Inflammatory imaging with ultrasmall superparamagnetic iron oxide

The purpose of this study was to investigate the usefulness and feasibility of magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-enhanced MRI) for imaging inflammatory tissues. First, we investigated the relationship between the apparent transverse relaxation rate (R2*) and the concentration of USPIO by phantom studies and measured the apparent transverse relaxivity (r2*) of USPIO. Second, we performed animal experiments using a total of 30 mice. The mice were divided into five groups [A (n=6), B (n=6), C (n=6), sham control (n=6), and control (n=6)]. The mice in Groups A, B, C and control were subcutaneously injected with 0.1 ml of turpentine oil on Day 0, while those in the sham control group were subcutaneously injected with 0.1 ml of saline. The mice in Groups A, B, C and sham control were intraperitoneally injected with 200 μmol Fe per kilogram body weight of USPIO (28 nm in diameter) immediately after the first MRI study on Days 3, 5, 7 and 7, respectively, and those in the control group were not injected with USPIO. The second and third MRI studies were performed at 24 and 48 h after USPIO administration, respectively. The maps of R2* were generated from the apparent transverse relaxation time (T2*)-weighted images with six different echo times. The phantom studies showed that there was a linear relationship between R2* and the concentration of USPIO (r=0.99) and the r2* value of USPIO was 105.7 mM⁻¹ s⁻¹. There was a significant increase of R2* in inflammatory tissues in Group C at 24 h after USPIO administration compared with the precontrast R2* value. Our results suggest that USPIO-enhanced MRI combined with R2* measurement is useful for detecting inflammatory tissues.     

In vivo hypoxia characterization using blood oxygen level dependent magnetic resonance imaging in a preclinical glioblastoma mouse model

PurposeHypoxia measurements can provide crucial information regarding tumor aggressiveness, however current preclinical approaches are limited. Blood oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) has the potential to continuously monitor tumor pathophysiology (including hypoxia). The aim of this preliminary work was to develop and evaluate BOLD MRI followed by post-image analysis to identify regions of hypoxia in a murine glioblastoma (GBM) model.MethodsA murine orthotopic GBM model (GL261-luc2) was used and independent images were generated from multiple slices in four different mice. Image slices were randomized and split into training and validation cohorts. A 7 T MRI was used to acquire anatomical images using a fast-spin-echo (FSE) T2-weighted sequence. BOLD images were taken with a T2*-weighted gradient echo (GRE) and an oxygen challenge. Thirteen images were evaluated in a training cohort to develop the MRI sequence and optimize post-image analysis. An in-house MATLAB code was used to evaluate MR images and generate hypoxia maps for a range of thresholding and ΔT2* values, which were compared against respective pimonidazole sections to optimize image processing parameters. The remaining (n = 6) images were used as a validation group. Following imaging, mice were injected with pimonidazole and collected for immunohistochemistry (IHC). A test of correlation (Pearson's coefficient) and agreement (Bland-Altman plot) were conducted to evaluate the respective MRI slices and pimonidazole IHC sections.ResultsFor the training cohort, the optimized parameters of “thresholding” (20 ≤ T2* ≤ 35 ms) and ΔT2* (±4 ms) yielded a Pearson's correlation of 0.697. These parameters were applied to the validation cohort confirming a strong Pearson's correlation (0.749) when comparing the respective analyzed MR and pimonidazole images.ConclusionOur preliminary study supports the hypothesis that BOLD MRI is correlated with pimonidazole measurements of hypoxia in an orthotopic GBM mouse model. This technique has further potential to monitor hypoxia during tumor development and therapy.     

Towards intrinsic R2* imaging in the prostate at 3 and 7 tesla

PurposeHypoxia is an important marker for resistance to therapy. In this study, we quantify the macroscopic effects of R2* mapping in prostate cancer patients incorporating susceptibility matching and field strengths effects.Materials and methods91 patients were scanned without endorectal coil (ERC) at 3 T. Only when rectal gas was absent, data was included for analysis. Another group of 10 patients was scanned using a susceptibility matched ERC. To assess the residual contamination of R2 and macroscopic field non-uniformities, a group of 10 patients underwent ultra-high resolution 7 T MRI.ResultsOf the patients scanned at 3 T 60% presented rectal gas and were excluded, due to susceptibility artifacts. At 3 T the tumor was significantly different (P < 0.01) from the healthy surrounding tissue in R2* values at intrapatient level. Using the measured median R2* value of 24.9 s^− 1 at 3 T and 43.2 s^− 1 at 7 T of the peripheral zone, the minimum contribution of macroscopic susceptibility effects is 15% at 3 T.ConclusionR2* imaging might be a promising tool for hypoxia imaging, particularly when minimizing macroscopic susceptibility effects contaminating intrinsic R2* of tissue, such as rectal gas. At 3 T macroscopic effects still contribute 15% in the R2* value, compared to ultra-high resolution R2* mapping at 7 T.     

In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model

ObjectivesTo assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model.MethodsFifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm²), 2 b values (0 and 500 s/mm²) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57–24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies.ResultsTrue diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381–0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD.ConclusionsMultiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.     

Quantification of myocardial oxygenation in heart failure using blood-oxygen-level-dependent T2* magnetic resonance imaging: Comparison with cardiopulmonary exercise test

PurposeQuantification of myocardial oxygenation (MO) in heart failure (HF) has been less than satisfactory. This has necessitated the use of invasive techniques to measure MO directly or to determine the oxygen demand during exercise using the cardiopulmonary exercise (CPX) test. We propose a new quantification method for MO using blood-oxygen-level-dependent (BOLD) myocardial T2* magnetic resonance imaging (M-T2* MRI), and investigate its correlation with CPX results.MethodsThirty patients with refractory HF who underwent cardiac MRI and CPX test for heart transplantation, and 24 healthy, age-matched volunteers as controls were enrolled. M-T2* imaging was performed using a 3-Tesla and multi-echo gradient-echo sequence. M-T2* was calculated by fitting the signal intensity data for the mid-left ventricular septum to a decay curve. M-T2* was measured under room-air (T2*-air) and after inhalation of oxygen for 10 min at a flow rate of 10 L/min (T2*-oxy). MO was defined as the difference between the two values (ΔT2*). Changes in M-T2* at the two conditions and ΔT2* between the two groups were compared. Correlation between ΔT2* and CPX results was analyzed using the Pearson coefficient.ResultsT2*-oxy was significantly greater than T2*-air in patients with HF (29.9 ± 7.3 ms vs. 26.7 ± 6.0 ms, p < 0.001), whereas no such difference was observed in controls (25.5 ± 4.0 ms vs. 25.4 ± 4.4 ms). ΔT2* was significantly greater for patients with HF than for controls (3.2 ± 4.5 ms vs. -0.1 ± 1.3 ms, p < 0.001). A significant correlation between ΔT2* and CPX results (peak VO₂, r = − 0.46, p < 0.05; O₂ pulse, r = − 0.54, p < 0.005) was observed.ConclusionΔT2* is increased T2*-oxy is greater in patients with HF, and is correlated with oxygen metabolism during exercise as measured by the CPX test. Hence, ΔT2* can be used as a surrogate marker of MO instead of CPX test.     

Intravoxel incoherent motion magnetic resonance imaging for breast cancer: A comparison with molecular subtypes and histological grades

PurposeThe purpose of this paper is to investigate whether the IVIM parameters (D, D *, f) helps to determine the molecular subtypes and histological grades of breast cancer.MethodsFifty-one patients with breast cancer were included in the study. All subjects were examined by 3 T Magnetic Resonance Imaging (MRI). Diffusion-weighted imaging (DWI) was undertaken with 16 b-values. IVIM parameters [D (true diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction)] were calculated. Histopathological reports were reviewed to histological grade, histological type, and immunohistochemistry. IVIM parameters of tumors with different histological grades and molecular subtypes were compared.ResultsD* and f were significantly different between molecular subtypes (p = 0.019, p = 0.03 respectively). D* and f were higher in the HER-2 group and lower in Triple negative (−) group (D*:36.8 × 10⁻³ ± 5.3 × 10⁻³ mm²/s, f:29.5%, D*:29.8 × 10⁻³ ± 5.6 × 10⁻³ mm²/s, f:21.5% respectively). There was a significant difference in D* and f between HER-2 and Triple (−) subgroups (p = 0,028, p = 0.024, respectively). D* was also significantly different between the HER-2 group and the Luminal group (p = 0,041). While histological grades increase, D and f values tend to decrease, and D* tends to increase. While the Ki-67 index increases, D* and f values tend to increase, and D tend to decrease.ConclusionD* and f values measured with IVIM imaging were useful for assessing breast cancer molecular subtyping. IVIM imaging may be an alternative to breast biopsy for sub-typing of breast cancer with further research.     

Automated analysis of immediate reliability of T2 and T2* relaxation times of hip joint cartilage from 3 T MR examinations

BackgroundMagnetic resonance (MR) T2 and T2* mapping sequences allow in vivo quantification of biochemical characteristics within joint cartilage of relevance to clinical assessment of conditions such as hip osteoarthritis (OA).PurposeTo evaluate an automated immediate reliability analysis of T2 and T2* mapping from MR examinations of hip joint cartilage using a bone and cartilage segmentation pipeline based around focused shape modelling.Study typeTechnical validation.Subjects17 asymptomatic volunteers (M: F 7:10, aged 22–47 years, mass 50–90 kg, height 163-189 cm) underwent unilateral hip joint MR examinations. Automated analysis of cartilage T2 and T2* data immediate reliability was evaluated in 9 subjects (M: F 4: 5) for each sequence.Field strength/sequenceA 3 T MR system with a body matrix flex-coil was used to acquire images with the following sequences: T2 weighted 3D-trueFast Imaging with Steady-State Precession (water excitation; 10.18 ms repetition time (TR); 4.3 ms echo time (TE); Voxel Size (VS): 0.625 × 0.625 × 0.65 mm; 160 mm field of view (FOV); Flip Angle (FA): 30 degrees; Pixel Bandwidth (PB): 140 Hz/pixel); a multi-echo spin echo (MESE) T2 mapping sequence (TR/TE: 2080/18–90 ms (5 echoes); VS: 4 × 0.78 × 0.78 mm; FOV: 200 mm; FA: 180 degrees; PB: 230 Hz/pixel) and a MESE T2* mapping sequence (TR/TE: 873/3.82–19.1 ms (5 echoes); VS: 3 × 0.625 × 0.625 mm; FOV: 160 mm; FA: 25 degrees; PB: 250 Hz/pixel).AssessmentAutomated cartilage segmentation and quantitative analysis provided T2 and T2* data from test-retest MR examinations to assess immediate reliability.Statistical testsCoefficient of variation (CV) and intraclass correlations (ICC_{2, 1}) to analyse automated T2 and T2* mapping reliability focusing on the clinically important superior cartilage regions of the hip joint.ResultsComparisons between test-retest T2 and (T2*) data revealed mean CV's of 3.385% (1.25%), mean ICC_{2, 1}′s of 0.871 (0.984) and median mean differences of −1.139ms (+0.195ms).ConclusionThe T2 and T2* times from automated analyses of hip cartilage from test-retest MR examinations had high (T2) and excellent (T2*) immediate reliability.     

The value of ESWAN in diagnosis and differential diagnosis of prostate cancer: Preliminary study

ObjectiveTo evaluate the value of enhanced T2 star-weighted angiography (ESWAN) in diagnosis and differential diagnosis of prostate cancer by comparing the multiple indices of ESWAN in benign prostatic hyperplasia (BPH), prostate cancer (PCa) and the normal peripheral zone (PZ).MethodsTraditional MRI and ESWAN were performed on forty-nine clinically-diagnosed PCa patients, sixty BPH patients, and forty-six normal adult males. The ESWAN indices (magnitude value, phase value, R2* value and T2* value) measured on different regions of interest (ROIs) were analyzed. Additionally, receiver operating characteristic (ROC) analysis was performed to obtain the area under the curve (AUC), sensitivity, specificity, and optimal cut-off points of PCa and BPH, PCa and PZ respectively.ResultsThe magnitude value, phase value, R2* value and T2* value of PZ were 1529.43 ± 254.43, 0.0689 ± 0.1619, 16.57 ± 8.11, 82.75 ± 53.87, respectively; the magnitude value, phase value, R2* value, and T2* value of PCa were 1540.18 ± 338.62, − 0.0176 ± 0.0919, 26.93 ± 11.31, and 45.99 ± 17.43, respectively; the magnitude value, phase value, R2* value, and T2* value of BPH were 1579.49 ± 285.28, 0.0209 ± 0.0839, 20.69 ± 3.95, and 51.56 ± 8.90, respectively. Compared with normal PZ, phase value of PCa was lower (t = − 3.302, P = 0.001), R2* value higher (t = 5.326, P = 0.000), and T2* value lower (t = − 4.570, P = 0.000); compared with BPH, phase value of PCa was lower (t = − 2.261, P = 0.026), R2* value higher (t = 3.988, P = 0.000), and T2* value lower (t = − 2.155, P = 0.033). When PCa and PZ were distinguished, the AUC of magnitude value, phase value, R2* value, and T2* value were respectively 0.539 (P = 0.510), 0.679 (P = 0.0007), 0.811 (P < 0.0001), and 0.762 (P < 0.0001); the diagnosis efficiency of R2* value was higher than that of T2* value (P = 0.037), while the diagnosis efficiency of T2* value was equivalent to phase value (P = 0.256). When PCa was differentiated from BPH, the AUC of magnitude value, phase value, R2* value, and T2* value were 0.518 (P = 0.752), 0.612 (P = 0.039), 0.705 (P = 0.0001), and 0.685 (P = 0.0006), respectively; there was no statistical difference in the diagnostic efficiency of phase value, R2* value, and T2* value.ConclusionsThe phase value, R2* value and T2* value can distinguish PCa and normal PZ, PCa and BPH, so they are valuable for the diagnosis and differential diagnosis of PCa, moreover, the diagnostic efficiency of R2* value is better than other indices.     

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.     

A fast method for the quantification of fat fraction and relaxation times: Comparison of five sites of bone marrow

PurposeBone marrow is found either as red bone marrow, which mainly contains haematopoietic cells, or yellow bone marrow, which mainly contains adipocytes. In adults, red bone marrow is principally located in the axial skeleton. A recent study has introduced a method to simultaneously estimate the fat fraction (FF), the T1 and T2* relaxation times of water (T1w, T2*w) and fat (T1f and T2*f) in the vertebral bone marrow. The aim of the current study was to measure FF, T1w, T1f, T2*w and T2*f in five sites of bone marrow, and to assess the presence of regional variations.MethodsMRI experiments were performed at 1.5 T on five healthy volunteers (31.6 ± 15.6 years) using a prototype chemical-shift-encoded 3D multi-gradient-echo sequence (VIBE) acquired with two flip angles. Acquisitions were performed in the shoulders, lumbar spine and pelvis, with acquisition times of < 25 seconds per sequence. Signal intensities of magnitude images of the individual echoes were used to fit the signal and compute FF, T1w, T1f, T2*w and T2*f in the humerus, sternum, vertebra, ilium and femur.ResultsRegional variations of fat fraction and relaxation times were observed in these sites, with higher fat fraction and longer T1w in the epiphyses of long bones. A high correlation between FF and T1w was measured in these bones (R = 0.84 in the humerus and R = 0.84 in the femur). In most sites, there was a significant difference between water and fat relaxation times, attesting the relevance of measuring these parameters separately.ConclusionThe method proposed in the current study allowed for measurements of FF, T1w, T1f, T2*w and T2*f in five sites of bone marrow. Regional variations of these parameters were observed and a strong negative correlation between the T1 of water and the fat fraction in bones with high fat fractions was found.     

Early changes in intravoxel incoherent motion MRI parameters can potentially predict response to chemoradiotherapy in rectal cancer: An animal study

Imaging-based approaches for early predicting response of rectal cancer to neoadjuvant chemoradiotherapy remain an ongoing-challenge. In this study, we aimed to monitor the changes of intravoxel incoherent motion (IVIM) MRI parameters during the early post-treatment period in mouse models of human rectal carcinoma, and to test whether these changes relate to the final response. Thirty-two mice with subcutaneous-tumor were randomly divided into control (n = 11), chemoradiotherapy (n = 10) and chemotherapy (n = 11) group. Tumors were monitored by IVIM at day 0, 3, 7, 9 after treatment. The final tumor response was determined by tumor remission-rate and necrosis scores. The results indicated that within 9 days after treatment, D values increased in both treated groups, but remained stable in control group. D values were significantly higher in chemotherapy group at day 7 and in each treated group at day 9 than in control group (day 7, p = 0.004; day 9: p = 0.011 and 0.009, respectively). D* values decreased in treated groups, and showed significantly lower than in control group at day 7 (p < 0.001). There was a strong positive correlation between delta D*% (D*_{day0 – day7}/D*_day0) and tumor remission rate (r = 0.707, p < 0.001), and a mild negative correlation between delta D% and tumor necrosis scores (r = −0.526, p = 0.014). D and D* values in rectal carcinoma xenograft models appeared tendency change during the early post-treatment period. In conclusion, early changes of D and D* values may have potential for predicting the final efficacy of chemoradiotherapy.     

Quantitative ferumoxytol-enhanced MRI in pregnancy: A feasibility study in the nonhuman primate

ObjectivesTo assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model.Materials and methodsIn this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test.ResultsIn fetuses, a slope of 0.3 s⁻¹/day (P = 0.008), 0.00 ppm/day (P = 0.699) and − 0.2 s⁻¹/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points.ConclusionsThis work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.     

Early diagnosis of degenerative changes in the articular/fibrocartilaginous disc of the temporomandibular joint in patients with temporomandibular disorders using delayed gadolinium-enhanced MRI at 3 Tesla – preliminary results

BackgroundDelayed gadolinium enhanced MRI of cartilage (dGEMRIC) is a quantitative method for assessment of glycosaminoglycan content in connective tissues. We hypothesize that the early diagnosis of degenerative changes in the temporomandibular joint could be diagnosed using dGEMRIC technique.PurposeTo test the compositional MRI technique, dGEMRIC, at 3 Tesla to diagnosis early the degenerative changes in the fibrocartilaginous disc of the temporomandibular joint (TMJ) in patients with temporomandibular disorders (TMD) and to compare the dGEMRIC index of patients to the healthy volunteers.MethodsSix volunteers (two men, four women; 20.8÷28.1 years) and eleven patients (22 TMJs, seven women, four men; 24÷54 years) were recruited for this prospective trial. Only patients with no morphological abnormality on MRI and without disc dislocations were included. Volunteers were used as a control group. The PD-weighted FSE sequence and the 3D GRE (DESS) sequence protocols were performed for morphological assessment. The Inversion recovery (IR) sequence was performed for T1 relaxation time measurements and intra-venous (IV) contrast agent administration was used according to the dGEMRIC protocol. T1 maps were calculated offline and ROIs were drawn on TMJ discs by a specialist trained in TMD disorders. Statistical evaluation was performed by ANOVA and correlations were calculated.ResultsThe difference between the dGEMRIC values in the TMJ articular discs of the patients and the volunteers was statistically significant (P = .019). After contrast agent administration the T1 values dropped in both groups. In patient group was the T1 drop stronger (−54% from initial pre-contrast value), while in control group was the T1 drop less pronounced (−46% from initial pre-contrast value).ConclusionsdGEMRIC seems to be a useful, compositional, quantitative method, suitable also for small joints, such as the articular disc of the TMJ. The results of the dGEMRIC index in the articular disc of the TMJ imply a lower GAG content in patients with TMJ disorders.     

Quantitative MRI of the liver: Evaluation of extracellular volume fraction and other quantitative parameters in comparison to MR elastography for the assessment of hepatopathy

BackgroundChronic liver diseases pose a major health problem worldwide, while common tests for diagnosis and monitoring of diffuse hepatopathy have considerable limitations. Preliminary data on the quantification of hepatic extracellular volume fraction (ECV) with magnetic resonance imaging (MRI) for non-invasive assessment of liver fibrosis are encouraging, with ECV having the potential to overcome several of these constraints.PurposeTo clinically evaluate ECV provided by quantitative MRI for assessing the severity of liver disease.Materials and methodsIn this prospective study, multiparametric liver MRI, including T1 mapping and magnetic resonance elastography (MRE), was performed in subjects with and without hepatopathy between November 2018 and October 2019. T1, T2, T2*, proton density fat fraction and stiffness were extracted from parametric maps by regions of interest and ECV was calculated from T1 relaxometries. Serum markers of liver disease were obtained by clinical database research. For correlation analysis, Spearman rank correlation was used. ROC analysis of serum markers and quantitative MRI data for discrimination of liver cirrhosis was performed with MRE as reference standard.Results109 participants were enrolled (50.7 ± 16.1 years, 61 men). ECV, T1 and MRE correlated significantly with almost all serum markers of liver disease, with ECV showing the strongest associations (up to r = 0.67 with MELD, p < 0.01). ECV and T1 correlated with MRE (0.75 and 0.73, p < 0.01 each). ECV (AUC 0.89, cutoff 32.2%, sensitivity 85%, specificity 87%) and T1 mapping (AUC 0.85, cutoff 592.5 ms, sensitivity 83%, specificity 75%) featured good performances in detection of liver cirrhosis with only ECV performing significantly superior to model of end stage liver disease (MELD), AST/ALT ratio and international normalized ratio (p < 0.01, respectively).ConclusionQuantification of hepatic extracellular volume fraction with MRI is suitable for estimating the severity of liver disease when using MRE as the standard of reference. It represents a promising tool for non-invasive assessment of liver fibrosis and cirrhosis.     

A comparison of ferumoxytol with gadolinium as contrast agents for the diagnostic magnetic resonance imaging of osteomyelitis

BackgroundFerumoxytol, an FDA-approved superparamagnetic iron oxide nanoparticle (SPION) preparation used for the treatment of iron deficiency anemia, is also known to be taken up by macrophages in areas of infection or inflammation, where it produces negative contrast changes on T2-weighted MR images.PurposeWe sought to compare Ferumoxytol-induced MRI contrast changes with those observed using standard-of-care Gadolinium in patients presenting with symptoms suggestive of osteomyelitis.SubjectsOut of eighteen enrolled patients, 15 had MR imaging with both ferumoxytol and gadolinium. Based on clinical and/or pathologic criteria, 7 patients were diagnosed with osteomyelitis, 5 patients had osteomyelitis ruled out, and in 3 patients a definitive diagnosis could not be made.Field strength1.5 Tesla.SequencesUsed included STIR, T1-weighted and T2-weighted spin echo.AssessmentThe mean contrast changes upon ferumoxytol and gadolinium administration were measured from lesion regions of interest and compared with control regions.Statistical testsStudent's t-test, propagation of errors. Data are reported as means ± S.E.ResultsThe mean contrast changes, ΔC, associated with a diagnosis of osteomyelitis were found to be ΔCFe = −2.7 ± 0.7 when Ferumoxytol and T2w imaging sequences were used and ΔCGd = +3.1 ± 1.1 (P < 0.001) when Gadolinium and a T1w imaging sequence was used. The MRI contrast changes for both agents correlated with systemic markers of inflammation, such as the erythrocyte sedimentation rate. In patients without osteomyelitis, no significant contrast changes were observed in T2-weighted, Ferumoxytol-contrasted MRI. The macrophages in osteomyelitic lesions were found to take up at least 16 times as much iron as benign bone marrow.Data conclusionWe conclude that in terms of its MRI diagnostic accuracy for osteomyelitis Ferumoxytol-contrasted MRI is a promising approach for diagnosing osteomyelitis that merits further study.     

Variations in T(2)* and fat content of murine brown and white adipose tissues by chemical-shift MRI

Purpose

The purpose was to compare T₂* relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice.

Materials and Methods

A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T₂*-corrected chemical-shift-based water–fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T₂* and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T₂* and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test.

Results

Significant differences (P<.01) in BAT T₂* and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T₂* and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T₂* and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images.

Conclusion

T₂* and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter.     

Cardiac MRI for the prognostication of heart failure with preserved ejection fraction: A systematic review and meta-analysis

BackgroundCardiac magnetic resonance imaging (MRI) is emerging as an important imaging tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This systematic review and meta-analysis aim to synthesise and consolidate the current literature on cardiac MRI for prognostication of HFpEF.Methods designSystematic review and meta-analysis. Data sources: Scopus (PubMed and Embase) for studies published between 2008 and 2019. Eligibility criteria for study selection were studies that evaluated the prognostic role of cardiac MRI in HFpEF. Random effects meta-analyses of the reported hazard ratios (HR) for clinical outcomes was performed.ResultsInitial screening identified 97 studies. From these, only nine (9%) studies met all the criteria. The main cardiac MRI methods that demonstrated association to prognosis in HFpEF included late gadolinium enhancement (LGE) assessment of scar (n = 3), tissue characterisation with T1-mapping (n = 4), myocardial ischaemia (n = 1) and right ventricular dysfunction (RVSD) (n = 1). The pooled HR for all 9 studies was 1.52 (95% CI 1.05–1.99, P < 0.01). Sub-evaluation by cardiac MRI methods revealed varying HRs: LGE (net n = 402, HR = 1.6, 95% CI 0.42–2.78, P = 0.008); T1-mapping (n = 1623, HR = 1.25, 95% CI 0.891–1.60, P < 0.001); myocardial ischaemia or RVSD (n = 325, HR = 3.19, 95% CI 0.30–6.08, P = 0.03).ConclusionThis meta-analysis demonstrates that multiparametric cardiac MRI has value in prognostication of patients with HFpEF. HFpEF patients with a detectable scar on LGE, fibrosis on T1-mapping, myocardial ischaemia or RVSD appear to have a worse prognosis.PROSPERO registration numberCRD42020187228.     

Preliminary quantitative analysis of vertebral microenvironment changes in type 2 diabetes mellitus using FOCUS IVIM-DWI and IDEAL-IQ sequences

PurposeTo explore the application of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI) on account of field-of-view optimized and constrained undistorted single shot (FOCUS) and iteraterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation(IDEAL-IQ) sequences in evaluating the vertebral microenvironment changes of type 2 diabetes mellitus(T2DM) patients and the correlation with bone mineral density(BMD).Method128 T2DM patients (mean age 63.4 ± 5.28 years) underwent both dual-energy X-ray absorptiometry (DEXA) and spine MRI. The FOCUS IVIM-DWI and IDEAL-IQ derived parameters of the vertebral body(L1, L2, L3, L4)were measured on corresponding maps of the lumbar spine. The subjects were divided into 3 groups according to T-scores as follows: normal (n = 37), osteopenia (n = 43), and osteoporosis(n = 48) group.One-way analysis of variance (ANOVA) were used to compare the vertebral parameters(ADC_slow, ADC_fast, f, FF, R2*) among three BMD cohorts.Receiver operating characteristic (ROC) analyses and Spearman's rank correlation were performed to test the diagnostic performance and the correlation between them respectively.ResultsThere were significant differences in vertebral ADC_slow, ADC_fast, FF and R2* between the three groups (P < 0.05).Statistically, BMD was moderately negatively correlated with FF (r = −0.584, P < 0.001) and weakly positively with ADC_slow (r = 0.334, P < 0.001), meanwhile moderately positively correlated with R2*(r = 0.509, P < 0.001) and ADC_fast(0.545, P < 0.001).ADC_fast was moderately negatively correlated with FF (r = −0.417, P < 0.001), weakly positively correlated with R2*(0.359, P < 0.001).Compared with the area under the curve (AUC) of ADC_slow, ADC_fast, FF and R2*, the AUC of ADC_fast was higher in identifying between normal and abnormal(osteopenia and osteoporosis), normal from osteopenia, while the AUC of FF was higher in identifying osteopenia from osteoporosis.ConclusionsFOCUS IVIM-DWI and IDEAL-IQ of lumbar spine might be useful to evaluate the vertebral microenvironment changes of T2DM patients.     

Associations between histogram analysis parameters derived from dynamic-contrast enhanced MRI and PD L1-expression in head and neck squamous cell carcinomas. A preliminary study

PurposeProgrammed death 1 ligand (PD-L 1) plays an essential role in oncology. It might be crucial to predict its expression non-invasively by imaging. Dynamic-contrast enhanced MRI (DCE MRI) is one of the important imaging modalities in head and neck squamous cell cancer (HNSCC). The aim of the present study was to analyze possible associations between histogram analysis parameters of DCE MRI and PD-L 1 expression in HNSCCMethodsOverall, 26 patients with primary HNSCC of different localizations were involved in the study. DCE MRI was obtained on a 3 T MRI and analyzed with a whole lesion measurement using a histogram approach. PD-L 1 expression was estimated on bioptic samples before any form of treatment using 3 scores (Tumor positive score (TPS), Immune cell score (ICS) and Combined positive score (CPS)).ResultsCPS correlated with mode derived from Ktrans (r = 0.40, p = .04). Also CPS correlated with P90 derived from Kep (r = 0.40, p = .04). ICS correlated with the maximum derived from Kep (r = 0.41, p = .03) and entropy derived from Kep (r = 0.43, p = .02). There were no associations between DCE MRI parameters and TPS.ConclusionKtrans and Kep related histogram analysis parameters derived from DCE MRI correlated moderately with PD-L 1 expression of immune cells in HNSCC.