Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

BackgroundAlthough the contrast-enhancing (CE) lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden.MethodsFifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy.ResultsThe Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data.ConclusionsThe similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM

Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.

BackgroundA specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors.MethodsIn a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age <21 years and 16 patients who did not receive CRT, we determined the presence of CMBs on brain MRIs. Neurocognitive function was assessed using a computerized testing program (CogState). We used survival analysis to determine cumulative incidence of CMBs and Poisson regression to examine risk factors for CMBs. Linear regression models were used to assess effect of CMBs on neurocognitive function.ResultsThe cumulative incidence of CMBs was 48.8% (95% CI: 38.3-60.5) at 5 years. Children who had whole brain irradiation developed CMBs at a rate 4 times greater than those treated with focal irradiation (P < .001). In multivariable analysis, children with CMBs performed worse on the Groton Maze Learning test (GML) compared with those without CMBs (Z-score -1.9; 95% CI: -2.7, -1.1; P < .001), indicating worse executive function when CMBs are present. CMBs in the frontal lobe were associated with worse performance on the GML (Z-score -2.4; 95% CI: -2.9, -1.8; P < .001). Presence of CMBs in the temporal lobes affected verbal memory (Z-score -2.0; 95% CI: -3.3, -0.7; P = .005).ConclusionCMBs are common and associated with neurocognitive dysfunction in pediatric brain tumor survivors treated with radiation

Relationship between radiation dose and microbleed formation in patients with malignant glioma

Abstract Background Cranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified. Methods SWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4 years after chemoradiotherapy to 60 Gy. The median age at the time of treatment was 41 years (range 25 – 74 years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (45 Gy) dose regions was computed. Results Twelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (>3 years from treatment) compared to early (<3 years) timepoints (early median 6 CMBs; late median 27 CMBs; p = 0.001), and there were proportionally more CMBs at lower doses for late scans (p = 0.006). 88% of all CMBs were observed in regions receiving at least 30 Gy, but the CMB density within medium and high dose regions was not significantly different (p = 0.33 and p = 0.9, respectively, for early and late time points). Conclusions CMBs predominantly form in regions receiving at least 30 Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose–response relationship at doses above 30 Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation

Relationship between radiation dose and microbleed formation in patients with malignant glioma.

BackgroundCranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified.MethodsSWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4&nbsp;years after chemoradiotherapy to 60&nbsp;Gy. The median age at the time of treatment was 41&nbsp;years (range 25 - 74&nbsp;years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (&lt;30&nbsp;Gy), median (30-45&nbsp;Gy), and high (&gt;45&nbsp;Gy) dose regions was computed.ResultsTwelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (&gt;3&nbsp;years from treatment) compared to early (&lt;3&nbsp;years) timepoints (early median 6 CMBs; late median 27 CMBs; p&nbsp;=&nbsp;0.001), and there were proportionally more CMBs at lower doses for late scans (p&nbsp;=&nbsp;0.006). 88% of all CMBs were observed in regions receiving at least 30&nbsp;Gy, but the CMB density within medium and high dose regions was not significantly different (p&nbsp;=&nbsp;0.33 and p&nbsp;=&nbsp;0.9, respectively, for early and late time points).ConclusionsCMBs predominantly form in regions receiving at least 30&nbsp;Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose-response relationship at doses above 30&nbsp;Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation

Toward Automatic Detection of Radiation-Induced Cerebral Microbleeds Using a 3D Deep Residual Network

Cerebral microbleeds, which are small focal hemorrhages in the brain that are prevalent in many diseases, are gaining increasing attention due to their potential as surrogate markers of disease burden, clinical outcomes, and delayed effects of therapy. Manual detection is laborious and automatic detection and labeling of these lesions is challenging using traditional algorithms. Inspired by recent successes of deep convolutional neural networks in computer vision, we developed a 3D deep residual network that can distinguish true microbleeds from false positive mimics of a previously developed technique based on traditional algorithms. A dataset of 73 patients with radiation-induced cerebral microbleeds scanned at 7&nbsp;T with susceptibility-weighted imaging was used to train and evaluate our model. With the resulting network, we maintained 95% of the true microbleeds in 12 test patients and the average number of false positives was reduced by 89%, achieving a detection precision of 71.9%, higher than existing published methods. The likelihood score predicted by the network was also evaluated by comparing to a neuroradiologist's rating, and good correlation was observed

QSMGAN: Improved Quantitative Susceptibility Mapping using 3D Generative Adversarial Networks with increased receptive field

Quantitative susceptibility mapping (QSM) is a powerful MRI technique that has shown great potential in quantifying tissue susceptibility in numerous neurological disorders. However, the intrinsic ill-posed dipole inversion problem greatly affects the accuracy of the susceptibility map. We propose QSMGAN: a 3D deep convolutional neural network approach based on a 3D U-Net architecture with increased receptive field of the input phase compared to the output and further refined the network using the WGAN with gradient penalty training strategy. Our method generates accurate QSM maps from single orientation phase maps efficiently and performs significantly better than traditional non-learning-based dipole inversion algorithms. The generalization capability was verified by applying the algorithm to an unseen pathology--brain tumor patients with radiation-induced cerebral microbleeds