TMS solutions based on science

The term navigated has been borrowed from the field of neurosurgery, where the principles of using images of the inside of the brain to guide surgical tools were developed. Originally, this technique was termed stereotactic surgery. Stereotactic meaning "touch in space". With the introduction of frameless stereotactic surgery, where a head tracker also permitted the patient head movement, the term intraoperative neuronavigation became popular among neurosurgeons. 

Neuronavigated systems are based on commercially-available tracking systems, which today offer extremely high spatial accuracy. These tracking systems comprise an infrared-based camera, highly-reflective “tracker” spheres and positioning software. The reflecting spheres are fixed on all the tools needed and are also attached to the patient’s head, via a headband, or headframe. Navigation of surgical tools inside the brain is achieved using the data from an MRI scan of the patient’s head. Once a neuronavigated system is “aligned” or co-registered to a patient’s own MRI-scan, the position of any tool can be located, whether it is outside the head or deep inside the brain. An accurate, three-dimensional alignment can be elegantly achieved by matching multiple landmark sites corresponding to the nose, ears and apex of the skull visible on the MRI with the corresponding, real-life landmarks of the patient’s head. Typically, T1-weighted MRI scans with 1 × 1 × 1 mm voxels are used for intraoperative neuronavigation. Requiring less than 1 GB of storage space, these scans are easily portable on various media.

Leaning on decades of experience in neurosurgery, it is a small step to treat a TMS coil as one of the tools to be tracked. This allows for a completely non-invasive neuronavigated system – one which can be used for other applications than intraoperative guidance, for example pre-surgical planning. In principle, coil-navigated TMS only requires adding reflecting spheres to the coil housing, as for any other tool. However, the challenge for tracking TMS is that we are not so interested in the physical location of the coil outside the head, but rather the location of the induced E-field inside the cortex. 
The first attempts at neuronavigation of TMS coils assumed that any E-field was induced directly under the center point of the coil windings, a line-of-sight or “line-navigation” approximation. The induced E-field being assumed to be precisely perpendicular to the stimulating magnetic field, which, in turn, is assumed to be precisely perpendicular to the coil winding surface. 

Scientific research has, however, shown that coil-navigated TMS using a line-of-sight assumption is a deceptive over-simplification, the human head is far from being a uniform sphere. Coil navigation of TMS has some validity only when the TMS coil is very carefully positioned tangentially against the head before each and every stimulus is given. In practise, coil navigation of TMS can err by up to 10 mm and in worse cases identify the wrong gyrus for the motor cortex.***

Mapping the cortex requires continuous orientation of the TMS coil, including changes in the tilt, as the operator stimulates over the patient's head. Accurately locating the “hand knob” in the motor cortex is important in therapy applications, as setting the stimulation intensity is standardized to the cortical excitability of the patient's primary motor cortex.

The "gold-standard" technique for cortex localization is direct electrocortical stimulation (DES or DCS). DES is a highly invasive procedure. The term “direct” refers to the fact that there is a direct cause-and-effect relationship between the input (E-field) and the output (for example quantitative measurement of muscle EMG amplitude). TMS is the only non-invasive modality that is fully analogous to DES in that both techniques are based on electrical stimulation of a small volume of brain tissue and the direct measurement of the induced effects. The clinical utility of DES is perceived to be very high by neurosurgeons and, although its absolute accuracy is impossible to verify. The accuracy of NBS has been validated by comparing the concordance of pre-operative NBS mapping results with the results of subsequent intraoperative DES in the same patients. 

Independent, peer-reviewed articles have shown the ability of NBS to target cortical motor sites to within approximately 2.1 mm compared to DES (Tarapore, 2012). A meta-analysis of all peer-reviewed articles on the accuracy of the NBS System in brain tumor patients found that the mean distance between motor cortex identified by NBS and DES was 6.18 mm (Takahashi et al. 2013), this result is similar in magnitude to the standard deviation intrinsic to DES localization. The FDA cleared the NBS System for mapping the motor cortex in December, 2009, indicating that the device reliably mapped the motor cortex to the same gyrus as the gold standard, DES. 

In the 8 years following the FDA clearance of the NBS System, 54 original neurosurgical articles for preprocedural planning covering 2,350 patients were published. These articles included five presurgical motor-mapping studies with a combined total of 633 patients reporting the impact of NBS-derived motor maps on better clinical outcomes** 

There is little data on the accuracy of coil-navigated, "line-navigated", TMS. The largest published study comparing line-navigated TMS to E-field-navigated TMS found significantly different results from the two methods, with only a partial overlap of the derived motor maps and, in several patients, line-navigated TMS located the targeted motor hotspot in different gyri compared to NBS.***

The user of an NBS System can be confident that whatever location, angle or tilt of the TMS coil relative to the head, a stimulus with the calculated and displayed E-field will be reliably delivered to the targeted cortical location.