Diffusion weighted imaging in small rodents using clinical MRI scanners

Diffusion weighted imaging (DWI) has emerged as a unique and powerful non-invasive magnetic resonance imaging (MRI) technique with a major potential impact on imaging-based diagnosis in a variety of clinical applications including oncology and tissue viability assessment. In light of increasing demand for applying this technique in preclinical investigations using small animals, we have explored the potentials of a clinical magnet for acquiring the DWI in rats and mice with either cerebral ischemia or solid tumors. Through technical adaptation and optimization, we have been able to perform a series of clinically relevant animal studies with conclusions based on DWI quantification. Focusing more on practical aspects and cross-referencing with the current literature, this paper is aimed to summarize our ongoing DWI studies on small rodents with stroke and tumors, and to provide protocols for researchers to replicate similar techniques in their own preclinical and clinical studies.     

Abdominal magnetic resonance imaging in small rodents using a clinical 1.5 T MR scanner

Because of superior soft-tissue contrast compared to other imaging techniques, non-invasive abdominal magnetic resonance imaging (MRI) is ideal for monitoring organ regeneration, tissue repair, cancer stage, and treatment effects in a wide variety of experimental animal models. Currently, sophisticated MR protocols, including technically demanding procedures for motion artefact compensation, achieve an MRI resolution limit of < 100 microm under ideal conditions. However, such a high spatial resolution is not required for most experimental rodent studies. This article describes both a detailed imaging protocol for MR data acquisition in a ubiquitously and commercially available 1.5 T MR unit and 3-dimensional volumetry of organs, tissue components, or tumors. Future developments in MR technology will allow in vivo investigation of physiological and pathological processes at the cellular and even the molecular levels. Experimental MRI is crucial for non-invasive monitoring of a broad range of biological processes and will further our general understanding of physiology and disease.     

A prototype manipulator for magnetic resonance-guided interventions inside standard cylindrical magnetic resonance imaging scanners

The aim of this work is to develop a remotely controlled manipulator to perform minimally invasive diagnostic and therapeutic interventions in the abdominal and thoracic cavities, with real-time magnetic resonance imaging (MRI) guidance inside clinical cylindrical MR scanners. The manipulator is composed of a three degree of freedom Cartesian motion system, which resides outside the gantry of the scanner, and serves as the holder and global positioner of a three degree of freedom arm which extends inside the gantry of the scanner At its distal end, the arm's end-effector can carry an interventional tool such as a biopsy needle, which can be advanced to a desired depth by means of a seventh degree of freedom. These seven degrees of freedom, provided by the entire assembly, offer extended manipulability to the device and a wide envelope of operation to the user, who can select a trajectory suitable for the procedure. The device is constructed of nonmagnetic and nonconductive fiberglass, and carbon fiber composite materials, to minimize artifacts and distortion on the MR images as well as eliminate effects on its operation from the high magnetic field and the fast switching magnetic field gradients used in MR imaging. A user interface was developed for man-in-the-loop control of the device using real-time MR images. The user interface fuses all sensor signals (MR and manipulator information) in a visualization, planning, and control command environment. Path planning is performed with graphical tools for setting the trajectory of insertion of the interventional tool using multislice and/or three dimensional MR images which are refreshed in real time. The device control is performed with an embedded computer which runs real-time control software. The manipulator compatibility with the MR environment and image-guided operation was tested on a 1.5 T MR scanner.     

Quantifying mixing using magnetic resonance imaging

Mixing is a unit operation that combines two or more components into a homogeneous mixture. This work involves mixing two viscous liquid streams using an in-line static mixer. The mixer is a split-and-recombine design that employs shear and extensional flow to increase the interfacial contact between the components. A prototype split-and-recombine (SAR) mixer was constructed by aligning a series of thin laser-cut Poly (methyl methacrylate) (PMMA) plates held in place in a PVC pipe. Mixing in this device is illustrated in the photograph in Fig. 1. Red dye was added to a portion of the test fluid and used as the minor component being mixed into the major (undyed) component. At the inlet of the mixer, the injected layer of tracer fluid is split into two layers as it flows through the mixing section. On each subsequent mixing section, the number of horizontal layers is duplicated. Ultimately, the single stream of dye is uniformly dispersed throughout the cross section of the device. Using a non-Newtonian test fluid of 0.2% Carbopol and a doped tracer fluid of similar composition, mixing in the unit is visualized using magnetic resonance imaging (MRI). MRI is a very powerful experimental probe of molecular chemical and physical environment as well as sample structure on the length scales from microns to centimeters. This sensitivity has resulted in broad application of these techniques to characterize physical, chemical and/or biological properties of materials ranging from humans to foods to porous media (1, 2). The equipment and conditions used here are suitable for imaging liquids containing substantial amounts of NMR mobile (1)H such as ordinary water and organic liquids including oils. Traditionally MRI has utilized super conducting magnets which are not suitable for industrial environments and not portable within a laboratory (Fig. 2). Recent advances in magnet technology have permitted the construction of large volume industrially compatible magnets suitable for imaging process flows. Here, MRI provides spatially resolved component concentrations at different axial locations during the mixing process. This work documents real-time mixing of highly viscous fluids via distributive mixing with an application to personal care products.     

Anaesthesia of small rodents during magnetic resonance imaging

The use of experimental animals for magnetic resonance studies requires anaesthesia to provide immobility and acquire signals with minimal stress and maximal reproducibility. However, the conduct of anaesthesia within a magnetic resonance imaging (MRI) suite implicates many problems, because most of the anaesthetic and monitoring equipment contains ferromagnetic substances. To decrease disturbances during anaesthesia and make data interpretation more accurate, it is mandatory that investigators become familiar with methods and physiologic effects of anaesthesia under these special conditions. This article is intended to give an overview of anaesthetic medication, administration routes and practical instructions for anaesthesia in small rodents during MRI.     

In-vivo studies of mammary development in the goat using magnetic resonance imaging (MRI)

Mammary development and regression were measured in goats in vivo using magnetic resonance imaging (MRI). Measurements were made during the first and second cycles of pregnancy, lactation and involution. In primiparous goats, and exponential pattern of growth was evident during gestation and for the first 2 weeks of lactation. Parenchyma volume correlated significantly with milk yield across goats during early lactation, and across stage of lactation within goats. Milking was discontinued in Week 26 of the first lactation. Involution was characterized by an initial accumulation of fluid (over 2 days) followed by reabsorption; parenchyma volume did not decrease significantly until the 3rd week of involution, which was also the time at which these goats were mated to start their second gestation. Their udders still contained significant quantities of fluid (40-60% of the gross volume), but parenchyma volume was also greater (by 4.7-fold) than in goats beginning their first gestation. By Week 15 of gestation there was no longer a parity difference in parenchyma; the udders of first-gestation goats had grown significantly, but those of second-gestation goats had not. Conversely, between gestation Week 15 and lactation Week 2 mammary growth was significantly more rapid in the second cycle, such that the udder was larger at the start of the second lactation.     

Subjective symptoms and their evolution in a small group of magnetic resonance imaging (MRI) operators recently engaged

Abstract

Using a specific questionnaire, we examined subjective symptoms in a group of 17 physicians (9 males and 8 females, mean age 32.9?±?3.71), attending a Postgraduate Medical School in Radiology and engaged in MRI for less than 1 year. Sixteen subjects (94%) reported the presence of at least one of the investigated symptoms during the period of MRI activity. The main symptoms were: unusual drowsiness/tiredness (88%), concentration problems (82%), headaches (76%), sleep disorders (47%), nausea (47%), illusion of movement (47%) and dizziness/vertigo (35%); the former two were subjectively related to MRI by the majority of the operators. These symptoms appeared (or worsened) in more than 15?min and, in the vast majority disappeared 30?min, or more, after the end of exposure. In 13 subjects (81%), the symptom (or some symptoms) appeared at least weekly. In this small group of health care workers recently exposed to MRI, the prevalence of subjective symptoms was higher than reported in other similar studies but, notably, the majority of subjects (77%) reported a regression within 4–8 weeks, suggesting some form of adaptation.     

Integrated lymphography using fluorescence imaging and magnetic resonance imaging in intact mice

We assessed lymph drainage in living mice by an integrated imaging method using fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Mice were subcutaneously injected with quantum dots and gadofluorine 8 into the right rear footpad. They were fixed on a transparent flat plate and underwent FLI and MRI successively. Small markers were attached to the mouse surface for spatial coregistration, and image fusion of FLIs and MRIs was performed. Two-dimensional fluorescence reflectance imaging was used for FLI. FLI and MRI provided generally consistent results and demonstrated lymphatic flow to the popliteal, sacral, and iliac lymph nodes in most mice and to the renal, inguinal, and lumbar-aortic lymph nodes in some mice. On the fusion images, the locations of the lymph nodes in the mouse trunk were in good agreement between FLI and MRI, indicating successful spatial registration even for the deep structures. The popliteal node tended to be visualized a little farther caudally in FLI than in MRI, presumably because the overlying tissues were thicker in the cranial portion. Integrated FLI/MRI lymphography with image fusion appears to be a useful tool for analysis of the murine lymphatic system.     

In vivo moment arm calculations at the ankle using magnetic resonance imaging (MRI)

In vivo moment arm lengths for the Achilles tendon and tibialis anterior (TA) were determined in 10 adult male subjects. Moment arms were measured as the perpendicular distance between the joint center of rotation (CR) and the center of the muscle's tendon on a series of sagittal plane magnetic resonance images. The first set of calculations used a fixed CR and the second a moving CR. The position of the CR was determined using a modification of the graphical method of Reuleaux. For both moving and fixed CR conditions, moment arms increased by approximately 20% for the Achilles tendon and decreased by approximately 30% for the TA when the ankle moved from maximum dorsiflexion to maximum plantarflexion. Moment arms averaged 3.1% greater for the Achilles tendon and 2.5% greater for the TA when calculated using a fixed CR. These data suggest that the averaged moment arm lengths for the Achilles tendon and the TA were relatively unaffected by the use of a fixed vs moving CR.     

Development of a dynamic imaging method for gravitropism in pea sprouts using clinical magnetic resonance imaging system

Although magnetic resonance imaging (MRI) is a useful technique, only a few studies have investigated the dynamic behavior of small subjects using MRI owing to constraints such as experimental space and signal amount. In this study, to acquire high-resolution continuous three-dimensional gravitropism data of pea (Pisum sativum) sprouts, we developed a small-bore MRI signal receiver coil that can be used in a clinical MRI and adjusted the imaging sequence. It was expected that such an arrangement would improve signal sensitivity and improve the signal-to-noise ratio (SNR) of the acquired image. All MRI experiments were performed using a 3.0-T clinical MRI scanner. An SNR comparison using an agarose gel phantom to confirm the improved performance of the small-bore receiver coil and an imaging experiment of pea sprouts exhibiting gravitropism were performed. The SNRs of the images acquired with a standard 32-channel head coil and the new small-bore receiver coil were 5.23±0.90 and 57.75±12.53, respectively. The SNR of the images recorded using the new coil was approximately 11-fold higher than that of the standard coil. In addition, when the accuracy of MR imaging that captures the movement of pea sprout was verified, the difference in position information from the optical image was found to be small and could be used for measurements. These results of this study enable the application of a clinical MRI system for dynamic plant MRI. We believe that this study is a significant first step in the development of plant MRI technique.     

Radiation dosimetry using Fricke-infused gels and magnetic resonance imaging

We have witnessed the advancements of MRI-Fricke-infused gel dosimetry since its commencing in 1984. Over the years, many efforts have been spent to improve the method's efficacy, i.e., to improve its dose-response sensitivity, reproducibility and measurement accuracy. In this article, we give a review of the development of this relatively new dosimetric method. An example of applying this method to gamma knife stereotactic radiosurgery dose distribution mapping is also given.     

Differentiation between hemosiderin- and ferritin-bound brain iron using nuclear magnetic resonance and magnetic resonance imaging.

MRI is an optimal clinical (research) tool to provide information on brain morphology and pathology and to detect metal ions that possess intrinsic magnetic properties. Non-heme iron is abundantly present in the brain in three different forms: "low molecular weight" complexes, iron bound to "medium molecular weight complexes" metalloproteins such as transferrin, and "high molecular weight" complexes as ferritin and hemosiderin. The total amount and form of iron may differ in health and disease, and MRI can possibly quantify and monitor such changes. Ferritin-bound iron is the main storage form of iron and is present predominantly in the extrapyramidal nuclei where its amounts normally increase as a function of age. Ferritin is water soluble and shortens both, T1 and T2 relaxation, with as result a signal change on the MR images. Hemosiderin, a degradation product of ferritin, is water-insoluble with a stronger T2 shortening effect than ferritin. The larger cluster size of hemosiderin and its water-insolubility also explain a lack of significant T1-shortening effect on T1-weighted images. Using both in vitro specimens and intact brain tissue in vivo we demonstrate here that MRI may be able to distinguish between ferritin- and hemosiderin-bound iron.     

Plaque imaging and characterization using magnetic resonance imaging: towards molecular assessment

Identification of high-risk atherosclerotic lesions prone to rupture and thrombosis may greatly decrease the morbidity and mortality associated with atherosclerosis. High-resolution magnetic resonance imaging (MRI) has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor its progression. The development of MRI contrast agents that specifically target components of the atherosclerotic plaque may enable non-invasive detection of high-risk lesions. This review discusses the use of high-resolution MRI for plaque detection and characterization and the potentials of "Molecular Imaging" using a variety of molecules present in atherosclerotic plaques that may serve as targets for specific contrast agents to allow the identification of high-risk atherosclerotic lesions in-vivo. Ultimately, such agents may enable treatment of "high-risk" patients prior to lesion progression and occurrence of complications.     

Velocity profiles in stenosed tube models using magnetic resonance imaging

A time-of-flight MRI velocity measurement technique is evaluated against corresponding LDV measurements in a constriction tube model over a range of physiologic flow conditions. Results from this study show that MR displacement images can: 1) be obtained within both laminar and turbulent jets (maximum stenotic Re approximately equal to 4,200), 2) measure mean jet velocities up to 172 cm/s, and, 3) detect low forward and reverse stenosis (0 less than or equal to L/D less than or equal to 2). Regions between the jet termination point and re-establishment of laminar flow (Re greater than or equal to 1500, greater than or equal to 1000, and greater than or equal to 110 downstream of 40, 60, and 80 percent stenosis, respectively) cannot presently be detected by this technique.     

Model studies of nonsteady flow using magnetic resonance imaging

A bolus-tracking magnetic resonance imaging (MRI) method has been employed to measure velocity profiles for oscillatory flow with and without a steady flow component as well as pulsatile flow in an axisymmetric tube model. A range of flow conditions within normal physiological limits was tested. The imaged velocity profiles were observed to be generally in accord with theoretical predictions. Instantaneous flow rates calculated from the MR images agreed well with those assessed using an ultrasonic flowmeter. Because MRI is noninvasive and poses few risks to subjects, this technique is potentially useful for studying vascular hemodynamics in vivo.     

Structural changes of hip osteoarthritis using magnetic resonance imaging

Introduction

Few data are available concerning structural changes at the hip observed by magnetic resonance imaging (MRI) in people with or without hip osteoarthritis (OA). The aim of this study was to compare cartilage volume and the presence of cartilage defects and bone marrow lesions (BMLs) in participants with and without diagnosed hip OA.

Methods

Femoral head cartilage volume was measured by MRI for 141 community-based persons with no diagnosed hip OA, and 19 with diagnosed hip OA. Cartilage defects and BMLs were regionally scored at the femoral head and acetabulum.

Results

Compared with those without diagnosed hip OA, people with diagnosed hip OA had less femoral head cartilage volume (1763 mm³ versus 3343 mm³; p <0.001) and more prevalent cartilage defects and BMLs (all p ≤0.05) at all sites other than the central inferomedial region of the femoral head. In those with no diagnosed hip OA, cartilage defects in the anterior and central superolateral region of the femoral head were associated with reduced femoral head cartilage volume (all p ≤0.02). Central superolateral BMLs at all sites were associated with reduced femoral head cartilage volume (all p ≤0.003), with a similar trend occurring when BMLs were located in the anterior region of the hip (all p ≤0.08).

Conclusions

Compared with community-based adults with no diagnosed hip OA, people with diagnosed hip OA have less femoral head cartilage volume and a higher prevalence of cartilage defects and BMLs. For people with no diagnosed hip OA, femoral head cartilage volume was reduced where cartilage defects and/or BMLs were present in the anterior and central superolateral regions of the hip joint. Cartilage defects and BMLs present in the anterior and central superolateral regions may represent early structural damage in the pathogenesis of hip OA.     

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

Background

Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles.

Methods

This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses.

Results

Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005).

Conclusion

Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.