Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer.

Use of simulated annealing for the design of multiple repetition time balanced steady-state free precession imaging.

Balanced steady-state free precession is an ultrafast sequence with high signal-to-noise efficiency, but it also generates a strong fat signal which can mask important features. One method of fat suppression is to modify the balanced steady-state free precession spectrum using multiple repetition times to create a wide stopband over the fat frequency. However, with three or more pulse repetition times, the number of parameters creates a vast search space with many local minima of a cost function. We report on the initial results of using simulated annealing to find optimal sequences for two applications of multiple-pulse repetition time balanced steady-state free precession: positive contrast imaging and fat suppression.

Single shot concentric shells trajectories for ultra fast fMRI.

MR-encephalography is a technique that allows real-time observation of functional changes in the brain with a time-resolution of 100 ms. The high sampling rate is enabled by the use of undersampled image acquisition with regularized reconstruction. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on undersampled, single-shot concentric shells trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in blood oxygenation level dependent signal as a measure of brain physiology at very high temporal resolution.

Combined prospective and retrospective motion correction to relax navigator requirements.

Prospective motion correction can prevent motion artifacts in magnetic resonance imaging of the brain. However, for high-resolution imaging, the technique relies on precise tracking of head motion. This precision is often limited by tracking noise, which leads to residual errors in the prospectively-corrected k-space data and artifacts in the image. This work shows that it is possible to estimate these tracking errors, and hence the true k-space sample locations, by applying a two-sided filter to the tracking data after imaging. A conjugate gradient reconstruction is compared to gridding as a means of using this information to retrospectively correct for the effects of the residual errors.

Three-dimensional MR-encephalography: fast volumetric brain imaging using rosette trajectories.

MR-Encephalography (MREG) is a technique that allows real time observation of functional changes in the brain that appears within 100 msec. The high sampling rate is achieved at the cost of some spatial resolution. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on rosette trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in brain physiology at very high temporal resolution. A highly undersampled three-dimensional rosette trajectory is chosen, to perform single shot acquisition of k-space data within 23 msec. By using a 32-channel head coil array and regularized nonuniform Fourier transformation reconstruction, the spatial resolution is sufficient to detect even subtle centers of activation (e.g. human MT+). The method was applied to visual block design paradigms and compared with echo planar imaging-based functional MRI. As a proof-of-principle of the method's ability to detect local differences in the hemodynamic response functions, the analyzed MR-encephalography data revealed a spatially dependent delay of the arrival of the blood oxygenation level dependent response within the visual cortex.

Multiplex RARE: a simultaneous multislice spin-echo sequence that fulfils CPMG conditions.

This work presents a new imaging sequence in which multiple slices are simultaneously excited and refocused in a spin-echo train. The multiple spin-echo trains are interleaved in such a manner that (i) the Carr-Purcell-Meiboom-Gill conditions are fulfilled at all times, and (ii) the signals from slices can be separated, preventing aliasing. This paper also demonstrates how the sequence may be used in a novel fat-water Dixon method that enables fast volume coverage. The technique is demonstrated in phantoms and in vivo.

Compressed sensing in hyperpolarized 3He lung MRI.

In this work, the application of compressed sensing techniques to the acquisition and reconstruction of hyperpolarized (3)He lung MR images was investigated. The sparsity of (3)He lung images in the wavelet domain was investigated through simulations based on fully sampled Cartesian two-dimensional and three-dimensional (3)He lung ventilation images, and the k-spaces of 2D and 3D images were undersampled randomly and reconstructed by minimizing the L1 norm. The simulation results show that temporal resolution can be readily improved by a factor of 2 for two-dimensional and 4 to 5 for three-dimensional ventilation imaging with (3)He with the levels of signal to noise ratio (SNR) (approximately 19) typically obtained. The feasibility of producing accurate functional apparent diffusion coefficient (ADC) maps from undersampled data acquired with fewer radiofrequency pulses was also demonstrated, with the preservation of quantitative information (mean ADC(cs) approximately mean ADC(full) approximately 0.16 cm(2) sec(-1)). Prospective acquisition of 2-fold undersampled two-dimensional (3)He images with a compressed sensing k-space pattern was then demonstrated in a healthy volunteer, and the results were compared to the equivalent fully sampled images (SNR(cs) = 34, SNR(full) = 19).

Multimodal assessments of Zika virus immune pathophysiological responses in marmosets.

Animal models that recapitulate the human pathophysiology have been developed as useful research tools. Although laboratory mice are widely used, they are phylogenetically "distant" to humans. New world monkeys, such as the common marmoset (Callithrix jacchus) have steadily gained prominence. In this report, marmosets are explored as an alternate in vivo model to investigate infection and immunity of Zika virus (ZIKV). Multimodal platforms, including ultrasound and magnetic resonance imaging (MRI), flow cytometry, and multiplex microbead immunoassays were established to comprehensively decipher immune responses and pathophysiological outcomes. While ZIKV-infected marmosets had detectable ZIKV RNA load in various body fluids, animals did not develop any observable lesions in their testes and brains as shown by ultrasound and MRI. Immune-phenotyping detected differences in the numbers of B cells, CD8+ T cells and HLADR+ NK cells during the first two weeks of infection. Neutralizing ZIKV-specific antibodies were elicited to high levels and targeted epitopes in the E protein. This study presents a one-stop-shop platform to study infection and pathophysiology in marmosets. While marmoset-specific research tools are being refined, the research values of these animals present them as a good model for immune-based therapies.

General parameter relations for the Shinnar-Le Roux pulse design algorithm.

The magnetization ripple amplitudes from a pulse designed by the Shinnar-Le Roux algorithm are a non-linear function of the Shinnar-Le Roux A and B polynomial ripples. In this paper, the method of Pauly et al. [J. Pauly, P. Le Roux, D. Nishimura, A. Macovski, Parameter relations for the Shinnar-Le Roux selective excitation pulse design algorithm, IEEE Transactions on Medical Imaging 10 (1991) 56-65.] has been extended to derive more general parameter relations. These relations can be used for cases outside the five classes considered by Pauly et al., in particular excitation pulses for flip angles that are not small or 90 degrees. Use of the new relations, together with an iterative procedure to obtain polynomials with the specified ripples from the Parks-McClellan algorithm, are shown to give simulated slice profiles that have the desired ripple amplitudes.

SNR phase order k-space encoding (SPOKE).

A method of determining the phase-encode order for MR Fourier-encoded imaging is described, which provides an additional option for optimizing images from samples with signals that change during data acquisition. Examples are in hyperpolarized helium gas imaging of the lungs where polarization is lost with each RF pulse or the signal changes observed in rapid dynamic studies with T(1) or T(2)* contrast agents when mixing is taking place. The method uses a single frequency-encoded projection in the proposed phase-encoding direction. The projection is subsequently sorted into signal-to-noise ratio (SNR) order. The indices of the sorted array are then used to create the phase-encode table to be used for the scan. This phase table is sorted in descending SNR order for signals that decrease during data acquisition and in ascending order for signals that increase during data acquisition. Simulations suggest that this technique can produce higher resolution than centric-ordered phase encoding at the expense of increased modulation (ghosting) artifact for dynamically changing signals. Initial practical implementation of the technique has been carried out on a dedicated 0.2-T Niche MR system, and the test object results agree well with simulations. Hyperpolarized 3-He lung images have also been acquired and postprocessed using the SNR phase order k-space encoding (SPOKE) methodology and show potential for improved imaging with high flip angles where polarization is rapidly lost. Applications may also be found for 3D volumetric acquisitions where two dimensions can be SPOKE encoded.

Automated gamma knife radiosurgery treatment planning with image registration, data-mining, and Nelder-Mead simplex optimization.

Gamma knife treatments are usually planned manually, requiring much expertise and time. We describe a new, fully automatic method of treatment planning. The treatment volume to be planned is first compared with a database of past treatments to find volumes closely matching in size and shape. The treatment parameters of the closest matches are used as starting points for the new treatment plan. Further optimization is performed with the Nelder-Mead simplex method: the coordinates and weight of the isocenters are allowed to vary until a maximally conformal plan specific to the new treatment volume is found. The method was tested on a randomly selected set of 10 acoustic neuromas and 10 meningiomas. Typically, matching a new volume took under 30 seconds. The time for simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and 8/10 meningiomas, the automatic method found plans with conformation number equal or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10 meningiomas, both overtreatment and undertreatment ratios were equal or better in automated plans. In conclusion, data-mining of past treatments can be used to derive starting parameters for treatment planning. These parameters can then be computer optimized to give good plans automatically.

Simultaneous parallel inclined readout image technique.

Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.

Slice profile effects in 2D slice-selective MRI of hyperpolarized nuclei.

This work explores slice profile effects in 2D slice-selective gradient-echo MRI of hyperpolarized nuclei. Two different sequences were investigated: a Spoiled Gradient Echo sequence with variable flip angle (SPGR-VFA) and a balanced Steady-State Free Precession (SSFP) sequence. It is shown that in SPGR-VFA the distribution of flip angles across the slice present in any realistically shaped radiofrequency (RF) pulse leads to large excess signal from the slice edges in later RF views, which results in an undesired non-constant total transverse magnetization, potentially exceeding the initial value by almost 300% for the last RF pulse. A method to reduce this unwanted effect is demonstrated, based on dynamic scaling of the slice selection gradient. SSFP sequences with small to moderate flip angles (<40 degrees ) are also shown to preserve the slice profile better than the most commonly used SPGR sequence with constant flip angle (SPGR-CFA). For higher flip angles, the slice profile in SSFP evolves in a manner similar to SPGR-CFA, with depletion of polarization in the center of the slice.

Parallel imaging of hyperpolarized helium-3 with simultaneous slice excitation.

Hyperpolarized (HP) gas imaging of the lungs is an ideal potential application for parallel imaging. This is due to the fact that there is limited scan time (breath hold of 20 s) and limited non-renewable polarization. Reduced phase encode parallel imaging is demanding on hardware in that it requires multiple receivers. In this work, simultaneous parallel acquisition of hyperpolarized (HP) 3He images from multiple slices was demonstrated in phantoms and in vivo using a simultaneous slice excitation method, at a field strength of 1.5 T. The pulse sequence allows simultaneous acquisition of n slices per RF excitation, thus reducing the number of RF pulses needed to fully cover a given volume with multi-slicing. Unlike conventional parallel imaging, this method does not require prior reference scan information, which would consume some of the finite longitudinal polarization in lung ventilation studies with HP gas.

Interleaved pulsed MAMBA: a new parallel slice imaging method.

A method of acquiring slices in parallel is described which uses interleaved sets of pulsed B(0) field coils to generate discrete regions of uniform field within the main magnetic field known as interleaved MAMBA (multiple acquisition micro B(0) array). Simulations of a number of coil designs were performed using the Biot-Savart law. A six-step coil was built and interfaced to a 0.17 T Niche MRI system and the field steps measured using an imaging technique. Measured field steps were in good agreement with the values predicted by simulation. The coil design was then scaled up by a factor of three, interfaced to a 1.5 T whole-body MRI system, and scans of the hands and arms of volunteers were acquired from up to four field steps using standard spin and gradient echo sequences. Images were also acquired simultaneously from two field steps with no frequency encode aliasing and one excitation. The one-dimensional interleaved pulsed MAMBA step field technique shows great promise for enabling many slices to be acquired simultaneously along the axis of the coil for rapid volumetric studies without the need for multiple shot Hadamard encoding. Extension of interleaved coil design to two or three dimensions is feasible, which could provide full spatial coverage combined with ultra-rapid data acquisition.

B1AC-MAMBA: B1 array combined with multiple-acquisition micro B0 array parallel magnetic resonance imaging.

The combination of an in-plane B(1) sensitivity encoding (SENSE) technique with a simultaneous multiple-slice B(0) field step technique (multiple-acquisition micro B(0) array (MAMBA)) has produced high scan time reduction factors (R < or = 8). In this study, two slices were acquired simultaneously in combination with x2 and x4 SENSE in-plane encoding using a MAMBA stepped B(0) field coil inside a four-channel phased-array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal-to-noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. The B(1) array combined with MAMBA (B(1)AC-MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole-body screening for disease.