Abstract
Water concentration is tightly regulated in the healthy human brain and changes only slightly with age and gender in healthy subjects. Consequently, changes in water content are important for the characterization of disease. MRI can be used to measure changes in brain water content, but as these changes are usually in the low percentage range, highly accurate and precise methods are required for detection. The method proposed here is based on a long-TR (10 s) multiple-echo gradient-echo measurement with an acquisition time of 7:21 min. Using such a long TR ensures that there is no T1 weighting, meaning that the image intensity at zero echo time is only proportional to the water content, the transmit field, and to the receive field. The receive and transmit corrections, which are increasingly large at higher field strengths and for highly segmented coil arrays, are multiplicative and can be approached heuristically using a bias field correction. The method was tested on 21 healthy volunteers at 3T field strength. Calibration using cerebral-spinal fluid values (~100% water content) resulted in mean values and standard deviations of the water content distribution in white matter and gray matter of 69.1% (1.7%) and 83.7% (1.2%), respectively. Measured distributions were coil-independent, as seen by using either a 12-channel receiver coil or a 32-channel receiver coil. In a test-retest investigation using 12 scans on one volunteer, the variation in the mean value of water content for different tissue types was ~0.3% and the mean voxel variability was ~1%. Robustness against reduced SNR was assessed by comparing results for 5 additional volunteers at 1.5T and 3T. Furthermore, water content distribution in gray matter is investigated and regional contrast reported for the first time. Clinical applicability is illustrated with data from one stroke patient and one brain tumor patient. It is anticipated that this fast, stable, easy-to-use, high-quality mapping method will facilitate routine quantitative MR imaging of water content.
Highlights
Water concentration is highly regulated in the healthy human brain and changes only slightly with age and gender [1,2,3]
The reliance on nonspecific treatments for brain oedema is a result of an incomplete understanding of specific cellular mechanisms by which brain water content is controlled under physiological conditions [12]
In contrast to its beneficial role in cytotoxic oedema, AQP4 deficiency produces more brain swelling in mouse models of vasogenic oedema, including brain tumor, infusion of normal saline into brain extracellular space (ECS), and focal cortical freeze injury, the latter leading to a leaky blood-brain barrier (BBB) [14]
Summary
Water concentration is highly regulated in the healthy human brain and changes only slightly with age and gender [1,2,3]. The normal adult human intracranial cavity (∼1.4 L) comprises several compartments including blood (∼100 mL), CSF (∼100 mL) and brain parenchyma intracellular (∼1.1 L), and interstitial (∼100 mL) spaces [4]. Water flows between these compartments in response to osmotic and hydrostatic forces. Aquaporin (AQP) inhibitors, in contrast, may slow tumor growth These recent results and understanding [4] suggest possible applications of AQP-channel modulators—which are, yet to be developed—to be used for treating several brain conditions including trauma, tumor, hydrocephalus, and seizures. MRI in the clinic is not applicable as a means of constant monitoring, correlating MRI-based water content measurements at a few time points with indirect measures, such as thermal tissue conductivity [15], might provide means of introducing brain water content as an important parameter for monitoring patients with acute neurologic injury
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