Non‐Gaussian diffusion imaging with a fractional order calculus model to predict response of gastrointestinal stromal tumor to second‐line sunitinib therapy

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Over the past decade, diffusion‐weighted imaging (DWI) has been used increasingly in the abdomen, not only for cancer detection and characterization, but also for early evaluation of tumor response to therapies 1. For instance, a recent study indicates that apparent diffusion coefficient (ADC) can predict responses of gastrointestinal stromal tumor (GIST)—the most common mesenchymal tumor initiated from the gastrointestinal tract 7—to first‐line imatinib targeted therapy as early as 1 week after the initiation of treatment 3. The good performance of ADC has been attributed to its association with tissue cellularity. Despite the great success of ADC for treatment prediction, ADC is derived from an overly simplified Gaussian diffusion model, which may not adequately capture a wealth of tissue structural and heterogeneity changes as a result of therapy.
In GIST patients who develop resistance to first‐line imatinib and are subsequently treated with second‐line sunitinib 8, approximately 40% of patients can develop progressive disease within 3 months 8. Unlike lesions before first‐line imatinib treatment, the progressive GIST lesions to be treated with second‐line sunitinib typically exhibit increased and varying degrees of heterogeneity as a consequence of the first‐line treatment, resulting in complex tissue structures such as “nodule within a mass” 10. This tissue heterogeneity prior to sunitinib therapy may provide a new avenue to predicting treatment response in combination with ADC.
Recognizing that information on tissue microstructures or heterogeneity is not directly provided by the prevailing Gaussian diffusion models, several research groups have proposed more sophisticated non‐Gaussian diffusion models 12 in an attempt to extract additional tissue structural information. One of these models, known as the fractional order calculus (FROC) model 14, features a new parameter, fractional order derivative in space β, which has been linked to intravoxel tissue heterogeneity 20. The goal of this study is to demonstrate the clinical value of the FROC diffusion model for early prediction of the response of GIST to second‐line sunitinib targeted therapy.

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