An MRI-Compatible High Frequency AC Resistive Heating System for Homeothermic Maintenance in Small Animals

Gilchrist, Stuart; Gomes, Ana L.; Kinchesh, Paul; Kersemans, Veerle; Allen, Danny; Smart, Sean

doi:10.1371/journal.pone.0164920

Cited by 10 publications

(10 citation statements)

References 8 publications

(11 reference statements)

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“…Mice were anesthetized and maintained at a body temperature of 35°C using an MRI compatible electrical heating system 23 and a respiration rate of 50–60 breaths per min. Dynamic contrast enhanced MRI (DCE-MRI) was performed at 7.0 T (VNMRS, Varian) using a 25 mm diameter, 35 mm long quadrature birdcage RF coil (Rapid Biomedical) operated in transmit/receive mode.…”

Section: Methodsmentioning

confidence: 99%

Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3

Lauder

Smart

Kersemans

et al. 2020

J Immunother Cancer

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BackgroundDespite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors.MethodsMice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later.ResultsAs observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8+ T cells, T cell factor 1 (TCF1)+ T cells and CD69− T cells, compatible with induction of a sustained tumor-specific T cell response. Treg numbers were significantly reduced in both regressor and non-regressor tumors compared with untreated tumors. The remaining Treg in non-regressor tumors were however significantly enriched with cells expressing the coinhibitory receptor LAG3, compared with Treg in regressor and untreated tumors. This striking difference prompted us to sequentially block PI3Kδ and LAG3. This combination enabled successful therapy of all mice, demonstrating the functional importance of LAG3 in non-regression of tumors on PI3Kδ inhibition therapy. Follow-up studies, performed using additional cancer cell lines, namely MC38 and CT26, indicated that a partial initial response to PI3Kδ inhibition is an essential prerequisite to a sequential therapeutic benefit of anti-LAG3 antibodies.ConclusionsThese data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies.

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Section: Methodsmentioning

confidence: 99%

Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3

Lauder

Smart

Kersemans

et al. 2020

J Immunother Cancer

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“…MRI and CT Measurements-Animal Handling: Animals were handled in accordance with the UK Animals Scientific Procedure Act of 1986, under licenses approved by the UK Home Office, and with the approval of the University of Oxford ethical review committee, under PPL 30/3266. Details of animal preparation and handling are adapted from Gilchrist et al [28] MRI and CT Measurements-Animal Preparation: CBA mice (Charles River) were housed in individual ventilated cages, maintained at 22°C and 50% humidity, with a 12 h dark/light cycle. Animals were provided with autoclaved bedding material, cage enrichment, filtered water ad libitum, and a certified rodent diet.…”

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confidence: 99%

Electromagnetically Transparent Graphene Respiratory Sensors for Multimodal Small Animal Imaging

Tweedie

Kersemans

Gilchrist

et al. 2020

Adv Healthcare Materials

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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. Stable, high-resolution images in magnetic resonance imaging (MRI) and computed tomography (CT) scanning minimize

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“…An in-house built alternating-current resistive heating setup was constructed to create an NMR-compatible heating setup that does not interfere with the multinuclear NMR acquisition 56 . A signal generator (B071HJ31WN, KKmoon, China), operating at 100 kHz was connected to a 130W class D amplifier (TPA3250D2EVM, Texas instruments Inc., USA).…”

Section: Methodsmentioning

confidence: 99%

Multinuclear absolute magnetic resonance thermometry

et al. 2019

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Non-invasive measurement of absolute temperature is important for proper characterization of various pathologies and for evaluation of thermal dose during interventional procedures. The proton magnetic resonance (MR) frequency shift method can be used to map relative temperature changes in tissues; however, spatiotemporal variations in the main magnetic field and the lack of an internal frequency reference at each location challenge the determination of absolute temperature. Here, we introduce a novel multinuclear method for absolute MR thermometry, based on the fact that the proton and sodium nuclei exhibit a unique and distinct characteristic frequency dependence with temperature. A one-to-one mapping between the precession frequency difference of the two nuclei and absolute temperature is demonstrated. Proof-of-concept experiments were conducted in aqueous solutions with different NaCl concentrations, in agarose gel samples, and in freshly excised ex vivo mouse * Shared last authorship

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An MRI-Compatible High Frequency AC Resistive Heating System for Homeothermic Maintenance in Small Animals

Cited by 10 publications

References 8 publications

Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3

Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3

Electromagnetically Transparent Graphene Respiratory Sensors for Multimodal Small Animal Imaging

Multinuclear absolute magnetic resonance thermometry

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