Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.

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 1.5 mm isotropic whole-brain acquisitions at 3 T 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.

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; 3.0 mm or 1.5 mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5 mm 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.

Quantitative imaging aims to provide in vivo neuroimaging biomarkers with high research and diagnostic value that are sensitive to underlying tissue microstructure. In order to use these data to examine intra-cortical differences or to define boundaries between different myelo-architectural areas, high resolution data are required. The quality of such measurements is degraded in the presence of motion hindering insight into brain microstructure. Correction schemes are therefore vital for high resolution, whole brain coverage approaches that have long acquisition times and greater sensitivity to motion. Here we evaluate the use of prospective motion correction (PMC) via an optical tracking system to counter intra-scan motion in a high resolution (800 μm isotropic) multi-parameter mapping (MPM) protocol. Data were acquired on six volunteers using a 2 × 2 factorial design permuting the following conditions: PMC on/off and motion/no motion. In the presence of head motion, PMC-based motion correction considerably improved the quality of the maps as reflected by fewer visible artifacts and improved consistency. The precision of the maps, parameterized through the coefficient of variation in cortical sub-regions, showed improvements of 11–25% in the presence of deliberate head motion. Importantly, in the absence of motion the PMC system did not introduce extraneous artifacts into the quantitative maps. The PMC system based on optical tracking offers a robust approach to minimizing motion artifacts in quantitative anatomical imaging without extending scan times. Such a robust motion correction scheme is crucial in order to achieve the ultra-high resolution required of quantitative imaging for cutting edge in vivo histology applications.

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.

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 PRF/T1 approach for simultaneously measuring proton resonance frequency (PRF) shift temperatures in water-based tissues and T1 changes in fat-based tissues. The hybrid PRF/T1 sequence is a standard RF 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 T1 information is extracted every two time frames using a variable flip angle (VFA) approach. Simulation studies, ex vivo high intensity focused ultrasound (HIFU) heating experiments, and in vivo stability experiments were performed to test the feasibility of the approach. The results indicate that the hybrid PRF/T1 approach provides PRF temperature maps of the same quality as those obtained by traditional PRF methods while simultaneously being able to track T1 changes in fat-based tissues. While several potential error sources exist for the T1 measurements, the approach is a promising start towards realizing quantitative temperature measurements in both water-based and fat-based tissues.

Purpose This paper develops a method to obtain optimal estimates of absolute magnetization phase from multiple-coil MRI data. 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. Conclusions The proposed virtual reference coil method determines a phase distribution for each coil from which an optimal phase map can be obtained.

Accelerated data acquisition with simultaneous multi-slice (SMS) imaging for functional MRI studies leads to interacting and opposing effects that influence the sensitivity to blood oxygen level-dependent (BOLD) signal changes. Image signal to noise ratio (SNR) is decreased with higher SMS acceleration factors and shorter repetition times (TR) due to g-factor noise penalties and saturation of longitudinal magnetization. However, the lower image SNR is counteracted by greater statistical power from more samples per unit time and a higher temporal Nyquist frequency that allows for better removal of spurious non-BOLD high frequency signal content. This study investigated the dependence of the BOLD sensitivity on these main driving factors and their interaction, and provides a framework for evaluating optimal acceleration of SMS-EPI sequences. functional magnetic resonance imaging (fMRI) data from a scenes/objects visualization task was acquired in 10 healthy volunteers at a standard neuroscience resolution of 3 mm on a 3T MRI scanner. SMS factors 1, 2, 4, and 8 were used, spanning TRs of 2800 ms to 350 ms. Two data processing methods were used to equalize the number of samples over the SMS factors. BOLD sensitivity was assessed using g-factors maps, temporal SNR (tSNR), and t-score metrics. tSNR results show a dependence on SMS factor that is highly non-uniform over the brain, with outcomes driven by g-factor noise amplification and the presence of high frequency noise. The t-score metrics also show a high degree of spatial dependence: the lower g-factor noise area of V1 shows significant improvements at higher SMS factors; the moderate-level g-factor noise area of the parahippocampal place area shows only a trend of improvement; and the high g-factor noise area of the ventral-medial pre-frontal cortex shows a trend of declining t-scores at higher SMS factors. This spatial variability suggests that the optimal SMS factor for fMRI studies is region dependent. For task fMRI studies done with similar parameters as were used here (3T scanner, 32-channel RF head coil, whole brain coverage at 3 mm isotropic resolution), we recommend SMS accelerations of 4x (conservative) to 8x (aggressive) for most studies and a more conservative acceleration of 2x for studies interested in anterior midline regions.