A simplified method to correct saturation of arterial input function for cardiac magnetic resonance first-pass perfusion imaging: validation with simultaneously acquired PET.

BACKGROUND: First-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on 13N-ammonia positron emission tomography (PET). METHODS: Sixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 mCi of 13N-ammonia. The MRI perfusion acquisition started simultaneously with the start of the PET acquisition after the injection of a 0.075 mmol/kg gadolinium contrast agent. Cardiac stress imaging was initiated after the administration of regadenoson 20 s prior to PET-MRI scanning. The saturation part of the MRI AIF data was modeled as a gamma variate curve, which was then estimated for a true AIF by minimizing a cost function according to various boundary conditions. A standard AHA 16-segment model was used for comparative analysis of absolute MBF from PET and MRI. RESULTS: Overall, there were 256 segments in 16 patients, mean resting perfusion for PET was 1.06 ± 0.34 ml/min/g and 1.04 ± 0.30 ml/min/g for MRI (P = 0.05), whereas mean stress perfusion for PET was 2.00 ± 0.74 ml/min/g and 2.12 ± 0.76 ml/min/g for MRI (P < 0.01). Linear regression analysis in MBF revealed strong correlation (r = 0.91, slope = 0.96, P < 0.001) between PET and MRI. Myocardial perfusion reserve, calculated from the ratio of stress MBF over resting MBF, also showed a strong correlation between MRI and PET measurements (r = 0.82, slope = 0.81, P < 0.001). CONCLUSION: The results demonstrated the feasibility of the simplified AIF estimation method for the accurate quantification of MBF by MRI with single sequence and single contrast injection. The MRI MBF correlated strongly with PET MBF obtained simultaneously. This post-processing technique will allow easy transformation of clinical perfusion imaging data into quantitative information.

Implementation and prospective clinical validation of AI-based planning and shimming techniques in cardiac MRI.

PURPOSE: Cardiovascular magnetic resonance (CMR) is a vital diagnostic tool in the management of cardiovascular diseases. The advent of advanced CMR technologies combined with artificial intelligence (AI) has the potential to simplify imaging, reduce image acquisition time without compromising image quality (IQ), and improve magnetic field uniformity. Here, we aim to implement two AI-based deep learning techniques for automatic slice alignment and cardiac shimming and evaluate their performance in clinical cardiac magnetic resonance imaging (MRI). METHODS: Two deep neural networks were developed, trained, and validated on pre-acquired cardiac MRI datasets (>500 subjects) to achieve automatic slice planning and shimming (implemented in the scanner) for CMR. To examine the performance of our automated cardiac planning (EasyScan) and AI-based shim (AI shim), two prospective studies were performed subsequently. For the EasyScan validation, 10 healthy subjects underwent two identical CMR protocols: with manual cardiac planning and with AI-based EasyScan to assess protocol scan time difference and accuracy of cardiac plane prescriptions on a 1.5 T clinical MRI scanner. For the AI shim validation, a total of 20 subjects were recruited: 10 healthy and 10 cardio-oncology patients with referrals for a CMR examination. Cine images were obtained with standard cardiac volume shim and with AI shim to assess signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), overall IQ (sharpness and MR image degradation), ejection fraction (EF), and absolute wall thickening. A hybrid statistical method using of nonparametric (Wilcoxon) and parametric (t-test) assessments was employed for statistical analyses. RESULTS: CMR protocol with AI-based plane prescriptions, EasyScan, minimized operator dependence and reduced overall scanning time by over 2 min (∼13 % faster, p < 0.001) compared to the protocol with manual cardiac planning. EasyScan plane prescriptions also demonstrated more accurate (less plane angulation errors from planes manually prescribed by a certified cardiac MRI technologist) cardiac planes than previously reported strategies. Additionally, AI shim resulted in improved B0 field homogeneity. Cine images obtained with AI shim revealed a significantly higher SNR (12.49%; p = 0.002) than those obtained with volume shim (volume shim: 32.90 ± 7.42 vs. AI shim: 37.01 ± 8.87) for the left ventricle (LV) myocardium. LV myocardium CNR was 12.48% higher for cine imaging with AI shim (149.02 ± 39.15) than volume shim (132.49 ± 33.94). Images obtained with AI shim resulted in sharper images than those obtained with volume shim (p = 0.012). The LVEF and absolute wall thickening also showed that differences exist between the two shimming methods. The LVEF by AI shim was shown to be slightly larger than LVEF by volume shim in two groups: 2.87% higher with AI shim for the healthy group and 1.70% higher with AI shim for the patient group. The LV absolute wall thickening (in mm) also showed that differences exist between shimming methods for each group with larger changes observed in the patient group (healthy: 3.31%, p = 0.234 and patient group: 7.29%, p = 0.059). CONCLUSIONS: CMR exams using EasyScan for cardiac planning demonstrated accelerated cardiac exam compared to the CMR protocol with manual cardiac planning. Improved and more uniform B0 magnetic field homogeneity also achieved using AI shim technique compared to volume shimming.

Potent cyclometallated Pd(II) antitumor complexes bearing α-amino acids: synthesis, structural characterization, DNA/BSA binding, cytotoxicity and molecular dynamics simulation.

A rational approach was adopted to design high-potential metal-based antitumor agents. A series of organometallic Pd(ii) complexes with a general formula of [Pd{κ2(C,C)-[(C6H4-2)PPh2]CH(CO)C6H4Ph-4}{κ2(N,O)}] (N,O = alanine (Pd-A), valine (Pd-V), leucine (Pd-L), l-isoleucine (Pd-I) and phenylalanine (Pd-F)) were prepared by cyclopalladation of the phosphorus ylide, bridge cleavage reaction and subsequent chelation of natural α-amino acids. The complexes were fully identified using IR and multinuclear 1H, 13C, 31P NMR spectroscopic methods. X-ray crystallography exhibited that the Pd(ii) atom is located in a slightly distorted square-planar environment surrounded by C,C-orthometallated phosphorus ylide as well as NO-pendant amino acid functionality. In vitro cytotoxicity evaluation of new cyclometallated Pd(ii) complexes toward a human leukemia (K562) cancer cell line indicated promising results. The highest cytotoxic activity was discovered in the case of phenylalanine (CH2C6H5). IC50 values of this complex on a panel of human tumor cell lines representative of liver (HepG2), breast (SKBR-3), and ovarian (A2780-Resistance/Sensitive) cancers also indicated promising antitumor effects in comparison with standard cisplatin. The binding interaction ability of the phenylalanine-containing orthopalladated complex, as the most efficient compound, with calf-thymus deoxyribonucleic acid (CT-DNA) and bovine serum albumin (BSA) was investigated. UV-Vis spectroscopy, competitive emission titration, and circular dichroism (CD) techniques demonstrated the intercalative binding of the Pd(ii) complex with DNA. Molecular docking studies also fully agreed with the experimental data. Examination of the reactivity towards the protein BSA revealed that the static quenching mechanism of BSA intrinsic fluorescence by the Pd(ii) complex with a binding constant (Kb) of ∼105 is indicative of the high affinity of the complex. The competitive binding experiment using site markers with definite binding sites demonstrated that the hydrophobic cavities of site I (subdomain IIA) are responsible for the bimolecular interaction between protein BSA and the complex. Molecular docking studies effectively confirmed the significance of hydrophobic interactions in Pd(ii)-BSA binding. The results of this study could greatly contribute to exploring new potent metal-based anticancer drugs.