Correlation Of The Apparent Diffusion Coefficient Of Water Assessed By Diffusion-Weighted MR Imaging With Treatment Outcome In Refractory Non-Hodgkin Lymphoma Patients

The contrast of MR images can be made sensitive to the average motion of water molecules (diffusivity) in the various tissue compartments giving rise to diffusion-weighted imaging (DWI). Intensity maps of the apparent diffusion constant (ADC) of water can be generated from the DWI information and average ADC values of anatomical regions of interest can be assessed. Malignant tissues generally exhibit hypercellularity, increased nucleus-to-cytoplasm ratios, and an increased amount of macromolecular proteins, resulting in decreased water diffusivity (i.e., lower ADC). Additionally, a response-related ADC increase has been demonstrated in malignancies under therapy. We previously reported that the ADC mean value (in 10^-3 mm² s^-1 [SD, n]) of tumor masses of refractory non-Hodgkin lymphoma (NHL) patients prior to start a new treatment was lower than the ADC mean value of lymph nodes of healthy volunteers (0.91 [0.23, 15] vs. 1.13 [0.14, 10], respectively). This difference was statistically significant (p< 0.01) despite of a large dispersion on the ADC data from the refractory NHL patients. Given this dispersion, we wanted to assess if refractory NHL patients with lower ADC values prior to therapy responded differently than patients with higher ADC values.

Under ethical review board approval, refractory NHL patients underwent a pretreatment MR exam using a 1.5T Philips Achieva whole body scanner (Philips Healthcare, Best, The Netherlands), which included clinical MRI and DWI. DWI was acquired using echo-planar imaging with fat suppression and b-values of 0 and 1000 s/mm² to obtain the ADC of water in the tumor. Treatment outcome was assessed determining the time to treatment failure (TTF) defined as the time between the end of one treatment and the start of a new one.

DWI and TTF were obtained in 12 NHL patients refractory to previous treatments. Patients were divided into those with TTF ≤ 75 days and those with TTF > 75 days. The ADC mean value [SD, n] in refractory NHL patients with TTF ≤ 75 days was 0.73 [0.20, 5] while in patients with TTF > 75 days was 1.04 [0.20, 7]. When compared, these mean values were significantly different (p< 0.02). Furthermore, the comparison of the ADC mean value of lymph nodes of healthy volunteers with the ADC mean value of refractory NHL patients with TTF ≤ 75 days was highly significant (p< 0.0005) while the comparison of ADC mean values between healthy volunteers and patients with TTF > 75 days was not significantly different.

Our results demonstrate that refractory NHL patients with tumor masses displaying abnormally low ADC values prior to the start of treatment have poorer treatment outcome than those patients with ADC tumor values that are comparable to values in normal lymph nodes. Although the appropriate biophysical interpretation of the ADC value remains controversial, the restricted diffusivity of water indicated by ADC reduction is considered secondary to increased tumor cellularity. The correlation between outcome and tumor cellularity could be possibly explained by reduced drug availability in the tumor when cellularity increases, thus explaining the substandard outcome in patients with lower ADC values. However, even though the correlation between lower ADC and poorer outcome is not yet understood, our results demonstrate an important predictive value of the ADC determination by DWI in refractory patients with NHL. This together with the fact that DWI is a noninvasive technique that requires no administration of contrast medium and its acquisition is fairly short makes the determination of ADC by DWI a technique that could become critical for the clinical examination of the patient with refractory NHL.

No relevant conflicts of interest to declare.