Bimodal Interventional Instrument Markers for Magnetic Particle Imaging and Magnetic Resonance Imaging-A Proof-of-Concept Study.

The purpose of this work was to develop instrument markers that are visible in both magnetic particle imaging (MPI) and magnetic resonance imaging (MRI). The instrument markers were based on two different magnetic nanoparticle types (synthesized in-house KLB and commercial Bayoxide E8706). Coatings containing one of both particle types were fabricated and measured with a magnetic particle spectrometer (MPS) to estimate their MPI performance. Coatings based on both particle types were then applied on a segment of a nonmetallic guidewire. Imaging experiments were conducted using a commercial, preclinical MPI scanner and a preclinical 1 tesla MRI system. MPI image reconstruction was performed based on system matrices measured with dried KLB and Bayoxide E8706 coatings. The bimodal markers were clearly visible in both methods. They caused circular signal voids in MRI and areas of high signal intensity in MPI. Both the signal voids as well as the areas of high signal intensity were larger than the real marker size. Images that were reconstructed with a Bayoxide E8706 system matrix did not show sufficient MPI signal. Instrument markers with bimodal visibility are essential for the perspective of monitoring cardiovascular interventions with MPI/MRI hybrid systems.

Statistically Segregated k-Space Sampling for Accelerating Multiple-Acquisition MRI.

A central limitation of multiple-acquisition magnetic resonance imaging (MRI) is the degradation in scan efficiency as the number of distinct datasets grows. Sparse recovery techniques can alleviate this limitation via randomly undersampled acquisitions. A frequent sampling strategy is to prescribe for each acquisition a different random pattern drawn from a common sampling density. However, naive random patterns often contain gaps or clusters across the acquisition dimension that, in turn, can degrade reconstruction quality or reduce scan efficiency. To address this problem, a statistically segregated sampling method is proposed for multiple-acquisition MRI. This method generates multiple patterns sequentially while adaptively modifying the sampling density to minimize k-space overlap across patterns. As a result, it improves incoherence across acquisitions while still maintaining similar sampling density across the radial dimension of k-space. Comprehensive simulations and in vivo results are presented for phase-cycled balanced steady-state free precession and multi-echo [Formula: see text]-weighted imaging. Segregated sampling achieves significantly improved quality in both Fourier and compressed-sensing reconstructions of multiple-acquisition datasets.

Projection onto Epigraph Sets for Rapid Self-Tuning Compressed Sensing MRI.

The compressed sensing (CS) framework leverages the sparsity of MR images to reconstruct from the undersampled acquisitions. CS reconstructions involve one or more regularization parameters that weigh sparsity in transform domains against fidelity to acquired data. While parameter selection is critical for reconstruction quality, the optimal parameters are subject and dataset specific. Thus, commonly practiced heuristic parameter selection generalizes poorly to independent datasets. Recent studies have proposed to tune parameters by estimating the risk of removing significant image coefficients. Line searches are performed across the parameter space to identify the parameter value that minimizes this risk. Although effective, these line searches yield prolonged reconstruction times. Here, we propose a new self-tuning CS method that uses computationally efficient projections onto epigraph sets of the l1 and total-variation norms to simultaneously achieve parameter selection and regularization. In vivo demonstrations are provided for balanced steady-state free precession, time-of-flight, and T1-weighted imaging. The proposed method achieves an order of magnitude improvement in computational efficiency over line-search methods while maintaining near-optimal parameter selection.

Seeing SPIOs Directly In Vivo with Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is a new molecular imaging technique that directly images superparamagnetic tracers with high image contrast and sensitivity approaching nuclear medicine techniques-but without ionizing radiation. Since its inception, the MPI research field has quickly progressed in imaging theory, hardware, tracer design, and biomedical applications. Here, we describe the history and field of MPI, outline pressing challenges to MPI technology and clinical translation, highlight unique applications in MPI, and describe the role of the WMIS MPI Interest Group in collaboratively advancing MPI as a molecular imaging technique. We invite interested investigators to join the MPI Interest Group and contribute new insights and innovations to the MPI field.

Low drive field amplitude for improved image resolution in magnetic particle imaging.

PURPOSE: Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. METHODS: The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. RESULTS: The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. CONCLUSIONS: To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast.

Effects of pulse duration on magnetostimulation thresholds.

PURPOSE: Medical imaging techniques such as magnetic resonance imaging and magnetic particle imaging (MPI) utilize time-varying magnetic fields that are subject to magnetostimulation limits, which often limit the speed of the imaging process. Various human-subject experiments have studied the amplitude and frequency dependence of these thresholds for gradient or homogeneous magnetic fields. Another contributing factor was shown to be number of cycles in a magnetic pulse, where the thresholds decreased with longer pulses. The latter result was demonstrated on two subjects only, at a single frequency of 1.27 kHz. Hence, whether the observed effect was due to the number of cycles or due to the pulse duration was not specified. In addition, a gradient-type field was utilized; hence, whether the same phenomenon applies to homogeneous magnetic fields remained unknown. Here, the authors investigate the pulse duration dependence of magnetostimulation limits for a 20-fold range of frequencies using homogeneous magnetic fields, such as the ones used for the drive field in MPI. METHODS: Magnetostimulation thresholds were measured in the arms of six healthy subjects (age: 27 ± 5 yr). Each experiment comprised testing the thresholds at eight different pulse durations between 2 and 125 ms at a single frequency, which took approximately 30-40 min/subject. A total of 34 experiments were performed at three different frequencies: 1.2, 5.7, and 25.5 kHz. A solenoid coil providing homogeneous magnetic field was used to induce stimulation, and the field amplitude was measured in real time. A pre-emphasis based pulse shaping method was employed to accurately control the pulse durations. Subjects reported stimulation via a mouse click whenever they felt a twitching/tingling sensation. A sigmoid function was fitted to the subject responses to find the threshold at a specific frequency and duration, and the whole procedure was repeated at all relevant frequencies and pulse durations. RESULTS: The magnetostimulation limits decreased with increasing pulse duration (T(pulse)). For T(pulse) < 18 ms, the thresholds were significantly higher than at the longest pulse durations (p < 0.01, paired Wilcoxon signed-rank test). The normalized magnetostimulation threshold (B(Norm)) vs duration curve at all three frequencies agreed almost identically, indicating that the observed effect is independent of the operating frequency. At the shortest pulse duration (T(pulse) ≈ 2 ms), the thresholds were approximately 24% higher than at the asymptotes. The thresholds decreased to within 4% of their asymptotic values for T(pulse) > 20 ms. These trends were well characterized (R(2) = 0.78) by a stretched exponential function given by B(Norm)=1+αe(-T(pulse)/ß(γ)) , where the fitted parameters were α = 0.44, ß = 4.32, and γ = 0.60. CONCLUSIONS: This work shows for the first time that the magnetostimulation thresholds decrease with increasing pulse duration, and that this effect is independent of the operating frequency. Normalized threshold vs duration trends are almost identical for a 20-fold range of frequencies: the thresholds are significantly higher at short pulse durations and settle to within 4% of their asymptotic values for durations longer than 20 ms. These results emphasize the importance of matching the human-subject experiments to the imaging conditions of a particular setup. Knowing the dependence of the safety limits to all contributing factors is critical for increasing the time-efficiency of imaging systems that utilize time-varying magnetic fields.

Magnetic particle imaging with tailored iron oxide nanoparticle tracers.

Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2(∗) -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

Magnetostimulation limits in magnetic particle imaging.

For magnetic particle imaging (MPI), specific absorption rate (SAR) and more critically magnetostimulation (i.e., dB/dt) safety limits will determine the optimal scan parameters, such as the drive field strength and frequency. These parameters will impact the scanning speed, field-of-view (FOV) and signal-to-noise ratio in MPI. Understanding the potential safety hazards of the drive field is critical for scaling MPI for human use. In this work, we demonstrate that magnetostimulation is the primary magnetic safety consideration in MPI, and we describe the first human-subject magnetostimulation threshold experiments for MPI using homogeneous coils. Our experiments, performed on the arm and leg, indicate that magnetostimulation thresholds monotonically decrease with increasing frequency. Additionally, we show for the first time that a strong inverse correlation exists between the threshold and the body part size. The chronaxie time, on the other hand, did not vary with body part size. We conclude with an estimation of the magnetostimulation thresholds for a full-body MPI scanner: a mean asymptotic threshold of 14.3 mT-pp (peak-to-peak) with a mean chronaxie time of 289 µs, which correspond to a magnetostimulation threshold of about 15 mT-pp for frequencies between 25 and 50 kHz. These findings will have a great impact on the optimization of MPI parameters, especially in determining the number of partial FOVs required to cover a region of interest.

High-resolution diffusion-weighted imaging for monitoring breast cancer treatment response.

RATIONALE AND OBJECTIVES: The aim of this work was to compare a high-resolution diffusion-weighted imaging (HR-DWI) acquisition (voxel size = 4.8 mm(3)) to a standard diffusion-weighted imaging (STD-DWI) acquisition (voxel size = 29.3 mm(3)) for monitoring neoadjuvant therapy-induced changes in breast tumors. MATERIALS AND METHODS: Nine women with locally advanced breast cancer were imaged with both HR-DWI and STD-DWI before and after 3 weeks (early treatment) of neoadjuvant taxane-based treatment. Tumor apparent diffusion coefficient (ADC) metrics (mean and histogram percentiles) from both DWI methods were calculated, and their relationship to tumor volume change after 12 weeks of treatment (posttreatment) measured by dynamic contrast enhanced magnetic resonance imaging was evaluated with a Spearman's rank correlation. RESULTS: The HR-DWI pretreatment 15th percentile tumor ADC (P = .03) and early treatment 15th, 25th, and 50th percentile tumor ADCs (P = .008, .010, .04, respectively) were significantly lower than the corresponding STD-DWI percentile ADCs. The mean tumor HR-ADC was significantly lower than STD-ADC at the early treatment time point (P = .02), but not at the pretreatment time point (P = .07). A significant early treatment increase in tumor ADC was found with both methods (P < .05). Correlations between HR-DWI tumor ADC and posttreatment tumor volume change were higher than the STD-DWI correlations at both time points and the lower percentile ADCs had the strongest correlations. CONCLUSION: These initial results suggest that the HR-DWI technique has potential for improving characterization of low tumor ADC values over STD-DWI and that HR-DWI may be of value in evaluating tumor change with treatment.

Linearity and shift invariance for quantitative magnetic particle imaging.

Magnetic Particle Imaging (MPI) is a promising tracer imaging modality that employs a kidney-safe contrast agent and does not use ionizing radiation. MPI already shows high contrast and sensitivity in small animal imaging, with great potential for many clinical applications, including angiography, cancer detection, inflammation imaging, and treatment monitoring. Currently, almost all clinically relevant imaging techniques can be modeled as systems with linearity and shift invariance (LSI), characteristics crucial for quantification and diagnostic utility. In theory, MPI has been proven to be LSI. However, in practice, high-pass filters designed to remove unavoidable direct feedthrough interference also remove information crucial to ensuring LSI in MPI scans. In this work, we present a complete theoretical and experimental description of the image artifacts from filtering. We then propose and validate a robust algorithm to completely restore the lost information for the x-space MPI method. We provide the theoretical, simulated, and experimental proof that our algorithm indeed restores the LSI properties of MPI.

Magnetic particle imaging (MPI) for NMR and MRI researchers.

Magnetic Particle Imaging (MPI) is a new tracer imaging modality that is gaining significant interest from NMR and MRI researchers. While the physics of MPI differ substantially from MRI, it employs hardware and imaging concepts that are familiar to MRI researchers, such as magnetic excitation and detection, pulse sequences, and relaxation effects. Furthermore, MPI employs the same superparamagnetic iron oxide (SPIO) contrast agents that are sometimes used for MR angiography and are often used for MRI cell tracking studies. These SPIOs are much safer for humans than iodine or gadolinium, especially for Chronic Kidney Disease (CKD) patients. The weak kidneys of CKD patients cannot safely excrete iodine or gadolinium, leading to increased morbidity and mortality after iodinated X-ray or CT angiograms, or after gadolinium-MRA studies. Iron oxides, on the other hand, are processed in the liver, and have been shown to be safe even for CKD patients. Unlike the "black blood" contrast generated by SPIOs in MRI due to increased T2* dephasing, SPIOs in MPI generate positive, "bright blood" contrast. With this ideal contrast, even prototype MPI scanners can already achieve fast, high-sensitivity, and high-contrast angiograms with millimeter-scale resolutions in phantoms and in animals. Moreover, MPI shows great potential for an exciting array of applications, including stem cell tracking in vivo, first-pass contrast studies to diagnose or stage cancer, and inflammation imaging in vivo. So far, only a handful of prototype small-animal MPI scanners have been constructed worldwide. Hence, MPI is open to great advances, especially in hardware, pulse sequence, and nanoparticle improvements, with the potential to revolutionize the biomedical imaging field.

Diffusion tensor imaging and T2 relaxometry of bilateral lumbar nerve roots: feasibility of in-plane imaging.

Lower back pain is a common problem frequently encountered without specific biomarkers that correlate well with an individual patient's pain generators. MRI quantification of diffusion and T2 relaxation properties may provide novel insight into the mechanical and inflammatory changes that occur in the lumbosacral nerve roots in patients with lower back pain. Accurate imaging of the spinal nerve roots is difficult because of their small caliber and oblique course in all three planes. Two-dimensional in-plane imaging of the lumbosacral nerve roots requires oblique coronal imaging with large field of view (FOV) in both dimensions, resulting in severe geometric distortions using single-shot echo planar imaging (EPI) techniques. The present work describes initial success using a reduced-FOV single-shot spin-echo EPI acquisition to obtain in-plane diffusion tensor imaging (DTI) and T2 mapping of the bilateral lumbar nerve roots at the L4 level of healthy subjects, minimizing partial volume effects, breathing artifacts and geometric distortions. A significant variation in DTI and T2 mapping metrics is also reported along the course of the normal nerve root. The fractional anisotropy is statistically significantly lower in the dorsal root ganglia (0.287 ± 0.068) than in more distal regions in the spinal nerve (0.402 ± 0.040) (p < 10(-5) ). The T2 relaxation value is statistically significantly higher in the dorsal root ganglia (78.0 ± 11.9 ms) than in more distal regions in the spinal nerve (59.5 ± 7.4 ms) (p < 10(-5) ). The quantification of nerve root DTI and T2 properties using the proposed methodology may identify the specific site of any degenerative and inflammatory changes along the nerve roots of patients with lower back pain.

Projection x-space magnetic particle imaging.

Projection magnetic particle imaging (MPI) can improve imaging speed by over 100-fold over traditional 3-D MPI. In this work, we derive the 2-D x-space signal equation, 2-D image equation, and introduce the concept of signal fading and resolution loss for a projection MPI imager. We then describe the design and construction of an x-space projection MPI scanner with a field gradient of 2.35 T/m across a 10 cm magnet free bore. The system has an expected resolution of 3.5 × 8.0 mm using Resovist tracer, and an experimental resolution of 3.8 × 8.4 mm resolution. The system images 2.5 cm × 5.0 cm partial field-of views (FOVs) at 10 frames/s, and acquires a full field-of-view of 10 cm × 5.0 cm in 4 s. We conclude by imaging a resolution phantom, a complex "Cal" phantom, mice injected with Resovist tracer, and experimentally confirm the theoretically predicted x-space spatial resolution.

High-resolution diffusion-weighted magnetic resonance imaging in patients with locally advanced breast cancer.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate differences in tumor depiction and measured tumor apparent diffusion coefficient (ADC) with the use of a high-resolution diffusion-weighted (DW) magnetic resonance imaging (MRI) sequence, compared to a standard DW MRI sequence, in patients with locally advanced breast cancer. MATERIALS AND METHODS: Patients with locally advanced breast cancer were scanned with a reduced-field of view (rFOV) DW MRI sequence (high resolution) and a standard-field of view diffusion sequence (standard resolution), and differences between the two sequences were evaluated quantitatively (by calculating tumor ADC distribution parameters) and qualitatively (by radiologists' visual assessments of images). RESULTS: Although the mean tumor ADC for both sequences was similar, differences were found in other parameters, including the 12.5th percentile (P = .042) and minimum tumor ADC (P = .003). Qualitatively, visualization of tumor morphologic detail, heterogeneity, and conspicuity was improved with rFOV DW MRI, and image quality was higher. CONCLUSIONS: Differences in ADC distribution parameters and qualitative image features suggest that the sequences differ in their ability to capture tumor heterogeneity. These differences are not apparent when the mean is used to evaluate tumor ADC. In particular, differences found in lower ADC values are compatible with reduced partial voluming in rFOV DW MRI, suggesting that rFOV DW MRI may be valuable in imaging the lower ADCs expected to correspond to viable tumor in most invasive breast cancers.

Signal compensation and compressed sensing for magnetization-prepared MR angiography.

Magnetization-prepared acquisitions offer a trade-off between image contrast and scan efficiency for magnetic resonance imaging. Because the prepared signals gradually decay, the contrast can be improved by frequently repeating the preparation, which in turn significantly increases the scan time. A common solution is to perform the data collection progressing from low- to high-spatial-frequency samples following each preparation. Unfortunately, this leads to loss of spatial resolution, and thereby image blurring. In this work, a new technique is proposed that first corrects the signal decay in high-frequency data to mitigate the resolution loss and improve the image contrast without reducing the scan efficiency. The proposed technique then employs a sparsity-based nonlinear reconstruction to further improve the image quality. In addition to reducing the amplified high-frequency noise, this reconstruction extrapolates missing k-space samples in the case of undersampled compressed-sensing acquisitions. The technique is successfully demonstrated for noncontrast-enhanced flow-independent angiography of the lower extremities, an application that substantially benefits from both the signal compensation and the nonlinear reconstruction.

SNR dependence of optimal parameters for apparent diffusion coefficient measurements.

Optimizing the diffusion-weighted imaging (DWI) parameters (i.e., the b-value and the number of image averages) to the tissue of interest is essential for producing high-quality apparent diffusion coefficient (ADC) maps. Previous investigation of this optimization was performed assuming Gaussian noise statistics for the ADC map, which is only valid for high signal-to-noise ratio (SNR) imaging. In this work, the true statistics of the noise in ADC maps are derived, followed by an optimization of the DWI parameters as a function of the imaging SNR. Specifically, it is demonstrated that the optimum b-value is a monotonically increasing function of the imaging SNR, which converges to the optimum b-value from previously proposed approaches for high-SNR cases, while exhibiting a significant deviation from this asymptote for low-SNR situations. Incorporating the effects of T(2) weighting further increases the SNR dependence of the optimal parameters. The proposed optimization scheme is particularly important for high-resolution DWI, which intrinsically suffers from low SNR and therefore cannot afford the use of the conventional high b-values. Comparison scans were performed for high-resolution DWI of the spinal cord, demonstrating the improvements in the resulting images and the ADC maps achieved by this method.

Full-brain coverage and high-resolution imaging capabilities of passband b-SSFP fMRI at 3T.

Passband balanced-steady-state free precession (b-SSFP) fMRI is a recently developed method that utilizes the passband (flat portion) of the b-SSFP off-resonance response to measure MR signal changes elicited by changes in tissue oxygenation following increases in neuronal activity. Rapid refocusing and short readout durations of b-SSFP, combined with the relatively large flat portion of the b-SSFP off-resonance spectrum allows distortion-free full-brain coverage with only two acquisitions. This allows for high-resolution functional imaging, without the spatial distortion frequently encountered in conventional high-resolution functional images. Finally, the 3D imaging compatibility of the b-SSFP acquisitions permits isotropic-voxel-size high-resolution acquisitions. In this study we address some of the major technical issues involved in obtaining passband b-SSFP-based functional brain images with practical imaging parameters and demonstrate the advantages through breath-holding and visual field mapping experiments.