Indirect evidence for the potential ability of magnetic resonance imaging to evaluate the myocardial iron content in patients with transfusional iron overload

The purpose of this study was to evaluate the potential ability of magnetic resonance imaging (MRI) for evaluation of myocardial iron deposits. The applied MRI technique has earlier been validated for quantitative determination of the liver iron concentration. The method involves cardiac gating and may, therefore, also be used for simultaneous evaluation of myocardial iron. The tissue signal intensities were measured from spin echo images and the myocardium muscle signal intensity ratio was determined. The SI ratio was converted to tissue iron concentration values based on a modified calibration curve from the liver model. The crucial steps of the method were optimized; i.e. recognition and selection of the myocardial slice for analysis and positioning of the regions of interest (ROIs) within the myocardium and the skeletal muscle. This made the myocardial MRI measurements sufficiently reproducible. We applied this method in 41 multiply transfused patients. Our data demonstrate significant positive linear relationships between different iron store parameters and the MRI-derived myocardial iron concentration, which was significantly related to the serum ferritin concentration (ρ = 0.62.P < 0.0001) and to the MRI-determined liver iron concentration (ρ = 0.36,P = 0.02). The myocardial MRI iron concentrations demonstrated also a significant positive correlation with the number of blood units given (ρ = 0.45,P = 0.005) and the aminotransferase serum concentration (ρ = 0.54,P = 0.0008). Our data represents indirect evidence for the ability of MRI techniques based on myocardium/muscle signal intensity ratio measurements to evaluate myocardial iron overload.     

T2 relaxation time study of iron overload in b-thalassemia

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18–44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml^-1). Results were compared with nine controls, with a mean age of 25 (18–43) years. Heart T2 relaxation time in controls (44.3 ± 3.5 ms) was higher than in group A (29.9 ± 5.7 ms,P< 0.001) and group B (33.4 ± 6.8 ms,P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 ± 0.27) was lower than in group B (0.82 ± 0.33,P < 0.001) and the controls (1.15 ± 0.20,P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels(r = - 0.52, P<0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time. © 1998 Elsevier Science B.V. All rights reserved.     

Liver and spleen enhancement after intravenous injection of carboxydextran magnetite: effect of dose,delay of imaging,and field strength in anex vivo model

It has been predicted that liver and spleen enhancement after administration of superparamagnetic contrast agents may be different, depending on the strength of the main magnetic field. With the use of anex vivo model, we investigated at 0.3, 0.5, and 1.5 T the effects on liver and spleen signal intensity of 5, 15, and 45 µmol/kg body weight of dextran magnetite (SHU 555A) in 54 rats. Nine rats served as controls. At different time delays since injection, the animals were killed, and after perfusion with saline, the liver, brain, and spleen were fixed in formalin. The specimens were embedded in an agar gel matrix and imaged with inversion recovery T1-weighted, proton density spin echo, and T2*-weighted gradient recalled echo (GRE) sequences. At each magnetic field strength, peak liver and spleen signal loss increased with increasing dose of the contrast medium. Signal loss was significantly more conspicuous after a dose of 15 than 5 µmol/kg body weight, but not after a dose of 45 compared with 15 µmol/kg. No signal change was observed in the brain. GRE images showed higher enhancement than proton density-weighted spin echo and inversion recovery images but were noisier. The enhancement showed a plateau between 30 min and 24 hours. Only the signal decrease of the liver after a low dose of contrast medium on GRE images was significantly higher (p<0.01) at 1.5 than at 0.5 and 0.3 T. Other differences in respect to the field strength were less significant (p<0.05) or nonsignificant. Differences in the spleen enhancement were nonsignificant. SHU 555A at a dose of 15 µmol/kg is an efficient intracellular contrast agent for liver and spleen at low, mid, and high field strength. Proton density spin echo images are probably the sequence of choice to exploit SHU 555A contrast effects and a wide time window for imaging after its intravenous injection does exist.     

Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Object: Demonstrating the feasibility of magnetic resonance imaging (MRI) at 1.5 T of ultrasmall particle iron oxide (USPIO)-antibody bound to tumor cells in vitro and in a murine xenotransplant model. Methods: Human D430B cells or Raji Burkitt lymphoma cells were incubated in vitro with different amounts of commercially available USPIO-anti-CD20 antibodies and cell pellets were stratified in a test tube. For in vivo studies, D430B cells and Raji lymphoma cells were inoculated subcutaneously in immunodeficient mice. MRI at 1.5 T was performed with T1-weighted three-dimensional fast field echo sequences (17/4.6/13°) and T2-weighted three-dimensional fast-field echo sequences (50/12/7°). For in vivo studies MRI was performed before and 24 h after USPIO-anti-CD20 administration. Results: USPIO-anti-CD20-treated D430B cells, showed a dose-dependent decrease in signal intensity (SI) on T2*-weighted images and SI enhancement on T1-weighted images in vitro. Raji cells showed lower SI changes, in accordance to the fivefold lower expression of CD20 on Raji with respect to D430B cells. In vivo 24 h after USPIO-anti-CD20 administration, both tumors showed an inhomogeneous decrease of SI on T2*-weighted images and SI enhancement on T1-weighted images. Conclusions: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.     

Relative assessment of brain iron levels using MRI at 3 tesla

High field MR (magnetic resonance) images can be made sensitive to the relative concentration of tissue iron through the use ofT*₂-weighted contrast. This has enabled tissue iron levels to be assessed noninvasively by quantification of transverse relaxation rates. High field MRI may provide a new method to investigate neurological diseases which result in alteration of brain iron levels in specific areas of the human brain. Parkinson's disease (PD) results in an increase in iron concentration within the lateral region of the substantia nigra (SN), and provides one potential application of this methodology. Preliminary results of our findings are that there is a significant difference in SN iron levels in PD patients compared with age-matched controls, assessed by quantification of the reversible line-broadening component of transverse relaxation rate,R₂.     

Volumetric imaging with homogenised excitation and static field at 9.4 T

Objectives

To overcome the challenges of B₀ and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B₀ and flip-angle homogenisation was implemented on a human 9.4 T scanner.

Materials and methods

Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B₀- and B₁-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B₀ shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T₁- and T ₂ ^* -weighted images with MPRAGE and 3D EPI, respectively.

Results

Over six in vivo acquisitions, the B₀-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode’s 30.5 ± 0.9 to 9.2 ± 0.7 % with all B ₁ ⁺  voids eliminated. The SNR inhomogeneities and contrast variations in the T₁- and T ₂ ^* -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T₁-weighted image.

Conclusion

A 15-minute B₀- and flip-angle homogenisation workflow, including the B₀- and B₁-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.

     

Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance images: an experimental study in rat livers with gadolinium chloride-induced Kupffer cell damage

Objective

Hepatic signal recovery, rather than reduction, in ferucarbotran-enhanced magnetic resonance imaging (MRI) is a potential diagnostic marker of liver damage. We investigated hepatic signal recovery in rats with gadolinium chloride (GdCl₃)-induced Kupffer cell (KC) damage.

Materials and methods

Twelve rats received 8 μmol iron/kg of ferucarbotran 1 day after 0–7.5 mg/kg GdCl₃ injection (experiment A). Another 12 rats received ferucarbotran followed by GdCl₃ injection 6 h later (experiment B). In each experiment, three rats without GdCl₃ (“no injury group”) served as control. Another six rats received GdCl₃ alone without ferucarbotran. Hepatic signals were assessed on T ₂ ^* -weighted images for up to 29 days. Iron deposits were histologically examined on day 29.

Results

Hepatic signal recovery was delayed in a GdCl₃ dose-dependent manner in experiment A. Gadolinium chloride alone reduced hepatic signal 15 % during this experiment. Hepatic signal recovery was delayed only in rats that received 7.5 mg/kg GdCl₃ in experiment B. Hepatic signals negatively correlated with iron deposits in KCs and hepatocytes.

Conclusion

Hepatic signal recovery on ferucarbotran-enhanced MRI was delayed in the context of GdCl₃-induced KC damage due to increased hepatic iron deposits. Hepatic signal recovery may be used as a clinical marker of KC damage in liver disorders, including radiation-induced hepatitis.     

Post-processing water-fat imaging technique for fat suppression in a low-field MR imaging system,evaluation in patients with rheumatoid arthritis

Purpose: To evaluate the feasibility of the phase difference-based post-processing water-fat imaging method for fat suppression at low-field in imaging of arthritic joints.Materials and methods: Thirty joints (wrist, 10; elbow, 10; knee, 10) in 30 patients with rheumatoid arthritis were imaged using a 0.23TMRI unit. Contrast-enhanced Tl-weighted (Tlw) three-dimensional (3D) gradient-echo (GRE) images with and without fat suppression along with short inversion time inversion-recovery (STIR) images were evaluated by two radiologists. Contrast-enhanced Tlw 3D GRE images and corresponding post-processed fat-suppressed images were scored for conspicuity and delineation of enhancing synovial hypertrophy. The uniformity of fat suppression was evaluated between Tlw 3D GRE fat-suppressed images and STIR images, and general image quality was estimated for all of the three techniques by consensus. For a quantitative analysis, the enhancing synovial hypertrophy-to-fat contrast-to-noise (CNR) values for the T1W 3D GRE images with and without fat suppression were measured. For comparison, synovial bright signal-to-fat CNR values for the STIR images were measured.Results: The post-processing water-fat imaging technique for fat suppression was successfully applied in all examinations. Conspicuity and delineation of enhancing tissue were superior in fat-suppressed Tlw 3D GRE images compared to non-fat-suppressed images (P < 0.0001). As expected, the enhancing synovial hypertrophy tissue-to-fat CNRs were significantly higher in fat-suppressed Tlw 3D GRE images compared to non-fat-suppressed images (P < 0.0001). General image quality was assessed to be best in non-fat-suppressed images, and the difference was significant compared to fat-suppressed images (P < 0.05) and STIR images (P < 0.05).Conclusion: The phase difference-based post-processing water-fat imaging technique for fat suppression can be successfully used at low-field, and it provides high-quality fat suppression images in imaging of arthritic joints.     

Magnetic resonance evaluation of autonomous thyroid nodules treated by percutaneous ethanol injection

Magnetic resonance (MR) imaging was used to evaluate the effect of ultrasound-guided percutaneous ethanol injection (PEI) of autonomous thyroid nodules (ATNs). Nine patients affected with ATN (3.7–32.2 mL volume) underwent PEI (4–19 mL ethanol, subdivided in 3–6 weekly procedures). MR imaging (1.5 T) was performed before each alcoholization and 1 month after the last PEI procedure with the following parameters:T ₁-(550/12) andT ₂-weighted (2200/160) spin-echo images; 4-mm slices, 10% gap; coronal planes. A further seven patients with normal thyroid function, who had undergone PEI 6–18 months before, underwent an MR examination with the same parameters. The signal-to-noise ratio (S/N) of ATN and extranodular gland, as well as ATN volume, were evaluated on theT ₂-weighted images. OnT ₁-weighted images, ATNs appeared mostly hypointense before treatment, with hyperintense areas during treatment, and were lightly hyperintense 6–18 months after treatment. S/N onT ₂-weighted images: extranodular gland 3.5–9.2; ATNs, before treatment 13.2–19.7, before the last procedure 7.7–11.6, 1 month after the last procedure 5.6–10.9; previously treated ATNs, 4.3–8.2. No significant volume reduction was observed with MR 1 month after the last procedure. The MR examination time was about 15 minutes. In conclusion, the effect of PEI on ATNs can be evaluated with an MR examination that is not very time consuming.     

Semi-quantitative approach to estimating GFR by magnetic resonance imaging

Objective: The purpose of this study was to compare a semi-quantitative approach to estimating glomerular filtration rate (GFR) by magnetic resonance imaging with radionuclide calculation of GFR, and to investigate whether spin echo or gradient echo is more suitable for estimating GFR.Methods and patients: Fourteen kidneys of seven patients (GFR ranging from 26 to 57 ml/min) were studied. Spin echo and gradient echo sequences interleaving each other at every excitation were used. After intravenous injection of gadopentetate dimeglumine, serial scans were performed. The signal intensities measured in the regions of interest were converted to time-transverse relaxation rate changes for both spin echo (ΔR2) and gradient echo (ΔR2^*). The areas under the time-ΔR2 and time-ΔR2^* curves were calculated as a semi-quantitative index of GFR for both spin echo and gradient echo images, and the results were compared by GFR measured by radionuclide imaging.Results: The semi-quantitative index of the GFR calculated from spin echo images showed a significant correlation with the GFR measured by radionuclide imaging (r=0.85,P<0.001). On the other hand, the semi-quantitative index of the GFR calculated from gradient echo images showed no such correlation (r=0.46,P=0.10).Conclusion: Spin echo sequences may be more suitable than gradient echo sequences for the evaluation of GFR.     

Dose and scanning delay using USPIO for central nervous system macrophage imaging

Rationale and objectives: In experimental allergic encephalomyelitis (EAE), central nervous system (CNS) macrophage imaging is achievable by MRI using AMI-227 an ultra-small particle iron oxide contrast agent at a dose of 300 μmol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 μmol/kg Fe.Methods: Two groups of EAE rats were tested with AMI-227 using 45 and 300 μmol/kg Fe respectively. Following i.v. injection of AMI-227, they were scanned after a delay of 4–6 and 20–24 h.Results: With a high dose of AMI-227, all animals showed low signal intensity related to iron-loaded macrophages in the CNS. At low dose no abnormalities were found in the CNS. Furthermore, a delay of 4–6 h failed to demonstrate abnormalities even at high dose.Conclusions: Dose, scanning delay after administration and blood half-life are major parameters for T2^* CNS macrophage imaging.     

Volumetric assessment of myocardial viability in rats using 3D double contrast enhanced T1 and T2-weighted MRI

Objective: Volumetric evaluation of the myocardial viability post-infarction in rats using 3D in vivo MR imaging at 7 T using injection of an extracellular paramagnetic contrast agent and intravascular superparamagnetic iron oxide nanoparticles in the same imaging session. Materials and methods: Five hours after induction of permanent myocardial infarction in rats (n=6), 3D in vivo T1- and T2-weighted MR Imaging was performed prior to and after Gd-DOTA injection (0.2 mmol/kg) and prior to and after nanoparticle injection (5 mg Fe/kg) to assess infarct size and myocardial viability. Results: 3D MR Imaging using a successive contrast agent injection showed a difference of infarct size after Gd-DOTA injection on T1-weighted images compared to the one measured on T2-weighted images after Gd-DOTA and nanoparticle injection. Conclusion: The use of 3D T1- and T2-weighted MR Imaging using a double contrast agents protocol made possible the accurate characterization of myocardial infarction volume and allowed the detection of myocardial viability post-infarction in rats     

A comparison of phase imaging and quantitative susceptibility mapping in the imaging of multiple sclerosis lesions at ultrahigh field

Objective

The aim of this study was to compare the use of high-resolution phase and QSM images acquired at ultra-high field in the investigation of multiple sclerosis (MS) lesions with peripheral rings, and to discuss their usefulness for drawing inferences about underlying tissue composition.

Materials and methods

Thirty-nine Subjects were scanned at 7 T, using 3D T ₂*-weighted and T ₁-weighted sequences. Phase images were then unwrapped and filtered, and quantitative susceptibility maps were generated using a thresholded k-space division method. Lesions were compared visually and using a 1D profiling algorithm.

Results

Lesions displaying peripheral rings in the phase images were identified in 10 of the 39 subjects. Dipolar projections were apparent in the phase images outside of the extent of several of these lesions; however, QSM images showed peripheral rings without such projections. These projections appeared ring-like in a small number of phase images where no ring was observed in QSM. 1D profiles of six well-isolated example lesions showed that QSM contrast corresponds more closely to the magnitude images than phase contrast.

Conclusions

Phase images contain dipolar projections, which confounds their use in the investigation of tissue composition in MS lesions. Quantitative susceptibility maps correct these projections, providing insight into the composition of MS lesions showing peripheral rings.

     

NMR microscopy of single neurons at 500 MHZ

Previous NMR microimaging studies at 360 MHz have demonstrated a clear differentiation between the nucleus and cytoplasm in isolated single neurons. In particular, theT ₂ of the cell nucleus is 2.5 times larger than that of the cytoplasm. In order to determine the magnitude of possibleT ₂ ^* influences on these observations, images of single cells have been obtained at 500 MHz using spin-echo and line-narrowing sequences. Comparison of the images acquired by the two sequences, and of the spin-echo images at 360 and 500 MHz, imply that anyT ₂ ^* contributions are relatively small. Consequently, the measuredT ₂ differences in spin-echo imaging represent a true difference in theT ₂ relaxation in the two cellular compartments.     

Fast three-dimensional sodium imaging of human brain

A three-dimensional sodium imaging technique with a minimum echo time of 0.9 ms is described in a 2.0 Tesla whole-body system. The relaxation behaviour in vivo of sodium was analysed: a lastT ₂ ^* relaxation component between 1.2 and 1.6 ms and a slowT ₂ ^* relaxation component between 7.1 ms and 8.4 ms were quantified in brain tissue of three volunteers. Three-dimensional sodium images of the human brain were acquired in 8.5 min with a resolution of 4.7 × 4.7 × 10 mm (0.2 cc voxel size) and a signal-to-noise ratio of 20 in brain tissue and 30 in cerebrospinal fluid.     

Single-shot t1-and t2-weighted magnetic resonance imaging of the heart with black blood: preliminary experience

Purpose: To implement and evaluate two robust methods for T1-and T2-weighted snapshot imaging of the heart with data acquisition within a single heart beat and suppression of blood signal. Methods: Both Tl-and T2-weighted diastolic images of the heart can be obtained with half Fourier single-shot turbo spin echo (HASTE) and turbo fast low-angle shot (turboFLASH) sequences, respectively, in less than 350 ms. Signal from flowing blood in the ventricles and large vessels can be suppressed by a preceding inversion recovery preparing pulse pair (PRESTO). Fifteen volunteers and five patients have been evaluated quantitatively for signal-to-noise ratio (SNR) contrast-to-noise ratio (CNR) and flow void and qualitatively for image quality, artifacts, and black-blood effect. Results: Both PRESTO-HASTE and PRESTO-turboFLASH achieved consistently good image quality and blood signal suppression. In contrast to gradient-echo (GRE) echo-planar imaging techniques, (EPI) HASTE and turboFLASH are much less sensitive to local susceptibility differences in the thorax, resulting in a more robust imaging technique without the need for time-consuming system tuning. Compared to standard spin-echo sequences with cardiac triggering, HASTE and turboFLASH have significantly shorter image acquisition times and are not vulnerable to respiratory motion artifacts. Conclusion: PRESTO-HASTE and PRESTO-turboFLASH constitute suitable methods for fast and high-quality cardiac magnetic resonance imaging (MRI).     

MDEFT imaging of the human brain at 8 T

T ₁-weighted images of the human brain obtained with the MDEFT sequence at 8 T are presented. These images are characterized by an excellent contrast and good signal to noise ratio. Importantly, results were obtained with adiabatic spin inversion and demonstrate that such pulses can be used event in the ultra high frequency (>300 MHz) range. It is thus possible to obtain high quality results at this field strength without violating SAR guidelines.     

Utilizing different methods for visualizing susceptibility from a single multi-gradient echo dataset

Purpose  

Objects that cause a susceptibility gradient can generate regions of hypo-intensity in MRI. MR techniques developed for positive enhancement of such objects require sequence parameter optimization. Thus comparison of images acquired successively using different techniques is difficult since different parameter settings result in variations in signal and noise. A new method is presented that allows production of positive contrast images, a relaxation rate R₂^*{{\rm R}_{2}^{\ast}}-map and negative contrast images from a single dataset by post-processing.     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution²⁰¹Thallium (²⁰¹Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between²⁰¹Tl uptake and MRI signal intensity, i.e. infarcted tissue (low²⁰¹Tl uptake) had increased MR signal intensity. Segments were separated into normal (²⁰¹Tl uptake >90%) and infarcted (<60%). Infarcted MRI segments had greater signal intensity than normal segments (179±50 vs. 102±14%;P<0.0001). WTI in normal segments increased by 18±8.5% (P<0.0001) from baseline to 10 μg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8±7.2% (P=0.17). Thus regions of myocardium that were infarcted as defined by reduced²⁰¹Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.