Artificial Neural Network-Derived Cerebral Metabolic Rate of Oxygen for Differentiating Glioblastoma and Brain Metastasis in MRI: A Feasibility Study

Glioblastoma may appear similar to cerebral metastasis on conventional MRI in some cases, but their therapies differ significantly. This prospective feasibility study was aimed at differentiating them by applying the quantitative susceptibility mapping and quantitative blood-oxygen-level-dependent (QSM + qBOLD) model to these entities for the first time. We prospectively included 15 untreated patients with glioblastoma (n = 7, median age: 68 years, range: 54–84 years) or brain metastasis (n = 8, median age 66 years, range: 50–78 years) who underwent preoperative MRI including multi-gradient echo and arterial spin labeling sequences. Oxygen extraction fraction (OEF), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were calculated in the contrast-enhancing tumor (CET) and peritumoral non-enhancing T2 hyperintense region (NET2), using an artificial neural network. We demonstrated that OEF in CET was significantly lower (p = 0.03) for glioblastomas than metastases, all features were significantly higher (p = 0.01) in CET than in NET2 for metastasis patients only, and the ratios of CET/NET2 for CBF (p = 0.04) and CMRO2 (p = 0.01) were significantly higher in metastasis patients than in glioblastoma patients. Discriminative power of a support-vector machine classifier was highest with a combination of two features, yielding an area under the receiver operating characteristic curve of 0.94 with 93% diagnostic accuracy. QSM + qBOLD allows for robust differentiation of glioblastoma and cerebral metastasis while yielding insights into tumor oxygenation.

Non-Invasive measurement of the cerebral metabolic rate of oxygen using MRI in rodents

Malfunctions of oxygen metabolism are suspected to play a key role in a number of neurological and psychiatric disorders, but this hypothesis cannot be properly investigated without an in-vivo non-invasive measurement of brain oxygen consumption. We present a new way to measure the Cerebral Metabolic Rate of Oxygen (CMRO2) by combining two existing magnetic resonance imaging techniques, namely arterial spin-labelling and oxygen extraction fraction mapping. This method was validated by imaging rats under different anaesthetic regimes and was strongly correlated to glucose consumption measured by autoradiography.

Non-Invasive measurement of the cerebral metabolic rate of oxygen using MRI in rodents

Malfunctions of oxygen metabolism are suspected to play a key role in a number of neurological and psychiatric disorders, but this hypothesis cannot be properly investigated without an in-vivo non-invasive measurement of brain oxygen consumption. We present a new way to measure the Cerebral Metabolic Rate of Oxygen (CMRO2) by combining two existing magnetic resonance imaging techniques, namely arterial spin-labelling and oxygen extraction fraction mapping. This method was validated by imaging rats under different anaesthetic regimes and was strongly correlated to glucose consumption measured by autoradiography.

Zero Echo Time 17O-MRI Reveals Decreased Cerebral Metabolic Rate of Oxygen Consumption in a Murine Model of Amyloidosis

The cerebral metabolic rate of oxygen consumption (CMRO2) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO2 can be measured by direct 17O magnetic resonance imaging (17O-MRI) of H217O signal changes during inhalation of 17O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.7 T to measure CMRO2 in the APPswe/PS1dE9 mouse model of amyloidosis. We found that CMRO2 was significantly lower in the APPswe/PS1dE9 brain than in wild-type at 12–14 months. We also estimated cerebral blood flow (CBF) from the post-inhalation washout curve and found no difference between groups. These results suggest that the lower CMRO2 observed in APPswe/PS1dE9 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the 17O-MRI data using different quantification models (linear and 3-phase model) showed that the choice of the model does not affect group comparison results. However, the simplified linear model significantly underestimated the absolute CMRO2 values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients

Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. Methods In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. Results Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 μmol · 100 g−1 · min−1; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 1.5 [−13.3 to 16.3] μmol · 100 g−1 · min−1 [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 μmol · 100 g−1 · min−1; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 8.2 [−2.0 to 18.5] μmol · 100 g−1 · min−1 [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g−1 · min−1 [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], −0.6 [−14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], −0.1 [− 12.1 to 12.0]% [P = 0.989]) were comparable between groups. Conclusions The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New