MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation.

Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T2 * magnetic resonance (MR) relaxometry is a more accurate alternative for follow-up in pediatric patients before and after allogenic SCT. Twenty-three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T2 * relaxometry on a 1.5 T MR-scanner to estimate liver iron concentrations from the T2 * values ("MR-Fe"). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR-Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR-Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR-Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.

Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions.

BACKGROUND: Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE: The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS: ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS: We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION: Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.

Deformation-based brain morphometry in rats.

Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra-high field dedicated animal MRI systems. Here, we developed a novel deformation-based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of-interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats.

Possibilities and limitations for high resolution small animal MRI on a clinical whole-body 3T scanner.

OBJECT: To investigate the potential of a clinical 3 T scanner to perform MRI of small rodents. MATERIALS AND METHODS: Different dedicated small animal coils and several imaging sequences were evaluated to optimize image quality with respect to SNR, contrast and spatial resolution. As an application, optimal grey-white-matter contrast and resolution were investigated for rats. Furthermore, manganese-enhanced MRI was applied in mice with unilateral crush injury of the optic nerve to investigate coil performance on topographic mapping of the visual projection. RESULTS: Differences in SNR and CNR up to factor 3 and more were observed between the investigated coils. The best grey-white matter contrast was achieved with a high resolution 3D T (2)-weighted TSE (SPACE) sequence. Delineation of the retino-tectal projection and detection of defined visual pathway damage on the level of the optic nerve could be achieved by using a T (1)-weighted, 3D gradient echo sequence with isotropic resolution of (0.2 mm)(3). CONCLUSIONS: Experimental studies in small rodents requiring high spatial resolution can be performed by using a clinical 3 T scanner with appropriate dedicated coils.

Resolving arterial phase and temporal enhancement characteristics in DCE MRM at high spatial resolution with TWIST acquisition.

PURPOSE: To investigate the potential of a view-sharing 3D fast gradient-echo sequence using pseudo random trajectories (TWIST) to achieve very short acquisition times with high in-plane resolution and good volume coverage and its application to dynamic contrast-enhanced (DCE) breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Two versions of a 3D fast gradient echo TWIST sequence were implemented and applied to patients: First, an ultrafast TWIST acquisition (TA = 5.7 sec) in combination with a routine DCE MRM protocol to allow the extraction of arterial input functions and to resolve the first pass of the contrast agent. Second, a dynamic full coverage TWIST DCE acquisition (TA = 10.6 sec) in a repeat examination, replacing the routine DCE MRM sequence. RESULTS: The ultrafast acquisition enabled extraction of arterial input functions and the monitoring of the contrast agent's first pass through vessels and lesions. The dynamic full coverage TWIST acquisition captured the initial dynamic slope of the signal time curve of lesions accurately, in contrast to the routine protocol. CONCLUSION: TWIST acquisitions proved very robust and offer high flexibility in protocol timing. The ultrafast protocol achieved 5.7 seconds time resolution with good image quality and can be combined with any established routine protocol. The full dynamics TWIST DCE protocol offers improved time resolution of the CE dynamic time-course and closely matches the image quality of the routine protocol.

Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results.

BACKGROUND: Routine assessment of body iron load in patients with acute leukemia is usually done by serum ferritin (SF) assay; however, its sensitivity is impaired by different conditions including inflammation and malignancy. OBJECTIVE: To estimate, using MRI, the extent of liver iron overload in children with acute leukemia and receiving blood transfusions, and to examine the association between the degree of hepatic iron overload and clinical parameters including SF and the transfusion iron load (TIL). MATERIAL AND METHODS: A total of 25 MRI measurements of the liver were performed in 15 children with acute leukemia (mean age 9.75 years) using gradient-echo sequences. Signal intensity ratios between the liver and the vertebral muscle (L/M ratio) were calculated and compared with SF-levels. TIL was estimated from the cumulative blood volume received, assuming an amount of 200 mg iron per transfused red blood cell unit. RESULTS: Statistical analysis revealed good correlation between the L/M SI ratio and TIL (r = -0.67, P = 0.002, 95% confidence interval CI = -0.83 to -0.34) in patients with acute leukemia as well as between L/M SI ratio and SF (r = -0.76, P = 0.0003, 95% CI = -0.89 to -0.52). CONCLUSION: SF may reliably reflect liver iron stores as a routine marker in patients suffering from acute leukemia.

Long-term prevalence of NIRF-labeled magnetic nanoparticles for the diagnostic and intraoperative imaging of inflammation.

Inflammation is a very common disease worldwide. In severe cases, surgery is often the method of choice. Today, there is a general need for the implementation of image-based guidance methodologies for reliable target resection. We investigated new near infrared fluorescence (NIRF)-nanoparticles (NPs) as a simple but effective bimodal magnetic resonance imaging (MRI) and optical contrast agent for diagnosis and intraoperative imaging of inflammation. Physicochemical analysis revealed that these NPs were highly fluorescent with similar characteristics like unlabeled NPs (hydrodynamic diameter about 130 nm and zeta potential about -10 mV). NP-uptake and NIR-dye labeling was biocompatible to macrophages (no impact on cellular ATP and reactive oxygen species production). These cells could successfully be tracked with MRI and NIRF-optical imaging. I.v. injection of fluorescent NPs into mice led to highly specific T2-weighted signal of edema due to uptake by phagocytic cells and subsequent migration to the site of inflammation. NIRF signals of the edema region were well detectable for up to 4 weeks, underlining the potential of the NPs for systematic planning and flexible time scheduling in intraoperative applications. NPs were degraded over a time period of 12 weeks, which was not altered due to inflammation. Redistribution of iron might be primarily due to inflammation and not to the presence of NPs per se in a concentration suitable for imaging. Our findings highlight the potential of the NPs to be used as a suitable tool for pre- and intraoperative imaging of inflammation.

A plasma protein corona enhances the biocompatibility of Au@Fe3O4 Janus particles.

Au@Fe3O4 Janus particles (JPs) are heteroparticles with discrete domains defined by different materials. Their tunable composition and morphology confer multimodal and versatile capabilities for use as contrast agents and drug carriers in future medicine. Au@Fe3O4 JPs have colloidal properties and surface characteristics leading to interactions with proteins in biological fluids. The resulting protein adsorption layer ("protein corona") critically affects their interaction with living matter. Although Au@Fe3O4 JPs displayed good biocompatibility in a standardized in vitro situation, an in-depth characterization of the protein corona is of prime importance to unravel underlying mechanisms affecting their pathophysiology and biodistribution in vitro and in vivo. Here, we comparatively analyzed the human plasma corona of Au-thiol@Fe3O4-SiO2-PEG JPs (NH2-functionalized and non-functionalized) and spherical magnetite (Fe3O4-SiO2-PEG) particles and investigated its effects on colloidal stability, biocompatibility and cellular uptake. Label-free quantitative proteomic analyses revealed that complex coronas including almost 180 different proteins were formed within only one minute. Remarkably, in contrast to spherical magnetite particles with surface NH2 groups, the Janus structure prevented aggregation and the adhesion of opsonins. This resulted in an enhanced biocompatibility of corona sheathed JPs compared to spherical magnetite particles and corona-free JPs.

MRI compatible small animal monitoring and trigger system for whole body scanners.

Performing magnetic resonance imaging (MRI) experiments with small animals requires continuous monitoring of vital parameters, especially the respiration rate. Clinical whole-body MR scanners represent an attractive option for preclinical imaging as dedicated animal scanners are cost-intensive in both investment and maintenance, thus limiting their availability. Even though impressive image quality is achievable with clinical MR systems in combination with special coils, their built-in physiologic monitoring and triggering units are often not suited for small animal imaging. In this work, we present a simple, MRI compatible low cost solution to monitor the respiration and heart rate of small animals in a clinical whole-body MR scanner. The recording and processing of the biosignals as well as the optimisation of the respiratory trigger generation is decribed. Additionally rat and mouse in-vivo MRI experiments are presented to illustrate the effectiveness of the monitoring and respiratory trigger system in suppressing motion artifacts.