A Novel SPECT-Based Approach Reveals Early Mechanisms of Central and Peripheral Inflammation after Cerebral Ischemia

Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on brain injury and overall outcome are improperly understood, in part because the earliest inflammatory events after brain injury are not revealed by current imaging tools. Here, we show that single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood brain barrier (BBB) injury after experimental stroke well before changes can be detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene triamine pentaacetic acid) signal changes predict infarct development and systemic inflammation preceding experimental stroke leads to very early perfusion deficits and increased BBB injury within 2 hours after the onset of ischemia. Acute brain injury also leads to peripheral inflammation and immunosuppression, which contribute to poor outcome of stroke patients. The SPECT imaging revealed early (within 2 hours) changes in perfusion, barrier function and inflammation in the lungs and the gut after experimental stroke, with good predictive value for the development of histopathologic changes at later time points. Collectively, visualization of early inflammatory changes after stroke could open new translational research avenues to elucidate the interactions between central and peripheral inflammation and to evaluate in vivo ‘multi-system’ effects of putative anti-inflammatory treatments.

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A Dual-Labeled Annexin A5 is not Suited for SPECT Imaging of Brain Cell Death in Experimental Murine Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.115 ◽

2014 ◽

Vol 34 (9) ◽

pp. e1-e7 ◽

Cited By ~ 4

Author(s):

Marietta Zille ◽

Denise Harhausen ◽

Marijke De Saint-Hubert ◽

Roger Michel ◽

Chris P Reutelingsperger ◽

...

Keyword(s):

Cell Death ◽

Fluorescence Microscopy ◽

Single Photon ◽

Ex Vivo ◽

Photon Emission ◽

Spect Imaging ◽

Experimental Stroke ◽

Emission Computed Tomography ◽

Annexin A5

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (An×A5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled An×A5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding An×A5 or the nonfunctional An×A5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled An×A5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled An×A5 appears to be unsuited for visualizing death of brain cells in this MCAO model.

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From Zn(II) to Cu(II) Detection by MRI Using Metal-Based Probes: Current Progress and Challenges

Pharmaceuticals ◽

10.3390/ph13120436 ◽

2020 ◽

Vol 13 (12) ◽

pp. 436

Author(s):

Kyangwi P. Malikidogo ◽

Harlei Martin ◽

Célia S. Bonnet

Keyword(s):

Contrast Agents ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Advantages And Disadvantages ◽

Positron Emission ◽

Recent Developments ◽

Hyperfine Shift ◽

Magnetic Resonance Imaging Mri

Zinc and copper are essential cations involved in numerous biological processes, and variations in their concentrations can cause diseases such as neurodegenerative diseases, diabetes and cancers. Hence, detection and quantification of these cations are of utmost importance for the early diagnosis of disease. Magnetic resonance imaging (MRI) responsive contrast agents (mainly Lanthanide(+III) complexes), relying on a change in the state of the MRI active part upon interaction with the cation of interest, e.g., switch ON/OFF or vice versa, have been successfully utilized to detect Zn2+ and are now being developed to detect Cu2+. These paramagnetic probes mainly exploit the relaxation-based properties (T1-based contrast agents), but also the paramagnetic induced hyperfine shift properties (paraCEST and parashift probes) of the contrast agents. The challenges encountered going from Zn2+ to Cu2+ detection will be stressed and discussed herein, mainly involving the selectivity of the probes for the cation to detect and their responsivity at physiologically relevant concentrations. Depending on the response mechanism, the use of fast-field cycling MRI seems promising to increase the detection field while keeping a good response. In vivo applications of cation responsive MRI probes are only in their infancy and the recent developments will be described, along with the associated quantification problems. In the case of relaxation agents, the presence of another method of local quantification, e.g., synchrotron X-Ray fluorescence, single-photon emission computed tomography (SPECT) or positron emission tomography (PET) techniques, or 19F MRI is required, each of which has its own advantages and disadvantages.

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Κατασκευή εξειδικευμένων συστημάτων Γ- κάμερας απεικόνισης πειραματόζωων και μικρών οργάνων

10.12681/eadd/37897 ◽

2016 ◽

Author(s):

Μαρία Γεωργίου

Keyword(s):

Computed Tomography ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Single Photon Emission ◽

Positron Emission ◽

Single Photon Emission Computed ◽

Magnetic Resonance Imaging Mri ◽

Photon Emission Computed Tomography

Η μοριακή απεικόνιση ορίζεται ως η in-vivo μη επεμβατική απεικόνιση, αξιολόγηση και ποσοτικοποίηση των φυσιολογικών και παθολογικών διεργασιών ενός ζωντανού οργανισμού σε πραγματικό χρόνο. Οι ιχνηθέτες που έχουν αναπτυχθεί τα τελευταία χρόνια για την μοριακή απεικόνιση είναι κατάλληλα σχεδιασμένοι ώστε να στοχεύουν σε συγκεκριμένα μόρια που εκφράζουν τις διεργασίες του οργανισμού σε λειτουργικό και μεταβολικό επίπεδο. Τα δεδομένα που παράγονται από τις μελέτες μοριακής απεικόνισης βοηθούν στην κατανόηση βιολογικών φαινομένων, στην αναγνώριση παθολογικών περιοχών και στην ανάδειξη των παθοφυσιολογικών μηχανισμών των νόσων. Επομένως, η μοριακή απεικόνιση συνεισφέρει σημαντικά όχι μόνο στην πρόγνωση αλλά και στη διάγνωση, στην παρακολούθηση των θεραπευτικών σχημάτων και στην ανακάλυψη νέων φαρμάκων. Σήμερα, υπάρχουν πέντε κύριες μέθοδοι μοριακής απεικόνισης: α) η απεικόνιση μαγνητικού συντονισμού (Magnetic Resonance Imaging –MRI), β) η απεικόνιση αξονικής τομογραφίας (Computed Tomography – CT), γ) η υπερηχοτομογραφία (Ultrasound – US), δ) η οπτική απεικόνιση (Optical Imaging) και ε) οι ραδιοϊσοτοπικές απεικονιστικές μέθοδοι υπολογιστικής τομογραφίας μονοφωτονιακής εκπομπής (Single Photon Emission Computed Tomography - SPECT) και τομογραφίας εκπομπής ποζιτρονίων (Positron Emission Tomography - ΡΕΤ). Αναλόγως της βιοχημικής φυσιολογικής ή παθολογικής διεργασίας του οργανισμού που θέλουμε να απεικονίσουμε, επιλέγεται η κατάλληλη απεικονιστική μέθοδος με κατάλληλο ιχνηθέτη, αν και ο συνδυασμός περισσότερων μεθοδολογιών παρέχει συμπληρωματική πληροφορία. Σημαντική θέση στην μοριακή απεικόνιση κατέχουν οι ραδιοϊσοτοπικές μέθοδοι καθώς μαζί με τις οπτικές μεθόδους αποτελούν την αφετηρία αυτής. Τα εμπορικά διαθέσιμα κλινικά SPECT και ΡΕΤ συστήματα όπως και τα υβριδικά συστήματα SPECT/CT και ΡΕΤ/CT ή ΡΕΤ/MRI χρησιμοποιούνται ευρέως στην ογκολογία για τη διάγνωση, σταδιοποίηση και παρακολούθηση της θεραπείας της νόσου, αλλά και για τη διάγνωση άλλων ασθενειών όπως νευρολογικές και καρδιολογικές παθήσεις. Με την εξέλιξη της τεχνολογίας, τα απεικονιστικά συστήματα βελτιώνονται συνεχώς και η τάση που επικρατεί τη τελευταία δεκαετία είναι η ανάπτυξη εξειδικευμένων απεικονιστικών συστημάτων συγκεκριμένων οργάνων, πχ εγκέφαλος, μαστός, καρδιά, προστάτης, τα οποία προσφέρουν πολύ υψηλές επιδόσεις συγκριτικά με τα αντίστοιχα κλινικά που είναι σχεδιασμένα για ένα μεγάλο εύρος εφαρμογών. Τα νέα εξειδικευμένα συστήματα SPECT και ΡΕΤ βασίζονται στους φωτοπολλαπλασιαστές νέας γενιάς (φωτοπολλαπλασιαστές ευαισθησίας θέσης), οι οποίοι έχουν μικρές διαστάσεις, υψηλή χωρική διακριτική ικανότητα και έτσι επιτρέπουν την κατασκευή ανιχνευτών που να απεικονίζουν μόνο το υπο-εξέταση όργανο μειώνοντας την επίδραση της ακτινοβολίας των υπόλοιπων οργάνων. Με αυτό τον τρόπο είναι δυνατή η απεικόνιση δομών σε επίπεδο μερικών χιλιοστών (1-2 mm) σε αντίθεση με τα κλινικά συστήματα των οποίων η χωρική διακριτική ικανότητα είναι της τάξης των 5-8 mm. Εκτός από την κλινική πράξη, τα εξειδικευμένα SPECT και ΡΕΤ συστήματα βρίσκουν ιδιαίτερη εφαρμογή στην απεικόνιση πειραματόζωων, ένα πεδίο που συνήθως αποτελεί το βασικό χώρο καινοτομίας πριν την κλινική μεταφορά.Η παρούσα διδακτορική διατριβή στοχεύει στη σχεδίαση, βελτιστοποίηση και κατασκευή εξειδικευμένων σπινθηρογραφικών συστημάτων για την απεικόνιση πειραματόζωων, τη σπινθηρομαστογραφία και την απεικόνιση του λεμφαδένα. Συγκεκριμένα, αρχικά μελετήθηκε ένα πρότυπο σύστημα σπινθηρομαστογραφίας και ακολούθως κατασκευάστηκαν δύο ολοκληρωμένα συστήματα, το πρώτο για την ολόσωμη απεικόνιση μυών και το δεύτερο για την απεικόνιση των λεμφαδένων με υψηλή ευαισθησία.

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Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190304120011 ◽

2019 ◽

Vol 19 (12) ◽

pp. 950-960

Author(s):

Soghra Farzipour ◽

Seyed Jalal Hosseinimehr

Keyword(s):

Tumor Targeting ◽

Single Photon ◽

Specific Binding ◽

Specific Interaction ◽

Photon Emission ◽

Emission Computed Tomography ◽

Mixed Effect ◽

Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

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Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa084 ◽

2020 ◽

Author(s):

Lidia Bellés ◽

Andrea Dimiziani ◽

Stergios Tsartsalis ◽

Philippe Millet ◽

François R Herrmann ◽

...

Keyword(s):

Ventral Striatum ◽

Single Photon ◽

Ex Vivo ◽

Photon Emission ◽

Dorsal Striatum ◽

Reaction Time Task ◽

Emission Computed Tomography ◽

Novelty Preference ◽

Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

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Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽

10.3390/pharmaceutics13060770 ◽

2021 ◽

Vol 13 (6) ◽

pp. 770

Author(s):

Patrick M. Perrigue ◽

Richard A. Murray ◽

Angelika Mielcarek ◽

Agata Henschke ◽

Sergio E. Moya

Keyword(s):

Drug Delivery ◽

Laser Scanning ◽

Single Photon ◽

Photon Emission ◽

Correlation Spectroscopy ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Emission Computed Tomography ◽

Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

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Relationships of Pelvic Vein Diameter and Reflux with Clinical Manifestations of Pelvic Venous Disorder

Diagnostics ◽

10.3390/diagnostics12010145 ◽

2022 ◽

Vol 12 (1) ◽

pp. 145

Author(s):

Sergey Gavrilov ◽

Anatoly Karalkin ◽

Nadezhda Mishakina ◽

Oksana Efremova ◽

Anastasia Grishenkova

Keyword(s):

Single Photon ◽

Photon Emission ◽

Clinical Manifestations ◽

Emission Computed Tomography ◽

Type I ◽

Pelvic Vein ◽

Asymptomatic Patients ◽

Strong Positive Relationship ◽

Vein Diameter

The causes of chronic pelvic pain (CPP) in patients with pelvic venous disorder (PeVD) are not completely understood. Various authors consider dilation of pelvic veins (PeVs) and pelvic venous reflux (PVR) as the main mechanisms underlying symptomatic forms of PeVD. The aim of this study was to assess relationships of pelvic vein dilation and PVR with clinical manifestations of PeVD. This non-randomized comparative cohort study included 80 female patients with PeVD who were allocated into two groups with symptomatic (n = 42) and asymptomatic (n = 38) forms of the disease. All patients underwent duplex scanning and single-photon emission computed tomography (SPECT) of PeVs with in vivo labeled red blood cells (RBCs). The PeV diameters, the presence, duration and pattern of PVR in the pelvic veins, as well as the coefficient of pelvic venous congestion (CPVC) were assessed. Two groups did not differ significantly in pelvic vein diameters (gonadal veins (GVs): 7.7 ± 1.3 vs. 8.5 ± 0.5 mm; parametrial veins (PVs): 9.8 ± 0.9 vs. 9.5 ± 0.9 mm; and uterine veins (UVs): 5.6 ± 0.2 vs. 5.5 ± 0.6 mm). Despite this, CPVC was significantly higher in symptomatic versus asymptomatic patients (1.9 ± 0.4 vs. 0.7 ± 0.2, respectively; p = 0.008). Symptomatic patients had type II or III PVR, while asymptomatic patients had type I PVR. The reflux duration was found to be significantly greater in symptomatic versus asymptomatic patients (median and interquartile range: 4.0 [3.0; 5.0] vs. 1.0 [0; 2.0] s for GVs, p = 0.008; 4.0 [3.0; 5.0] vs. 1.1 [1.0; 2.0] s for PVs, p = 0.007; and 2.0 [2.0; 3.0] vs. 1.0 [1.0; 2.0] s for UVs, p = 0.04). Linear correlation analysis revealed a strong positive relationship (Pearson’s r = 0.78; p = 0.007) of CPP with the PVR duration but not with vein diameter. The grade of PeV dilation may not be a determining factor in CPP development in patients with PeVD. The presence and duration of reflux in the pelvic veins were found to be predictors of the development of symptomatic PeVD.

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Interpretasi Hasil Pemeriksaan MRI Kardiak pada Penyakit Jantung Koroner

Indonesian Journal of Cardiology ◽

10.30701/ijc.v34i1.301 ◽

2013 ◽

pp. 60-5

Author(s):

Sony Hilal Wicaksono ◽

Fachmi Ahmad Muslim ◽

Vienna Rossimarina

Keyword(s):

Computed Tomography ◽

Ct Scan ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Spect Mpi ◽

Single Photon Emission Computed ◽

Magnetic Resonance Imaging Mri ◽

Photon Emission Computed Tomography ◽

Tomography Scan

Seorang pasien dapat didiagnosis penyakit jantung koroner (PJK) melalui empat cara: kematian jantung mendadak, sindrom koroner akut, angina pektoris stabil paska revaskularisasi, dan hasil diagnostik noninvasif (Computed Tomography scan/CT scan koroner, Single Photon Emission Computed Tomography Myocardial Perfusion Imaging/SPECT MPI nuklir atau Magnetic Resonance Imaging/MRI)1. Pemeriksaan noninvasif memegang peranan penting, yaitu sebagai satu-satunya cara mendiagnosis PJK asimtomatik. Oleh sebab itu, pemahaman mengenai interpretasi hasil pemeriksaan noninvasif seperti CT scan koroner, SPECT MPI nuklir atau MRI kardiak dimasukkan dalam kompetensi dasar program pendidikan spesialis jantung dan pembuluh darah menurut Kolegium PERKI.

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Imaging Amyloid-β Deposits In Vivo

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200209000-00001 ◽

2002 ◽

Vol 22 (9) ◽

pp. 1035-1041 ◽

Cited By ~ 76

Author(s):

Brian J. Bacskai ◽

William E. Klunk ◽

Chester A. Mathis ◽

Bradley T. Hyman

Keyword(s):

Single Photon ◽

Senile Plaques ◽

Photon Emission ◽

Multiphoton Microscopy ◽

Amyloid Β ◽

Neuronal Loss ◽

High Sensitivity ◽

Emission Computed Tomography ◽

Tissue Samples

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

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Basic principles and technological state of the art: SPECT

ESC CardioMed ◽

10.1093/med/9780198784906.003.0119_update_001 ◽

2018 ◽

pp. 573-577

Author(s):

Alessia Gimelli ◽

Riccardo Liga

Keyword(s):

Single Photon ◽

Imaging Modality ◽

Photon Emission ◽

Nuclear Imaging ◽

The Body ◽

Emission Computed Tomography ◽

Non Invasive ◽

Photon Emission Computed Tomography ◽

Invasive Evaluation

Single-photon emission computed tomography (SPECT) photons as a medical imaging technique detects the radiation emitted by radioisotopes injected into the body to provide in vivo measurements of regional tissue function. From its introduction in the cardiologic clinical field, nuclear imaging has classically represented the reference technique for the non-invasive evaluation of myocardial perfusion, becoming the most frequently performed imaging modality for the functional assessment of patients with ischaemic heart disease.

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