Design and validation of a patient-specific stereotactic frame for transcranial ultrasound therapy.

Transcranial focused ultrasound (tFUS) procedures such as neuromodulation and blood brain barrier opening require precise focus placement within the brain. MRI is currently the most reliable tool for focus localization but can be prohibitive for procedures requiring recurrent therapies. We designed, fabricated, and characterized a patient-specific, 3D-printed, stereotactic frame for repeated tFUS therapy. The frame is compact with minimal footprint, can be removed and re-secured between treatments while maintaining sub-mm accuracy and will allow for precise and repeatable transcranial FUS treatment without the need for MR-guidance following the initial calibration scan. Focus localization and repeatability were assessed via MR-thermometry and MR-ARFI on an ex vivo skull-phantom and in vivo non-human primates (NHP), respectively. Focal localization, registration, steering, and re-steering were accomplished during the initial MRI calibration scan session. Keeping steering coordinates fixed in subsequent therapy and imaging sessions, we found good agreement between steered foci and intended target, with target registration error of 1.2 ± 0.3 (n = 4, ex vivo) and 1.0 ± 0.5 (n = 3, in vivo) mm. Focus position (steered and non-steered) was consistent, with sub-mm variation in each dimension between studies. Our 3D-printed, patient-specific stereotactic frame can reliably position and orient the ultrasound transducer for repeated targeting of brain regions using a single MR-based calibration. The compact frame allows for high-precision tFUS to be carried out outside the magnet, and could help reduce the cost of tFUS treatments where repeated application of an ultrasound focus is required with high precision.

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei.

BACKGROUND: MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. OBJECTIVE: To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. FINDINGS: BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. CONCLUSIONS: The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.

Dark band artifact in transcranial MR-guided focused ultrasound: Mechanism and mitigation with passive crossed wire antennas.

Current FDA-approved transcranial MR-guided focused ultrasound (tcMRgFUS) transducers cause a curved dark band in 3 T brain images that runs through midbrain targets of ablative treatments for essential tremor and other applications, and signal is reduced by at least 25% elsewhere in the brain. This limits the set of scans that can be performed to guide and assess the effects of treatment. An electromagnetic simulation study was performed to elucidate the mechanisms causing the dark band. Based on the results, a pair of passive antennas in a "propeller-beanie" configuration were designed to manipulate the reflected waves to avoid signal cancellation within the brain. The antennas were optimized and validated with in-vivo experiments and hydrophone measurements. The simulation study revealed that the dark band is caused by RF waves reflected from the transducer's ground plane, which cancel with incoming waves from the scanner's body coil. The passive antennas shifted the dark band out of the brain and increased transmit efficiency in the center of brain 2.3 times while improving field homogeneity by 50%. They also increased receive sensitivity and SNR in anatomic and temperature imaging. They caused no detectable distortion in hydrophone-measured focal pressure profiles. The conductive ground planes and coupling media used in tcMRgFUS and other piezoelectric FUS transducers interact with a 3 T scanner's RF fields to reduce transmit efficiency and SNR. For tcMRgFUS scenario, "propeller beanie" passive reflecting antennas alleviated these effects. This could make a broader set of imaging sequences available to guide tcMRgFUS treatment.

Individually tailored spatial-spectral pulsed CEST MRI for ratiometric mapping of myocardial energetic species at 3T.

PURPOSE: CEST MRI has been used to probe changes in cardiac metabolism via assessment of CEST contrast from Cr. However, B1 variation across the myocardium leads to spatially variable Cr CEST contrast in healthy myocardium. METHODS: We developed a spatial-spectral (SPSP) saturation pulsed CEST protocol to compensate for B1 variation. Flip angle maps were used to individually tailor SPSP pulses comprised of a train of one-dimensional spatially selective subpulses selective along the principal B1 gradient dimension. Complete Z-spectra in the hearts of (n = 10) healthy individuals were acquired using conventional Gaussian saturation and SPSP schemes and supported by phantom studies. RESULTS: In simulations, the use of SPSP pulses reduced the average SD of the effective saturation B1 values within the myocardium (n = 10) from 0.12 ± 0.02 µT to 0.05 ± 0.01 µT (p < 0.01) and reduced the average SD of Cr CEST contrast in vivo from 10.0 ± 4.3% to 6.1 ± 3.5% (p < 0.05). Results from the hearts of human subjects showed a significant reduction of CEST contrast distribution at 2 ppm, as well as amplitude, when using SPSP saturation. Corresponding phantom experiments revealed PCr-specific contrast generation at body temperature when SPSP saturation was used but combined PCr and Cr contrast generation when Gaussian saturation was used. CONCLUSION: The use of SPSP saturation pulsed CEST resulted in PCr-specific contrast generation and enabled ratiometric mapping of PCr to total Cr CEST contrast in the human heart at 3T.

Appearance and modeling of bubble artifacts in intracranial magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) temperature images.

PURPOSE: To understand if unexplained signal artifacts in MRg-LITT proton resonance frequency- (PRF-) shift thermometry images are caused by air bubbles or hemorrhages, and to characterize their effects on temperature measurements. METHODS: Retrospective image data from an IRB-approved clinical trial of intracranial MRg-LITT were inspected for asymmetric distortions observed in phase data during ablations, which have been previously reported as likely hemorrhages. A total of eight patient cases were selected: seven with artifact occurrence and one without. Mathematical image models for air bubbles or hemorrhages were implemented to estimate the size of the air bubble or hemorrhage needed to explain the clinically observed phase artifacts. Correlations and Bland-Altman analyses were used to determine if an air bubble model or a hemorrhage model was better correlated to the clinical data. The model was used to inject bubbles into clean PRF phase data without artifacts to examine how temperature profile distortions change with slice orientation. The simulated air-bubble injected data were compared to clinical data containing artifacts to examine the bubbles' effects on temperature and thermal damage estimates. RESULTS: The model demonstrated that air bubbles up to approximately 1 cm in diameter could explain the clinically observed phase artifacts. The bubble model predicts that a hemorrhage would have to be 2.2 times as large as an air bubble in order to explain the same extent of phase distortion observed in clinical data. Air bubbles had 16% percent higher correlations to the clinical PRF phase data than hemorrhages, even after rescaling the hemorrhage phases to better match the data. The air bubble model also explains how the phase artifacts lead to both large positive and large negative temperature errors, up to ±100 °C, which could cascade to damage estimate errors of several millimeters. CONCLUSION: Results showed that the artifacts are likely caused by air bubbles rather than hemorrhages, which may be introduced before heating or appear during heating. Manufacturers and users of devices that rely upon PRF-shift thermometry should be aware these phase distortions from bubble artifacts can result in large temperature errors.

High-resolution motion- and phase-corrected functional MRI at 7 T using shuttered multishot echo-planar imaging.

PURPOSE: To achieve high-resolution multishot echo-planar imaging (EPI) for functional MRI (fMRI) with reduced sensitivity to in-plane motion and between-shot phase variations. METHODS: Two-dimensional radiofrequency pulses were incorporated in a multishot EPI sequence at 7T which selectively excited a set of in-plane bands (shutters) in the phase encoding direction, which moved between shots to cover the entire slice. A phase- and motion-corrected reconstruction was implemented for the acquisition. Brain imaging experiments were performed with instructed motion to evaluate image quality for conventional multishot and shuttered EPI. Temporal stability was assessed in three subjects by quantifying temporal SNR (tSNR) and artifact levels, and fMRI activation experiments using visual stimulation were performed to assess the strength and distribution of activation, using both conventional multishot and shuttered EPI. RESULTS: In the instructed motion experiment, ghosting was lower in shuttered EPI images without or with corrections and image quality metrics were improved with motion correction. tSNR was improved by phase correction in both conventional multishot and shuttered EPI and the acquisitions had similar tSNR without and with phase correction. However, while phase correction was necessary to maximize tSNR in conventional multishot EPI, it also increased intermittent ghosting, but did not increase intermittent ghosting in shuttered EPI. Phase correction increased activation strength in both conventional multishot and shuttered EPI, but caused increased spurious activation outside the brain and in frontal brain regions in conventional multishot EPI. CONCLUSION: Shuttered EPI supports multishot segmented EPI acquisitions with lower sensitivity to artifacts from motion for high-resolution fMRI.

Detection of laser-associated heating in the brain during simultaneous fMRI and optogenetic stimulation.

PURPOSE: To calculate temperatures from T2 *-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. METHODS: fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T2 *-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. RESULTS: The temperature SD was 0.05°C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13°C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. CONCLUSION: The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.

Differential dose responses of transcranial focused ultrasound at brain regions indicate causal interactions.

We have previously shown that focused ultrasound (FUS) pulses in low pressure range exerted bidirectional and brain state-dependent neuromodulation in the nonhuman primate somatosensory cortices by fMRI. Here we aim to gain insights about the proposed neuron selective modulation of FUS and probe feedforward versus feedback interactions by simultaneously quantifying the stimulus (FUS pressures: 925, 425, 250 kPa) and response (% BOLD fMRI changes) function at the targeted area 3a/3b and off-target cortical areas at 7T. In resting-state, lowered intensities of FUS resulted in decreased fMRI signal changes at the target area 3a/3b and off-target area 1/2, S2, MCC, insula and auditory cortex, and no signal difference in thalamic VPL and MD nuclei. In activated states, concurrent high-intensity FUS significantly enhanced touch-evoked signals in area 1/2. Medium- and low-intensity FUS significantly suppressed touch-evoked BOLD signals in all areas except in the auditory cortex, VPL and MD thalamic nuclei. Distinct state dependent and dose-response curves led us to hypothesize that FUS's neuromodulatory effects may be mediated through preferential activation of different populations of neurons. Area 3a/3b may have distinct causal feedforward and feedback interactions with Area 1/2, S2, MCC, insula, and VPL. FUS offers a noninvasive neural stimulation tool for dissecting brain circuits and probing causal functional connections.

Reduced-field of view three-dimensional MR acoustic radiation force imaging with a low-rank reconstruction for targeting transcranial focused ultrasound.

PURPOSE: To rapidly image and localize the focus in MR-guided focused ultrasound (FUS) while maintaining a low ultrasound duty cycle to minimize tissue effects. METHODS: MR-acoustic radiation force imaging (ARFI) is key to targeting FUS procedures such as neuromodulation, and works by encoding ultrasound-induced displacements into the phase of MR images. However, it can require long scan times to cover a volume of tissue, especially when minimizing the FUS dose during targeting is paramount. To simultaneously minimize scan time and the FUS duty cycle, a 2-min three-dimensional (3D) reduced-FOV spin echo ARFI scan with two-dimensional undersampling was implemented at 3T with a FUS duty cycle of 0.85%. The 3D k-space sampling scheme incorporated uniform undersampling in one phase-encoded axis and partial Fourier (PF) sampling in the other. The scan interleaved FUS-on and FUS-off data collection to improve displacement map quality via a joint low-rank image reconstruction. Experiments in agarose and graphite phantoms and living macaque brains for neuromodulation and blood-brain barrier opening studied the effects of the sampling and reconstruction strategy on the acquisition, and evaluated its repeatability and accuracy. RESULTS: In the phantom, the distances between displacement centroids of 10 prospective reconstructions and a fully sampled reference were below 1 mm. In in vivo brain, the distances between centroids ranged from 1.3 to 2.1 mm. Results in phantom and in vivo brain both showed that the proposed method can recover the FUS focus compared to slower fully sampled scans. CONCLUSION: The proposed 3D MR-ARFI reduced-FOV method enables rapid imaging of the FUS focus while maintaining a low FUS duty cycle.

On the design and manufacturing of miniaturized microstripline power splitters for driving multicoil transmit arrays with arbitrary ratios at 7 T.

The purpose of the current study was to implement unequal microstrip power splitters for parallel transmission at 7 T that are optimized for size and loss and that can be configured for a wide range of power ratios. The splitters will enable the use of more transmit coils without a corresponding increase in the number of transmit channels or amplifiers to control specific absorption rate, shorten RF pulses, and shim inhomogeneous RF fields. Wilkinson unequal power splitters based on a novel microstrip network design were optimized to minimize their size under 8 cm in length and 9 cm in width, enabling them to be included in coil housing or cascaded in multiple stages. Splitters were designed and constructed for a wide range of output power ratios at 298 MHz. Simulations and bench tests were performed for each ratio, and a methodology was established to adapt the designs to other ratios and frequencies. The designs and code are open source and can be reproduced as is or reconfigured. The single-stage designs achieved good matches and isolations between output ports (worst isolation -15.9 dB, worst match -15.1 dB). A two-stage cascaded (one input to four outputs) power splitter with 1:2.5, 1:10, 1:3, and 1:6 ratio outputs was constructed. The worst isolation between output ports was -19.7 dB in simulation and the worst match of the three ports was -17.8 dB. The measured ratios for one- and two-stage boards were within 10% of the theoretical ratios. The power-handling capability of the smallest trace was approximately 70 W. Power loss for the one- and two-stage boards ranged from 1% to 3% in simulation compared with 5.1% to 7.2% on the bench. It was concluded that Wilkinson unequal microstrip power splitters can be implemented with a small board size (low height) and low loss, and across a wide range of output power ratios. The splitters can be cascaded in multiple stages while maintaining the expected ratios and low loss. This will enable the construction of large fixed transmit array-compression matrices with low loss.

Selective excitation localized by the Bloch-Siegert shift and a B1+ gradient.

PURPOSE: To perform B1+$$ {B}_1^{+} $$ -selective excitation using the Bloch-Siegert shift for spatial localization. THEORY AND METHODS: A B1+$$ {B}_1^{+} $$ -selective excitation is produced by an radiofrequency (RF) pulse consisting of two summed component pulses: an off-resonant pulse that induces a B1+$$ {B}_1^{+} $$ -dependent Bloch-Siegert frequency shift and a frequency-selective excitation pulse. The passband of the pulse can be tailored by adjusting the frequency content of the frequency-selective pulse, as in conventional B0$$ {B}_0 $$ gradient-localized excitation. Fine magnetization profile control is achieved by using the Shinnar-Le Roux algorithm to design the frequency-selective excitation pulse. Simulations analyzed the pulses' robustness to off-resonance, their suitability for multi-echo spin echo pulse sequences, and how their performance compares to that of rotating-frame selective excitation pulses. The pulses were evaluated experimentally on a 47.5 mT MRI scanner using an RF gradient transmit coil. Multiphoton resonances produced by the pulses were characterized and their distribution across B1+$$ {B}_1^{+} $$ predicted. RESULTS: With correction for varying B1+$$ {B}_1^{+} $$ across the desired profile, the proposed pulses produced selective excitation with the specified profile characteristics. The pulses were robust against off-resonance and RF amplifier distortion, and suitable for multi-echo pulse sequences. Experimental profiles closely matched simulated patterns. CONCLUSION: The Bloch-Siegert shift can be used to perform B0$$ {B}_0 $$ -gradient-free selective excitation, enabling the excitation of slices or slabs in RF gradient-encoded MRI.

High-Density MRI RF Arrays Using Mixed Dipole Antennas and Microstrip Transmission Line Resonators.

OBJECTIVE: High-density multi-coil arrays are desirable in MRI because they provide high signal-to-noise ratios (SNR), enable highly accelerated parallel imaging, and provide more uniform transmit fields at high fields. For high-density arrays such as a head array with 16 elements in a row, popular dipole antennas and microstrip transmission line (also referred to as "MTL") resonators both have severe coupling issues. METHODS: In this work, we show that dipoles and MTLs have naturally low coupling and propose a novel array configuration in which they are interleaved. We first show the electromagnetic (EM) coupling between a single dipole and a single MTL across different separations in bench tests. Then we validate and analyze this through EM simulations. Finally, we construct a 16-channel mixed dipole and MTL array and evaluate its performance on the bench and through MRI experiments. RESULTS: Without any decoupling treatments, the worst coupling between a dipole and an MTL was only -15.8 dB when their center-to-center distance was 4.7 cm (versus -5.4 dB for two dipole antennas and -6.0 dB for two MTL resonators). Even in a dense 16-channel mixed array, the inter-element isolation among all elements was better than -14 dB. CONCLUSION: This study reveals, analyzes, and validates a novel finding that the popular dipole antennas and MTL resonators used in ultrahigh field MRI have naturally low coupling. SIGNIFICANCE: These findings will simplify the construction of high-density arrays, enable new applications, and benefit imaging performance in ultrahigh field MRI.

Dual-Tuned Lattice Balun for Multi-Nuclear MRI and MRS.

Balun or trap circuits are critical components for suppressing common-mode currents flowing on the outer conductors of coaxial cables in RF coil systems for Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS). Common-mode currents affect coils' tuning and matching, induce losses, pick up extra noise from the surrounding environment, lead to undesired cross-talk, and cause safety concerns in animal and human imaging. First proposed for microwave antenna applications, the Lattice balun has been widely used in MRI coils. It has a small footprint and can be easily integrated with coil tuning/matching circuits. However, the Lattice balun is typically a single-tuned circuit and cannot be used for multi-nuclear MRI and MRS with two RF frequencies. This work describes a dual-tuned Lattice balun design that is suitable for multi-nuclear MRI/MRS. It was first analyzed theoretically to derive component values. RF circuit simulations were then performed to validate the theoretical analysis and provide guidance for practical construction. Based on the simulation results, a dual-tuned balun circuit was built for 7T 1H/23Na MRI and bench tested. The fabricated dual-tuned balun exhibits superior performance at the Larmor frequencies of both 1H and 23Na, with less than 0.15 dB insertion loss and better than 17 dB common-mode rejection ratio at both frequencies.

External Dynamic InTerference Estimation and Removal (EDITER) for low field MRI.

PURPOSE: Point-of-care MRI requires operation outside of Faraday shielded rooms normally used to block image-degrading electromagnetic interference (EMI). To address this, we introduce the EDITER method (External Dynamic InTerference Estimation and Removal), an external sensor-based method to retrospectively remove image artifacts from time-varying external interference sources. THEORY AND METHODS: The method acquires data from multiple EMI detectors (tuned receive coils as well as untuned electrodes placed on the body) simultaneously with the primary MR coil during and between image data acquisition. We calculate impulse response functions dynamically that map the data from the detectors to the time varying artifacts then remove the transformed detected EMI from the MR data. Performance of the EDITER algorithm was assessed in phantom and in vivo imaging experiments in an 80 mT portable brain MRI in a controlled EMI environment and with an open 47.5 mT MRI scanner in an uncontrolled EMI setting. RESULTS: In the controlled setting, the effectiveness of the EDITER technique was demonstrated for specific types of introduced EMI sources with up to a 97% reduction of structured EMI and up to 76% reduction of broadband EMI in phantom experiments. In the uncontrolled EMI experiments, we demonstrate EMI reductions of up to 99% using an electrode and pick-up coil in vivo. We demonstrate up to a nine-fold improvement in image SNR with the method. CONCLUSION: The EDITER technique is a flexible and robust method to improve image quality in portable MRI systems with minimal passive shielding and could reduce the reliance of MRI on shielded rooms and allow for truly portable MRI.

Hybrid-pair ratio adjustable power splitters for add-on RF shimming and array-compressed parallel transmission.

PURPOSE: A ratio adjustable power splitter (RAPS) circuit was recently proposed for add-on RF shimming and array-compressed parallel transmission. Here we propose a new RAPS circuit design based on off-the-shelf components for improved performance and manufacturability. THEORY AND METHODS: The original RAPS used a pair of home-built Wilkinson splitter and hybrid coupler connected by a pair of connectorized coaxial cables. Here we propose a new hybrid-pair RAPS (or HP-RAPS) circuit that replaces the home-built circuits with two commercially available hybrid couplers and replaces connectorized cables with interchangeable microstrip lines. We derive the relation between the desired splitting ratio and the required phase shifts for HP-RAPS and investigate how to generate arbitrary splitting ratios using paired meandering and straight lines. Several HP-RAPSs with different splitting ratios were fabricated and tested on the workbench and MRI experiments. RESULTS: The splitting ratio of an HP-RAPS circuit has a tan or cot dependence on the meandering line's additional length compared to the straight line. The fabricated HP-RAPSs exhibit accurate splitting ratios as expected (<4% deviations) and generate transmit fields that well agree with predicted fields. They also demonstrated a low insertion loss of 0.33 dB, high output isolation of -26 dB, and acceptable impedance matching of -16 dB. CONCLUSION: A novel HP-RAPS circuit was developed and implemented. It is easy-to-fabricate/reproduce with minimal expertise. It also preserves the features of the original RAPS circuit (ratio-adjustable, small footprint, etc.) with lower insertion loss.

Bidirectional and state-dependent modulation of brain activity by transcranial focused ultrasound in non-human primates.

Transcranial focused ultrasound (FUS) stimulation under MRI guidance, coupled with functional MRI (fMRI) monitoring of effects, offers a precise, noninvasive technology to dissect functional brain circuits and to modulate altered brain functional networks in neurological and psychiatric disorders. Here we show that ultrasound at moderate intensities modulated neural activity bi-directionally. Concurrent sonication of somatosensory areas 3a/3b with 250 kHz FUS suppressed the fMRI signals produced there by peripheral tactile stimulation, while at the same time eliciting fMRI activation at inter-connected, off-target brain regions. Direct FUS stimulation of the cortex resulted in different degrees of BOLD signal changes across all five off-target regions, indicating that its modulatory effects on active and resting neurons differed. This is the first demonstration of the dual suppressive and excitative modulations of FUS on a specific functional circuit and of ability of concurrent FUS and MRI to evaluate causal interactions between functional circuits with neuron-class selectivity.

Ultra-high spatial resolution BOLD fMRI in humans using combined segmented-accelerated VFA-FLEET with a recursive RF pulse design.

PURPOSE: To alleviate the spatial encoding limitations of single-shot echo-planar imaging (EPI) by developing multi-shot segmented EPI for ultra-high-resolution functional MRI (fMRI) with reduced ghosting artifacts from subject motion and respiration. THEORY AND METHODS: Segmented EPI can reduce readout duration and reduce acceleration factors, however, the time elapsed between segment acquisitions (on the order of seconds) can result in intermittent ghosting, limiting its use for fMRI. Here, "FLEET" segment ordering, where segments are looped over before slices, was combined with a variable flip angle progression (VFA-FLEET) to improve inter-segment fidelity and maximize signal for fMRI. Scaling a sinc pulse's flip angle for each segment (VFA-FLEET-Sinc) produced inconsistent slice profiles and ghosting, therefore, a recursive Shinnar-Le Roux (SLR) radiofrequency (RF) pulse design was developed (VFA-FLEET-SLR) to generate unique pulses for every segment that together produce consistent slice profiles and signals. RESULTS: The temporal stability of VFA-FLEET-SLR was compared against conventional-segmented EPI and VFA-FLEET-Sinc at 3T and 7T. VFA-FLEET-SLR showed reductions in both intermittent and stable ghosting compared to conventional-segmented and VFA-FLEET-Sinc, resulting in improved image quality with a minor trade-off in temporal SNR. Combining VFA-FLEET-SLR with acceleration, we achieved a 0.6-mm isotropic acquisition at 7T, without zoomed imaging or partial Fourier, demonstrating reliable detection of blood oxygenation level-dependent (BOLD) responses to a visual stimulus. To counteract the increased repetition time from segmentation, simultaneous multi-slice VFA-FLEET-SLR was demonstrated using RF-encoded controlled aliasing. CONCLUSIONS: VFA-FLEET with a recursive RF pulse design supports acquisitions with low levels of artifact and spatial blur, enabling fMRI at previously inaccessible spatial resolutions with a "full-brain" field of view.

k-Space Domain Parallel Transmit Pulse Design.

PURPOSE: To accelerate the design of (under- or oversampled) multidimensional parallel transmission pulses. METHODS: A k-space domain parallel transmission pulse design algorithm was proposed that produces a sparse matrix relating a complex-valued target excitation pattern to the pulses that produce it, and can be finely parallelized. The algorithm was applied in simulations to the design of 3D SPINS pulses for inner volume excitation in the brain at 7 Tesla. It was characterized in terms of the dependence of computation time, excitation error, and required memory on algorithm parameters, and it was compared to an iterative spatial domain pulse design method in terms of computation time, excitation error, Gibbs ringing, and ability to compensate off-resonance. RESULTS: The proposed algorithm achieved approximately 80% faster pulse design compared to the spatial domain method with the same number of parallel threads, with the tradeoff of increased excitation error and RMS RF amplitude. It reduced the memory required to store the design matrix by 99% compared to a full matrix solution. Even with a coarse design grid, the algorithm produced patterns that were free of Gibbs ringing. It was similarly sensitive to k-space undersampling as the spatial domain method, and was similarly capable of compensating for off-resonance. CONCLUSIONS: The proposed k-space domain algorithm accelerates and finely parallelizes parallel transmission pulse design, with a modest tradeoff of excitation error and RMS RF amplitude.

Rapid quantitative imaging of high intensity ultrasonic pressure fields.

High intensity focused ultrasound (FUS) is a noninvasive technique for treatment of tissues that can lie deep within the body. There is a need for methods to rapidly and quantitatively map FUS pressure beams for quality assurance and accelerate development of FUS systems and techniques. However, conventional ultrasound pressure beam mapping instruments, including hydrophones and optical techniques, are slow, not portable, and expensive, and most cannot map beams at actual therapeutic pressure levels. Here, a rapid projection imaging method to quantitatively map FUS pressure beams based on continuous-wave background-oriented schlieren (CW-BOS) imaging is reported. The method requires only a water tank, a background pattern, and a camera and uses a multi-layer deep neural network to reconstruct two-dimensional root-mean-square (RMS) projected pressure maps that resolve the ultrasound propagation dimension and one lateral dimension. In this work, the method was applied to collect beam maps over a 3 × 1 cm2 field-of-view with 0.425 mm resolution for focal pressures up to 9 MPa. Results at two frequencies and comparisons to hydrophone measurements show that CW-BOS imaging produces high-resolution quantitative RMS projected FUS pressure maps in under 10 s, the technique is linear and robust to beam rotations and translations, and it can map aberrated beams.

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition.

BACKGROUND AND OBJECTIVES: The objective of this study is to assess the hypothesis that the length of axon heated, defined here as block length (BL), affects the temperature required for thermal inhibition of action potential propagation applied using laser heating. The presence of such a phenomenon has implications for how this technique, called infrared neural inhibition (INI), may be applied in a clinically safe manner since it suggests that temperatures required for therapy may be reduced through the proper spatial application of light. Here, we validate the presence of this phenomenon by assessing how the peak temperatures during INI are reduced when two different BLs are applied using irradiation from either one or two adjacent optical fibers. STUDY DESIGN/MATERIALS AND METHODS: Assessment of the role of BL was carried out over two phases. First, a computational proof of concept was performed in the neural conduction simulation environment, NEURON, simulating the response of action potentials to increased temperatures applied at different full-width at half-maxima (FWHM) along axons. Second, ex vivo validation of these predictions was performed by measuring the radiant exposure, peak temperature rise, and FWHM of heat distributions associated with INI from one or two adjacent optical fibers. Electrophysiological assessment of radiant exposures at inhibition threshold were carried out in ex vivo Aplysia californica (sea slug) pleural abdominal nerves ( n = 6), an invertebrate with unmyelinated axons. Measurement of the maximum temperature rise required for induced heat block was performed in a water bath using a fine wire thermocouple. Finally, magnetic resonance thermometry (MRT) was performed on a nerve immersed in saline to assess the elevated temperature distribution at these radiant exposures. RESULTS: Computational modeling in NEURON provided a theoretical proof of concept that the BL is an important factor contributing to the peak temperature required during neural heat block, predicting a 11.7% reduction in temperature rise when the FWHM along an axon is increased by 42.9%. Experimental validation showed that, when using two adjacent fibers instead of one, a 38.5 ± 2.2% (mean ± standard error of the mean) reduction in radiant exposure per pulse per fiber threshold at the fiber output (P = 7.3E-6) is measured, resulting in a reduction in peak temperature rise under each fiber of 23.5 ± 2.1% ( P = 9.3E-5) and 15.0 ± 2.4% ( P = 1.4E-3) and an increase in the FWHM of heating by 37.7 ± 6.4% ( P = 1E-3), 68.4 ± 5.2% ( P = 2.4E-5), and 51.9 ± 9.9% ( P = 1.7E-3) in three MRT slices. CONCLUSIONS: This study provides the first experimental evidence for a phenomenon during the heat block in which the temperature for inhibition is dependent on the BL. While more work is needed to further reduce the temperature during INI, the results highlight that spatial application of the temperature rise during INI must be considered. Optimized implementation of INI may leverage this cellular response to provide optical modulation of neural signals with lower temperatures over greater time periods, which may increase the utility of the technique for laboratory and clinical use. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.