Carsten Warmuth

Fractional encoding of harmonic motions in MR elastography

In MR elastography (MRE) shear waves are magnetically encoded by bipolar gradients that usually oscillate with the same frequency fv as the mechanical vibration. As a result, both the repetition time (TR) and echo time (TE) of such an MRE sequence are greater than the vibration period 1/fv. This causes long acquisition times and considerable signal dephasing in tissue with short transverse relaxation times. Here we propose a reverse concept with TR ≤ 1/fv which we call “fractional” MRE, i.e., only a fraction of one vibration cycle per TR, can be used for motion sensitization. The benefit of fractional MRE is twofold: 1) acquisition times in seconds can be achieved for a single‐phase difference wave image, and 2) materials that combine low elasticity, high viscosity, and short T  2* relaxation times show an increased phase‐to‐noise ratio (PNR). A twofold increase of the phase signal is predicted for liver‐like materials. Volunteer studies performed in liver and biceps show the benefit of fractional MRE. Furthermore, we demonstrate the feasibility of the technique for in vivo myocardial MRE by visualizing transverse wave propagation in the interventricular septum (IVS). Magn Reson Med 57:388–395, 2007.

Brain tumor perfusion: Comparison of dynamic contrast enhanced magnetic resonance imaging using T1, T2, and T 2 * contrast, pulsed arterial spin labeling, and H215O positron emission tomography

OBJECTIVES Different techniques for measuring of perfusion are clinically available, but these are usually applied to healthy brain tissue. MATERIAL AND METHODS Five different techniques were used here in 12 patients with brain tumors to investigate the impact of tumor vascularization on the perfusion signal: three qualitative dynamic contrast-enhanced/susceptibility-contrast magnetic resonance imaging (DCE-MRI/DSC-MRI) techniques exploiting T(1), T(2), T(2)(*) contrast, and two quantitative techniques, pulsed arterial spin labeling (PASL) and H(2)(15)O positron emission tomography (H(2)(15)O-PET). RESULTS In a first approximation, a linear correlation was found between all five imaging modalities regarding the perfusion signal of both, normal brain tissue and tumor. The estimated values for tumor perfusion differed significantly between the techniques (1=methodical mean in arbitrary units): PASL: 0.83, H(2)(15)O-PET: 0.62, T(1)-DCE: 1.73, T(2)-DCE: 0.69, T(2)(*)-DSC: 0.89. CONCLUSIONS The tumor perfusion values, determined with different techniques are not comparable. The T(2)(*)-DSC, here applied with contrast agent presaturation of extravascular space, and PASL depict median perfusion most reliably.

Protease-Specific Nanosensors for Magnetic Resonance Imaging

Imaging of enzyme activity is a central goal of molecular imaging. With the introduction of fluorescent smart probes, optical imaging has become the modality of choice for experimental in vivo detection of enzyme activity. Here, we present a novel high-relaxivity nanosensor that is suitable for in vivo imaging of protease activity by magnetic resonance imaging. Upon specific protease cleavage, the nanoparticles rapidly switch from a stable low-relaxivity stealth state to become adhesive, aggregating high-relaxivity particles. To demonstrate the principle, we chose a cleavage motif of matrix metalloproteinase 9 (MMP-9), an enzyme important in inflammation, atherosclerosis, tumor progression, and many other diseases with alterations of the extracellular matrix. On the basis of clinically tested very small iron oxide particles (VSOP), the MMP-9-activatable protease-specific iron oxide particles (PSOP) have a hydrodynamic diameter of only 25 nm. PSOP are rapidly activated, resulting in aggregation and increased T2*-relaxivity.

High Spatial Resolution T1-weighted Mr Imaging of Liver and Biliary Tract During Uptake Phase of a Hepatocyte-specific Contrast Medium

Objectives:The hypothesis for this prospective study was that T1-weighted respiratory triggered high spatial resolution images of the liver acquired during the uptake phase of a hepatobiliary contrast medium are technically feasible and provide significantly improved image quality compared with breath-hold images. Materials and Methods:An inversion recovery-prepared spoiled gradient echo sequence was developed that can be obtained with respiratory triggering. This sequence was acquired in 20 patients with a total of 41 focal liver lesions and compared with axial and coronal breath-hold spoiled gradient echo sequences. All 3 sequences were obtained in the hepatobiliary phase after intravenous injection of Gd-EOB-DTPA at a dosage of 0.025 mmol/kg of body weight. Quantitative evaluation measured the contour sharpness index of the common bile duct and calculated the relative contrast between liver lesions (common bile duct, respectively) and liver parenchyma. In the qualitative assessment, 2 readers independently scored the depiction of focal liver lesions and 3 segments of the biliary tract, the sharpness of hepatic vessels, and the level of artifacts. Statistical significance was assumed at P < 0.05. Results:The respiratory-triggered sequence was technically successful in all 20 patients, revealed significantly higher liver-lesion contrast, contour-sharpness index and scores for depiction of focal liver lesions, biliary tree, and sharpness of hepatic vessels compared with the respective breath-hold sequence. The relative contrast between the common bile duct and the liver parenchyma was significantly higher for the coronal breath-hold sequence compared with the respiratory-triggered sequence. No significant difference was found with respect to the level of artifacts. The 2 readers agreed in 77.9% of the qualitative assessments. Conclusions:T1-weighted respiratory triggered high spatial resolution images obtained in the hepatobiliary phase are technically feasible and significantly improve the image quality compared with breath-hold images.

Accuracy of blood flow values determined by arterial spin labeling: a validation study in isolated porcine kidneys.

To validate the accuracy of quantitative blood flow values determined using pulsed arterial spin labeling (ASL) in the preserved and reperfused porcine kidney.

Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.

UNLABELLED To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE(-/-) mice. Accumulation was evaluated by ex vivo MRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells. In vivo MRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE(-/-) mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens. FROM THE CLINICAL EDITOR The presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy.

Whole-heart coronary magnetic resonance angiography: contrast-enhanced high-resolution, time-resolved 3D imaging.

Objectives:To test the feasibility and performance of a 4D magnetic resonance coronary angiography sequence compared with conventional inversion recovery (IR) prepared gradient echo imaging. Materials and Methods:A 4D sequence with 100 milliseconds temporal resolution was implemented on a 1.5 T system. Five minipigs were examined after administration of very small superparamagnetic iron oxide particles. Coronary angiographies with an isotropic resolution of 0.82 mm were performed in the pigs using 4D and IR sequences. Results:The 4D sequence allowed visualization of the coronary arteries, the effect of their movement and that of the entire heart without prolonging scan time. The contrast-to-noise ratio of the IR images was on average 38% higher than that of the corresponding 4D phase. Conclusions:4D magnetic resonance imaging is superior in that no trigger delay time needs to be determined and an additional whole-heart cine study can be obtained.

Cardiac Magnetic Resonance Angiography using Blood-Pool Contrast Agents: Comparison of Citrate-Coated Very Small Superparamagnetic Iron Oxide Particles with Gadofosveset Trisodium in Pigs

PURPOSE To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs. MATERIALS AND METHODS Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06  mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03  mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60  min after injection. At each time point, three different inversion times (TI; 200  msec, 300  msec, and 400  msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models. RESULTS No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5  min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200  msec and 300 msec were applied (TI of 200  msec at 3 min: 8.2 ± 0.7 vs. 5.4 ± 0.7; TI of 200  msec at 5 min: 7.9 ± 0.7 vs. 3.5 ± 0.8; TI of 300  msec at 3  min: 11.7 ± 0.7 vs. 8.8 ± 0.8; TI of 300  msec at 5  min: 11.4 ± 0.7 vs. 8.0 ± 0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40  min irrespective of TI (p < 0.05). CONCLUSION VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA.

Whole-heart coronary magnetic resonance angiography at 1.5 Tesla: does a blood-pool contrast agent improve diagnostic accuracy?

Objectives:To evaluate the impact of the blood-pool contrast agent gadofosveset trisodium on diagnostic accuracy of whole-heart coronary magnetic resonance angiography (CMRA) at 1.5 Tesla. Materials and Methods:Thirty consecutive patients with suspected coronary artery disease underwent free-breathing whole-heart CMRA at 1.5 Tesla. CMRA was performed with a T2-prepared steady-state free precession sequence (unenhanced CMRA) and an inversion-recovery-prepared steady-state free precession sequence after administration of gadofosveset trisodium (contrast-enhanced CMRA). Two readers independently performed a per-segment evaluation of CMRA (8 proximal and mid coronary segments) for detection of significant stenosis (≥50%) using invasive coronary angiography as reference. Disagreement was settled by consensus reading and interobserver variability was assessed using an unweighted kappa statistic. Results:Whole-heart CMRA was successfully performed in 27 patients. The percentage of assessable segments was significantly lower on unenhanced CMRA compared with contrast-enhanced CMRA (Reader 1: 79% [170/216] vs. 89% [192/216], respectively; Reader 2: 73% [157/216] vs. 87% [188/216], respectively; P < 0.001). Intention-to-diagnose analysis of the consensus reading yielded sensitivity, specificity, and diagnostic accuracy of unenhanced versus contrast-enhanced CMRA as follows: 73.1% versus 73.1% (P = 1.0), 68.3% versus 80.2% (P = 0.002), and 68.9% versus 79.3% (P = 0.004), respectively. The kappa value for interobserver agreement was 0.61 (95% confidence interval = 0.50–0.72) for unenhanced CMRA and 0.72 (95% confidence interval = 0.62–0.82) for contrast-enhanced CMRA. Conclusions:The blood-pool contrast agent gadofosveset trisodium increased the number of assessable coronary segments on whole-heart CMRA in comparison to unenhanced whole-heart CMRA. The impact of gadofosveset trisodium on diagnostic accuracy, however, was only minor.

Gadofosveset trisodium-enhanced magnetic resonance angiography of the left atrium—A feasibility study

AIM Imaging of the left atrium is regularly performed prior to pulmonary vein isolation. The aim of the study was to evaluate the feasibility of contrast-enhanced high-resolution magnetic resonance angiography (MRA) of the left atrium using the blood-pool contrast agent gadofosveset trisodium in comparison to noncontrast MRA. MATERIALS AND METHODS Twenty consecutive patients were examined by free-breathing electrocardiogram-gated whole-heart MRA (reconstructed spatial resolution, 0.7mm x 0.6mm x 0.8mm) with a noncontrast T2-prepared steady state free precession sequence (T2-prep SSFP) and a gadofosveset trisodium-enhanced inversion-recovery SSFP sequence (CE IR-SSFP). Contrast-to-noise ratio (CNR) of blood in the left atrium was determined. Depiction of the left atrium was rated by two radiologists in consensus. A cardiologist segmented the MR data sets and rated depiction of the left atrium. RESULTS Five of 20 patients had irregular breathing patterns with navigator efficiency less than 35% and were excluded from evaluation. CNR was significantly higher for CE IR-SSFP compared with T2-prep SSFP (18.4+/-5.3 vs. 11.7+/-3.5, p<0.01). Depiction of the left atrium by T2-prep SSFP was rated as good in four patients, moderate in ten patients, and poor in one patient, whereas depiction of the left atrium by CE IR-SSFP was rated as excellent in nine patients, good in four patients, and moderate in two patients. CE IR-SSFP allowed for semiautomated segmentation of the left atrium in 15 patients, whereas T2-prep SSFP allowed for segmentation only in ten patients. CONCLUSION Gadofosveset trisodium-enhanced MRA of the left atrium is feasible with significantly improved image quality compared to noncontrast MRA.