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Background An early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates. Methods In response to potential threat, AT and brain metabolism were assessed in 46 young rhesus monkeys. We identified AT-related transcripts using RNA-sequencing data from dorsal amygdala tissue (including central nucleus of the amygdala [Ce] and dorsal regions of the basal nucleus). Based on the results, we overexpressed the neurotrophin-3 gene, NTF3, in the dorsal amygdala using intraoperative magnetic resonance imaging–guided surgery (n = 5 per group). Results This discovery-based approach identified AT-related alterations in the expression of well-established and novel genes, including an inverse association between NTRK3 expression and AT. NTRK3 is an interesting target because it is a relatively unexplored neurotrophic factor that modulates intracellular neuroplasticity pathways. Overexpression of the transcript for NTRK3's endogenous ligand, NTF3, in the dorsal amygdala resulted in reduced AT and altered function in AT's neural circuit. Conclusions Together, these data implicate neurotrophin-3/NTRK3 signaling in the dorsal amygdala in mediating primate anxiety. More generally, this approach provides an important step toward understanding the molecular underpinnings of early-life AT and will be useful in guiding the development of treatments to prevent the development of stress-related psychopathology.

INTRODUCTION The spatial and temporal resolution limits of functional MRI (fMRI) brain mapping provide primarily correlative information on brain connectivity. Determining how one region causally modulates and mediates activity in other regions remains difficult with fMRI. We demonstrate a simple means to add causality in resting state functional connectivity MRI (rs-fcMRI) using techniques developed first for convection-enhanced delivery (CED) of therapeutics. Here we use CED to guide and monitor pharmacologic alteration of a local brain region in anaesthetized Rhesus monkeys while monitoring rs-fcMRI signal changes. METHODS Pre-surgical MRI was used to determine skull locations for craniotomies for installation of NavigusTMbrain ports in two untrained monkeys slated for euthanasia. The ports were aligned in real–time to provide trajectories aimed at the central nucleus of the amygdala (CeA). Fused silica catheters were then inserted into the CeA where 24 mg of muscimol (inhibitory agent) was infused in 24 ml of buffered solution under pressure over 12 minutes, first on the right side and then on the left side. rs-fcMRI studies were done for 45 minutes before and after the unilateral infusion and then after the bilateral infusion. RESULTS Catheters were successfully aligned and inserted into the CeA targets with sub-mm accuracy. T2-weighted imaging detected the enhanced T2 from the infusion’s buffer. Pre-infusion rs-fcMRI provides results consistent with prior studies, which have shown that the CeA is most strongly connected to the contralateral CeA. This connectivity was significantly reduced following both unilateral and bilateral injections of muscimol into the CeA, demonstrating the effectiveness of the muscimol infusions. Conditional Grainger Causality (CGC) analysis shows unexpected new connectivity after the unilateral infusion. Upon the bilateral infusion, global effective connectivity in the region is reduced. CONCLUSION Expected and unexpected changes in resting state functional connectivity resulted from unilateral and bilateral infusions of inhibitory agents.

Background Nonhuman primate models are critical for understanding mechanisms underlying human psychopathology. We established a nonhuman primate model of anxious temperament (AT) for studying the early-life risk to develop anxiety and depression. Studies have identified the central nucleus of the amygdala (Ce) as an essential component of AT's neural substrates. Corticotropin-releasing factor (CRF) is expressed in the Ce, has a role in stress, and is linked to psychopathology. Here, in young rhesus monkeys, we combined viral vector technology with assessments of anxiety and multimodal neuroimaging to understand the consequences of chronically increased CRF in the Ce region. Methods Using real-time intraoperative magnetic resonance imaging-guided convection-enhanced delivery, five monkeys received bilateral dorsal amygdala Ce-region infusions of adeno-associated virus serotype 2 containing the CRF construct. Their cagemates served as unoperated control subjects. AT, regional brain metabolism, resting functional magnetic resonance imaging, and diffusion tensor imaging were assessed before and 2 months after viral infusions. Results Dorsal amygdala CRF overexpression significantly increased AT and metabolism within the dorsal amygdala. Additionally, we observed changes in metabolism in other AT-related regions, as well as in measures of functional and structural connectivity. Conclusions This study provides a translational roadmap that is important for understanding human psychopathology by combining molecular manipulations used in rodents with behavioral phenotyping and multimodal neuroimaging measures used in humans. The results indicate that chronic CRF overexpression in primates not only increases AT but also affects metabolism and connectivity within components of AT's neural circuitry.

Induced pluripotent stem cell (iPSC)-derived neurons represent an opportunity for cell replacement strategies for neurodegenerative disorders such as Parkinson's disease (PD). Improvement in cell graft targeting, distribution, and density can be key for disease modification. We have previously developed a trajectory guide system for real-time intraoperative magnetic resonance imaging (RT-IMRI) delivery of infusates, such as viral vector suspensions for gene therapy strategies. Intracerebral delivery of iPSC-derived neurons presents different challenges than viral vectors, including limited cell survival if cells are kept at room temperature for prolonged periods of time, precipitation and aggregation of cells in the cannula, and obstruction during injection, which must be solved for successful application of this delivery approach. To develop procedures suitable for RT-IMRI cell delivery, we first performed in vitro studies to tailor the delivery hardware (e.g., cannula) and defined a range of parameters to be applied (e.g., maximal time span allowable between cell loading in the system and intracerebral injection) to ensure cell survival. Then we performed an in vivo study to evaluate the feasibility of applying the system to nonhuman primates. Our results demonstrate that the RT-IMRI delivery system provides valuable guidance, monitoring, and visualization during intracerebral cell delivery that are compatible with cell survival.

Purpose To develop and demonstrate the feasibility of a new formulation for quantitative perfusion modeling in the liver using interrupted DCE-MRI data acquired during multiple sequential breathholds. Materials and Methods A new mathematical formulation to estimate quantitative perfusion parameters using interrupted data was developed. Using this method, we investigated whether a second degree-of-freedom in the tissue residue function (TRF) improves quality-of-fit criteria when applied to a dual-input single-compartment perfusion model. We subsequently estimated hepatic perfusion parameters using DCE-MRI data from 12 healthy volunteers and 9 cirrhotic patients with a history of hepatocellular carcinoma (HCC); and examined the utility of these estimates in differentiating between healthy liver, cirrhotic liver, and HCC. Results Quality-of-fit criteria in all groups were improved using a Weibull TRF (2 degrees-of-freedom) versus an exponential TRF (1 degree-of-freedom), indicating nearer concordance of source DCE-MRI data with the Weibull model. Using the Weibull TRF, arterial fraction was greater in cirrhotic versus normal liver (39 ± 23% versus 15 ± 14%, P = 0.07). Mean transit time (20.6 ± 4.1 s versus 9.8 ± 3.5 s, P = 0.01) and arterial fraction (39 ± 23% versus 73 ± 14%, P = 0.04) were both significantly different between cirrhotic liver and HCC, while differences in total perfusion approached significance. Conclusion This work demonstrates the feasibility of estimating hepatic perfusion parameters using interrupted data acquired during sequential breathholds. J. Magn. Reson. Imaging 2014;39:853–865. © 2013 Wiley Periodicals, Inc.

Purpose Detection, characterization, and monitoring of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging due to their variable and rapid arterial enhancement. Multiphase dynamic contrast-enhanced MRI (CE-MRI) is used clinically for HCC assessment, but suffers from limited temporal resolution and difficulty in coordinating imaging and breath-hold timing within a narrow temporal window of interest. We demonstrate a volumetric, high spatial resolution, high temporal resolution dynamic contrast enhanced liver imaging method for improved detection and characterization of HCC.

Radial trajectories facilitate high-resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k-space. A number of radial bSSFP methods that support fat-water separation have been developed; however, most of these methods require an environment with limited B0 inhomogeneity. In this work, high-resolution bSSFP with fat-water separation is achieved in more challenging B0 environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual-pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multiecho acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5-min scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T.

Background: Delivery of multiple collinear payloads utilizing convection-enhanced delivery (CED) has historically been performed by retraction of a needle or catheter from the most distal delivery site. Few studies have addressed end-infusion morphology and associated payload reflux in stacked and collinear infusions, and studies comparing the advancement with the retraction mode are lacking. Objective: To compare advancement versus retraction mode infusion results. Methods: Infusion cloud pairs were created with the advancement and retraction technique in agarose gel using both open end-port SmartFlow™ (SF) and valve tip (VT) catheter infusion systems. Backflow, radius of infusion, and morphology were assessed. Results: Infusions with the SF catheter, in contrast to the VT catheter, exhibited significantly more backflow in retraction mode at the shallow infusion site. Infusion morphology differed with the second infusion after retraction: the infusate at the proximal site first filling the channel left by the retraction and then being convected into gel in a pronouncedly non-spherical shape during the second infusion. Conclusions: Significant differences in cloud morphology were noted with respect to external catheter geometry with retraction versus penetration between infusions in an agarose gel model of the brain. Further study is warranted to determine optimal protocols for human clinical trials employing CED with multiple collinear payloads.

Background: Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. Purpose: The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. Methods: In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 µL/min and 2 µL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 µL/min for 30 minutes. The fourth brain received a total of 45 µL infused at a rate of 1 µL/min for 15 minutes followed by 2 µL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 µL. Subjects 1 and 2 received infusions at 1.0 µL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 µL/ min. Results: MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). Conclusions: We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials.

Fat/water separation methods such as fluctuating equilibrium magnetic resonance and linear combination steady-state free precession have not yet been successfully implemented at 3.0 T due to extreme limitations on the time available for spatial encoding with the increase in magnetic field strength. We present a method to utilize a three-dimensional radial sequence combined with linear combination steady-state free precession at 3.0 T to take advantage of the increased signal levels over 1.5 T and demonstrate high spatial resolution compared to Cartesian techniques. We exploit information from the two half-echoes within each pulse repetition time to correct the accumulated phase on a point-by-point basis, thereby fully aligning the phase of both half-echoes. The correction provides reduced sensitivity to static field (B(0)) inhomogeneity and robust fat/water separation. Resultant images in the knee joint demonstrate the necessity of such a correction, as well as the increased isotropic spatial resolution attainable at 3.0 T. Results of a clinical study comparing this sequence to conventional joint imaging sequences are included.

Non-Cartesian and rapid imaging sequences are more sensitive to scanner imperfections such as gradient delays and eddy currents. These imperfections vary between scanners and over time and can be a significant impediment to successful implementation and eventual adoption of non-Cartesian techniques by scanner manufacturers. Differences between the k-space trajectory desired and the trajectory actually acquired lead to misregistration and reduction in image quality. While early calibration methods required considerable scan time, more recent methods can work more quickly by making certain approximations. We examine a rapid gradient calibration procedure applied to multiecho three-dimensional projection reconstruction (3DPR) acquisitions in which the calibration runs as part of every scan. After measuring the trajectories traversed for excitations on each of the orthogonal gradient axes, trajectories for the oblique projections actually acquired during the scan are synthesized as linear combinations of these measurements. The ability to do rapid calibration depends on the assumption that gradient errors are linear and time-invariant (LTI). This work examines the validity of these assumptions and shows that the assumption of linearity is reasonable, but that gradient errors can vary over short time periods (due to changes in gradient coil temperature) and thus it is important to use calibration data matched to the scan data.

The purpose of this work is to detect dynamic gas trapping in three dimensions during forced exhalation at isotropic high spatial resolution and high temporal resolution using hyperpolarized helium-3 MRI. Ten subjects underwent hyperpolarized helium-3 MRI and multidetector CT. MRI was performed throughout inspiration, breath-hold, and forced expiration. A multiecho three-dimensional projection acquisition was used to improve data collection efficiency and an iterative constrained reconstruction was implemented to improve signal to noise ratio (SNR) and increase robustness to motion. Two radiologists evaluated the dynamic MRI and breath-held multidetector CT data for gas and air trapping, respectively. Phantom studies showed the proposed technique significantly improved depiction of moving objects compared to view-sharing methods. Gas trapping was detected using MRI in five of the six asthmatic subjects who displayed air trapping with multidetector CT. Locations in disagreement were found to represent small to moderate regions of air trapping. The proposed technique provides whole-lung three-dimensional imaging of respiration dynamics at high spatial and temporal resolution and compares well to the current standard, multidetector CT. While multidetector CT can provide information about static regional air trapping, it is unable to depict dynamics in a setting more comparable to a spirometry maneuver and explore the longitudinal time evolution of the trapped regions.

Time-resolved contrast-enhanced magnetic resonance (MR) angiography (CE-MRA) has gained in popularity relative to X-ray Digital Subtraction Angiography because it provides three-dimensional (3-D) spatial resolution and it is less invasive. We have previously presented methods that improve temporal resolution in CE-MRA while providing high spatial resolution by employing an undersampled 3-D projection (3D PR) trajectory. The increased coverage and isotropic resolution of the 3D PR acquisition simplify visualization of the vasculature from any perspective. We present a new algorithm to develop a set of time-resolved 3-D image volumes by preferentially weighting the 3D PR data according to its acquisition time. An iterative algorithm computes a series of density compensation functions for a regridding reconstruction, one for each time frame, that exploit the variable sampling density in 3D PR. The iterative weighting procedure simplifies the calculation of appropriate density compensation for arbitrary sampling patterns, which improve sampling efficiency and, thus, signal-to-noise ratio and contrast-to-noise ratio, since it is does not require a closed-form calculation based on geometry. Current medical workstations can display these large four-dimensional studies, however, interactive cine animation of the data is only possible at significantly degraded resolution. Therefore, we also present a method for interactive visualization using powerful graphics cards and distributed processing. Results from volunteer and patient studies demonstrate the advantages of dynamic imaging with high spatial resolution.

For optimized CE-MRA of the chest and abdomen, the scan time and breath-hold must be coordinated with the arrival of contrast. A 3D fluoroscopy system is demonstrated that performs real-time 3D projection reconstruction acquisition, reconstruction, and visualization using only the standard scanner hardware and operator console workstation. Unlike 2D fluorotriggering techniques, no specification of a monitoring slab or careful placement of the imaging volume is required. 3DPR data are acquired continuously throughout the examination using an eight-channel receiver and 1 s interleaved subframes. The data are reconstructed using 1 s segments for real-time monitoring with 0.8-cm isotropic spatial resolution over the entire torso, allowing full-volume axial, coronal, and sagittal MIPs to be displayed simultaneously with minimal latency. The system later uses the same scan data to generate high-spatial-resolution time-resolved sequences of the breath-hold interval. The 3D fluoroscopy system was validated on phantoms and human volunteers. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc.

To develop and demonstrate the feasibility of a new formulation for quantitative perfusion modeling in the liver using interrupted DCE-MRI data acquired during multiple sequential breathholds.A new mathematical formulation to estimate quantitative perfusion parameters using interrupted data was developed. Using this method, we investigated whether a second degree-of-freedom in the tissue residue function (TRF) improves quality-of-fit criteria when applied to a dual-input single-compartment perfusion model. We subsequently estimated hepatic perfusion parameters using DCE-MRI data from 12 healthy volunteers and 9 cirrhotic patients with a history of hepatocellular carcinoma (HCC); and examined the utility of these estimates in differentiating between healthy liver, cirrhotic liver, and HCC.Quality-of-fit criteria in all groups were improved using a Weibull TRF (2 degrees-of-freedom) versus an exponential TRF (1 degree-of-freedom), indicating nearer concordance of source DCE-MRI data with the Weibull model. Using the Weibull TRF, arterial fraction was greater in cirrhotic versus normal liver (39 ± 23% versus 15 ± 14%, P = 0.07). Mean transit time (20.6 ± 4.1 s versus 9.8 ± 3.5 s, P = 0.01) and arterial fraction (39 ± 23% versus 73 ± 14%, P = 0.04) were both significantly different between cirrhotic liver and HCC, while differences in total perfusion approached significance.This work demonstrates the feasibility of estimating hepatic perfusion parameters using interrupted data acquired during sequential breathholds.

Radial trajectories facilitate high-resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k-space. A number of radial bSSFP methods that support fat-water separation have been developed; however, most of these methods require an environment with limited B0 inhomogeneity. In this work, high-resolution bSSFP with fat-water separation is achieved in more challenging B0 environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual-pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multi-echo acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5-minute scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T.

Non-Cartesian imaging sequences and navigational methods can be more sensitive to scanner imperfections that have little impact on conventional clinical sequences, an issue which has repeatedly complicated the commercialization of these techniques by frustrating transitions to multicenter evaluations. One such imperfection is phase errors caused by resonant frequency shifts from eddy currents induced in the cryostat by time-varying gradients, a phenomenon known as B(0) eddy currents. These phase errors can have a substantial impact on sequences that use ramp sampling, bipolar gradients, and readouts at varying azimuthal angles. We present a method for measuring and correcting phase errors from B(0) eddy currents and examine the results on two different scanner models. This technique yields significant improvements in image quality for high-resolution joint imaging on certain scanners. This result suggests that correcting short-time B(0) eddy currents that do not affect conventional clinical sequences may simplify the adoption of non-Cartesian methods.

There is a growing need for high-frame-rate low-latency visualization solutions as medical practice moves toward interventional procedures. We present a cost-effective visualization system well suited for off-line visualization and interventional procedures. Users can view large time-resolved multi-dimensional datasets in real time with GPU cluster visualization. In addition, computational pre-processing can be hidden by rendering across distributed graphics cards, leading to improved frame-rates over a single graphics card solution. Finally, rendering on graphics cards offloads CPU cycles for generating the next time frame in the visualization. We have developed a network arbitration protocol for GPU cluster visualization called “token scheduling.” Our protocol reduces communication latency, which in turn lowers visualization latency and improves system stability and scalability. In addition, we evaluate GPU cluster behavior and performance through a timing analysis. This analysis leads to a better understanding of cluster size needed to achieve the desired frame rate of a given problem.

Real-time MRI has the potential to significantly improve intraoperative surgical processes. However, development of these technologies is complicated by the need for software tools that support task-oriented visualization of 2D and 3D datasets, enable flexible real-time image processing pathways, and interface with proprietary scanner hardware. Developing such tools requires substantial software engineering effort for these low-level tasks that distracts from a focus on developing and implementing algorithms that relate to the surgical technique in question. RTHawk and Vurtigo are extensible software platforms that simplify the development of tools for performing real-time MRI-guided procedures. We present here initial work on a system for performing intracerebral drug infusion under real-time MRI guidance using the Navigus pivot point-based MRI-compatible external trajectory guide. Initial testing performed using a GE scanner targeting a rigid object in a water-filled phantom allowed realtime aiming and infusion monitoring with 1 mm targeting accuracy. In vivo testing is forthcoming.

PURPOSE To provide a framework for characterizing the frequency response of multipoint chemical shift based species separation techniques. MATERIALS AND METHODS Multipoint chemical shift based species separation techniques acquire complex images at multiple echo times and perform maximum likelihood estimation to decompose signal from different species into separate images. In general, after a nonlinear process of estimating and demodulating the field map, these decomposition methods are linear transforms from the echo-time domain to the chemical-shift-frequency domain, analogous to the discrete Fourier transform (DFT). In this work we describe a technique for finding the magnitude and phase of chemical shift decomposition for input signals over a range of frequencies using numerical and experimental modeling and examine several important cases of species separation. RESULTS Simple expressions can be derived to describe the response to a wide variety of input signals. Agreement between numerical modeling and experimental results is very good. CONCLUSION Chemical shift-based species separation is linear, and therefore can be fully described by the magnitude and phase curves of the frequency response. The periodic nature of the frequency response has important implications for the robustness of various techniques for resolving ambiguities in field inhomogeneity.

Purpose To assess a 3D radial balanced steady-state free precession (SSFP) technique that provides submillimeter isotropic resolution and inherently registered fat and water image volumes in comparison to conventional T2-weighted RARE imaging for lesion characterization in breast magnetic resonance imaging (MRI). Materials and Methods 3D projection SSFP (3DPR-SSFP) combines a dual half-echo radial k-space trajectory with a linear combination fat/water separation technique (linear combination SSFP). A pilot study was performed in 20 patients to assess fat suppression and depiction of lesion morphology using 3DPR-SSFP. For all patients fat suppression was measured for the 3DPR-SSFP image volumes and depiction of lesion morphology was compared against corresponding T2-weighted fast spin echo (FSE) datasets for 15 lesions in 11 patients. Results The isotropic 0.63 mm resolution of the 3DPR-SSFP sequence demonstrated improved depiction of lesion morphology in comparison to FSE. The 3DPR-SSFP fat and water datasets were available in a 5-minute scan time while average fat suppression with 3DPR-SSFP was 71% across all 20 patients. Conclusion 3DPR-SSFP has the potential to improve the lesion characterization information available in breast MRI, particularly in comparison to conventional FSE. A larger study is warranted to quantify the effect of 3DPR-SSFP on specificity. J. Magn. Reson. Imaging 2009;30:135–144. © 2009 Wiley-Liss, Inc.

A method is presented for high-resolution 3D imaging of the whole lung using inhaled hyperpolarized (HP) He-3 MR with multiple half-echo radial trajectories that can accelerate imaging through undersampling. A multiple half-echo radial trajectory can be used to reduce the level of artifact for undersampled 3D projection reconstruction (PR) imaging by increasing the amount of data acquired per unit time for HP He-3 lung imaging. The point spread functions (PSFs) for breath-held He-3 MRI using multiple half-echo trajectories were evaluated using simulations to predict the effects of T2* and gas diffusion on image quality. Results from PSF simulations were consistent with imaging results in volunteer studies showing improved image quality with increasing number of echoes using up to 8 half-echoes. The 8-half-echo acquisition is shown to accommodate lost breath-holds as short as 6 sec using a retrospective reconstruction at reduced resolution and also to allow reduced breath-hold time compared with an equivalent Cartesian trajectory. Furthermore, preliminary results from a 3D dynamic inhalation-exhalation maneuver are demonstrated using the 8-half-echo trajectory. Results demonstrate the first high-resolution 3D PR imaging of ventilation and respiratory dynamics in humans using HP He-3 MR. Magn Reson Med 59:1062–1071, 2008. © 2008 Wiley-Liss, Inc.

Chemical-shift artifacts associated with non-Cartesian imaging are more complex to model and less clinically acceptable than the bulk fat shift that occurs with conventional spin-warp Cartesian imaging. A novel k-space based iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) approach is introduced that decomposes multiple species while simultaneously correcting distortion of off-resonant species. The new signal model accounts for the additional phase accumulated by off-resonant spins at each point in the k-space acquisition trajectory. This phase can then be corrected by adjusting the decomposition matrix for each k-space point during the final IDEAL processing step with little increase in reconstruction time. The technique is demonstrated with water-fat decomposition using projection reconstruction (PR)/radial, spiral, and Cartesian spin-warp imaging of phantoms and human subjects, in each case achieving substantial correction of chemical-shift artifacts. Simulations of the point-spread-function (PSF) for off-resonant spins are examined to show the nature of the chemical-shift distortion for each acquisition. Also introduced is an approach to improve the signal model for species which have multiple resonant peaks. Many chemical species, including fat, have multiple resonant peaks, although such species are often approximated as a single peak. The improved multipeak decomposition is demonstrated with water-fat imaging, showing a substantial improvement in water-fat separation.

During the last eight years our group has developed radial acquisitions with angular undersampling factors of several hundred that accelerate MRI in selected applications. As with all previous acceleration techniques, SNR typically falls as least as fast as the inverse square root of the undersampling factor. This limits the SNR available to support the small voxels that these methods can image over short time intervals in applications like time-resolved contrast-enhanced MR angiography (CE-MRA). Instead of processing each time interval independently, we have developed constrained reconstruction methods that exploit the significant correlation between temporal sampling points. A broad class of methods, termed HighlY Constrained Back PRojection (HYPR), generalizes this concept to other modalities and sampling dimensions.

The University of Wisconsin-Madison Snowmobile Team has designed and constructed a hybrid-electric snowmobile for entry in the 2005 Society of Automotive Engineers’ Clean Snowmobile Challenge. Built on a 2003 cross-country touring chassis, this machine features a 784 cc fuel-injected four-stroke engine in parallel with a 48 V electric golf cart motor. The 12 kg electric motor increases powertrain torque up to 25% during acceleration and recharges the snowmobile’s battery pack during steady-state operation. Air pollution from the gasoline engine is reduced to levels far below current best available technology in the snowmobile industry. The four-stroke engine’s closed-loop EFI system maintains stoichiometric combustion while dual three-way catalysts reduce NOx, HC and CO emissions by up to 94% from stock. In addition to the use of three way catalysts, the fuel injection strategy has been modified to further reduce engine emissions from the levels measured in the CSC 2004 competition. The entire hybrid drivetrain including battery pack and a twostage muffler is packaged in a manner that maintains the snowmobile’s aggressive OEM appearance.

Three-dimensional projection reconstruction (3D PR)-based techniques are advantageous for steady-state free precession (SSFP) imaging for several reasons, including the capability to achieve short repetition times (TRs). In this paper, a multi-half-echo technique is presented that dramatically improves the data-sampling efficiency of 3D PR sequences while it retains this short-TR capability. The k-space trajectory deviations are measured quickly and corrected on a per-sample point basis. A two-pass RF cycling technique is then applied to the dual-half-echo implementation to generate fat/water-separated images. The resultant improvement in the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was demonstrated in volunteer studies. Volumetric images with excellent spatial resolution, coverage, and contrast were obtained with high speed. The non-contrast-enhanced SSFP studies show that this technique has promising potential for MR angiography (MRA).

Purpose To investigate the application of time-resolved vastly undersampled isotropic projection reconstruction (VIPR) in contrast-enhanced magnetic resonance angiography of the distal extremity (single station), and peripheral run-off vasculature in the abdomen, thigh, and calf (three stations). Materials and Methods Time-resolved distal extremity imaging was performed using VIPR sequence through the comparison of two acquisition matrix sizes: 256 with TR/TE = 3.7/1.4 msec and 320 with TR/TE = 4.5/1.8 msec under the same scan time of two minutes. VIPR acquisition was combined with a bolus-chase technique to image the peripheral run-off vasculature. The time-resolved images were reconstructed using a revised sliding window reconstruction filter whose temporal aperture remained narrow for low spatial frequencies and increased quadratically to include all the projection data for high spatial frequencies. Results The new temporal filter significantly suppressed the undersampling streak artifacts and venous contamination, while maintaining a high temporal resolution. Both high spatial resolution (ranging from 1.56 × 1.56 × 1.56 mm to 1.25 × 1.25 × 1.25 mm) and high temporal resolution (three seconds per frame) distal extremity images and peripheral run-off images were generated using time-resolved VIPR acquisition, which provides isotropic spatial resolution and isotropic coverage. Conclusion Time-resolved VIPR acquisition was demonstrated to be well suited for distal extremity imaging by providing isotropic spatial resolution, isotropic coverage, and high temporal resolution. The combination of time-resolved VIPR and bolus chase technique provided a novel approach for peripheral run-off examinations. J. Magn. Reson. Imaging 2004;20:894–900. © 2004 Wiley-Liss, Inc.

The University of Wisconsin - Madison FutureTruck Team has designed and built a four-wheel drive, charge sustaining, parallel hybrid-electric sport utility vehicle for entry into the FutureTruck 2002 competition. This is a two-year project with tiered goals; the base vehicle for both years is a 2002 Ford Explorer. Wisconsin's FutureTruck, nicknamed the 'Moolander', weighs approximately 2050 kg. The vehicle uses a high efficiency, 2.5 liter, turbo-charged, compression ignition common rail, direct-injection engine supplying approximately 100 kW of peak power and a AC induction motor that provides an additional 33 kW of peak power. This hybrid drivetrain is an attractive alternative to the large displacement V6 drivetrain, as it provides comparable performance with similar emissions and drastically reduced fuel consumption. The PNGV Systems Analysis Toolkit (PSAT) model predicts a Federal Testing Procedure (FTP) combined driving cycle fuel economy of 16.74 km/L (39.4 mpg) with California Ultra Low Emission Vehicle (ULEV) emissions levels. These goals will be met while maintaining the full passenger/cargo capacity, appearance, and towing capacity of 2495 kg.

Convection-enhanced delivery (CED) is an advanced infusion technique used to deliver therapeutic agents into the brain. CED has shown promise in recent clinical trials. Independent verification of published parameters is warranted with benchmark testing of published parameters in applicable models such as gel phantoms, ex vivo tissue and in vivo non-human animal models to effectively inform planned and future clinical therapies. In the current study, specific performance characteristics of two CED infusion catheter systems, such as backflow, infusion cloud morphology, volume of distribution (mm(3)) versus the infused volume (mm(3)) (Vd/Vi) ratios, rate of infusion (µl min(-1)) and pressure (mmHg), were examined to ensure published performance standards for the ERG valve-tip (VT) catheter. We tested the hypothesis that the ERG VT catheter with an infusion protocol of a steady 1 µl min(-1) functionality is comparable to the newly FDA approved MRI Interventions Smart Flow (SF) catheter with the UCSF infusion protocol in an agarose gel model. In the gel phantom models, no significant difference was found in performance parameters between the VT and SF catheter. We report, for the first time, such benchmark characteristics in CED between these two otherwise similar single-end port VT with stylet and end-port non-stylet infusion systems. Results of the current study in agarose gel models suggest that the performance of the VT catheter is comparable to the SF catheter and warrants further investigation as a tool in the armamentarium of CED techniques for eventual clinical use and application.