Zero Echo Time 17O-MRI Reveals Decreased Cerebral Metabolic Rate of Oxygen Consumption in a Murine Model of Amyloidosis.
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ABSTRACT:
SUBMITTER: Baligand C
PROVIDER: S-EPMC8145383 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The global cerebral metabolic rate of oxygen (CMRO2), which reflects metabolic activity of the brain under various physiologic conditions, can be quantified using a method, referred to as 'OxFlow', which simultaneously measures hemoglobin oxygen saturation in a draining vein (Yv) and total cerebral blood flow (tCBF). Conventional OxFlow (Conv-OxFlow) entails four interleaves incorporated in a single pulse sequence - two for phase-contrast based measurement of tCBF in the supplying arteries of the neck, and two to measure the intra- to extravascular phase difference in the superior sagittal sinus to derive Yv [Jain et al., JCBFM 2010]. However, this approach limits achievable temporal resolution thus precluding capture of rapid changes of brain metabolic states such as the response to apneic stimuli. Here, we developed a time-efficient, multiplexed OxFlow method and evaluated its potential for measuring dynamic alterations in global CMRO2 during a breath-hold challenge. Two different implementations of multiplexed OxFlow were investigated: 1) simultaneous-echo-refocusing based OxFlow (SER-OxFlow) and 2) simultaneous-multi-slice imaging-based dual-band OxFlow (DB-OxFlow). The two sequences were implemented on 3T scanners (Siemens TIM Trio and Prisma) and their performance was evaluated in comparison to Conv-OxFlow in ten healthy subjects for baseline CMRO2 quantification. Comparison of measured parameters (Yv, tCBF, CMRO2) revealed no significant bias of SER-OxFlow and DB-OxFlow, with respect to the reference Conv-OxFlow while improving temporal resolution two-fold (12.5 versus 25s). Further acceleration shortened scan time to 8 and 6s for SER and DB-OxFlow, respectively, for time-resolved CMRO2 measurement. The two sequences were able of capturing smooth transitions of Yv, tCBF, and CMRO2 over the time course consisting of 30s of normal breathing, 30s of volitional apnea, and 90s of recovery. While both SER- and DB-OxFlow techniques provide significantly improved temporal resolution (by a factor of 3 - 4 relative to Conv-OxFlow), DB-OxFlow was found to be superior for the study of short physiologic stimuli.
| S-EPMC5377447 | biostudies-literature
Project description:We present a technique for quantifying global cerebral metabolic rate of oxygen consumption (CMRO2) in absolute physiologic units at 3-second temporal resolution and apply the technique to quantify the dynamic CMRO2 response to volitional apnea. Temporal resolution of 3 seconds was achieved via a combination of view sharing and superior sagittal sinus-based estimation of total cerebral blood flow (tCBF) rather than tCBF measurement in the neck arteries. These modifications were first validated in three healthy adults and demonstrated to produce minimal errors in image-derived blood flow and venous oxygen saturation (SvO2) values. The technique was then applied in 10 healthy adults during an apnea paradigm of three repeated 30-second breath-holds. Subject-averaged baseline tCBF, arteriovenous oxygen difference (AVO2D), and CMRO2 were 48.6 ± 7.0 mL/100 g per minute, 29.4 ± 3.4 %HbO2, and 125.1 ± 11.4 μmol/100 g per minute, respectively. Subject-averaged maximum changes in tCBF and AVO2D were 43.5 ± 9.4% and -32.1 ± 5.7%, respectively, resulting in a small (6.0 ± 3.5%) but statistically significant (P=0.00044, two-tailed t-test) increase in average end-apneic CMRO2. This method could be used to investigate neurometabolic-hemodynamic relationships in normal physiology, to better define the biophysical origins of the BOLD signal, and to quantify neurometabolic responsiveness in diseases of altered neurovascular reactivity.
| S-EPMC3790925 | biostudies-other
Project description:Dual-calibrated fMRI is a multi-parametric technique that allows for the quantification of the resting oxygen extraction fraction (OEF), the absolute rate of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes during hypercapnic and hyperoxic gas challenges. Here we propose an extension to this methodology that permits the simultaneous quantification of the effective oxygen diffusivity of the capillary network (DC). The effective oxygen diffusivity has the scope to be an informative biomarker and useful adjunct to CMRO2, potentially providing a non-invasive metric of microvascular health, which is known to be disturbed in a range of neurological diseases. We demonstrate the new method in a cohort of healthy volunteers (n = 19) both at rest and during visual stimulation. The effective oxygen diffusivity was found to be highly correlated with CMRO2 during rest and activation, consistent with previous PET observations of a strong correlation between metabolic oxygen demand and effective diffusivity. The increase in effective diffusivity during functional activation was found to be consistent with previously reported increases in capillary blood volume, supporting the notion that measured oxygen diffusivity is sensitive to microvascular physiology.
| S-EPMC6264385 | biostudies-other
Project description:The cerebral metabolic rate of oxygen (CMRO2) is the rate of oxygen consumption by the brain, and is thought to be a direct index of energy homeostasis and brain health. However, in vivo measurement of CMRO2 is challenging, in particular for the neonatal population, in whom conventional radiotracer methods are not applicable because of safety concerns. In this study, we propose a method to quantify global CMRO2 in neonates based on arteriovenous differences in oxygen content, and employ separate measurements of oxygenation and cerebral blood flow (CBF) parameters. Specifically, arterial and venous oxygenation levels were determined with pulse oximetry and the novel T2 relaxation under spin tagging (TRUST) MRI, respectively. Global CBF was measured with phase contrast (PC) flow velocity MRI. The proposed method was implemented on a standard 3-T MRI scanner without the need for any exogenous tracers, and the total scan duration was less than 5?min. We demonstrated the feasibility of this method in 12 healthy neonates within an age range of 35-42 gestational weeks. CMRO2 values were successfully obtained from 10 neonates. It was found that the average CMRO2 in this age range was 38.3?±?17.7?µmol/100?g/min and was positively correlated with age (p?=?0.007; slope, 5.2?µmol/100?g/min per week), although the highest CMRO2 value in this age range was still less than half of the adult level. Test-retest studies showed a coefficient of variation of 5.8?±?2.2% between repeated CMRO2 measurements. In addition, given the highly variable blood flow velocity within this age range, it is recommended that the TRUST labeling thickness and position should be determined on a subject-by-subject basis, and an automatic algorithm was developed for this purpose. Although this method provides a global CMRO2 measure only, the clinical significance of an energy consumption marker and the convenience of this technique may make it a useful tool in the functional assessment of the neonatal population.
| S-EPMC3970939 | biostudies-literature
Project description:Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO2 intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 (P < .001) and T2* (P < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Friedrich in this issue.
| S-EPMC7053244 | biostudies-literature
Project description:The rate of oxygen consumption is a vital marker indicating cellular function during lifetime under normal or metabolically challenged conditions. It is used broadly to study mitochondrial function (Artal-Sanz and Tavernarakis, 2009; Palikaras et al., 2015; Ryu et al., 2016) or investigate factors mediating the switch from oxidative phosphorylation to aerobic glycolysis (Chen et al., 2015; Vander Heiden et al., 2009). In this protocol, we describe a method for the determination of oxygen consumption rates in the nematode Caenorhabditis elegans.
| S-EPMC5321503 | biostudies-literature
Project description:Brain injury following cardiac arrest (CA) is thought to be caused by a sudden loss of blood flow resulting in disruption in oxygen delivery, neural function and metabolism. However, temporal trajectories of the brain's physiology in the first few hours following CA have not been fully characterized. Furthermore, the extent to which these early measures can predict future neurological outcomes has not been determined. The present study sought to perform dynamic measurements of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) with MRI in the first 3 hours following the return of spontaneous circulation (ROSC) in a rat CA model. It was found that CBF, OEF and CMRO2 all revealed a time-dependent increase during the first 3 hours after the ROSC. Furthermore, the temporal trajectories of CBF and CMRO2 , but not OEF, were different across rats and related to neurologic outcomes at a later time (24 hours after the ROSC) (P < .001). Rats who manifested better outcomes revealed faster increases in CBF and CMRO2 during the acute stage. When investigating physiological parameters measured at a single time point, CBF (ρ = 0.82, P = .004) and CMRO2 (ρ = 0.80, P = .006) measured at ~ 3 hours post-ROSC were positively associated with neurologic outcome scores at 24 hours. These findings shed light on brain physiological changes following CA, and suggest that MRI measures of brain perfusion and metabolism may provide a potential biomarker to guide post-CA management.
| S-EPMC7541582 | biostudies-literature
Project description:Spin echo is a fundamental tool for quantum registers and biomedical imaging. It is believed that a strong magnetic field is needed for the spin echo to provide long memory and high resolution, since a degenerate spin cannot be controlled or addressed under a zero magnetic field. While a degenerate spin is never subject to dynamic control, it is still subject to geometric control. Here we show the spin echo of a degenerate spin subsystem, which is geometrically controlled via a mediating state split by the crystal field, in a nitrogen vacancy centre in diamond. The demonstration reveals that the degenerate spin is protected by inherent symmetry breaking called zero-field splitting. The geometric spin echo under zero field provides an ideal way to maintain the coherence without any dynamics, thus opening the way to pseudo-static quantum random access memory and non-invasive biosensors.
| S-EPMC4874036 | biostudies-literature
Project description:Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the brain's metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. However, in depth study of oxygen metabolism with MRI has so far been hindered by the lack of robust methods. One MRI method of mapping CMRO2 is based on the simultaneous acquisition of cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) weighted images during respiratory modulation of both oxygen and carbon dioxide. Although this dual-calibrated methodology has shown promise in the research setting, current analysis methods are unstable in the presence of noise and/or are computationally demanding. In this paper, we present a machine learning implementation for the multi-parametric assessment of dual-calibrated fMRI data. The proposed method aims to address the issues of stability, accuracy, and computational overhead, removing significant barriers to the investigation of oxygen metabolism with MRI. The method utilizes a time-frequency transformation of the acquired perfusion and BOLD-weighted data, from which appropriate feature vectors are selected for training of machine learning regressors. The implemented machine learning methods are chosen for their robustness to noise and their ability to map complex non-linear relationships (such as those that exist between BOLD signal weighting and blood oxygenation). An extremely randomized trees (ET) regressor is used to estimate resting blood flow and a multi-layer perceptron (MLP) is used to estimate CMRO2 and the oxygen extraction fraction (OEF). Synthetic data with additive noise are used to train the regressors, with data simulated to cover a wide range of physiologically plausible parameters. The performance of the implemented analysis method is compared to published methods both in simulation and with in-vivo data (n=30). The proposed method is demonstrated to significantly reduce computation time, error, and proportional bias in both CMRO2 and OEF estimates. The introduction of the proposed analysis pipeline has the potential to not only increase the detectability of metabolic difference between groups of subjects, but may also allow for single subject examinations within a clinical context.
| S-EPMC7116003 | biostudies-literature
Project description:Decreasing the oxygen consumption rate (OCR) of tumor cells is a powerful method for ameliorating tumor hypoxia. However, quantifying the change in OCR is challenging in complex experimental systems. We present a method for quantifying the OCR of two tumor cell lines using oxygen-sensitive dual-emissive boron nanoparticles (BNPs). We hypothesize that our BNP results are equivalent to the standard Seahorse assay. We quantified the spectral emissions of the BNP and accounted for external oxygen diffusion to quantify OCR over 24 h. The BNP-computed OCR of two breast cancer cell lines, E0771 and 4T07, were compared with their respective Seahorse assays. Both cell lines were also irradiated to quantify radiation-induced changes in the OCR. Using a Bland-Altman analysis, our BNPs OCR was equivalent to the standard Seahorse assay. Moreover, in an additional experiment in which we irradiated the cells at their 50% survival fraction, the BNPs were sensitive enough to quantify 24% reduction in OCR after irradiation. Our results conclude that the BNPs are a viable alternative to the Seahorse assay for quantifying the OCR in cells. The Bland-Altman analysis showed that these two methods result in equivalent OCR measurements. Future studies will extend the OCR measurements to complex systems including 3D cultures and in vivo models, in which OCR measurements cannot currently be made.
| S-EPMC7682476 | biostudies-literature