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To the editor:
Transcranial magnetic stimulation (TMS) is a non-invasive brain modulation technique. One important usage of TMS is the transient interruption of cognitive brain function (also named virtual lesion) for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS (rTMS). The spatial accuracy of the ‘Figure-8’ coil could be up to 3 mm with a TMS robot.2 Functional magnetic resonance imaging (fMRI) has been used to guide neuronavigation systems for precise positioning of TMS targets.3–6 While rTMS is a routine treatment approach in many hospitals, few practitioners are using neuronavigation systems. One major reason is the expense of neuronavigation systems which is usually more than CN¥350 000 (US$50 000) and more expensive than the TMS machine itself. Another reason is the complexity of its usage.
Here, we proposed a simple, precise and cheap method, named Caliper-based precise positioning of the target (CALIPPOT) for TMS without a neuronavigation system. After MRI scanning with two or more imageable marks, experimenters use two outside callipers to precisely locate the stimulation target on the scalp. Each outside calliper costs about CN¥200 (US$28) and is reusable. The imageable marks are disposable and cost about CN¥0.6 (US$0.08) for each participant. The positioning duration is less than 10 min. Two experimenters tested the accuracy in 10 participants. The mean error was 2.32 mm. All participants signed informed consent before scanning.
The following introduces the positioning steps and then the verification experiment.
Steps for scalp target positioning
Step 1. Marks on the scalp
MRI imageable marks were purchased from an e-shop (https://shop196017839.taobao.com)—this is a kind of anti-collision silica gel (round, 10 mm diameter, 2 mm thickness) with glue on one side. Before putting the marks on the scalp, we drew a point at the centre of the mark for positioning in order to measure the distances more accurately. At least two marks are needed to locate the scalp target. But in practice, we recommend using three marks (M1, M2 and M3): two (eg, M1 and M2) for positioning and another two (eg, M1 and M3) for validation. Additionally, to ensure that the markers do not detach during the localisation process, adhesive tape can also be applied simultaneously as an auxiliary measure to guarantee the stability of the markers. If the validation step shows an error of more than 3 mm, we suggest redoing the process. Another purpose for the redundant marks is that, if one mark is occasionally lost during scanning or positioning, the other two marks will still work (figure 1).
The scalp target positioning procedure of CALIper-based Precise POsitioning of the Target (CALIPPOT). M1–M3, imageable marks for positioning; MRI, magnetic resonance imaging; T, the predefined scalp target that needs to be positioned by CALIPPOT; T', positioned target by CALIPPOT.
Step 2. MRI scanning and target measurement
After MRI scanning and data analysis (eg, fMRI task activation and/or resting-state fMRI functional connectivity analysis), a cortical stimulation target in the superficial cortex could be defined. It should be noted that these targets were predefined scalp targets rather than cortical targets. The current study focus lay in demonstrating the localisation of scalp points so we did not encompass the process of converting cortical to scalp. And thereafter, the scalp target (ie, T in figure) was defined on the MRI images by using Euclidean distance from the cortical target. Then the Euclidean distances from the scalp target to the centre of marks were calculated.
Step 3. Positioning the scalp target
First, set the distance of the outside callipers as measured on the MRI images. Then, two experimenters simultaneously placed one end of the outside calliper at the centre of two marks (eg, M1 and M2), drew an arc with the other end of the outside calliper simultaneously on the scalp, and then could find out the intersection point. This intersection point was the scalp target, that is, T1'. This scalp target T1' was then marked on the scalp with a marker pen. Since the current method relies on calculating the Euclidean distance between at least two marks and the target for localisation, it necessitates the use of at least two callipers for measurements. It is not feasible for a single operator to simultaneously perform measurements on the scalp to find the intersection, which could pose potential safety risks to the subjects and lead to inaccurate localisation. Therefore, our method currently requires the involvement of two operators.
Step 4. Validation of the scalp target
This step was just like step 3 but used the other two marks (eg, M1 and M3) and to find the intersection point, that is, the scalp target T2'. If the distance between T1' and T2' (ie, location error) is more than 3 mm, redo step 3 and step 4. If this location error is less than 3 mm, just use the midpoint between T1' and T2' as the scalp target for TMS.
Steps for verification of positioning accuracy
We recruited 10 healthy adults (five men and five women, aged 24 (2.1) years). Two experimenters performed the verification steps as follows (online supplemental figure S1).
Supplemental material
Step 1. Marks on the scalp
Six imageable marks were pasted on the scalp, including (1) M1–M4 on the forehead for positioning purposes and (2) T1 and T2 taken as the predefined scalp targets on roughly the vertex.
Step 2. MRI scanning and target measurement
3D-T1 was scanned for each participant. On the T1 image, the Euclidean distance from the scalp targets (T1 and T2) to the marks (M1–M4) was measured, including T1-M1, T1-M2, T1-M3, T1-M4, T2-M1, T2-M2, T2-M3 and T2-M4.
Step 3. Verification points and verification distances
Two marks were labelled using a marker pen beside each of the two scalp targets (A1 and B1 for T1, A2 and B2 for T2). Then the distances between the scalp targets and verification points were measured, that is, A1-T1, B1-T1, A2-T2 and B2-T2, using a Vernier calliper.
We used a Vernier calliper instead of an outside calliper to measure the verification distance. Vernier calliper measurement is highly accurate when the distance is not very long. To test the measurement error of the Vernier calliper, three participants were measured by two experimenters (ie, raters) on the distances, including A1-T1, B1-T1, A2-T2 and B2-T2. The inter-rater error was 0.03–0.89 mm, with an average of 0.13 mm (online supplemental table S1).
Step 4. Positioning and verifying the scalp targets
The predefined marks on the scalp targets (ie, T1 and T2) were first removed. Then two experimenters used outside callipers to define and a Vernier calliper to verify the scalp targets. The following is an example of using marks M1 and M2 to define and verify the scalp target T1.
As was done in the positioning step (figure 1), two experimenters used outside callipers and positioned the scalp target T1'. Then, one experimenter used a Vernier calliper to measure the distance from A1 and B1 to the measured scalp target T1'. After one experimenter completed this step, the scalp target T1' mark was erased. Then the other experimenter repeated this step.
Two experimenters performed the above positioning and verifying steps twice for each scalp target of each participant. In each verification procedure, the marks of ‘M1 and M2’ or ‘M3 and M4’ were used for positioning. The error of each positioning is shown in online supplemental table S2. Generally, the mean error was 2.32 mm. It should be noted that, although there were a few big errors (eg, 6.55 mm), we did not intend to reduce the error by repeated measurement. In practice, we suggest using three marks, with two marks for positioning and the third mark for validation. If the distance error is larger than 3 mm, redo the positioning step. Currently, our approach to addressing this issue is to mark both the markers and the target with a marker pen. Before and after each stimulation, we used a marker pen to reinforce the trace of the target. In several days of stimulations, it is feasible to remark any traces before each treatment. Based on our experience, if participants do not intentionally clean off the marked areas, these markings will last for days.
Summary
This CALIPPOT method can precisely (mean error <3 mm) locate the scalp target defined by fMRI. Two reusable outside callipers cost about CN¥400 (US$56). The marks cost <CN¥1 (US$0.1) for each participant. The whole procedure takes less than 10 min. This method could be widely used in MRI-guided precise rTMS treatment. As compared with the TMS neuronavigation system, one drawback of the current CALIPPOT method is that it lacks continuous monitoring, although continuous monitoring is seldom used in treatment. Nowadays, the theta burst TMS (TBS) is increasingly used,7 8 which delivers hundreds of pulses within a very short period of time (eg, 600 pulses in 40 s). In such a short period, head motion is not a big problem. In such situations, continuous monitoring may not be necessary. Therefore, not having continuous monitoring may not be a big problem for the current CALIPPOT.
Supplementary video
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by the Ethics Committee of the Center for Cognition and Brain Disorders (CCBD) at Hangzhou Normal University (HZNU). Participants gave informed consent to participate in the study before taking part.
References
Yunsong Hu is a PHD candidate at Shanghai International Studies University in China. He obtained his master’s degree from the Center for Cognition and Brain Disorders of Hangzhou Normal University, China in 2022. His main research interests include neuroimaging of movement disorders and individualized precise fMRI-guided TMS treatment.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors YH, JW and YZ analysed the data and wrote the paper. RZ, JY and QG collected and processed the data. HW and ZF collected the data. All authors designed the experiments.
Funding Ministry Key Project (JW0890006), Key Realm R&D Program of Guangdong Province (2019B030335001), Department of Science and Technology of Sichuan Province (2022NSFSC0808), Key Medical Discipline of Hangzhou, The Cultivation Project of the Province-leveled Preponderant Characteristic Discipline of Hangzhou Normal University (18JYXK046, 20JYXK004).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.