Michael Schär

Cardiac SSFP imaging at 3 Tesla

Balanced steady‐state free precession (SSFP) techniques provide excellent contrast between myocardium and blood at a high signal‐to‐noise ratio (SNR). Hence, SSFP imaging has become the method of choice for assessing cardiac function at 1.5T. The expected improvement in SNR at higher field strength prompted us to implement SSFP at 3.0T. In this work, an optimized sequence protocol for cardiac SSFP imaging at 3.0T is derived, taking into account several partly adverse effects at higher field, such as increased field inhomogeneities, longer T1, and power deposition limitations. SSFP contrast is established by optimizing the maximum amplitude of the radiofrequency (RF) field strength for shortest TR, as well as by localized linear or second‐order shimming and local optimization of the resonance frequency. Given the increased SNR, sensitivity encoding (SENSE) can be employed to shorten breath‐hold times. Short‐axis, long‐axis, and four‐chamber cine views obtained in healthy adult subjects are presented, and three different types of artifacts are discussed along with potential methods for reducing them. Magn Reson Med 51:799–806, 2004.

Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart

Background— Stem cell labeling with iron oxide (ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats. Methods and Results— We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and β-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology (at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no β-galactosidase–positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively. Conclusions— The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart.

Positive contrast visualization of iron oxide‐labeled stem cells using inversion‐recovery with ON‐resonant water suppression (IRON)

In proton magnetic resonance imaging (MRI) metallic substances lead to magnetic field distortions that often result in signal voids in the adjacent anatomic structures. Thus, metallic objects and superparamagnetic iron oxide (SPIO)‐labeled cells appear as hypointense artifacts that obscure the underlying anatomy. The ability to illuminate these structures with positive contrast would enhance noninvasive MR tracking of cellular therapeutics. Therefore, an MRI methodology that selectively highlights areas of metallic objects has been developed. Inversion‐recovery with ON‐resonant water suppression (IRON) employs inversion of the magnetization in conjunction with a spectrally‐selective on‐resonant saturation prepulse. If imaging is performed after these prepulses, positive signal is obtained from off‐resonant protons in close proximity to the metallic objects. The first successful use of IRON to produce positive contrast in areas of metallic spheres and SPIO‐labeled stem cells in vitro and in vivo is presented. Magn Reson Med 58:1072–1077, 2007.

“MRI Stealth” robot for prostate interventions

The paper reports an important achievement in MRI instrumentation, a pneumatic, fully actuated robot located within the scanner alongside the patient and operating under remote control based on the images. Previous MRI robots commonly used piezoelectric actuation limiting their compatibility. Pneumatics is an ideal choice for MRI compatibility because it is decoupled from electromagnetism, but pneumatic actuators were hardly controllable. This achievement was possible due to a recent technology breakthrough, the invention of a new type of pneumatic motor, PneuStep 4, designed for the robot reported here with uncompromised MRI compatibility, high‐precision, and medical safety. MrBot is one of the “MRI stealth” robots today (the second is described in this issue by Zangos et al.). Both of these systems are also multi‐imager compatible, being able to operate with the imager of choice or cross‐imaging modalities. For MRI compatibility the robot is exclusively constructed of nonmagnetic and dielectric materials such as plastics, ceramics, crystals, rubbers and is electricity free. Light‐based encoding is used for feedback, so that all electric components are distally located outside the imagers room. MRI robots are modern, digital medical instruments in line with advanced imaging equipment and methods. These allow for accessing patients within closed bore scanners and performing interventions under direct (in scanner) imaging feedback. MRI robots could allow e.g. to biopsy small lesions imaged with cutting edge cancer imaging methods, or precisely deploy localized therapy at cancer foci. Our robot is the first to show the feasibility of fully automated in‐scanner interventions. It is customized for the prostate and operates transperineally for needle interventions. It can accommodate various needle drivers for different percutaneous procedures such as biopsy, thermal ablations, or brachytherapy. The first needle driver is customized for fully automated low‐dose radiation seed brachytherapy. This paper gives an introduction to the challenges of MRI robot compatibility and presents the solutions adopted in making the MrBot. Its multi‐imager compatibility and other preclinical tests are included. The robot shows the technical feasibility of MRI‐guided prostate interventions, yet its clinical utility is still to be determined.

Nuclear Overhauser Enhancement (NOE) Imaging in the Human Brain at 7 T

Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus a relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.

Intracranial arterial wall imaging using three-dimensional high isotropic resolution black blood MRI at 3.0 Tesla.

To develop a high isotropic‐resolution sequence to evaluate intracranial vessels at 3.0 Tesla (T).

Noninvasive Detection of Macrophage-rich Atherosclerotic Plaque in Hyperlipidemic Rabbits using ‘Positive Contrast’ Magnetic Resonance Imaging

OBJECTIVES This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Automatic Brachytherapy Seed Placement Under MRI Guidance

The paper presents a robotic method of performing low dose rate prostate brachytherapy under magnetic resonance imaging (MRI) guidance. The design and operation of a fully automated MR compatible seed injector is presented. This is used with the MrBot robot for transperineal percutaneous prostate access. A new image-registration marker and algorithms are also presented. The system is integrated and tested with a 3T MRI scanner. Tests compare three different registration methods, assess the precision of performing automated seed deployment, and use the seeds to assess the accuracy of needle targeting under image guidance. Under the ideal conditions of the in vitro experiments, results show outstanding image-guided needle and seed placement accuracy.

The ageing male heart: myocardial triglyceride content as independent predictor of diastolic function

AIMS In animal models of obesity and diabetes mellitus, myocardial TG accumulation is associated with decreased myocardial function. In the physiologically ageing heart, myocardial triglyceride (TG) accumulation may also occur due to reduced myocardial fatty acid oxidation. The role of myocardial TG in the ageing human heart is unknown. Therefore, the purpose of our study was to evaluate the effects of ageing on myocardial TG content, and to determine the association between myocardial TG content and heart function. METHODS AND RESULTS 1H-magnetic resonance spectroscopy and magnetic resonance imaging of the heart were performed in 43 healthy male subjects. Mean age (range) of the subjects was 44 (20-66) years. Body mass index (BMI), blood pressure, and biochemical markers were determined. Age correlated significantly to myocardial TG content (r = 0.57, P < 0.05) independently of BMI. Furthermore, myocardial TG content correlated negatively with left ventricular diastolic function (represented by E/A ratio, r = -0.68, P < 0.05). Multivariable analysis indicated myocardial TG content as independent predictor (P < 0.05) of the age related decrease in diastolic heart function. CONCLUSION Myocardial TG content increases in the physiologically ageing male heart and is associated with the age-related decline in diastolic function, independent of BMI, blood pressure, and biochemical blood markers.

Transperineal Prostate Intervention: Robot for Fully Automated MR Imaging—System Description and Proof of Principle in a Canine Model

The study was approved by the animal care and use committee. The purpose of the study was to prospectively establish proof of principle in vivo in canines for a magnetic resonance (MR) imaging-compatible robotic system designed for image-guided prostatic needle intervention. The entire robot is built with nonmagnetic and dielectric materials and in its current configuration is designed to perform fully automated brachytherapy seed placement within a closed MR imager. With a 3.0-T imager, in four dogs the median error for MR imaging-guided needle positioning and seed positioning was 2.02 mm (range, 0.86-3.18 mm) and 2.50 mm (range, 1.45-10.54 mm), respectively. The robotic system is capable of accurate MR imaging-guided prostatic needle intervention within a standard MR imager in vivo in a canine model.