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

Abstract

Chemical exchange saturation transfer 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 chemical exchange saturation transfer to breast cancer. As a result, the aims of this study were to (i) experimentally explore optimal scan parameters for breast chemical exchange saturation transfer 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. Chemical exchange saturation transfer measurements were experimentally optimized on cross-linked bovine serum albumin phantoms, and the reliability of APT imaging was assessed in 10 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 on 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.

Figure 1

Results from bovine serum albumin phantom studies. A) Amplitude of CEST saturation pulse was varied between 0.25 μT and 1.25 μT, B) duration of the pulse element was varied from 10 ms to 25 ms, and C) the number of pulses per TR was varied from 15 to 35.

Figure 2

CEST MRI results from a healthy control acquired at 3 Tesla. A) Complete CEST data set, 40 images taken with saturation pulse offset ranging between ± 6 ppm. B) Spectral results from the masked fibroglandular tissue for repeated CEST scans. Acquired data shown as black and gray points corresponding to the right y-axis and the residuals of these fits are shown as dashed lines corresponding to the left y-axis. The APT_residual maps are shown as overlays on the anatomical images for scan 1 (C) and 2 (D).

Figure 3

APT_residual maps for healthy controls testing the repeatability of the amide proton transfer measurement. The subject with the highest correspondence is shown in Panels A and B. Examples of average correspondence are found in Panels C and D, and the APT_residual maps for the subject with the worst repeatability results are shown in Panels E and F. The APT_residual maps are displayed as overlays on the CEST image without saturation.

Figure 4

Comprehensive repeatability results with APT_residual values plotted for each scan session of 10 healthy controls. Mean and standard deviation values denoted by the solid and dashed lines, respectively.

Figure 5

Bland-Altman plot for masked fibroglandular (FG) tissue of healthy controls. The differences between mean amide proton transfer (APT) measures from two scanning sessions are plotted against the average of the two mean FG APT values for each volunteer. The overall mean difference (d) was not significantly different from zero while the 95 % confidence interval (CI), dotted lines, was 0.70 % which represents the level of change that would be significant for a group of ten subjects. The dashed line represents the calculated repeatability, 1.91, which is the level of change that would be significant in an individual.

Figure 6

Patient Data. Overlay of tumor APT_residual maps on corresponding anatomical images before (left column) and after (right column) one cycle of neoadjuvant chemotherapy for a patient achieving complete response (panels A and B) and a patient with progressive disease (C and D).