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Letter: Commentary: Utilization of Quantitative Susceptibility Mapping for Direct Targeting of the Subthalamic Nucleus During Deep Brain Stimulation Surgery.

To the Editor: We thank Dr Alterman for his interest in our paper1 and for his commentary2 on our work. We appreciate his agreement that quantitative susceptibility mapping (QSM) may 1 d provide a means to target deep brain structures consistently without microelectrode recording (MER) confirmation. His commentary expressed 2 concerns: data analysis on comparing QSM vs MER, and a first-pass “miss rate”.2 Regarding data analysis on comparing QSM vs MER, QSM and MER data were measured independently. This is a standard laboratory practice in comparing 2 techniques, and here we explicitly clarify so. Dr Alterman’s main concern was in our use of the Bland-Altman (B-A) plot, instead of a regression analysis. It is well known that linear regression is not suitable to show agreement between 2 different techniques.3 The B-A plot is exactly designed to overcome this deficiency of linear regression.4,5 Specifically, in applying linear regression to the subthalamic nucleus (STN) thickness measurement, (i) very narrow range of true quantity (STN thickness) results in reduced correlation coefficient, and (ii) difference in standard deviations of measurements obtained by 2 approaches (QSM vs MER) leads to further tipping of the regression line away from the line of identity.4,6 Therefore, these 2 factors render simple regression analysis rather misleading. Thus, in order to demonstrate absence of proportional and fixed bias in QSM-based measurements, the B-A approach has to be employed. Due to substantial differences in resolutions provided by QSM and MER, data standardization was performed to demonstrate the concordance between the 2 techniques. Such standardization is quite commonly utilized, and its necessity was demonstrated during the peer revision process.7,8 Additionally, we provided t-test of differences between measurements.6 Thus, we believe our results can be viewed as a confirmation of agreement between estimations using MER and measurements on QSM images. Regarding the first-pass “miss rate”, we respectfully disagree with Dr Alterman’s assessment of the meaning of this observation. Our manuscript is not a referendum on the accuracy of stereotactic equipment/technique. Indeed, it is to demonstrate the use of an imaged-guided technique (QSM-based targeting) to refine deep brain stimulation (DBS) lead placement and compare it to a technique that has been historically used (MER). One must differentiate 2 independent types of errors: type 1—a miss due to lack of unambiguous identification of the anatomic features of interest (eg, STN borders) in the image; type 2—a miss due to the intraoperative factors (Leksell frame errors, inaccuracies of computed tomography / magnetic resonance registration, etc.). It is important to emphasize that our experience with QSM suggests that this 14% miss rate can be attributed almost entirely to the type 2 errors (ie, when the MER tip was deviated from the intended QSM target as determined by intraoperative imaging, the MER signal was poor). This conclusion is supported by the fact that, as we originally reported, once type 2 error sources were accounted for (ie, the targeting was refined and the MER tip was now at the intended QSM-defined target), no further misses were registered—the electrode tip was localized within the STN as defined by preoperative QSM and a traditionally-defined “satisfactory” MER signal was obtained. We believe this is an important finding that has to be brought to the attention of the DBS community.