Publications by authors named "Sean C Smart"

Purpose: Preclinical studies using ultra-high dose rate (FLASH) irradiation have demonstrated reduced normal tissue toxicity compared with conventional dose rate (CONV) irradiation, although this finding is not universal. We investigated the effect of temporal pulse structure and average dose rate of FLASH compared with CONV irradiation on acute intestinal toxicity.

Materials And Methods: Whole abdomens of C3H mice were irradiated with a single fraction to various doses, using a 6 MeV electron linear accelerator with single pulse FLASH (dose rate = 2-6 × 10 Gy/s) or conventional (CONV; 0.

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Background: There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease.

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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.

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Purpose: High resolution multi-gradient echo (MGE) scanning is typically used for detection of molecularly targeted iron oxide particles. The images of individual echoes are often combined to generate a composite image with improved SNR from the early echoes and boosted contrast from later echoes. In 3D implementations prolonged scanning at high gradient duty cycles induces a B shift that predominantly affects image alignment in the slow phase encoding dimension of 3D MGE images.

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A magnetic resonance (MR)-, computed tomography (CT)-, single-photon emission computed tomography (SPECT)-, and positron emission tomography (PET)-compatible carbon-fiber sheet resistor for temperature maintenance in small animals where space limitations prevent the use of circulating fluids was developed. A 250 Ω carbon-fiber sheet resistor was mounted to the underside of an imaging cradle. Alternating current, operating at 99 kHz, and with a power of 1-2 W, was applied to the resistor providing a cradle base temperature of ∼37°C.

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Purpose: Multi-slice scanning in the abdomen and thorax of small animals is compromised by the effects of respiration unless imaging and respiration are synchronised. To avoid the signal modulations that result from respiration motion and a variable TR, blocks of fully relaxed slices are typically acquired during inter-breath periods, at the cost of scan efficiency. This paper reports a conceptually simple yet effective prospective gating acquisition mode for multi-slice scanning in free breathing small animals at any fixed TR of choice with reduced sensitivity to respiratory motion.

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The identification and measurement of tumours is a key requirement in the study of tumour development in mouse models of human cancer. Disease burden in autochthonous tumours, such as those arising in the lung, can be seen with non-invasive imaging, but cannot be accurately measured using standard tools such as callipers. Lung imaging is further complicated in the mouse due to instabilities arising from the rapid but cyclic cardio-respiratory motions, and the desire to use free-breathing animals.

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Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors.

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Purpose: Cardiac and respiratory motion derived image artefacts are reduced when data are acquired with cardiac and respiratory synchronisation. Where steady state imaging techniques are required in small animals, synchronisation is most commonly performed using retrospective gating techniques but these invoke an inherent time penalty. This paper reports the development of prospective gating techniques for cardiac and respiratory motion desensitised MRI with significantly reduced minimum scan time compared to retrospective gating.

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Background: The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer.

Methods: A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post injection of I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively.

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Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC.

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The addition of fluorescence guidance in laparoscopic procedures has gained significant interest in recent years, particularly through the use of near infrared (NIR) markers. In this work we present a novel laparoscope camera coupler based on an electrically tunable fluidic lens that permits programmable focus control and has desirable achromatic performance from the visible to the NIR. Its use extends the lower working distance limit and improves detection sensitivity, important for work with molecularly targeted fluorescence markers.

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Purpose: To assess the efficacy of different schedules for combining external beam radiotherapy (EBRT) with molecular radiotherapy (MRT) using I-mIBG in the management of neuroblastoma.

Materials And Methods: BALB/c nu/nu mice bearing SK-N-SH neuroblastoma xenografts were assigned to five treatment groups: I-mIBG 24h after EBRT, EBRT 6days after I-mIBG, EBRT alone, I-mIBG alone and control (untreated). A total of 56 mice were assigned to 3 studies.

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Purpose: To demonstrate how reference data affect the quantification of the apparent diffusion coefficient (ADC) in long diffusion time measurements with diffusion-weighted stimulated echo acquisition mode (DW-STEAM) measurements, and to present a modification to avoid contribution from crusher gradients in DW-STEAM.

Methods: For DW-STEAM, reference measurements at long diffusion times have significant b value, because b = 0 cannot be achieved in practice as a result of the need for signal spoiling. Two strategies for acquiring reference data over a range of diffusion times were considered: constant diffusion weighting (fixed-b ) and constant gradient area (fixed-q ).

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Introduction: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse.

Methods: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated.

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Purpose: To develop an MRI-compatible resistive heater, using high frequency alternating current (AC), for temperature maintenance of anaesthetised animals.

Materials And Methods: An MRI-compatible resistive electrical heater was formed from narrow gauge wire connected to a high frequency (10-100 kHz) AC power source. Multiple gradient echo images covering a range of echo times, and pulse-acquire spectra were acquired with the wire heater powered using high frequency AC or DC power sources and without any current flowing in order to assess the sensitivity of the MRI acquisitions to the presence of current flow through the heater wire.

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The extent of tumor oxygenation is an important factor contributing to the efficacy of radiation therapy (RTx). Interestingly, several preclinical studies have shown benefit of combining RTx with drugs that inhibit tumor blood vessel growth, i.e.

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Introduction: Preclinical in vivo CT is commonly used to visualise vessels at a macroscopic scale. However, it is prone to many artefacts which can degrade the quality of CT images significantly. Although some artefacts can be partially corrected for during image processing, they are best avoided during acquisition.

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Purpose: To develop an MR-compatible resistive heater for temperature maintenance of anaesthetized animals.

Materials And Methods: An MR-compatible resistive electrical heater was formed from a tightly-wound twisted pair wire, interfaced to a homeothermic maintenance controller. Fat-suppressed images and localized spectra were acquired with the twisted pair heater and a near-identical single strand heater during operation at maximum power.

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Copper(II)bis(thiosemicarbazonato) complexes such as [(64)Cu]Cu-ATSM continue to be investigated for positron emission tomography (PET) imaging of tumour hypoxia. However, the currently proposed mechanisms for the mode of action of these complexes are unable to account fully for their observed biological behaviour. In order to examine the roles of the copper metal and the ligand, we designed a pair of (123)I/(64)Cu-copper bis(thiosemicarbazonates), radiolabelled at either the metal or at the ligand.

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Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule α(v)β(3) integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency.

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Unlabelled: (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazonate), (64)Cu-ATSM, continues to be investigated clinically as a PET agent both for delineation of tumor hypoxia and as an effective indicator of patient prognosis, but there are still aspects of the mechanism of action that are not fully understood.

Methods: The retention of radioactivity in tumors after administration of (64)Cu-ATSM in vivo is substantially higher for tumors with a significant hypoxic fraction. This hypoxia-dependent retention is believed to involve the reduction of Cu-ATSM, followed by the loss of copper to cellular copper processing.

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Purpose: To describe a combination of techniques using the excellent volumetric capacities of magnetic resonance imaging (MRI) while avoiding anesthesia and maintaining high-throughput capability for tumor volume measurement in the awake mouse. This approach presents an alternative to calipers which, although cheap, fast, and easy to use, introduce many biases for tumor volume estimation.

Materials And Methods: The murine CaNT subcutaneous xenograft model was used.

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Background: Preclinical imaging requires anaesthesia to reduce motion-related artefacts. For direct translational relevance, anaesthesia must not significantly alter experimental outcome. This study reports on the effects of both anaesthetic and carrier gas upon the uptake of [⁶⁴Cu]-CuATSM, [(⁹⁹m)Tc]-HL91 and [¹⁸F]-FMISO in a preclinical model of tumor hypoxia.

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