Diffusion-weighted imaging and diffusion kurtosis imaging for early evaluation of the response to docetaxel in rat epithelial ovarian cancer

Abstract

BackgroundTo investigate diffusion-weighted magnetic imaging (DWI) and diffusion kurtosis magnetic imaging (DKI) for the early detection of the response to docetaxel (DTX) chemotherapy in rat epithelial ovarian cancer (EOC).Methods7,12-Dimethylbenz[A]anthracene was applied to induce orthotopic EOC in Sprague–Dawley rats. Rats with EOC were treated with DTX on day 0 (treatment group) or were left untreated (control group). DWI and DKI were performed on days 0, 3, 7, 14 and 21 after treatment. On day 21, the tumors were categorized into the sensitive and insensitive groups according to the size change. The cutoff values of the DWI and DKI parameters for the early response were determined. The experiment was repeated, and the treatment group was divided into the sensitive and insensitive groups according to the initially obtained cutoff values. The DWI and DKI parameters were correlated with tumor size, proliferation, apoptosis and tumor necrosis.ResultsIn the sensitive vs. insensitive or control group, significant differences were found in the Δ% of the DWI and DKI parameters (ADC, D and K) from day 3 and in tumor size from day 14. Early on day 7, the Δ% of K had an AUC of 1 and sensitivity and specificity values of 100% and 100%, respectively, to detect the response to DTX using a cutoff value of 19.03% reduction in K. From day 7, significant differences were found in the Δ% of Ki-67 and CA125 in the sensitive vs. control group and from day 14 in the sensitive vs. insensitive group. From day 14, there were significant differences in the Δ% of Bcl-2, apoptosis and tumor necrosis in the sensitive vs. control or insensitive group. The Δ% values of ADC and D were negatively correlated with the Δ% values of tumor size, Ki-67, CA125 and Bcl-2 and were positively correlated with the Δ% values of apoptosis and tumor necrosis. The Δ% of K was positively correlated with the Δ% values of tumor size, Ki-67, CA125 and Bcl-2 and was negatively correlated with the Δ% values of apoptosis and tumor necrosis.ConclusionsDWI and DKI parameters, especially K, are superior for imaging tumor size for the early detection of the response to DTX chemotherapy in induced rat EOC.

Mapping early tumor response to radiotherapy using diffusion kurtosis imaging**

“…Several studies have shown that diffusion MRI is a sensitive and early indicator of both treatment response and overall survival in brain tumors, [43][44][45] kurtosis parameters showed early and larger changes in detecting response to docetaxel chemotherapy in rat epithelial ovarian cancer. 47 The current study showed the axial kurtosis metric to be more sensitive to studying early RT related changes in the tumor offering a 13.3% larger effect sizes than corresponding diffusion metrics in the active tumor regions. This increased sensitivity is also seen in the evaluation of microstructural changes in low-grade gliomas as compared to DTI imaging, where DKI offers significant increases in the effect sizes for delineating different regions of the gross tumor.…”

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis

“…20 In orthotopic preclinical models of solid ovarian tumours, the change in ADC following docetaxel also was shown to correlate negatively with Ki67, CA125 and Bcl-2, all of which predict residual tumour burden. 21 Although negative correlation between cell density and diffusivity is widely accepted, 22,23 the literature is inconclusive about the effect of stroma, fibrosis and inflammatory infiltrate on ADC values indicating that they are influenced by a complex interplay of biophysical processes. 24,25 In a tissue comprised primarily of fat, such as the omentum, the return of normal fatty stroma interspersed with residual tumour may obscure a posttreatment ADC rise.…”

“… 20 In orthotopic preclinical models of solid ovarian tumours, the change in ADC following docetaxel also was shown to correlate negatively with Ki67, CA125 and Bcl-2, all of which predict residual tumour burden. 21 …”

“…ADC increases post-treatment have been shown to correlate with percentage necrosis in preclinical studies. 21 A multicentre clinical trial in lung cancer concluded that presurgical ADC or change in ADC did not correlate with pathologist-assessed necrosis of resection specimens but assessment was dependent on a single pathologist reading. 32 Clinical evidence relating ADC change following chemotherapy to subsequent necrosis may be confounded by pre-existing microscopic necrosis within the tumour; ADC change has been linked to necrosis in tumour types without much pre-existing necrosis, but not in others.…”

Diffusion kurtosis imaging assessment of the response to radiotherapy in a VX2 bone tumor model: an animal study

“…The MD value increased significantly during treatment. This could be attributed to postradiotherapeutic changes, such as tumor lysis, loss of cell membrane integrity, and increased extracellular space, which promotes the movement of water molecules, thereby increasing the diffusion of water (14). Liu et al (15) reported that the MD of osteosarcoma The MK of the good response group was significantly lower than the pre-treatment value, and there was no significant difference in MK between good response and poor response groups.…”