Integrable Magnetic Fluid Hyperthermia Systems for 3D Magnetic Particle Imaging.

Background: Combining magnetic particle imaging (MPI) and magnetic fluid hyperthermia (MFH) offers the ability to perform localized hyperthermia and magnetic particle imaging-assisted thermometry of hyperthermia treatment. This allows precise regional selective heating inside the body without invasive interventions. In current MPI-MFH platforms, separate systems are used, which require object transfer from one system to another. Here, we present the design, development and evaluation process for integrable MFH platforms, which extends a commercial MPI scanner with the functionality of MFH. Methods: The biggest issue of integrating magnetic fluid hyperthermia platforms into a magnetic particle imaging system is the magnetic coupling of the devices, which induces high voltage in the imaging system, and is harming its components. In this paper, we use a self-compensation approach derived from heuristic algorithms to protect the magnetic particle imaging scanner. The integrable platforms are evaluated regarding electrical and magnetic characteristics, cooling capability, field strength, the magnetic coupling to a replica of the magnetic particle imaging system's main solenoid and particle heating. Results: The MFH platforms generate suitable magnetic fields for the magnetic heating of particles and are compatible with a commercial magnetic particle imaging scanner. In combination with the imaging system, selective heating with a gradient field and steerable heating positioning using the MPI focus fields are possible. Conclusion: The proposed MFH platforms serve as a therapeutic tool to unlock the MFH functionality of a commercial magnetic particle imaging scanner, enabling its use in future preclinical trials of MPI-guided, spatially selective magnetic hyperthermia therapy.

In situ theranostic platform combining highly localized magnetic fluid hyperthermia, magnetic particle imaging, and thermometry in 3D.

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.

Adaptive Micro-liter Fiducials for Pre-clinical MPI and MRI Imaging.

Magnetic Particle imaging (MPI) allows to measure and quantify background-free tracer distribution with a high temporal resolution. Anatomical structures are not displayed in MPI, rendering orientation within a sample error-prone and necessitating co-registration with other imaging modalities such as MRI. To support this challenge, defined external landmarks (fiducials) made from materials visible in each of the imaging modalities respectively were used in this work. Resulting signals can be aligned with the merged image containing both anatomical data and information about the tracer distribution. Defining the optimal fiducial placement is demanding and can drastically impact the 3D MPI-MRI image presentation. Here we present an adaptable 3D-printed fiducial system for preclinical co-registration of MRI and MPI data designed for easy visualisation. Clinical relevance- MPI is a promising imaging modality with many conceivable clinical applications. Simple and reliable co-registration with other imaging modalities will be crucial for a seamless transition into the clinic.

On the application of balanced steady-state free precession to MR microscopy.

OBJECTIVE: The applicability of the balanced steady-state free precession (bSSFP) sequence to the field of MR microscopy was investigated, since the potentially high SNR makes bSSFP attractive. However, particularly at ultra-high magnetic fields, a number of constraints emerge: the frequency sensitivity of the bSSFP signal, the duty cycle of the imaging gradients, and the intrinsic diffusion attenuation of the steady state due to the imaging gradients. MATERIALS AND METHODS: Optimization of the bSSFP sequence was performed on three imaging systems (7 T and 9.4 T) suited for MR microscopy. Since biological samples are often imaged in the very proximity of materials from sample containers/holder or devices such as electrodes, several microscopy phantoms representing such circumstances were fabricated and examined with 3D bSSFP. RESULTS: Artifact-free microscopic bSSFP images could be obtained with voxel sizes down to 16 µm × 16 µm × 78 µm and with an SNR gain of 25% over standard gradient echo images. CONCLUSION: With appropriate choice of phantom materials, optimization of the flip angle to the diffusion-attenuated steady state and protocols considering duty-cycle limitations, bSSFP can be a valuable tool in MR microscopy.

Intrinsic diffusion sensitivity of the balanced steady-state free precession (bSSFP) imaging sequence.

The purpose of this work was to analyze the intrinsic diffusion sensitivity of the balanced steady-state free precession (bSSFP) imaging sequence, meaning the observation of diffusion-induced attenuation of the bSSFP steady-state signal due to the imaging gradients. Although these diffusion effects are usually neglected for most clinical gradient systems, such strong gradient systems are employed for high resolution imaging of small animals or MR Microscopy. The impact on the bSSFP signal of the imaging gradients characterized by their b-values was analyzed with simulations and experiments at a 7T animal scanner using a gradient system with maximum gradient amplitude of approx. 700 mT/m. It was found that the readout gradients have a stronger impact on the attenuation than the phase encoding gradients. Also, as the PE gradients are varying with each repetition interval, the diffusion effects induce strong modulations of the bSSFP signal over the sequence repetition cycles depending on the phase encoding gradient table. It is shown that a signal gain can be obtained through a change of flip angle as a new optimal flip angle maximizing the signal can be defined. The dependency of the diffusion effects on relaxation times and b-values were explored with simulations. The attenuation increases with T2. In conclusion, diffusion attenuation of the bSSFP signal becomes significant for high resolution imaging voxel size (roughly < 100 µm) of long T2 substances.

A battery-driven, low-field NMR unit for thermally and hyperpolarized samples.

OBJECT: The design of a multinuclear low-field NMR unit with variable field strength <6 mT providing accurate spin manipulations and sufficient sensitivity for direct detection of samples in thermal equilibrium to aid parahydrogen-based hyperpolarization experiments. MATERIALS AND METHODS: An optimized, resistive magnet connected to a battery or wall-power driven current source was constructed to provide a magnetic field <6 mT. A digital device connected to a saddle-shaped transmit- and solenoid receive-coil enabled MR signal excitation and detection with up to 10(6) samples/s, controlled by a flexible pulse-programming software. RESULTS: The magnetization of thermally polarized samples at 1.8 and 5.7 mT is detected in a single acquisition with a SNR ≈10(1) and ≈10(2) and a line width of 42 and 32 Hz, respectively. Nuclear spins are manipulated to an uncertainty of ±1° by means of pulses, which can be arranged in an arbitrary combination. As a demonstration, standard experiments for the measurement of relaxation parameters of thermally polarized samples were implemented. The detection of much stronger hyperpolarized signal was exemplified employing parahydrogen. CONCLUSION: Direct detection of thermal and hyperpolarized (1)H-MR signal in a single acquisition and accurate spin manipulations at 1.8 and 5.5 mT were successfully demonstrated.

A continuous-flow, high-throughput, high-pressure parahydrogen converter for hyperpolarization in a clinical setting.

Pure parahydrogen (pH(2) ) is the prerequisite for optimal pH(2) -based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH(2) production on-site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH(2) converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH(2) at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, only ≈45 min of which are required for actual pH(2) conversion. A fast and simple quantification procedure is described. The lifetimes of pH(2) in a glass vial and aluminum storage cylinder are measured to be T(1C) (glass vial) =822 ± 29 min and T(1C) (Al cylinder) =129 ± 36 days, thus providing sufficiently long storage intervals and allowing the application of pH(2) on demand. A dependence of line width on pH(2) enrichment is observed. As examples, (1) H hyperpolarization of pyridine and (13) C hyperpolarization of hydroxyethylpropionate are presented.

On the spin order transfer from parahydrogen to another nucleus.

The hyperpolarization of nuclear spins holds great potential e.g. for biomedical research. Strong signal enhancements have been demonstrated e.g. by transforming the spin order of parahydrogen (pH(2)) to net polarization of a third nucleus (e.g. (13)C) by means of a spin-order-transfer (SOT) sequence. The polarization achieved is vitally dependent on the sequence intervals, which are a function of the J-coupling constants of the molecule to be polarized. How to derive the SOT sequence intervals, the actual values for molecules as well as the (theoretical) polarization yield and robustness, however, are not fully described. In this paper, (a) we provide the methods to obtain the SOT intervals for a given set of J-coupling constants (i.e. of a new hyperpolarization agent); (b) exemplify these methods on molecules from literature, providing the hitherto missing intervals and simulated polarization yield; and (c) assess the robustness of the sequences towards B(1) and J-coupling errors. Close to unity polarization is obtained for all molecules and sequences. Furthermore, the loss of polarization caused by erroneous B(1) and J-coupling constants is reduced by choosing the channel and phase of some pulses in the SOT sequences appropriately.