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Article ; Online: Determination of oxygen relaxivity in oxygen nanobubbles at 3 and 7 Tesla.

Bluemke, Emma / Young, Liam A J / Owen, Joshua / Smart, Sean / Kinchesh, Paul / Bulte, Daniel P / Stride, Eleanor

2022 Volume 35, Issue 5, Page(s) 817–826

Abstract: Objective: Oxygen-loaded nanobubbles have shown potential for reducing tumour hypoxia and improving treatment outcomes, however, it remains difficult to noninvasively measure the changes in partial pressure of oxygen (PO: Methods: T: Results: The ... ...

Abstract	Objective: Oxygen-loaded nanobubbles have shown potential for reducing tumour hypoxia and improving treatment outcomes, however, it remains difficult to noninvasively measure the changes in partial pressure of oxygen (PO Methods: T Results: The r Conclusion: This suggests that T
MeSH term(s)	Magnetic Resonance Imaging/methods ; Oxygen ; Phantoms, Imaging
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-04-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1160826-2
ISSN	1352-8661 ; 0968-5243
ISSN (online)	1352-8661
ISSN	0968-5243
DOI	10.1007/s10334-022-01009-3
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Zs.A 3788: Show issues

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Article: Magnetic resonance imaging of oxygen microbubbles.

Thompson, Elinor / Smart, Sean / Kinchesh, Paul / Bulte, Daniel / Stride, Eleanor

Healthcare technology letters

2019 Volume 6, Issue 5, Page(s) 138–142

Abstract: Oxygen loaded microbubbles are being investigated as a means of reducing tumour hypoxia in order to improve response to cancer therapy. To optimise this approach, it is desirable to be able to measure changes in tissue oxygenation in real-time during ... ...

Abstract	Oxygen loaded microbubbles are being investigated as a means of reducing tumour hypoxia in order to improve response to cancer therapy. To optimise this approach, it is desirable to be able to measure changes in tissue oxygenation in real-time during treatment. In this study, the feasibility of using magnetic resonance imaging (MRI) for this purpose was investigated. Longitudinal relaxation time (T1) measurements were made in simple hydrogel phantoms containing two different concentrations of oxygen microbubbles. T1 was found to be unaffected by the presence of oxygen microbubbles at either concentration. Upon application of ultrasound to destroy the microbubbles, however, a statistically significant reduction in T1 was seen for the higher microbubble concentration. Further work is needed to assess the influence of physiological conditions upon the measurements, but these preliminary results suggest that MRI could provide a method for quantifying the changes in tissue oxygenation produced by microbubbles during therapy.
Language	English
Publishing date	2019-08-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2782924-8
ISSN	2053-3713
ISSN	2053-3713
DOI	10.1049/htl.2018.5058
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Article ; Online: Developing a metabolic clearance rate framework as a translational analysis approach for hyperpolarized

Grist, James T / Bøgh, Nikolaj / Hansen, Esben Søvsø / Schneider, Anna M / Healicon, Richard / Ball, Vicky / Miller, Jack J J J / Smart, Sean / Couch, Yvonne / Buchan, Alastair M / Tyler, Damian J / Laustsen, Christoffer

Scientific reports

2023 Volume 13, Issue 1, Page(s) 1613

Abstract: Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized ... ...

Abstract	Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T
MeSH term(s)	Humans ; Rats ; Swine ; Animals ; Metabolic Clearance Rate ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Brain/metabolism ; Pyruvic Acid/metabolism ; Carbon Isotopes/metabolism ; Head
Chemical Substances	Pyruvic Acid (8558G7RUTR) ; Carbon Isotopes
Language	English
Publishing date	2023-01-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-28643-8
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Article ; Online: Electromagnetically Transparent Graphene Respiratory Sensors for Multimodal Small Animal Imaging.

Tweedie, Martin E P / Kersemans, Veerle / Gilchrist, Stuart / Smart, Sean / Warner, Jamie H

Advanced healthcare materials

2020 Volume 9, Issue 21, Page(s) e2001222

Abstract: Magnetic resonance imaging (MRI) and computed tomography (CT) imaging with X-rays are crucial diagnostic techniques in medicine, especially in oncology for evaluating the response to treatment. Body movement causes image blurring and synchronized gating ... ...

Abstract	Magnetic resonance imaging (MRI) and computed tomography (CT) imaging with X-rays are crucial diagnostic techniques in medicine, especially in oncology for evaluating the response to treatment. Body movement causes image blurring and synchronized gating to the respiratory and cardiac cycles is required. Degradation of MRI and CT imaging by the presence of metal in electronic respiratory sensors has limited their use, with a preference for pressure balloons for detecting respiration, but these are cumbersome and insensitive. Here, graphene's role is studied as an electromagnetically transparent electrode in a piezoelectric graphene respiratory sensor (GRS) device designed specifically for dual gated MRI and CT imaging of small animals. The GRS is integrated into a 3D-printed cradle with all-carbon-based device life support (heating pad) and monitoring of small animals (electrocardiogram), enabling both heartbeat and respiration detection, significant improvements to throughput and reproducibility, and reduced animal suffering. This shows graphene's potential for a wide range of electromagnetic transparent electronics for medical imaging and diagnostics, beyond conventional metal electrodes.
MeSH term(s)	Animals ; Graphite ; Heart ; Magnetic Resonance Imaging ; Reproducibility of Results ; Respiration
Chemical Substances	Graphite (7782-42-5)
Language	English
Publishing date	2020-09-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202001222
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Article ; Online: Protocol for tissue processing and paraffin embedding of mouse brains following ex vivo MRI.

Smart, Adele / Tisca, Cristiana / Huszar, Istvan N / Kor, Daniel / Ansorge, Olaf / Tachrount, Mohamed / Smart, Sean / Lerch, Jason P / Miller, Karla L / Martins-Bach, Aurea B

STAR protocols

2023 Volume 4, Issue 4, Page(s) 102681

Abstract: Combining histology and ex vivo MRI from the same mouse brain is a powerful way to study brain microstructure. Mouse brains prepared for ex vivo MRI are often kept in storage solution for months, potentially becoming brittle and showing reduced ... ...

Abstract	Combining histology and ex vivo MRI from the same mouse brain is a powerful way to study brain microstructure. Mouse brains prepared for ex vivo MRI are often kept in storage solution for months, potentially becoming brittle and showing reduced antigenicity. Here, we describe a protocol for mouse brain dissection, tissue processing, paraffin embedding, sectioning, and staining. We then detail registration of histology to ex vivo MRI data from the same sample and extraction of quantitative histological measurements.
MeSH term(s)	Mice ; Animals ; Paraffin Embedding ; Brain/diagnostic imaging ; Dissection ; Staining and Labeling ; Magnetic Resonance Imaging/methods
Language	English
Publishing date	2023-11-09
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102681
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Article ; Online: A System-Agnostic, Adaptable and Extensible Animal Support Cradle System for Cardio-Respiratory-Synchronised, and Other, Multi-Modal Imaging of Small Animals.

Kersemans, Veerle / Gilchrist, Stuart / Allen, Philip Danny / Wallington, Sheena / Kinchesh, Paul / Prentice, John / Tweedie, Martin / Warner, Jamie H / Smart, Sean C

Tomography (Ann Arbor, Mich.)

2021 Volume 7, Issue 1, Page(s) 39–54

Abstract: Standardisation of animal handling procedures for a wide range of preclinical imaging scanners will improve imaging performance and reproducibility of scientific data. Whilst there has been significant effort in defining how well scanners should operate ... ...

Abstract	Standardisation of animal handling procedures for a wide range of preclinical imaging scanners will improve imaging performance and reproducibility of scientific data. Whilst there has been significant effort in defining how well scanners should operate and how in vivo experimentation should be practised, there is little detail on how to achieve optimal scanner performance with best practices in animal welfare. Here, we describe a system-agnostic, adaptable and extensible animal support cradle system for cardio-respiratory-synchronised, and other, multi-modal imaging of small animals. The animal support cradle can be adapted on a per application basis and features integrated tubing for anaesthetic and tracer delivery, an electrically driven rectal temperature maintenance system and respiratory and cardiac monitoring. Through a combination of careful material and device selection, we have described an approach that allows animals to be transferred whilst under general anaesthesia between any of the tomographic scanners we currently or have previously operated. The set-up is minimally invasive, cheap and easy to implement and for multi-modal, multi-vendor imaging of small animals.
MeSH term(s)	Anesthetics ; Animals ; Heart/diagnostic imaging ; Multimodal Imaging ; Reproducibility of Results
Chemical Substances	Anesthetics
Language	English
Publishing date	2021-02-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-139X
ISSN (online)	2379-139X
DOI	10.3390/tomography7010004
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Article ; Online: A simple, open and extensible gating Control unit for cardiac and respiratory synchronisation control in small animal MRI and demonstration of its robust performance in steady-state maintained CINE-MRI.

Gilchrist, Stuart / Kinchesh, Paul / Kersemans, Veerle / Beech, John / Allen, Danny / Brady, Michael / Vojnovic, Borivoj / Schneider, Jurgen / Miller, Jack / Smart, Sean

Magnetic resonance imaging

2021 Volume 81, Page(s) 1–9

Abstract: Prospective cardiac gating during MRI is hampered by electromagnetic induction from the rapidly switched imaging gradients into the ECG detection circuit. This is particularly challenging in small animal MRI, as higher heart rates combined with a smaller ...

Abstract	Prospective cardiac gating during MRI is hampered by electromagnetic induction from the rapidly switched imaging gradients into the ECG detection circuit. This is particularly challenging in small animal MRI, as higher heart rates combined with a smaller myocardial mass render routine ECG detection challenging. We have developed an open-hardware system that enables continuously running MRI scans to be performed in conjunction with cardio-respiratory gating such that the relaxation-weighted steady state magnetisation is maintained throughout the scan. This requires that the R-wave must be detected reliably even in the presence of rapidly switching gradients, and that data previously acquired that were corrupted by respiratory motion re-acquired. The accurately maintained steady-state magnetisation leads to an improvement in image quality and removes alterations in intensity that may otherwise occur throughout the cardiac cycle and impact upon automated image analysis. We describe the hardware required to enable this and demonstrate its application and robust performance using prospectively cardio-respiratory gated CINE imaging that is operated at a single, constant TR. Schematics, technical drawings, component listing and assembly instructions are made publicly available.
MeSH term(s)	Animals ; Cardiac-Gated Imaging Techniques ; Heart/diagnostic imaging ; Magnetic Resonance Imaging ; Magnetic Resonance Imaging, Cine ; Prospective Studies
Language	English
Publishing date	2021-04-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604885-7
ISSN	1873-5894 ; 0730-725X
ISSN (online)	1873-5894
ISSN	0730-725X
DOI	10.1016/j.mri.2021.04.012
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Zs.A 1817: Show issues

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Article ; Online: Assessing the effect of anesthetic gas mixtures on hyperpolarized

Healicon, Richard / Rooney, Catriona H E / Ball, Vicky / Shinozaki, Ayaka / Miller, Jack J / Smart, Sean / Radford-Smith, Daniel / Anthony, Daniel / Tyler, Damian J / Grist, James T

Magnetic resonance in medicine

2022 Volume 88, Issue 3, Page(s) 1324–1332

Abstract: Purpose: To determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain.: Methods: Seven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1-: ... ...

Abstract	Purpose: To determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain. Methods: Seven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1- Results: There was a significant increase in bicarbonate:total Conclusions: These results demonstrate that the detection and quantification of cerebral metabolism and perfusion is dependent on the oxygen protocol used in the anesthetized rodent brain.
MeSH term(s)	Anesthetics, Inhalation/pharmacology ; Animals ; Bicarbonates/metabolism ; Brain/metabolism ; Carbon Isotopes/metabolism ; Magnetic Resonance Imaging/methods ; Oxygen/metabolism ; Pyruvic Acid/metabolism ; Rats
Chemical Substances	Anesthetics, Inhalation ; Bicarbonates ; Carbon Isotopes ; Pyruvic Acid (8558G7RUTR) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605774-3
ISSN	1522-2594 ; 0740-3194
ISSN (online)	1522-2594
ISSN	0740-3194
DOI	10.1002/mrm.29274
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Zs.A 1959: Show issues

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Article ; Online: The Histone Deacetylase Inhibitor Romidepsin Spares Normal Tissues While Acting as an Effective Radiosensitizer in Bladder Tumors in Vivo.

Paillas, Salome / Then, Chee K / Kilgas, Susan / Ruan, Jia-Ling / Thompson, James / Elliott, Amy / Smart, Sean / Kiltie, Anne E

International journal of radiation oncology, biology, physics

2020 Volume 107, Issue 1, Page(s) 212–221

Abstract: Purpose: Muscle-invasive bladder cancer has a 40% to 60% 5-year survival rate with radical treatment by surgical removal of the bladder or radiation therapy-based bladder preservation techniques, including concurrent chemoradiation. Elderly patients ... ...

Abstract	Purpose: Muscle-invasive bladder cancer has a 40% to 60% 5-year survival rate with radical treatment by surgical removal of the bladder or radiation therapy-based bladder preservation techniques, including concurrent chemoradiation. Elderly patients cannot tolerate current chemoradiation therapy regimens and often receive only radiation therapy, which is less effective. We urgently need effective chemotherapy agents for use with radiation therapy combinations that are nontoxic to normal tissues and tolerated by elderly patients. Methods and materials: We have identified histone deacetylase (HDAC) inhibitors as promising agents to study. Pan-HDAC inhibition, using panobinostat, is a good strategy for radiosensitization, but more selective agents may be more useful radiosensitizers in a clinical setting, resulting in fewer systemic side effects. Herein, we study the HDAC class I-selective agent romidepsin, which we predict to have fewer off-target effects than panobinostat while maintaining an effective level of tumor radiosensitization. Results: In vitro effects of romidepsin were assessed by clonogenic assay and showed that romidepsin was effective in the nanomolar range in different bladder cancer cells and radiosensitized these cells. The radiosensitizing effect of romidepsin was confirmed in vivo using superficial xenografts. The drug/irradiation combination treatment resulted in significant tumor growth delay but did not increase the severity of acute (3.75 days) intestinal normal tissue toxicity or late toxicity at 29 weeks. Moreover, we showed that romidepsin treatment impaired both homologous recombination and nonhomologous end joining DNA repair pathways, suggesting that the disruption of DNA repair pathways caused by romidepsin is a key mechanism for its radiosensitizing effect in bladder cancer cells. Conclusions: This study demonstrates that romidepsin is an effective radiosensitizer in vitro and in vivo and does not increase the acute and late toxicity after ionizing radiation. Romidepsin is already in clinical use for the cutaneous T-cell lymphoma, but a phase 1 clinical trial of romidepsin as a radiosensitizer could be considered in muscle-invasive bladder cancer.
MeSH term(s)	Acetylation/drug effects ; Acetylation/radiation effects ; Cell Line, Tumor ; DNA Breaks, Double-Stranded/drug effects ; DNA Breaks, Double-Stranded/radiation effects ; DNA Repair/drug effects ; DNA Repair/radiation effects ; Depsipeptides/adverse effects ; Depsipeptides/pharmacology ; Histone Deacetylase Inhibitors/adverse effects ; Histone Deacetylase Inhibitors/pharmacology ; Histones/metabolism ; Humans ; Organs at Risk/radiation effects ; Radiation-Sensitizing Agents/adverse effects ; Radiation-Sensitizing Agents/pharmacology ; Urinary Bladder Neoplasms/pathology ; Xenograft Model Antitumor Assays
Chemical Substances	Depsipeptides ; Histone Deacetylase Inhibitors ; Histones ; Radiation-Sensitizing Agents ; romidepsin (CX3T89XQBK)
Language	English
Publishing date	2020-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2020.01.015
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Zs.A 1218: Show issues

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Article ; Online: Microbubbles Containing Lysolipid Enhance Ultrasound-Mediated Blood-Brain Barrier Breakdown In Vivo.

Vince, Oliver / Peeters, Sarah / Johanssen, Vanessa A / Gray, Michael / Smart, Sean / Sibson, Nicola R / Stride, Eleanor

Advanced healthcare materials

2020 Volume 10, Issue 3, Page(s) e2001343

Abstract: Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood-brain barrier (BBB) permeability to therapeutics. To reduce off-target effects, it is desirable to minimize the ultrasound pressures required. It has been shown ... ...

Abstract	Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood-brain barrier (BBB) permeability to therapeutics. To reduce off-target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso-MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso-MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso-MBs or control MBs and gadolinium-DTPA (Gd-DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak-negative pressures 160-480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd-DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso-MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid-shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain.
MeSH term(s)	Animals ; Blood-Brain Barrier/diagnostic imaging ; Drug Delivery Systems ; Female ; Magnetic Resonance Imaging ; Mice ; Mice, Inbred BALB C ; Microbubbles ; Ultrasonography
Language	English
Publishing date	2020-11-16
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202001343
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