Theranostic Trigger-Responsive Carbon Monoxide-Generating Microbubbles.

Carbon monoxide (CO) is a gaseous signaling molecule that modulates inflammation, cell survival, and recovery after myocardial infarction. However, handling and dosing of CO as a compressed gas are difficult. Here, light-triggerable and magnetic resonance imaging (MRI)-detectable CO release from dimanganese decacarbonyl (CORM-1) are demonstrated, and the development of CORM-1-loaded polymeric microbubbles (COMB) is described as an ultrasound (US)- and MRI-imageable drug delivery platform for triggerable and targeted CO therapy. COMB are synthesized via a straightforward one-step loading protocol, present a narrow size distribution peaking at 2 µm, and show excellent performance as a CORM-1 carrier and US contrast agent. Light irradiation of COMB induces local production and release of CO, as well as enhanced longitudinal and transversal relaxation rates, enabling MRI monitoring of CO delivery. Proof-of-concept studies for COMB-enabled light-triggered CO release show saturation of hemoglobin with CO in human blood, anti-inflammatory differentiation of macrophages, reduction of hypoxia-induced reactive oxygen species (ROS) production, and inhibition of ischemia-induced apoptosis in endothelial cells and cardiomyocytes. These findings indicate that CO-generating MB are interesting theranostic tools for attenuating hypoxia-associated and ROS-mediated cell and tissue damage in cardiovascular disease.

Confounding factors in breast magnetic resonance fingerprinting: B1+ , slice profile, and diffusion effects.

PURPOSE: Magnetic resonance fingerprinting (MRF) offers rapid quantitative imaging but may be subject to confounding effects (CE) if these are not included in the model-based reconstruction. This study characterizes the influence of in-plane B1+ , slice profile and diffusion effects on T1 and T2 estimation in the female breast at 1.5T. METHODS: Simulations were used to predict the influence of each CE on the accuracy of MRF and to investigate the influence of electronic noise and spiral aliasing artefacts. The experimentally observed bias in regions of fibroglandular tissue (FGT) and fatty tissue (FT) was analyzed for undersampled spiral breast MRF data of 6 healthy volunteers by performing MRF reconstruction with and without a CE. RESULTS: Theoretic analysis predicts T1 under-/T2 overestimation if the nominal flip angles are underestimated and inversely, T1 under-/T2 overestimation if omitting slice profile correction, and T1 under-/T2 underestimation if omitting diffusion in the signal model. Averaged over repeated signal simulations, including spiral aliasing artefacts affected precision more than accuracy. Strong in-plane B1+ effects occurred in vivo, causing T2 left-right inhomogeneity between both breasts. Their correction decreased the T2 difference from 29 to 5 ms in FGT and from 29 to 9 ms in FT. Slice profile correction affected FGT T2 most strongly, resulting in -22% smaller values. For the employed spoiler gradient strengths, diffusion did not affect the parameter maps, corresponding well with theoretic predictions. CONCLUSION: Understanding CEs and their relative significance for an MRF sequence is important when defining an MRF signal model for accurate parameter mapping.

Spiral blurring correction with water-fat separation for magnetic resonance fingerprinting in the breast.

PURPOSE: Magnetic resonance fingerprinting (MRF) with spiral readout enables rapid quantification of tissue relaxation times. However, it is prone to blurring because of off-resonance effects. Hence, fat blurring into adjacent regions might prevent identification of small tumors by their quantitative T1 and T2 values. This study aims to correct for the blurring artifacts, thereby enabling fast quantitative mapping in the female breast. METHODS: The impact of fat blurring on spiral MRF results was first assessed by simulations. Then, MRF was combined with 3-point Dixon water-fat separation and spiral blurring correction based on conjugate phase reconstruction. The approach was assessed in phantom experiments and compared to Cartesian reference measurements, namely inversion recovery (IR), multi-echo spin echo (MESE), and Cartesian MRF, by normalized root-mean-square error (NRMSE) and SD calculations. Feasibility is further demonstrated in vivo for quantitative breast measurements of 6 healthy female volunteers, age range 24-31 y. RESULTS: In the phantom experiment, the blurring correction reduced the NRMSE per phantom vial on average from 16% to 8% for T1 and from 18% to 11% for T2 when comparing spiral MRF to IR/MESE sequences. When comparing to Cartesian MRF, the NRMSE reduced from 15% to 8% for T1 and from 12% to 7% for T2 . Furthermore, SDs decreased. In vivo, the blurring correction removed fat bias on T1 /T2 from a rim of ~7-8 mm width adjacent to fatty structures. CONCLUSION: The blurring correction for spiral MRF yields improved quantitative maps in the presence of water and fat.

(Hybrid) SPECT and PET Technologies.

SPECT and PET are nuclear tomographic imaging modalities that visualize functional information based on the accumulation of radioactive tracer molecules. However, SPECT and PET lack anatomical information, which has motivated their combination with an anatomical imaging modality such as CT or MRI. This chapter begins with an overview over the fundamental physics of SPECT and PET followed by a presentation of the respective detector technologies, including detection requirements, principles and different detector concepts. The reader is subsequently provided with an introduction into hybrid imaging concepts, before a dedicated section presents the challenges that arise when hybridizing SPECT or PET with MRI, namely, mutual distortions of the different electromagnetic fields in MRI on the nuclear imaging system and vice versa. The chapter closes with an overview about current hybrid imaging systems of both clinical and preclinical kind. Finally, future developments in hybrid SPECT and PET technology are discussed.

RF shielding materials for highly-integrated PET/MRI systems.

Integration of magnetic resonance imaging (MRI) and positron emission tomography (PET) into a simultaneous device calls for adaptations of the radio frequency (RF) shielding concept. Conventional PET module housings fully encase the entire PET detector to reduce mutual interference. Excluding passive components, i.e. scintillators, from the housings, offers integration advantages, e.g. by reducing the overall housing volume or utilizing bigger scintillators. However, locating the scintillator outside of the RF shielding requires an optically transparent RF shielding interface between the scintillators and the photodetector to close the aperture. Therefore, a careful evaluation and selection of RF materials is essential to ensure an excellent PET/MRI system performance. To this end, we examined 10 materials (coated glasses, coated foils, meshes). The shielding effectiveness (SE) was evaluated at 100 and 300 MHz. PET performance was tested for single event registration and coincident events by integrating the material into the PET detector stack between the digital silicon photomultiplier photodetector array and one-to-one coupled scintillator. We determined photon attenuation (PA), energy resolution (dE/E), and coincidence resolving time (CRT) and compared to reference measurements for each material group. MRI compatibility was assessed by analyzing the material influence on the main magnetic field (B0) homogeneity. The coated glasses and foils exhibited SEs of up to 25 dB at 300 MHz. Both had a PA < 23% with dE/E and CRT comparable to the reference measurements, and no measurable impact on the B0field was registered. The meshes exhibited higher SEs up to 56 dB, but also a PA > 58% with a higher impact on dE/E and CRT. Only one mesh affected B0homogeneity. Overall, we recommend the coated foil HS 9400 for integration concepts as it exhibited a good performance with SE = 25 dB, PA = 22%, resulting in a PET performance of dE/E = 12% and CRT = 274 ps.

Evaluation of the radiofrequency performance of a wide-bore 1.5 T positron emission tomography/magnetic resonance imaging body coil for radiotherapy planning.

BACKGROUND AND PURPOSE: The restricted bore diameter of current simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) systems can be an impediment to achieving similar patient positioning during PET/MRI planning and radiotherapy. Our goal was to evaluate the B1 transmit (B1 +) uniformity, B1 + efficiency, and specific absorption rate (SAR) of a novel radiofrequency (RF) body coil design, in which RF shielded PET detectors were integrated with the specific aim of enabling a wide-bore PET/MRI system. MATERIALS AND METHODS: We designed and constructed a wide-bore PET/MRI RF body coil to be integrated with a clinical MRI system. To increase its inner bore diameter, the PET detectors were positioned between the conductors and the RF shield of the RF body coil. Simulations and experiments with phantoms and human volunteers were performed to compare the B1 + uniformity, B1 + efficiency, and SAR between our design and the clinical body coil. RESULTS: In the simulations, our design achieved nearly the same B1 + field uniformity as the clinical body coil and an almost identical SAR distribution. The uniformity findings were confirmed by the physical experiments. The B1 + efficiency was 38% lower compared to the clinical body coil. CONCLUSIONS: To achieve wide-bore PET/MRI, it is possible to integrate shielding for PET detectors between the body coil conductors and the RF shield without compromising MRI performance. Reduced B1 + efficiency may be compensated by adding a second RF amplifier. This finding may facilitate the application of simultaneous whole-body PET/MRI in radiotherapy planning.

MR image corrections for PET-induced gradient distortions.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) by using PET inserts in existing MRI scanners is an attractive approach. When designing the PET insert, mutual influences of both imaging modalities need to be minimized. The gradient magnetic fields induce eddy currents in all conductive components of the PET insert. Eddy currents produce superimposing magnetic fields distorting the gradient magnetic field. However, the gradient magnetic fields determine how the MRI data is acquired in the k-space. A distorted gradient shape produces a distorted k-space trajectory which then results in a distorted image. The dynamic performance of the gradient system can be characterized by measuring its gradient impulse response function (GIRF). Knowledge of the GIRF enables to correct the k-space trajectory and thereby enables to reduce image distortions. We characterized the influence of a preclinical PET insert, i.e. the Hyperion IID, on the gradient performance of a 3 T MRI scanner. The GIRFs up to the second order spherical harmonics were determined with and without the PET insert by measuring frequency-swept gradient pulses with an NMR probe. We calculated a corrected k-space trajectory of a single-shot spiral sequence using the measured GIRFs. The low-pass characteristic of the gradient system only slightly increased in the presence of the PET insert. We showed a minor influence of the PET insert on the GIRFs, demonstrating the high gradient transparency of the PET insert. The single-shot spiral image measured in the presence of the PET insert and reconstructed with the uncorrected k-space trajectory was blurred and distorted. We strongly reduced the blurring and distortion by using the corrected k-space trajectory predicted with the measured GIRFs up to the first order spherical harmonics. Slight blurring remained in the corrected image caused by either second order spherical harmonics or distortions of the static magnetic field.

MR and PET-CT monitoring of tissue-engineered vascular grafts in the ovine carotid artery.

The modification of biomaterials to comply with clinically employed monitoring techniques is a promising strategy to support clinical translation in regenerative medicine. Here, multimodal imaging of tissue-engineered vascular grafts (TEVG) was enabled by functionalizing the textile scaffold with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The resulting MR-imageable grafts (iTEVG) were monitored non-invasively throughout their whole life-cycle, from initial quality control to longitudinal functional evaluation in an ovine model for up to 8 weeks. Crucial features such as the complete embedding of the textile mesh in the developing tissue and the grafts' structural stability were assessed in vitro using 1T-, 3T- and 7T-MRI scanners. In vivo, the grafts were imaged by 3T-MRI and PET-CT. Contrary to unlabeled constructs, iTEVG could be delineated from native arteries and precisely localized by MRI. USPIO labeling neither induced calcifications, nor negatively affected their remodeling with respect to tissue-specific extracellular matrix composition and endothelialization. Functionality was confirmed by MR-angiography. 18F-FDG uptake (assessed via PET-CT) indicated only transient post-surgical inflammation. In conclusion, USPIO-labeling enables accurate localization of TEVG and opens up opportunities for multimodal imaging approaches to assess transplant acceptance and function. Thereby, it can support clinical decision-making on the need for further pharmacological or surgical interventions.

Characterization methods for comprehensive evaluations of shielding materials used in an MRI.

PURPOSE: In order to integrate electronic devices into a magnetic resonance imaging (MRI) scanner, shielding of the electronics with respect to the radio frequency (RF) transmit and receive system of the MRI scanner is required. Furthermore, MRI uses time-varying low-frequency magnetic fields for spatial encoding, i.e., the gradient magnetic fields. Time-varying magnetic fields induce eddy currents in all conductive elements. The eddy currents result in opposing magnetic fields, which can cause distortions of the magnetic resonance (MR) image. As shielding of lower frequencies is not feasible in this respect, an ideal shielding element should be transparent for gradient magnetic fields while providing a high RF shielding effectiveness. Furthermore, it should offer a low susceptibility to prevent distortion of the main magnetic field of the MRI. In this work, we characterize the aforesaid shielding parameters of different shielding samples. METHODS: We developed a nuclear magnetic resonance (NMR) probe to measure the magnetic fields to quantify the field distortions time-resolvedly. The relative distortion was introduced as a proportionality constant relating the eddy-current-inducing field changes and the field distortions. The relative distortion was measured in the frequency range from 0 to 10 kHz for all shielding samples using the NMR probe. We characterized the shielding effectiveness of the samples in the frequency range from 1 to 150 MHz using a network analyzer. We conducted all measurements with three different materials, two carbon fiber composites and copper, each in various thicknesses. RESULTS: The relative distortion of the magnetic fields induced by the carbon fiber composites samples was at least a factor of seven lower than the copper sample. A linear dependency on the sample thickness was measured for the main field distortion, the relative distortion and the shielding effectiveness. The relative distortion was roughly independent of the gradient frequency contrary to the shielding effectiveness, highly depending on the RF frequency. CONCLUSIONS: We presented a very sensitive method to characterize the distortion of the main field distortion and the gradient transparency using an NMR probe. We analyzed different shielding materials regarding the main field distortion, the gradient transparency, and the shielding effectiveness. From the tested materials, we identified a carbon fiber composite with the lowest distortion on the MRI.

Maximum likelihood positioning algorithm for high-resolution PET scanners.

PURPOSE: In high-resolution positron emission tomography (PET), lightsharing elements are incorporated into typical detector stacks to read out scintillator arrays in which one scintillator element (crystal) is smaller than the size of the readout channel. In order to identify the hit crystal by means of the measured light distribution, a positioning algorithm is required. One commonly applied positioning algorithm uses the center of gravity (COG) of the measured light distribution. The COG algorithm is limited in spatial resolution by noise and intercrystal Compton scatter. The purpose of this work is to develop a positioning algorithm which overcomes this limitation. METHODS: The authors present a maximum likelihood (ML) algorithm which compares a set of expected light distributions given by probability density functions (PDFs) with the measured light distribution. Instead of modeling the PDFs by using an analytical model, the PDFs of the proposed ML algorithm are generated assuming a single-gamma-interaction model from measured data. The algorithm was evaluated with a hot-rod phantom measurement acquired with the preclinical hyperion II (D) PET scanner. In order to assess the performance with respect to sensitivity, energy resolution, and image quality, the ML algorithm was compared to a COG algorithm which calculates the COG from a restricted set of channels. The authors studied the energy resolution of the ML and the COG algorithm regarding incomplete light distributions (missing channel information caused by detector dead time). Furthermore, the authors investigated the effects of using a filter based on the likelihood values on sensitivity, energy resolution, and image quality. RESULTS: A sensitivity gain of up to 19% was demonstrated in comparison to the COG algorithm for the selected operation parameters. Energy resolution and image quality were on a similar level for both algorithms. Additionally, the authors demonstrated that the performance of the ML algorithm is less prone to missing channel information. A likelihood filter visually improved the image quality, i.e., the peak-to-valley increased up to a factor of 3 for 2-mm-diameter phantom rods by rejecting 87% of the coincidences. A relative improvement of the energy resolution of up to 12.8% was also measured rejecting 91% of the coincidences. CONCLUSIONS: The developed ML algorithm increases the sensitivity by correctly handling missing channel information without influencing energy resolution or image quality. Furthermore, the authors showed that energy resolution and image quality can be improved substantially by rejecting events that do not comply well with the single-gamma-interaction model, such as Compton-scattered events.