Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after (chemo)radiotherapy: Correlation between radiologic and histopathologic findings

Purpose: To investigate the value of diffusion weighted magnetic resonance imaging (DW-MRI) in differentiating persistent or recurrent head and neck squamous cell carcinoma (HNSCC) from nontumoral postradiotherapeutic alterations.

Methods and Materials: In 26 patients with suspicion of persistent or recurrent HNSCC, MRI of the head and neck was performed, including routine turbo spin-echo (TSE) sequences and an additional echo-planar DW-MRI sequence, using a large range of b-values (0–1000 s/mm²). Apparent diffusion coefficient (ADC) maps were calculated. In the suspect areas at the primary site and in the suspect lymph nodes, signal intensity was measured on the native b0 and b1000 images and ADC values were calculated for these tissues. The same was done for surrounding irradiated normal tissue. Imaging results were correlated to histopathology.

Results: Signal intensity on native b0 images was significantly lower for HNSCC than for nontumoral postradiotherapeutic tissue (p < 0.0001), resulting in a sensitivity of 66.2%, specificity of 60.8%, and accuracy of 62.4%. Signal intensity on native b1000 images was significantly higher for HNSCC than for nontumoral tissue (p < 0.0001), resulting in a sensitivity of 71.6%, specificity of 71.3%, and accuracy of 71.4%. ADC values were significantly lower for HNSCC than for nontumoral tissue (p < 0.0001), resulting in a sensitivity of 94.6%, specificity of 95.9%, and accuracy of 95.5%. When compared with computed tomography, TSE-MRI and fluorodeoxyglucose-positron emission tomography, DW-MRI yielded fewer false-positive results in persistent primary site abnormalities and in persistent adenopathies, and aided in the detection of subcentimetric nodal metastases.

Conclusions: Diffusion weighted-MRI accurately differentiates persistent or recurrent HNSCC from nontumoral tissue changes after (chemo)radiotherapy.

Introduction

At the time of diagnosis, head and neck squamous cell carcinoma (HNSCC) usually presents as locoregional disease, for which both surgery and (chemo)radiotherapy (CRT) are primary treatment options (1, 2, 3). Treatment failure in the head and neck after CRT is mainly related to locoregional tumor recurrence, whereas distant metastases less frequently occur as an isolated event (4). To increase the chances of a salvage procedure to be curative, posttreatment surveillance should aim at detecting locoregional recurrent or persistent disease at an early stage (5).

Conventional imaging with computed tomography (CT) has a relatively high accuracy for detecting recurrent HNSCC after radiotherapy (RT), allowing earlier identification of treatment failure than clinical examination alone (6). However, false-positive and false-negative results occur, mainly as a result of RT-induced tissue distortions. This problem cannot be resolved by conventional magnetic resonance imaging (MRI) techniques (7). Eighteen fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET) provides complementary information to anatomic imaging modalities, potentially allowing earlier diagnosis of recurrent HNSCC. However, inflammatory changes, as well as the low spatial resolution of this technique, limit its diagnostic accuracy in the post-RT setting (8).

Characterizing tissues by probing their microstructure provides a novel approach in oncologic imaging (9). Diffusion-weighted (DW)-MRI is able to characterize tissue and generate image contrast based on differences in tissue water mobility (10). Two equally large, but opposite, gradient pulses in the diffusion sequence make the signal intensity dependent on the movement of water molecules. The first gradient pulse induces a phase shift of water molecules, followed by incomplete rephasing after the second gradient pulse with a phase difference depending on the mobility of the water molecules. Incomplete rephasing results in a net signal loss on the images. The strength of these gradient pulses is determined by the b-value (11). This incomplete rephasing of water molecules will be less pronounced in hypercellular tissue, characterized by less signal loss, and more pronounced in hypocellular tissue showing increased signal loss on DW-MRI (12). By repeating the sequence with different b-values, the observed signal loss can be quantified using the apparent diffusion coefficient (ADC); hypercellular tissue will, hence, show low ADC values. On an ADC map, tissues with low ADC values are depicted as low signal regions.

Previous studies showed a correlation between signal intensity (SI) on native DW-MRIs and the ADC value with tumor cellularity in experimental models. This correlation has been clinically validated recently in treatment follow-up of brain tumors (13, 14). Pilot studies have shown that DW-MRI can be used for tissue characterization in the head and neck region (15, 16).

The radiotherapeutically-induced nontumoral tissue changes such as edema, inflammation, fibrosis, and necrosis are expected to show low cellularity, in strong contrast with recurrent or persistent tumor. These completely different microstructures are expected to produce different signal intensities and ADC values on DW-MRI.

The purpose of this study was to investigate whether DW-MRI is able to differentiate recurrent or persistent tumor from postradiotherapeutic alterations and necrosis compared with routine imaging methods and histopathology of the resected specimens.