to standard CEST, such as multi-peak and Bloch simulation fittings [9, 55]. However, currently, we anticipate that the bSSFPX results will be easiest to interpret for the CEST agents with small chemical shift difference, such as choline, glycine, glycogen or glycosaminoglycan.…”

“…It employs selective saturation of protons in a specific chemical group which transfers to water via chemical exchange to (i) indirectly visualize the low concentration metabolites which are not observable in conventional MR scans and (ii) indicate quantitative environmental parameters such as pH. Many promising preclinical and clinical applications have been investigated using CEST imaging techniques including but not limited to: brain tumor imaging [3–6], brain ischemia [7], prostate cancer [8], breast cancer [9, 10], kidney pH measurement [11] and cartilage quality assessment [12, 13]. …”