Purpose:

Intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) is a non-invasive magnetic resonance (MR) technique that enables measuring the cellularity and vascularity of tumor tissue without contrast agents¹. Quantitative imaging metrics derived from IVIM-DWI have shown promise in the assessment of treatment response in various cancers, including head and neck (HN) cancers^2-4. However, a repeatability measure of IVIM-DWI-derived quantitative imaging metric values is needed to examine the therapy-related response from the measurement variations. IVIM-DWI has been shown to have a tendency towards better repeatability for the measurement of D whereas f and D* are still exploratory in nature^5-7. This is the first study to determine the repeatability of IVIM-DWI-derived metrics from HN cancer patients undergoing chemoradiation therapy.

Material and Methods: IVIM-DWI data acquisition:

Eight HN cancer patients with metastatic nodes (M/F: 6/2, median age: 61 years) were studied before initiation of the treatment (pre-TX) and 16 IVIM-DWI datasets were obtained. Additionally, 14 IVIM-DWI datasets were acquired at intra-TX week 1 (during chemoradiation therapy) from seven patients (M/F: 6/1, median age: 59 years). Our institutional review board approved this retrospective study.The MR imaging (MRI) scan consisted of multi-planar T1/T2-weighted imaging followed by IVIM-DWI with multi b-values on a 3.0T scanner (Ingenia, Philips Healthcare, Netherlands) using a 20-channel neurovascular phased-array coil. The IVIM- DWI images were acquired using a single-shot spin echo planar imaging sequence with TR = 4000 ms, TE = 80-100 ms, field of view = 20-24 cm, matrix = 128 × 128, slices = 8-10, slice thickness = 5 mm, NEX = 2 and b = 0, 20, 50, 80, 200, 300, 500, 800, 1500, and 2000 s/mm2. Two IVIM-DWI datasets were acquired at the same MR exam for each patient to test for the repeatability of the metrics, totalling 30 IVIM-DWI datasets.

IVIM-DWI data analysis:

Regions of Interest (ROIs) were delineated on the neck nodal metastases by a team of radiation oncologists and neuro radiologist who were in consensus on the IVIM DW-MRI image (b = 0 s/mm2) using Image J⁸. The ROIs were then exported to an in-house MATLAB platform for data analysis which includes (a) mono-exponential model to calculate apparent diffusion coefficient (ADC), and (b) bi-exponential model to estimate the diffusion coefficient (D), perfusion fraction (f) and pseudo diffusion coefficient (D*)^{1, 8}.

Statistical analysis:

A Wilcoxon Rank-Sum test was used to compare the metrics between repeated measurements. The test/retest repeatability of metrics were analyzed using the within-subject coefficient of variation CV (wCV, %) and were visualized by Bland-Altman plots^9-10.

Results:

The metric values for ADC, D, f, and D* at the pre-TX is shown in Figure 1. ADC, D, f, and D* values were not significantly different between the repeated measurements (p > 0.05) at the pre-TX and intra-TX week 1. The differences in ADC and D values between the repeated measurements against the mean ADC and D at the pre-TX and intra-TX week 1 are displayed in Figures 2 and 3, respectively. No relationship between the difference and the mean of repeated measurements for any of the parameters measured was found. Table 1 shows the wCV for the quantitive imaging metrics. The wCV (%) for the ADC, D, D*, and f in eight subjects at the pre-TX were 4.0%, 3.9%, 3.8%, and 25%, respectively. At the intra-TX week 1, wCV (%) for the ADC, D, D*, and f in seven subjects were 2.4%, 6.0%, 4.4%, and 19.6%, respectively.

Discussion:

Mean ADC, D, and D* values of tumors are repeatable within the coefficient of variation wCV (%) were ≤ to 6% for both pre- and intra-TX week 1 whereas f wCV (%) was ≤ to 25% for both pre- and intra-TX week 1. This is the first study assessing repeatability and exhibiting that ADC, D, and D* are robust imaging metrics for assessing treatment response in HN cancer patients. Quantitative imaging biomarker development requires repeatability data for the imaging metrics so that they can be used in clinical applications.

Conclusion:

After appropriate validation in a larger HN cancer patient population, these findings may be useful for evaluating treatment response in clinical trials.

Acknowledgements

This work was supported by the MSKCC internal IMRAS grant and in part through the NIH/NCI Cancer Center Support Grant: P30 CA008748.

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