Three‐dimensional mapping of brain venous oxygenation using oximetry

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Cerebral venous oxygenation (Yv) is closely associated with the brain's oxygen extraction, metabolism, and to some extent neural activity, and is a promising biomarker in several major neurological diseases including stroke 1, tumor 3, and Alzheimer's disease 4. However, measurement of cerebral venous oxygenation in humans has proven difficult. 15O positron emission tomography was one of the first methods developed to measure Yv, but this method requires inhalation of radioactive gas, arterial blood sampling, and an onsite cyclotron to produce the short half‐life 15O tracer 7. As a result, only a small number of laboratories are still performing such experiments in recent years.
An active research topic in the MRI field, therefore, is the development of new techniques to noninvasively measure Yv in humans. To this end, measurement of global, whole‐brain venous oxygenation is now relatively well‐established. One can either use the T2 relaxation under spin tagging (TRUST) 8 or phase susceptometry method 9 to determine cerebral Yv within approximately 1 min. In contrast, considerable technical development is still needed for MRI techniques of regional Yv quantification, which would have a greater potential for clinical applications. Although all such techniques are based on the paramagnetic property of deoxyhemoglobin, different types of methods have focused on magnitude 10 or phase 13 manifestations of these effects. One particular line of techniques is based on a calibratable relationship between blood R2 (or JOURNAL/mrim/04.02/01445475-201803000-00009/math_9MM1/v/2018-01-24T161827Z/r/image-png ) and oxygenation (Y) 15. By designing advanced MR pulse sequences to accurately measure blood transverse relaxation in vivo, one can obtain a quantitative assessment of cerebral oxygenation without using any contrast agent or physiological challenge. Although several efforts have demonstrated promising results 18, the spatial coverage of these previous works has been limited to a single slice. Therefore, to have a practical utility in clinical settings, expansion of these techniques to 3D, ideally with whole‐brain coverage, is highly desirable.
The goal of this study is to develop 3D acquisition and analysis schemes to measure blood oxygenation in human cerebral veins after accounting for partial voluming between blood and tissue. The proposed method uses velocity‐encoded phase‐contrast imaging to differentiate flowing blood signal from static tissue, and applies flow‐compensated multi‐gradient‐echo acquisition to rapidly map blood JOURNAL/mrim/04.02/01445475-201803000-00009/math_9MM2/v/2018-01-24T161827Z/r/image-png . In vivo experiments were performed to demonstrate the feasibility and reproducibility of this method. Sensitivity of the method to known effect of oxygenation change was tested by hyperoxia physiological challenge. In vitro experiments were performed to establish the JOURNAL/mrim/04.02/01445475-201803000-00009/math_9MM3/v/2018-01-24T161827Z/r/image-png ‐Y calibration plot, from which the in vivo JOURNAL/mrim/04.02/01445475-201803000-00009/math_9MM4/v/2018-01-24T161827Z/r/image-png values could be converted to physiological value of venous oxygen saturation fraction. Validation was performed by comparing the Yv measured with this new sequence to an established method of global Yv21. Finally, tradeoff between in‐plane and through‐plane resolution in 3D acquisition was investigated.

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