Compact Magnetic Resonance Imaging Research Articles

Development of a non-invasive method for testicular toxicity evaluation using a novel compact magnetic resonance imaging system.

In non-clinical animal studies for drug discovery, histopathological evaluation is the most powerful tool to assess testicular toxicity. However, histological analysis is extremely invasive; many experimental animals are needed to evaluate changes in the pathology and anatomy of the testes over time. As an alternative, small animal magnetic resonance imaging (MRI) offers a non-invasive methodology to examine testicular toxicity without radiation. The present study demonstrated the suitability of a new, ready-to-use compact MRI platform using a high-field permanent magnet to assist with the evaluation of testicular toxicity. To validate the utility of the MRI platform, male mice were treated with busulfan (40 mg/kg, intraperitoneal injection). Twenty-eight days after treatment, both testes in busulfan-treated and control mice (n = 6/group) were non-invasively scanned in situ by MRI at 1 tesla. On a T1-weighted 3D gradient-echo MRI sequences (voxel size: 0.23 × 0.23 × 0.50 mm), the total testicular volume in busulfan-treated mice was significantly smaller than in controls. On T1-weighted images, the signal intensity of the testes was significantly higher in busulfan-treated mice than in controls. The mice were sacrificed, and the testes were isolated for histopathological analysis. The weight of the testes in busulfan-treated mice significantly decreased, similar to the results of the non-invasive analysis. Additionally, periodic acid-Schiff stain-positive effusions were observed in the interstitium of the busulfan-treated mouse testes, potentially explaining T1 shortening due to a high concentration of glycoproteinaceous content. The present data demonstrated a rapid evaluation of testicular toxicity in vivo by compact MRI.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.

A Novel Switch Design for Compact HTS Flux Pump

High temperature superconducting (HTS) magnets are becoming more and more attractive for many commercial applications. HTS magnets, however, need an external power supply to operate in persistent current mode. One way to charge an HTS magnet is using a conventional power supply. This, however, is not the most efficient way to charge an HTS magnet due to losses from the current leads. Flux pumping is an alternative method to charge an HTS magnet. Over the years different types of flux pumps have been proposed specific to different applications. Transformer-rectifier flux pump is one of the many types of flux pumps that have been researched widely. The design of switches plays a central role in a transformer-rectifier flux pump. In this paper, we propose a novel switch design for a half-wave transformer-rectifier flux pump. The switch proposed in this study will be used in compact and mobile HTS Magnetic Resonance Imaging (MRI) instruments.

Compact pediatric cardiac magnetic resonance imaging protocols.

Cardiac MRI is in many respects an ideal modality for pediatric cardiovascular imaging, enabling a complete noninvasive assessment of anatomy, morphology, function and flow in one radiation-free and potentially non-contrast exam. Nonetheless, traditionally lengthy and complex imaging acquisition strategies have often limited its broader use beyond specialized centers. In this review, the author presents practical cardiac MRI imaging protocols to facilitate the performance of succinct yet successful exams that provide the most salient clinical data for the majority of congenital and acquired pediatric cardiac disease. In addition, the author reviews newer and evolving techniques that permit more rapid but similarly diagnostic MRI, including compressed sensing and artificial intelligence/machine learning reconstruction, four-dimensional flow acquisition and blood pool contrast agents. With the modern armamentarium of cardiac MRI methods, the goal of compact yet comprehensive exams in children can now be realized.

The Application of Magnetic Resonance Imaging in Skeletal Age Assessment.

Method The study includes 80 patients identified from an endocrine clinic, two males and two females from each of 5 age groups (<5, 5 to 7, 8 to 10, 11 to 13, and 14 to 16 years). Skeletal age as determined from an open MRI scanner and radiographs performed on the same day was compared for each child. Two observers assess the skeletal age from radiographs and MRI images independently. After a period of at least three weeks, observers determined the skeletal age of all patients independently. All of the images were in different and random orders, on both of the assessment occasions. The agreement was assessed using the interclass correlation coefficient and Bland Altman plots. Problem Statement. The recurrent use of left-hand radiography in children with chronic conditions might result in the patient being exposed to the same image several times throughout the course of their lives. Use of radiation-free methods such as magnetic resonance imaging (MRI) may be able to assist in reducing the risks associated with radiation exposure, if done properly. Results Patients' age ranged from 3 to 16 years, in which the mean of the chronological age was 9.3 years (±2.9) and 9.8 years (±2.7) in girls and boys, respectively. The interrater agreement for skeletal age determination was 0.984 for radiographs and 0.976 for MRI scans. Using the G&P technique, for Observer 1, intraobserver agreement for radiographs and DXA was 0.993 and 0.983, respectively, and 0.995 and 0.994, respectively, for Observer 2. Plotting the rater readings against the line of equality shows no significant differences between readings acquired from radiographs and MRI scans. Conclusion For the study contribution, it is possible to employ open compact MRI to determine the skeletal age of a person. Our results showed that left-hand MRI scans were of better quality than the radiographs.

B0-Shimming Methodology for Affordable and Compact Low-Field Magnetic Resonance Imaging Magnets

Low-field (B0 &amp;lt; 0.2 T) magnetic resonance imaging (MRI) is emerging as a low cost, point-of-care alternative to provide access to diagnostic imaging technology even in resource scarce environments. MRI magnets can be constructed based on permanent neodymium-iron-boron (NdFeB) magnets in discretized arrangements, leading to substantially lower mass and costs. A challenge with these designs is, however, a good B0 field homogeneity, which is needed to produce high quality images free of distortions. In this work, we describe an iterative approach to build a low-field MR magnet based on a B0-shimming methodology using genetic algorithms. The methodology is tested by constructing a small bore (inner bore diameter = 130 mm) desktop MR magnet (&amp;lt;15 kg) at a field strength of B0 = 0.1 T and a target volume of 4 cm in diameter. The configuration consists of a base magnet and shim inserts, which can be placed iteratively without modifying the base magnet assembly and without changing the inner dimensions of the bore or the outer dimensions of the MR magnet. Applying the shims, B0 field inhomogeneity could be reduced by a factor 8 from 5,448 to 682 ppm in the target central slice of the magnet. Further improvements of these results can be achieved in a second or third iteration, using more sensitive magnetic field probes (e.g., nuclear magnetic resonance based magnetic field measurements). The presented methodology is scalable to bigger magnet designs. The MR magnet can be reproduced with off-the-shelf components and a 3D printer and no special tools are needed for construction. All design files and code to reproduce the results will be made available as open source hardware.

MRI-based Glucose Assay Using Magnetic Nanoparticle Sensors.

Glucose sensors for NMR relaxometry and magnetic resonance imaging (MRI) can be used for the direct measurement of glucose in turbid biological specimens. Here, we proposed a magnetic glucose sensor based on superparamagnetic iron oxide (SPIO) nanoparticles conjugated to a mannopyranoside derivative and concanavalin A (ConA). The binding of mannopyranoside groups to ConA produced a nanoparticle cluster that was dissociated by competitive binding of glucose to ConA, resulting in changes in the transverse relaxation time (T2) in a glucose-dependent manner. The sensor gave rise to significant T2 changes in physiological glucose levels of 3 - 8 mM at a nanoparticle concentration of 0.5 nM. Significant T2 responses were observed within 6 min of 5 mM glucose detection. Sensor-based MRI by a benchtop 1 tesla scanner permitted a measurement of multiple samples within 8 min. These results demonstrate that the relaxometric glucose sensor could lead to high throughput direct assay of blood samples by using a compact MRI scanner for point-of-care testing.

Current Status in Building a Compact and Mobile HTS MRI Instrument

Magnetic Resonance Imaging (MRI) is an indispensable tool in monitoring lipid-rich tissues and the musculoskeletal system. It however requires maintaining a huge homogeneous (1 to 7 T) field. That is where superconductors come into play since they are the only feasible way to create such fields. The state-of-the-art technology utilizes low critical temperature superconductors (LTS) which require cooling down to liquid helium temperatures (4.2K). The new generation superconductors, aka the high critical temperature superconductors (HTS), can operate up to relatively elevated temperatures (technically above 100K's). In addition to that, they can withstand larger magnetic field strengths which can theoretically go up to the order of hundred Teslas in magnitude. It is evident that LTS wires of current MRI magnet technology is at their limits and new pursuits such as reaching higher fields and reducing operational/maintenance costs are in the favor of HTS tapes. There is, in fact, another advantage beyond minimization of the cryogenic costs, namely the compactness of the overall system. Utilizing certain auxiliary techniques such as flux pumping and conductive cooling of the tapes, MRI magnets can be reduced in size substantially. That, in turn, enables constructing much smaller thus mobile MRI scanners which can be brought to patients' doorsteps. Here we present the current status of our project aiming to build an HTS MRI machine dedicated to use as a mobile head scanner.

Changes in Liver Mechanical Properties and Water Diffusivity During Normal Pregnancy Are Driven by Cellular Hypertrophy.

During pregnancy, the body’s hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 ± 15%, p < 0.001), (ii) increased liver stiffness (12 ± 15%, p = 0.012), (iii) decreased viscosity (−23 ± 14%, p < 0.001), and (iv) increased water diffusivity (12 ± 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context.

A Receiving Coil for a Specialized Compact Magnetic Resonance Imaging System

A receiving coil was developed for a specialized magnetic resonance imaging system based on a permanent magnet with a magnetic field induction of 0.4 T for imaging human joints. The mathematical simulation was performed for the spatial distribution of the magnetic field in the working area of the coil and its optimal configuration was determined. Taking the simulation into account, a prototype of the coil was manufactured and its characteristics were measured. Using this coil, images of a hand were obtained on a prototype of the magnetic resonance imaging system.

Magnetic Resonance Imaging (MRI) Results Following Discontinuation of Methotrexate in Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab: The COMP-ACT MRI Substudy.

To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX. In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to discontinue MTX (TCZ monotherapy; mono) or continue TCZ + MTX until Week 52. In a subset of patients, 1.5-Tesla MRI was used to obtain images of bilateral hands and wrists at weeks 24 and 40. Outcomes included changes in MRI-assessed synovitis, osteitis, erosion, and cartilage loss from Week 24 to Week 40, and in the proportion of patients with progression of each score. Of 296 patients who achieved DAS28-ESR ≤ 3.2 at Week 24, 79 were enrolled in the pilot MRI substudy and randomized to TCZ mono (n = 38) or TCZ + MTX (n = 41). Treatment with either TCZ mono or TCZ + MTX suppressed erosion progression, synovitis, osteitis, and cartilage loss. The proportion of patients with no progression in each outcome measure was similar between groups (range, TCZ mono: 84.8-97.0%; TCZ + MTX: 92.3-100%). In a subset of patients who achieved low disease activity with TCZ + MTX, MRI changes were minimal in intraarticular inflammation and damage measures in patients who discontinued MTX versus those who continued TCZ + MTX.

Development of a small car-mounted magnetic resonance imaging system for human elbows using a 0.2 T permanent magnet.

Portable magnetic resonance imaging (MRI) scanners can provide opportunities for mobile operation in many environments including disease screening and primary care suites. Here, we develop a new, compact transportable MRI system for imaging small joints of the extremities using a 0.2 T, 200 kg permanent magnet. The whole system, including the magnet, gradient coils, RF probes, and MRI consoles (80 kg in weight) was installed in a standard-size minivan-style vehicle. The use of the open-geometry magnet enables easy patient positioning within the limited space of the vehicle. We show that our portable MRI system provides clinically relevant images of screening for elbow injuries induced by overuse of overhand throwing. This transportable system is deployable during sport events or in environments with poor access to MRI systems, and could be applicable for mass screening, early diagnosis, and case finding.

Planar Gradient Coil Design Using L1 and L2 Norms

We present a novel and general formulation for the optimisation of gradient coils, wherein the minimization of the conductor length and the simplicity of construction are two of the main design parameters. The bi-planar gradient coils are intended to be part of a new compact neonatal magnetic resonance imaging (MRI) scanner based on a 0.35 T permanent magnet. It is shown that minimizing the current density vector is equivalent to minimizing the wire length. The gradient coil design involves a convex optimization method where the Euclidian and Manhattan norms of the current density vector are minimized under the field linearity, wire width, force and shielding constraints. The design problem is solved iteratively in order to include the influence of the magnetization of the pole and iron ring over the gradient field linearity. A suite of gradient coils using both norms and resistance minimization are designed and their performances are compared. Gradient coils designed using Euclidian norm show shorter wire length and slightly better performance than that designed using Manhattan norms; however, the presence of straight wires in the current pattern is very convenient for manufacturing purpose.

Compact Magnetic Resonance Imaging Systems-Novel Cost-Effective Tools for Preclinical Drug Safety and Efficacy Evaluation.

Practical magnetic resonance imaging for use in investigative and preclinical toxicology studies is now feasible. Newly developed, self-containing imaging systems provide an efficient and cost-effective means to rapidly obtain in vivo and ex vivo magnetic resonance imaging images to improve how we perform toxicology and toxicologic pathology.

Compact MRI for the detection of teratoma development following intrathecal human embryonic stem cell injection in NOD-SCID mice

Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls. In vivo MRI was performed on days 25 and 48, and ex vivo MRI was performed after scheduled euthanization (day 55). MRI results were compared to histopathology findings. Two animals injected with hESCs developed hind-limb paresis and paralysis, necessitating premature euthanization. MRI examination revealed abnormal pale areas in the spinal cord and brain, which correlated histopathologically with teratomas. This preliminary study shows the efficacy of compact MRI systems in the detection of small teratomas following intrathecal injection of hESCs in a highly sensitive manner. Although these results should be validated in larger studies, they provide further evidence that the use of MRI in longitudinal studies offers a new monitoring strategy for preclinical testing of stem cell applications.

Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations in Vitro and in Vivo.

Although magnetic resonance imaging (MRI) has potential in assessments of formulations, few studies have been conducted because of the size and expense of the instrument. In the present study, the processes of in vitro and in vivo release in a gelatin capsule formulation model were visualized using a compact MRI system with 1.5 T permanent magnets, which is more convenient than the superconducting MRI systems typically used for clinical and experimental purposes. A Gd-chelate of diethylenetriamine-N,N,N',N″,N″-pentaacetic acid, a contrast agent that markedly enhances proton signals via close contact with water, was incorporated into capsule formulations as a marker compound. In vitro experiments could clearly demonstrate the preparation-dependent differences in the release/disintegration of the formulations. In some preparations, the penetration of water into the formulation and generation of bubbles in the capsule were also observed prior to the disintegration of the formulation. When capsule formulations were orally administered to rats, the release of the marker into the stomach and its transit to the duodenum were visualized. These results strongly indicate that the compact MRI system is a powerful tool for pharmaceutical studies.

Freezing xylem conduits with liquid nitrogen creates artifactual embolisms in water-stressed broadleaf trees

Freezing with liquid nitrogen promotes the expansion of air in water columns of water-stressed, intact trees that are not transpiring. In analyses of the distribution of water-filled and embolized conduits, xylem sap is frozen with liquid nitrogen and visualized using cryo-scanning electron microscopy (cryo-SEM). However, artifacts may be introduced during preparation of samples for these analyses. If the xylem is frozen intact, conduits may embolize during freezing when xylem water potential (Ψ xylem) is substantially negative, whereas rehydration to release negative pressure may induce artifactual refilling. To evaluate these sampling phenomena during dehydration and rehydration, we monitored dynamic changes in xylem functional status in the stem of Dendropanax trifidus by compact magnetic resonance imaging (CMRI). We also visualized the water distribution in xylem (under low Ψ xylem and with no transpiration) after freezing D. trifidus and Carpinus tschonoskii stems with liquid nitrogen. Artifactual refilling of embolized conduits was sometimes observed in D. trifidus samples cut underwater prior to freezing; however, the extent of refilling may have no influence on hydraulic measurements. Living cells in all samples were dramatically restored after rehydration by cutting underwater. In the current-year xylem, intact saplings of C. tschonoskii frozen with liquid nitrogen after dehydration had a greater number of embolized vessels than samples cut underwater. When a low Ψ xylem (≤−2.5 MPa) was maintained, artifactual embolisms were rarely observed in samples directly frozen after rehydration. Thus, relaxation of negative Ψ xylem and rehydration are important factors for consideration when assessing the distribution of embolized conduits by cryo-SEM.

Vulnerability to cavitation differs between current-year and older xylem: non-destructive observation with a compact magnetic resonance imaging system of two deciduous diffuse-porous species.

Development of xylem embolism during water stress in two diffuse-porous hardwoods, Katsura (Cercidiphyllum japonicum) and Japanese white birch (Betula platyphylla var. japonica), was observed non-destructively under a compact magnetic resonance imaging (MRI) system in addition to conventional quantitation of hydraulic vulnerability to cavitation from excised stem segments. Distribution of white and dark areas in MR images corresponded well to the distribution of water-filled/embolized vessels observed by cryo-scanning electron microscopy in both species. Water-filled vessels were observed in MR images as white areas in Katsura and as white dots in Japanese white birch, respectively, and embolisms could be detected as a change to dark areas. The increase in the relative embolized area (REA: %) in the cross-sectional area of total xylem during water stress, which was estimated from the binarized MR images, was consistent with the hydraulic vulnerability curves of these species. From the non-destructive MRI observations, cavitation induced by water stress was shown to develop earlier in 1- or 2-year-old xylem than in the current-year xylem in both species; that is, the vulnerability to cavitation differs between vessels in the current-year xylem and those in older annual rings.

Practical Applications of in Vivo and ex Vivo MRI in Toxicologic Pathology Using a Novel High-performance Compact MRI System.

Magnetic resonance imaging (MRI) is widely used in preclinical research and drug development and is a powerful noninvasive method for assessment of phenotypes and therapeutic efficacy in murine models of disease. In vivo MRI provides an opportunity for longitudinal evaluation of tissue changes and phenotypic expression in experimental animal models. Ex vivo MRI of fixed samples permits a thorough examination of multiple digital slices while leaving the specimen intact for subsequent conventional hematoxylin and eosin (H&E) histology. With the advent of new compact MRI systems that are designed to operate in most conventional labs without the cost, complexity, and infrastructure needs of conventional MRI systems, the possibility of MRI becoming a practical modality is now viable. The purpose of this study was to investigate the capabilities of a new compact, high-performance MRI platform (M2™; Aspect Imaging, Israel) as it relates to preclinical toxicology studies. This overview will provide examples of major organ system pathologies with an emphasis on how compact MRI can serve as an important adjunct to conventional pathology by nondestructively providing 3-dimensional (3-D) digital data sets, detailed morphological insights, and quantitative information. Comparative data using compact MRI for both in vivo and ex vivo are provided as well as validation using conventional H&E.

Application of a compact magnetic resonance imaging system for toxicologic pathology: evaluation of lithium-pilocarpine-induced rat brain lesions.

Magnetic resonance imaging (MRI) is a useful noninvasive tool used to detect lesions in clinical and veterinary medicine. The present study evaluated the suitability of a new easy-to-use compact MRI platform (M2 permanent magnet system, Aspect Imaging, Shoham, Israel) for assisting with preclinical toxicologic pathology examination of lesions in the rat brain. In order to induce brain lesions, male Sprague-Dawley rats were treated once with lithium chloride (127 mg/kg, intraperitoneal [i.p.]) followed by pilocarpine (30 mg/kg, i.p.). One week after dosing, the perfused, fixed brains were collected, analyzed by the MRI system and examined histopathologically. MRI of the brain of treated rats revealed areas of high T1 and middle to low T2 signals, when compared with the controls, in the piriform cortex, lateral thalamic nucleus, posterior paraventricular thalamic nucleus and posterior hypothalamic nucleus of the cerebrum. The altered MRI signal areas were consistent with well-circumscribed foci of neuronal cell degeneration/necrosis accompanied by glial cell proliferation. The present data demonstrated that quick analysis of fixed organs by the MRI system can detect the presence and location of toxicologic lesions and provide useful temporal information for selection of appropriate sections for histopathologic examination before routine slide preparation, especially in complex and functionally heterogeneous organs such as the brain.