Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver

PurposeTo investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions.MethodsTwenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n = 20) or Gd-DOTA (n = 5) concluded with IVIM-DWI. Diffusion (D_slow), microperfusion (D_fast), its fraction (f_fast), wash-in-rate (R_early) and late-enhancement-rate (R_late) of Gd-EOB-DTPA were calculated voxel-wise for the liver. Parenchyma and lesions were segmented. Pre-contrast IVIM was compared 1) between low, medium and high R_early for parenchyma 2) to post-contrast IVIM substantiated with simulations 3) between low and high R_late per lesion type.ResultsD_fast and f_fast increased (P < 0.001) with 25.6% and 33.8% between low and high R_early of Gd-EOB-DTPA. D_slow decreased (− 15.0%; P < 0.001) with increasing R_early. Gd-DOTA demonstrated similar observations. f_fast (+ 10%; P < 0.001) and D_fast (+ 6.6%; P < 0.001) increased after Gd-EOB-DTPA, while decreasing after Gd-DOTA (− 4.2% and − 5.7%, P < 0.001) and were confirmed by simulations. For focal nodular hyperplasia lesions (n = 5) D_fast and f_fast increased (P < 0.001) with increasing R_late, whereas for hepatocellular carcinoma (n = 4) and adenoma (n = 7) no differences were found.ConclusionMicroperfusion measured by IVIM reflects perfusion in a way resembling CE-MRI. Also IVIM separated intra- and extracellular MR contrast media. This underlines the potential of IVIM in quantitative liver imaging.     

Intravoxel incoherent motion diffusion-weighted imaging as an adjunct to dynamic contrast-enhanced MRI to improve accuracy of the differential diagnosis of benign and malignant breast lesions

PurposeTo investigate the value of use of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) as an adjunct to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish benign from malignant breast lesions.Materials and methodsRetrospective analysis of data pertaining to 117 patients with breast lesions who underwent DCE-MRI and IVIM-DWI examination with 3.0 T MRI was conducted. A total of 128 lesions were pathologically confirmed (47 benign and 81 malignant). Between-group differences in DCE-MRI parameters (Morphology, enhancement pattern, maximum slope of increase (MSI) and time–signal curve (TIC) type) and IVIM-DWI parameters (f value, D value and D* value) were assessed. Multivariate logistic regression was performed to identify variables that distinguished benign from malignant breast lesions. The diagnostic performance of DCE-MRI and DCE-MRI plus IVIM-DWI, to distinguish benign from malignant breast lesions, was evaluated using pathology results as the gold standard.ResultsLesion morphology, MSI, and TIC type (P < 0.05), but not the enhancement pattern (P > 0.05), were significantly different between the benign and malignant groups. The f (8.53 ± 2.14) and D* (7.64 ± 2.07) values in the malignant group were significantly higher than those in the benign group (7.68 ± 1.97 and 6.83 ± 2.13, respectively), while the D value (0.99 ± 0.22) was significantly lower than that (1.34 ± 0.17) in the benign group (P < 0.05 for all). On logistic regression analysis, the sensitivity, specificity and accuracy of DCE-MRI were 90.1%, 70.2% and 82.8% respectively; the corresponding figures for the combination of IVIM-DWI and DCE-MRI were 88.8%, 85.1%, and 87.5%respectively.ConclusionIVIM-DWI method as an adjunct to DCE-MRI can improve the specificity and accuracy in differential diagnosis of benign and malignant lesions of breast.     

Dynamic contrast-enhanced MRI of gastric cancer: Correlations of the pharmacokinetic parameters with histological type,Lauren classification,and angiogenesis

PurposeTo compare the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in gastric cancers of different histological type and Lauren classification, and to investigate whether DCE-MRI parameters correlate with vascular endothelial growth factor (VEGF) expression levels in gastric cancer.MethodsIncluded were 32 patients with gastric cancer who underwent DCE-MRI of the upper abdomen before tumor resection. DCE-MRI parameters including the volume transfer coefficient (K^trans), reverse reflux rate constant (K_ep), and extracellular extravascular volume fraction (V_e) were calculated from the tumor region. Post-operative specimens were used for determination of histological differentiation (i.e., non-mucinous, mucinous, or signet-ring-cell adenocarcinoma) as well as Lauren classification (intestinal type or diffuse type). VEGF expression was examined for assessing angiogenesis. DCE-MRI parameters with different histological type and Lauren classification were compared using independent samples t-test and analysis of variance, respectively. Correlations between DCE-MRI parameters and VEGF expression grades were tested using Spearman correlation analysis.ResultsAmong gastric adenocarcinomas of three different histological types, mucinous adenocarcinomas showed a higher V_e and lower K^trans than the others (P < 0.01). Between the two Lauren classifications, the diffuse type showed a higher V_e than the intestinal type (P < 0.001). The mean K^trans showed a significantly positive correlation with VEGF (r = 0.762, P < 0.001).ConclusionDCE-MRI permits noninvasive prediction of tumor histological type and Lauren classification and estimation of tumor angiogenesis in gastric cancer. DCE-MRI parameters can be used as imaging biomarkers to predict the biologic aggressiveness of a tumor as well as patient prognosis.     

Perfusion of the uterine junctional zone in nulliparous and primiparous women assessed by DCE-MRI,as a function of menstrual cycle and hormonal contraception

PurposeTo evaluate the perfusion parameters of inner and outer myometrium in healthy nulliparous and primiparous women who are and who are not currently using hormonal contraceptives by means of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Material and methodsWe performed pelvic 1.5 T DCE-MRI on 98 women: 18 nulliparous non-users, 30 nulliparous users, 12 primiparous non-users and 38 primiparous users of hormonal contraception (mean age respectively 26.4, 25.8, 30.23 and 28.18 years). The nulliparous non-users underwent DCE-MRI investigations during their follicular, ovulatory and luteal phase. Perfusion parameters (iAUC/volume, Ktrans, Kep and Ve) were assessed in the anterior and posterior junctional zone (JZ), outer myometrium and cervix.ResultsIn nulliparous non-users, the mean Ktrans and iAUC/volume showed a decrease from follicular to luteal phase (0.82 vs 0.55 min^− 1 for Ktrans, p = 0/027 and 1.28 vs 0.68 for iAUC/volume, p < 0.001). The anterior JZ demonstrated lower Ktrans (p = 0.050) and higher Kep (p = 0.012), in nulliparous non-users, lower Ktrans in nulliparous users (p < 0.001) and lower Ve in primiparous users (p = 0.012) than the anterior outer myometrium. Ktrans at the anterior and posterior JZ wall in nulliparous users was lower than in non-users (p = 0.001 and p = 0.013) and Ve at the anterior JZ wall in primiparous users was lower than in non-users (p = 0.044).ConclusionThis study provides data on normal perfusion parameters of inner and outer myometrium, which may be potentially useful in assisted reproductive therapy.     

Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes

IntroductionTo assess if parameters in intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) can be used to evaluate early renal fibrosis in a mouse model of diabetic nephropathy.Materials & methodsIn a population of 38 male CD1 mice (8 weeks old, 20–30 g), streptozotocin induced diabetes was created in 20 mice via a single intraperitoneal injection of streptozotocin at 150 mg/kg, while 18 mice served as control group. IVIM parameters were acquired at 0, 12 and 24 weeks after injection of streptozotocin using a range of b values from 0 to 1200 s/mm². DTI parameters were obtained using 12 diffusion directions and lower b values of 0, 100 and 400 s/mm². DTI and IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of the right kidney was performed in all mice. Results were analyzed using an unpaired t-test with P < 0.05 considered statistically significant.ResultsRenal cortex fractional anisotropy (FA) was significantly lower in the diabetes group at week 12 as compared with the control group. Renal cortex apparent diffusion coefficient and tissue diffusivity were significantly higher in the diabetes group at week 12 compared with the control group at 12 weeks. Blood flow was significantly decreased at the renal medulla at 24 weeks. Histopathological analysis confirmed fibrosis in the diabetes group at 24 weeks.ConclusionFA is significantly reduced in diabetic nephropathy. FA might serve a potential role in the detection and therapy monitoring of early diabetic nephropathy.     

Effects of arterial input function selection on kinetic parameters in brain dynamic contrast-enhanced MRI

PurposeKinetic parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) were suggested as a possible instrument for multi-parametric lesion characterization, but have not found their way into clinical practice yet due to inconsistent results. The quantification is heavily influenced by the definition of an appropriate arterial input functions (AIF). Regarding brain tumor DCE-MRI, there are currently several co-existing methods to determine the AIF frequently including different brain vessels as sources. This study quantitatively and qualitatively analyzes the impact of AIF source selection on kinetic parameters derived from commonly selected AIF source vessels compared to a population-based AIF model.Material and methods74 patients with brain lesions underwent 3D DCE-MRI. Kinetic parameters [transfer constants of contrast agent efflux and reflux K^trans and k_ep and, their ratio, v_e, that is used to measure extravascular-extracellular volume fraction and plasma volume fraction v_p] were determined using extended Tofts model in 821 ROI from 4 AIF sources [the internal carotid artery (ICA), the closest artery to the lesion, the superior sagittal sinus (SSS), the population-based Parker model]. The effect of AIF source alteration on kinetic parameters was evaluated by tissue type selective intra-class correlation (ICC) and capacity to differentiate gliomas by WHO grade [area under the curve analysis (AUC)].ResultsArterial AIF more often led to implausible v_e > 100% values (p < 0.0001). AIF source alteration rendered different absolute kinetic parameters (p < 0.0001), except for k_ep. ICC between kinetic parameters of different AIF sources and tissues were variable (0.08–0.87) and only consistent > 0.5 between arterial AIF derived kinetic parameters. Differentiation between WHO III and II glioma was exclusively possible with v_p derived from an AIF in the SSS (p = 0.03; AUC 0.74).ConclusionThe AIF source has a significant impact on absolute kinetic parameters in DCE-MRI, which limits the comparability of kinetic parameters derived from different AIF sources. The effect is also tissue-dependent. The SSS appears to be the best choice for AIF source vessel selection in brain tumor DCE-MRI as it exclusively allowed for WHO grades II/III and III/IV glioma distinction (by v_p) and showed the least number of implausible v_e values.     

Selective microvascular muscle perfusion imaging in the shoulder with intravoxel incoherent motion (IVIM)

The evaluation of local muscle recruitment during a specific movement can be done indirectly by measuring changes in local blood flow. Intravoxel incoherent motion perfusion imaging exploits some properties of the magnetic resonance to measure locally microvascular perfusion, and seems ideally suited for this task. We studied the selectivity of the increase in intravoxel incoherent motion blood flow related parameter fD* in the muscles of 24 shoulders after two physical exam maneuvers, Jobe and Lift-off test (test order reversed in half of the volunteers) each held 2 min against resistance. After a lift-off, IVIM blood flow-related fD* was increased in the subscapularis (in 10⁻³ mm² s⁻¹, 3.24 ± 0.86 vs. rest 1.37 ± 0.58, p < 0.001) and the posterior bundle of deltoid (2.62 ± 1.34 vs. rest 0.77 ± 0.32, p < 0.001). Those increases were selective when compared with other rotator cuff muscles and deltoid bundles respectively. After a Jobe test, increase in fD* was scattered within the rotator cuff muscles, but was selective for the lateral deltoid compared to the other deltoid bundles (anterior, p < 0.001; posterior, p < 0.05). Those results were similar when the testing order was reversed. In conclusion, this study demonstrated a selective increase in local microvascular perfusion after specific muscle testing of the shoulder muscles with IVIM. This technique has the potential to non-invasively characterize perfusion-related musculoskeletal physiological as well as pathological processes.     

Differentiation of myeloma and metastatic cancer in the spine using dynamic contrast-enhanced MRI

Spinal myeloma and metastatic cancer cause similar symptoms and show similar imaging presentations, thus making them difficult to differentiate. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to differentiate between 9 myelomas and 22 metastatic cancers that present as focal lesions in the spine. The characteristic DCE parameters, including the peak signal enhancement percentage (SE%), the steepest wash-in SE% during the ascending phase and the wash-out SE%, were calculated by normalizing to the precontrast signal intensity. The two-compartmental pharmacokinetic model was used to obtain K^trans and k_ep. All nine myelomas showed the wash-out DCE pattern. Of the 22 metastatic cancers, 12 showed wash-out, 7 showed plateau, and 3 showed persistent enhancing patterns. The fraction of cases that showed the wash-out pattern was significantly higher in the myeloma group than the metastatic cancer group (9/9 = 100% vs. 12/22 = 55%, P = .03). Compared to the metastatic cancer group, the myeloma group had a higher peak SE% (226% ± 72% vs. 165% ± 60%, P = .044), a higher steepest wash-in SE% (169% ± 51% vs. 111% ± 41%, P = .01), a higher K^trans (0.114 ± 0.036 vs. 0.077 ± 0.028 1/min, P = .016) and a higher k_ep (0.88 ± 0.26 vs. 0.49 ± 0.23 1/min, P = .002). The receiver operating characteristic analysis to differentiate between these two groups showed that the area under the curve was 0.798 for K^trans, 0.864 for k_ep and 0.919 for combined K^trans and k_ep. These results show that DCE-MRI may provide additional information for making differential diagnosis to aid in choosing the optimal subsequent procedures or treatments for spinal lesions.     

Parotid perfusion in nasopharyngeal carcinoma patients in early-to-intermediate stage after low-dose intensity-modulated radiotherapy: Evaluated by fat-saturated dynamic contrast-enhanced magnetic resonance imaging

PurposeTo investigate parotid perfusion in early-to-intermediate stage after parotid-sparing radiation dose using fat-saturated DCE-MRI, and to verify whether the perfusion alteration was related to radiation dose and the PSV.Methods and MaterialsThirty-two parotid glands from 16 consecutive patients with pathologically proven nasopharyngeal carcinoma treated by IMRT were examined. The parotid glands received a radiation dose of 28.9 ± 3.9 Gy with a PSV of 43.1% ± 13.9%. Perfusion parameters were calculated using time-shifted Brix model from fat-saturated DCE-MRI data before (pre-RT) and in early-to-intermediate stage after (post-RT) IMRT. Paired t-test was used to evaluate perfusion changes, while Pearson's correlation test was used to examine perfusion dependency on radiation dose and PSV. For multiple comparisons Bonferroni correction was applied.ResultsSuccessful fat saturation was achieved in 29 of 32 parotid glands. Compared with pre-RT, the post-RT parotid glands showed significantly higher A, peak enhancement, and wash-in slope, plus a lower K_el, suggesting a mixed effect of increased vascular permeability and acinar loss. Linear regression showed that peak enhancement was positively associated with radiation dose in post-RT parotid glands. K_el and slope were negatively associated with PSV, while time-to-peak was positively associated with PSV significantly.ConclusionsOur results suggest that time-shifted Brix model is feasible for quantifying parotid perfusion using DCE-MRI. The perfusion alterations in early-to-intermediate stage after IMRT might be related to a mixed effect of increased vascular permeability and acinar loss with dose and PSV dependencies.     

Early responses assessment of neoadjuvant chemotherapy in nasopharyngeal carcinoma by serial dynamic contrast-enhanced MR imaging

PurposeTo evaluate the feasibility of utilizing serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) prospectively for early prediction of neoadjuvant chemotherapy (NAC) response in nasopharyngeal carcinoma (NPC) patients.Materials and methodsSixty-three advanced NPC patients were recruited and received three DCE-MRI exams before treatment (Pre-Tx), 3 days (Day3-Tx) and 20 days (Day20-Tx) after initiation of chemotherapy (one NAC cycle). Early response to NAC was determined based on the third MRI scan and classified partial response (PR) as responders and stable disease (SD) as non-responders. After intensity-modulated radiotherapy (IMRT), complete response (CR) patients were classified as responders. The kinetic parameters (K^trans, K_ep, v_e, and v_p) derived from extended Tofts' model analysis and their corresponding changes ΔMetrics_(0–X) (X = 3 or 20 days) were compared between the responders and non-responders using the Student's T-test or Mann–Whitney U test.ResultsCompared to the SD group, the PR group after one NAC cycle presented significantly higher mean K^trans values at baseline (P = 0.011) and larger ΔK^trans_(0–3) and ΔK_ep(0–3) values (P = 0.003 and 0.031). For the above parameters, we gained acceptable sensitivity (range: 66.8–75.0%) and specificity (range: 60.0–66.7%) to distinguish the non-responders from the responders and their corresponding diagnosis efficacy (range: 0.703–0.767). The PR group patients after one NAC cycle showed persistent inhibition of tumor perfusion by NAC as explored by DCE-MRI parameters comparing to the SD group (P < 0.05) and presented a higher cure ratio after IMRT than those who did not (83.3% vs. 73.8%).ConclusionsThis primarily DCE-MRI based study showed that the early changes of the kinetic parameters during therapy were potential imaging markers to predicting response right after one NAC cycle for NPC patients.     

Flow versus permeability weighting in estimating the forward volumetric transfer constant (Ktrans) obtained by DCE-MRI with contrast agents of differing molecular sizes

PurposeTo quantify the differential plasma flow- (F_p-) and permeability surface area product per unit mass of tissue- (PS-) weighting in forward volumetric transfer constant (K^trans) estimates by using a low molecular (Gd-DTPA) versus high molecular (Gadomer) weight contrast agent in dynamic contrast enhanced (DCE) MRI.Materials and methodsDCE MRI was performed using a 7T animal scanner in 14 C57BL/6J mice syngeneic for TRAMP tumors, by administering Gd-DTPA (0.9 kD) in eight mice and Gadomer (35 kD) in the remainder. The acquisition time was 10 min with a sampling rate of one image every 2 s. Pharmacokinetic modeling was performed to obtain K^trans by using Extended Tofts model (ETM). In addition, the adiabatic approximation to the tissue homogeneity (AATH) model was employed to obtain the relative contributions of F_p and PS.ResultsThe K^trans values derived from DCE-MRI with Gd-DTPA showed significant correlations with both PS (r² = 0.64, p = 0.009) and F_p (r² = 0.57, p = 0.016), whereas those with Gadomer were found only significantly correlated with PS (r² = 0.96, p = 0.0003) but not with F_p (r² = 0.34, p = 0.111). A voxel-based analysis showed that K^trans approximated PS (< 30% difference) in 78.3% of perfused tumor volume for Gadomer, but only 37.3% for Gd-DTPA.ConclusionsThe differential contributions of F_p and PS in estimating K^trans values vary with the molecular weight of the contrast agent used. The macromolecular contrast agent resulted in K^trans values that were much less dependent on flow. These findings support the use of macromolecular contrast agents for estimating tumor vessel permeability with DCE-MRI.     

Quantitative Dixon MRI sequences to relate muscle atrophy and fatty degeneration with range of motion and muscle force in brachial plexus injury

BackgroundAssessment of muscle atrophy and fatty degeneration in brachial plexus injury (BPI) could yield valuable insight into pathophysiology and could be used to predict clinical outcome. The objective of this study was to quantify and relate fat percentage and cross-sectional area (CSA) of the biceps to range of motion and muscle force of traumatic brachial plexus injury (BPI) patients.MethodsT1-weighted TSE sequence and three-point Dixon images of the affected and non-affected biceps brachii were acquired on a 3 Tesla magnetic resonance scanner to determine the fat percentage, total and contractile CSA of 20 adult BPI patients. Regions of interest were drawn by two independent investigators to determine the inter-observer reliability. Paired Students' t-test and multivariate analysis were used to relate fat percentage, total and contractile CSA to active flexion and biceps muscle force.ResultsThe mean fat percentage 12 ± 5.1% of affected biceps was higher than 6 ± 1.0% of the non-affected biceps (p < 0.001). The mean contractile CSA 8.1 ± 5.1 cm² of the affected biceps was lower than 19.4 ± 4.9 cm² of the non-affected biceps (p < 0.001). The inter-observer reliability was excellent (ICC 0.82 to 0.96). The contractile CSA contributed most to the reduction in active flexion and muscle force.ConclusionQuantitative measurement of fat percentage, total and contractile CSA using three-point Dixon sequences provides an excellent reliability and relates with active flexion and muscle force in BPI.     

Free breathing whole-heart 3D CINE MRI with self-gated Cartesian trajectory

PurposeTo present a method that uses a novel free-running self-gated acquisition to achieve isotropic resolution in whole heart 3D Cartesian cardiac CINE MRI.Material and methods3D cardiac CINE MRI using navigator gating results in long acquisition times. Recently, several frameworks based on self-gated non-Cartesian trajectories have been proposed to accelerate this acquisition. However, non-Cartesian reconstructions are computationally expensive due to gridding, particularly in 3D. In this work, we propose a novel highly efficient self-gated Cartesian approach for 3D cardiac CINE MRI. Acquisition is performed using CArtesian trajectory with Spiral PRofile ordering and Tiny golden angle step for eddy current reduction (so called here CASPR-Tiger). Data is acquired continuously under free breathing (retrospective ECG gating, no preparation pulses interruption) for 4–5 min and 4D whole-heart volumes (3D + cardiac phases) with isotropic spatial resolution are reconstructed from all available data using a soft gating technique combined with temporal total variation (TV) constrained iterative SENSE reconstruction.ResultsFor data acquired on eight healthy subjects and three patients, the reconstructed images using the proposed method had good contrast and spatio-temporal variations, correctly recovering diastolic and systolic cardiac phases. Non-significant differences (P > 0.05) were observed in cardiac functional measurements obtained with proposed 3D approach and gold standard 2D multi-slice breath-hold acquisition.ConclusionThe proposed approach enables isotropic 3D whole heart Cartesian cardiac CINE MRI in 4 to 5 min free breathing acquisition.     

Advanced diffusion models in head and neck squamous cell carcinoma patients: Goodness of fit,relationships among diffusion parameters and comparison with dynamic contrast-enhanced perfusion

PurposeWe assessed advanced fitting models of diffusion weighted imaging (DWI) in head/neck squamous cell carcinoma (HNSCC) patients to determine the best goodness of fit and correlations among diffusion parameters. We compared these results with those of dynamic contrast-enhanced (DCE) perfusion parameters.Materials and methodsWe retrospectively evaluated 32 HNSCC patients (12 sinonasal, 20 pharynx/oral cavity). The DWI acquisition used single-shot spin-echo echo-planar imaging (EPI) with 12 b-values (0 − 2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, and tri-exponential models, stretched exponential model (SEM) and diffusion kurtosis imaging (DKI) models. We compared each model's goodness of fit using the residual sum of squares (RSS), Akaike Information Criterion (AIC) and Bayesian information criterion (BIC) value. We determined the correlation between each pair of DWI parameters and between each DWI parameter and DCE perfusion parameter.ResultsThe tri-exponential fit's RSS, AIC and BIC values were significantly smaller than those for bi-exponential fit. The RSS, AIC and BIC values of the SEM fit and DKI fit were significantly smaller than mono-exponential model. Significant correlations were observed in 30 pairs (sinonasal cavity) and 31 (sinonasal cavity group) among 91 DWI parameter combinations. Significant correlations were also observed in nine pairs (both sinonasal cavity and pharynx/oral cavity group) among 64 DWI/DCE perfusion parameter pairs, in particular, high positive correlations between the tri-exponential model's intermediate diffusion fraction (f₂) and the volume of the extracellular extravascular space per unit volume of tissue (v_e) were observed in both patient groups.ConclusionWe identified several correlations between DWI parameters by advanced fitting models and correlations between DWI and DCE parameters. These will help determine HNSCC patients' detailed tissue structures.     

Enhanced Laws textures: A potential MRI surrogate marker of hepatic fibrosis in a murine model

PurposeTo compare enhanced Laws textures derived from parametric proton density (PD) maps to other MRI surrogate markers (T₂, PD, apparent diffusion coefficient (ADC)) in assessing degrees of liver fibrosis in an ex vivo murine model of hepatic fibrosis imaged using 11.7T MRI.MethodsThis animal study was IACUC approved. Fourteen male, C57BL/6 mice were divided into control and experimental groups. The latter were fed a 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T scanner, from which the parametric PD, T₂, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. A sequential enhanced Laws texture analysis was applied to the PD maps: automated dual-clustering algorithm, optimal thresholding algorithm, global grayscale correction, and Laws texture features extraction. Degrees of fibrosis were independently assessed by digital image analysis (a.k.a. %Area Fibrosis). Scatterplot graphs comparing enhanced Laws texture features, T₂, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated.ResultsHepatic fibrosis and the enhanced Laws texture features were strongly correlated with higher %Area Fibrosis associated with higher Laws textures (r = 0.89). Without the proposed enhancements, only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture features (r = 0.70). Correlation also existed between %Area Fibrosis and ADC (r = 0.86), PD (r = 0.65), and T₂ (r = 0.66).ConclusionsHigher degrees of hepatic fibrosis are associated with increased Laws textures. The proposed enhancements could improve the accuracy of Laws texture features significantly.     

Effect of ultrasound processing on anthocyanins and color of red grape juice

Grape juice samples were sonicated with processing variables of amplitude level (24.4–61.0 μm) and treatment time (0–10 min) at a constant frequency of 20 kHz and pulse durations of 5 s on and 5 s off. A full factorial experimental design with regression modeling was employed to investigate the main effects of amplitude level and treatment time on anthocyanins and color parameters. Significant effects of sonication on major anthocyanins cyanidin-3-O-glucosides (CA), malvanidin-3-O-glucosides (MA) and delphinidin-3-O-glucosides (DA), color values (L*, a*, b*) and color index (CI) were observed. Prediction models were found to be significant (p < 0.05) with low standard errors and high coefficients of determination (R²). Model predictions for critical quality parameters of anthocyanins (CA; MA; DA), color values (L*, a*, b*), TCD and CI inactivation were closely correlated to the experimental results obtained. Significant retention of anthocyanin content in grape juice was observed for CA (97.5 %); MA (48.2 %) and DA (80.9%) during sonication. CI and other color combinations (L*a*b*, L*a*/b* and L*b*/a*) were found to be strongly correlated with anthocyanin content. This study shows that sonication could be employed for as a preservation technique for fruit juice processing where anthocyanin retention is desired.     

Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI

PurposeAim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI).Material and methodsSixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with > 10 years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC).ResultThe diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity = 1.00, specificity = 0.96, p < 0.001) compared to the non-expert user (sensitivity = 0.65, specificity = 0.78, p < 0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity = 0.89, specificity = 0.87, p = 0.001) and rCBV_GM (sensitivity = 0.81, specificity = 0.78, p = 0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa = 0.96, agreement 98.33%, p < 0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa = 0.76,p < 0.001) with histopathological grading.ConclusionIt was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach.     

MRI protocol optimization for quantitative DCE-MRI of the spine

PurposeIn this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM).Materials and methodsIn 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2 ml/kg body weight) was injected intravenously at a speed of 3 ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T₁ map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model.ResultsSagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T₂* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient–echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5 s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5 mm and two acquisitions.ConclusionThe proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.     

Modeling of electrical and optical characteristics of near room-temperature CdS/ZnSe based NIR photodetectors

Results of modeled photodetector characteristics in (CdS/ZnSe)/BeTe multi-well diode with p–i–n polarity are reported. The dark current density (J–V) characteristics, the temperature dependence of zero-bias resistance area product (R₀A), the dynamic resistance as well as bias dependent dynamic resistance (R_d) and have been analyzed to investigate the mechanisms limiting the electrical performance of the modeled photodetectors. The quantum efficiency, the responsivity and the detectivity have been also studied as function of the operating wavelength. The suitability of the modeled photodetector is demonstrated by its feasibility of achieving good device performance near room temperature operating at 1.55 μm wavelength required for photodetection in optical communication. Quantum efficiency of ∼95%, responsivity ∼0.6 A/W and D^* ∼ 5.7 × 10¹⁰ cm Hz^1/2/W have been achieved at 300 K in X BeTe conduction band minimum.     

Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles

Sonoporation—transient plasma membrane perforation elicited by the interaction of ultrasound waves with microbubbles—has shown great potential for drug delivery and gene therapy. However, the heterogeneity of sonoporation introduces complexities and challenges in the realization of controllable and predictable drug delivery. The aim of this investigation was to understand how non-acoustic parameters (bubble related and bubble-cell interaction parameters) affect sonoporation. Using a customized ultrasound-exposure and fluorescence-imaging platform, we observed sonoporation dynamics at the single-cell level and quantified exogenous molecular uptake levels to characterize the degree of sonoporation. Sonovue microbubbles were introduced to passively regulate microbubble-to-cell distance and number, and bubble size. 1 MHz ultrasound with 10-cycle pulse duration and 0.6 MPa peak negative pressure were applied to trigger the inertial collapse of microbubbles. Our data revealed the impact of non-acoustic parameters on the heterogeneity of sonoporation. (i) The localized collapse of relatively small bubbles (diameter, D < 5.5 μm) led to predictable sonoporation, the degree of which depended on the bubble-to-cell distance (d). No sonoporation was observed when d/D > 1, whereas reversible sonoporation occurred when d/D < 1. (ii) Large bubbles (D > 5.5 μm) exhibited translational movement over large distances, resulting in unpredictable sonoporation. Translation towards the cell surface led to variable reversible sonoporation or irreversible sonoporation, and translation away from the cell caused either no or reversible sonoporation. (iii) The number of bubbles correlated positively with the degree of sonoporation when D < 5.5 μm and d/D < 1. Localized collapse of two to three bubbles mainly resulted in reversible sonoporation, whereas irreversible sonoporation was more likely following the collapse of four or more bubbles. These findings offer useful insight into the relationship between non-acoustic parameters and the degree of sonoporation.