Real-time trajectory guide tracking for intraoperative MRI-guided neurosurgery.

PURPOSE: In current intraoperative MRI (IMRI) methods, an iterative approach is used to aim trajectory guides at intracerebral targets: image MR-visible features, determine current aim by fitting model to image, manipulate device, repeat. Infrequent updates are produced by such methods, compared to rapid optically tracked stereotaxy used in the operating room. Our goal was to develop a real-time interactive IMRI method for aiming. METHODS: The current trajectory was computed from two points along the guide's central axis, rather than by imaging the entire device. These points were determined by correlating one-dimensional spokes from a radial sequence with the known cross-sectional projection of the guide. The real-time platform RTHawk was utilized to control MR sequences and data acquisition. On-screen updates were viewed by the operator while simultaneously manipulating the guide to align it with the planned trajectory. Accuracy was quantitated in a phantom, and in vivo validation was demonstrated in nonhuman primates undergoing preclinical gene ( n = 5 $$ n=5 $$ ) and cell ( n = 4 $$ n=4 $$ ) delivery surgeries. RESULTS: Updates were produced at 5 Hz In 10 phantom experiments at a depth of 48 mm, the cannula tip was placed with radial error of (min, mean, max) = (0.16, 0.29, 0.68) mm. Successful in vivo delivery of payloads to all 14 targets was demonstrated across nine surgeries with depths of (min, mean, max) = (33.3, 37.9, 42.5) mm. CONCLUSION: A real-time interactive update rate was achieved, reducing operator fatigue without compromising accuracy. Qualitative interpretation of images during aiming was rendered unnecessary by objectively computing device alignment.

High-spatial and high-temporal resolution dynamic contrast-enhanced perfusion imaging of the liver with time-resolved three-dimensional radial MRI.

PURPOSE: Detection, characterization, and monitoring the treatment of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging because of their variable and rapid arterial enhancement. Multiphase dynamic contrast-enhanced MRI is used clinically for HCC assessment; however, the method suffers from limited temporal resolution and difficulty in coordinating imaging and breath-hold timing within a narrow temporal window of interest. In this article, a volumetric, high-spatial resolution, and high-temporal resolution dynamic contrast-enhanced liver imaging method for improved detection and characterization of HCC is demonstrated. METHODS: A time-resolved three-dimensional radial acquisition with iterative sensitivity-encoding reconstruction images the entire abdomen and thorax with high spatial and temporal resolution, using real-time three-dimensional fluoroscopy to match the breath hold to contrast arrival. The sequence was tested on 17 subjects, including eight patients with HCC or other hypervascular focal lesions. RESULTS: This technique was successful in acquiring volumetric imaging of the entire liver with 2.1-mm isotropic spatial and true 4-s temporal resolution. CONCLUSION: This technique may be suitable for detecting, characterizing, and monitoring the treatment of HCC. It also holds significant potential for perfusion modeling, which may provide a noninvasive means to rapidly determine the efficacy of chemotherapeutic agents in these tumors over the entire liver volume.

High-resolution 3D radial bSSFP with IDEAL.

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.

Quantitative hepatic perfusion modeling using DCE-MRI with sequential breathholds.

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.

Rapid measurement and correction of phase errors from B0 eddy currents: impact on image quality for non-Cartesian imaging.

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.

Frequency response of multipoint chemical shift-based spectral decomposition.

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.

Characterizing and correcting gradient errors in non-cartesian imaging: Are gradient errors linear time-invariant (LTI)?

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.

Three-dimensional imaging of ventilation dynamics in asthmatics using multiecho projection acquisition with constrained reconstruction.

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.

Dorsal Amygdala Neurotrophin-3 Decreases Anxious Temperament in Primates.

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.

Generation and visualization of four-dimensional MR angiography data using an undersampled 3-D projection trajectory.

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.

Overexpressing Corticotropin-Releasing Factor in the Primate Amygdala Increases Anxious Temperament and Alters Its Neural Circuit.

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.

Pilot study of improved lesion characterization in breast MRI using a 3D radial balanced SSFP technique with isotropic resolution and efficient fat-water separation.

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.

Generalized k-space decomposition with chemical shift correction for non-Cartesian water-fat imaging.

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.

3D hyperpolarized He-3 MRI of ventilation using a multi-echo projection acquisition.

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 T(2)* 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.