B Klumpp

MRI of muscular fat

An MRI technique with high selectivity and sensitivity to the signal components in the chemical shift range of methylene and methyl protons of fatty acids has been developed for noninvasive assessment of muscular fat in vivo. A spoiled gradient‐echo sequence with spatial‐spectral excitation by six equidistant pulses with 2°‐(−9°)‐17°‐(−17°)‐9°‐(−2°) and a multi‐echo train (TE = 16, 36, 56, 76, 96, and 116 ms) allowed a series of images to be recorded with a receiver bandwidth of 78 Hz per pixel. SIs from phantoms with lipid contents between 0.1% and 100% were compared to those from pure water. Thirty healthy volunteers underwent fat‐selective imaging of their lower leg, and parallel localized proton spectroscopy of the tibialis anterior and the soleus muscle by a single‐voxel stimulated echo acquisition mode (STEAM) technique (TR = 2 s, TE = 10 ms, TM = 15 ms). Results show a high correlation (r = 0.91) between fat imaging and the spectroscopic approach in the soleus muscle, considering the percentage total fat content of musculature. The correlation coefficient was clearly lower (r = 0.55) in the tibialis anterior muscle due to signal contaminations from adjacent subcutaneous fat in the images, inhomogeneous fat distribution, and generally lower lipid content in this muscle. Applications of the new imaging technique showed marked intra‐ and interindividual variability in the spatial distribution of lipids in the musculature of the lower leg. No significant correlation of the muscular fat with the thickness of the subcutaneous fat layer was found. In addition, the body mass index does not appear to determine muscular fat content, except in very obese cases. Magn Reson Med 47:720–727, 2002.

Assessment of myocardial viability using delayed enhancement magnetic resonance imaging at 3.0 Tesla.

Objective:Cardiac magnetic resonance imaging (MRI) at 3.0 T has recently become available and potentially provides a significant improvement of tissue contrast in T1-weighted imaging techniques relying on Gd-based contrast enhancement. Imaging at high-field strength may be especially advantageous for methods relying on strong T1-weighting and imaging after contrast material administration. The aim of this study was to compare cardiac delayed enhancement (DE) MRI at 3.0 T and 1.5 T with respect to image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) between infarcted and normal myocardium. Materials and Methods:Forty consecutive patients with history of myocardial infarction were examined at 3.0 T (n = 20) or at 1.5 T (n = 20). Myocardial function was assessed using cine steady-state-free-precession (SSFP) sequences (TR 3.1 milliseconds, TE 1.6 milliseconds, flip angle 70°, and a matrix of 168 × 256 at 1.5 T and TR 3.4 milliseconds, TE 1.7 milliseconds, flip angle 50° and a matrix of 168 × 256 at 3.0 T), acquired in long- and short-axes views. DE images were obtained 15 minutes after the administration of 0.15 mmol of Gd-DTPA/kg body weight using a segmented inversion recovery prepared gradient echo sequence at 1.5 T (TR 9.6 milliseconds, TE 4.4 milliseconds, flip angle 25°, matrix 160 × 256, bandwidth 140 Hertz/pixel) and at 3.0 T (TR 9.8 milliseconds, TE 4.3 milliseconds, flip angle 30°, matrix 150 × 256, bandwidth 140 Hertz/pixel). For image analysis, standardized SNR and CNR measurements were performed in infarcted and remote myocardial regions. Two independent observers rated image quality on a 4-point scale (0 = poor image quality, 1 = sufficient image quality, 2 = good image quality, 3 = excellent image quality). Results:High diagnostic image quality was obtained in all patients. Rating of mean image quality was 2.2 ± 0.8 at 1.5 T and 2.5 ± 0.6 at 3.0 T (P = 0.012) for observer 1 and 2.2 ± 0.7 at 1.5 T and 2.6 ± 0.6 at 3.0 T (P = 0.003) for observer 2, respectively. Interobserver agreement was good (κ = 0.68 at 1.5 T and 0.78 at 3.0 T). SNR measurements yielded a mean SNR of 37.8 ± 13.9/22.9 ± 6.0 in infarcted myocardium (P < 0.001) and 5.6 ± 2.2/5.9 ± 2.4 in normal myocardium (P = 0.45) at 3.0 T/1.5 T, respectively. CNR measurements revealed mean values of 32.4 ± 13.0/16.7 ± 5.4 (P<0.001) at 3.0 T/1.5 T, respectively. Conclusions:Delayed enhancement MRI at 3.0 T is feasible and provides superior image quality compared with 1.5 T. Furthermore, using identical contrast doses, increased SNR and CNR values were recorded at 3.0 T.

A Comprehensive Approach to the Analysis of Contrast Enhanced Cardiac MR Images

Current magnetic resonance imaging (MRI) technology allows the determination of patient-individual coronary tree structure, detection of infarctions, and assessment of myocardial perfusion. Joint inspection of these three aspects yields valuable information for therapy planning, e.g., through classification of myocardium into healthy tissue, regions showing a reversible hypoperfusion, and infarction with additional information on the corresponding supplying artery. Standard imaging protocols normally provide image data with different orientations, resolutions and coverages for each of the three aspects, which makes a direct comparison of analysis results difficult. The purpose of this work is to develop methods for the alignment and combined analysis of these images. The proposed approach is applied to 21 datasets of healthy and diseased patients from the clinical routine. The evaluation shows that, despite limitations due to typical MRI artifacts, combined inspection is feasible and can yield clinically useful information.

Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases

Brain metastases are the most common cause of death in patients with metastatic melanoma, and the RAF‐MEK‐ERK and PI3K‐AKT signaling pathways are key players in melanoma progression and drug resistance. The BRAF inhibitor vemurafenib significantly improved overall survival. However, brain metastases still limit the effectiveness of this therapy. In a series of patients, we observed that treatment with vemurafenib resulted in substantial regression of extracerebral metastases, but brain metastases developed. This study aimed to identify factors that contribute to treatment resistance in brain metastases. Matched brain and extracerebral metastases from melanoma patients had identical ERK, p‐ERK, and AKT immunohistochemistry staining patterns, but there was hyperactivation of AKT (p‐AKT) and loss of PTEN expression in the brain metastases. Mutation analysis revealed no differences in BRAF, NRAS, or KIT mutation status in matched brain and extracerebral metastases. In contrast, AKT, p‐AKT, and PTEN expression was identical in monolayer cultures derived from melanoma brain and extracerebral metastases. Furthermore, melanoma cells stimulated by astrocyte‐conditioned medium showed higher AKT activation and invasiveness than melanoma cells stimulated by fibroblast‐conditioned medium. Inhibition of PI3K‐AKT signaling resensitized melanoma cells isolated from a vemurafenib‐resistant brain metastasis to vemurafenib. Brain‐derived factors appear to induce hyperactivation of the AKT survival pathway and to promote the survival and drug resistance of melanoma cells in the brain. Thus, inhibition of PI3K‐AKT signaling shows potential for enhancing and/or prolonging the antitumor effect of BRAF inhibitors or other anticancer agents in melanoma brain metastases.

Lipid content in the musculature of the lower leg assessed by fat selective MRI: Intra‐ and interindividual differences and correlation with anthropometric and metabolic data

To assess the muscular lipid content (LC) in different muscle groups of the lower leg by a magnetic resonance imaging technique working with chemical shift selective excitation, and comparison with anthropometric and metabolic data.

Assessment of myocardial viability in a reperfused porcine model: evaluation of different MSCT contrast protocols in acute and subacute infarct stages in comparison with MRI.

Objective: To assess myocardial viability in acute and subacute infarcts using different multislice spiral computed tomography contrast protocols with magnetic resonance imaging (MRI) correlation. Methods: Seven pigs were studied with 64-multislice spiral computed tomography and MRI (1.5 T) at a median of 1 and 21 days after temporary occlusion of the second diagonal branch. Computed tomography was performed at 3, 5, 10, and 15 minutes after injection of contrast medium. Contrast agent was applied either as a bolus (protocol 1; n = 7 for the first; n = 5 for the second scan) or as a bolus plus 30 mL of subsequent 0.1 mL/s low-flow (protocol 2; n = 7 for the first; n = 6 for the second scan). Finally, histological sections were obtained. Volumes of infarcted myocardium were assessed as the percentage of the left ventricle. Computed tomography attenuation values were obtained, and image quality was assessed. Results: When compared with protocol 1, protocol 2 provided greater Hounsfield unit attenuation difference between viable and nonviable myocardium at 5, 10, and 15 minutes (P = 0.19; 0.003; 0.0006) and an additional significant contrast between nonviable myocardium and ventricular blood at 3 and 5 minutes (P < 0.001). Image quality was rated significantly higher with the use of protocol 2 at 5, 10, and 15 minutes (P ≤ 0.027) and for all time points use of protocol 2 resulted in improved correlation of acute and subacute infarct size with MRI. Conclusions: Good correlation of infarct zones with MRI was achieved for both acute and subacute infarcts. With the use of a bolus/low-flow protocol, image quality was substantially improved by means of a higher tissue contrast.

Ultrafast Whole-Body MR Angiography with Two-dimensional Parallel Imaging at 3.0 T: Feasibility Study

The study was approved by the local ethics committee, and informed consent was provided by all participants prior to the examination. The aim of the study was to assess the feasibility of whole-body three-dimensional (3D) contrast material-enhanced magnetic resonance (MR) angiography with parallel imaging in the phase- and section-encoding directions (ie, integrated parallel acquisition technique [iPAT(2); Siemens, Erlangen, Germany]) for all anatomic imaging stations in combination with a single injection of contrast material. Whole-body contrast-enhanced MR angiography was performed in 23 patients at 3.0 T. Images were evaluated by two independent observers for quality on a four-point scale (where a score of 1 indicated poor image quality and a score of 4, excellent image quality); signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated for representative vessel regions in each station. Mean image quality scores were 3.13 +/- 1.15 (standard deviation) and 3.17 +/- 1.14 for observers 1 and 2, respectively (kappa = 0.81). Signal intensity measurements revealed mean SNR values between 36.2 +/- 8.0 and 56.2 +/- 17.7 and mean CNR values between 29.0 +/- 7.4 and 48.2 +/- 15.7. The data suggest that contrast-enhanced MR angiography with iPAT(2) is feasible for whole-body applications and allows acquisition of 3D data sets with adequate spatial resolution within short measurement times, facilitating a single injection of contrast material.

Low-Dose, Time-Resolved, Contrast-Enhanced 3D MR Angiography in the Assessment of the Abdominal Aorta and Its Major Branches at 3 Tesla

RATIONALE AND OBJECTIVES The aims of this study were to evaluate the effectiveness of low-dose, contrast-enhanced (CE), time-resolved, three-dimensional magnetic resonance angiography (MRA) in the assessment of the abdominal aorta and its major branches at 3 T and to compare the results with those of high-spatial resolution CE MRA. MATERIALS AND METHODS Twenty-two consecutive patients (eight men, 14 women; mean age, 43.9 +/- 17.9 years) underwent CE time-resolved three-dimensional MRA and high-spatial resolution three-dimensional MRA. Studies were performed using a 3-T magnetic resonance system; gadolinium-based contrast medium was administered at a dose of 3 to 5 mL for time-resolved MRA, followed by 0.1 mmol/kg gadopentetate dimeglumine for single-phase CE MRA. For analysis purposes, the abdominal arterial system was divided into 11 arterial segments, and image quality as well as the presence and degree of vascular pathology were evaluated by two independent magnetic resonance radiologists. RESULTS A total of 242 arterial segments were visualized with good image quality. Time-resolved MRA was able to visualize the majority of arterial segments with good definition in the diagnostic range. Vascular pathologies (stenosis, occlusion) or abnormal vascular anatomy was detected in 19 arterial segments, with good interobserver agreement (kappa = 0.78). All image findings were detected with time-resolved CE MRA by both observers and were confirmed by correlative imaging. CONCLUSION Low-dose, time-resolved MRA at 3 T yields rapid and important anatomic and functional information in the evaluation of the abdominal vasculature. Because of its limited spatial resolution, time-resolved MRA is inferior to CE MRA in demonstrating fine vascular details.

Quantitative assessment of ventricular function using three‐dimensional SSFP magnetic resonance angiography

To evaluate three‐dimensional (3D), free‐breathing, steady‐state free precession (SSFP) magnetic resonance angiography (MRA) for volumetric assessment of ventricular function.

Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting

BackgroundPrevious experiences of whole body MR angiography are predominantly available in linear 0.5 M gadolinium-containing contrast agents. The aim of this study was to compare image quality on a four-point scale (range 1–4) and diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80 patients) with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85 patients) on a 1.5 T whole body MR system. Digital subtraction angiography served as standard of reference.ResultsAll examinations yielded diagnostic image quality. There was no significant difference in image quality (3.76 ± 0.3 versus 3.78 ± 0.3, p = n.s.) and diagnostic accuracy observed. Sensitivity and specificity of the detection of hemodynamically relevant stenoses was 93%/95% in the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group, respectively.ConclusionThe high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products) recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis.