Introduction: Peripheral nerve field stimulation (PNFS) for facial pain delivers subcutaneous electrical stimulation to reduce pain. Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) can be used to characterize central effects of neuromodulation techniques such as deep brain stimulation and spinal cord stimulation (SCS). However, the safety and utility of MRI in patients with PNFS have not been established, limiting both clinical MRI use and the application of fMRI in this population. This study evaluated the MRI safety and feasibility of imaging an active SCS implant used for PNFS in patients with facial pain; and defined sequence parameters for concurrent BOLD fMRI acquisition. Methods: An anthropomorphic 3D-printed phantom filled with tissue-mimicking gel and fitted with an SCS implant replicating a patient with PNFS was used for in vitro safety testing. Two phantom experiments evaluated the relationship between (i) head-averaged specific absorption rate (SAR), (ii) time-averaged positive radiofrequency magnetic field component (B1rms+) and maximal temperature rises at critical locations (i.e., distal lead electrodes, cranial coiling, and implantable pulse generator) across clinical and research-based structural and fMRI sequences. For validation, a PNFS patient was scanned using localizer, T1-weighted magnetization-prepared rapid gradient echo, T2-weighted sampling perfection with application-optimized contrasts using different flip angle evolutions, and BOLD fMRI sequences informed by phantom experiments. Results: FMRI during active PNFS is safe under specific conditions, with temperature increases remaining below the 2°C threshold at all monitored locations. Heating had a stronger relationship with head SAR (higher adjusted coefficient of determination [R2] value) than B1rms+, particularly at distal lead electrodes. These in vitro findings informed selection of safe fMRI protocols for in vivo scanning. A patient (n = 1) underwent MRI with no device- or patient-related adverse events. Successful fMRI acquisition was achieved, demonstrating engagement of pain-related regions in the patient. Conclusion: Phantom testing confirmed the safety and feasibility of MRI with an active SCS device configured for facial PNFS. These findings, specific to the tested conditions, underscore the need for context-specific safety evaluations to enable safe MRI in such implantable medical devices.

BackgroundDeep brain stimulation targeting the subcallosal cingulate (SCC-DBS) is a promising therapy for treatment-resistant depression. However, the lack of a consistent, rapid behavioural response to SCC-DBS complicates the selection of optimal stimulation settings following implantation, requiring a prolonged and burdensome trial-and-error process. Immediate biomarkers of effective stimulation could overcome this problem.MethodsIn this proof-of-concept study, three patients with SCC-DBS implants were scanned at 3 T using a block-design paradigm in which stimulation alternated between "ON" and "OFF" states in 30-s cycles during a single 6.5-min acquisition. Scans were performed using participants' clinically optimized parameters. Blood-oxygen-level-dependent (BOLD) response maps were generated by contrasting DBS-ON and DBS-OFF conditions, and exploratory correlations with clinical outcome-indexed by percentage reduction in Hamilton Depression Rating Scale scores at 12 months-were also assessed.ResultsContrasting stimulation settings enabled the identification of regional BOLD signal changes associated with DBS, revealing consistent hemodynamic changes in several brain regions during active stimulation. Specifically, the precuneus, posterior cingulate cortex, middle frontal gyrus, and frontal pole exhibited decreased BOLD responses during active DBS, while the occipital cortex, middle temporal gyrus, inferior parietal lobule, and superior frontal gyrus showed increased BOLD responses. Exploratory analysis further suggested a potential correlation between precuneus BOLD signal change and clinical improvement (R = -0.98, ppermute = 0.09).ConclusionThese findings speak to the utility of block-design fMRI with cycling DBS stimulation as a tool to identify objective, brain-based biomarkers of effective SCC-DBS, potentially expediting stimulation parameter selection and therapeutic optimization.

INTRODUCTION:Magnetic resonance imaging (MRI) is both a crucial clinical and research tool for patients with deep brain stimulation (DBS) devices. However, safety concerns predominantly related to device heating have limited such imaging. Rigorous safety testing has demonstrated that scanning outside of vendor guidelines may be both safe and feasible, unlocking unique opportunities for advanced imaging in this patient population. Currently, however, 3T MRI safety data including advanced MRI sequences in novel directional and sensing DBS devices is lacking. METHODS:An anthropomorphic phantom replicating bilateral DBS system was used to assess the temperature rise at the electrode tips, implantable pulse generator, and cranial loop during acquisition of routine clinical sequences (three dimensional [3D] T1, GRE T2*, T2 FSE) and advanced imaging sequences including functional MRI (fMRI), arterial spin labelling (ASL), and diffusion weighted imaging (DWI). Measures of radiofrequency exposure (specific absorption rate [SAR] and root-mean square value of the MRI effective component of the radiofrequency transmission field [B1+rms]) were also recorded as an indirect measure of heating. Testing involved both a new directional and sensing DBS device (Medtronic: B30015 leads and Percept PC neurostimulator) and a previous-generation DBS device (Medtronic: 3,387 leads and Percept PC neurostimulator) in combination with a state-of-the-art (Siemens MAGNETOM Prisma) and a previous-generation (GE Signa HDxt) 3T MRI scanner. RESULTS:On the state-of-the-art 3T MRI scanner, the new DBS device produced safe temperature rises with clinically used sequences and fMRI but not with other advanced sequences such as DWI and ASL, which also exceeded B1+rms vendor guidelines (i.e., ≤2 μT). When scanned on the previous MRI scanner, the recent DBS device produced overall lower and slower temperature rises compared to the previous DBS model. Among the sequences performed on this scanner, several (3D T1, DWI, T2 FSE, and ASL) exceeded the approved SAR vendor limit (<1 W/kg), but only ASL resulted in an unacceptable temperature rise during scanning of the previous DBS model. CONCLUSION:These phantom safety data show that both clinically used MRI sequences and research sequences such as fMRI can be successfully acquired on 3T MRI scanners with a novel directional and sensing DBS model. As several of these sequences were obtained outside regulatory-approved vendor guidelines, preemptive safety testing should be done. As directional leads become increasingly common, improving MRI safety knowledge is crucial to expand clinical and research possibilities. INTRODUCTION:Magnetic resonance imaging (MRI) is both a crucial clinical and research tool for patients with deep brain stimulation (DBS) devices. However, safety concerns predominantly related to device heating have limited such imaging. Rigorous safety testing has demonstrated that scanning outside of vendor guidelines may be both safe and feasible, unlocking unique opportunities for advanced imaging in this patient population. Currently, however, 3T MRI safety data including advanced MRI sequences in novel directional and sensing DBS devices is lacking. METHODS:An anthropomorphic phantom replicating bilateral DBS system was used to assess the temperature rise at the electrode tips, implantable pulse generator, and cranial loop during acquisition of routine clinical sequences (three dimensional [3D] T1, GRE T2*, T2 FSE) and advanced imaging sequences including functional MRI (fMRI), arterial spin labelling (ASL), and diffusion weighted imaging (DWI). Measures of radiofrequency exposure (specific absorption rate [SAR] and root-mean square value of the MRI effective component of the radiofrequency transmission field [B1+rms]) were also recorded as an indirect measure of heating. Testing involved both a new directional and sensing DBS device (Medtronic: B30015 leads and Percept PC neurostimulator) and a previous-generation DBS device (Medtronic: 3,387 leads and Percept PC neurostimulator) in combination with a state-of-the-art (Siemens MAGNETOM Prisma) and a previous-generation (GE Signa HDxt) 3T MRI scanner. RESULTS:On the state-of-the-art 3T MRI scanner, the new DBS device produced safe temperature rises with clinically used sequences and fMRI but not with other advanced sequences such as DWI and ASL, which also exceeded B1+rms vendor guidelines (i.e., ≤2 μT). When scanned on the previous MRI scanner, the recent DBS device produced overall lower and slower temperature rises compared to the previous DBS model. Among the sequences performed on this scanner, several (3D T1, DWI, T2 FSE, and ASL) exceeded the approved SAR vendor limit (<1 W/kg), but only ASL resulted in an unacceptable temperature rise during scanning of the previous DBS model. CONCLUSION:These phantom safety data show that both clinically used MRI sequences and research sequences such as fMRI can be successfully acquired on 3T MRI scanners with a novel directional and sensing DBS model. As several of these sequences were obtained outside regulatory-approved vendor guidelines, preemptive safety testing should be done. As directional leads become increasingly common, improving MRI safety knowledge is crucial to expand clinical and research possibilities.

A total of 15 individuals with cervical dystonia and good outcome after pallidal deep brain stimulation underwent resting‐state functional magnetic resonance imaging under three conditions: stimulation using a priori clinically determined optimal settings (ON‐Op), non‐optimal settings (ON‐NOp), and stimulation off (OFF). ON‐Op > OFF and ON‐Op > ON‐NOp were both associated with significant deactivation within sensorimotor cortex (changes not seen with ON‐NOp > OFF). Brain responses to stimulation were related to individual long‐term clinical improvement (R = 0.73, R2 = 0.53, p = 0.001). The relationship was consistent when this model included four additional patients with generalized or truncal dystonia. These findings highlight the potential for immediate imaging‐based biomarkers of clinical efficacy. ANN NEUROL 2022;92:418–424

Using 3T functional MRI, Elias et al. show that subcallosal cingulate DBS acutely alters activity in brain regions implicated in mood, including dorsal anterior cingulate cortex, in patients with symptoms of depression. The observed changes correlate with both immediate mood fluctuations and long-term antidepressant outcomes. Deep brain stimulation targeting the subcallosal cingulate area, a hub with multiple axonal projections, has shown therapeutic potential for treatment-resistant mood disorders. While subcallosal cingulate deep brain stimulation drives long-term metabolic changes in corticolimbic circuits, the brain areas that are directly modulated by electrical stimulation of this region are not known. We used 3.0 T functional MRI to map the topography of acute brain changes produced by stimulation in an initial cohort of 12 patients with fully implanted deep brain stimulation devices targeting the subcallosal cingulate area. Four additional subcallosal cingulate deep brain stimulation patients were also scanned and employed as a validation cohort. Participants underwent resting state scans (n = 78 acquisitions overall) during (i) inactive deep brain stimulation; (ii) clinically optimal active deep brain stimulation; and (iii) suboptimal active deep brain stimulation. All scans were acquired within a single MRI session, each separated by a 5-min washout period. Analysis of the amplitude of low-frequency fluctuations in each sequence indicated that clinically optimal deep brain stimulation reduced spontaneous brain activity in several areas, including the bilateral dorsal anterior cingulate cortex, the bilateral posterior cingulate cortex, the bilateral precuneus and the left inferior parietal lobule (P-Bonferroni < 0.0001). Stimulation-induced dorsal anterior cingulate cortex signal reduction correlated with immediate within-session mood fluctuations, was greater at optimal versus suboptimal settings and was related to local cingulum bundle engagement. Moreover, linear modelling showed that immediate changes in dorsal anterior cingulate cortex, posterior cingulate cortex and precuneus activity could predict individual long-term antidepressant improvement. A model derived from the primary cohort that incorporated amplitude of low-frequency fluctuations changes in these three areas (along with preoperative symptom severity) explained 55% of the variance in clinical improvement in that cohort. The same model also explained 93% of the variance in the out-of-sample validation cohort. Additionally, all three brain areas exhibited significant changes in functional connectivity between active and inactive deep brain stimulation states (P-Bonferroni < 0.01). These results provide insight into the network-level mechanisms of subcallosal cingulate deep brain stimulation and point towards potential acute biomarkers of clinical response that could help to optimize and personalize this therapy.

OBJECTIVE:Many centers are hesitant to perform clinically indicated MRI in patients who have undergone deep brain stimulation (DBS). Highly restrictive guidelines prohibit the use of most routine clinical MRI protocols in these patients. The authors' goals were to assess the safety of spine MRI in patients with implanted DBS devices, first through phantom model testing and subsequently through validation in a DBS patient cohort. METHODS:A phantom was used to assess DBS device heating during 1.5-T spine MRI. To establish a safe spine protocol, routinely used clinical sequences deemed unsafe (a rise in temperature > 2°C) were modified to decrease the rise in temperature. This safe phantom-based protocol was then used to prospectively run 67 spine MRI sequences in 9 DBS participants requiring clinical imaging. The primary outcome was acute adverse effects; secondary outcomes included long-term adverse clinical effects, acute findings on brain MRI, and device impedance stability. RESULTS:The increases in temperature were highest when scanning the cervical spine and lowest when scanning the lumbar spine. A temperature rise < 2°C was achieved when 3D sequences were modified to 2D and when the number of slices was decreased by the minimum amount compared to routine spine MRI protocols (but there were still more slices than allowed by vendor guidelines). Following spine MRI, no acute or long-term adverse effects or acute findings on brain MR images were detected. Device impedances remained stable. CONCLUSIONS:Patients with DBS devices may safely undergo spine MRI with a fewer number of slices compared to those used in routine clinical protocols. Safety data acquisition may allow protocols outside vendor guidelines with a maximized number of slices, reducing the need for radiologist supervision.Clinical trial registration no.: NCT03753945 (ClinicalTrials.gov).