Cardiac pulsatility mapping and vessel type identification using laser speckle contrast imaging

Systemic flow variations caused by the cardiac cycle can play a role or be an important marker in both normal and pathological conditions. The shape, magnitude and propagation speed of the flow pulse reflect mechanical properties of the vasculature and are known to vary significantly with vascular diseases. Most conventional techniques are not capable of imaging cardiac activity in the microcirculation due to spatial and/or temporal resolution limitations and instead make inferences about propagation speed by making measurements at two points along an artery. Here, we apply laser speckle contrast imaging to images with high spatial resolution in the high frequency harmonics of cardiac activity in the cerebral cortex of a mouse. We reveal vessel dependent variation in the cardiac pulse activity and use this information to automatically identify arteries and veins.Novo Nordisk Foundation, Denmark (NNF17OC0025224); National Institutes of Health (NIH) (R01-MH111359, R01-EB021018, and R01-NS108472). (NNF17OC0025224 - Novo Nordisk Foundation, Denmark; R01-MH111359 - National Institutes of Health (NIH); R01-EB021018 - National Institutes of Health (NIH); R01-NS108472 - National Institutes of Health (NIH))https://www.osapublishing.org/boe/abstract.cfm?uri=boe-9-12-6388Published versio

Choosing a model for laser speckle contrast

Laser speckle contrast imaging (LSCI) is a real-time full-field non-invasive technique, which is broadly applied to visualize blood flow in biomedical applications. In its foundation is the link between the speckle contrast and dynamics of light scattering particles–erythrocytes. The mathematical form describing this relationship, which is critical for accurate blood flow estimation, depends on the sample’s light-scattering properties. However, in biological applications, these properties are often unknown, thus requiring assumptions to be made to perform LSCI analysis. Here, we review the most critical assumptions in the LSCI theory and simulate how they affect blood flow estimation accuracy. We show that the most commonly applied model can severely underestimate the flow change, particularly when imaging brain parenchyma or other capillary perfused tissue (e.g. skin) under ischemic conditions. Based on these observations and guided by the recent experimental results, we propose an alternative model that allows measuring blood flow changes with higher accuracy

Neurovascular coupling is preserved in chronic stroke recovery after targeted photothrombosis

Functional neuroimaging, which measures hemodynamic responses to brain activity, has great potential for monitoring recovery in stroke patients and guiding rehabilitation during recovery. However, hemodynamic responses after stroke are almost always altered relative to responses in healthy subjects and it is still unclear if these alterations reflect the underlying brain physiology or if the alterations are purely due to vascular injury. In other words, we do not know the effect of stroke on neurovascular coupling and are therefore limited in our ability to use functional neuroimaging to accurately interpret stroke pathophysiology. To address this challenge, we simultaneously captured neural activity, through fluorescence calcium imaging, and hemodynamics, through intrinsic optical signal imaging, during longitudinal stroke recovery. Our data suggest that neurovascular coupling was preserved in the chronic phase of recovery (2 weeks and 4 weeks post-stoke) and resembled pre-stroke neurovascular coupling. This indicates that functional neuroimaging faithfully represents the underlying neural activity in chronic stroke. Further, neurovascular coupling in the sub-acute phase of stroke recovery was predictive of long-term behavioral outcomes. Stroke also resulted in increases in global brain oscillations, which showed distinct patterns between neural activity and hemodynamics. Increased neural excitability in the contralesional hemisphere was associated with increased contralesional intrahemispheric connectivity. Additionally, sub-acute increases in hemodynamic oscillations were associated with improved sensorimotor outcomes. Collectively, these results support the use of hemodynamic measures of brain activity post-stroke for predicting functional and behavioral outcomes

Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury:A hyperacute role for neutrophils in persistent traffic jams

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2–24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke

Retrospective analysis of children with myelin oligodendrocyte glycoprotein antibody-related disorders

Background: Knowledge has been expanding on myelin oligodendrocyte glycoprotein (MOG) antibody-associated central nervous system disorders. We delineate the clinical and paraclinical findings and outcome of our pediatric patients with MOG antibody seropositive disease

Scalable Thousand Channel Penetrating Microneedle Arrays on Flex for Multimodal and Large Area Coverage BrainMachine Interfaces

The Utah array powers cutting-edge projects for restoration of neurological function, such as BrainGate, but the underlying electrode technology has itself advanced little in the last three decades. Here, advanced dual-side lithographic microfabrication processes is exploited to demonstrate a 1024-channel penetrating silicon microneedle array (SiMNA) that is scalable in its recording capabilities and cortical coverage and is suitable for clinical translation. The SiMNA is the first penetrating microneedle array with a flexible backing that affords compliancy to brain movements. In addition, the SiMNA is optically transparent permitting simultaneous optical and electrophysiological interrogation of neuronal activity. The SiMNA is used to demonstrate reliable recordings of spontaneous and evoked field potentials and of single unit activity in chronically implanted mice for up to 196 days in response to optogenetic and to whisker air-puff stimuli. Significantly, the 1024-channel SiMNA establishes detailed spatiotemporal mapping of broadband brain activity in rats. This novel scalable and biocompatible SiMNA with its multimodal capability and sensitivity to broadband brain activity will accelerate the progress in fundamental neurophysiological investigations and establishes a new milestone for penetrating and large area coverage microelectrode arrays for brain-machine interfaces

A Suite of Neurophotonic Tools to Underpin the Contribution of Internal Brain States in fMRI

Recent developments in optical microscopy, applicable for large-scale and longitudinal imaging of cortical activity in behaving animals, open unprecedented opportunities to gain a deeper understanding of neurovascular and neurometabolic coupling during different brain states. Future studies will leverage these tools to deliver foundational knowledge about brain state-dependent regulation of cerebral blood flow and metabolism as well as regulation as a function of brain maturation and aging. This knowledge is of critical importance to interpret hemodynamic signals observed with functional magnetic resonance imaging (fMRI)