Quantitative liver iron measurement by magnetic resonance imaging: in vitro and in vivo assessment of the liver to muscle signal intensity and the R2* methods

Purpose

To evaluate the liver-to-muscle signal intensity and R2* methods to gain a transferable, clinical application for liver iron measurement.

Materials and Methods

Sixteen liver phantoms and 33 human subjects were examined using three 1.5-T MRI scanners from two different vendors. Phantom-to-muscle and liver-to-muscle signal intensity ratios were analyzed to determine MRI estimated phantom and hepatic iron concentration (M-PIC and M-HIC, respectively). R2* was calculated for the phantoms and the liver of human subjects. Seven patients' biochemical hepatic iron concentration was obtained.

Results

M-PIC and R2* results of three scanners correlated linearly to phantom iron concentrations (r=0.984 to 0.989 and r=0.972 to 0.981, respectively), and no significant difference between the scanners was found (P=.482 and P=.846, respectively) in vitro. The patients' R2* correlated linearly to M-HIC of the standard scanner (r=0.981). M-HIC values did not differ from those obtained from the biopsy specimens (P=.230). The difference in M-HIC was significant, but the difference in R2* was not significant between the scanners (P<.0001 and P=.505, respectively) in vivo.

Conclusion

Both methods, M-HIC and R2*, are reliable iron concentration indicators with linear dependence on iron concentration in vivo and in vitro. The R2* method was found to be comparable among different scanners. Transferability testing is needed for the use of the methods at various scanners.     

Improved T2* assessment in liver iron overload by magnetic resonance imaging

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.     

Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia

A magnetic resonance imaging cardiac magnetic susceptometry (MRI-CS) technique for assessing cardiac tissue iron concentration based on phase mapping was developed. Normal control subjects (n=9) and thalassemia patients (n=13) receiving long-term blood transfusion therapy underwent MRI-CS and MRI measurements of the cardiac relaxation rate R2*. Using MRI-CS, subepicardium and subendocardium iron concentrations were quantified exploiting the hemosiderin/ferritin iron specific magnetic susceptibility. The average of subepicardium and subendocardium iron concentrations and R2* of the septum were found to be strongly correlated (r=0.96, P<.0001), and linear regression analysis yielded CIC (μg Fe/g_{wet tissue})=(6.4±0.4)·R2* _septum (s⁻¹) − (120±40). The results demonstrated that septal R2* indeed measures cardiac iron level.     

Optimal region-of-interest MRI R2* measurements for the assessment of hepatic iron content in thalassaemia major

Objectives

To evaluate the performance of region-of-interest (ROI)-based MRI R2* measurements by using the first-moment noise-corrected model (M¹NCM) to correct the non-central Chi noise in magnitude images from phased arrays for hepatic iron content (HIC) assessment.

Methods

R2* values were quantified using the M¹NCM model. Three approaches were employed to determine the representative R2*: fitting of the ROI-averaged signal (average-then-fit, ATF); outputting the median and mean of R2*s from the pixel-wise fitting of decay signals within the ROI (denoted as PWFmed and PWFmea, respectively). The accuracy and precision of the three approaches were evaluated on synthesized data. The agreement among these approaches and their intra- and inter-observer reproducibility were assessed on 105 thalassaemia major patients.

Results

Simulations showed that ATF consistently yielded the highest accuracy and precision at varying noise levels. By contrast, PWFmed and PWFmea slightly and significantly overestimated high R2* at poor signal-to-noise ratios, respectively. Patient study showed that ATF agreed well with PWFmed, whereas PWFmea produced high R2* measurements for patients with severe HIC. No significant difference was observed in the reproducibility of the three approaches.

Conclusions

PWFmea tends to overestimate high R2*, whereas ATF and PWFmed can produce more accurate R2* measurements for HIC assessment.     

GESFIDE-PROPELLER Approach for Simultaneous R2 and R2* Measurements in the Abdomen

Purpose

To investigate the feasibility of combining GESFIDE with PROPELLER sampling approaches for simultaneous abdominal R2 and R2* mapping.

Materials and Methods

R2 and R2* measurements were performed in 9 healthy volunteers and phantoms using the GESFIDE-PROPELLER and the conventional Cartesian-sampling GESFIDE approaches.

Results

Images acquired with the GESFIDE-PROPELLER sequence effectively mitigated the respiratory motion artifacts, which were clearly evident in the images acquired using the conventional GESFIDE approach. There was no significant difference between GESFIDE-PROPELLER and reference MGRE R2* measurements (p = 0.162) whereas the Cartesian-sampling based GESFIDE methods significantly overestimated R2* values compared to MGRE measurements (p < 0.001).

Conclusion

The GESFIDE-PROPELLER sequence provided high quality images and accurate abdominal R2 and R2* maps while avoiding the motion artifacts common to the conventional Cartesian-sampling GESFIDE approaches.     

The use of T2*-weighted multi-echo GRE imaging as a novel method to diagnose hepatocellular carcinoma compared with gadolinium-enhanced MRI: a feasibility study

Background

The goal of the study was to assess a T2*-weighted MRI sequence for the ability to identify hepatocellular carcinoma (HCC).

Methods

Hepatic iron deposition, which is common in chronic liver disease (CLD), may increase the conspicuity of HCC on GRE imaging due to increased T2* signal decay in liver parenchyma. In this study, a breath-hold T2*-weighted MRI sequence was evaluated by a blinded observer for HCC and the results compared to a reference standard of gadolinium-enhanced MRI in these same patients. Forty-one patients (mean age 56.2 years; 17 females) were included in this approved, retrospective study.

Results

By the reference standard, 14 of 41 patients had a total of 25 HCCs. The sensitivity of the T2*-weighted MR sequence for identifying HCC, per lesion, was 60%, while the specificity was 100%. There was a significantly lower T2* value of liver parenchyma in patients with HCC identified by the T2*-weighted sequence than in those with HCCs which were not identified by the T2*-weighted sequence (27.8±2.2 vs. 21.9±2.1 ms; P=.02).

Conclusions

A T2*-weighted MRI sequence can identify HCC in patients with CLD. This technique may be beneficial for imaging of patients contraindicated for gadolinium.     

Cardiac T2 measurements in patients with iron overload: a comparison of imaging parameters and analysis techniques

Measurement of cardiac T2 has emerged as an important tool to noninvasively quantify cardiac iron concentration in order to detect preclinical evidence of toxic levels and titrate chelation therapy. However, there exists variation among practitioners in cardiac T2 measurement methods. This study examines the impact of different imaging parameters and data analysis techniques on the calculated cardiac R2 (1/T2) in patients at risk for cardiac siderosis. The study group consisted of 36 patients with thalassemia syndromes who had undergone clinical magnetic resonance imaging assessment of cardiac siderosis using a standardized protocol and who were selected to yield a broad range of cardiac R2 values. Cardiac R2 measurements were performed on a 1.5-T scanner using an electrocardiogram-gated, segmented, multiecho gradient echo sequence obtained in a single breath-hold. R2 was calculated from the signal intensity versus echo time data in the ventricular septum on a single midventricular short-axis slice. There was good agreement between R2 measured with a blood suppression prepulse (black blood technique) and without (mean difference 6.0 ± 10.7 Hz). The black blood technique had superior within-study reproducibility (R2 mean difference 1.6 ± 8.6 Hz versus 2.7 ± 14.6 Hz) and better interobserver agreement (R2 mean difference 3.4 ± 8.2 Hz versus 8.3 ± 16.5 Hz). With the same minimum echo time, the use of small (1.0 ms) versus large (2.2 ms) echo spacing had minimal impact on cardiac R2 (mean difference 0.3 ± 8.7 Hz). The application of a region-of-interest-based versus a pixel-based data analysis also had little effect on cardiac R2 calculation (mean difference 8.4 ± 6.9 Hz). With black blood images, fitting the signal curve to a monoexponential decay or to a monoexponential decay with a constant offset yielded similar R2 values (mean difference 3.4 ± 8.1 Hz). In conclusion, the addition of a blood suppression prepulse for cardiac R2 measurement yields similar R2 values and improves reproducibility and interobserver agreement. The findings regarding other variations may be helpful in establishing a broadly accepted imaging and analysis technique for cardiac R2 calculation.     

Comparison between multi-echo T2* with and without fat saturation pulse for quantification of liver iron overload

Purpose

To test a magnetic resonance image (MRI) technique that uses an additional pulse in multi-echo T2* sequence that works to suppress the fat signal, in subjects with liver iron overload and concomitant presence of fat in the liver, which have been revealed as a major drawback that compromises the correct iron quantification by MRI.

Materials and Methods

Fifty magnetic resonance images of the liver (1.5 T scanner) of individuals with blood ferritin increases were retrospectively reviewed for the presence of steatosis, using the sequence in and out of phase, and iron overloading, using two sequences T2 * multi-echo: one standard and other with additional fat suppression pulse. T2 * values and their standard deviations were analyzed statistically.

Results

Our results showed that a significantly lower standard deviation of T2* values is obtained when the fat saturation pulse is applied in patients with steatosis. We found that modulation of fat signal on liver iron overload resulted in a different categorization of some patients. In one case, the patient was re-classified within normal levels of liver iron.

Conclusion

Our findings may contribute to a better measure of liver iron overload with relevant implications for patient treatment and care.     

Area of paradoxical signal drop after the administration of superparamagnetic iron oxide on the T2-weighted image of a patient with lymphangitic metastasis of the liver

We report a geographic area of prominent hypointensity in T2-weighted images vs. normal adjacent liver parenchyma in a patient with cholangiocarcinoma and lymphangitic metastasis of the liver after superparamagnetic iron oxide (SPIO) administration. The area showing this prominent signal drop showed Kupffer cell proliferation and lymphangitic metastasis during a pathologic examination.     

Superparamagnetic iron oxide nanoparticles as a liver MRI contrast agent: Contribution of microencapsulation to improved biodistribution

We have developed a new method of synthetizing superparamagnetic iron oxide nanoparticles, consisting in the modifications of Molday's method, which ensures high relaxivity (2.4 10⁵ s⁻¹·M⁻¹·L), good chemical stability, singular biodistribution and a considerable safety margin. The ED (Efficace Dose) to LD50 ratio is instead of for Gd-DTPA. In order to develop a magnetite-delivery system to the liver we have incorporated the nanoparticles into biodegradable synthetic microcapsules. Encapsulated ⁵⁹Fe oxide nanoparticles are injected into rats; in these conditions the sequestration is 9-fold greater in liver and 6 and 5 times lower in blood and carcase, respectively. This modification of the biodistribution enables the use of magnetite containing microcapsules at only 0.3 mg/kg iron to obtain an improved contrast in liver.     

Detection and grading for esophageal varices in patients with chronic liver damage: comparison of gadolinium-enhanced and unenhanced steady-state coherent MR images

The purpose of this study was to compare observer interpreted steady-state coherent coronal images and gadolinium-enhanced axial images in terms of the detection and grading of esophageal varices. Magnetic resonance imaging (MRI) and gastrointestinal endoscopy were performed within 2 weeks in 90 patients with chronic liver damage, including 55 with untreated esophageal varices, for periodic screening purposes. Two blinded readers retrospectively reviewed T1- and T2-weighted images with gadolinium-enhanced (gadolinium image set) and steady-state coherent (coherent image set) images. Sensitivity for the detection of esophageal varices was higher (P<.001) in the gadolinium image set (76%) than in the coherent image set (35%); on the other hand, specificity was higher (P<.001) in the coherent image set (91%) than in the gadolinium image set (66%). Furthermore, area under the ROC curve was higher for the gadolinium image set (Az=0.823) than the coherent image set (Az=0.761) (P=.48). Moderate and weak positive correlations with endoscopic grades were found for the gadolinium image (r=0.48, P<.01) and coherent image sets (r=0.34, P=.018). The addition of steady-state coherent imaging to the current routine liver imaging protocol did not improve the detection or grading of esophageal varices, whereas gadolinium-enhanced imaging was found to be potentially valuable. Nevertheless, endoscopy was confirmed to be mandatory in patients with esophageal varices suspected by MRI of the liver.     

Weighing Neutrinos in f(R) Gravity in Light of BICEP2

We constrain the neutrino mass in f(R) gravity using the latest observations from the Planck, BAO and BICEP2 data. We find that the measurement on the B-modes can break the degeneracy between the massive neutrinos and the f(R) gravity. We find a non-zero value of the Compton wavelengths B₀ at a 68% confidence level for the f(R) model in the presence of massive neutrinos when the BICEP2 data is used. Furthermore, the tension on the tensor-to-scalar ratios between the measured values from Plank and BICEP2 is significantly reconciled in our model.     

手性分子2, 3-丁二醇的旋光拉曼光谱研究

本文从拉曼峰和旋光拉曼峰出发,通过键极化率和微分键极化率分析研究(2R, 3R)-2, 3-丁二醇. 通过分子C₁和C₂两种点群的优化结构,获得不依赖于这两种结构的结果 和有关这个手性系统物理图像的丰富信息.对分子拉曼键极化率分析,得出在拉曼弛豫过程中, 电荷主要从外围流向骨架结构.对分子微分键极化率的分析,显示在不对称C原子和与其相联系的H原子 两侧化学键, C-O和C-CH₃的微分键极化率的符号正好相反,意味着这个分子具有相当好的手性 不对称性质.对比对称和反对称的键极化率、微分键极化率,本文得到这样的结论: 对于(特别是键伸缩的)键极化率,(大体上是)对称的大于反对称的; 而对于微分键极化率则是反对称的大于对称的. 关键词： 旋光拉曼 键极化率 微分键极化率 2,3-丁二醇     

Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R₂ relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R₂ and the liver iron concentration, when R₂ was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T₂ relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.     

Feasibility of similarity coefficient map for improving morphological evaluation of T2* weighted MRI for renal cancer

The purpose of this paper is to investigate the feasibility of using a similarity coefficient map(SCM) in improving the morphological evaluation of T2* weighted(T2*W) magnatic resonance imaging(MRI) for renal cancer.Simulation studies and in vivo 12-echo T2*W experiments for renal cancers were performed for this purpose.The results of the first simulation study suggest that an SCM can reveal small structures which are hard to distinguish from the background tissue in T2*W images and the corresponding T2* map.The capability of improving the morphological evaluation is likely due to the improvement in the signal-to-noise ratio(SNR) and the carrier-to-noise ratio(CNR) by using the SCM technique.Compared with T2* W images,an SCM can improve the SNR by a factor ranging from 1.87 to 2.47.Compared with T2* maps,an SCM can improve the SNR by a factor ranging from 3.85 to 33.31.Compared with T2*W images,an SCM can improve the CNR by a factor ranging from 2.09 to 2.43.Compared with T2* maps,an SCM can improve the CNR by a factor ranging from 1.94 to 8.14.For a given noise level,the improvements of the SNR and the CNR depend mainly on the original SNRs and CNRs in T2*W images,respectively.In vivo experiments confirmed the results of the first simulation study.The results of the second simulation study suggest that more echoes are used to generate the SCM,and higher SNRs and CNRs can be achieved in SCMs.In conclusion,an SCM can provide improved morphological evaluation of T2*W MR images for renal cancer by unveiling fine structures which are ambiguous or invisible in the corresponding T2*W MR images and T2* maps.Furthermore,in practical applications,for a fixed total sampling time,one should increase the number of echoes as much as possible to achieve SCMs with better SNRs and CNRs.     

Structural and optical properties of chromotrope 2R thin films of different thicknesses

Chromotrope 2R (CHR) films of different thicknesses have been prepared using spin coater. The material has been characterized using FT-IR, DTA and X-ray diffraction. The XRD of the material in powder and thin film forms showed polycrystalline structure with triclinic phase. Preferred orientation at the (1 1 4) plane is observed for the deposited films. Initial indexing of the XRD pattern was performed using “Crystalfire” computer program. Miller indices, h k l, values for each diffraction line in X-ray diffraction (XRD) spectrum were calculated and indexed for the first time. The DTA thermograms of CHR powder have been recorded in the temperature range 25–350 °C with different heating rates. The spectra of the infra-red absorption allow characterization of vibration modes for the powder and thin film. The effect of film thickness on the optical properties has been studied in the UV-visible-NIR regions. The films show high transmittance exceeding 0.90 in the NIR region λ > 800 nm. The intensity of the absorption peaks for λ < 800 nm are enhanced as the film thickness increase. The absorption bands are attributed to the (π–π*) and (n–π*) molecular transitions. The optical properties have been analyzed according to the single-oscillator model and the dispersion energy parameters as well as the free charge carrier concentration have been determined. The optical energy gap as well as the oscillator strength and electric dipole strength have been calculated.     

R2Fe17-xAlx化合物中R-T交换耦合常量的计算

讨论了利用分子场近似结合中子衍射或X射线衍射的实验结果计算R2Fe17型稀土过渡族化合物中稀土磁矩与过渡族磁矩之间交换耦合常量的方法,并据此计算了R2Fe17-xAlx(R=Tb,Dy,Ho,Er,Gd,x=7或8)化合物中稀土磁矩与过渡族磁矩之间的交换耦合常量.计算结果与实验值符合较好.     

CO2/R170共沸混合制冷剂应用于冷柜系统的热力学性能分析

基于一套小型冷柜系统建立了热力学模型,将纯CO2制冷剂和CO2/R170共沸混合制冷剂分别应用于该系统,详细计算了系统的性能参数和[火用]效率,并进行了全面的对比。研究结果表明:CO2/R170共沸制冷剂可显著降低排气温度,在所研究的范围内,最高可达16℃;在系统COP及[火用]效率方面,CO2/R170共沸制冷剂存在劣势;随着气冷器出口温度升高,系统的COP及[火用]效率方面的劣势不断减小,而降低排气温度方面的优势在持续增大,且压缩机的压缩比越来越低。因此,将CO2/R170共沸制冷剂应用于冷柜具有很强的可靠性,且更适用于气冷器出口温度较高的系统。     

Bi-exponential proton transverse relaxation rate (R2) image analysis using RF field intensity-weighted spin density projection: potential for R2 measurement of iron-loaded liver

A bi-exponential proton transverse relaxation rate (R(2)) image analysis technique has been developed that enables the discrimination of dual compartment transverse relaxation behavior in systems with rapid transverse relaxation enhancement. The technique is particularly well suited to single spin-echo imaging studies where a limited number of images are available for analysis. The bi-exponential R(2) image analysis is facilitated by estimation of the initial proton spin density signal within the region of interest weighted by the RF field intensities. The RF field intensity-weighted spin density map is computed by solving a boundary value problem presented by a high spin density, long T(2) material encompassing the region for analysis. The accuracy of the bi-exponential R(2) image analysis technique is demonstrated on a simulated dual compartment manganese chloride phantom system with relaxation rates and relative population densities between the two compartments similar to the bi-exponential transverse relaxation behavior expected of iron loaded liver. Results from analysis of the phantoms illustrate the potential of bi-exponential R(2) image analysis with RF field intensity-weighted spin density projection for quantifying transverse relaxation enhancement as it occurs in liver iron overload.     

In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking

Iron oxide nanocrystals are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Colloidal solutions of magnetic nanoparticles (ferrofluids) with a high magnetite content are highly desirable for most molecular imaging applications. In this paper, we present a method for in situ coating of superparamagnetic iron oxide (SPIO) with chitosan in order to increase the content of magnetite. Iron chloride salts (Fe³⁺ and Fe²⁺) were directly coprecipitated inside a porous matrix of chitosan by Co-60 γ-ray irradiation in an aqueous solution of acetic acid. Following sonication, iron oxide nanoparticles were formed inside the chitosan matrix at a pH value of 9.5 and a temperature of 50 °C. The [Fe³⁺]:[Fe²⁺]:[NH₄OH] molar ratio was 1.6:1:15.8. The final ferrofluid was formed with a pH adjustment to approximately 2.0/3.0, alongside with the addition of mannitol and lactic acid. We subsequently characterized the particle size, the zeta potential, the iron concentration, the magnetic contrast, and the cellular uptake of our ferrofluid. Results showed a z-average diameter of 87.2 nm, a polydispersity index (PDI) of 0.251, a zeta potential of 47.9 mV, and an iron concentration of 10.4 mg Fe/mL. The MRI parameters included an R1 value of 22.0 mM⁻¹ s⁻¹, an R2 value of 202.6 mM⁻¹ s⁻¹, and a R2/R1 ratio of 9.2. An uptake of the ferrofluid by mouse macrophages was observed. Altogether, our data show that Co-60 γ-ray radiation on solid chitosan may improve chitosan coating of iron oxide nanoparticles and tackle its aqueous solubility at pH 7. Additionally, our methodology allowed to obtain a ferrofluid with a higher content of magnetite and a fairly unimodal distribution of monodisperse clusters. Finally, MRI and cell experiments demonstrated the potential usefulness of this product as a potential MRI contrast agent that might be used for cell tracking.