Ultrasound‐based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham‐controlled clinical studies.

Despite there being an increasing number of installations of ultra high field MR systems (>3T) in clinical environments, no functional patient investigations have yet examined possible benefits for functional diagnostics. Here we performed presurgical localization of the primary motor hand area on 3T and 7T Siemens scanners with identical investigational procedures and comparable system specific sequence optimizations. Results from 17 patients showed significantly higher functional sensitivity of the 7T system measured via percent signal change, mean t-values, number of suprathreshold voxels and contrast to noise ratio. On the other hand, 7T data suffered from a significant increase of artifacts (ghosting, head motion). We conclude that ultra high field systems provide a clinically relevant increase of functional sensitivity for patient investigations.

Objectives: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). Methods: Twenty two patients (10 males, 12 females, mean age 39 years, range 10–65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. Results: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). Conclusions: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Purpose: To evaluate the impact of data quality on the localization of brain activation in functional magnetic resonance imaging (fMRI) and to explore whether the temporal contrast‐to‐noise‐ratio (CNR) provides a quantitative parameter to estimate fMRI quality.Materials and Methods: We investigated two methods for defining the CNR by comparing them on a single‐run, single session, as well as on a group‐wise basis. The CNRs of healthy subjects and a group of patients with brain lesions were calculated using two different strategies: one based on a general linear model (GLM) analysis (CNR_SPM), and one that acts as an adaptive low‐pass filter and assumes that the high‐frequency components contain the temporal noise (CNR_SG). Runs with low CNR were identified as outliers using a common exclusion criterion (2 × standard deviation (SD)).Results: The results of the two CNR methods are highly correlated. Both between and within subjects and patients the CNR showed quite large variations, but the average CNR did not differ between a group of healthy subjects and a patient group. In total, seven of 213 runs (3.3% of all runs) had to be excluded when CNR_SG was used, and 14 of 213 (6.6%) runs had to be excluded when CNR_SPM was used.Conclusion: Calculating the CNR using an adaptive low‐pass filter gives similar results to a GLM‐based approach and could be advantageous for cases in which the hemodynamic response function (HRF) differs significantly from common assumptions. The CNR can be used to identify and exclude runs with suboptimal CNR, and to identify sessions with insufficient data quality. The CNR may serve as a quantitative and intuitive parameter to assess the performance and quality of clinical fMRI investigations, including information on both functional performance (contrast) and data quality (noise caused by the system and physiology). J. Magn. Reson. Imaging 2007;25:1263–1270.

Within the last decade, ultrasound has been “rediscovered” as a technique for brain therapies. Modern technologies allow focusing ultrasound through the human skull for highly focal tissue ablation, clinical neuromodulatory brain stimulation, and targeted focal blood‐brain‐barrier opening. This article gives an overview on the state‐of‐the‐art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly.

Introduction: Ultrasound for the brain is a revolutionary therapeutic concept. The first clinical data indicate that 2–4 weeks of therapy with transcranial pulse stimulation (TPS) improve functional networks and cognitive performance of Alzheimer's disease (AD) patients for up to 3 months. No data currently exist on possible benefits concerning brain morphology, namely the cortical atrophy characteristic of AD. Methods: We performed a pre‐/post‐therapy analysis of cortical thickness in a group of N = 17 AD patients. Results: We found a significant correlation between neuropsychological improvement and cortical thickness increase in AD‐critical brain areas. Discussion: AD patients who benefit from TPS appear to manifest reduced cortical atrophy within the default mode network in particular, whose memory‐related subsystems are believed to be disrupted in AD. TPS may therefore hold promise as a new add‐on therapy for AD.