Real-time assessment of right and left ventricular volumes and function in children using high spatiotemporal resolution spiral bSSFP with compressed sensing

Background

Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques.

Methods

A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis.

Results

Acquisition time for the entire short axis stack (~?13 slices) using the spiral real-time technique was ~?20 s, compared to ~?348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p?<?0.001) and lower edge definition (p?<?0.001) in spiral real-time images than standard breath hold images, with lower quantitative edge sharpness and estimates of image contrast (p?<?0.001).There was a small but statistically significant (p?<?0.05) overestimation of left ventricular (LV) end-systolic volume (1.0?±?3.5 mL), and underestimation of LV end-diastolic volume (??1.7?±?4.6 mL), LV stroke volume (??2.6?±?4.8 mL) and LV ejection fraction (??1.5?±?3.0%) using the real-time technique. We also observed a small underestimation of right ventricular stroke volume (??1.8?±?4.9 mL) and ejection fraction (??1.4?±?3.7%) using the real-time imaging technique. No difference in inter-observer or intra-observer variability were observed between the BH and real-time sequences.

Conclusions

Real-time bSSFP imaging using spiral trajectories combined with a compressed sensing reconstruction showed good agreement for quantification of biventricular metrics in children with heart disease, despite slightly lower image quality. This technique holds the potential for free breathing data acquisition, with significantly shorter scan times in children.

     

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units.     

Superb Micro-vascular Imaging (SMI): a Doppler ultrasound technique with potential to identify,classify, and follow up endoleaks in patients after Endovascular Aneurysm Repair (EVAR)

Purpose

The aim of the study was to assess the effectiveness of Superb Micro-vascular Imaging (SMI) as an alternative to Contrast-Enhanced Ultrasound (CEUS) and Computed Tomography Angiography (CTA) for endoleak detection and classification in patients followed up after endovascular abdominal aortic aneurysm repair (EVAR).

Materials and methods

From May 2015 to January 2017, 30 patients underwent post-EVAR follow-up with Color Doppler Ultrasound (CDUS), CEUS, SMI, and CTA examinations. Aneurysmal sac diameter and graft patency were evaluated; endoleaks were identified and classified. Sensitivity, specificity, and accuracy values were calculated for each of the four diagnostic methods of endoleak detection. A percentage of agreement and Cohen’s Kappa coefficient were calculated for comparison of methods in terms of endoleak identification.

Results

CTA revealed fifteen endoleaks (50%): three type Ia, nine type II, and three type III. The sensitivity of CDUS, CEUS, and SMI relative to CTA was 27%, 100%, and 100%, respectively. Specificity was 93%, 93%, and 93%, respectively. Accuracy was 60%, 97%, and 97%, respectively. There were no differences between SMI and CEUS in terms of sensitivity, specificity, or accuracy (100%, 93%, and 97%). We do not observe statistically significant differences between CTA, CEUS, and SMI concerning endoleak identification ability. The weakest method in endoleak identification was CDUS.

Conclusions

The analysis showed that SMI is effective, repeatable, and comparable with the CEUS modality in identification endoleaks after EVAR; it may be considered as a potential tool to monitor patients after EVAR implantation, especially those with renal insufficiency or with an allergy to any contrast media.

     

The effect of the intramolecular C–H⋯O interactions on the conformational preferences of bis-arylsulfones – 5-HT6 receptor antagonists and beyond

The development of compounds with enhanced activity and selectivity by a conserved spatial orientation of the pharmacophore elements has a long history in medicinal chemistry. Rigidified compounds are an example of this concept. However, the intramolecular interactions were seldom used as a basis for conformational restraints. Here, we show the weak intramolecular interactions that contribute to the relatively well-conserved geometry of N1-arylsulfonyl indole derivatives. The structure analysis along with quantum mechanics calculations revealed a crucial impact of the sulfonyl group on the compound geometry. The weak intramolecular C–H⋯O interaction stabilizes the mutual "facing" orientation of two aromatic fragments. These findings extend the pharmacological interpretation of the sulfonyl group role from the double hydrogen bond acceptor to the conformational scaffold based on intramolecular forces. This feature has, to date, been omitted in in silico drug discovery. Our results should increase the awareness of researchers to consider the conformational preference when designing new compounds or improving computational methods.

The impact of weak intramolecular C–H⋯O interactions on the conformational stability of bis-arylsulfones is discussed, suggesting different role of sulfonyl group in the ligand – 5HT₆ receptor interaction.     

New synthetic pathway leading to oxospirochlorins

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between molecular structure and optical properties for the obtained title compounds is discussed.

Oxospirochlorins – novel analogs of porphyrinoids were synthesized and characterized by various methods including X-ray, NMR spectroscopy and mass spectrometry.     

Inflammatory bowel disease in children 5 years of age and younger

OBJECTIVES: Clinicians are becoming increasingly aware that inflammatory bowel disease (IBD) can affect all age groups, although it has not been well described in infants and young children. Our aim was to evaluate early onset IBD in patients 5 yr of age and younger. METHODS: Medical records of patients diagnosed with early onset IBD at The Children's Hospital of Philadelphia between 1977 and 2000 were reviewed. Patients were divided into three categories: those with Crohn's disease (CD), those with ulcerative colitis (UC), and those with indeterminant colitis (IC). RESULTS: A total of 82 patients fulfilled the criteria. In 12 patients (15%), the IBD diagnosis was changed during the course of illness. At the end of the follow-up period, linear growth failure was present in 10 of 35 (29%) children with CD, one of 30 (3%) with UC, and three of 17 (18%) with IC. Failure to thrive was a frequent presenting symptom in children with CD (44%) and IC (39%), whereas in all four patients with UC and failure to thrive the diagnosis was subsequently changed to CD or IC. A high proportion of patients with CD had large bowel (89%), and perianal (34%) disease. None of the tested patients were positive for anti-Saccharomyces cerevisiae antibody (ASCA), and 10 tested positive for perinuclear antineutrophil cytoplasmic antibody (three of five patients with CD, five of seven with UC, and two of three with IC). CONCLUSIONS: Failure to thrive, at the time of presentation, is indicative of a final diagnosis of CD or IC, not UC. Linear growth failure is a common finding in patients with early onset CD. A high proportion of patients with CD have failure to thrive, colonic, and perianal disease. The IBD serology panel is of limited clinical relevance in providing definitive diagnostic information in this pediatric population.     

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.