Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

Our research aims to understand the details of transcranial ultrasound stimulation to cause measurable effects in humans, including parameter specifications and its ability to modulate deep brain structures. Our protocol streamlines the planning steps required to complete transcranial ultrasound stimulation experiments in humans. It is efficient, easy to use, and involves using open-source, accessible planning tools.

Our recent findings have shed light on the effect of optimal parameter selection in transcranial ultrasound stimulation to achieve neuronal inhibition. This will help in developing and designing future experiments in humans, significantly contributing to our understanding and advancement of this technology. After performing the high-resolution magnetic resonance imaging, convert T1-weighted, T2-weighted, and Zero Time Echo DICOM Scan files from DICOM to NIFTI format using the dcm2niix tool.

Using SimNIBS charm tool, execute co-registration and tissue mask extraction. Next open Braighsight. Click on New Empty Project, and load the participant's T1-weighted NIFTI image.

Click on the Reconstructions tab. Then on the New Reconstruction dropdown menu. Click on Skin, followed by Compute Skin in the new window.

Once complete, click on the Close button in the top left corner of the window. Within the Reconstructions tab, click on the New Reconstruction dropdown menu, followed by Full Brain Curvilinear. Now adjust the position of the green box on the sagittal, coronal, and transverse planes by dragging its edges to tightly surround the brain.

Scroll through all the slices to ensure no tissue edges overlap. Click on Compute Curvilinear, and and adjust the Peel depth to four millimeters. Then click on the Landmarks tab on Brainsight, followed by Configure Landmarks.

Place the crosshairs on the tip of the nose, and in the Name field, label the landmark Nose. Then place the crosshairs between the eyes above the bridge of the nose and label the landmark Nasion. Next, place the crosshairs on the left ear, and label the landmark L Ear.

Then place the crosshairs on the right ear and label the landmark R Ear. Afterward, click on the Targets tab, followed by Configure Targets. Place the crosshairs on the location of the desired target, and use the angle toggles on the right side of the screen to set the trajectory angle.

Once the desired target and trajectory are selected, click on the new dropdown menu and choose Trajectory. To name the target, type into the text box next to Name. Click on Export to export the target, and save it in the appropriate subject folder.

Open BabelBrain, and select the required files for acoustic and thermal simulations. To select the text file previously exported from Brainsight, click on Select Trajectory, and choose the appropriate participant file. Click on Select SimNIBS to choose the SimNIBS file created earlier.

Click on select T1W, and choose the T1-weighted image produced and used previously for target and trajectory mapping. Now choose real CT for CT scans, ZTE for ZTE scans, or NO To use a simplified mask generated by the charm tool. When using a CT or ZTE image, click on the Coreg dropdown menu, followed by CT to MR.Click on Select, and choose the corresponding image from the appropriate participant file.

Click Select Thermal profile, and choose the thermal profile file that describes the experiment's sonication parameters in terms of duration on, duration off, and duty cycle. Then click on the dropdown menu beside Transducer, and select the transducer used for experimentation. Click on the dropdown menu beside Computing backend, and choose the computing backend of the computer running the simulations.

Once all information is entered, click on CONTINUE to complete the rest of the simulations. Now select the transducer's ultrasound frequency and the appropriate points per wavelength. Click on Calculate planning mask.

Inspect the image to ensure the bounds for the skin, skull, and brain were accurately recognized. For acoustic simulation, click on the Step 2 AC Sim tab to open. Adjust the distance from the cone to the focal spot by typing in the appropriate distance.

To execute the simulation, click on the Calculate Fields button. Adjust the Z Steering value so the cross hairs are in the center of the focal point. Press the up or down arrows or manually enter the required value.

Then click on Calculate Fields. For thermal simulation, click on the Step 3 Thermal Sim tab. Then click on Calculate Thermal Fields.

After performing the skull reconstruction and simulations using the acquired MRI scans, open Brainsight, and click on Open Existing Project. Select the Brainsight file created and saved during trajectory and target mapping. Click on Sessions to begin a new experimentation session.

Click on the dropdown and select New, followed by Online Session. Then click on the target name, followed by Add a next step to add the target to the experiment session and continue to the Experimentation window. Click on Window and Tool Calibration.

Select the tools to be used, and then click Recalibrate. Attach the subject tracker to the participant's head using a headband placed above the ears and eyebrows. Next, click on the Registration tab in Brainsight.

Place the pointer on the first landmark, stabilizing it with both hands. Then click on Sample, and go to next landmark. Click on the Validation tab to validate the participant registration.

Lightly place the pointer on various positions along the scalp, and ensure all points are less than three millimeters. Then secure the participant's head with the chin rest and stabilizer placed on the back of the head to prevent movement. Ensure they are seated comfortably in the chair for the duration of the experiment.

Click on Perform. Use the mechanical arm to position the transducer over the target of interest along the selected trajectory.