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Article ; Online: PET/MRI in paediatric disease.

Sepehrizadeh, Tara / Jong, Ian / DeVeer, Michael / Malhotra, Atul

2021 Volume 144, Page(s) 109987

Abstract: Nuclear medicine and molecular imaging have a small but growing role in the management of paediatric and neonatal diseases. During the past decade, combined PET/MRI has emerged as a clinically important hybrid imaging modality in paediatric medicine due ... ...

Abstract	Nuclear medicine and molecular imaging have a small but growing role in the management of paediatric and neonatal diseases. During the past decade, combined PET/MRI has emerged as a clinically important hybrid imaging modality in paediatric medicine due to diagnostic advantages and reduced radiation exposure compared to alternative techniques. The applications for nuclear medicine, radiopharmaceuticals and combined PET/MRI in paediatric diagnosis is broadly similar to adults, however there are some key differences. There are a variety of clinical applications for PET/MRI imaging in children including, but not limited to, oncology, neurology, cardiovascular, infection and chronic inflammatory diseases, and in renal-urological disorders. In this article, we review the applications of PET/MRI in paediatric and neonatal imaging, its current role, advantages and disadvantages over other hybrid imaging techniques such as PET/CT, and its future applications. Overall, PET/MRI is a powerful imaging technology in diagnostic medicine and paediatric diseases. Higher soft tissue contrasts and lower radiation dose of the MRI makes it the superior technology compared to other conventional techniques such as PET/CT or scintigraphy. However, this relatively new hybrid imaging has also some limitations. MRI based attenuation correction remains a challenge and although methodologies have improved significantly in the last decades, most remain under development.
MeSH term(s)	Adult ; Child ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Multimodal Imaging ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed
Chemical Substances	Radiopharmaceuticals
Language	English
Publishing date	2021-10-01
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	138815-0
ISSN	1872-7727 ; 0720-048X
ISSN (online)	1872-7727
ISSN	0720-048X
DOI	10.1016/j.ejrad.2021.109987
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Article ; Online: Stroke Alters the Function of Enteric Neurons to Impair Smooth Muscle Relaxation and Dysregulates Gut Transit.

Kumar, Kathryn Prame / Wilson, Jenny L / Nguyen, Huynh / McKay, Liam D / Wen, Shu Wen / Sepehrizadeh, Tara / de Veer, Michael / Rajasekhar, Pradeep / Carbone, Simona E / Hickey, Michael J / Poole, Daniel P / Wong, Connie H Y

Journal of the American Heart Association

2024 Volume 13, Issue 3, Page(s) e033279

Abstract: Background: Gut dysmotility is common after ischemic stroke, but the mechanism underlying this response is unknown. Under homeostasis, gut motility is regulated by the neurons of the enteric nervous system that control contractile/relaxation activity of ...

Abstract	Background: Gut dysmotility is common after ischemic stroke, but the mechanism underlying this response is unknown. Under homeostasis, gut motility is regulated by the neurons of the enteric nervous system that control contractile/relaxation activity of muscle cells in the gut wall. More recently, studies of gut inflammation revealed interactions of macrophages with enteric neurons are also involved in modulating gut motility. However, whether poststroke gut dysmotility is mediated by direct signaling to the enteric nervous system or indirectly via inflammatory macrophages is unknown. Methods and results: We examined these hypotheses by using a clinically relevant permanent intraluminal midcerebral artery occlusion experimental model of stroke. At 24 hours after stroke, we performed in vivo and ex vivo gut motility assays, flow cytometry, immunofluorescence, and transcriptomic analysis. Stroke-induced gut dysmotility was associated with recruitment of muscularis macrophages into the gastrointestinal tract and redistribution of muscularis macrophages away from myenteric ganglia. The permanent intraluminal midcerebral artery occlusion model caused changes in gene expression in muscularis macrophages consistent with an altered phenotype. While the size of myenteric ganglia after stroke was not altered, myenteric neurons from post-permanent intraluminal midcerebral artery occlusion mice showed a reduction in neuronal nitric oxide synthase expression, and this response was associated with enhanced intestinal smooth muscle contraction ex vivo. Finally, chemical sympathectomy with 6-hydroxydopamine prevented the loss of myenteric neuronal nitric oxide synthase expression and stroke-induced slowed gut transit. Conclusions: Our findings demonstrate that activation of the sympathetic nervous system after stroke is associated with reduced neuronal nitric oxide synthase expression in myenteric neurons, resulting in impaired smooth muscle relaxation and dysregulation of gut transit.
MeSH term(s)	Mice ; Animals ; Nitric Oxide Synthase Type I/genetics ; Nitric Oxide Synthase Type I/metabolism ; Enteric Nervous System/metabolism ; Neurons/physiology ; Muscle Relaxation ; Stroke/metabolism
Chemical Substances	Nitric Oxide Synthase Type I (EC 1.14.13.39)
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.033279
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Article: Combination of Histone Deacetylase Inhibitor Panobinostat (LBH589) with β-Catenin Inhibitor Tegavivint (BC2059) Exerts Significant Anti-Myeloma Activity Both In Vitro and In Vivo.

Savvidou, Ioanna / Khong, Tiffany / Whish, Sophie / Carmichael, Irena / Sepehrizadeh, Tara / Mithraprabhu, Sridurga / Horrigan, Stephen K / de Veer, Michael / Spencer, Andrew

Cancers

2022 Volume 14, Issue 3

Abstract: Over the last three decades changes in the treatment paradigm for newly diagnosed multiple myeloma (MM) have led to a significant increase in overall survival. Despite this, the majority of patients relapse after one or more lines of treatment while ... ...

Abstract	Over the last three decades changes in the treatment paradigm for newly diagnosed multiple myeloma (MM) have led to a significant increase in overall survival. Despite this, the majority of patients relapse after one or more lines of treatment while acquiring resistance to available therapies. Panobinostat, a pan-histone deacetylase inhibitor, was approved by the FDA in 2015 for patients with relapsed MM but how to incorporate panobinostat most effectively into everyday practice remains unclear. Dysregulation of the Wnt canonical pathway, and its key mediator β-catenin, has been shown to be important for the evolution of MM and the acquisition of drug resistance, making it a potentially attractive therapeutic target. Despite concerns regarding the safety of Wnt pathway inhibitors, we have recently shown that the β-catenin inhibitor Tegavivint is deliverable and effective in in vivo models of MM. In this study we show that the combination of low concentrations of panobinostat and Tegavivint have significant in vitro and in vivo anti-MM effects including in the context of proteasome inhibitor resistance, by targeting both aerobic glycolysis and mitochondrial respiration and the down-regulation of down-stream β-catenin targets including myc, cyclinD1, and cyclinD2. The significant anti-MM effect of this novel combination warrants further evaluation for the treatment of MM patients with relapsed and/or refractory MM.
Language	English
Publishing date	2022-02-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14030840
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Article ; Online: A Biodistribution Study of the Radiolabeled Kv1.3-Blocking Peptide DOTA-HsTX1[R14A] Demonstrates Brain Uptake in a Mouse Model of Neuroinflammation.

Reddiar, Sanjeevini Babu / de Veer, Michael / Paterson, Brett M / Sepehrizadeh, Tara / Wai, Dorothy C C / Csoti, Agota / Panyi, Gyorgy / Nicolazzo, Joseph A / Norton, Raymond S

Molecular pharmaceutics

2022 Volume 20, Issue 1, Page(s) 255–266

Abstract: The voltage-gated potassium channel Kv1.3 regulates the pro-inflammatory function of microglia and is highly expressed in the post-mortem brains of individuals with Alzheimer's and Parkinson's diseases. HsTX1[R14A] is a selective and potent peptide ... ...

Abstract	The voltage-gated potassium channel Kv1.3 regulates the pro-inflammatory function of microglia and is highly expressed in the post-mortem brains of individuals with Alzheimer's and Parkinson's diseases. HsTX1[R14A] is a selective and potent peptide inhibitor of the Kv1.3 channel (IC
MeSH term(s)	Mice ; Animals ; Neuroinflammatory Diseases ; Tissue Distribution ; Lipopolysaccharides ; Gallium Radioisotopes/metabolism ; Mice, Inbred C57BL ; Peptides/chemistry ; Brain/diagnostic imaging ; Brain/metabolism ; Inflammation/metabolism ; Positron-Emission Tomography
Chemical Substances	1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (1HTE449DGZ) ; Lipopolysaccharides ; Gallium Radioisotopes ; Peptides
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.2c00614
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Article ; Online: Gpr88

Spark, Daisy L / Vermeulen, Michela H / de la Fuente Gonzalez, Rocío A / Hatzipantelis, Cassandra J / Rueda, Patricia / Sepehrizadeh, Tara / De Veer, Michael / Mannoury la Cour, Clotilde / Fornito, Alex / Langiu, Monica / Stewart, Gregory D / Nithianantharajah, Jess / Langmead, Christopher J

Biological psychiatry global open science

2022 Volume 3, Issue 4, Page(s) 1053–1061

Abstract: Background: Disrupted motivational control is a common-but poorly treated-feature of psychiatric disorders, arising via aberrant mesolimbic dopaminergic signaling. GPR88 is an orphan G protein-coupled receptor that is highly expressed in the striatum ... ...

Abstract	Background: Disrupted motivational control is a common-but poorly treated-feature of psychiatric disorders, arising via aberrant mesolimbic dopaminergic signaling. GPR88 is an orphan G protein-coupled receptor that is highly expressed in the striatum and therefore well placed to modulate disrupted signaling. While the phenotype of Methods: In male and female Results: We showed that male and female Conclusions: Our results highlight that GPR88 regulates motivational control but that disruption of such behaviors following
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Journal Article
ISSN	2667-1743
ISSN (online)	2667-1743
DOI	10.1016/j.bpsgos.2022.10.008
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Article ; Online: Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum.

Reichenbach, Alex / Clarke, Rachel E / Stark, Romana / Lockie, Sarah Haas / Mequinion, Mathieu / Dempsey, Harry / Rawlinson, Sasha / Reed, Felicia / Sepehrizadeh, Tara / DeVeer, Michael / Munder, Astrid C / Nunez-Iglesias, Juan / Spanswick, David C / Mynatt, Randall / Kravitz, Alexxai V / Dayas, Christopher V / Brown, Robyn / Andrews, Zane B

eLife

2022 Volume 11

Abstract: Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic- ...

Abstract	Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase (
MeSH term(s)	Agouti-Related Protein/genetics ; Agouti-Related Protein/metabolism ; Animals ; Corpus Striatum/physiology ; Dopamine/physiology ; Homeostasis ; Mice ; Mice, Knockout ; Neurons/physiology ; Signal Transduction
Chemical Substances	Agouti-Related Protein ; Agrp protein, mouse ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.72668
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Article ; Online: Bone Marrow Adipose Tissue Quantification by Imaging.

Bani Hassan, Ebrahim / Ghasem-Zadeh, Ali / Imani, Mahdi / Kutaiba, Numan / Wright, David K / Sepehrizadeh, Tara / Duque, Gustavo

Current osteoporosis reports

2019 Volume 17, Issue 6, Page(s) 416–428

Abstract: Purpose of review: The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and ... ...

Abstract	Purpose of review: The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and inflammation. Recent findings: Changes in the MAT volume and fatty acid composition appear to drive bone and hematopoietic marrow deterioration, and studying it may open new horizons to predict bone fragility and anemia development. MAT has the potential to negatively impact bone volume and strength through several mechanisms that are partially described by inflammaging and lipotoxicity terminology. Evidence indicates paramount importance of MAT in age-associated decline of bone and red marrow structure and function. Currently, MAT measurement is being tested and validated by several techniques. However, purpose-specific adaptation of existing imaging technologies and, more importantly, development of new modalities to quantitatively measure MAT are yet to be done.
MeSH term(s)	Adipose Tissue/anatomy & histology ; Adipose Tissue/diagnostic imaging ; Adipose Tissue/pathology ; Animals ; Bone Marrow/anatomy & histology ; Bone Marrow/diagnostic imaging ; Bone Marrow/pathology ; Bone and Bones/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Organ Size ; Tomography, X-Ray Computed
Language	English
Publishing date	2019-11-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-019-00539-5
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Article ; Online: Advanced MRI analysis to detect white matter brain injury in growth restricted newborn lambs.

Malhotra, Atul / Sepehrizadeh, Tara / Dhollander, Thijs / Wright, David / Castillo-Melendez, Margie / Sutherland, Amy E / Pham, Yen / Ditchfield, Michael / Polglase, Graeme R / de Veer, Michael / Jenkin, Graham / Pannek, Kerstin / Shishegar, Rosita / Miller, Suzanne L

NeuroImage. Clinical

2019 Volume 24, Page(s) 101991

Abstract: Background: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not ... ...

Abstract	Background: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. Methods: Surgery was undertaken in twin bearing pregnant ewes at 88-90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. Results: FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistically significant differences between groups in the ROIs. Fixel-based analysis of 3-tissue CSD, however, did reveal a decrease in fibre cross-section (FC, p < .05) but not in fibre density (FD) or combined fibre density and cross-section (FDC) in FGR vs. AGA lamb brains. The specific tracts that showed a decrease in FC were in the regions of the periventricular white matter, hippocampus and cerebellar white matter, and were supported by histological evidence of white matter hypomyelination and disorganisation in corresponding FGR lamb brain regions. Conclusions: The neuropathology associated with FGR in neonatal preterm lambs is subtle and imaging detection may require advanced MRI and tract-based analysis techniques. Fixel-based analysis of 3-tissue CSD demonstrates that the preterm neonatal FGR brain shows evidence of macrostructural (cross-sectional) deficits in white matter subsequent to altered antenatal development. These findings can inform analysis of similar brain pathology in neonatal infants.
MeSH term(s)	Animals ; Animals, Newborn ; Brain Injuries/diagnostic imaging ; Diffusion Tensor Imaging ; Disease Models, Animal ; Fetal Growth Retardation/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Neuroimaging/methods ; Sheep ; White Matter/diagnostic imaging
Language	English
Publishing date	2019-08-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2019.101991
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Article ; Online: Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection.

Shim, Raymond / Wen, Shu Wen / Wanrooy, Brooke J / Rank, Michelle / Thirugnanachandran, Tharani / Ho, Luke / Sepehrizadeh, Tara / de Veer, Michael / Srikanth, Velandai K / Ma, Henry / Phan, Thanh G / Sobey, Christopher G / Wong, Connie H Y

Translational stroke research

2019 Volume 11, Issue 3, Page(s) 387–401

Abstract: Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle- ... ...

Abstract	Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.
Language	English
Publishing date	2019-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541897-X
ISSN	1868-601X ; 1868-4483
ISSN (online)	1868-601X
ISSN	1868-4483
DOI	10.1007/s12975-019-00738-3
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Article ; Online: Functional Brush Poly(2-ethyl-2-oxazine)s: Synthesis by CROP and RAFT, Thermoresponsiveness and Grafting onto Iron Oxide Nanoparticles.

Klein, Tobias / Parkin, Joshua / de Jongh, Patrick A J M / Esser, Lars / Sepehrizadeh, Tara / Zheng, Gang / De Veer, Michael / Alt, Karen / Hagemeyer, Christoph E / Haddleton, David M / Davis, Thomas P / Thelakkat, Mukundan / Kempe, Kristian

Macromolecular rapid communications

2019 Volume 40, Issue 10, Page(s) e1800911

Abstract: Brush polymers are highly functional polymeric materials combining the properties of different polymer classes and have found numerous applications, for example, in nanomedicine. Here, the synthesis of functional phosphonate-ester-bearing brush polymers ... ...

Abstract	Brush polymers are highly functional polymeric materials combining the properties of different polymer classes and have found numerous applications, for example, in nanomedicine. Here, the synthesis of functional phosphonate-ester-bearing brush polymers based on poly(2-oxazine)s is reported through a combination of cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazine and reversible addition-fragmentation chain transfer (RAFT) polymerization. In this way, a small library of well-defined (Đ ≤ 1.17) poly(oligo(2-ethyl-2-oxazine) methacrylate) P(OEtOzMA)
MeSH term(s)	Cations ; Colloids/chemistry ; Contrast Media/chemical synthesis ; Contrast Media/chemistry ; Esters/chemistry ; Ferric Compounds/chemistry ; Humans ; Magnetic Resonance Imaging ; Methacrylates/chemistry ; Nanoparticles/chemistry ; Organophosphonates/chemistry ; Polyamines/chemical synthesis ; Polyamines/chemistry ; Polymerization ; Temperature
Chemical Substances	Cations ; Colloids ; Contrast Media ; Esters ; Ferric Compounds ; Methacrylates ; Organophosphonates ; Polyamines ; poly(2-ethyl-2-oxazoline) ; ferric oxide (1K09F3G675)
Language	English
Publishing date	2019-02-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1475027-2
ISSN	1521-3927 ; 1022-1336
ISSN (online)	1521-3927
ISSN	1022-1336
DOI	10.1002/marc.201800911
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