Transcranial focused ultrasound (FUS) ablation is an emerging incision-less treatment for neurological disorders. The factors affecting FUS treatment efficiency are not well understood. Kranion is open-source software that allows the user to simulate the planning stages of FUS treatment and to “replay” previous treatments for off-line analysis. This study aimed to investigate the relationship between skull parameters and treatment efficiency and to create a metric to estimate temperature rise during FUS. CT images from 28 patients were analyzed to validate the use of Kranion. For stereotactic targets within each patient, individual transducer element incident angles, skull density ratio, and skull thickness measurements were recorded. A penetration metric (the “beam index”) was calculated by combining the energy loss from incident angles and the skull thickness. Kranion accurately estimated the patient’s skull and treatment parameters. The authors observed significant changes in incident angles with different targets in the brain. Using the beam index as a predictor of temperature rise in a linear-mixed-effects model, they were able to predict the average temperature rise at the focal point during ablation with < 21% error (55°C ± 3.8°C) in 75% of sonications, and with < 44% (55°C ± 7.9°C) in 97% of sonications. This research suggests that the beam index can improve the prediction of temperature rise during FUS. Additional work is required to study the relationship between temperature rise and lesion shape and clinical outcomes.
Francesco Sammartino, Dylan W. Beam, John Snell, and Vibhor Krishna
Report of 6 cases
Alberto Feletti, Giannantonio Zanata Santi, Francesco Sammartino, Marzio Bevilacqua, Piero Cisotto, and Pierluigi Longatti
Peripheral nerve field stimulation has been successfully used for many neuropathic syndromes. However, it has been reported as a treatment for trigeminal neuropathic pain or persistent idiopathic facial pain only in the recent years.
The authors present a review of the literature and their own series of 6 patients who were treated with peripheral nerve stimulation for facial neuropathic pain, reporting excellent pain relief and subsequent better social relations and quality of life.
On average, pain scores in these patients decreased from 10 to 2.7 on the visual analog scale during a 17-month follow-up (range 0–32 months). The authors also observed the ability to decrease trigeminal pain with occipital nerve stimulation, clinically confirming the previously reported existence of a close anatomical connection between the trigeminal and occipital nerves (trigeminocervical nucleus).
Peripheral nerve field stimulation of the trigeminal and occipital nerves is a safe and effective treatment for trigeminal neuropathic pain and persistent idiopathic facial pain, when patients are strictly selected and electrodes are correctly placed under the hyperalgesia strip at the periphery of the allodynia region.
Francesco Sammartino, Rachel Marsh, Fang-Cheng Yeh, Anders Sondergaard, Barbara Kelly Changizi, and Vibhor Krishna
Globus pallidus (GP) lesioning improves motor symptoms of Parkinson’s disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was recently found to have a distinct radiological signature on diffusion MRI (dMRI), potentially related to its unique cellular content and organization (or tissue architecture). In this study, the authors hypothesize that the magnitude of water diffusivity, a surrogate for tissue architecture, will radiologically distinguish motor from nonmotor GP subregions in patients with PD. They also hypothesize that the therapeutic focused ultrasound pallidotomy lesions will preferentially overlap the motor subregion.
Diffusion MRI from healthy subjects (n = 45, test-retest S1200 cohort) and PD patients (n = 33) was parcellated based on the magnitude of water diffusivity in the GP, as measured orientation distribution function (ODF). A clustering algorithm was used to identify GP parcels with distinct ODF magnitude. The individual parcels were used as seeds for tractography to distinguish motor from nonmotor subregions. The locations of focused ultrasound lesions relative to the GP parcels were also analyzed in 11 patients with PD.
Radiologically, three distinct parcels were identified within the GP in healthy controls and PD patients: posterior, central, and anterior. The posterior and central parcels comprised the motor subregion and the anterior parcel was classified as a nonmotor subregion based on their tractography connections. The focused ultrasound lesions preferentially overlapped with the motor subregion (posterior more than central). The hotspots for motor improvement were localized in the posterior GP parcel.
Using a data-driven approach of ODF-based parcellation, the authors radiologically distinguished GP motor subregions in patients with PD. This method can aid stereotactic targeting in patients with PD undergoing surgical treatments, especially focused ultrasound ablation.
Vibhor Krishna, Francesco Sammartino, Philip Yee, David Mikulis, Matthew Walker, Gavin Elias, and Mojgan Hodaie
The diagnosis of Chiari malformation Type I (CM-I) is primarily based on the degree of cerebellar tonsillar herniation even though it does not always correlate with symptoms. Neurological dysfunction in CM-I presumably results from brainstem compression. With the premise that conventional MRI does not reveal brain microstructural changes, this study examined both structural and microstructural neuroimaging metrics to distinguish patients with CM-I from age- and sex-matched healthy control subjects.
Eight patients with CM-I and 16 controls were analyzed. Image postprocessing involved coregistration of anatomical T1-weighted with diffusion tensor images using 3D Slicer software. The structural parameters included volumes of the posterior fossa, fourth ventricle, and tentorial angle. Fractional anisotropy (FA) was calculated separately in the anterior and posterior compartments of the lower brainstem.
The mean age of patients in the CM-I cohort was 42.6 ± 10.4 years with mean tonsillar herniation of 12 mm (SD 0.7 mm). There were no significant differences in the posterior fossa volume (p = 0.06) or fourth ventricular volume between the 2 groups (p = 0.11). However, the FA in the anterior brainstem compartment was significantly higher in patients with CM-I preoperatively (p = 0.001). The FA values normalized after Chiari decompression except for persistently elevated FA in the posterior brainstem compartment in patients with CM-I and syrinx.
In this case-control study, microstructural alterations appear to be reliably associated with the diagnosis of CM-I, with a significantly elevated FA in the lower brainstem in patients with CM-I compared with controls. More importantly, the FA values normalized after decompressive surgery. These findings should be validated in future studies to determine the significance of diffusion tensor imaging–based assessment of brainstem microstructural integrity as an adjunct to the clinical assessment in patients with CM-I.
Alexandre Boutet, Ileana Hancu, Utpal Saha, Adrian Crawley, David S. Xu, Manish Ranjan, Eugen Hlasny, Robert Chen, Warren Foltz, Francesco Sammartino, Ailish Coblentz, Walter Kucharczyk, and Andres M. Lozano
Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.
A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.”
In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.
In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.
Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.
Nicolas Kon Kam King, Vibhor Krishna, Diellor Basha, Gavin Elias, Francesco Sammartino, Mojgan Hodaie, Andres M. Lozano, and William D. Hutchison
The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM).
Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13–30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM.
Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13–30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM.
The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.
Francesco Sammartino, Vibhor Krishna, Tejas Sankar, Jason Fisico, Suneil K. Kalia, Mojgan Hodaie, Walter Kucharczyk, David J. Mikulis, Adrian Crawley, and Andres M. Lozano
The aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems.
This study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging.
During phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed.
To the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.
Rosa Q. So, Vibhor Krishna, Nicolas Kon Kam King, Huijuan Yang, Zhuo Zhang, Francesco Sammartino, Andres M. Lozano, Richard A. Wennberg, and Cuntai Guan
The authors explored the feasibility of seizure detection and prediction using signals recorded from the anterior thalamic nucleus, a major target for deep brain stimulation (DBS) in the treatment of epilepsy.
Using data from 5 patients (13 seizures in total), the authors performed a feasibility study and analyzed the performance of a seizure prediction and detection algorithm applied to simultaneously acquired scalp and thalamic electroencephalography (EEG). The thalamic signal was obtained from DBS electrodes. The applied algorithm used the similarity index as a nonlinear measure for seizure identification, with patient-specific channel and threshold selection. Receiver operating characteristic (ROC) curves were calculated using data from all patients and channels to compare the performance between DBS and EEG recordings.
Thalamic DBS recordings were associated with a mean prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr. In comparison, scalp EEG recordings were associated with a mean prediction rate of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC curves, when considering all channels, DBS outperformed EEG for both detection and prediction of seizures.
This is the first study to compare automated seizure detection and prediction from simultaneous thalamic and scalp EEG recordings. The authors have demonstrated that signals recorded from DBS leads are more robust than EEG recordings and can be used to predict and detect seizures. These results indicate feasibility for future designs of closed-loop anterior nucleus DBS systems for the treatment of epilepsy.