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Webb, T. D.

Publications and source records attributed to Webb, T. D..

5 recordsLinked to original sources

Impact of acoustic property uncertainty on transcranial ultrasound simulation

Subject-specific simulations of wave propagation are commonly used to plan and report acoustic and thermal exposure during transcranial ultrasound (TUS) interventions. Their accuracy depends on acoustic and thermal tissue property assumptions, including sound speed, density, and attenuation. Reported property measurements vary widely across the literature, precluding consensus point estimates for simulation. How this property uncertainty affects estimated exposure has not been quantified. We compile literature-based bounds for seven acoustic and thermal properties of skull and brain tissue and assess their individual impact on simulated intensity and temperature rise using two independent simulation platforms (PRESTUS/k-Wave and BabelBrain). Variations in skull attenuation and absorption produced the largest outcome uncertainty: peak intensity in the brain varied roughly threefold across the reported range of skull attenuation alone, while absorption most strongly affected temperature rise within the skull. The direction of each parameter's effect was consistent across platforms and, with one exception, across skull thickness. This allowed bounds to be combined into setups that bracket transmission and temperature rise. Compared to these extremes, default property sets of three simulation toolboxes (k-Plan, BabelBrain, PRESTUS) yielded similar brain intensity but divergent skull heating, driven mainly by differing assumptions on skull absorption and heat capacity. These results indicate that uncertainty in skull acoustic properties is a major source of variability in TUS exposure estimates, and that refined measurements of these properties, together with explicit reporting of exposure uncertainty, are needed to support safe, effective, and reproducible transcranial ultrasound planning.

neuroscience↗

Focused Ultrasound Neuromodulation of the Central Lateral Thalamus in a Non-Human Primate Model of Disorders of Consciousness

Objectives: Disorders of consciousness (DOC) affect an estimated 200,000 patients in the United States. Effective treatment options have remained elusive. Focused ultrasound neuromodulation (FUS) of brain regions controlling consciousness, such as the central lateral thalamus (CLT), has emerged as a promising non-invasive treatment. However, prior studies have been limited by broad effective stimulation volumes, missing control conditions, and limited target validation. This study investigated the effects of FUS of the CLT in a non-human primate model of DOC with robust control conditions and more robust targeting than previous experiments. Materials and Methods: Two male rhesus macaques underwent 1-hour propofol anesthesia sessions as a model of DOC. Bilateral CLT targets were sonicated using a stereotactically mounted 256-element phased-array focused ultrasound system. Focused and unfocused (random phases) paradigms were tested in both animals, and a spotlighting (sonicating multiple targets) paradigm was tested in one animal. Arousal was monitored via EEG beta power, pulse oximetry, breathing rate, and movement, and compared between sonication and control sessions for each paradigm. Results: Paired Wilcoxon signed-rank tests showed no significant differences for any of the four measures across the three paradigms (all pFDR [≥] 0.30). The largest observed effect was increased body movement under the unfocused paradigm (rrb = +0.58), though this did not reach statistical significance. Animals remained physiologically stable throughout sessions and recovery periods, with no clinically significant changes in heart rate, breathing rate, blood oxygen saturation, or other safety concerns. Conclusions: Under the tested parameters, FUS of the CLT did not produce measurable changes in arousal. The absence of adverse physiological effects supports the safety of this FUS paradigm. The largest effect occurring under spatially distributed sonication, consistent with prior evidence that broader stimulation volumes produce stronger arousal responses, suggests that distributed network stimulation may warrant investigation as an alternative to focal targeting. Future studies should investigate this possibility and should include robust control conditions to properly quantify effects.

neuroscience↗

Remotely controlled drug release in deep brain regionsof non-human primates

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound--remotely applied, depth-penetrating energy--may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/561539v3_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1c4c3acorg.highwire.dtl.DTLVardef@10a5e6borg.highwire.dtl.DTLVardef@1bce636org.highwire.dtl.DTLVardef@adf9a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Noninvasive, Systematic, and Sustained Modulation of Deep Brain Circuits in Awake Subjects

Transcranial focused ultrasound has the potential to noninvasively and systematically modulate deep brain circuits and impart sustained, neuroplastic effects in awake subjects. The intersection of these properties is critical for effective treatments of brain disorders, yet remains to be shown. Harnessing the full potential of transcranial ultrasound, we delivered 30-second stimuli into deep brain targets (left/right lateral geniculate nucleus) of non-human primates while they performed a visual discrimination task. This brief stimulation induced sustained and target-specific behavioral preference that persisted up to 15 minutes following the ultrasound offset. The polarity of the behavioral and neural effects suggested that ultrasound excited the stimulated circuits. The ultrasound was delivered into the deep brain daily for a period of more than 6 months, which enabled us to evaluate the safety of longterm stimulation. There were no detrimental effects on the animals discrimination accuracy over the course of this stimulation regimen. This study demonstrates ultrasounds capacity to condition deep brain circuits in a safe and treatment-relevant manner in awake subjects, and provides a basis for effective and safe translations into humans. HighlightsO_LITranscranial ultrasound induces effective and sustained modulation of deep brain circuits. C_LIO_LIThe deep brain modulation biases choice behavior of non-human primates. C_LIO_LIThe deep brain modulation produces sustained elevation of high gamma activity. C_LIO_LIThe stimulation, applied daily for several months, is safe. C_LI

neuroscience↗

Platform for Incisionless, Focal, and Multisite Brain Interventions

MotivationTranscranial focused ultrasound brings personalized medicine to the human brain. Ultrasound can modulate neural activity or release drugs in specific neural circuits but this personalized approach requires a system that delivers ultrasound into specified targets flexibly and on command. SummaryWe developed a remote ultrasound system (Remus) that programmatically targets deep brain regions with high spatiotemporal precision and in a multi-focal manner. We validated these functions by safely modulating two deep brain nuclei--the left and right lateral geniculate nucleus-in a task-performing non-human primate. This flexible system will enable researchers and clinicians to diagnose and treat specific deep brain circuits in a noninvasive yet targeted manner, thus embodying the promise of personalized treatments of brain disorders. Animated graphical abstract: onetarget.us/download/rem.

neuroscience↗