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McLean, M. A.

Publications and source records attributed to McLean, M. A..

2 recordsLinked to original sources
bioRxiv2017

Multi-Parametric and Multi-Regional Histogram Analysis of MRI: Revealing Imaging Phenotypes of Glioblastoma Correlated with Patient Survival

IntroductionGlioblastoma is characterized by its remarkable heterogeneity and dismal prognosis. Histogram analysis of quantitative magnetic resonance imaging (MRI) is an important in vivo method to study intratumoral heterogeneity. With large amounts of histogram features generated, integrating these modalities effectively for clinical decision remains a challenge.\n\nMethodsA total of 80 patients with supratentorial primary glioblastoma were recruited. All patients received surgery and standard regimen of temozolomide chemoradiotherapy. Diagnosis was confirmed by pathology. Anatomical T2-weighted, T1-weighted post-contrast and FLAIR images, as well as dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging were acquired preoperatively using a 3T MRI scanner. DTI-p, DTI-q, relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated. Contrast-enhancing (CE) and non-enhancing (NE) regions of interest were manually delineated. Voxel intensity histograms were constructed from the CE and NE regions independently. Patient clustering was performed by the Multi-View Biological Data Analysis (MVDA) approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of the patient clustering to survival. The histogram features selected from MVDA approach were evaluated using receiver operator characteristics (ROC) curve analysis. The metabolic signatures of the patient clusters were analyzed by multivoxel MR spectroscopy (MRS).\n\nResultsThe MVDA approach yielded two final patient clusters, consisting of 53 and 27 patients respectively. The two patient subgroups showed significance for overall survival (p = 0.007, HR = 0.32) and progression-free survival (p < 0.001, HR = 0.33) in multivariate Cox regression analysis. Among the features selected by MVDA, higher mean value of DTI-q in the non-enhancing region contributed to a worse OS (HR = 1.40, p = 0.020) and worse PFS (HR = 1.36, p = 0.031). Multivoxel MRS showed N-acetylaspartate/creatine (NAA/Cr) ratio between the two clusters, both in the CE region (p < 0.001) and NE region (p = 0.013). Glutamate/Cr (Glu/Cr) ratio and glutamate + glutamine/Cr (Glx/Cr) of the cluster 1 was significantly lower than cluster 2 (p = 0.037, and 0.027 respectively) In the NE region.\n\nDiscussionThis study demonstrated that integrating multi-parametric and multi-regional MRI histogram features may help to stratify patients. The histogram features selected from the proposed approach may be used as potential imaging markers in personalized treatment strategy and response determination.

bioinformatics↗
bioRxiv2017

Low Perfusion Compartments in Glioblastoma Quantified by Advanced Magnetic Resonance Imaging: Correlation with Patient Survival

BackgroundGlioblastoma exhibits profound intratumoral heterogeneity in blood perfusion, which may cause inconsistent therapy response. Particularly, low perfusion may create hypoxic microenvironment and induce resistant clones. Thus, developing validated imaging approaches that define low perfusion compartments is crucial for clinical management.\n\nMethodsA total of 112 newly-diagnosed supratentorial glioblastoma patients were prospectively recruited for maximal safe resection. Preoperative MRI included anatomical, dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging (CSI). The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from DTI and DSC respectively. Using thresholding methods, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified. Volumetric analysis was performed. Lactate and macromolecule/lipid levels were determined from multivoxel spectroscopy. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier and multivariate Cox regression analyses.\n\nResultsTwo compartments displayed higher lactate and macromolecule/lipid levels than normal controls (each P < 0.001), suggesting hypoxic and pro-inflammatory microenvironment. The proportional volume of ADCL-rCBVL compartment was associated with a larger infiltration area (P < 0.001, rho = 0.42). Lower lactate in this compartment was associated with a less invasive phenotype visualized on DTI. Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with a worse survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005).\n\nConclusionsThe ADCL-rCBVL compartment represent a treatment resistant sub-region associated with glioblastoma invasiveness. This approach was based on clinically available imaging modalities and could thus provide crucial pretreatment information for clinical decision making.

cancer biology↗