Using Functional Ultrasound (Fus) To Map Brain Functionality And Tumor Vasculature With Micrometer-Millisecond Precision

Abstract OBJECTIVE In the early 20th century, Dr. Cushing first demonstrated the use of electrical stimulation mapping (ESM) to define motor and sensory cortices during neurosurgical procedures. Essentially, little has changed in what guides a neurosurgeon’s intra-operative decision-making since. Inherent limitations of ESM such as limited depth penetration and risk of seizure elicitation, warrant the development of new image-guided resection tools. Here, we present functional Ultrasound (fUS)-imaging as a new, high-resolution tool to guide intra-operative decision-making during awake tumor removal. METHODS fUS relies on high-frame-rate ultrasound, which offers images at thousands of frames-per-second. As such, fUS is sensitive to very small motions caused by vascular dynamics (µDoppler), allowing measurements of changes in cerebral blood volume (CBV). This facilitates the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling and 2) visualize high-resolution vascular morphology of tumor and healthy tissue. During conventional awake craniotomy surgery, n= 10 patients were asked to perform 60s functional tasks to elicit cortical responses. Simultaneously, a conventional 5 MHz ultrasound probe connected to an experimental acquisition system, was placed over ESM-defined functional areas. After image acquisition, correlation analyses with the corresponding tasks revealed functional and non-functional areas. In addition, 3D vascular maps were reconstructed from subsequent 2D-Power Doppler Images (PDIs). RESULTS fUS was able to detect functional areas as activated using conventional motor tasks, as well as complex language-related tasks. In addition, both 2D-PDIs and 3D-reconstructions revealed the ability of fUS to detect unique high-resolution onco-vascular characteristics in high- and low-grade malignancies. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5-2.0 msec) precision at imaging depths > 5 cm. CONCLUSIONS Applying fUS-imaging successfully in this awake craniotomy series serves as a clear demonstration of the technique’s revolutionary potential for maximizing safe tumor removal.