Manabu Kinoshita, Hideyuki Arita, Yoshiko Okita, Naoki Kagawa, Haruhiko Kishima, Naoya Hashimoto, Hisashi Tanaka, Yoshiyuki Watanabe, Eku Shimosegawa, Jun Hatazawa, Yasunori Fujimoto and Toshiki Yoshimine
Diffusion MRI is attracting increasing interest for tissue characterization of gliomas, especially after the introduction of antiangiogenic therapy to treat malignant gliomas. The goal of the current study is to elucidate the actual magnitude of the correlation between diffusion MRI and cell density within the tissue. The obtained results were further extended and compared with metabolic imaging with 11C-methionine (MET) PET.
Ninety-eight tissue samples from 37 patients were stereotactically obtained via an intraoperative neuronavigation system. Diffusion tensor imaging (DTI) and MET PET were performed as routine presurgical imaging studies for these patients. DTI was converted into fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps, and MET PET images were registered to Gd-administered T1-weighted images that were used for navigation. Metrics of FA, ADC, and tumor-to-normal tissue ratio of MET PET along with relative values of FA (rFA) and ADC (rADC) compared with normal-appearing white matter were correlated with cell density of the stereotactically obtained tissues.
rADC was significantly lower in lesions obtained from Gd-enhancing lesions than from nonenhancing lesions. Although rADC showed a moderate but statistically significant negative correlation with cell density (p = 0.010), MET PET showed a superb positive correlation with cell density (p < 0.0001). On the other hand, rFA showed little correlation with cell density.
The presented data validated the use of rADC for estimating the treatment response of gliomas but also caution against overestimating its limited accuracy compared with MET PET.
Yasuyoshi Chiba, Manabu Kinoshita, Yoshiko Okita, Akihiro Tsuboi, Kayako Isohashi, Naoki Kagawa, Yasunori Fujimoto, Yusuke Oji, Yoshihiro Oka, Eku Shimosegawa, Satoshi Morita, Jun Hatazawa, Haruo Sugiyama, Naoya Hashimoto and Toshiki Yoshimine
Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of 11C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OSWT1).
Fourteen patients with recurrent malignant glioma were included in the study, and OSWT1 was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of 11C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy.
The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in 11C-methionine uptake pre- and posttreatment; 2) area with increased 11C-methionine uptake posttreatment (PRM+MET); and 3) area with decreased 11C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OSWT1 (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM+MET area showed excellent correlation (p = 0.008) with OSWT1.
This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001.
Takero Hirata, Manabu Kinoshita, Keisuke Tamari, Yuji Seo, Osamu Suzuki, Nobuhide Wakai, Takamune Achiha, Toru Umehara, Hideyuki Arita, Naoki Kagawa, Yonehiro Kanemura, Eku Shimosegawa, Naoya Hashimoto, Jun Hatazawa, Haruhiko Kishima, Teruki Teshima and Kazuhiko Ogawa
It is important to correctly and precisely define the target volume for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission tomography (PET) holds promise for detecting areas of glioma cell infiltration: the authors’ previous research showed that the magnitude of disruption of MET and 18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely reflects glioma cell invasion. The purpose of the present study was to analyze volumetric and geometrical properties of RT target delineation based on DS and compare them with those based on MRI.
Twenty-five patients with a diagnosis of malignant glioma were included in this study. Three target volumes were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and 3) lesions showing high DS (DS ≥ 3; hDS). The geometrical differences of these target volumes were assessed by calculating the probabilities of overlap and one encompassing the other. The correlation of geometrical features of RT planning and recurrence patterns was further analyzed.
The analysis revealed that T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6 (24%) patients, which indicates that microscopic invasion of glioma cells often extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage of high DS regions with RT target volumes was suggested to be a risk for out-of-field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher values of “[T1Gd + 2 cm]/hDS”) had a trend to positively impact overall and progression-free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside the Gd-enhanced core lesion, indicative of out-of-field reoccurrence.
The findings of this study indicate that MRI is inadequate for target delineation for RT in malignant glioma treatment. Expanding the treated margins substantially beyond the MRI-based target volume may reduce the risk of undertreatment, but it may also result in unnecessary irradiation of uninvolved regions. As MET/FDG PET-DS seems to provide more accurate information for target delineation than MRI in malignant glioma treatment, this method should be further evaluated on a larger scale.