A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO<sub>2</sub>)

Germuska, Michael; Chandler, Harold L.; Okell, Thomas W.; Fasano, Fabrizio; Tomassini, Valentina; Murphy, Kevin; Wise, Richard G.

doi:10.1101/660357

Cited by 3 publications

(16 citation statements)

References 44 publications

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“…With respect to the in-vivo validation using dc-fMRI, a limiting factor was related to the investigation of the proposed model proportionality constant A · ρ/k and P m O 2,0 . These estimates were evaluated assuming the OEF 0 derived from the dc-fMRI machine learning analysis 22 to be exact. In fact, noise in the dc-fMRI OEF 0 limited our investigation of the model parameters to global evaluation within the GM.…”

Section: Discussionmentioning

confidence: 99%

“…35 Moreover, we expect a value for the oxygen effective permeability k of around 3 μmol/mmHg/ml/min. 22 This value is derived from the literature using a different formalism where oxygen diffusion is assumed to happen at the endothelial wall of capillaries. 36 In equations (9) and (10), we create a practical grouping of A, ρ and k into one multiplicative parameter A · ρ/k.…”

Section: Methodsmentioning

confidence: 99%

“…The two respiratory stimuli decouple the contribution to M of OEF 0 and the dHb 0 -sensitive cerebral blood volume, CBV v,0 , when Hb concentration in blood [Hb] 4,14 is known. Although dc-fMRI has been applied in exemplar clinical studies, 17–21 its adoption is limited by the low signal to noise ratio (SNR) 22 and by the complex gas challenge paradigm required.…”

Section: Introductionmentioning

confidence: 99%

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A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI

Chiarelli

Germuska

Chandler

et al. 2022

J Cereb Blood Flow Metab

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One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10−3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI

Chiarelli

Germuska

Chandler

et al. 2022

J Cereb Blood Flow Metab

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“…For the regional OEF measurement, a major challenge is the low SNR, because the local blood volume is very small and many techniques rely on complex model fittings that are sensitive to noise. Some authors have proposed exploiting machine‐learning methods to denoise the OEF maps and reduce the computational cost 177,187,188 . Future technical developments designed to improve the SNR are critical for the robustness of regional OEF measurement.…”

Section: Mri Techniques For Oef Measurementmentioning

confidence: 99%

“…176 Machine-learning-based methods have also been proposed. 177 dc-fMRI allows simultaneous measurement of OEF, CBF, and CMRO 2 . In addition, cerebrovascular reactivity (CVR) can also be extracted from the dc-fMRI data, 23,176 which itself is an important index of cerebrovascular health.…”

Section: Dual-calibrated Fmrimentioning

confidence: 99%

Cerebral oxygen extraction fractionMRI: Techniques and applications

Jiang

2022

Magnetic Resonance in Med

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The human brain constitutes 2% of the body's total mass but uses 20% of the oxygen. The rate of the brain's oxygen utilization can be derived from a knowledge of cerebral blood flow and the oxygen extraction fraction (OEF). Therefore, OEF is a key physiological parameter of the brain's function and metabolism.OEF has been suggested to be a useful biomarker in a number of brain diseases.With recent advances in MRI techniques, several MRI-based methods have been developed to measure OEF in the human brain. These MRI OEF techniques are based on the T 2 of blood, the blood signal phase, the magnetic susceptibility of blood-containing voxels, the effect of deoxyhemoglobin on signal behavior in extravascular tissue, and the calibration of the BOLD signal using gas inhalation.Compared to 15 O PET, which is considered the "gold standard" for OEF measurement, MRI-based techniques are non-invasive, radiation-free, and are more widely available. This article provides a review of these emerging MRI-based OEF techniques. We first briefly introduce the role of OEF in brain oxygen homeostasis. We then review the methodological aspects of different categories of MRI OEF techniques, including their signal mechanisms, acquisition methods, and data analyses. The strengths and limitations of the techniques are discussed.Finally, we review key applications of these techniques in physiological and pathological conditions.

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Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

Chandler

Stickland

Patitucci

et al. 2022

J Cereb Blood Flow Metab

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Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF ( p = 0.010), CMRO2 ( p < 0.001) and DC ( p = 0.002), and increased PmO2 ( p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb ( p = 0.389), OEF ( p = 0.358), or GM volume ( p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.

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A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO₂)

Abstract: 18

Cited by 3 publications

References 44 publications

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI

Cerebral oxygen extraction fractionMRI: Techniques and applications

Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

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A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2)

Abstract: 18

Cited by 3 publications

References 44 publications

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI

Cerebral oxygen extraction fractionMRI: Techniques and applications

Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

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Product

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A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO₂)

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO₂) with single gas calibrated fMRI