Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Pediatric Application of Dynamic Contrast-Enhanced MR Imaging (DCE-MR) in the Management of Extra-Cranial Tumor: Experience in Routine Clinical Practice

Background: Dynamic contrast-enhanced MR imaging (DCE-MR) is becoming a widely accepted complementary method for diagnosing breast cancer and other cancers in adults. It is useful to predict tumor response to anticancer therapy and monitor the tumor response to the therapy. This form of imaging techniques has not been adequately explored in pediatric oncology patients. Objective: To determine the potential role of dynamic contrast-enhanced MR imaging (DCE-MR) in the diagnosis and treatment response monitoring of childhood and young adult extra-cranial tumors in routine clinical setting. Methods: Children with suspected extra-cranial solid tumors, including newly diagnosed or follow-up cases of confirmed tumors, were recruited. DCE-MR was performed with intravenous injection of 0.1 mmol/kg contrast. The enhancement time curves were plotted and the enhancement patterns were categorized into type 1, 2 and 3 curves. Enhancement curve patterns and maximal enhancement intensity were compared with types of tumor in newly diagnosed cases. The preoperative percentiles of inactive area on the colour map were compared with the necrotic areas on histologic sections of the resected specimens in follow-up cases. Pearson Chi-square test and Unpaired two-sample t-test were used for statistical analysis. Results: There were 36 patients, involving 28 malignant and 8 benign cases. There were 14 type 3 curves, (all of them were malignant tumors), 6 type 2 curves and 16 type 1 curves. All the benign cases (n = 8) demonstrated type 1 curve (accuracy & negative predictive value = 100%). All the malignant cases after treatment showed type 2 or 1 curve. For those cases with operation done afterwards, the extent of tumor necrosis was correlated closely with pathology findings (accuracy = 93.3%). Conclusion: Type 1 curve was a good predictor of benign lesion. DEC-MR may have a role to play in the monitoring of the progress of treatment and extent of tumor necrosis.

Feasibility and value of quantitative dynamic contrast enhancement MR imaging in the evaluation of sinonasal tumors

Background Quantitative dynamic contrast enhancement MR imaging （DCE-MRI）,used to measure properties of tissue microvasculature and tumor angiogenesis,is a promising method for distinguishing benign and malignant tumors and characterizing tumor response to antiangiogenic treatment.The aim of this study was to assess the feasibility of quantitative parameters derived from clinically used DCE-MRI for distinguishing benign from malignant tumors in the sinonasal area,which may be potentially useful for prediction and monitoring of treatment response to chemoradiotherapy of sinonasal tumors.Methods One hundred and forty-three patients with sinonasal tumors,including 78 malignant tumors and 65 benign tumors and tumor-like lesions,underwent clinically used DCE-MRI.Parametric maps were obtained for quantitative parameters including Ktrans,kep and ve.Two radiologists reviewed these maps and measured Ktrans,kep and ve in the tumor tissue.Data were analyzed using independent T-test or Mann-Whitney U test analysis and receiver operating characteristic curves.Results Ktrans,kep and ve showed significant differences between benign and malignant tumors in the sinonasal area （P=-0.000 1）.The accuracy of Ktrans,kep and ve in differentiation between benign and malignant sinonasal tumors were 72.0％,76.2％ and 67.1％,respectively.There were significant differences in kep and ve between malignant epithelial sinonasal tumors and lymphomas （P ＜0.05）.Using a ve value of 0.213 as the threshold value differentiated malignant epithelial tumors from lymphomas with an accuracy of 78.3％,sensitivity of 88.2％,specificity of 68.0％,positive predictive value of 66.7％,and negative predictive value of 90.9％.However,no significant difference in Ktrans and kep was found between malignant epithelial and non-epithelial tumors in the sinonasal area （P ＞0.05）.Conclusions It is feasible that quantitative parameters of tumors can be derived from clinically used DCE-MRI in the sinonasal region.Preliminary findings suggest an increased value for quantitative DCE-MRI in the evaluation of sinonasal tumors in clinical practice.

Classification of breast lesions based on a dual S-shaped logistic model in dynamic contrast enhanced magnetic resonance imaging

This study proposes a novel dual S-shaped logistic model for automatically quantifying the characteristic kinetic curves of breast lesions and for distinguishing malignant from benign breast tumors on dynamic contrast enhanced (DCE) magnetic resonance (MR) images.D(,) is the diagnostic parameter derived from the logistic model.Significant differences were found in D(,) between the malignant benign groups.Fisher's Linear Discriminant analysis correctly classified more than 90% of the benign and malignant kinetic breast data using the derived diagnostic parameter (D(,)).Receiver operating characteristic curve analysis of the derived diagnostic parameter (D(,)) indicated high sensitivity and specificity to differentiate malignancy from benignancy.The dual S-shaped logistic model was effectively used to fit the kinetic curves of breast lesions in DCE-MR.Separation between benign and malignant breast lesions was achieved with sufficient accuracy by using the derived diagnostic parameter D(,) as the lesion's feature.The proposed method therefore has the potential for computer-aided diagnosis in breast tumors.

Tumor infiltration of bone marrow in patients with hemato-logical malignancies: dynamic contrast-enhanced magnetic resonance imaging

Background Conventional magnetic resonance （MR） scanning techniques can identify bone marrow （BM） containing mostly fat cells. But they are not able to differentiate BM tumor infiltration, BM fibrosis and normal red BM. This is particularly problematic in assessment of recurrent or refractory hematological malignancy. This pilot study used dynamic contrast-enhanced MR imaging （DCE-MRI） to evaluate the bone marrow status and to determine whether several calculated parameters derived from the DCE-MRI correlate with histological characteristics of marrow, especially with the tumor fraction （TF）. Methods DCE-MRI scans were performed in 25 patients with proven or known hematological malignancy who were about to undergo bone marrow biopsy of the posterior iliac crest. The location chosen for biopsy was examined with MRI approximately one hour prior to the biopsy. Time-signal intensity curves （TIC） were generated from the region of the iliac crest corresponding to the planned biopsy site. Enhancement parameters were calculated, including peak enhancement ratio （PER）, maximum enhancement slope （S1opemax）, time to peak （TTP） and mean time （MT）. The biopsy specimen was reported synoptically, with relevant reported parameters including cellularity and tumor fraction （TF）. Results PER values were significantly higher for the bone marrow tumor infiltration group than for the normal bone marrow group （P〈0.05）. A significant positive correlation was found between PER and TF as well as S1opemax and TF. A negative correlation was found between TTP and TF. There was no significant difference in the mean TTP and MT values between the BM tumor infiltration group and the normal bone marrow group. Conclusions The presence of diffuse bone marrow infiltration in patients with haematological malignancies could be verified using DCE-MRI.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Differential study of DCE-MRI parameters in spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis

Objective： In the present study, spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis werequantitatively analyzed using dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） to assess thevalue of DCE-MRI in the differential diagnosis of these diseases.Methods： Patients with brucellar spondylitis, spinal tuberculosis or a spinal metastatic tumor （30 cases of each）received conventional MRI and DCE-MRI examination. The volume transfer constant （Ktrans）, rate constant （Kep）,extravascular extracellular volume fraction （Ve） and plasma volume fraction （Vp） of the diseased vertebral bodieswere measured on the perfusion parameter map, and the differences in these parameters between the patients werecompared.Results： For pathological vertebrae in cases of spinal metastatic tumor, brucellar spondylitis and spinaltuberculosis, respectively, the Ktrans values （median ＋ quartile pitch） were 0.989±0.014, 0.720±0.011 and0.317±0.005 min-1; the Kep values were 2.898±0.055, 1.327±0.017 and 0.748±0.006 min-1; the Ve values were0.339±0.008, 0.542±0.013 and 0.428±0.018; the Vp values were 0.048±0.008, 0.035±0.004 and 0.028±0.009; thecorresponding H values were 50.25 （for Ktrans）, 52.47 （for Kep）, 48.33 （for Ve） and 46.56 （for Vp）, and all differenceswere statistically significant （two-sided P〈0.05）.Conclusions： The quantitative analysis of DCE-MRI has a certain value in the differential diagnosis of spinalmetastatic tumor, brucellar spondylitis and spinal tuberculosis.

Intra-individual comparison of different gadolinium-based contrast agents in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging

This experiment aimed to compare the ionic （Gadodiamide, Gd-DTPA-BMA） and non-ionic （Gadopentetate dimeglumine, Gd-DTPA） gadolinium-based contrast agents （GBCA） in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. A C6 glioma model was established in 12 Wistar rats, and magnetic resonance （MR） scans were performed six days after tumor implantation. Imaging was performed using a 3.0-T MR scanner with a 7-inch handmade circular coil. Pre-contrast T1 mapping and dynamic contrast-enhanced T1WI after a bolus injection （0.2 mL s 1） of GBCA at 0.4 mmol kg-1 were performed. Each rat received two DCE-MRI scans, 24 h apart. The first and second scans were performed using Gd-DTPA-BMA and Gd-DTPA, respectively. Image data were processed using the Patlak model. Both Kns and Vp maps were generated. Tumors were manually segmented on all 3D K and Vp maps. Pixel counts and mean values were recorded for use in a paired t-test. Three radiologists independently performed the tumor segmentation and value calculation. The agreements from different observers were subjective to the intra-class correlation coefficient （ICC）. Readers demonstrated that the pixel counts of tumors in/Crns maps were higher with Gd-DTPA-BMA than with Gd-DTPA （P〈0.001, all readers）. Although the/（r,,s values were higher with Gd-DTPA-BMA than with Gd-DTPA, there was no statistical significance （P〉0.05, all readers）. The pixel counts of tumors in Vp maps, as well as Vp values, showed no obvious difference between the two agents （P〉0.05, all readers）. Excellent interobserver measurement reproducibility and reliability were demonstrated in the ICC tests. The Gd-DTPA-BMA contrast agent had significantly higher pixel counts of glioma in the maps, and an increased tendency for average/Us values, indicating that DCE-MRI with Gd-DTPA-BMA may be more suitable and sensitive for the evaluation of glioma.

Diagnostic Value of Quantitative Parameters of DCE-MRI in Endometrial Carcinoma and Its Correlation with Clinicopathological Factors

In the study,108 patients with endometrial cancer were selected as the observation group,and 105 patients with benign endometrial lesions were selected as the control group.After DCE-MRI examination,it was found that the volume transfer constant(K^(trans)),rate constant(K_(e))and extracellular space volume ratio(V_(e))in the observation group were higher than those in the control group(P<0.05).The area under curve(AUC)of combined K^(trans),K_(e) and V_(e) values in the diagnosis of endometrial cancer was 0.841.The values of K^(trans),K_(e )and V_(e) were positively correlated with the clinical stage and the degree of muscular invasion,but negatively correlated with the degree of differentiation(P<0.05).The results of the study suggested that DCE-MRI quantitative parameters have a certain value in the differential diagnosis of endometrial cancer,which helped to further distinguish the degree of muscular invasion,clinical stage,and differentiation of endometrial cancer patients.

The application of DCE-MRI in diagnosing breast cancer

Objective The aim of the study was to further explore the diagnostic value of breast dynamic contrast enhancement (DCE), and improve specificity of breast cancer diagnosis.

Fast T_(1)mapping MRI in preclinical and clinical settings using subspace-constrained joint-domain reconstructions

This work aims to develop fast T_(1)mapping methods for preclinical and clinical scanners based on subspace-constrained reconstructions.Two sequences are explored for rapid T_(1)characterizations:1)Interleaved spatiotemporal encoding incorporating variable repetition times.2)Inversion recovery gradient echo with random sampling of the phaseencoding(PE)dimension.For both sequences,the subspace reconstruction of the signal recovery was applied,to jointly reconstruct the down-sampled images while characterizing the T_(1)relaxation.In vivo scans on human brains and abdomens confirmed the efficiency of the proposed methods,including compatibility with breath-holding.In addition,Scans on animals with abdominal tumors and dynamic contrast-enhanced T_(1)mapping on kidneys support the applicability of the proposed methods also in preclinical settings.

Real-time monitoring of tumor vascular disruption induced by radiofrequency assisted gadofullerene

The anti-vascular therapy has been extensively studied for high performance tumor therapy by suppressing the tumor angiogenesis or cutting off the existing tumor vasculature. We have previously reported a novel anti-tumor treatment technique using radiofrequency （RF）-assisted ga- dofullerene nanocrystals （GFNCs） to selectively disrupt the tumor vasculature. In this work, we further revealed the changes on morphology and functionality of the tumor vas-culature during the high-performance RF-assisted GFNCs treatment in vivo. Here, a dearly evident mechanism of this technique in tumor vascular disruption was elucidated. Based on the H22 tumor bearing mice with dorsal skin flap chamber （DSFC） mode] and the dynamic contrast enhanced magnetic resonance imaging （DCE-MRI） technique, it was revealed that the GFNCs would selectively inset in the gaps of tumor vas-culature due to the innately incomplete structures and unique microenvironment of tumor vasculature,＇ and they damaged the surrounding endothelia cells excited by the RF to induce a phase transition accompanying with size expansion. Soon afterwards, the blood flow of the tumor blood vessels was permanently shut off, causing the entire tumor vascular net- work to collapse within 24 h after the treatment. The RF-as- sistant GFNCs technique was proved to aim at the tumor vasculatnre precisely, and was harmless to the normal vascu- lature. The current studies provide a rational explanation on the high efficiency anticancer activity of the RF-assisted GFNCs treatment, suggesting a novel technique with potent clinical application.

Neovascularization in the carotid atherosclerotic plaque is not associated with inflammatory cell aggregation

Background Monocytes and macrophages in atherosclerotic plaque lead to plaque instability.The aim of the study was to determine if plaque neovascularization led to inflammation.Methods Patients were consecutively enrolled if their carotid intimal media thickness was ＞2 mm,as revealed by duplex ultrasound.The patients then underwent dynamic contrast enhanced magnetic resonance imaging （DCE MRI） and fluorine-18 fluorodeoxyglucose （18F-FDG） positron emission tomography combined with computed tomography （PET CT）.A target to background ratio （TBR） of ＞1.25 or ＜1.25 served as the cutoff point for the presence and absence of inflammation,respectively.Results Twenty-six patients underwent bilateral carotid DCE MRI and 24 patients also underwent PET CT.One hundred and fifty-five plaques were evaluated by both DCE MRI and PET CT.There was no significant difference in plaque morphology between the TBR ＞1.25 （n=61） and TBR ＜1.25 （n=94） groups.No significant differences were found in plasma volume and transfer constant between the TBR ＞1.25 and TBR ＜1.25 groups.Conclusion Our study did not find a significant correlation between plaque neovascularization and the aggregation of inflammatory cells.

Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver:follow-up of DCE-MRI and pathological observations

Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Neuroimaging Features of Pituicytomas

Pituicytoma is a distinct low-grade glioma arising from pituicytes of the neurohypophysis and infundibulum. Due to the rarity of this tumor, most of the reported cases in the literature were originally misdiagnosed as pituitary adenoma, meningiomas, and craniopharyngioma. It is of vital importance to accurately identify this tumor because this tumor, unlike pituitary adenomas, is prone to heavy bleeding during the surgical resection.