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The aim of this study was to investigate the diagnostic accuracy and reader confidence for late-gadolinium enhancement (LGE) detection of a novel free-breathing, image-based navigated 3D whole-heart LGE sequence with fat-water separation, compared to a free-breathing motion-corrected 2D LGE sequence in patients with ischemic and non-ischemic cardiomyopathy. Cardiac MRI patients including the respective sequences were retrospectively included. Two independent, blinded readers rated image quality, depiction of segmental LGE and documented acquisition time, SNR, CNR and amount of LGE. Results were compared using the Friedman or the Kruskal-Wallis test. For LGE rating, a jackknife free-response receiver operating characteristic analysis was performed with a figure of merit (FOM) calculation. Forty-two patients were included, thirty-two were examined with a 1.5 T-scanner and ten patients with a 3 T-scanner. The mean acquisition time of the 2D sequence was significantly shorter compared to the 3D sequence (07:12 min vs. 09:24 min; p < 0.001). The 3D scan time was significantly shorter when performed at 3 T compared to 1.5 T (07:47 min vs. 09:50 min; p < 0.001). There were no differences regarding SNR, CNR or amount of LGE. 3D imaging had a significantly higher FOM (0.89 vs. 0.78; p < 0.001). Overall image quality ratings were similar, but 3D sequence ratings were higher for fine anatomical structures. Free-breathing motion-corrected 3D LGE with high isotropic resolution results in enhanced LGE-detection with higher confidence and better delineation of fine structures. The acquisition time for 3D imaging was longer, but may be reduced by performing on a 3 T-scanner., (© 2022. The Author(s).)

Overview: Cardiovascular disease remains a leading cause of death worldwide, with vulnerable plaque rupture the underlying cause of many heart attacks and strokes. Much research is focused on identifying an imaging biomarker to differentiate stable and vulnerable plaque. Magnetic Resonance Imaging (MRI) is a non-ionising and non-invasive imaging modality with excellent soft tissue contrast. However, MRI has relatively low sensitivity (micromolar) for contrast agent detection compared to nuclear imaging techniques. There is also an increasing emphasis on developing MRI probes that are not based on gadolinium chelates because of increasing concerns over associated systemic toxicity and deposits 1 . To address the sensitivity and safety concerns of gadolinium this project focused on the development of a high relaxivity probe based on superparamagnetic iron oxide nanoparticles for the imaging of atherosclerotic plaque with MRI. With development, this may facilitate differentiating stable and vulnerable plaque in vivo. Aim: To develop a range of MRI contrast agents based on superparamagnetic iron oxide nanoparticles (SPIONs), and test them in a murine model of advanced atherosclerosis. Methods: Nanoparticles of four core sizes were synthesised by thermal decomposition and coated with poly(maleicanhydride-alt-1-octadecene) (PMAO), poly(ethyleneimine) (PEI) or alendronate, then characterised for core size, hydrodynamic size, surface potential and relaxivity. On the basis of these results, one candidate was selected for further studies. In vivo studies using 10 nm PMAO-coated SPIONs were performed in ApoE -/- The lead SPION agent consisted of a 10 nm iron oxide core with poly(maleicanhydride-alt-1-octadecene), (-36.21 mV, r ApoE -/- mice were fed a normal chow diet and were not instrumented. Mice were scanned on a 3T MR scanner (Philips Achieva) with the novel SPION contrast agent, and an elastin-targeted gadolinium agent that was shown previously to enable visualisation of plaque burden. Histological analysis was undertaken to confirm imaging findings through staining for macrophages, CX3CL1, elastin, tropoelastin, and iron. Results: The lead SPION agent consisted of a 10 nm iron oxide core with poly(maleicanhydride-alt-1-octadecene), (-36.21 mV, r 2 18.806 mmol -1 /s -1 ). The irregular faceting of the iron oxide core resulted in high relaxivity and the PMAO provided a foundation for further functionalisation on surface -COOH groups. The properties of the contrast agent, including the negative surface charge and hydrodynamic size, were designed to maximise circulation time and evade rapid clearance through the renal system or phagocytosis. In vitro testing showed that the SPION agent was non-toxic. In vivo results show that the novel contrast agent accumulates in similar vascular regions to a gadolinium-based contrast agent (Gd-ESMA) targeted to elastin, which accumulates in plaque. There was a significant difference in SPION signal between the instrumented and the contralateral non-instrumented vessels in diseased mice (p = 0.0411, student's t-test), and between the instrumented diseased vessel and control vessels (p = 0.0043, 0.0022, student's t-test). There was no significant difference between the uptake of either contrast agent between stable and vulnerable plaques (p = 0.3225, student's t-test). Histological verification was used to identify plaques, and Berlin Blue staining confirmed the presence of nanoparticle deposits within vulnerable plaques and co-localisation with macrophages. Conclusion: This work presents a new MRI contrast agent for atherosclerosis which uses an under-explored surface ligand, demonstrating promising properties for in vivo behaviour, is still in circulation 24 hours post-injection with limited liver uptake, and shows good accumulation in a murine plaque model., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: CMRA in pediatrics remains challenging due to the smaller vessel size, high heart rates (HR), potential image degradation caused by limited patient cooperation and long acquisition times. High-relaxivity contrast agents have been shown to improve coronary imaging in adults, but limited data is available in children. We sought to investigate whether gadobenate dimeglumine (Gd-BOPTA) together with self-navigated inversion-prepared coronary magnetic resonance angiography (CMRA) sequence design improves coronary image quality in pediatric patients., Methods: Forty consecutive patients (mean age 6±2.8years; 73% males) were prospectively recruited for a 1.5-T MRI study under general anesthesia. Two electrocardiographic-triggered free breathing steady-state free precession (SSFP) angiography sequences (A and B) with isotropic spatial resolution (1.3mm 3 ) were acquired using a recently developed image-based self-navigation technique. Sequence A was acquired prior to contrast administration using T2 magnetization preparation (T2prep). Sequence B was acquired 5-8min after a bolus of Gd-BOPTA with the T2prep replaced by an inversion recovery (IR) pulse to null the signal from the myocardium. Scan time, signal-to noise and contrast-to-noise ratios (SNR and CNR), vessel wall sharpness (VWS) and qualitative visual score for each sequence were compared., Results: Scan time was similar for both sequences (5.3±1.8 vs 5.2±1.5min, p=.532) and average heart rate (78±14.7 vs 78±14.5bpm, p=.443) remained constant throughout both acquisitions. Sequence B resulted in higher SNR (12.6±4.4 vs 31.1±7.4, p<.001) and CNR (9.0±1.8 vs 13.5±3.7, p<.001) and provided improved coronary visualization in all coronary territories (VWS A=0.53±0.07 vs B=0.56±0.07, p=.001; and visual scoring A=3.8±0.59 vs B=4.1±0.53, p<.001). The number of non-diagnostic coronary segments was lower for sequence B [A=42 (13.1%) segments vs B=33 (10.3%) segments; p=.002], and contrary to the pre-contrast sequence, never involved a proximal segment. These results were independent of the patients' age, body surface area and HR., Conclusions: The use of Gd-BOPTA with a 3D IR SSFP CMRA sequence results in improved coronary visualization in small infants and young children with high HR within a clinically acceptable scan time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Image-navigated 3-dimensional late gadolinium enhancement (iNAV-3D LGE) is an advanced imaging technique that allows for direct respiratory motion correction of the heart. Its feasibility in a routine clinical setting has not been validated., Methods: Twenty-three consecutive patients referred for cardiovascular magnetic resonance (CMR) examination including late gadolinium enhancement (LGE) imaging were prospectively enrolled. Image-navigated free-breathing 3-dimensional (3D) T1-weighted gradient-echo LGE and two-dimensional (2D LGE) images were acquired in random order on a 1.5 T CMR system. Images were assessed for global, segmental LGE detection and transmural extent. Objective image quality including signal-to-noise (SNR), contrast-to-noise (CNR) and myocardial/blood sharpness were performed., Results: Interpretable images were obtained in all 2D-LGE and in 22/23 iNAV-3D LGE exams, resulting in a total of 22 datasets and 352 segments. LGE was detected in 5 patients with ischemic pattern, in 7 with non-ischemic pattern, while it was absent in 10 cases. There was an excellent agreement between 2D and 3D data sets with regard to global, segmental LGE detection and transmurality. Blood-myocardium sharpness measurements were also comparable between the two techniques. SNR blood and CNR blood-myo was significantly higher for 2D LGE (P < 0.001, respectively), while SNR myo was not statistically significant between 2D LGE and iNAV-3D LGE., Conclusion: Diagnostic performance of iNAV-3D LGE was comparable to 2D LGE in a prospective clinical setting. SNR blood and CNR blood-myo was significantly lower in the iNAV-3D LGE group.

Purpose: To assess the diagnostic value of three-dimensional late enhancement (3D-LGE) for the detection of myocardial necrosis in a routine clinical setting. 3D-LGE has been proposed as a novel magnetic resonance (MR) technique for the accurate detection of myocardial scar in both the ventricles and atria. Its performance in clinical practice has been poorly examined., Materials and Methods: Fifty-seven patients referred for cardiac MR examination including scar imaging were prospectively enrolled. Gadolinium enhanced single breathhold 3D T1-weighted gradient-echo inversion recovery sequence and a conventional 2D-LGE sequence were performed using a 1.5 Tesla clinical MR imaging system. The presence, pattern and transmurality of LGE, diagnostic accuracy and level of diagnostic confidence as well as image quality (median quality, mean LGE signal intensity, sharpness, virtual scan time) were graded on a 4-point scale., Results: Interpretable images were obtained in 52/57 2D-LGE and in 47/57 3D high-resolution exams. LGE was detected in 10 patients with ischemic pattern, 9 with nonischemic pattern, while it was absent in 28, resulting in a total of 47 complete datasets. The detection of global and segmental LGE as well as its transmural extent were similar for both techniques (P = 0.65, P = 0.305, and P = 0.15, respectively). Image quality (median quality, LGE/ myocardial and LGE/ blood pool sharpness) was similar for both techniques (P = 0.740, P = 0.34, and P = 1.00, respectively), but LGE signal intensity was higher with 2D (P = 0.020)., Conclusion: 3D-LGE diagnostic and quality scores were comparable to 2D-LGE in a routine clinical setting. Further technical refinement is required for 3D LGE to offer a reliable alternative for high quality scar imaging., Level of Evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1675-1683., (© 2016 International Society for Magnetic Resonance in Medicine.)

Aqueous bifunctional semiconductor polymer nanoparticles (SPNs), approximately 30 nm in diameter (as measured from electron microscopy), were synthesised using hydrophobic conjugated polymers, amphiphilic phospholipids and a gadolinium-containing lipid. Their fluorescence quantum yields and extinction coefficients were determined, and their MRI T₁-weighted relaxation times in water were measured. The bimodal nanoparticles were readily taken up by HeLa and murine macrophage-like J774 cells as demonstrated by confocal laser scanning microscopy, and were found to be MRI-active, generating a linear relationship between T₁-weighted relaxation rates and gadolinium concentrations The synthesis is relatively simple, and can easily result in milligrams of materials, although we fully expect scale-up to the gram level to be easily realised.

Coronary wall imaging by cardiovascular magnetic resonance (CMR) emerges as a promising method to detect vascular injury and remodeling directly within the coronary vascular wall. In this review, the current evidence on coronary wall enhancement using CMR is presented and summarized, with particular focus on its ability to detect inflammation in atherosclerosis, Takayasu's arteritis, acute coronary syndromes and immune-mediated inflammatory vasculitides. The authors review the possible mechanisms of coronary wall contrast enhancement on CMR and discuss the technical considerations and limitations. Lastly, the potential clinical applications and possibilities for future research are proposed.

Background: The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951)., Methods and Results: Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4; P<0.001). The area of enhancement correlated well with the area of remodeling obtained from histological data (R(2)=0.86, P<0.05)., Conclusions: We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.

Purpose: To investigate a blood pool contrast agent and water-selective excitation imaging at 3 T for high spatial and high contrast imaging of brain vessels including the veins., Methods and Results: 48 clinical patients (47 ± 18 years old) were included. Based on clinical findings, twenty-four patients received a single dose of standard extracellular Gadoterate-meglumine (Dotarem®) and 24 received the blood pool contrast agent Gadofosveset (Vasovist®). After finishing routine MR protocols, all patients were investigated with two high spatial resolution (0.15 mm (3) voxel size) gradient echo sequences in random order in the equilibrium phase (steady-state) as approved by the review board: A standard RF-spoiled gradient-echo sequence (HR-SS, TR/TE 5.1/2.3 msec, FA 30°) and a fat-suppressed gradient-echo sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE 8.8/3.8 msec, FA 30°). The images were subjectively assessed (image quality with vessel contrast, artifacts, depiction of lesions) by two investigators and contrast-to-noise ratios (CNR) were compared using the Student's t-test. The image quality and CNR in the HR-FS were significantly superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was also improved when using the blood pool agent but only to a minor extent while the subjective image quality was similar for both contrast agents., Conclusion: The utilized sequence with water-selective excitation improved image quality and CNR properties in high spatial resolution imaging of brain arteries and veins. The used blood pool contrast agent improved the CNR only to a minor extent over the extracellular contrast agent., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To investigate the potential of Gadofluorine M for targeted lymph node imaging in a human size animal model and on a clinical MR scanner at 1.5 and 3 T., Materials and Methods: Pelvic and cervical lymph nodes in a swine model were investigated prior to and 24 hours after intravenous administration of 50 micromol/kg body weight Gadofluorine M, an experimental contrast agent. MR imaging was carried out on clinical 1.5 T and 3 T whole-body MR systems using clinically available coils and T 1-weighted sequences. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) with respect to the surrounding tissue were assessed and compared using the Student's t-test. The Gd concentration in the lymph nodes (n = 43) was measured post mortem by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES)., Results: Gadofluorine M allowed for high signal and high contrast visualization of lymph nodes in all stations on post-contrast images with a significantly increased SNR and CNR (SNR pelvic lymph nodes post vs. pre: 46 +/- 7 vs.14 +/- 3, SNR cervical lymph nodes post vs. pre: 105 +/- 64 vs. 32 +/- 21; CNR pelvic lymph node vs. muscle post vs. pre 28 +/- 5 vs. 0.2 +/- 0.5, CNR cervical lymph node vs. muscle post vs. pre 76 +/- 53 vs. 11 +/- 15, p < 0.05 for all comparisons). The SNR and CNR in the pelvis were further improved using 3 T compared to 1.5 T scanners (SNR lymph nodes 3 T vs. 1.5 T 84 +/- 6 vs. 46 +/- 7, CNR lymph node vs. muscle 3 T vs. 1.5 T 53 +/- 9 vs. 28 +/- 5 respectively, p < 0.05). A high concentration of Gd in the lymph nodes was found (149 +/- 25 mmol Gd/L)., Conclusion: Gadofluorine M accumulates in the lymph nodes and allows for selective targeted high contrast MR imaging of lymph node tissue in a large animal model using clinically available MR imaging techniques. 3 T further improves SNR and CNR compared to 1.5 T., (Georg Thieme Verlag KG Stuttgart, New York.)

Abundant data now link composition of the vascular wall, rather than the degree of luminal narrowing, with the risk for acute ischemic syndromes in the coronary, central nervous system, and peripheral arterial beds. Over the past few years, magnetic resonance angiography has evolved as a well-established method to determine the location and severity of advanced, lumen-encroaching atherosclerotic lesions. In addition, more recent studies have shown that high spatial resolution, multisequence MRI is also a promising tool for noninvasive, serial imaging of the aortic and carotid vessel wall, which potentially can be applied in the clinical setting. Because of the limited spatial resolution of current MRI techniques, characterization of coronary vessel wall atherosclerosis, however, is not yet possible and remains the holy grail of plaque imaging. Recent technical developments in MRI technology such as dedicated surface coils, the introduction of 3.0-T high-field systems and parallel imaging, as well as developments in the field of molecular imaging such as contrast agents targeted to specific plaque constituents, are likely to lead to the necessary improvements in signal to noise ratio, imaging speed, and specificity. These improvements will ultimately lead to more widespread application of this technology in clinical practice. In the present review, the current status and future role of MRI for plaque detection and characterization are summarized. [ABSTRACT FROM AUTHOR]