Pétrographie characterization of rocks from the Mirabello bay region, Crete, and its application to Minoan archaeology: the provenance of stone implements from Minoan sites

Οι άνθρωποι της Μινωικής Εποχής, στην Ανατολική Κρήτη, χρησιμοποιούσαν μαγματικά και μεταμορφωμένα πετρώματα για την κατασκευή διαφόρων λίθινων σκευών. Αυτά τα συνέλλεγαν από τις κοίτες των ποταμών και την ακτή στην περιοχή κατά μήκος του κόλπου του Μιραμπέλλο ή από ένα κροκαλοπαγές επίκλυσης, το οποίο κυριαρχεί γεωλογικά στην περιοχή αυτή και περιέχει κροκάλες από μαγματικά, μεταμορφωμένα και ιζηματογενή πετρώματα. Η λεπτομερής πετρογραφική περιγραφή φυσικών δειγμάτων, που συλλέχθηκαν από αυτούς τους σχηματισμούς και η σύγκριση τους με λίθινα σκεύη από ανασκαφές, αφενός καθιστά γνωστούς τους λιθολογικούς τύπους που χρησιμοποιήθηκαν και αφετέρου επιβεβαιώνει την πηγή προέ?χυσής τους. Με τη έρευνα αυτή καθίσταται προφανές ότι οι άνθρωποι της Μινωικής Εποχής μπορούσαν μα εκτιμήσουν τη σκληρότητα των λίθων που συνέλλεγαν, σύμφωνα με την επιθυμητή χρήση, καθώς και την αναμενόμενη κόπωση των υλικών, ανάλογα με τη χρήση για την οποία τα προόριζαν, αποφεύγοντας παράλληλα την ανεπιθύμητα χρονοβόρα κατεργασία τους. Με την επιβεβαίωση της λιθολογίας και της πηγής προέλευσης των λίθινων πρώτων υλών γίνεται επίσης αντιληπτό το γεγονός ότι οι άνθρωποι της Μινωικής Εποχής ήταν γνώστες του φυσικού περιβάλλοντος, στον ευρύτερο χώρο των οικισμών τους. Επίσης, μπορεί να εκτιμηθεί και ο χρόνος τον οποίο διέθεταν προκειμένου να βρουν και να συλλέξουν την πρώτη ύλη αλλά και να αξιολογηθεί ο χρόνος κατεργασίας των υλικών, προκειμένου να διαμορφωθούν σε κατάλληλα σκεύη, ανάλογα με τη σκληρότητα τους.The Minoans of East Crete used a variety of igneous and metamorphic rocks as stone implements. These were probably procured in dry riverbeds and beaches located in a region along the Bay of Mirabello or from an onlap conglomerate, which geologically dominates that region and contains rock types of igneous, metamorphic and sedimentary origin. Several rock samples were collected for pétrographie investigation to examine and confirm the source for the igneous rocks. Detailed pétrographie description of natural samples provides the identification of the rocks employed by Minoans and confirms the source of their origin. Apparently the Minoans were able to evaluate the hardness of the stones procured according to the desirable usage and their expected fatigue, thus avoiding unnecessary timeconsuming treatment. The identification of the variable lithotypes used for these implements and the verification of their source regions reveal the time it took to procure the raw materials as well as the time period during which the rocks were employed

Filament tension and phase-locked drift of meandering scroll waves

Rotating scroll waves are self-organising patterns which are found in many oscillating or excitable systems. Here we show that quasi-periodic (meandering) scroll waves, which include the rotors that organise cardiac arrhythmias, exhibit filament tension when averaged over the meander cycle. With strong filament curvature or medium thickness gradients, however, scroll wave dynamics are governed by phase-locked drift instead of filament tension. Our results are validated in computational models of cycloidal meander and a cardiac tissue model with linear core.Comment: accepted for publication in Physical Review Letters (December 2017

The Development of a Smart Magnetic Resonance Imaging and Chemical Exchange Saturation Transfer Contrast Agent for the Imaging of Sulfatase Activity

The molecular imaging of biomarkers plays an increasing role in medical diagnostics. In particular, the imaging of enzyme activity is a promising approach, as it enables the use of its inherent catalytic activity for the amplification of an imaging signal. The increased activity of a sulfatase enzyme has been observed in several types of cancers. We describe the development and in vitro evaluation of molecular imaging agents that allow for the detection of sulfatase activity using the whole-body, non-invasive MRI and CEST imaging methods. This approach relies on a responsive ligand that features a sulfate ester moiety, which upon sulfatase-catalyzed hydrolysis undergoes an elimination process that changes the functional group, coordinating with the metal ion. When Gd3+ is used as the metal, the complex can be used for MRI, showing a 25% decrease at 0.23T and a 42% decrease at 4.7T in magnetic relaxivity after enzymatic conversion, thus providing a "switch-off" contrast agent. Conversely, the use of Yb3+ as the metal leads to a "switch-on" effect in the CEST imaging of sulfatase activity. Altogether, the results presented here provide a molecular basis and a proof-of-principle for the magnetic imaging of the activity of a key cancer biomarker. </p

A retrospective analysis of the diagnostic performance of 11C-choline PET/CT for detection of hyperfunctioning parathyroid glands after prior negative or discordant imaging in primary hyperparathyroidism

BACKGROUND: Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the diagnostic performance of 11C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging. METHODS: This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing 11C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the 11C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard. RESULTS: In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on 11C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of 11C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions. CONCLUSIONS: In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by 11C-choline PET/CT with high sensitivity and accuracy

A Photocleavable Contrast Agent for Light-Responsive MRI

Thanks to its innocuousness and high spatiotemporal resolution, light is used in several established and emerging applications in biomedicine. Among them is the modulation of magnetic resonance imaging (MRI) contrast agents' relaxivity with the aim to increase the sensitivity, selectivity and amount of functional information obtained from this outstanding whole-body medical imaging technique. This approach requires the development of molecular contrast agents that show high relaxivity and strongly pronounced photo-responsiveness. To this end, we report here the design and synthesis of a light-activated MRI contrast agent, together with its evaluation using UV-vis spectroscopy, Fast Field Cycling (FFC) relaxometry and relaxometric measurements on clinical MRI scanners. The high relaxivity of the reported agent changes substantially upon irradiation with light, showing a 17% decrease in relaxivity at 0.23T upon irradiation with lambda = 400 nm (violet) light for 60 min. On clinical MRI scanners (1.5T and 3.0T), irradiation leads to a decrease in relaxivity of 9% and 19% after 3 and 60 min, respectively. The molecular design presents an important blueprint for the development of light-activatable MRI contrast agents

Targeted optical fluorescence imaging:a meta-narrative review and future perspectives

Purpose: The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods: A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results: Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion: Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice

Focused ultrasound for opening blood-brain barrier and drug delivery monitored with positron emission tomography

Focused ultrasound (FUS) is a minimally-invasive technology used for treatment of many diseases, including diseases related to the colon, uterus, prostate, and brain. Although it has been mainly used for ablative procedures, the ability of FUS to open the blood-brain barrier (BBB) presents a promising new application. However, the mechanism of BBB opening by FUS remains unclear. This review focuses on the use of FUS to open the BBB for enhancing drug delivery and investigating how Positron Emission Tomography (PET) provides insight into the underlying mechanism

The effects of molar activity on [F-18]FDOPA uptake in patients with neuroendocrine tumors

BACKGROUND: 6-[(18)F]fluoro-l-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [(18)F]FDOPA is decarboxylated to [(18)F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [(18)F]FDOPA has been developed, [(18)F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([(18)F]FDOPA-L). AIMS: This study aimed to investigate whether the difference in molar activity affects the [(18)F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [(18)F]FDOPA-H would be equal to or higher than [(18)F]FDOPA-L. METHODS: We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [(18)F]FDOPA-H and [(18)F]FDOPA-L within a time span of 5 years. A total of 98 [(18)F]FDOPA scans (49 [(18)F]FDOPA-L and 49 [(18)F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1–2 lesions) and higher tumor load (3–10 lesions). RESULTS: Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [(18)F]FDOPA-H compared to [(18)F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [(18)F]FDOPA-H group with 3–10 lesion (SUVmax 6.83 vs. 5.19, p < 0.001). In the other groups, no significant differences were seen between H and L. CONCLUSION: [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV’s, with slight increases in uptake of [(18)F]FDOPA-H in comparison to [(18)F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [(18)F]FDOPA