Toolkit/functional ultrasound imaging

functional ultrasound imaging

Assay Method·Research·Since 2021

Also known as: fUS, fUSi

Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

Functional ultrasound imaging (fUSi) is an emerging neuroimaging technique that can be used to transcranially detect changes in cerebral blood volume following introduction of a stimulus.

Usefulness & Problems

Why this is useful

fUSi is used to transcranially detect changes in cerebral blood volume after stimulation. In this study it was used to identify stimulus-evoked responses in regions expressing optogenetic channels.; transcranial detection of stimulus-evoked cerebral blood volume changes; non-invasive functional readout after optogenetic stimulation; Functional ultrasound imaging is a hemodynamic neuroimaging method used to measure brain activity across a large field of view with high spatial and temporal resolution. The review frames it as especially useful for systems-level functional connectomics.; interrogating brain activity at the systems level; studying intrinsic functional connectivity; mapping brain-wide pathways associated with an external event; behavior-compatible functional neuroimaging

Source:

fUSi is used to transcranially detect changes in cerebral blood volume after stimulation. In this study it was used to identify stimulus-evoked responses in regions expressing optogenetic channels.

Source:

transcranial detection of stimulus-evoked cerebral blood volume changes

Source:

non-invasive functional readout after optogenetic stimulation

Source:

Functional ultrasound imaging is a hemodynamic neuroimaging method used to measure brain activity across a large field of view with high spatial and temporal resolution. The review frames it as especially useful for systems-level functional connectomics.

Source:

interrogating brain activity at the systems level

Source:

studying intrinsic functional connectivity

Source:

mapping brain-wide pathways associated with an external event

Source:

behavior-compatible functional neuroimaging

Problem solved

It offers a non-invasive way to functionally assess whether optogenetically targeted brain regions respond to stimulation.; provides non-invasive monitoring of functional responses in target tissue; It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.; provides systems-level functional neuroimaging with high spatiotemporal resolution and large field of view; enables connectomics-oriented mapping of correlated activity and event-associated pathways

Source:

It offers a non-invasive way to functionally assess whether optogenetically targeted brain regions respond to stimulation.

Source:

provides non-invasive monitoring of functional responses in target tissue

Source:

It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.

Source:

provides systems-level functional neuroimaging with high spatiotemporal resolution and large field of view

Source:

enables connectomics-oriented mapping of correlated activity and event-associated pathways

Problem links

enables connectomics-oriented mapping of correlated activity and event-associated pathways

Literature

It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.

Source:

It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.

provides non-invasive monitoring of functional responses in target tissue

Literature

It offers a non-invasive way to functionally assess whether optogenetically targeted brain regions respond to stimulation.

Source:

It offers a non-invasive way to functionally assess whether optogenetically targeted brain regions respond to stimulation.

provides systems-level functional neuroimaging with high spatiotemporal resolution and large field of view

Literature

It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.

Source:

It helps map intrinsic functional connectivity and brain-wide pathways associated with external events while remaining compatible with behavioral experiments.

Published Workflows

Objective: Perform fully non-invasive optogenetics in mice by combining non-invasive focused ultrasound-mediated viral delivery with transcranial functional ultrasound imaging readout.

Why it works: The workflow pairs a non-invasive delivery method that enables optogenetic gene transfer with a transcranial imaging method that can detect stimulus-evoked cerebral blood volume changes in expressing regions.

focused ultrasound-mediated blood-brain barrier opening for viral entryexpression of light-sensitive ion channels in target tissuestimulus-evoked cerebral blood volume changes as functional readoutfocused ultrasoundfunctional ultrasound imaging

Stages

  1. 1.
    Non-invasive viral delivery by FUS-mediated BBB opening(confirmatory_validation)

    This stage exists to replace invasive craniotomy-based direct injections with a non-invasive delivery route.

    Selection: Use focused ultrasound-mediated BBB opening to facilitate non-invasive gene delivery for optogenetics in mice.

  2. 2.
    Transcranial functional readout with fUSi(confirmatory_validation)

    This stage exists because successful transduction and expression are otherwise typically validated with invasive craniotomies or postmortem histology.

    Selection: Detect stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.

Steps

  1. 1.
    Deliver ChrimsonR-encoding viruses using focused ultrasound-mediated BBB openingdelivery harness

    Introduce the optogenetic payload into the brain non-invasively.

    Delivery must occur before functional imaging can assess stimulus-evoked responses in expressing tissue.

  2. 2.
    Use transcranial fUSi to identify stimulus-evoked cerebral blood volume changes in expressing regionsfunctional imaging assay

    Functionally validate that regions expressing the light-sensitive ion channels show stimulus-evoked responses without invasive validation procedures.

    This step follows delivery because it is used to validate successful transduction and expression after the optogenetic construct has been introduced.

Taxonomy & Function

Primary hierarchy

Technique Branch

Method: A concrete measurement method used to characterize an engineered system.

Target processes

recombination

Input: Light

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: sensor

It requires functional ultrasound imaging hardware and a stimulus paradigm that produces measurable cerebral blood volume changes.; requires functional ultrasound imaging instrumentation; depends on cerebral blood volume changes as the measured signal; The abstract supports that the method relies on hemodynamic imaging and is primarily used in animal models. No further hardware or protocol prerequisites are specified in the provided source text.; hemodynamic-based readout; primarily applied in animal models according to the abstract

The abstract does not claim that fUSi alone improves cell-specific targeting or directly replaces all molecular confirmation methods in every context.; transcranial ultrasound imaging still requires improvement according to the abstract; The abstract does not claim direct cellular-resolution or non-hemodynamic readout, and it notes the technique is primarily used in animal models.; described as primarily used in animal models

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Observations

successMouseapplication demomouse

functional ultrasound imaging

Inferred from claim c3 during normalization. Functional ultrasound imaging identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels. Derived from claim c3. Quoted text: fUSi successfully identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.

Source:

Supporting Sources

Ranked Claims

Claim 1comparative advantagesupports2023Source 1needs review

Focused ultrasound-mediated BBB opening non-invasively facilitates gene delivery for optogenetics in mice compared with invasive craniotomy-based delivery.

A recently proposed alternative in which non-invasive optogenetics is performed with focused ultrasound (FUS)-mediated blood-brain barrier (BBB) openings has been found to non-invasively facilitate gene delivery for optogenetics in mice.
Claim 2delivery successsupports2023Source 1needs review

Focused ultrasound successfully delivered viruses encoding ChrimsonR in all treated subjects.

FUS successfully delivered viruses encoding the red-shifted channelrhodopsin variant ChrimsonR in all treated subjects.
treated subjects with successful delivery all treated subjects
Claim 3functional detectionsupports2023Source 1needs review

Functional ultrasound imaging identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.

fUSi successfully identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.
Claim 4method implementationsupports2023Source 1needs review

The study implemented a fully non-invasive combined FUS-fUSi technique for performing optogenetics in mice.

In this study, we implemented a fully non-invasive combined FUS-fUSi technique for performing optogenetics in mice.
Claim 5application summarysupports2021Source 2needs review

Functional ultrasound imaging can be used to map brain-wide pathways associated with an external event.

Second, fUS can also be used to map brain-wide pathways associated with an external event.
Claim 6application summarysupports2021Source 2needs review

Functional ultrasound imaging can be used to study intrinsic functional connectivity as patterns of correlated activity between brain regions.

First, fUS can be used to study intrinsic functional connectivity, namely patterns of correlated activity between brain regions.
Claim 7capability summarysupports2021Source 2needs review

Functional ultrasound imaging is a hemodynamic-based functional neuroimaging technique that combines high spatiotemporal resolution, large field of view, and compatibility with behavior.

Functional ultrasound (fUS) is a hemodynamic-based functional neuroimaging technique, primarily used in animal models, that combines a high spatiotemporal resolution, a large field of view, and compatibility with behavior.
Claim 8future directionsupports2021Source 2needs review

Technological improvements and new analytical tools are expected to boost functional ultrasound capabilities, and incorporation into multimodal studies is presented as a promising future avenue.

Finally, technological improvements and the application of new analytical tools promise to boost fUS capabilities. As brain coverage and the range of behavioral contexts that can be addressed with fUS keep on increasing, we believe that fUS-guided connectomics will only expand in the future. In this regard, we consider the incorporation of fUS into multimodal studies combining diverse techniques and behavioral tasks to be the most promising research avenue.
Claim 9paired modality summarysupports2021Source 2needs review

Combining functional ultrasound imaging with optogenetics is presented as an attractive way to map the brain-wide connections of defined neuronal populations.

Additionally, combining fUS with direct circuit manipulations such as optogenetics is an attractive way to map the brain-wide connections of defined neuronal populations.
Claim 10use case summarysupports2021Source 2needs review

Functional ultrasound imaging is especially suited to interrogating brain activity at the systems level and can contribute to functional connectomics.

These assets make fUS especially suited to interrogating brain activity at the systems level. In this review, we describe the technical capabilities offered by fUS and discuss how this technique can contribute to the field of functional connectomics.

Approval Evidence

2 sources7 linked approval claimsfirst-pass slug functional-ultrasound-imaging
Functional ultrasound imaging (fUSi) is an emerging neuroimaging technique that can be used to transcranially detect changes in cerebral blood volume following introduction of a stimulus.

Source:

Functional ultrasound (fUS) is a hemodynamic-based functional neuroimaging technique, primarily used in animal models, that combines a high spatiotemporal resolution, a large field of view, and compatibility with behavior.

Source:

functional detectionsupports

Functional ultrasound imaging identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.

fUSi successfully identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels.

Source:

application summarysupports

Functional ultrasound imaging can be used to map brain-wide pathways associated with an external event.

Second, fUS can also be used to map brain-wide pathways associated with an external event.

Source:

application summarysupports

Functional ultrasound imaging can be used to study intrinsic functional connectivity as patterns of correlated activity between brain regions.

First, fUS can be used to study intrinsic functional connectivity, namely patterns of correlated activity between brain regions.

Source:

capability summarysupports

Functional ultrasound imaging is a hemodynamic-based functional neuroimaging technique that combines high spatiotemporal resolution, large field of view, and compatibility with behavior.

Functional ultrasound (fUS) is a hemodynamic-based functional neuroimaging technique, primarily used in animal models, that combines a high spatiotemporal resolution, a large field of view, and compatibility with behavior.

Source:

future directionsupports

Technological improvements and new analytical tools are expected to boost functional ultrasound capabilities, and incorporation into multimodal studies is presented as a promising future avenue.

Finally, technological improvements and the application of new analytical tools promise to boost fUS capabilities. As brain coverage and the range of behavioral contexts that can be addressed with fUS keep on increasing, we believe that fUS-guided connectomics will only expand in the future. In this regard, we consider the incorporation of fUS into multimodal studies combining diverse techniques and behavioral tasks to be the most promising research avenue.

Source:

paired modality summarysupports

Combining functional ultrasound imaging with optogenetics is presented as an attractive way to map the brain-wide connections of defined neuronal populations.

Additionally, combining fUS with direct circuit manipulations such as optogenetics is an attractive way to map the brain-wide connections of defined neuronal populations.

Source:

use case summarysupports

Functional ultrasound imaging is especially suited to interrogating brain activity at the systems level and can contribute to functional connectomics.

These assets make fUS especially suited to interrogating brain activity at the systems level. In this review, we describe the technical capabilities offered by fUS and discuss how this technique can contribute to the field of functional connectomics.

Source:

Comparisons

Source-stated alternatives

The abstract contrasts non-invasive fUSi-based validation with invasive longitudinal craniotomies and postmortem histology.; The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

Source:

The abstract contrasts non-invasive fUSi-based validation with invasive longitudinal craniotomies and postmortem histology.

Source:

The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

Source-backed strengths

transcranial readout; identified stimulus-evoked cerebral blood volume changes preferentially in regions expressing light-sensitive ion channels; high spatiotemporal resolution; large field of view; compatibility with behavior; suited to systems-level brain activity interrogation

Source:

transcranial readout

Source:

identified stimulus-evoked cerebral blood volume changes preferentially in regions expressing light-sensitive ion channels

Source:

high spatiotemporal resolution

Source:

large field of view

Source:

compatibility with behavior

Source:

suited to systems-level brain activity interrogation

The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

Shared frame: source-stated alternative in extracted literature

Strengths here: transcranial readout; identified stimulus-evoked cerebral blood volume changes preferentially in regions expressing light-sensitive ion channels; high spatiotemporal resolution.

Relative tradeoffs: transcranial ultrasound imaging still requires improvement according to the abstract; described as primarily used in animal models.

Source:

The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

Shared frame: source-stated alternative in extracted literature

Strengths here: transcranial readout; identified stimulus-evoked cerebral blood volume changes preferentially in regions expressing light-sensitive ion channels; high spatiotemporal resolution.

Relative tradeoffs: transcranial ultrasound imaging still requires improvement according to the abstract; described as primarily used in animal models.

Source:

The review emphasizes multimodal studies combining fUS with diverse techniques and behavioral tasks, and specifically highlights pairing with optogenetics as an attractive complementary approach.

Ranked Citations

  1. 1.

    Extracted from this source document.

  2. 2.
    StructuralSource 2NeuroImage2021Claim 5Claim 6Claim 7

    Seeded from load plan for claim cl1. Extracted from this source document.