Transcranial MR-guided Focused Ultrasound Research Articles

A novel high-precision fiber tractography for nuclear localization in transcranial magnetic resonance-guided focused ultrasound surgery: a pilot study.

In transcranial MR-guided focused ultrasound (TcMRgFUS), fiber tractography using diffusion tensor imaging (DTI) has been proposed as a direct method to identify the ventral intermediate nucleus (Vim), the ventral caudal nucleus (Vc), and the pyramidal tract (PT). However, the limitations of the DTI algorithm affect the accuracy of visualizing anatomical structures due to its low-quality fiber tractography, whereas the application of the generalized q-sampling imaging (GQI) algorithm enables the visualization of high-quality fiber tracts, offering detailed insights into the spatial distribution of motor cortex fibers. This retrospective study aimed to investigate the usefulness of high-precision fiber tractography using the GQI algorithm as a planning image in TcMRgFUS to achieve favorable clinical outcomes. This study included 20 patients who underwent TcMRgFUS. The Clinical Rating Scale for Tremor (CRST) scores and MR images were evaluated pretreatment and at 24 hours and 3-6 months after treatment. Cases were classified based on the presence and adversity of adverse events (AEs): no AEs, mild AEs without additional treatment, and severe AEs requiring prolonged hospitalization. Fiber tractography of the Vim, Vc, and PT was visualized using the DTI and GQI algorithm. The overlapping volume between Vim fibers and the lesion was measured, and correlation analysis was performed. The relationship between AEs and the overlapping volume of the Vc and PT fibers within the lesions was examined. The cutoff value to achieve a favorable clinical outcome and avoid AEs was determined using receiver operating characteristic curve analysis. All patients showed improvement in tremors 24 hours after treatment, with 3 patients experiencing mild AEs and 1 patient experiencing severe AEs. At the 3- to 6-month follow-up, 5 patients experienced recurrence, and 2 patients had persistent mild AEs. Although fiber visualization in the motor cortex using the DTI algorithm was insufficient, the GQI algorithm enabled the visualization of significantly higher-quality fibers. A strong correlation was observed between the overlapping volume that intersects the lesion and Vim fibers and the degree of tremor improvement (r = 0.72). Higher overlapping volumes of Vc and PT within the lesion were associated with an increased likelihood of AEs (p < 0.05); the cutoff volume of Vim fibers within the lesion for a favorable clinical outcome was 401 mm3, while the volume of Vc and PT within the lesion to avoid AEs was 99 mm3. This pilot study suggests that incorporating the high-precision GQI algorithm for fiber tractography as a planning imaging technique for TcMRgFUS has the potential to enhance targeting precision and achieve favorable clinical outcomes.

Microbubble-enhanced transcranial MR-guided focused ultrasound brain hyperthermia: heating mechanism investigation using finite element method

Recently, our group developed a synergistic brain drug delivery method to achieve simultaneous transcranial hyperthermia and localized blood–brain barrier opening via MR-guided focused ultrasound (MRgFUS). In a rodent model, we demonstrated that the ultrasound power required for transcranial MRgFUS hyperthermia was significantly reduced by injecting microbubbles (MBs). However, the specific mechanisms underlying the power reduction caused by MBs remain unclear. The present study aims to elucidate the mechanisms of MB-enhanced transcranial MRgFUS hyperthermia through numerical studies using the finite element method. The microbubble acoustic emission (MAE) and the viscous dissipation (VD) were hypothesized to be the specific mechanisms. Acoustic wave propagation was used to model the FUS propagation in the brain tissue, and a bubble dynamics equation for describing the dynamics of MBs with small shell thickness was used to model the MB oscillation under FUS exposures. A modified bioheat transfer equation was used to model the temperature in the rodent brain with different heat sources. A theoretical model was used to estimate the bubble shell’s surface tension, elasticity, and viscosity losses. The simulation reveals that MAE and VD caused a 40.5% and 52.3% additional temperature rise, respectively. Compared with FUS only, MBs caused a 64.0% temperature increase, which is consistent with our previous animal experiments. Our investigation showed that MAE and VD are the main mechanisms of MB-enhanced transcranial MRgFUS hyperthermia.

Improving Sonication Efficiency in Transcranial MR-Guided Focused Ultrasound Treatment: A Patient-Data Simulation Study.

The potential improvement in sonication efficiency achieved by tilting the focused ultrasound (FUS) transducer of the transcranial MR-guided FUS system is presented. A total of 56 cases of patient treatment data were used. The relative position of the clinical FUS transducer to the patient's head was reconstructed, and region-specific skull density and porosity were calculated based on the patient's CT volume image. The total transmission coefficient of acoustic waves emitted from each channel was calculated. Then, the total energy penetrating the human skull-which represents the sonication efficiency-was estimated. As a result, improved sonication efficiency was by titling the FUS transducer to a more appropriate angle achieved in all 56 treatment cases. This simulation result suggests the potential improvement in transcranial-focused ultrasound treatment by simply adjusting the transducer angle.

Simultaneous Localized Brain Mild Hyperthermia and Blood-Brain Barrier Opening via Feedback-Controlled Transcranial MR-Guided Focused Ultrasound and Microbubbles.

Non-invasive methods to enhance drug delivery and efficacy in the brain have been pursued for decades. Focused ultrasound hyperthermia (HT) combined with thermosensitive therapeutics have been demonstrated promising in enhancing local drug delivery to solid tumors. We hypothesized that the presence of microbubbles (MBs) combined with transcranial MR-guided focused ultrasound (MRgFUS) could be used to reduce the ultrasound power required for HT while simultaneously increasing drug delivery by locally opening the blood-brain barrier (BBB). Transcranial HT (42 °C, 10 min) was performed in wild-type mice using a small animal MRgFUS system incorporated into a 9.4T Bruker MR scanner, with infusions of saline or Definity MBs with doses of 20 or 100 µl/kg/min (denoted as MB-20 and MB-100). MR thermometry data was continuously acquired as feedback for the ultrasound controller during the procedure. Spatiotemporally precise transcranial HT was achieved in both saline and MB groups. A significant ultrasound power reduction (-45.7%, p = 0.006) was observed in the MB-20 group compared to saline. Localized BBB opening was achieved in MB groups confirmed by CE-T1w MR images. There were no structural abnormalities, edema, hemorrhage, or acutemicroglial activation in all groups, confirmed by T2w MR imaging and histology. Our investigations showed that it is feasible and safe to achieve spatiotemporally precise brain HT at significantly reduced power and simultaneous localized BBB opening via transcranial MRgFUS and MBs. This study provides a new synergistic brain drug delivery method with clinical translation potential.

The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound.

Transcranial MR-guided focused ultrasound (MRgFUS) is a minimally invasive treatment for movement disorders. Considerable interpatient variability in skull transmission efficiency exists with the current clinical devices, which is thought to be dependent on each patient's specific skull morphology. Lower skull density ratio (SDR) values are thought to impede acoustic energy transmission across the skull, attenuating or preventing the therapeutic benefits of MRgFUS. Patients with SDR values below 0.4 have traditionally been deemed poor candidates for MRgFUS. Although considerable anecdotal evidence has suggested that SDR is a reliable determinant of procedural and clinical success, relationships between SDR and clinical outcomes have yet to be formally investigated. Moreover, as transcranial MRgFUS is becoming an increasingly widespread procedure, knowledge of SDR distribution in the general population may enable improved preoperative counseling and preparedness. A total of 98 patients who underwent MRgFUS thalamotomy at the authors' institutions between 2012 and 2018 were analyzed (cohort 1). The authors retrospectively assessed the relationships between SDR and various clinical outcomes, including tremor improvement and adverse effects, as well as procedural factors such as sonication parameters. An SDR was also prospectively obtained in 163 random emergency department patients who required a head CT scan for various clinical indications (cohort 2). Patients' age and sex were used to explore relationships with SDR. In the MRgFUS treatment group, 17 patients with a thalamotomy lesion had an SDR below 0.4. Patients with lower SDRs required more sonication energy; however, their low SDR did not influence their clinical outcomes. In the emergency department patient group, about one-third of the patients had a low SDR (< 0.4). SDR did not correlate with age or sex. Although lower SDR values correlated with higher energy requirements during MRgFUS thalamotomy, within the range of this study population, the SDR did not appreciably impact or provide the ability to predict the resulting clinical outcomes. Sampling of the general population suggests that age and sex have no relationship with SDR. Other variables, such as local variances in bone density, should also be carefully reviewed to build a comprehensive appraisal of a patient's suitability for MRgFUS treatment.

Correlation between fractional anisotropy changes in the targeted ventral intermediate nucleus and clinical outcome after transcranial MR-guided focused ultrasound thalamotomy for essential tremor: results of a pilot study.

This study evaluated changes of fractional anisotropy (FA) in the ventral intermediate nucleus (VIM) of the thalamus after transcranial MR-guided focused ultrasound (TcMRgFUS) thalamotomy and their associations with clinical outcome. Clinical and radiological data of 12 patients with medically refractory essential tremor (mean age 76.5 years) who underwent TcMRgFUS thalamotomy with VIM targeting were analyzed retrospectively. The Clinical Rating Scale for Tremor (CRST) score was calculated before and at 1 year after treatment. Measurements of the relative FA (rFA) values, defined as ratio of the FA value in the targeted VIM to the FA value in the contralateral VIM, were performed before thalamotomy, and 1 day and 1 year thereafter. TcMRgFUS thalamotomy was well tolerated and no long-term complications were noted. At 1-year follow-up, 8 patients demonstrated relief of tremor (improvement group), whereas in 4 others persistent tremor was noted (recurrence group). In the entire cohort, mean rFA values in the targeted VIM before treatment, and at 1 day and 1 year after treatment, were 1.12 ± 0.15, 0.44 ± 0.13, and 0.82 ± 0.22, respectively (p < 0.001). rFA values were consistently higher in the recurrence group compared with the improvement group, and the difference reached statistical significance at 1 day (p < 0.05) and 1 year (p < 0.01) after treatment. There was a statistically significant (p < 0.01) positive correlation between rFA values in the targeted VIM at 1 day after thalamotomy and CRST score at 1 year after treatment. Receiver operating characteristic curve analysis revealed that the optimal cutoff value of rFA at 1 day after thalamotomy for prediction of symptomatic improvement at 1-year follow-up is 0.54. TcMRgFUS thalamotomy results in significant decrease of rFA in the targeted VIM, at both 1 day and 1 year after treatment. Relative FA values at 1 day after treatment showed significant correlation with CRST score at 1-year follow-up. Therefore, FA may be considered a possible imaging biomarker for early prediction of clinical outcome after TcMRgFUS thalamotomy for essential tremor.

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note.

Background: MR-guided focused ultrasound (MRgFUS) offers new perspectives for safe and efficient lesioning inside the brain. The issue of target coverage remains primordial and sub-optimally addressed or solved in the field of functional neurosurgery.Objective: To provide an optimized planning and operative strategy to perform a pallidothalamic tractotomy (PTT) in chronic therapy-resistant Parkinson's disease (PD) with the technology of MRgFUS.Methods and results: Histological sections and maps from 6 human brain hemispheres were analyzed and outlines of the pallidothalamic tract on Myelin-stained sections were drawn and superimposed. We determined a standardized PTT target coverage characterized by 5 to 7 preplanned target lesion sub-units of 1.5 × 1.5 × 3.0 mm, which were placed using focal point displacements and shortest possible times, under thermal dose control.Conclusion: We hereby present our current approach to the MRgFUS PTT on the basis of a histological reappraisal and optimized heat application to the pallidothalamic tract in the H1 field of Forel.

Ultrashort echo-time MRI as a substitute to CT for skull aberration correction in transcranial focused ultrasound: in vitro comparison on human calvaria

Clinical transcranial MR-guided focused ultrasound (TcMRgFUS) brain treatment systems compensate for skull-induced beam aberrations by adjusting the phase and amplitude of individual ultrasound transducer elements. These corrections are currently calculated based on a pre-acquired CT scan of the patient’s head. The purpose of the work presented here is to demonstrate the feasibility of using ultrashort echo-time (UTE) MRI instead of CT to calculate and apply aberration corrections on a clinical TcMRgFUS system.

Acoustic characterization of a neonate skull using a clinical MR-guided high intensity focused ultrasound system for pediatric neurological disorder treatment planning

Transcranial MR-guided Focused Ultrasound (TcMRgFUS) treatments are now clinically performed on adult patients for brain tumor or essential tremor therapies. However, no application has been proposed for children despite their thinner skull being less of an acoustic barrier and the presence of a fontanelle on neonates, which could constitute a natural acoustic window for the transmission of ultrasound waves. As there is minimal literature data on the attenuation and speed-of-sound of the skull in neonatal patients, the aim of this study was to perform the acoustic characterization of a neonate skull.

MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo swine brain

To present the use of MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo brain tissue as a planning indicator for MR-guided focused ultrasound (MRgFUS).Calcifications were implanted in ex vivo swine brain and imaged using SWI, MR-ARFI, and computed tomography (CT). SWI-filtered phase images used 3D gradient recalled echo (GRE) images with a Fourier-based unwrapping algorithm. The MR-ARFI pulse sequence used a 2DFT spin-echo with repeated bipolar encoding gradients in the direction of the longitudinal ultrasound beam. MR-ARFI interrogations scanned a subregion (14 × 10 × 12 mm) of the brain surrounding the calcification. They were combined into a single displacement weighted map, using the sum of squares method. Calcification size estimates were based on image profiles plotted along the ±x and ±z direction, at the full-width half-maximum.Both MR-ARFI and SWI were able to visualize the calcifications. The contrast ratio was 150 for CT, 12 for SWI, and 12 for MR-ARFI. Profile measures were 1.35 × 1.28 mm on CT, 1.24 × 1.73 mm on SWI, and 2.45 × 3.02 mm on MR-ARFI. MR-ARFI displacement showed a linear increase with acoustic power (20-80 W), and also increased with calcification size.The use of SWI-filtered phase and MR-ARFI have the potential to provide a clinical indicator of calcification relevance in the planning of a transcranial MRgFUS treatment.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance–guided focused ultrasound

Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

Evaluation of three-dimensional temperature distributions produced by a low-frequency transcranial focused ultrasound system within ex vivo human skulls

Transcranial MR-guided focused ultrasound (TcMRgFUS) provides a potential noninvasive alternative to surgical resection and for other treatments for brain disorders. Use of low-frequency ultrasound provides several advantages for TcMRgFUS, but is potentially limited by reflection and standing wave effects that may cause secondary hotspots within the skull cavity. The purpose of this work was to use volumetric magnetic resonance temperature imaging (MRTI) and ex vivo human skulls filled with tissue-mimicking phantom material to search for heating distant from the focal point that may occur during sonication with a TcMRgFUS system as a result of reflections or standing wave effects. Heating during 120-s sonications was monitored within the entire skull volume for 12 different locations in two different skulls. The setup used a hemispheric array operating at 220 kHz. Multiple sonications were delivered at each location while varying the MRTI slice positions to provide full coverage of the skull cavity. An automated routine was used evaluate the MRTI to detect voxel regions that appeared to be heated by ultrasound. No secondary hotspots with a temperature rise of 15% or more of the focal heating were found. The MRTI noise level prevented the identification of possible hotspots with a lower temperature rise. These results suggest that significant secondary heating by this TcMRgFUS system at points distant from the focal point are not common.