Amide proton transfer (APT) imaging is a promising functional MRI technique (1-4) that investigates the chemical exchange processes between free water and mobile amide protons in cancer proteins/peptides and is sensitive to small variations in these amide protons. The potential value of APT in head and neck cancer is unknown (5). The aim of this preliminary study was to determine whether APT imaging could be performed successfully in head and neck cancers, and whether it could detect differences between undifferentiated nasopharyngeal carcinoma (NPC) and head and neck squamous cell carcinoma (SCC).

Patients

This prospective study was performed with local institutional board approval and written informed consent. 20 consecutive patients with undifferentiated NPC and 20 consecutive patients with head and neck SCC were recruited.

Image acquisition

Patients were scanned on a Philips Achieva TX 3-T scanner with a body coil for radiofrequency transmission and a 16-channel neurovascular phased-array coil for reception. T2-weighted images were used to localize the primary tumour and APT was performed through the slice with the greatest tumour diameter using a single-slice TSE sequence with chemical shift-selective fat suppression. Localized high-order shimming was performed to reduce ΔB0. A baseline image without application of the saturation pulse was acquired first, and then the saturated images at positive and negative offsets were obtained in an interleaved fashion at (±0.25, ±0.5, ±1, ±1.5, ±2, ±2.5, ±3, ±3.5, ±4, ±4.5, ±5, ±5.5, ±6.5, ±7.5) parts per million (ppm). Saturation was obtained using a continuous rectangular RF pulse with a B1 field strength of 2 μT and duration of 200 ms. Other imaging parameters were: FOV, 230 × 230mm²; voxel size, 2×2mm²; slice thickness, 4 mm; TE/TR = 8 ms/2000 ms; echo train length (ETL), 14; SENSE factor, 2; partial Fourier factor, 0.7.

Image processing and data analysis

Data processing was performed using a Matlab (MathWorks, Natick, MA, USA) program. The voxel-wise Z spectrum was fitted by a 12th-order polynomial model, and the fitted curve was then interpolated to a finer resolution of 0.001 ppm. The interpolated Z spectra were shifted along the offset axis to correct for ΔB0. The APT effect was quantified by calculating the asymmetric magnetization transfer ratio (MTRasym) at the offset of 3.5ppm The MTRasym image (APTw image) at 3.5ppm and ΔB0 map were produced by calculating the voxel-wise MTRasym and ΔB0 values. In addition, the voxel-wise coefficient of determination R² was also calculated to evaluate the goodness-of-fit of Z-spectrum fitting. The solid tumour area was contoured (excluding necrosis), the APT mean, standard deviation (SD), skewness and kurtosis were measured and compared between NPCs and SCCs using the Mann Whitney U-test. A p-value of less than 0.05 was considered to indicate a statistically significant difference.

40 patients with head and neck cancer (31 male, 9 female, mean age of 55.7) underwent APT imaging. APT was successful in 19/20 (95%) NPCs (figure 1) and 13/20 (65%) SCCs (figure 2). APT was unsuccessful in SCC sites in the hypopharynx (2/6), larynx (2/3), tongue (2/5) and oropharynx (1/6). No significant differences were found between the APT parameters of NPC and SCC (Table 1).

The APT Imaging protocol was set up for use in the head and neck. The technique was successful in a high percentage of tumours in the nasopharynx which is a site less prone to movement. However, it was less successful in SCC which involved other sites along the aerodigestive tract where it failed in one third of patients. It was especially difficult to perform in the larynx where artifact from the adjacent airway and movement degraded the images.

Unlike other functional MRI techniques such as diffusion weighted imaging (DWI) (6), dynamic contrast enhanced (DCE) MRI (7) and proton magnetic resonance spectroscopy (MRS) (8), APT imaging was unable to show any significant difference in the APT parameters of NPC and SCC. However the sample size in this preliminary study was small and in addition the MTRasym was small, so a longer and stronger saturation pulse may be needed in future studies. In addition because of time constraints currently data can only be obtained from one slice which limits the ability of APT to study heterogeneity of the whole tumour.

APT imaging of head and neck cancers is feasible, although the success rate varies with tumour site. No differences between the APT parameters of NPC and SCC have been shown in these preliminary results but larger studies are needed.