New targets in cardiovascular imaging

Nieuwe aanknopingspunten voor evaluatie aderverkalking Atherosclerose, in de volksmond beter bekend als aderverkalking, is een veelvoorkomende hart- en vaatziekte. De ziekte heeft een gecompliceerd en langzaam verloop. In de loop van jaren wordt een vetachtige stof (‘plaque’) afgezet in de wand van slagaders. De bloedvaten worden daardoor nauwer. Wanneer de plaque loslaat, kan deze complicaties veroorzaken, zoals een hart- of herseninfarct. Reza Golestani onderzocht hoe het moleculaire proces van aderverkalking met visuele technieken zoals PET-scans in beeld kan worden gebracht. Golestani ontwikkelde een beeldvormende techniek voor het visualiseren en meten van de moleculaire en cellulaire doelwitten die betrokken zijn bij atherosclerotische ziekten. Hij deed dat onder andere door diermodellen van de ziekte te onderzoeken en stukjes verwijderde plaque uit de halsslagaders. De promovendus concludeert dat zijn onderzoek veelbelovende doelen heeft geïdentificeerd om de ziekte van buitenaf in beeld te brengen. Op basis van deze nieuwe inzichten, die nog preklinisch van aard zijn, moet het in de toekomst makkelijker worden om patiënten in verschillende risicogroepen in te delen of om nieuwe medicijnen te ontwikkelen die de progressie van de ziekte moeten stoppen

New targets in cardiovascular imaging

Nieuwe aanknopingspunten voor evaluatie aderverkalking Atherosclerose, in de volksmond beter bekend als aderverkalking, is een veelvoorkomende hart- en vaatziekte. De ziekte heeft een gecompliceerd en langzaam verloop. In de loop van jaren wordt een vetachtige stof (‘plaque’) afgezet in de wand van slagaders. De bloedvaten worden daardoor nauwer. Wanneer de plaque loslaat, kan deze complicaties veroorzaken, zoals een hart- of herseninfarct. Reza Golestani onderzocht hoe het moleculaire proces van aderverkalking met visuele technieken zoals PET-scans in beeld kan worden gebracht. Golestani ontwikkelde een beeldvormende techniek voor het visualiseren en meten van de moleculaire en cellulaire doelwitten die betrokken zijn bij atherosclerotische ziekten. Hij deed dat onder andere door diermodellen van de ziekte te onderzoeken en stukjes verwijderde plaque uit de halsslagaders. De promovendus concludeert dat zijn onderzoek veelbelovende doelen heeft geïdentificeerd om de ziekte van buitenaf in beeld te brengen. Op basis van deze nieuwe inzichten, die nog preklinisch van aard zijn, moet het in de toekomst makkelijker worden om patiënten in verschillende risicogroepen in te delen of om nieuwe medicijnen te ontwikkelen die de progressie van de ziekte moeten stoppen

In Vitro Study of Mebendazole (Anthelmintic drug) Effects on the Aspartate Aminotransferase (AST) Enzyme Activity of Hydatid Cyst Parasite

Hydatid disease is caused by the larva of Echinococcus granulosus parasite. Mebendazole (MBZ) is used as an alternative choice for the treatment of the disease. Aspartate aminotransferase (AST) is an essential enzyme in amino acid metabolism. The aim of the present study is to evaluate the effect of MBZ on AST activity of hydatid cyst parasite in order to detect enzymatic parameter for drug efficiency. In the present study, AST activity was estimated in the extracts of untreated parasite (hydatid cyst protoscolices) and treated samples by MBZ (100 µg final concentration). Samples’ protein quantity and quality were detected by Bradford and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) methods respectively. For the purpose of determining the significant difference between the two independent samples, t-test was conducted. The values of the assayed AST specific activities of treated and untreated parasite samples were measured as 0.18 and 1.53U/ml/mg protein respectively. The difference between AST activities mean values of the two groups proved to be significant (P<0.05). SDS-PAGE demonstrated protein band of 50 kDa for AST enzyme. Considering the effect of the MBZ drug on AST activity in parasite, it can be concluded that this enzyme is useful for improving the drug efficiency

Comparison of Visual, Refractive and Aberration Measurements of INTACS versus Tricyclic ICL Lens Implantation; A Four-year Follow-up

This study was performed to evaluate the visual, refractive, and aberration measurement results of 2 implants, including Intacs Intracorneal Ring Segments (ICRS) and phakic Toric Implantable Collamer Lens (TICL), in patients with moderate Keratoconus (KCN). In this retrospective cross-sectional study, 30 patients with KCN with a mean age of 29.83 years were included in 2 groups, including the Intacs Intracorneal Ring Segments (ICRS) group and the phakic Toric Implantable Collamer Lens (TICL) group. Preoperative data as well as 6-month, 1-, 2-, 3- and 4-year follow-up data after the operation were collected and analyzed with the SPSS software (ver. 23.0, SPSS, Inc., Chicago, IL), using the paired t-test, independent t-test, repeated measures Analysis of Variance (ANOVA), and one-way ANOVA. This study included 30 patients with KCN with a mean age of 29.83 years and range of 25 to 35 years, including 17 males with a mean age of 30.11 years and 13 female with a mean age of 29.25 years. Except for preoperative Uncorrected Distance Visual Acuity (UCDVA), Spherical Equivalent (SE) and astigmatism, there was a significant difference between the 2 groups regarding other variables. The TICL group had a significantly better UCDVA and Best Corrected Distance Visual Acuity (BCDVA) in all post-operative follow-ups, and SE and astigmatism values were significantly lower in all post-operative follow-ups when compared with the ICRS group. There was a significant reduction in corneal and total coma as well as internal trefoil aberrations (P<0.01, P<0.01, and P=0.014, respectively) in the ICRS group, and TICL led to a significant reduction in internal trefoil aberration with P<0.03. Comparison of the 2 groups revealed a significant difference in corneal spherical (P<0.01) and total coma (P=0.02) aberrations and no significant differences in other HOA. Both ICRS and TICL are useful in patients with moderate KCN. However, TICL appears to have more stable and predictable vision results.Â

Folate receptor-β imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque

UNLABELLED: In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. METHODS: Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro culturing. Messenger RNA levels of specific M1 and M2 markers were measured by reverse-transcription polymerase chain reaction and expression of FR-β, CD86, and CD163 by flow cytometry. RESULTS: There was a heterogeneous accumulation of (99m)Tc-folate in plaques (median, 2.45 [0.77-6.40] MBq/g). Slices with the highest (99m)Tc-folate accumulation of each plaque showed significantly more expression of FR-β and CD163, compared with slices with the lowest (99m)Tc-folate accumulation, which showed significantly more expression of iNOS. In in vitro polarized macrophages, messenger RNA expression of FR-β, mannose receptor, IL-10, and matrix metalloproteinase-9 was significantly increased in M2-like macrophages, compared with M1-like macrophages. On a receptor level, CD86 was shown to be overexpressed on M1-like macrophages whereas FR-β and CD163 were overexpressed on M2-like macrophages measured by flow cytometry. CONCLUSION: Higher numbers of M2-like macrophages were present in areas of high (99m)Tc-folate accumulation than areas with low accumulation. It is anticipated that (99m)Tc-folate imaging using SPECT as a marker for M2-like macrophages in atherosclerosis might be a good indicator for plaque vulnerability

PET and MRI for the evaluation of regional myocardial perfusion and wall thickening after myocardial infarction

Deterioration of left ventricular (LV) function after myocardial infarction (MI) is a major cause of heart failure. Myocardial perfusion performance may play an important role in deterioration or improvement in LV function after MI. The aim of this study was to evaluate the myocardial perfusion reserve (MPR) and stress perfusion in deteriorating and non-deteriorating LV segments in patients after MI by PET and MRI, respectively. Regional wall thickening of 352 segments in 22 patients was assessed at 4 and 24 months after MI by cardiac MRI. PET was performed to evaluate MPR and adenosine stress N-13-ammonia perfusion 24 months after MI. Segments were divided into four groups according to deterioration or improvement in wall thickening. Normal functional segments at 4 months after MI that remained stable had a significantly higher mean MPR and mean stress perfusion PET value than deteriorated segments (p < 0.001). Furthermore, dysfunctional segments that improved had a significantly higher mean stress perfusion PET value than dysfunctional segments that remained dysfunctional (p < 0.001). This study demonstrated the additional value of myocardial perfusion assessment in relation to the functional integrity of the injured myocardium. Segmental functional LV improvement after MI was associated with better regional myocardial perfusion characteristics. Furthermore, the amount of wall thickening reduction was associated with regional myocardial perfusion abnormalities in patients after MI

Small-animal SPECT and SPECT/CT: application in cardiovascular research

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease

Molecular Imaging of Angiogenesis and Vascular Remodeling in Cardiovascular Pathology

Angiogenesis and vascular remodeling are involved in a wide array of cardiovascular diseases, from myocardial ischemia and peripheral arterial disease, to atherosclerosis and aortic aneurysm. Molecular imaging techniques to detect and quantify key molecular and cellular players in angiogenesis and vascular remodeling (e.g., vascular endothelial growth factor and its receptors, αvβ3 integrin, and matrix metalloproteinases) can advance vascular biology research and serve as clinical tools for early diagnosis, risk stratification, and selection of patients who would benefit most from therapeutic interventions. To target these key mediators, a number of molecular imaging techniques have been developed and evaluated in animal models of angiogenesis and vascular remodeling. This review of the state of the art molecular imaging of angiogenesis and vascular (and valvular) remodeling, will focus mostly on nuclear imaging techniques (positron emission tomography and single photon emission tomography) that offer high potential for clinical translation