Predicting Bone Marrow Damage in the Skull After Clinical Transcranial MRI-Guided Focused Ultrasound With Acoustic and Thermal Simulations.
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ABSTRACT:
SUBMITTER: McDannold N
PROVIDER: S-EPMC7529866 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This work explored an elementwise approach to model transcranial MRI-guided focused ultrasound (TcMRgFUS) thermal ablation, a noninvasive approach to neurosurgery. Each element of the phased array transducer was simulated individually and could be simultaneously loaded into computer memory, allowing for rapid (~2.5 s) calculation of the pressure field for different phase offsets used for beam steering and aberration correction. We simulated the pressure distribution for 431 sonications in 32 patients, applied the phase and magnitude values used during treatment, and estimated the resulting temperature rise. We systematically varied the relationship between CT (computerized tomography)-derived skull density and the acoustic attenuation and sound speed to obtain the best agreement between the predictions and MR temperature imaging (MRTI). The optimization was validated with simulations of 396 sonications from 40 additional treatments. After optimization, the predicted and measured heating agreed well (R2: 0.74 patients 1-32; 0.71 patients 33-72). The dimensions and obliquity of the heating in the simulated temperature maps were correlated with the MRTI (R2: 0.62, 0.74, respectively), but the measured heating was more spatially diffuse. The energy needed to achieve ablation varied by an order of magnitude (3.3-36.1 kJ). While this elementwise approach required more computation time up front (the combined simulation matrices were approximately 4.6 times higher than a single large simulation), it could be performed in parallel on a computing cluster. It allows for rapid calculation of the three-dimensional heating at the focus for different phase and magnitude values on the array. We also show how this approach can be used to optimize the relationship between CT-derived skull density and acoustic properties. While the relationships found here need further validation in a larger patient population, these results demonstrate the promise of this approach to model TcMRgFUS.
| S-EPMC8218657 | biostudies-literature
Project description:Transcranial focused ultrasound stimulation is a promising therapeutic modality for human brain disorders because of its noninvasiveness, long penetration depth, and versatile spatial control capability through beamforming and beam steering. However, the skull presents a major hurdle for successful applications of ultrasound stimulation. Specifically, skull-induced focal aberration limits the capability for accurate and versatile targeting of brain subregions. In addition, there lacks a fully functional preclinical neuromodulation system suitable to conduct behavioral studies. Here, we report a miniature ultrasound system for neuromodulation applications that is capable of highly accurate multiregion targeting based on acoustic holography. Our work includes the design and implementation of an acoustic lens for targeting brain regions with compensation for skull aberration through time-reversal recording and a phase conjugation mirror. Moreover, we utilize MEMS and 3D-printing technology to implement a 0.75-g lightweight neuromodulation system and present in vivo characterization of the packaged system in freely moving mice. This preclinical system is capable of accurately targeting the desired individual or multitude of brain regions, which will enable versatile and explorative behavior studies using ultrasound neuromodulation to facilitate widespread clinical adoption.
| S-EPMC10085992 | biostudies-literature
Project description:Pharmacological treatment of gliomas and other brain-infiltrating tumors remains challenging due to limited delivery of most therapeutics across the blood-brain barrier (BBB). Transcranial MRI-guided focused ultrasound (FUS), an emerging technology for noninvasive brain treatments, enables transient opening of the BBB through acoustic activation of circulating microbubbles. Here, we evaluate the safety and utility of transcranial microbubble-enhanced FUS (MB-FUS) for spatially targeted BBB opening in patients with infiltrating gliomas. In this Phase 0 clinical trial (NCT03322813), we conducted comparative and quantitative analyses of FUS exposures (sonications) and their effects on gliomas using MRI, histopathology, microbubble acoustic emissions (harmonic dose [HD]), and fluorescence-guided surgery metrics. Contrast-enhanced MRI and histopathology indicated safe and reproducible BBB opening in all patients. These observations occurred using a power cycling closed feedback loop controller, with the power varying by nearly an order of magnitude on average. This range underscores the need for monitoring and titrating the exposure on a patient-by-patient basis. We found a positive correlation between microbubble acoustic emissions (HD) and MR-evident BBB opening (P = 0.07) and associated interstitial changes (P < 0.01), demonstrating the unique capability to titrate the MB-FUS effects in gliomas. Importantly, we identified a 2.2-fold increase of fluorescein accumulation in MB-FUS-treated compared to untreated nonenhancing tumor tissues (P < 0.01) while accounting for vascular density. Collectively, this study demonstrates the capabilities of MB-FUS for safe, localized, controlled BBB opening and highlights the potential of this technology to improve the surgical and pharmacologic treatment of brain tumors.
| S-EPMC8449371 | biostudies-literature
Project description:PurposeTo analyze clinical data indicating a reduction in the induced energy-temperature efficiency relationship during transcranial focused ultrasound (FUS) Essential Tremor (ET) thalamotomy treatments at higher acoustic powers, establish its relationship with the spatial distribution of the focal temperature elevation, and explore its cause.MethodsA retrospective observational study of patients (n = 19) treated between July 2015 and August 2016 for (ET) by FUS thalamotomy was performed. These data were analyzed to compare the relationships between the applied power, the applied energy, the resultant peak temperature achieved in the brain, and the dispersion of the focal volume. Full ethics approval was received and all patients provided signed informed consent forms before the initiation of the study. Computer simulations, animal experiments, and clinical system tests were performed to determine the effects of skull heating, changes in brain properties and transducer acoustic output, respectively. All animal procedures were approved by the Animal Care and Use Committee and conformed to the guidelines set out by the Canadian Council on Animal Care. MATLAB was used to perform statistical analysis.ResultsThe reduction in the energy efficiency relationship during treatment correlates with the increase in size of the focal volume at higher sonication powers. A linear relationship exists showing that a decrease in treatment efficiency correlates positively with an increase in the focal size over the course of treatment (P < 0.01), supporting the hypothesis of transient skull and tissue heating causing acoustic aberrations leading to a decrease in efficiency. Changes in thermal conductivity, perfusion, absorption rates in the brain, as well as ultrasound transducer acoustic output levels were found to have minimal effects on the observed reduction in efficiency.ConclusionsThe reduction in energy-temperature efficiency during high-power FUS treatments correlated with observed increases in the size of the focal volume and is likely caused by transient changes in the tissue and skull during heating.
| S-EPMC6041137 | biostudies-literature
Project description:Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.
| S-EPMC4348665 | biostudies-literature
Project description:ObjectiveWe present the development of a non-contrast multi-parametric magnetic resonance (MPMR) imaging biomarker to assess treatment outcomes for magnetic resonance-guided focused ultrasound (MRgFUS) ablations of localized tumors. Images obtained immediately following MRgFUS ablation were inputs for voxel-wise supervised learning classifiers, trained using registered histology as a label for thermal necrosis.MethodsVX2 tumors in New Zealand white rabbits quadriceps were thermally ablated using an MRgFUS system under 3 T MRI guidance. Animals were re-imaged three days post-ablation and euthanized. Histological necrosis labels were created by 3D registration between MR images and digitized H&E segmentations of thermal necrosis to enable voxel-wise classification of necrosis. Supervised MPMR classifier inputs included maximum temperature rise, cumulative thermal dose (CTD), post-FUS differences in T2-weighted images, and apparent diffusion coefficient, or ADC, maps. A logistic regression, support vector machine, and random forest classifier were trained in red a leave-one-out strategy in test data from four subjects.ResultsIn the validation dataset, the MPMR classifiers achieved higher recall and Dice than a clinically adopted 240 cumulative equivalent minutes at 43 °C (CEM 43) threshold (0.43) in all subjects. The average Dice scores of overlap with the registered histological label for the logistic regression (0.63) and support vector machine (0.63) MPMR classifiers were within 6% of the acute contrast-enhanced non-perfused volume (0.67).ConclusionsVoxel-wise registration of MPMR data to histological outcomes facilitated supervised learning of an accurate non-contrast MR biomarker for MRgFUS ablations in a rabbit VX2 tumor model.
| S-EPMC10768718 | biostudies-literature
Project description:Thermosensitive liposomes represent an important paradigm in oncology, where hyperthermia-mediated release coupled with thermal bioeffects enhance the effectiveness of chemotherapy. Their widespread clinical adoption hinges upon performing controlled targeted hyperthermia, and a leading candidate to achieve this is temperature-based magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS). However, the current approach to hyperthermia involves exposures lasting tens of minutes to hours, which is not possible to achieve in many circumstances because of blood vessel cooling and respiratory motion. Here, we investigate a novel approach to overcome these limitations: to use fractionated ultrashort (~30 s) thermal exposures (~41° to 45°C) to release doxorubicin from a thermosensitive liposome. This is first demonstrated in a dorsal chamber tumor model using two-photon microscopy. Thermal exposures were then conducted with a rabbit tumor model using a custom MRgFUS system incorporating temperature feedback control. Drug release was confirmed, and longitudinal experiments demonstrated profoundly enhanced tumor growth inhibition and survival.
| S-EPMC7467687 | biostudies-literature
Project description:ObjectiveThe object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C-54°C.MethodsSeventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors' institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = -0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance-induced spatial-shifting artifacts.ResultsMean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C-54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor.ConclusionsIn transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.
| S-EPMC7139920 | biostudies-literature
Project description:X-linked dystonia-parkinsonism (XDP) is a neurodegenerative condition found among males with maternal ancestry from Panay Island, Philippines. The treatment options are limited. We report on our experience of three XDP patients who underwent transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy. The three patients were all genetically confirmed XDP, with a mean XDP-Movement Disorder Society of the Philippines (MDSP) Scale score of 68.7/200. All patients were on stable doses of their oral medications and their last botulinum toxin injection was 12 months prior to study. Two patients complained of moderate to severe arm pain 2-7 months after the procedure. There was an overall improvement in the XDP-MDSP Scale score of 36.2% (18.7 vs. 15) at 6 months and 30.1% (68.7 vs. 45.5) at 1 year. Notably, there was worsening of the nonmotor subscale (part IIIB, nonbehavioral aspect) by 350% at 1 year. While these numbers are encouraging, there is a need to do a larger study on the safety and efficacy of tcMRgFUS on XDP.
| S-EPMC8145494 | biostudies-literature
Project description:Background and purposeTranscranial MR imaging-guided focused ultrasound is a promising novel technique to treat multiple disorders and diseases. Planning for transcranial MR imaging-guided focused ultrasound requires both a CT scan for skull density estimation and treatment-planning simulation and an MR imaging for target identification. It is desirable to simplify the clinical workflow of transcranial MR imaging-guided focused ultrasound treatment planning. The purpose of this study was to examine the feasibility of deep learning techniques to convert MR imaging ultrashort TE images directly to synthetic CT of the skull images for use in transcranial MR imaging-guided focused ultrasound treatment planning.Materials and methodsThe U-Net neural network was trained and tested on data obtained from 41 subjects (mean age, 66.4 ± 11.0 years; 15 women). The derived neural network model was evaluated using a k-fold cross-validation method. Derived acoustic properties were verified by comparing the whole skull-density ratio from deep learning synthesized CT of the skull with the reference CT of the skull. In addition, acoustic and temperature simulations were performed using the deep learning CT to predict the target temperature rise during transcranial MR imaging-guided focused ultrasound.ResultsThe derived deep learning model generates synthetic CT of the skull images that are highly comparable with the true CT of the skull images. Their intensities in Hounsfield units have a spatial correlation coefficient of 0.80 ± 0.08, a mean absolute error of 104.57 ± 21.33 HU, and a subject-wise correlation coefficient of 0.91. Furthermore, deep learning CT of the skull is reliable in the skull-density ratio estimation (r = 0.96). A simulation study showed that both the peak target temperatures and temperature distribution from deep learning CT are comparable with those of the reference CT.ConclusionsThe deep learning method can be used to simplify workflow associated with transcranial MR imaging-guided focused ultrasound.
| S-EPMC7661089 | biostudies-literature