Dynamic susceptibility contrast (DSC) MRI is commonly part of brain tumor imaging. For quantitative analysis, measurement of the arterial input function and tissue concentration time curve is required. Usually, a linear relationship between the MR signal changes and contrast agent concentration ([Gd]) is assumed, even though this is a known simplification. The aim of this study was to develop a realistic 3D simulation model as an efficient method to assess the relationship between ΔR2(*) and [Gd] both in whole blood and brain tissue. We modified an open-source 3D simulation model to study different red blood cell configurations for assessing whole-blood ΔR2(*) versus [Gd]. The results were validated against previously obtained 2D data and in vitro data. Furthermore, hematocrit levels (30%–50%) and field strengths (1.5–3.0–7.0 T) were varied. Subsequently, realistic tumor vascular networks were derived from intraoperative high framerate Doppler ultrasound data to study the influence of vascular structure and orientation with respect to the main magnetic field (1.5–3.0–7.0 T) for the calculation of ΔR2(*) versus [Gd] in brain tissue. For whole blood, good agreement of the 3D model was found with in vitro and 2D simulation data when red blood cells were aligned with the blood flow. For brain tissue, minor differences were found between the vascular networks. The effect of vessel direction with respect to B0 was apparent in case of clear directionality of the main vessels. The dependency on field strength agreed with previous reports. In conclusion, we have shown that the relationship between ΔR2(*) and [Gd] is affected by the organization of red blood cells and orientation of blood vessels with respect to the main magnetic field, as well as the field strength. These findings are important for further optimization of the realistic 3D model that could eventually be used to improve the estimation of hemodynamic parameters from DSC-MRI.

Background and Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. Methods: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. Results: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 μm and 1.5–2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics. Conclusion: The current study presents the potential of applying fUS during awake brain surgery. We illustrate the relevance of fUS for awake brain surgery based on its ability to capture both task-evoked functional cortical responses as well as differences in vascular characteristics between tumor and healthy tissue. As current neurosurgical practice is still pre-dominantly leaning on inherently limited pre-operative imaging techniques for tumor resection-guidance, fUS enters the scene as a promising alternative that is both anatomically and physiologically informative.

Recent advances in ultrasound Doppler imaging have facilitated the technique of functional ultrasound (fUS) which enables visualization of brain-activity due to neurovascular coupling. As of yet, this technique has been applied to rodents as well as to human subjects during awake craniotomy surgery and human newborns. Here we demonstrate the first successful fUS studies on awake pigeons subjected to auditory and visual stimulation. To allow successful fUS on pigeons we improved the temporal resolution of fUS up to 20,000 frames per second with real-time visualization and continuous recording. We show that this gain in temporal resolution significantly increases the sensitivity for detecting small fluctuations in cerebral blood flow and volume which may reflect increased local neural activity. Through this increased sensitivity we were able to capture the elaborate 3D neural activity pattern evoked by a complex stimulation pattern, such as a moving light source. By pushing the limits of fUS further, we have reaffirmed the enormous potential of this technique as a new standard in functional brain imaging with the capacity to unravel unknown, stimulus related hemodynamics with excellent spatiotemporal resolution with a wide field of view.