Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping

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 i

How to Identify Responders and Nonresponders to Dorsal Root Ganglion-Stimulation Aimed at Eliciting Motor Responses in Chronic Spinal Cord Injury: Post Hoc Clinical and Neurophysiological Tests in a Case Series of Five Patients

OBJECTIVE: While integrity of spinal pathways below injury is generally thought to be an important factor in the success-rate of neuromodulation strategies for spinal cord injury (SCI), it is still unclear how the integrity of these pathways conveying the effects of stimulation should be assessed. In one of our institutional case series of five patients receiving dorsal root ganglion (DRG)-stimulation for elicitation of immediate motor response in motor complete SCI, only two out of five patients presented as responders, showing immediate muscle activation upon DRG-stimulation. The current study focuses on post hoc clinical-neurophysiological tests performed within this patient series to illustrate their use for prediction of spinal pathway integrity, and presumably, responder-status. MATERIALS AND METHODS: In a series of three nonresponders and two responders (all male, American Spinal Injury Association [ASIA] impairment scale [AIS] A/B), a test-battery consisting of questionnaires, clinical measurements, as well as a series of neurophysiological measurements was performed less than eight months after participation in the initial study. RESULTS: Nonresponders presented with a complete absence of spasticity and absence of leg reflexes. Additionally, nonresponders presented with close to no compound muscle action potentials (CMAPs) or Hofmann(H)-reflexes. In contrast, both responders presented with clear spasticity, elicitable leg reflexes, CMAPs, H-reflexes, and sensory nerve action potentials, although not always consistent for all tested muscles. CONCLUSIONS: Post hoc neurophysiological measurements were limited in clearly separating responders from nonresponders. Clinically, complete absence of spasticity-related complaints in the nonresponders was a distinguishing factor between responders and nonresponders in this case series, which mimics prior reports of epidural electrical stimulation, potentially illustrating similarities in mechanisms of action between the two techniques. However, the problem remains that explicit use and report of preinclusion clinical-neurophysiological measurements is missing in SCI literature. Identifying proper ways to assess these criteria might therefore be unnecessarily difficult, especially for nonestablished neuromodulation techniques

Efficient and Flexible Spatiotemporal Clutter Filtering of High Frame Rate Images Using Subspace Tracking

Current methods to measure blood flow using ultrafast Doppler imaging often make use of a Singular Value Decomposition (SVD). The SVD has been shown to be an effective way to remove clutter signals associated with slow moving tissue. Conventionally, the SVD is calculated from an ensemble of frames, after which the first dominant eigenvectors are removed. The Power Doppler Image (PDI) is then computed by averaging over the remaining components. The SVD method is computationally intensive and lacks flexibility due to the fixed ensemble length. We propose a method, based on the Projection Approximation Subspace Tracking (PAST) algorithm, which is computationally efficient and allows us to sequentially estimate and remove the principal components, while also offering flexibility for calculating the PDI, e.g. by using any convolutional filter. During a functional ultrasound (fUS) measurement, the intensity variations over time for every pixel were correlated to a known stimulus pattern. The results show that for a pixel chosen around the location of the stimulation electrode, the PAST algorithm achieves a higher Pearson correlation coefficient than the state-of-the-art SVD method, highlighting its potential to be used for fUS measurements.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Circuits and System

Efficient and Flexible Spatiotemporal Clutter Filtering of High Frame Rate Images Using Subspace Tracking

Current methods to measure blood flow using ultrafast Doppler imaging often make use of a Singular Value Decomposition (SVD). The SVD has been shown to be an effective way to remove clutter signals associated with slow moving tissue. Conventionally, the SVD is calculated from an ensemble of frames, after which the first dominant eigenvectors are removed. The Power Doppler Image (PDI) is then computed by averaging over the remaining components. The SVD method is computationally intensive and lacks flexibility due to the fixed ensemble length. We propose a method, based on the Projection Approximation Subspace Tracking (PAST) algorithm, which is computationally efficient and allows us to sequentially estimate and remove the principal components, while also offering flexibility for calculating the PDI, e.g. by using any convolutional filter. During a functional ultrasound (fUS) measurement, the intensity variations over time for every pixel were correlated to a known stimulus pattern. The results show that for a pixel chosen around the location of the stimulation electrode, the PAST algorithm achieves a higher Pearson correlation coefficient than the state-of-the-art SVD method, highlighting its potential to be used for fUS measurements.</p

Male-female differences in aortic valve and combined aortic valve/coronary surgery: A national cohort study in the Netherlands

Objective The outcome of female patients after adult cardiac surgery has been reported to be less favourable compared with the outcome of male patients. This study compares men with women with respect to patient and procedural characteristics and early mortality in a contemporary national cohort of patients who underwent aortic valve (AV) and combined aortic valve/coronary (CABG/AV) surgery. Methods All patients who underwent AV (n=8717, 56% male) or a combined CABG/AV surgery (n=5867, 67% male) in the Netherlands between January 2007 and December 2011 were included. Results In both groups, women were generally older than men (p<0.001) and presented with higher logistic EuroSCORES. In isolated AV surgery, men and women had comparable in-hospital mortality (OR 1.20, 95% CI 0.90 to 1.61; p=0.220). In concomitant CABG/AV surgery, in-hospital mortality was higher in women compared with men (OR 2.00, 95% CI 1.44 to 2.79; p<0.001). The area under the curve for logistic EuroSCORE 1 was systematically higher for men versus women in isolated AV surgery 0.82 (95% CI 0.78 to 0.86) vs 0.75 (95% CI 0.69 to 0.80) and in concomitant CABG/AV surgery 0.78 (95% CI 0.73 to 0.82) vs 0.69 (95% CI 0.63 to 0.74). Finally, (the weight of) risk factors associated with in-hospital mortality differed between men and women. Conclusions There are substantial male-female differences in patient presentation and procedural aspects in isolated AV and concomitant CABG/AV surgery in the Netherlands. Further studies are necessary to explore the mechanisms underlying the observed differences. In addition, the observation that standard risk scores perform worse in women warrants exploration of male-female specific risk models for patients undergoing cardiac surgery

Wireless closed-loop optogenetics across the entire dorsoventral spinal cord in mice.

Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice