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Objective Magnetic resonance imaging is the standard imaging modality to assess articular cartilage. As the imaging surrogate of degenerative joint disease, cartilage thickness is commonly quantified after tissue segmentation. In lack of a standard method, this study systematically compared five methods for automatic cartilage thickness measurements across the knee joint and as a function of region and sub-region: 3D mesh normals (3D-MN), 3D nearest neighbors (3D-NN), 3D ray tracing (3D-RT), 2D centerline normals (2D-CN), and 2D surface normals (2D-SN). Design Based on the manually segmented femoral and tibial cartilage of 507 human knee joints, mean cartilage thickness was computed for the entire femorotibial joint, 4 joint regions, and 20 subregions using these methods. Inter-method comparisons of mean cartilage thickness and computation times were performed by one-way analysis of variance (ANOVA), Bland-Altman analyses and Lin’s concordance correlation coefficient (CCC). Results Mean inter-method differences in cartilage thickness were significant in nearly all subregions ( P < 0.001). By trend, mean differences were smallest between 3D-MN and 2D-SN in most (sub)regions, which is also reflected by highest quantitative inter-method agreement and CCCs. 3D-RT was prone to severe overestimation of up to 2.5 mm. 3D-MN, 3D-NN, and 2D-SN required mean processing times of ≤5.3 s per joint and were thus similarly efficient, whereas the time demand of 2D-CN and 3D-RT was much larger at 133 ± 29 and 351 ± 10 s per joint ( P < 0.001). Conclusions In automatic cartilage thickness determination, quantification accuracy and computational burden are largely affected by the underlying method. Mesh and surface normals or nearest neighbor searches should be used because they accurately capture variable geometries while being time-efficient.

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.

PURPOSE: Magnetic Resonance Fingerprinting (MRF) with spiral readout enables rapid quantification of tissue relaxation times. However, it is prone to blurring due to 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 standard deviation (STD) calculations. Feasibility is further demonstrated in-vivo for quantitative breast measurements of 6 healthy female volunteers, age range 24-31 years. 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, STDs decreased. In-vivo, the blurring correction removed fat bias on T1/T2 from a rim of about 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., Submitted to Magnetic Resonance in Medicine. 13 pages, 7 figures, 3 tables

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.

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-planeSimulations 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.Theoretic analysis predicts TUnderstanding CEs and their relative significance for an MRF sequence is important when defining an MRF signal model for accurate parameter mapping.

Microbubbles (MB) are used as ultrasound (US) contrast agents and can be efficiently targeted against markers of angiogenesis and inflammation. Due to their gas core, MB locally alter susceptibilities in magnetic resonance imaging (MRI), but unfortunately, the resulting contrast is low and not sufficient to generate powerful molecular MRI probes. Therefore, we investigated whether a potent molecular MR agent can be generated by encapsulating superparamagnetic iron oxide nanoparticles (SPION) in the polymeric shell of poly (n-butylcyanoacrylate) (PBCA) MB and targeted them against α vβ3 integrins on the angiogenic vasculature of 4T1 murine breast carcinomas. SPION-MB consist of an air core and a multi-layered polymeric shell enabling efficient entrapment of SPION. The mean size of SPION-MB was 1.61 ± 0.32 μm. Biotin-streptavidin coupling was employed to functionalize the SPION-MB with cyclic RGDfK (Arg-Gly-Asp) and RADfK (Arg-Ala-Asp) peptides. Cells incubated with RGD-SPION-MB showed enhanced transverse relaxation rates compared with SPION-MB and blocking α vβ3 integrin receptors with excess free cRGDfK significantly reduced RGD-SPION-MB binding. Due to the fast binding of RGD-SPION-MB in vivo , dynamic susceptibility contrast MRI was employed to track their retention in tumors in real-time. Higher retention of RGD-SPION-MB was observed compared with SPION-MB and RAD-SPION-MB. To corroborate our MRI results, molecular US was performed the following day using the destruction-replenishment method. Both imaging modalities consistently indicated higher retention of RGD-SPION-MB in angiogenic vessels compared with SPION-MB and RAD-SPION-MB. Competitive blocking experiments in mice further confirmed that the binding of RGD-SPION-MB to α vβ3 integrin receptors is specific. Overall, this study demonstrates that RGD-SPION-MB can be employed as molecular MR/US contrast agents and are capable of assessing the αvβ3 integrin expression in the neovasculature of malignant tumors.

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.