Characterization of central manifestations in patients with Niemann-Pick disease type C.

PURPOSE: Niemann-Pick disease type C (NPC) is a rare lysosomal storage disease characterized by progressive neurodegeneration and neuropsychiatric symptoms. This study investigated pathophysiological mechanisms underlying motor deficits, particularly speech production, and cognitive impairment. METHODS: We prospectively phenotyped 8 adults with NPC and age-sex-matched healthy controls using a comprehensive assessment battery, encompassing clinical presentation, plasma biomarkers, hand-motor skills, speech production, cognitive tasks, and (micro-)structural and functional central nervous system properties through magnetic resonance imaging. RESULTS: Patients with NPC demonstrated deficits in fine-motor skills, speech production timing and coordination, and cognitive performance. Magnetic resonance imaging revealed reduced cortical thickness and volume in cerebellar subdivisions (lobule VI and crus I), cortical (frontal, temporal, and cingulate gyri) and subcortical (thalamus and basal ganglia) regions, and increased choroid plexus volumes in NPC. White matter fractional anisotropy was reduced in specific pathways (intracerebellar input and Purkinje tracts), whereas diffusion tensor imaging graph theory analysis identified altered structural connectivity. Patients with NPC exhibited altered activity in sensorimotor and cognitive processing hubs during resting-state and speech production. Canonical component analysis highlighted the role of cerebellar-cerebral circuitry in NPC and its integration with behavioral performance and disease severity. CONCLUSION: This deep phenotyping approach offers a comprehensive systems neuroscience understanding of NPC motor and cognitive impairments, identifying potential central nervous system biomarkers.

The neurovascular response is attenuated by focused ultrasound-mediated disruption of the blood-brain barrier.

Focused ultrasound (FUS)-induced disruption of the blood-brain barrier (BBB) is a non-invasive method to target drug delivery to specific brain areas that is now entering into the clinic. Recent studies have shown that the method has several secondary effects on local physiology and brain function beyond making the vasculature permeable to normally non-BBB penetrant molecules. This study uses functional MRI methods to investigate how FUS BBB opening alters the neurovascular response in the rat brain. Nine rats underwent actual and sham FUS induced BBB opening targeted to the right somatosensory cortex (SI) followed by four runs of bilateral electrical hind paw stimulus-evoked fMRI. The neurovascular response was quantified using measurements of the blood oxygen level dependent (BOLD) signal and cerebral blood flow (CBF). An additional three rats underwent the same FUS-BBB opening followed by stimulus-evoked fMRI with high resolution BOLD imaging and BOLD imaging of a carbogen-breathing gas challenge. BOLD and CBF measurements at two different stimulus durations demonstrate that the neurovascular response to the stimulus is attenuated in both amplitude and duration in the region targeted for FUS-BBB opening. The carbogen results show that the attenuation in response amplitude, but not duration, is still present when the signaling mechanism originates from changes in blood oxygenation instead of stimulus-induced neuronal activity. There is some evidence of non-local effects, including a possible global decrease in baseline CBF. All effects are resolved by 24 h after FUS-BBB opening. Taken together, these results suggest that FUS-BBB opening alters that state of local brain neurovascular physiology in such a way that hinders its ability to respond to demands for increased blood flow to the region. The mechanisms for this effect need to be elucidated.

Modulation of brain function by targeted delivery of GABA through the disrupted blood-brain barrier.

The technology of transcranial focused ultrasound (FUS) enables a novel approach to neuromodulation, a tool for selective manipulation of brain function to be used in neurobiology research and with potential applications in clinical treatment. The method uses transcranial focused ultrasound to non-invasively open the blood-brain barrier (BBB) in a localized region such that a systemically injected neurotransmitter chemical can be delivered to the targeted brain site. The approach modulates the chemical signaling that occurs in and between neurons, making it complimentary to most other neuromodulation techniques that affect the electrical properties of neuronal activity. Here, we report delivering the inhibitory neurotransmitter GABA to the right somatosensory cortex of the rat brain during bilateral hind paw electrical stimulation and measure the inhibition of activation using functional MRI (fMRI). In a 2 × 2 factorial design, we evaluated conditions of BBB Closed vs BBB Open and No GABA vs GABA. Results from fMRI measurements of the blood oxygen level-dependent (BOLD) signal show: 1) intravenous GABA injection without FUS-mediated BBB opening does not have an effect on the BOLD response; 2) FUS-mediated BBB opening alone significantly alters the BOLD signal response to the stimulus, both in amplitude and shape of the time course; 3) the combination of FUS-mediated BBB opening and GABA injection further reduces the peak amplitude and spatial extent of the BOLD signal response to the stimulus. The data support the thesis that FUS-mediated opening of the BBB can be used to achieve non-invasive delivery of neuroactive substances for targeted manipulation of brain function.

Focused ultrasound induced opening of the blood-brain barrier disrupts inter-hemispheric resting state functional connectivity in the rat brain.

Focused ultrasound (FUS) is a technology capable of delivering therapeutic levels of energy through the intact skull to a tightly localized brain region. Combining the FUS pressure wave with intravenously injected microbubbles creates forces on blood vessel walls that open the blood-brain barrier (BBB). This noninvasive and localized opening of the BBB allows for targeted delivery of pharmacological agents into the brain for use in therapeutic development. It is possible to use FUS power levels such that the BBB is opened without damaging local tissues. However, open questions remain related to the effects that FUS-induced BBB opening has on brain function including local physiology and vascular hemodynamics. We evaluated the effects that FUS-induced BBB opening has on resting state functional magnetic resonance imaging (rs-fMRI) metrics. Data from rs-fMRI was acquired in rats that underwent sham FUS BBB vs. FUS BBB opening targeted to the right primary somatosensory cortex hindlimb region (S1HL). FUS BBB opening reduced the functional connectivity between the right S1HL and other sensorimotor regions, including statistically significant reduction of connectivity to the homologous region in the left hemisphere (left S1HL). The effect was observed in all three metrics analyzed: functional connectivity between anatomically defined regions, whole brain voxel-wise correlation maps based on anatomical seeds, and spatial patterns from independent component analysis. Connectivity metrics for other regions where the BBB was not perturbed were not affected. While it is not clear whether the effect is vascular or neuronal in origin, these results suggest that even safe levels of FUS BBB opening have an effect on the physiological processes that drive the signals measured by BOLD fMRI. As such these effects must be accounted for when carrying out studies using fMRI to evaluate the effects of pharmacological agents delivered via FUS-induced BBB opening.

Accurate modeling of temporal correlations in rapidly sampled fMRI time series.

Rapid imaging techniques are increasingly used in functional MRI studies because they allow a greater number of samples to be acquired per unit time, thereby increasing statistical power. However, temporal correlations limit the increase in functional sensitivity and must be accurately accounted for to control the false-positive rate. A common approach to accounting for temporal correlations is to whiten the data prior to estimating fMRI model parameters. Models of white noise plus a first-order autoregressive process have proven sufficient for conventional imaging studies, but more elaborate models are required for rapidly sampled data. Here we show that when the "FAST" model implemented in SPM is used with a well-controlled number of parameters, it can successfully prewhiten 80% of grey matter voxels even with volume repetition times as short as 0.35 s. We further show that the temporal signal-to-noise ratio (tSNR), which has conventionally been used to assess the relative functional sensitivity of competing imaging approaches, can be augmented to account for the temporal correlations in the time series. This amounts to computing the t-score testing for the mean signal. We show in a visual perception task that unlike the tSNR weighted by the number of samples, the t-score measure is directly related to the t-score testing for activation when the temporal correlations are correctly modeled. This score affords a more accurate means of evaluating the functional sensitivity of different data acquisition options.

Evaluation of 2D multiband EPI imaging for high-resolution, whole-brain, task-based fMRI studies at 3T: Sensitivity and slice leakage artifacts.

Functional magnetic resonance imaging (fMRI) studies that require high-resolution whole-brain coverage have long scan times that are primarily driven by the large number of thin slices acquired. Two-dimensional multiband echo-planar imaging (EPI) sequences accelerate the data acquisition along the slice direction and therefore represent an attractive approach to such studies by improving the temporal resolution without sacrificing spatial resolution. In this work, a 2D multiband EPI sequence was optimized for 1.5mm isotropic whole-brain acquisitions at 3T with 10 healthy volunteers imaged while performing simultaneous visual and motor tasks. The performance of the sequence was evaluated in terms of BOLD sensitivity and false-positive activation at multiband (MB) factors of 1, 2, 4, and 6, combined with in-plane GRAPPA acceleration of 2× (GRAPPA 2), and the two reconstruction approaches of Slice-GRAPPA and Split Slice-GRAPPA. Sensitivity results demonstrate significant gains in temporal signal-to-noise ratio (tSNR) and t-score statistics for MB 2, 4, and 6 compared to MB 1. The MB factor for optimal sensitivity varied depending on anatomical location and reconstruction method. When using Slice-GRAPPA reconstruction, evidence of false-positive activation due to signal leakage between simultaneously excited slices was seen in one instance, 35 instances, and 70 instances over the ten volunteers for the respective accelerations of MB 2×GRAPPA 2, MB 4×GRAPPA 2, and MB 6×GRAPPA 2. The use of Split Slice-GRAPPA reconstruction suppressed the prevalence of false positives significantly, to 1 instance, 5 instances, and 5 instances for the same respective acceleration factors. Imaging protocols using an acceleration factor of MB 2×GRAPPA 2 can be confidently used for high-resolution whole-brain imaging to improve BOLD sensitivity with very low probability for false-positive activation due to slice leakage. Imaging protocols using higher acceleration factors (MB 3 or MB 4×GRAPPA 2) can likely provide even greater gains in sensitivity but should be carefully optimized to minimize the possibility of false activations.

Evaluation of a three-dimensional MR acoustic radiation force imaging pulse sequence using a novel unbalanced bipolar motion encoding gradient.

PURPOSE: MR guided focused ultrasound procedures require accurate focal spot localization in three dimensions. This study presents a three-dimensional (3D) pulse sequence for acoustic radiation force imaging (ARFI) that efficiently localizes the focal spot by means of ultrasound induced tissue displacement over a large field-of-view. METHODS: A novel unbalanced bipolar motion encoding gradient was implemented to maximize time available for motion encoding, reduce echo times, and allow for longer echo train lengths. Two advanced features, kz reduction factor (KZRF) and kz -level interleaving, were implemented to reduce tissue heating. Studies in gelatin phantoms compared the location of peak displacement and temperature measured by 3D MR thermometry. MR-ARFI induced tissue heating was evaluated through a parametric study of sequence parameters and MR thermometry measurements during repeated application of ARFI sonication patterns. Sequence performance was characterized in the presence of respiration and tissue inhomogeneity. RESULTS: The location of peak displacement and temperature rise agreed within 0.2 ± 0.1 mm and 0.5 ± 0.3 mm in the transverse and longitudinal direction, respectively. The 3D displacement maps were acquired safely, and the KZRF and kz -level interleaving features reduced tissue heating by 51%. High quality displacement maps were obtained despite respiration and tissue inhomogeneities. CONCLUSION: This sequence provides a safe, accurate, and simple approach to localizing the focal spot in three dimensions with a single scan. Magn Reson Med 76:803-813, 2016. © 2015 Wiley Periodicals, Inc.

Model predictive filtering MR thermometry: Effects of model inaccuracies, k-space reduction factor, and temperature increase rate.

PURPOSE: Evaluate effects of model parameter inaccuracies (thermal conductivity, k, and ultrasound power deposition density, Q), k-space reduction factor (R), and rate of temperature increase ( T˙) in a thermal model-based reconstruction for MR-thermometry during focused-ultrasound heating. METHODS: Simulations and ex vivo experiments were performed to investigate the accuracy of the thermal model and the model predictive filtering (MPF) algorithm for varying R and T˙, and their sensitivity to errors in k and Q. Ex vivo data was acquired with a segmented EPI pulse sequence to achieve large field-of-view (192 × 162 × 96 mm) four-dimensional temperature maps with high spatiotemporal resolution (1.5 × 1.5 × 2.0 mm, 1.7 s). RESULTS: In the simulations, 50% errors in k and Q resulted in maximum temperature root mean square errors (RMSE) of 6 °C for model only and 3 °C for MPF. Using recently developed methods, estimates of k and Q were accurate to within 3%. The RMSE between MPF and true temperature increased with R and T˙. In the ex vivo study the RMSE remained below 0.7 °C for R ranging from 4 to 12 and T˙ of 0.28-0.75 °C/s. CONCLUSION: Errors in MPF temperatures occur due to errors in k and Q. These MPF temperature errors increase with increase in R and T˙, but are smaller than those obtained using the thermal model alone.

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2 × 2 × 3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p<0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies.

In vivo evaluation of multi-echo hybrid PRF/T1 approach for temperature monitoring during breast MR-guided focused ultrasound surgery treatments.

PURPOSE: To evaluate the precision of in vivo temperature measurements in adipose and glandular breast tissue using a multi-echo hybrid PRF/T1 pulse sequence. METHODS: A high-bandwidth, multi-echo hybrid PRF/T1 sequence was developed for monitoring temperature changes simultaneously in fat- and water-based tissues. The multiple echoes were combined with the optimal weightings for magnitude and phase images, allowing for precise measurement of both T1 and the proton resonance frequency (PRF) shift. The sequence was tested during in vivo imaging of 10 healthy volunteers in a breast-specific MR-guided focused ultrasound system and also during focused ultrasound heating of excised breast adipose tissue. RESULTS: The in vivo results indicated that the sequence can measure PRF temperatures with 1.25 × 1.25 × 3.5 mm resolution, 1.9 s temporal resolution, and 1.0°C temperature precision, and can measure T1 values with 3.75 × 3.75 × 3.5 mm resolution, 3.8 s temporal resolution, and 2.5%-4.8% precision. The excised tissue heating experiments demonstrate the sequence's ability to monitor temperature changes simultaneously in water- and fat-based tissues. CONCLUSION: The addition of a high-bandwidth, multi-echo readout to the hybrid PRF/T1 sequence improves the precision of each measurement, providing a sequence that will be beneficial to several MR-guided thermal therapies.

Phase reconstruction from multiple coil data using a virtual reference coil.

PURPOSE: This study develops a method to obtain optimal estimates of absolute magnetization phase from multiple-coil MRI data. THEORY AND METHODS: The element-specific phases of a multi-element receiver coil array are accounted for by using the phase of a real or virtual reference coil that is sensitive over the entire imaged volume. The virtual-reference coil is generated as a weighted combination of measurements from all receiver coils. The phase-corrected multiple coil complex images are combined using the inverse covariance matrix. These methods are tested on images of an agar phantom, an in vivo breast, and an anesthetized rabbit obtained using combinations of four, nine, and three receiver channels, respectively. RESULTS: The four- and three-channel acquisitions require formation of a virtual-reference receiver coil while one channel of the nine-channel receive array has a sensitivity profile covering the entire imaged volume. Referencing to a real or virtual coil gives receiver phases that are essentially identical except for the individual receiver channel noise. The resulting combined images, which account for receiver channel noise covariance, show the expected reduction in phase variance. CONCLUSION: The proposed virtual reference coil method determines a phase distribution for each coil from which an optimal phase map can be obtained.

Toward real-time temperature monitoring in fat and aqueous tissue during magnetic resonance-guided high-intensity focused ultrasound using a three-dimensional proton resonance frequency T1 method.

PURPOSE: To present a three-dimensional (3D) segmented echoplanar imaging (EPI) pulse sequence implementation that provides simultaneously the proton resonance frequency shift temperature of aqueous tissue and the longitudinal relaxation time (T1 ) of fat during thermal ablation. METHODS: The hybrid sequence was implemented by combining a 3D segmented flyback EPI sequence, the extended two-point Dixon fat and water separation, and the double flip angle T1 mapping techniques. High-intensity focused ultrasound (HIFU) heating experiments were performed at three different acoustic powers on excised human breast fat embedded in ex vivo porcine muscle. Furthermore, T1 calibrations with temperature in four different excised breast fat samples were performed, yielding an estimate of the average and variation of dT1 /dT across subjects. RESULTS: The water only images were used to mask the complex original data before computing the proton resonance frequency shift. T1 values were calculated from the fat-only images. The relative temperature coefficients were found in five fat tissue samples from different patients and ranged from 1.2% to 2.6%/°C. CONCLUSION: The results demonstrate the capability of real-time simultaneous temperature mapping in aqueous tissue and T1 mapping in fat during HIFU ablation, providing a potential tool for treatment monitoring in organs with large fat content, such as the breast.

Toward real-time availability of 3D temperature maps created with temporally constrained reconstruction.

PURPOSE: To extend the previously developed temporally constrained reconstruction (TCR) algorithm to allow for real-time availability of three-dimensional (3D) temperature maps capable of monitoring MR-guided high intensity focused ultrasound applications. METHODS: A real-time TCR (RT-TCR) algorithm is developed that only uses current and previously acquired undersampled k-space data from a 3D segmented EPI pulse sequence, with the image reconstruction done in a graphics processing unit implementation to overcome computation burden. Simulated and experimental data sets of HIFU heating are used to evaluate the performance of the RT-TCR algorithm. RESULTS: The simulation studies demonstrate that the RT-TCR algorithm has subsecond reconstruction time and can accurately measure HIFU-induced temperature rises of 20°C in 15 s for 3D volumes of 16 slices (RMSE = 0.1°C), 24 slices (RMSE = 0.2°C), and 32 slices (RMSE = 0.3°C). Experimental results in ex vivo porcine muscle demonstrate that the RT-TCR approach can reconstruct temperature maps with 192 × 162 × 66 mm 3D volume coverage, 1.5 × 1.5 × 3.0 mm resolution, and 1.2-s scan time with an accuracy of ±0.5°C. CONCLUSION: The RT-TCR algorithm offers an approach to obtaining large coverage 3D temperature maps in real-time for monitoring MR-guided high intensity focused ultrasound treatments.

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy.

PURPOSE: Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up. MATERIALS AND METHODS: The controller realises time savings by modelling the heated treatment cell's future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell. Selected tissues are safeguarded by a configurable temperature constraint. Simulations quantified the time savings realised by each controller feature as well as the trade-offs between competing safety and treatment time parameters. In vivo experiments in rabbit thighs established the controller's effectiveness and reliability. RESULTS: In all in vivo experiments the target thermal dose of at least 240 CEM43 was delivered everywhere in the treatment volume. The controller's temperature safety limit reliably activated and constrained all protected tissues to <9 CEM43. Simulations demonstrated the path independence of the controller, and that a path which successively proceeds to the hottest untreated neighbouring cell leads to significant time savings, e.g. when compared to a concentric spiral path. Use of the AMPC produced a compounding time-saving effect; reducing the treatment cells' heating times concurrently reduced heating of normal tissues, which eliminated cooling periods. CONCLUSIONS: Adaptive model-predictive control can automatically deliver safe, effective MRgFUS treatments while significantly reducing treatment times.

Focused ultrasound-mediated delivery of viral neuronal tracers in marmosets.

In this issue of Cell Reports Methods, Parks et al. present an approach to non-invasively deliver adeno-associated viruses in a marmoset model using focused ultrasound (FUS) for neuronal tracing. The optimization of this technique in this non-human primate model is highly valuable for future FUS-mediated drug delivery studies.

Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood-brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies include direct injections into the central nervous system, which are invasive and can result in poor diffusion of viral particles through the brain parenchyma. Focused ultrasound (FUS) is an alternative approach that can be used to non-invasively deliver AAVs by temporarily disrupting the BBB. Here, we investigate FUS-mediated delivery of a single-stranded AAV9 bearing a cDNA for GFP in 2-month-old wild-type mice and the zQ175 HD mouse model at 2-, 6-, and 12-months. FUS treatment improved AAV9 delivery for all mouse groups. The delivery efficacy was similar for all WT and HD groups, with the exception of the zQ175 12-month cohort, where we observed decreased GFP expression. Astrocytosis did not increase after FUS treatment, even within the zQ175 12-month group exhibiting higher baseline levels of GFAP expression. These findings demonstrate that FUS can be used to non-invasively deliver an AAV9-based gene therapy to targeted brain regions in a mouse model of Huntington's disease.

Irreversible change in the T1 temperature dependence with thermal dose using the proton resonance frequency-T1 technique.

Denaturation of macromolecules within the tissues is believed to be the major factor contributing to the damage of tissues upon hyperthermia. As a result, the value of the spin-lattice relaxation time T1 of the tissue water, which is related to the translational and rotational rates of water, represents an intrinsic probe for investigating structural changes in tissues at high temperature. Therefore, the goal of this work is to investigate whether the simultaneous measurement of temperature and T1 using a hybrid proton resonance frequency (PRF)-T1 measurement technique can be used to detect irreversible changes in T1 that might be indicative of tissue damage. A new hybrid PRF-T1 sequence was implemented based on the variable flip angle driven-equilibrium single-pulse observation (DESPOT)1 method from a standard three dimensional segmented echo-planar imaging sequence by alternating two flip angles from measurement to measurement. The structural changes of the heated tissue volumes were analyzed based on the derived T1 values and the corresponding PRF temperatures. Using the hybrid PRF-T1 technique, we demonstrate that the change of spin lattice relaxation time T1 is reversible with temperature for low thermal dose (thermal dose ≤ 240 cumulative equivalent minutes [CEM] 43°C) and irreversible with temperature after significant accumulation of thermal dose in ex vivo chicken breast tissue. These results suggest that the hybrid PRF-T1 method may be a potentially powerful tool to investigate the extent and mechanism of heat damage of biological tissues.

Hybrid proton resonance frequency/T1 technique for simultaneous temperature monitoring in adipose and aqueous tissues.

Thermal therapy procedures being carried out under MR guidance would be safer if temperature changes could be accurately monitored in both water-based and fat-based tissues. To this end, we present a hybrid proton resonance frequency (PRF)/T(1) approach for simultaneously measuring PRF shift temperatures in water-based tissues and T(1) changes in fat-based tissues. The hybrid PRF/T(1) sequence is a standard radiofrequency spoiled gradient echo sequence executed in a dynamic mode with two flip angles alternating every time frame. The PRF information is extracted every time frame using the image phase in the standard approach, and the T(1) information is extracted every two time frames using a variable flip angle approach. Simulation studies, ex vivo high intensity focused ultrasound heating experiments, and in vivo stability experiments were performed to test the feasibility of the approach. The results indicate that the hybrid PRF/T(1) approach provides PRF temperature maps of the same quality as those obtained by traditional PRF methods while simultaneously being able to track T(1) changes in fat-based tissues. Although several potential error sources exist for the T(1) measurements, the approach is a promising start toward realizing quantitative temperature measurements in both water-based and fat-based tissues.

Reconstruction of fully three-dimensional high spatial and temporal resolution MR temperature maps for retrospective applications.

Many areas of MR-guided thermal therapy research would benefit from temperature maps with high spatial and temporal resolution that cover a large three-dimensional volume. This article describes an approach to achieve these goals, which is suitable for research applications where retrospective reconstruction of the temperature maps is acceptable. The method acquires undersampled data from a modified three-dimensional segmented echo-planar imaging sequence and creates images using a temporally constrained reconstruction algorithm. The three-dimensional images can be zero-filled to arbitrarily small voxel spacing in all directions and then converted into temperature maps using the standard proton resonance frequency shift technique. During high intensity focused ultrasound heating experiments, the proposed method was used to obtain temperature maps with 1.5 mm × 1.5 mm × 3.0 mm resolution, 288 mm × 162 mm × 78 mm field of view, and 1.7 s temporal resolution. The approach is validated to demonstrate that it can accurately capture the spatial characteristics and time dynamics of rapidly changing high intensity focused ultrasound-induced temperature distributions. Example applications from MR-guided high intensity focused ultrasound research are shown to demonstrate the benefits of the large coverage fully three-dimensional temperature maps, including characterization of volumetric heating trajectories and near- and far-field heating.

HIFU treatment time reduction through heating approach optimisation.

PURPOSE: This study evaluated the HIFU treatment time reductions attainable for several scan paths when optimising the heating approach used (single, discrete pulses versus volumetric scanning) and the paths' focal zone heating locations'; number (N(FZL)), spacings, sequencing order, number of heating cycles (N(CYCLES)), and heating times. Also evaluated were the effects of focal zone size, increased tissue absorptivity due to heating, and optimisation technique. MATERIALS AND METHODS: Treatments of homogeneous constant property tumours were simulated for several simple generic tumour shapes and sizes. The concentrated heating approach (which delivered the desired thermal dose to each location in one discrete heating pulse (N(CYCLES) = 1)) was compared to the fractionated heating approach (which dosed the tumour using multiple, shorter pulses repeatedly scanned around the heating path (i.e. 'volumetric scanning' with N(CYCLES) > 1)). Treatment times were minimised using both simultaneous, collective pulse optimisation (which used full a priori knowledge of the interacting effects of all pulses) and sequential, single pulse optimisation (which used only the information from previous pulses and cooling of the current pulse). RESULTS: Optimised concentrated heating always had shorter treatment times than optimised fractionated heating, and concentrated heating resulted in less normal tissue heating. When large, rapid tissue absorptivity changes were present (doubled or quadrupled immediately after heating) the optimal ordering of the scan path's sequence of focal zone locations changed. CONCLUSIONS: Concentrated heating yields significant treatment time reductions and less normal tissue heating when compared to all fractionated scanning approaches, e.g. volumetric scanning.