Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma

Abstract

Diffuse malignant gliomas, the most common type of brain tumor, carry a dire prognosis and are poorly responsive to initial treatment. The response to treatment is typically evaluated by measurements obtained from radiographic images several months after the start of treatment; therefore, an early biomarker of tumor response would be useful for making early treatment decisions and for prognostic information. Thirty-four patients with malignant glioma were examined by diffusion MRI before treatment and 3 weeks later. These images were coregistered, and differences in tumor-water diffusion values were calculated as functional diffusion maps (fDM), which were correlated with the radiographic response, time-to-progression (TTP), and overall survival (OS). Changes in fDM at 3 weeks were closely associated with the radiographic response at 10 weeks. The percentage of the tumor undergoing a significant change in the diffusion of water (V T ) was different between patients with progressive disease (PD) vs. stable disease (SD) (P < 0.001). Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter TTP compared with SD (median TTP, 4.3 vs. 7.3 months; P < 0.04). By using fDM, early patient stratification also was correlated with shorter OS in the PD group compared with SD patients (median survival, 8.0 vs. 18.2 months; P < 0.01). On the basis of fDM, tumor assessment provided an early biomarker for response, TTP, and OS in patients with malignant glioma. Further evaluation of this technique is warranted to determine whether it may be useful in the individualization of treatment or evaluation of the response in clinical protocols.diffusion MRI ͉ human glioma ͉ treatment assessment ͉ surrogate marker

Microvascular MRI and Unsupervised Clustering Yields Histology-Resembling Images in Two Rat Models of Glioma

“…Indeed, it is well known that a developing tumor impacts vessel wall permeability, blood volume and flow, oxygenation and others physiologic parameters. [25][26][27][28][29] Moreover, the physiologic links between CBF, CBV, StO 2 , CMRO 2 are altered in tumors, as can be seen from the independent variations of perfusion estimates between clusters (Figure 3). Microvasculature is also a target for several anti-tumoral strategies.…”

Noninvasive Molecular Imaging Sheds Light on the Synergy between 5-Fluorouracil and TRAIL/Apo2L for Cancer Therapy

“…Diffusion MRI exploits the molecular motion of water as a biomarker for cellularity and has been shown to be a reliable indicator of tumor response to therapy both in preclinical and clinical studies (12,14,21,22). Moreover, a recent study highlighted the sensitivity of this approach in which diffusion MRI was able to detect in real-time the emergence of drug resistance during therapy (15).…”

“…18,20). An additional advantage of diffusion MRI is the direct clinical translatability of the technology, which could be used to monitor response to therapies in clinical trials (21,22). In this study, we explored the use of diffusion MRI as a surrogate marker for tumor response resulting from a predominantly proapoptotic therapy as evidenced by our bioluminescence reporter system.…”

Apparent Diffusion Coefficient of Glial Neoplasms: Correlation with Fluorodeoxyglucose–Positron-Emission Tomography and Gadolinium-Enhanced MR Imaging

“…[42][43][44][45][46][47] These reports stated that the restricted diffusion reflected the actual death of tumor cells. However, the current study was performed in a completely different clinical setting.…”