Quantifying hepatic fibrosis using a biexponential model of diffusion weighted imaging in ex vivo liver specimens

The purpose of this study was to evaluate the non-Gaussian behavior of diffusion related signal decay of the ex vivo murine liver tissues from a dietary model of hepatic fibrosis. To this end, a biexponential formalism was used to model high b-value diffusion imaging (up to 3500 s/mm²), the findings of which were correlated with liver histopathology and compared to a simple monoexponential model. The presence of a major, fast diffusing component and a minor, slow diffusing component was demonstrated. With increasing hepatic fibrosis, the fractional contribution of the fast diffusing component decreased, as did the diffusion coefficient of the fast diffusing component. Strong correlation between the degrees of liver fibrosis and a two-predictor regression model incorporating parameters of the biexponential model was found. Using Akaike's Information Criterion analyses, the biexponential model resulted in an improved fit of the high b-value diffusion data when compared to the monoexponential model.     

Quantification of low fat contents: a comparison of MR imaging and spectroscopy methods at 1.5 and 3 T

Magnetic resonance spectroscopy (MRS) has long been considered the golden standard for non-invasive measurement of tissue fat content. With improved techniques for fat/water separation, imaging has become an alternative to MRS for fat quantification. Several imaging models have been proposed, but their performance relative to MRS at very low fat contents is yet not fully established. In this work, imaging and spectroscopy were compared at 1.5 T and 3 T in phantoms with 0-3% fat fraction (FF). We propose a multispectral model with individual a priori R₂ relaxation rates for water and fat, and a common unknown R₂′ relaxation. Magnitude and complex image reconstructions were also compared. Best accuracy was obtained with the imaging method at 1.5 T. At 3 T, the FFs were underestimated due to larger fat-water phase shifts. Agreement between measured and true FF was excellent for the imaging method at 1.5 T (imaging: FF_meas= 0.98 FF_true− 0.01%, spectroscopy: FF_meas= 0.77 FF_true+ 0.08%), and fair at 3 T (imaging: FF_meas= 0.91 FF_true− 0.19%, spectroscopy: FF_meas= 0.79 FF_true+ 0.02%). The imaging method was able to quantify FFs down to approx. 0.5%. We conclude that the suggested imaging model is capable of fat quantification with accuracy and precision similar to or better than spectroscopy and offers an improvement vs. a model with a common R₂* relaxation only.     

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.     

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.     

T2 relaxation of the parotid gland of patients affected by pleomorphic adenoma.

The T2 behavior of parotid gland tissue was investigated in 11 patients affected by pleomorphic adenoma. A protocol that was previously set up to define acquisition and post-processing procedures, reaching an accuracy of 2.5% in phantoms and an in vivo long term reproducibility of 0.9-8.5%, was used for the evaluations. The measurements were carried out on a whole body, superconducting imager, using a neck coil as a receiver. Some reference gel samples were imaged together with the patient and used to correct T2 results. The sequence protocol was a multispin-echo, 16 echoes. Signals were fitted with mono and biexponential decay models and an automatic choice of the best model was performed using the two chisquared comparison. Two T2 maps (T2 monoexponential or short T2 component, and long T2 component) and chisquared maps were then produced. Pathologic and normal tissues showed a dominant monoexponential decay with a good level of biexponentiality (16%-27% of total fitted pixels) due to partial volume effects from the liquid content. Concerning the biexponentiality, no significant differences were found between the fitted pixel fraction of normal and pathologic tissue, because the T2 long component of the lesion was related both to the edema and saliva content, but probably the increase in the first compensated the decrease in the second. Chisquared maps showed that most of the lesions presented a monoexponential core surrounded by a biexponential border probably due to a solid component similar to normal tissue with partial volume effects from saliva content. Ninety-five percent confidence intervals for normal tissue were 69.40-87.80 ms (monoexponential relaxation), 38.19-44.67 ms and 285.84-691.28 ms (short and long components of biexponential relaxation). For pathologic tissue they resulted 172.17-275.83 ms, 53.86-89.98 ms and 442.10-814.58 ms. The monoexponential component, mostly present in the core of the lesion, was the parameter that better characterized pathologic tissue. A comparison was performed between normal tissue of patients and normal tissue of volunteers, whose statistics was collected in a previous study with the same evaluation protocol. Results showed no significant differences in the biexponential fitted fractions and the comparison of relaxation times. We conclude that, for tissue characterization, a multiexponential analysis should be carried out in order to improve accuracy and to obtain more reliable results. Moreover, other than relaxation calculations, a topographical analysis of relaxation distribution, using for instance the chisquared maps, might in the future give us more useful information on tissue structure.     

Biexponential apparent diffusion coefficients in prostate cancer

Purpose

The purpose of this study was to investigate the need for biexponential signal decay modeling for prostate cancer diffusion signal decays with b-factor over an extended b-factor range.

Materials and Methods

Ten healthy volunteers and 12 patients with a bulky prostate cancer underwent line scan diffusion-weighted MR imaging in which b-factors from 0 to 3000 s/mm² in 16 steps were sampled. The acquired signal decay curves were fit with both monoexponential and biexponential signal decay functions and a statistical comparison between the two fits was performed.

Results

The biexponential model provided a statistically better fit over the monoexponential model on the peripheral zone (PZ), transitional zone (TZ) and prostate cancer. The fast and slow apparent diffusion coefficients (ADCs) in the PZ, TZ and cancer were 2.9±0.2, 0.7±0.2×10⁻³ mm²/ms (PZ); 2.9±0.4, 0.7±0.2×10⁻³ mm²/ms (TZ); and 1.7±0.4, 0.3±0.1×10⁻³ mm²/ms (cancer), respectively. The apparent fractions of the fast diffusion component in the PZ, TZ and cancer were 70±10%, 60±10% and 50±10%, respectively. The fast and slow ADCs of cancer were significantly lower than those of TZ and PZ, and the apparent fraction of the fast diffusion component was significantly smaller in cancer than in PZ.

Conclusions

Biexponential diffusion decay functions are required for prostate cancer diffusion signal decay curves when sampled over an extended b-factor range, providing additional, unique tissue characterization parameters for prostate cancer.     

Evaluation of MRI fat fraction in the liver and spine pre and post SPIO infusion

This study evaluates the robustness of a magnetic resonance (MR) fat quantification method to changes in R2* caused by an intravenous infusion of superparamagnetic iron oxide (SPIO) contrast agent. The R2* and proton density fat fraction (PDFF) were measured in liver and spine in 14 subjects using an investigational sequence (IDEAL IQ) provided by the MR scanner vendor. Measurements were made before and after SPIO infusion. Results showed SPIO significantly increased R2* in both liver (p = 8.8 × 10^− 8) and spine (p =1.3 × 10^− 2) but PDFFs were not significantly different in either the liver (p = 5.5 × 10^− 1) or the spine (p = 5.6 × 10^− 1). These results confirm that the IDEAL IQ method of fat quantification is robust to changes in R2*.     

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.     

Effectiveness Evaluation of the Fat Percentage Determination in Multi-Echo T2-Corrected Single-Voxel Spectroscopy by Comparing the 3-Point Dixon and the 6-Point Interference Dixon Techniques

This study compared fat percentage in the HISTO method and chemical-shift imaging method, a 3-echo 3D gradient echo sequence with a T2*-corrected Dixon (3-point Dixon) and 6-echo interference Dixon magnetic resonance (MR) imaging (6-point Dixon) method, to evaluate clinical significance of fatty liver quantification by multi-echo T2*-corrected single-voxel spectroscopy Histo (HISTO). A total of 21 liver donors underwent MR imaging examination. The 3-T MR system (Siemens Healthcare Tim Verio, Erlangen, Germany) was used for all studies. For fat percentage evaluations, a 3-echo 3D gradient echo sequence with T2*-corrected Dixon (3-point Dixon) and 6-Echo Interference Dixon (6-point Dixon) pulse sequences, including HISTO, were applied in sequence. Using fat percentages obtained from each pulse sequence, levels of fatty liver were classified as: non-fatty liver, <5 %; mild fatty liver, >5 but <31 %; and severe fatty liver, >31 %. The correlation between methods was calculated with a correlation coefficient (R ²): HISTO and 3-point Dixon, 0.936 (p < 0.001); HISTO and 6-point Dixon, 0.944 (p < 0.001); and 3-point Dixon and 6-point Dixon, 0.984 (p < 0.001). The HISTO, which was used to investigate fat percentages after T2* correction, showed a high correlation with 3-point Dixon and 6-point Dixon, suggesting that the multi-echo method is useful for accurately determining fat percentages.     

Correlation between Hepatic Fat Content Using 3-Echo 3-D Dixon Method and Intravoxel Incoherent Motion (IVIM) Perfusion MR Imaging

Fat accumulates as droplets in the hepatocyte swelling, distortion of microcirculatory anatomy and compression of sinus. This study aims to investigate the correlation between the T2*-corrected fat fraction (FF) value acquired via gradient echo with a low flip angle and parenchymal pseudorandom blood perfusion (P _fraction), microcirculation (D _fast), and slow component of diffusion (D _slow), acquired via intravoxel incoherent motion (IVIM), and to investigate the blood microcirculation and diffusion components of liver parenchyma, according to fat deposition. A total of 126 patients underwent 3-T magnetic resonance imaging, including a 3-echo three-dimensional (3-D) gradient echo sequence with T2*-corrected Dixon reconstruction and IVIM sequence. Pearson’s correlation analysis was conducted to investigate the correlation of the FF obtained via the Dixon method with the apparent diffusion coefficient (ADC), D _slow, P _fraction, and D _fast obtained via IVIM. Correlation analysis was also conducted for the IVIM mapping images. A confidence level of p < 0.05 was set. A negative correlation was found between the T2*-corrected FF acquired using the 3-echo 3-D Dixon method and D _slow acquired via IVIM (r = ?0.181, p < 0.05). It was likely due to the increased extracellular collagen deposition and increased intracellular fat droplets during the progression of liver fibrosis.     

Comparison of different mathematical models of diffusion-weighted prostate MR imaging

Purpose

To evaluate which mathematical model (monoexponential, biexponential, statistical, kurtosis) fits best to the diffusion-weighted signal in prostate magnetic resonance imaging (MRI).

Materials and Methods

24 prostate 3-T MRI examinations of young volunteers (YV, n= 8), patients with biopsy proven prostate cancer (PC, n= 8) and an aged matched control group (AC, n= 8) were included. Diffusion-weighted imaging was performed using 11 b-values ranging from 0 to 800 s/mm².

Results

Monoexponential apparent diffusion coefficient (ADC) values were significantly (P<.001) lower in the peripheral (PZ) zone (1.18±0.16 mm²/s) and the central (CZ) zone (0.73±0.13 mm²/s) of YV compared to AC (PZ 1.92±0.17 mm²/s; CZ 1.35±0.21 mm²/s). In PC ADC_mono values (0.61±0.06 mm²/s) were significantly (P<.001) lower than in the peripheral of central zone of AC. Using the statistical analysis (Akaike information criteria) in YV most pixels were best described by the biexponential model (82%), the statistical model, respectively kurtosis (93%) each compared to the monoexponential model. In PC the majority of pixels was best described by the monoexponential model (57%) compared to the biexponential model.

Conclusion

Although a more complex model might provide a better fitting when multiple b-values are used, the monoexponential analyses for ADC calculation in prostate MRI is sufficient to discriminate prostate cancer from normal tissue using b-values ranging from 0 to 800 s/mm².     

Effect of hepatic steatosis on native T1 mapping of 3T magnetic resonance imaging in the assessment of T1 values for patients with non-alcoholic fatty liver disease

PurposeThis study investigated whether T1 values in native T1 mapping of 3T magnetic resonance imaging (MRI) of the liver were affected by the fatty component.MethodsThis prospective study involved 340 participants from a population-based cohort study between May 8, 2018 and August 8, 2019. Data obtained included: (1) hepatic stiffness according to magnetic resonance elastography (MRE); (2) T1 value according to T1 mapping; (3) fat fraction and iron concentration from multi-echo Dixon; and (4) clinical indices of hepatic steatosis including body mass index, waist circumference, history of diabetes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The correlations between T1 value and fat fraction, and between T1 value and liver stiffness were assessed using Pearson's correlation coefficient. The independent two-sample t-test was used to evaluate the differences in T1 values according to the presence or absence of hepatic steatosis, and the one-way analysis of variance was used to evaluate the difference in T1 value by grading of hepatic steatosis according to MRI-based proton density fat fraction (PDFF). In addition, univariate and multivariate linear regression analyses were performed to determine whether other variables influenced the T1 value.ResultsT1 value showed a positive correlation with the fat fraction obtained from PDFF (r = 0.615, P < 0.001) and with the liver stiffness obtained from MRE (r = 0.370, P < 0.001). Regardless of the evaluation method, the T1 value was significantly increased in subjects with hepatic steatosis (P < 0.001). When comparing hepatic steatosis grades based on MRI-PDFF, the mean T1 values were significantly different in all grades, and the T1 value tended to increase as the grade increased (P < 0.001, P for trend <0.001). On multiple linear regression analysis, the T1 value was influenced by MRI-PDFF, calculated liver iron concentration, liver stiffness, and serum aspartate aminotransferase level.ConclusionThe T1 value obtained by current T1 mapping of 3T MRI was affected by the liver fat component and several other factors such as liver stiffness, iron concentration, and inflammation.     

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.     

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.     

The impact of spin coupling signal loss on fat content characterization in multi-echo acquisitions with different echo spacing

PurposeThis study aimed to assess the effect of echo spacing in transverse magnetization (T2) signal decay of gel and fat (oil) samples. Additionally, we assess the feasibility of using spin coupling as a determinant of fat content.MethodsPhantoms of known T2 values, as well as vegetable oil phantoms, were scanned at 1.5 T scanner with a multi echo FSE sequence of variable echo spacing above and below the empirical threshold of 20 ms for echo train signal modulation (6.7, 13.6, 26.8, and 40 ms). T2 values were calculated from monoexponential fitting of the data. Relative signal loss between the four acquisitions of different echo spacing was calculated.ResultsAgreement in the T2 values of water gel phantom was observed in all acquisitions as opposed to fat phantom (oil) samples. Relative differences in signal intensity between two successive sequences of different echo spacing on composite fat/water regions of interest was found to be linearly correlated to fat fraction of the ROI.ConclusionThe sample specific degree of signal loss that was observed between different fat samples (vegetable oils) can be attributed to the composition of each sample in J coupled fat components. Hence, spin coupling may be used as a determinant of fat content.     

R1ρ at high spin-lock frequency could be a complementary imaging biomarker for liver iron overload quantification

PurposeTo compare the correlations among the R1ρ, R2, and R2* relaxation rates with liver iron concentration (LIC) in the assessment of rat liver iron content and explore the application potential of R1ρ in assessing liver iron content.MethodsIron dextran (dosage of 0, 25, 50, 100, and 200 mg/kg body weight) was injected into 35 male rats to increase the amount of iron storage in the liver. After one week, all rats were euthanized with isoflurane. A portion of the largest hepatic lobe was extracted to quantify the LIC by inductively coupled plasma, and the remaining liver tissue was stored in 4% buffered paraformaldehyde for 24 h before MRI. Spin-lock preparation with a RARE (rapid acquisition with relaxation enhancement) readout (9 different spin-lock times and 7 different spin-lock frequencies (FSLs)) and multi-echo UTE (ultrashort TE) pulses were developed to quantify R1ρ and R2 * on a Bruker 11.7 T MR system. For comparisons with R1ρ and R2*, R2 was acquired using the CPMG sequence.ResultsMean R1ρ values displayed dispersion, with decrease in R1ρ at higher FSLs. Spearman's correlation analysis (two-tailed) indicated that the R1ρ values were significantly associated with LIC at FSL = 2000, 2500, and 3000 Hz (r = 0.365 and P = 0.031, r = 0.608 and P < 0.001, and r = 0.764 and P < 0.001, respectively), and were not significantly associated with LIC at FSL = 500, 1000, 1250, and 1500 Hz (all P > 0.05). R2 and R2* showed significant linear correlations with LIC (r = 0.787 and P < 0.001, and r = 0.859 and P < 0.001, respectively). Correlation analysis across R1ρ, R2, and R* also suggested that the correlation strength between R1ρ and R2 and between R1ρ and R* showed an increasing trend with increase in FSL.ConclusionIn this study, a strong association was observed between R1ρ and LIC at high FSLs further confirming previous findings. The results demonstrated that R1ρ at high FSL might serve as a complementary imaging biomarker for liver iron overload quantification.     

Study of energy transfer in a solution of coumarin 460 and rhodamine 6G by time-resolved laser-induced fluorescence spectroscopy

A multi-photon fast analog technique has been used to study nonradiative energy transfer from coumarin 460 to rhodamine 6G molecules. At low acceptor concentrations (<10^-2 mol/1) the fluorescence decay from coumarin deviates markedly from monoexponential behavior. The complex decay of the donor fluorescence reflects the time-dependent population of donor-acceptor pairs. Various energy transfer kinetics were investigated. The donor decay was found to be consistent with Förster kinetics and the critical energy transfer radius was found to be (5.46±0.10) nm.     

Inversion recovery ultrashort echo time magnetic resonance imaging: A method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain – A feasibility study

Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (< 1 ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3 T scanner. The technique was first validated on a synthetic myelin phantom (myelin powder in D₂O) and a Feridex iron phantom. This was followed by studies of cadaveric MS specimens, healthy volunteers and MS patients. UTE imaging of the synthetic myelin phantom showed an excellent bi-component signal decay with two populations of protons, one with a T2* of 1.2 ms (residual water protons) and the other with a T2* of 290 μs (myelin protons). IR-UTE imaging shows sensitivity to a wide range of iron concentrations from 0.5 to ~ 30 mM. The IR-UTE signal from white matter of the brain of healthy volunteers shows a rapid signal decay with a short T2* of ~ 300 μs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter.     

Hepatocellular lesions with increased iron uptake on superparamagnetic iron oxide-enhanced magnetic resonance imaging in cirrhosis or chronic hepatitis: comparison of four magnetic resonance sequences for lesion conspicuity

Purpose

The aim of this study was to determine the adequate MR sequence for the lesion conspicuity of hepatocellular lesions with increased iron uptake on superparamagnetic iron oxide (SPIO)-enhanced MRI.

Materials and Methods

SPIO-enhanced MRI was performed using a 1.5-T system. Among 25 patients with hypovascular hepatocellular nodules on contrast-enhanced dynamic CT (no early enhancement at arterial phase and hypoattenuation at equilibrium phase), 39 lesions with increased iron uptake on SPIO-enhanced MRI were evaluated. SPIO-enhanced MRI included (1) T1-weighted in-phase gradient recalled echo (GRE) images, (2) T2-weighted fast spin echo (FSE) images, (3) T2*-weighted GRE with moderate TE (7 ms) and (4) long TE (12 ms). The lesion-to-liver contrast-to-noise ratios of the hepatocellular nodule and the signal-to-noise ratio (SNR) of the hepatic parenchyma were calculated by one radiologist for a quantitative assessment. MR images were reviewed retrospectively by two independent radiologists to compare the subjective lesion conspicuity in each image set based on a four-point rating scale.

Result

The mean lesion-to-liver contrast-to-noise ratios with T2*-weighted GRE with moderate TE (7 ms) was highest (5.79±3.71) and was significantly higher than those with T1-weighted, in-phase images (3.79±3.23, P<.01), T2-weighted images (2.72±1.52, P<.001) and T2*-weighted GRE with long TE (12 ms) (3.93±2.69, P<.05). The subjective rating of lesion conspicuity was best on the T2*-weighted GRE with moderate TE (7 ms), followed by that on the T2*-weighted GRE with moderate TE (7 ms; P<.05).

Conclusion

T2*-weighted GRE sequence with moderate TE (7 ms) showed high lesion-to-liver contrast-to-noise ratios in hepatocellular lesions with increased iron uptake on SPIO-enhanced MRI, indicating better lesion conspicuity of hypointense hepatocellular nodules in cirrhosis or chronic hepatitis.     

Decreasing iron susceptibility with temperature in quantitative susceptibility mapping: A phantom study

To clarify the temperature dependence of susceptibility estimated by quantitative susceptibility mapping (QSM) analysis, we investigated the relationship between temperature and susceptibility using a cylinder phantom with varying temperatures. Six solutions with various concentrations of superparamagnetic iron oxide (SPIO) nanoparticles were employed. These tubes were placed in a cylinder phantom and surrounded with water. The temperature of the circulated water was adjusted to change the temperature in the cylinder phantom from 25.8 °C to 42.5 °C. The cylinder phantom was scanned via a three-dimensional multiple spoiled gradient-echo sequence for R2* and QSM analyses with varying temperatures. The relationships between temperature, susceptibility, and R2* values were determined. Moreover, the temperature coefficients of susceptibility (χ-Tc) and (R2*-Tc) were calculated at each concentration and the linearities in these indices against each SPIO concentration were validated. Significant inverse correlations were found between temperature, susceptibility, and R2* values at each SPIO concentration due to the decrease in paramagnetic iron susceptibility that occurred with increasing temperature based on Curie's law. Moreover, although there were significant correlations between the susceptibility and R2* values at any temperature, the slopes of the regression lines grew in height with greater temperatures. The percentage of difference per Celsius degree in susceptibility in any SPIO concentration was lower than the corresponding finding among the R2* results. There were strong linearities between the SPIO concentration, χ-Tc (r = −0.994; p < 0.001), and R2*-Tc (r = −0.998; p < 0.001). The χ-Tc and R2*-Tc outcomes in a particular voxel varied considerably with the iron contents. Although there was an inverse correlation noted between temperature and susceptibility, the susceptibility analysis showed smaller temperature dependence relative to the R2* analysis. QSM analysis might be a more suitable option for magnetic resonance-based iron quantification in comparison with R2* relaxometry.