Intravoxel incoherent motion (IVIM) model-based analysis of diffusion-weighted imaging (DWI) is increasingly employed in oncologic imaging. Although first experiences with IVIM DWI for response analysis of hepatocellular carcinoma (HCC) after embolization therapies in general have recently been reported, response characteristics of specific treatment options are so far unknown. We describe differences in treatment response parameters of HCCs obtained by IVIM DWI in resin-radioembolization and glass-radioembolization.
Purpose
Intravoxel incoherent motion (IVIM) model-based analysis of diffusion-weighted imaging (DWI) data is increasingly employed in oncologic imaging of the liver, especially for lesion characterization and response assessment1-5. Recently, response characteristics of hepatocellular carcinoma (HCC) treated by radioembolization, chemoembolization, and ethanol-lipiodol embolization have been examined using a simplified IVIM analysis6 without differentiation between different therapy modalities. Radioembolization as an alternative to chemoembolization is increasingly being performed in the treatment of HCC using two different types of microspheres, resin and glass7. The purpose of our study was to investigate differences in treatment response of HCCs utilizing IVIM DWI after resin- and glass-radioembolization.Methods
37 HCC-patients (mean age 68 years) underwent 44 primary radioembolizations (26 resin, 18 glass) with 1.5T liver-MRI including respiratory-gated DWI with b0=0, b1=50, b2=800s/mm2 before and four weeks after treatment. Apparent diffusion coefficient ADC(0,800), estimated diffusion coefficient D’ and perfusion fraction f’ were determined voxelwise using a simplified IVIM-approach8-10. Hereby, D’ = ADC(50,800) = (ln(S(b1))-ln(S(b2)))/(b2-b1) and f’ = 1–S(b1)/(S(0)▪exp(-b1▪ADC(50,800)), S(b) and S(0) are the signal intensities with and without motion-probing gradients.
For each radioembolization, one HCC-nodule was analyzed using corresponding hand-drawn Regions-of-Interest (ROI) before and after therapy. Data were categorized into “response” (partial response/stable disease) and “non-response” (progressive disease) according to modified RECIST-criteria.
Results
27 HCCs responded (16 resin, 11 glass); 17 did not respond (10 resin, 7 glass).
Responders to resin-radioembolization showed significantly larger pre-interventional f’-values than non-responders (p=0.016), while responders to glass-radioembolization showed significantly smaller pre-interventional ADC(0,800)- and D’-values than non-responders (p=0.0005 and p=0.001, respectively).
After therapy responders showed increasing ADC(0,800)- and D'-values and decreasing f'-values both after resin-radioembolization (p=0.001, p<0.0001, p<0.0001, respectively) and after glass-radioembolization (p=0.006, p=0.001, p=0.016, respectively). In non-responders, however, f' was increased (p=0.006) while ADC and D' were unchanged after resin-radioembolization. After glass-radioembolization ADC(0,800) and D' decreased (p=0.023 and p=0.032, respectively) and f' was unchanged in non-responders.
For resin-radioembolization, responders and non-responders were best differentiated by f'-changes (AUC of 1.0), while for glass-radioembolization they were best differentiated by D'-changes (AUC of 1.0).
Discussion
DWI acquired with more than two b-values enables a refined analysis based on the intravoxel incoherent motion (IVIM) model as introduced by Le Bihan11. By assuming a bi-exponential behavior of the signal intensity, diffusion and perfusion effects on the DWI signal can be separated12. However, in malignant lesions a separation by widely used bi-exponential fitting is challenging because IVIM perfusion parameters are often lower than in liver tissue13,14.
In the simplified IVIM model used in this study8-10, the diffusion coefficient D and the perfusion fraction f is estimated as D' and f' which can deviate from the exact parameter values. f' should therefore be considered as an empirical global perfusion parameter, which does not only reflect the contribution of microvascular perfusion to the DWI signal, but also dependents on blood flow velocity and vessel architecture8.
The finding of increasing diffusion parameters and decreasing perfusion fraction in responders is in line with results of a previous study investigating response of HCCs to embolization therapies also by simplified IVIM analysis6. As a sign of necrosis, responding tumors show increasing diffusion and decreasing perfusion parameters. However, our results indicate that response to resin-radioembolization in contrast to glass-radioembolization is more closely related to changes in perfusion than in diffusion. A possible explanation may be, that in resin-radioembolization a considerably larger number of microspheres are administered to achieve the prescribed therapeutic radiation activity (due to a 50-fold higher radioactivity of glass-microspheres compared to resin)7. Resin-radioembolization is therefore associated with a more pronounced embolization effect than glass-radioembolization.
Conclusion
Response-prediction and early response-assessment after radioembolization of HCC is feasible using IVIM-analysis. Responding tumors show increasing diffusion and decreasing perfusion parameters regardless of the type of radioembolization. However, response to resin-embolization is more closely associated with perfusion changes (dominant embolization effect) and response to glass-radioembolization with diffusion changes. These differences may in future be helpful clinically for differential early post-interventional response assessment.1. Joo I, Lee JM, Han JK, Choi BI. Intravoxel incoherent motion diffusion-weighted MR imaging for monitoring the therapeutic efficacy of the vascular disrupting agent CKD-516 in rabbit VX2 liver tumors. Radiology. 2014;272(2):417-26.
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