Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging

Yamahara, Takahiro; Numa, Yoshihiro; Oishi, Tetsuya; Kawaguchi, Takuya; Seno, Toshitaka; Asai, Akio; Kawamoto, Keiji

doi:10.1007/s10014-010-0275-7

Cited by 116 publications

(80 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…But far from normal As indicated above, histopathological examination found tumor cell infiltration in one third of PBZ in contrast with radiological and macroscopic analyses, which is consistent with data from the literature [9][10][11]36]. Flow cytometry, genomic, transcriptomic, and primary cell culture approaches also identified these neoplastic features in PBZ.…”

Section: Discussionsupporting

confidence: 85%

“…Despite complete surgical resection, recurrence happens in almost all cases, mostly at the margin of the resection cavity in the peritumoral brain zone (PBZ) [7,8]. It is widely believed that tumor cell infiltration into the PBZ may promote recurrence [9][10][11]. However, few cellular and molecular analyses have been performed in this area.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

et al. 2015

View full text Add to dashboard Cite

Glioblastoma (GB) is the most frequent and aggressive type of primary brain tumor. Recurrences are mostly located at the margin of the resection cavity in the peritumoral brain zone (PBZ). Although it is widely believed that infiltrative tumor cells in this zone are responsible for GB recurrence, few studies have examined this zone. In this study, we analyzed PBZ left after surgery with a variety of techniques including radiology, histopathology, flow cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The resulting PBZ profiles were compared with those of the GB tumor zone and normal brain samples to identify characteristics specific to the PBZ. We found that tumor cell infiltration detected by standard histological analysis was present in almost one third of PBZ taken from an area that was considered normal both on standard MRI and by the neurosurgeon under an operating microscope. The panel of techniques used in this study show that the PBZ, similar to the tumor zone itself, is characterized by substantial inter-patient heterogeneity, which makes it difficult to identify representative markers. Nevertheless, we identified specific alterations in the PBZ such as the presence of selected tumor clones and stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is a growing field of interest and this region needs to be characterized further. This will facilitate the development of new, targeted therapies for patients with GB and the development of approaches to refine the per-operative evaluation of the PBZ to optimize the surgical resection of the tumor.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The maximum width of these ROIs was two voxels to maintain region homogeneity and specifically did not include any area that was contrast-enhancing. These two ROIs served as reference examples for near-tumor and far-from-tumor tissue, based on the expectation that they are likely to have relatively higher and lower infiltration respectively (21, 22), albeit they are merely modeling parameters and by no means imply anything about true underlying (unknown) infiltration.…”

Section: Methodsmentioning

confidence: 99%

Pattern Analysis of Dynamic Susceptibility Contrast-enhanced MR Imaging Demonstrates Peritumoral Tissue Heterogeneity

et al. 2014

View full text Add to dashboard Cite

Purpose The aim of this study is to augment the analysis of dynamic susceptibility contrast MRI (DSC-MRI) to uncover unique tissue characteristics that could potentially facilitate treatment planning through a better understanding of the peritumoral region of patients with glioblastoma. Materials and Methods IRB approval was obtained for this study with waiver of informed consent for retrospective review of medical records. DSC-MRI data was obtained for 79 patients and principal component analysis (PCA) was applied to the perfusion signal. The first six principal components (PCs) were sufficient to characterize more than 99% of variance in the temporal dynamics of blood perfusion in all regions of interest. The PCs were subsequently used in conjunction with a support vector machine (SVM) classifier to create a map of heterogeneity within the peritumoral region and the variance of this map served as the heterogeneity score. Results The calculated PCs allowed near perfect separability of tissue that was likely highly infiltrated from tissue that was unlikely infiltrated with tumor. The heterogeneity map created using the PCs showed a clear relationship between voxels judged by the SVM to be highly infiltrated and subsequent recurrence. The results demonstrated a significant correlation (r=0.46, p<0.0001) between the heterogeneity score and patient survival. The hazard ratio was 2.23 (95% CI, 1.4-3.6, p <0.01) between high and low heterogeneity score patients based on the median heterogeneity score. Conclusion Analysis of DSC-MRI data using PCA can identify imaging variables that can be subsequently utilized to evaluate the peritumoral region in glioblastoma. These variables are potentially indicative of tumor infiltration and may become useful tools in guiding therapy as well as individualized prognostication.

show abstract

“…We hypothesized that the EGFRvIII + tumors, which are thought to have aggressive, migratory and infiltrative phenotypes, would present imaging signatures consistent with deep infiltration throughout the peritumoral edematous tissue. In addition, we hypothesized that assessment of the tumor cell infiltration heterogeneity (30) in the peritumoral edema, may be discriminatory of the EGFRvIII status and hence lead to a distinctive imaging biomarker. Taking into consideration that edema is a result of infiltrating tumor cells, as well as a biological response to the angiogenic and vascular permeability factors released by the spatially adjacent tumor cells (31), Dynamic Susceptibility Contrast (DSC) MRI was used to indirectly measure changes in perfusion as they relate to EGFRvIII .…”

Section: Introductionmentioning

confidence: 99%

In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The ϕ-Index

Bakas

Akbari

Pisapia

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

PURPOSE The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor’s spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma non-invasively, using routine clinically-acquired imaging. EXPERIMENTAL DESIGN We found peritumoral infiltration and vascularization patterns being related to EGFRvIII status. We therefore constructed a quantitative within-patient peritumoral heterogeneity index (PHI/φ-index), by contrasting perfusion patterns of immediate and distant peritumoral edema. Application of φ-index in preoperative perfusion scans of independent discovery (n=64) and validation (n=78) cohorts, revealed the generalizability of this EGFRvIII imaging signature. RESULTS Analysis in both cohorts demonstrated that the obtained signature is highly accurate (89.92%), specific (92.35%) and sensitive (83.77%), with significantly distinctive ability (p=4.0033×10−10, AUC=0.8869). Findings indicated a highly infiltrative-migratory phenotype for EGFRvIII+ tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, EGFRvIII− tumors displayed perfusion dynamics consistent with peritumorally-confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation. CONCLUSIONS This EGFRvIII signature is potentially suitable for clinical translation, since obtained from analysis of clinically-acquired images. Use of within-patient heterogeneity measures, rather than population-based associations, renders φ-index potentially resistant to inter-scanner variations. Overall, our findings enable non-invasive evaluation of EGFRvIII for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation.

show abstract

Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging

Cited by 116 publications

References 25 publications

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

Pattern Analysis of Dynamic Susceptibility Contrast-enhanced MR Imaging Demonstrates Peritumoral Tissue Heterogeneity

In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The ϕ-Index

Contact Info

Product

Resources

About