Histogram Analysis of Intravoxel Incoherent Motion for Differentiating Recurrent Tumor from Treatment Effect in Patients with Glioblastoma: Initial Clinical Experience

BACKGROUND AND PURPOSE:Intravoxel incoherent motion can simultaneously measure diffusion and perfusion characteristics. Our aim was to determine whether the perfusion and diffusion parameters derived from intravoxel incoherent motion could act as imaging biomarkers for distinguishing recurrent tumor from treatment effect in patients with glioblastoma.MATERIALS AND METHODS:Fifty-one patients with pathologically confirmed recurrent tumor (n = 31) or treatment effect (n = 20) were assessed by means of intravoxel incoherent motion MR imaging. The histogram cutoffs of the 90th percentiles for perfusion and normalized CBV and the 10th percentiles for diffusion and ADC were calculated and correlated with the final pathology results. A leave-one-out cross-validation was used to evaluate the diagnostic performance of our classifiers.RESULTS:The mean 90th percentile for perfusion was significantly higher in the recurrent tumor group (0.084 ± 0.020) than in the treatment effect group (0.040 ± 0.010) (P < .001). The 90th percentile for perfusion provided a smaller number of patients within an overlap zone in which misclassifications can occur, compared with the 90th percentile for normalized CBV. The mean 10th percentile for diffusion was significantly lower in the recurrent tumor group than in the treatment effect group (P = .006). Receiver operating characteristic curve analyses showed the 90th percentile for perfusion to be a significant predictor for differentiation, with a sensitivity of 87.1% and a specificity of 95.0%. There was a significant positive correlation between the 90th percentiles for perfusion and normalized CBV (r = 0.674; P < .001).CONCLUSIONS:A histogram analysis of intravoxel incoherent motion parameters can be used as a noninvasive imaging biomarker for differentiating recurrent tumor from treatment effect in patients with glioblastoma.

In clinical practice, it is often difficult to determine whether a progressively enhancing lesion occurring after concurrent chemoradiotherapy is caused by a recurrent tumor or by treatment effect.¹ Several studies have used physiologic imaging techniques, such as T2*-weighted dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging, to differentiate recurrent tumor from treatment effect.^1,2 Intravoxel incoherent motion (IVIM) was introduced by Le Bihan et al^3,4 as a method for simultaneously measuring perfusion and diffusion. Le Bihan et al⁴ defined IVIM as the microscopic translational motions that occur in each image voxel in MR imaging. In biologic tissues, these incoherent motions include molecular diffusion of water and microcirculation of blood in the capillary network, called “perfusion.” These 2 phenomena account for the bi-exponential decay of the signal intensity on DWI when different diffusion b-values are applied. With the use of IVIM theory, both true molecular diffusion and water molecule motion in the capillary network can be estimated by means of a single diffusion imaging acquisition technique. The major advantages of IVIM MR imaging are as follows: it allows the simultaneous acquisition of diffusion and perfusion parameters, which can provide perfusion measures within corresponding solid lesions on ADC or the D-map without the requirement for a co-registration processing step; intravenous contrast injection is not required; and it allows processing and image analysis to be performed within a reasonable timeframe.In the present study, we attempted to validate IVIM-derived perfusion and diffusion parameters through the use of both the pathologic correlation and normalized CBV (nCBV) derived from DSC MR perfusion imaging, which has been commonly used as a perfusion parameter for assessing the glioblastoma treatment response. For pathologic correlation, we used IVIM MR imaging in patients with pathologically confirmed recurrent tumor or treatment effect.Our first hypothesis was that the difference in vascularity between recurrent tumor and treatment effect can be assessed by means of an IVIM-derived perfusion fraction (f), and it would correlate with the value of nCBV derived from DSC MR perfusion imaging. Our second hypothesis was that the true diffusion parameter (D), derived from a biexponential model that separates perfusion effects, may be more significantly different between the recurrent tumor and the treatment effect groups than ADC. The purpose of this study was to determine whether the perfusion (f) and diffusion (D) parameters derived from IVIM can act as imaging biomarkers for distinguishing recurrent tumor from treatment effect in patients with glioblastoma.