(Draft) Recommendations for acoustic output calibration, testing, and routine checks of equipment for transcranial focused ultrasound for neuromodulation

1. Background
2. Primary calibration
3. Secondary calibration / testing
4. Routine equipment checks
5. License

1. Background

The purpose of the proposed testing scheme is to provide a practical framework for reliable, repeatable acoustic energy exposures of participants, maintaining both safety (no treatment at a higher output than desired) and efficacy (no treatment at a level lower than desired). A hierarchy is proposed that involves the Equipment as received from the Manufacturer, extending to checks potentially performed before each subject exposure. The goal is to provide reasonable assurance of acoustic energy exposure without undue burden on the User or their facility.

Any measurement or test undertaken as part of this process must be quantifiable, repeatable, and directly related to relevant Acoustic Output (AO) quantities such as pressure, intensity, or power. Secondary measurements such as transmitter voltage/power and transducer electrical impedance are also valuable as they are quantifiable and directly impact AO. However, observations of performance such as color changes in thermochromic materials, height of a “fountain” above the water surface in a water tank, uncalibrated Schlieren imaging, or audible noise emitted from a transducer are not considered adequate for purposes of this recommendation. While those observations may have value in checking basic functionality (e.g. “transducer broken or not broken”), they are not sufficiently quantifiable for the purposes of establishing consistent acoustic exposure.

Another overall goal is to provide a means to ensure that the Equipment continues to produce the desired Acoustic Output in a manner sufficiently convenient that it will be followed by typical Users. Thus a combination of traceable initial calibration of the Equipment, and simple, quantifiable checks that are performed on a regular basis, is the minimum recommendation.

It should be noted that these recommendations do not describe electrical safety tests, which are covered elsewhere in medical device safety standards.

It should also be noted that this guidance is related to the acoustic output of equipment for transcranial focused ultrasound for neuromodulation, and does not provide guidance for measurement, or estimation of in situ acoustic parameters.

2. Primary calibration

Upon delivery of the Equipment to the User

The manufacturer of the Equipment shall provide to the User, at the time of purchase, traceable Acoustic Output (AO) information in a form that is readily accessible and understandable. At a minimum, the AO information should include the recommended elements of the ITRUSST reporting guide, as well as the relevant portions of national and international guidelines and standards (e.g. such as those published by the FDA or IEC). The exact format is at the discretion of the Manufacturer, and may be, for instance, a tabular list of AO for different voltage settings, or real-time on-screen display of AO, or some combination of the two. The User of the Equipment shall review the specifications and AO information provided in order to gain a full understanding of the capabilities of the Equipment with regard to subject exposure and subject safety.

It is preferable that the Equipment displays to the User the AO at the settings or treatment parameters that the User has programmed, prior to the start of the treatment.

The Manufacturer may specify a period over which the initial calibration is valid, and after which time a re-calibration is required. The time period may be specified in either real time (e.g. “Equipment must be calibrated every 12 months”) or in units of usage (e.g. “Equipment must be calibrated after 100 hours of use”).

3. Secondary calibration / testing

Optional depending upon the facilities available to the User

The User of the Equipment may perform their own AO measurement to ensure the continued operation of the Equipment at the specified settings. These tests may comprise radiation force balance measurements of acoustic power, hydrophone scans of acoustic pressure, or other similar quantifiable, calibrated AO measurement procedures, and it is recommended that they are carried out according to the existing relevant measurement standards or recommended procedures, where possible.

It is preferable that the Equipment conduct self-checks, such as monitoring output voltages or power. In this context, a self-check is a test or measurement performed automatically and internally by the equipment. If the check fails (e.g. a voltage falls outside the acceptable range), the outcome will be communicated to the User, for example via an error message or disabling of the output. These self-checks are performed at minimum at Equipment startup, or preferably both at startup and regularly during treatment. Failure of equipment self-checks should be reported to the manufacturer.

4. Routine equipment checks

To be performed at regular intervals

The User of the Equipment may perform regular checks of the operation of the Equipment to ensure that participants are exposed to the intended acoustic energy. The checks may be performed weekly, daily or prior to every subject exposure. Different checks may be appropriate depending upon the testing interval. It is understood that if the Equipment fails a Routine Equipment Check (REC), for example, AO is low and falls outside the accepted range, then any treatment using the Equipment since the last successful REC must be considered suspect. Any data from those treatments may be quarantined and potentially removed from the overall study results. It is up to the Manufacturer, in collaboration with the User, to establish the threshold for failure of an REC (e.g. ±10% or ±20% pressure deviation, or a ±5% or ±10% electrical power deviation).

Measurements made for REC need not have an absolute traceable calibration but must be stable and repeatable. Thus, an acoustic power meter, radiation force balance, or hydrophone does not need to demonstrate traceable calibration accuracy but must be temporally stable and provide the same test value output for the same AO applied. Measurements may be performed over a range of output settings but must encompass at least those typically used for treatment. Measurements do not have to be performed at the maximum possible output settings of the Equipment, as those settings may not be realistic for the intended clinical use and may shorten the lifetime of the transducer or other components of the Equipment. Other checks, such as measurement of transducer impedance, reflected electrical power, or transmitter voltage/power, are also suitable as quantifiable indicators of Equipment performance. Checks are preferably performed with the transducer coupled to water or other media with acoustic impedance properties similar to tissue. In-air measurements may be possible, but only at transmit levels approved by the Manufacturer. The testing recommendation does not preclude other checks using quantifiable, repeatable and AO relevant approaches such as laser displacement or high frequency microphones, as long as the Manufacturer has been consulted and approves of their use, or they are otherwise described in other external standards documents. Further guidance on performing Routine Equipment Checks is provided in the document ‘Recommendations for performing routine checks on equipment for transcranial focused ultrasound for neuromodulation’.

5. License

Unless otherwise separately undertaken by the Licensor, to the extent possible, the Licensor offers the Licensed Material as-is and as-available, and makes no representations or warranties of any kind concerning the Licensed Material, whether express, implied, statutory, or other. This includes, without limitation, warranties of title, merchantability, fitness for a particular purpose, non-infringement, absence of latent or other defects, accuracy, or the presence or absence of errors, whether or not known or discoverable. Where disclaimers of warranties are not allowed in full or in part, this disclaimer may not apply to You. To the extent possible, in no event will the Licensor be liable to You on any legal theory (including, without limitation, negligence) or otherwise for any direct, special, indirect, incidental, consequential, punitive, exemplary, or other losses, costs, expenses, or damages arising out of this Public License or use of the Licensed Material, even if the Licensor has been advised of the possibility of such losses, costs, expenses, or damages. Where a limitation of liability is not allowed in full or in part, this limitation may not apply to You. The disclaimer of warranties and limitation of liability provided above shall be interpreted in a manner that, to the extent possible, most closely approximates an absolute disclaimer and waiver of all liability.

This work is licensed under a Creative Commons Attribution 4.0 International License (CC-BY).

This work is licensed under a Creative Commons Attribution 4.0 International License.