Preclinical Magnetic Resonance Imaging Scanner Research Articles

Attention-Based MultiOffset Deep Learning Reconstruction of Chemical Exchange Saturation Transfer (AMO-CEST) MRI.

One challenge of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is the long scan time due to multiple acquisitions of images at different saturation frequency offsets. k-space under-sampling strategy is commonly used to accelerate MRI acquisition, while this could introduce artifacts and reduce signal-to-noise ratio (SNR). To accelerate CEST-MRI acquisition while maintaining suitable image quality, we proposed an attention-based multioffset deep learning reconstruction network (AMO-CEST) with a multiple radial k-space sampling strategy for CEST-MRI. The AMO-CEST also contains dilated convolution to enlarge the receptive field and data consistency module to preserve the sampled k-space data. We evaluated the proposed method on a mouse brain dataset containing 5760 CEST images acquired at a pre-clinical 3 T MRI scanner. Quantitative results demonstrated that AMO-CEST showed obvious improvement over zero-filling method with a PSNR enhancement of 11 dB, a SSIM enhancement of 0.15, and a NMSE decrease of [Formula: see text] in three acquisition orientations. Compared with other deep learning-based models, AMO-CEST showed visual and quantitative improvements in images from three different orientations. We also extracted molecular contrast maps, including the amide proton transfer (APT) and the relayed nuclear Overhauser enhancement (rNOE). The results demonstrated that the CEST contrast maps derived from the CEST images of AMO-CEST were comparable to those derived from the original high-resolution CEST images. The proposed AMO-CEST can efficiently reconstruct high-quality CEST images from under-sampled k-space data and thus has the potential to accelerate CEST-MRI acquisition.

Fast quantitative MRI: Spiral Acquisition Matching-Based Algorithm (SAMBA) for Robust T1 and T2 Mapping

Conventional diagnostic images from Magnetic Resonance Imaging (MRI) are typically qualitative and require subjective interpretation. Alternatively, quantitative MRI (qMRI) methods have become more prevalent in recent years with multiple clinical and preclinical imaging applications. Quantitative MRI studies on preclinical MRI scanners are being used to objectively assess tissues and pathologies in animal models and to evaluate new molecular MRI contrast agents. Low-field preclinical MRI scanners (≤3.0T) are particularly important in terms of evaluating these new MRI contrast agents at human MRI field strengths. Unfortunately, these low-field preclinical qMRI methods are challenged by long acquisition times, intrinsically low MRI signal levels, and susceptibility to motion artifacts. In this study, we present a new rapid qMRI method for a preclinical 3.0T MRI scanner that combines a Spiral Acquisition with a Matching-Based Algorithm (SAMBA) to rapidly and quantitatively evaluate MRI contrast agents. In this initial development, we compared SAMBA with gold-standard Spin Echo MRI methods using Least Squares Fitting (SELSF) in vitro phantoms and demonstrated shorter scan times without compromising measurement accuracy or repeatability. These initial results will pave the way for future in vivo qMRI studies using state-of-the-art chemical probes.

Extended curvature birdcage coil design for localized magnetic field in 9.4 T MRI for multiple mouse imaging

Magnetic resonance imaging (MRI) for preclinical analysis is useful for testing medical procedures, therapies, and drug development. Preclinical MRI uses small animals, such as mice, for multiple studies. Preclinical studies are often needed to control target mouse models with different parameters; thus, performing simultaneous MRIs is desired to reduce study time and provide a fair comparison. In this study, we propose a variation of a birdcage coil that is capable of providing the same field intensity for each mouse compared to a traditional birdcage coil configuration. The arrangement of the proposed birdcage coil produces a uniform and strongly localized magnetic |B1|-field in each of the four target mice. The design involves rotating the legs of the birdcage coil so that the current distribution produces a uniform field inside each mouse. Electromagnetic simulations were performed to validate the proposed design. The proposed design exhibited a better field intensity than the reference linear, circularly polarized mode birdcage coils and an eight-channel loop array coil. The proposed customized birdcage coil arrangement promises a better field intensity and uniformity across multiple mouse imaging using 9.4 T preclinical MRI scanners.

Magnetic guidewire steering at ultrahigh magnetic fields.

With remote magnetic steering capabilities, magnetically actuated guidewires have proven their potential in minimally invasive medical procedures. Existing magnetic steering strategies, however, have been limited to low magnetic fields, which prevents the integration into medical systems operating at ultrahigh fields (UHF), such as magnetic resonance imaging (MRI) scanners. Here, we present magnetic guidewire design and steering strategies by elucidating the magnetic actuation principles of permanent magnets at UHF. By modeling the uniaxial magnetization behavior of permanent magnets, we outline the magnetic torque and force and demonstrate unique magnetic actuation opportunities at UHF, such as in situ remagnetization. Last, we illustrate the proposed steering principles using a magnetic guidewire composed of neodymium magnets and a fiber optic rod in a 7-Tesla preclinical MRI scanner. The developed UHF magnetic actuation framework would enable next-generation magnetic robots to operate inside MRI scanners.

Tumor pH Imaging Using Chemical Exchange Saturation Transfer (CEST)-MRI.

Magnetic resonance imaging (MRI) is a noninvasive imaging technique that allows for physiological and functional studies of the tumor microenvironment. Within MRI, the emerging field of chemical exchange saturation transfer (CEST) has been largely exploited for assessing a salient feature of all solid tumors, extracellular acidosis. Iopamidol-based tumor pH imaging has been demonstrated to provide accurate and high spatial resolution extracellular tumor pH maps to elucidate tumor aggressiveness and for assessing response to therapy, with a high potential for clinical translation. Here, we describe the overall setup and steps for measuring tumor extracellular pH of tumor models in mice by exploiting MRI-CEST pH imaging with a preclinical MRI scanner following the administration of iopamidol. We address issues of pH calibration curve setup, animal handling, pH-responsive contrast agent injection, acquisition protocol, and image processing for accurate quantification and visualization of tumor acidosis.

MODL-24. ESTABLISHING A CLINICALLY RELEVANT CT AND ASSOCIATED RADIOMICS PIPELINE FOR INTRACRANIAL RODENT TUMOUR MODELS

Abstract While magnetic resonance imaging (MRI) is the predominant imaging modality for glioblastoma (GBM), pre-clinical MRI scanner availability is limited. As pre-clinical CT is more widely available and cost-effective, this study aimed to 1) establish preclinical-GBM CT and CT-radiomic workflows, 2) identify whether CE-CT could detect murine orthotopic GBM tumours on two CT instruments [TRIUMPHX-O-CT; IVISSPECTRUM-CT], 3) assess whether CT-radiomic features could distinguish tumour from normal tissue, and support earlier detection of tumours, 4) verify translation of pre-clinical CT-radiomic pipelines to, and assess pre-clinical CT-features in, clinical CE-CT scans.U87R-Luc2(n=25) and NFpp10a-Luc2(n=10) orthotopic GBM models were established and tumours monitored via bioluminescence imaging (BLI). Concurrently, mice underwent CE-CT (IV-iodine/300mg/mL/50kV-scan). Extracted radiomic features (PyRadiomics) underwent dimensionality reduction (Spearman correlation; >0.85). Remaining features were analysed (Recursive feature elimination (RFE)/RepeatedCV/randomforest) in normal and tumour tissue and across timepoints (TRIUMPHX-O-CT-Wk3vsWk6,Wk6vsWk9/12; IVISSPECTRUM-CT-Wk6vsWk9/12).CE-CT and radiomic pipelines were successfully established for orthotopic GBM models, using both CT-systems. On visual assessment of images, BLI was significantly more sensitive, with tumours detectable at Wk1 (BLI) vs Wk9 (CE-CT). However, RFE analysis identified CT-radiomic features (first_order&glcm) which differentiated tumour from normal tissue (TRIUMPHX-O-CT). A subsequent feature set (first_order,glcm,gldm&glzm) were identified (TRIUMPHX-O-CT/IVISSPECTRUM-CT), detecting tumours earlier (Wk3&Wk6) than possible by visual assessment of CTs. Preclinical radiomic methods were successfully applied to exploratory clinical CE-CT scans(n=10). Here, several preclinical CT-features (e.g. Zone_Entropy) showed increased intensity in tumour regions. Overall experimental BLI is the most sensitive method for pre-clinical intracranial tumour detection. However, analysis of clinically relevant CT-radiomic features may facilitate tumour identification and earlier tumour detection (Wk3/Wk6-TRIUMPHX-O-CT/Wk6-IVISSPECTRUM-CT) than possible by visual assessment of CT (Wk9). Clinically relevant CT-derived radiomic features may therefore support intracranial rodent tumour assessment. Importantly, preclinical radiomic methods successfully translate to clinical CT-radiomic analysis. Parallel trends in tumour-specific feature intensities across pre-clinical and clinical scans suggest species conservation of features.

Microscopic multifrequency magnetic resonance elastography of ex vivo abdominal aortic aneurysms for extracellular matrix imaging in a mouse model

An abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta, usually accompanied by thrombus formation. The current clinical imaging modalities cannot reliably visualize the thrombus composition. Remodeling of the extracellular matrix (ECM) during AAA development leads to stiffness changes, providing a potential imaging marker. 14 apolipoprotein E-deficient mice underwent surgery for angiotensin II-loaded osmotic minipump implantation. 4 weeks post-op, 5 animals developed an AAA. The aneurysm was imaged ex vivo by microscopic multifrequency magnetic resonance elastography (µMMRE) with an in-plane resolution of 40 microns. Experiments were performed on a 7-Tesla preclinical magnetic resonance imaging scanner with drive frequencies between 1000 Hz and 1400 Hz. Shear wave speed (SWS) maps indicating stiffness were computed based on tomoelastography multifrequency inversion. As control, the aortas of 5 C57BL/6J mice were examined with the same imaging protocol. The regional variation of SWS in the thrombus ranging from 0.44 ± 0.07 to 1.20 ± 0.31 m/s was correlated fairly strong with regional histology-quantified ECM accumulation (R2 = 0.79). Our results suggest that stiffness changes in aneurysmal thrombus reflect ECM remodeling, which is critical for AAA risk assessment. In the future, µMMRE could be used for a mechanics-based clinical characterization of AAAs in patients. Statement of significanceTo our knowledge, this is the first study mapping the stiffness of abdominal aortic aneurysms with microscopic resolution of 40 µm. Our work revealed that stiffness critically changes due to extracellular matrix (ECM) remodeling in the aneurysmal thrombus. We were able to image various levels of ECM remodeling in the aneurysm reflected in distinct shear wave speed patterns with a strong correlation to regional histology-quantified ECM accumulation. The generated results are significant for the application of microscopic multifrequency magnetic resonance elastography for quantification of pathological remodeling of the ECM and may be of great interest for detailed characterization of AAAs in patients.

WIKIBrainStem: An online atlas to manually segment the human brainstem at the mesoscopic scale from ultrahigh field MRI

The brainstem is one of the most densely packed areas of the central nervous system in terms of gray, but also white, matter structures and, therefore, is a highly functional hub. It has mainly been studied by the means of histological techniques, which requires several hundreds of slices with a loss of the 3D coherence of the whole specimen. Access to the inner structure of the brainstem is possible using Magnetic Resonance Imaging (MRI), but this method has a limited spatial resolution and contrast in vivo. Here, we scanned an ex vivo specimen using an ultra-high field (11.7T) preclinical MRI scanner providing data at a mesoscopic scale for anatomical T2-weighted (100 µm and 185 µm isotropic) and diffusion-weighted imaging (300 µm isotropic). We then proposed a hierarchical segmentation of the inner gray matter of the brainstem and defined a set of rules for each segmented anatomical class. These rules were gathered in a freely accessible web-based application, WIKIBrainStem (https://fibratlas.univ-tours.fr/brainstems/index.html), for 99 structures, from which 13 were subdivided into 29 substructures.This segmentation is, to date, the most detailed one developed from ex vivo MRI of the brainstem. This should be regarded as a tool that will be complemented by future results of alternative methods, such as Optical Coherence Tomography, Polarized Light Imaging or histology… This is a mandatory step prior to segmenting multiple specimens, which will be used to create a probabilistic automated segmentation method of ex vivo, but also in vivo, brainstem and may be used for targeting anatomical structures of interest in managing some degenerative or psychiatric disorders.

Magnetic Resonance Imaging-Compatible Optically Powered Miniature Wireless Modular Lorentz Force Actuators.

Minimally invasive medical procedures under magnetic resonance imaging (MRI) guidance have significant clinical promise. However, this potential has not been fully realized yet due to challenges regarding MRI compatibility and miniaturization of active and precise positioning systems inside MRI scanners, i.e., restrictions on ferromagnetic materials and long conductive cables and limited space around the patient for additional instrumentation. Lorentz force‐based electromagnetic actuators can overcome these challenges with the help of very high, axial, and uniform magnetic fields (3–7 Tesla) of the scanners. Here, a miniature, MRI‐compatible, and optically powered wireless Lorentz force actuator module consisting of a solar cell and a coil with a small volume of 2.5 × 2.5 × 3.0 mm3 is proposed. Many of such actuator modules can be used to create various wireless active structures for future interventional MRI applications, such as positioning needles, markers, or other medical tools on the skin of a patient. As proof‐of‐concept prototypes toward such applications, a single actuator module that bends a flexible beam, four modules that rotate around an axis, and six modules that roll as a sphere are demonstrated inside a 7 Tesla preclinical MRI scanner.

Development of concurrent magnetic resonance imaging and volumetric optoacoustic tomography: A phantom feasibility study.

Optoacoustic tomography (OAT) and magnetic resonance imaging (MRI) provide highly complementary capabilities for anatomical and functional imaging of living organisms. Herein, we investigate on the feasibility of combining both modalities to render concurrent images. This was achieved by introducing a specifically-designed copper-shielded spherical ultrasound array into a preclinical MRI scanner. Phantom experiments revealed that the OAT probe caused minimal distortion in the MRI images, while synchronization of the laser and the MRI pulse sequence enabled defining artifact-free acquisition windows for OAT. Good dynamic OAT contrast from superparamagnetic iron oxide nanoparticles, a commonly used agent for MRI contrast enhancement, was also observed. The hybrid OAT-MRI system thus provides an excellent platform for cross-validating functional readings of both modalities. Overall, this initial study serves to establish the technical feasibility of developing a hybrid OAT-MRI system for biomedical research.

Magnetic resonance-guided motorized transcranial ultrasound system for blood-brain barrier permeabilization along arbitrary trajectories in rodents.

BackgroundFocused ultrasound combined with microbubble injection is capable of locally and transiently enhancing the permeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) guidance enables to plan, monitor, and characterize the BBB disruption. Being able to precisely and remotely control the permeabilization location is of great interest to perform reproducible drug delivery protocols.MethodsIn this study, we developed an MR-guided motorized focused ultrasound (FUS) system allowing the transducer displacement within preclinical MRI scanners, coupled with real-time transfer and reconstruction of MRI images, to help ultrasound guidance. Capabilities of this new device to deliver large molecules to the brain on either single locations or along arbitrary trajectories were characterized in vivo on healthy rats and mice using 1.5 MHz ultrasound sonications combined with microbubble injection. The efficacy of BBB permeabilization was assessed by injecting a gadolinium-based MR contrast agent that does not cross the intact BBB.ResultsThe compact motorized FUS system developed in this work fits into the 9-cm inner diameter of the gradient insert installed on our 7-T preclinical MRI scanners. MR images acquired after contrast agent injection confirmed that this device can be used to enhance BBB permeability along remotely controlled spatial trajectories of the FUS beam in both rats and mice. The two-axis motor stage enables reaching any region of interest in the rodent brain. The positioning error when targeting the same anatomical location on different animals was estimated to be smaller than 0.5 mm. Finally, this device was demonstrated to be useful for testing BBB opening at various acoustic pressures (0.2, 0.4, 0.7, and 0.9 MPa) in the same animal and during one single ultrasound session.ConclusionsOur system offers the unique possibility to move the transducer within a high magnetic field preclinical MRI scanner, thus enabling the delivery of large molecules to virtually any rodent brain area in a non-invasive manner. It results in time-saving and reproducibility and could be used to either deliver drugs over large parts of the brain or test different acoustic conditions on the same animal during the same session, therefore reducing physiological variability.

170 In Vivocardiac magnetic resonance imaging of adult zebrafish

Introduction While the embryonic zebrafish has been widely used for basic cardiac research the adult zebrafish has been used less partly due to difficulties in evaluating the hearts structure and function in-vivo. Currently available cardiac imaging techniques are limited by the hearts small size and rapid rate. Successful development of cardiac MRI for the adult zebrafish could have significant scientific, ethical and economic benefits for cardiac research. Methods We have developed a novel magnetic resonance imaging (MRI) scanning system, designed to study cardiac structure and function in the live adult zebrafish. This has involved the development of an integrated zebrafish life support and monitoring system with an internal custom MRI solenoid microimaging coil – the ‘flow cell’ (Figure 1). Zebrafish are anesthetised (MS222) and held in position within a flow chamber that intersects the MRI coil for scanning (internal diameter 6.9 mm, SNR >130). Water flows through the system via a non-pulsatile pump from outside the scanner room (2.00 ml min –1 ). Water temperature and oxygenation of the flow cell is monitored using in line MRI compatible optical sensors (FirestingO 2 , PyroScience) to provide continuous monitoring of the fish while it is in the scanner. Scanning is performed on a 7T preclinical MRI scanner (Bruker BioSpec). FLASH and RARE based sequences are used for locator and structural information, while functional images are obtained using a retrospective cardiac gated gradient echo imaging sequence (IntragateFLASH). All scans are at Results We have created a working flow cell for obtaining cardiac MRI images from zebrafish (Figure 2). Zebrafish scanned under our current in vivo protocol have all successfully recovered from the experimental procedure (up to 40 mins) with no obvious signs of distress or injury allowing for longitudinal imaging studies. Conclusion Our aim is to deliver in vivo MRI images with spatial and temporal quality matching rodent MRI. While we have already met with significant success generating anatomical images further refinement is required, in terms of image contrast, quality and reproducibility, before deployment in full cardiac studies. Acknowledgement This work is funded by a BHF New Horizons grant.

A novel, non-invasive and in vivo approach to determine morphometric data in starfish

Starfish (Echinodermata: Asteroidea) are present in most benthic ocean habitats and play an important ecological role as keystone species or by dominating through sheer individual numbers. In order to assess nutritional and reproductive states in ecological studies on asteroids, invasive techniques to calculate organ indices are conventionally used. We present a non-invasive method that enables imaging and morphometric measurements in starfish in vivo. We used a clinical 1.5T magnetic resonance imaging (MRI) scanner to produce sectional images of three starfish species and employed these image stacks to generate 3D models of the pyloric ceca, gonads and the endoskeleton. In comparison to pre-clinical MRI scanners, that provide higher resolutions, clinical MRI is not limited to small objects, but allows the investigation of larger samples such as the starfish used in the present study. Volume data from MRI-based 3D reconstructions were compared to conventional invasive measurement techniques as well as high resolution MRI scans and were tested for inter-observer effects. Here we show that MRI is a suitable method for precise imaging and volumetric measurements in fixed and living marine specimens. Compared to other methods, it allows not only the production of time series data on single individuals as well as populations, but also non-destructive analyses of valuable specimens, such as museum material.

Preclinical multimodality phantom design for quality assurance of tumor size measurement

BackgroundEvaluation of changes in tumor size from images acquired by ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI) is a common measure of cancer chemotherapy efficacy. Tumor size measurement based on either the World Health Organization (WHO) criteria or the Response Evaluation Criteria in Solid Tumors (RECIST) is the only imaging biomarker for anti-cancer drug testing presently approved by the United States Food and Drug Administration (FDA). The aim of this paper was to design and test a quality assurance phantom with the capability of monitoring tumor size changes with multiple preclinical imaging scanners (US, CT and MRI) in order to facilitate preclinical anti-cancer drug testing.MethodsThree phantoms (Gammex/UTHSCSA Mark 1, Gammex/UTHSCSA Mark 2 and UTHSCSA multimodality tumor measurement phantom) containing tumor-simulating test objects were designed and constructed. All three phantoms were scanned in US, CT and MRI devices. The size of test objects in the phantoms was measured from the US, CT and MRI images. RECIST, WHO and volume analyses were performed.ResultsThe smaller phantom size, simplified design and better test object CT contrast of the UTHSCSA multimodality tumor measurement phantom allowed scanning of the phantom in preclinical US, CT and MRI scanners compared with only limited preclinical scanning capability of Mark 1 and Mark 2 phantoms. For all imaging modalities, RECIST and WHO errors were reduced for UTHSCSA multimodality tumor measurement phantom (≤1.69 ± 0.33%) compared with both Mark 1 (≤ -7.56 ± 6.52%) and Mark 2 (≤ 5.66 ± 1.41%) phantoms. For the UTHSCSA multimodality tumor measurement phantom, measured tumor volumes were highly correlated with NIST traceable design volumes for US (R2 = 1.000, p < 0.0001), CT (R2 = 0.9999, p < 0.0001) and MRI (R2 = 0.9998, p < 0.0001).ConclusionsThe UTHSCSA multimodality tumor measurement phantom described in this study can potentially be a useful quality assurance tool for verifying radiologic assessment of tumor size change during preclinical anti-cancer therapy testing with multiple imaging modalities.

Magnetically assisted delivery of cells using a magnetic resonance imaging system

A simple analytical model is presented which enables rapid interactive prediction and control of magnetically labelled cells in an arterial bifurcation using magnetic field gradients produced by a magnetic resonance imaging (MRI) system. This model is compared against experimental results for human mononuclear cells labelled with micrometre sized superparamagnetic iron oxide particles. Experimental and theoretical results highlight the importance of cell aggregation for magnetic targeting in a strong magnetic field. These predicted aggregates are confirmed via confocal endoscopy which allows the visualization of cell aggregates and their movement inside a vascular flow model in a 9.4 T preclinical MRI scanner.