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.

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High Temporal Resolution MRI Quantification of Global Cerebral Metabolic Rate of Oxygen Consumption in Response to Apneic Challenge

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.110 ◽

2013 ◽

Vol 33 (10) ◽

pp. 1514-1522 ◽

Cited By ~ 40

Author(s):

Zachary B Rodgers ◽

Varsha Jain ◽

Erin K Englund ◽

Michael C Langham ◽

Felix W Wehrli

Keyword(s):

Blood Flow ◽

Oxygen Consumption ◽

Metabolic Rate ◽

Temporal Resolution ◽

Healthy Adults ◽

High Temporal Resolution ◽

View Sharing ◽

Cerebral Metabolic Rate ◽

Sagittal Sinus ◽

Rate Of Oxygen Consumption

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.

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Quantification of whole‐brain oxygenation extraction fraction and cerebral metabolic rate of oxygen consumption in adults with sickle cell anemia using individual T 2 ‐based oxygenation calibrations

Magnetic Resonance in Medicine ◽

10.1002/mrm.27972 ◽

2019 ◽

Vol 83 (3) ◽

pp. 1066-1080 ◽

Cited By ~ 4

Author(s):

Wenbo Li ◽

Xiang Xu ◽

Peiying Liu ◽

John J. Strouse ◽

James F. Casella ◽

...

Keyword(s):

Oxygen Consumption ◽

Metabolic Rate ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Brain Oxygenation ◽

Whole Brain ◽

Cerebral Metabolic Rate ◽

Extraction Fraction ◽

Rate Of Oxygen Consumption

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Corrigendum: A Frequency-Domain Machine Learning Method for Dual-Calibrated fMRI Mapping of Oxygen Extraction Fraction (OEF) and Cerebral Metabolic Rate of Oxygen Consumption (CMRO2)

Frontiers in Artificial Intelligence ◽

10.3389/frai.2021.614245 ◽

2021 ◽

Vol 4 ◽

Author(s):

Michael Germuska ◽

Hannah Louise Chandler ◽

Thomas Okell ◽

Fabrizio Fasano ◽

Valentina Tomassini ◽

...

Keyword(s):

Machine Learning ◽

Oxygen Consumption ◽

Metabolic Rate ◽

Oxygen Extraction Fraction ◽

Machine Learning Method ◽

Learning Method ◽

Cerebral Metabolic Rate ◽

Extraction Fraction ◽

Rate Of Oxygen Consumption ◽

Calibrated Fmri

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Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen consumption and effective oxygen diffusivity

NeuroImage ◽

10.1016/j.neuroimage.2018.09.035 ◽

2019 ◽

Vol 184 ◽

pp. 717-728 ◽

Cited By ~ 13

Author(s):

M. Germuska ◽

H.L. Chandler ◽

R.C. Stickland ◽

C. Foster ◽

F. Fasano ◽

...

Keyword(s):

Oxygen Consumption ◽

Metabolic Rate ◽

Cerebral Metabolic Rate ◽

Oxygen Diffusivity ◽

Rate Of Oxygen Consumption ◽

Calibrated Fmri

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Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.34 ◽

2011 ◽

Vol 31 (7) ◽

pp. 1504-1512 ◽

Cited By ~ 73

Author(s):

Varsha Jain ◽

Michael C Langham ◽

Thomas F Floyd ◽

Gaurav Jain ◽

Jeremy F Magland ◽

...

Keyword(s):

Carbon Dioxide ◽

Oxygen Consumption ◽

Magnetic Resonance ◽

Metabolic Rate ◽

Vascular Reactivity ◽

Cerebral Metabolism ◽

Metabolic Effects ◽

Cerebral Metabolic Rate ◽

Rate Of Oxygen Consumption ◽

End Tidal

The effect of hypercapnia on cerebral metabolic rate of oxygen consumption ( CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation ( Sv O2) and total cerebral blood flow ( tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in Sv O2 and tCBF were observed during hypercapnia ( P < 0.005), no change in CMRO2 was noted ( P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide ( R2 = 0.72, P < 0.005), as well as baseline Sv O2 and tCBF ( R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity ( CVR) and baseline tCBF ( R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in Sv O2 and tCBF upon recovery from hypercapnia in six subjects.

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