Mesoporous MnSiO3@Fe3O4@C Nanoparticle as p H-responsive T1-T2* Dual-modal Magnetic Resonance Imaging Contrast Agent for Tumor Diagnosis

Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in serving as pH-responsive T1-T2^*dual-modal magnetic resonance(MR)imaging contrast agents.The released Mn^2+shortened T1 relaxation time,meanwhile the superparamagnetic Fe3O4 enhanced T2 contrast imaging.The release rate of Mn ions reaches 31.66%under the condition of pH=5.0,which is similar to tumor microenvironment and organelles.Cytotoxicity assays show that MnSiO3@Fe3O4@C NPs have minor toxicity,even at high concentrations.After intravenous injection of MnSiO3@Fe3O4@C NPs,a rapid contrast enhancement in tumors was achieved with a significant enhancement of 132%after 24 h of the administration.Moreover,a significant decreasement of 53.8%was witnessed in T2 MR imaging signal.It demonstrated that MnSiO3@Fe3O4@C NPs can act as both positive and negative MR imaging contrast agents.Besides,owing to the pH-responsive degradation of mesoporous MnSiO3,MnSiO3@Fe3O4@C NPs can also be used as potential drug systems for cancer theranostics.

The Applicability of Gd-DTPA Magnetic Resonance Imaging Contrast Agent for the Evaluation of Blood Compartment Flow Distribution in Hollow Fiber Hemodialyzers

Observation of flow distribution pattern in the hemodialyzers is significant as it is a valuable in-dication of the performance of these modules. Therefore, in this study, a feasible non-destructive Magnetic Resonance Imaging (MRI) technique is proposed to characterize the flow distribution in the blood compartment of hemodialyzers using Gd-DTPA MRI contrast agent. The distribution of flow is qualitatively observed in two commercial clinical dialyzers through an in-vitro experiment. The contrast enhanced T1 weighted images are acquired along the dialyzer length using Spin Echo (SE) pulse sequence after an injection of 0.5 mmol/L Gd-DTPA solution into the blood compartment. Although relatively uniform flow distribution pattern over the spatial volume of transverse images, close the dialyzer inlet is observed, the heterogeneity of flow distribution can be identified towards the blood outlet port. Furthermore, the signal intensity profiles formed by the injected Gd-DTPA are gradually decreased towards the outlet port. These results of the study suggest that although no advanced techniques and protocols available, MRI and Gd-DTPA contrast agent can be utilized to characterize the flow distribution within a dialyzer qualitatively.

Structural control of magnetic nanoparticles for positive nuclear magnetic resonance imaging

In addition to the tens of millions of medical doses consumed annually around the world,a vast number of nuclear magnetic resonance imaging(MRI)contrast agents are being deployed in MRI research and development,offering precise diagnostic information,targeting capabilities,and analyte sensing.Superparamagnetic iron oxide nanoparticles(SPIONs)are notable among these agents,providing effective and versatile MRI applications while also being heavy-metal-free,bioconjugatable,and theranostic.We designed and implemented a novel two-pronged computational and experimental strategy to meet the demand for the efficient and rigorous development of SPION-based MRI agents.Our MATLAB-based modeling simulation and magnetic characterization revealed that extremely small maghemite SPIONs in the 1-3 nm range possess significantly reduced transversal relaxation rates(R_(2))and are therefore preferred for positive(T_(1)-weighted)MRI.Moreover,X-ray diffraction and X-ray absorption fine structure analyses demonstrated that the diffraction pattern and radial distribution function of our SPIONs matched those of the targeted maghemite crystals.In addition,simulations of the X-ray near-edge structure spectra indicated that our synthesized SPIONs,even at 1 nm,maintained a spherical structure.Furthermore,in vitro and in vivo MRI investigations showed that our 1-nm SPIONs effectively highlighted whole-body blood vessels and major organs in mice and could be cleared through the kidney route to minimize potential post-imaging side effects.Overall,our innovative approach enabled a swift discovery of the desired SPION structure,followed by targeted synthesis,synchrotron radiation spectroscopic studies,and MRI evaluations.The efficient and rigorous development of our high-performance SPIONs can set the stage for a computational and experimental platform for the development of future MRI agents.

Effect of magnetic resonance imaging in liver metastases

This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving prognosis.This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

Is it a normal phenomenon for pediatric patients to have brain leptomeningeal contrast enhancement on 3-tesla magnetic resonance imaging?

Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clarify the pathophysiological changes of pLMCE.

Lactoferrin-Conjugated Polylactic Acid Nanobubbles Encapsulated Perfluoropentane as a Contrast Agent for Ultrasound/Magnetic Resonance Dual-Modality Imaging

The development of contrast agents that can be activated by multiple modes is of great significance for tumor diagnosis.In this study,the lactoferrin(Lf)-conjugated polylactic acid(PLLA)nanobubbles(Lf-PLLA NBs)were used to encapsulate liquid perfluoropentane(PFP)with the double emulsion method,creating PFP loaded(PFP/Lf-PLLA)NBs for the ultrasound/magnetic resonance dual-modality imaging of subcutaneous tumor.The parti-cle diameter and stability of nanobubbles were investigated by photon correlation spectroscopy.The biocompat-ibility of nanobubbles was preliminarily evaluated by cell proliferation and migration assay,hemolysis rate,and blood biochemistry analysis.A B-mode clinical ultrasound real-time imaging system was used to perform ultra-sonic imaging in vivo.Magnetic resonance imaging in vivo was applied with a clinical 3.0 T magnetic resonance imaging(MRI)scanner system.The mean particle diameter of PFP/Lf-PLLA NBs was 320.2±4.1 nm with a low polydispersity index(PDI,0.145±0.025),and the NBs were negatively charged(−11.4±0.4 mV).The transmis-sion electron microscopy(TEM)results showed that PFP/Lf-PLLA NBs exhibited highly monodispersed and pos-sessed an obvious spherical structure of nanocapsules.Nanobubbles had good stability at 4°C.Different concentrations of the PFP/Lf-PLLA NBs solution had no effect on the cell in cytotoxicity and cell migration,and the results of hemolysis rate and blood biochemistry assay also indicated the good biocompatibility of NBs.On the ultrasound/magnetic resonance imaging of tumor-bearing mice,PFP/Lf-PLLA NBs showed signifi-cantly enhanced contrast ability of tumor tissue.Therefore,PFP/Lf-PLLA NBs had great potential to be a contrast agent for tumor dual-modality imaging in vivo.

Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging

BACKGROUND The liver imaging reporting and data system(LI-RADS)diagnostic table has 15 cells and is too complex.The diagnostic performance of LI-RADS for hepatocellular carcinoma(HCC)is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging(EOB-MRI).AIM To evaluate the ability of the simplified LI-RADS(sLI-RADS)to diagnose HCC on EOB-MRI.METHODS A total of 331 patients with 356 hepatic observations were retrospectively analysed.The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLIRADS.The algorithms of sLI-RADS A-D are as follows:The single threshold for sLI-RADS A and B was 10 mm,that is,classified observations≥10mm using an algorithm of 10-19 mm observations(sLI-RADS A)and≥20 mm observations(sLI-RADS B)in the diagnosis table of LI-RADS v2018,respectively,while the classification algorithm remained unchanged for observations<10 mm;the single threshold for sLI-RADS C and D was 20 mm,that is,for<20 mm observations,the algorithms for<10 mm observations(sLI-RADS C)and 10-19 mm observations(sLI-RADS D)were used,respectively,while the algorithm remained unchanged for observations≥20 mm.With hepatobiliary phase(HBP)hypointensity as a major feature(MF),the final sLI-RADS(F-sLI-RADS)was formed according to the optimal sLI-RADS,and its diagnostic performance was evaluated.The times needed to classify the observations according to F-sLIRADS and LI-RADS v2018 were compared.RESULTS The optimal sLI-RADS was sLI-RADS D(with a single threshold of 20 mm),because its sensitivity was greater than that of LI-RADS v2018(89.8%vs 87.0%,P=0.031),and its specificity was not lower(89.4%vs 90.1%,P>0.999).With HBP hypointensity as an MF,the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018(93.0%vs 87.0%,P<0.001)and sLI-RADS D(93.0%vs 89.8%,P=0.016),without a lower specificity(86.5%vs 90.1%,P=0.062;86.5%vs 89.4%,P=0.125).Compared with that of LI-RADS v2018,the time to classify lesions according to FsLI-RADS was shorter(51±21 s vs 73±24 s,P<0.001).CONCLUSION The use of sLI-RADS with HBP hypointensity as an MF may improve the sensitivity of HCC diagnosis and reduce lesion classification time.

Dynamic contrast-enhanced magnetic resonance imaging of prostate cancer: A review of current methods and applications

In many areas of oncology, dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) has proven to be a clinically useful, non-invasive functional imaging technique to quantify tumor vasculature and tumor perfusion characteristics. Tumor angiogenesis is an essential process for tumor growth, proliferation, and metastasis. Malignant lesions demonstrate rapid extravasation of contrast from the intravascular space to the capillary bed due to leaky capillaries associated with tumor neovascularity. DCE-MRI has the potential to provide information regarding blood flow, areas of hypoperfusion, and variations in endothelial permeability and microvessel density to aid treatment selection, enable frequent monitoring during treatment and assess response to targeted therapy following treatment. This review will discuss the current status of DCE-MRI in cancer imaging, with a focus on its use in imaging prostate malignancies as well as weaknesses that limit its widespread clinical use. The latest techniques for quantification of DCE-MRI parameters will be reviewed and compared.

Diagnosis of focal liver lesions with deep learning-based multichannel analysis of hepatocyte-specific contrast-enhanced magnetic resonance imaging

BACKGROUND The nature of input data is an essential factor when training neural networks.Research concerning magnetic resonance imaging(MRI)-based diagnosis of liver tumors using deep learning has been rapidly advancing.Still,evidence to support the utilization of multi-dimensional and multi-parametric image data is lacking.Due to higher information content,three-dimensional input should presumably result in higher classification precision.Also,the differentiation between focal liver lesions(FLLs)can only be plausible with simultaneous analysis of multisequence MRI images.AIM To compare diagnostic efficiency of two-dimensional(2D)and three-dimensional(3D)-densely connected convolutional neural networks(DenseNet)for FLLs on multi-sequence MRI.METHODS We retrospectively collected T2-weighted,gadoxetate disodium-enhanced arterial phase,portal venous phase,and hepatobiliary phase MRI scans from patients with focal nodular hyperplasia(FNH),hepatocellular carcinomas(HCC)or liver metastases(MET).Our search identified 71 FNH,69 HCC and 76 MET.After volume registration,the same three most representative axial slices from all sequences were combined into four-channel images to train the 2D-DenseNet264 network.Identical bounding boxes were selected on all scans and stacked into 4D volumes to train the 3D-DenseNet264 model.The test set consisted of 10-10-10 tumors.The performance of the models was compared using area under the receiver operating characteristic curve(AUROC),specificity,sensitivity,positive predictive values(PPV),negative predictive values(NPV),and f1 scores.RESULTS The average AUC value of the 2D model(0.98)was slightly higher than that of the 3D model(0.94).Mean PPV,sensitivity,NPV,specificity and f1 scores(0.94,0.93,0.97,0.97,and 0.93)of the 2D model were also superior to metrics of the 3D model(0.84,0.83,0.92,0.92,and 0.83).The classification metrics of FNH were 0.91,1.00,1.00,0.95,and 0.95 using the 2D and 0.90,0.90,0.95,0.95,and 0.90 using the 3D models.The 2D and 3D networks'performance in the diagnosis of HCC were 1.00,0.80,0.91,1.00,and 0.89 and 0.88,0.70,0.86,0.95,and 0.78,respectively;while the evaluation of MET lesions resulted in 0.91,1.00,1.00,0.95,and 0.95 and 0.75,0.90,0.94,0.85,and 0.82 using the 2D and 3D networks,respectively.CONCLUSION Both 2D and 3D-DenseNets can differentiate FNH,HCC and MET with good accuracy when trained on hepatocyte-specific contrast-enhanced multi-sequence MRI volumes.

Discrimination of Metastatic from Non-metastatic Mesorectal Lymph Nodes in Rectal Cancer Using Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Preoperative detection of lymph nodes（LNs） metastasis is always highly challenging for radiologists nowadays. The utility of quantitative dynamic contrast-enhanced magnetic resonance imaging（QDCE-MRI） in identifying LNs metastasis is not well understood. In the present study, 59 patients with histologically proven rectal carcinoma underwent preoperative QDCE-MRI. The short axis diameter ratio, long axis diameter ratio, short-to-long axis diameter ratio and QDEC-MRI parameters（Ktrans, Kep, fPV and Ve） values were compared between the non-metastatic（n=44） and metastatic（n=35） LNs groups based on pathological examination. Compared with the non-metastatic group, the metastatic group exhibited significantly higher short axis diameter（7.558±0.668 mm vs. 5.427±0.285 mm）, Ktrans（0.483±0.198 min-1 vs. 0.218±0.116 min^-1） and Ve（0.399±0.118 vs. 0.203±0.096） values（all P〈0.05）. The short-to-long axis diameter ratio, long axis diameter ratio, Kep and fPV values did not show significant differences between the two groups. In conclusion, our results showed that for LNs larger than 5 mm in rectal cancer, there are distinctive differences in the Ktrans and Ve values between the metastatic and non-metastatic LNs, suggesting that QDCE-MRI may be potentially helpful in identifying LNs status.

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

Prediction of radiosensitivity in primary central nervous system germ cell tumors using dynamic contrast-enhanced magnetic resonance imaging

Objective： To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging（DCEMRI） for predicting tumor response to radiotherapy in patients with suspected primary central nervous system（CNS） germ cell tumors（GCTs）.Methods： DCE-MRI parameters of 35 patients with suspected primary CNS GCTs were obtained prior to diagnostic radiation, using the Tofts and Kermode model. Radiosensitivity was determined in tumors diagnosed 2 weeks after radiation by observing changes in tumor size and markers as a response to MRI. Taking radiosensitivity as the gold standard, the cut-off value of DCE-MRI parameters was measured by receiver operating characteristic（ROC） curve. Diagnostic accuracy of DCE-MRI parameters for predicting radiosensitivity was evaluated by ROC curve.Results： A significant elevation in transfer constant（K^trans） and extravascular extracellular space（Ve）（P=0.000）, as well as a significant reduction in rate constant（Kep）（P=0.000） was observed in tumors. K^trans, relative K^trans, and relative Kep of the responsive group were significantly higher than non-responsive groups. No significant difference was found in Kep, Ve, and relative Ve between the two groups. Relative K^trans showed the best diagnostic value in predicting radiosensitivity with a sensitivity of 100%, specificity of 91.7%, positive predictive value（PPV） of 95.8%, and negative predictive value（NPV） of 100%.Conclusions： Relative K^trans appeared promising in predicting tumor response to radiation therapy（RT）. It is implied that DCE-MRI pre-treatment is a requisite step in diagnostic procedures and a novel and reliable approach to guide clinical choice of RT.

Advances in magnetic nanoparticle-based magnetic resonance imaging contrast agents

Magnetic resonance imaging(MRI)has revolutionized medical imaging diagnostics with the advantages of non-invasive nature,absence of ionizing radiation,unrestricted penetration depth,high-resolution imaging of soft tissues,organs and blood vessels,and multi-parameter and multi-sequence imaging.Contrast agents(CAs)are crucial for enhancing image quality,detecting molecular-level changes,and providing comprehensive diagnostic information in contrast enhanced MRI.However,the performance of clinical Gd-based CAs represents a limitation to the improvement of MRI sensitivity,specificity,and versatility,thereby impeding the achievement of satisfactory imaging outcomes.In recent years,the development of magnetic nanoparticle-based CAs has emerged as a promising avenue to enhance the capabilities of MRI.Here,we review the advances in magnetic nanoparticle-based MRI CAs,including blood pool CAs,biochemically-targeted CAs,stimulus-responsive CAs,and ultra-high field MRI CAs,as well as the use of CAs for cell labeling and tracking.Additionally,we offer insights into the future prospects and challenges associated with the integration of these nanoparticles into clinical practice.

Oral Gd-DTPA as a negative gastrointestinal contrast agent in magnetic resonance cholangiopancreatography

Objective: To evaluate the value of oral Gd-DTPA as a negative contrast agent during magnetic resonance cholangiopancreatography (MRCP) to eliminate the high signals of the gastrointestinal tract. Methods: To select the optimal concentration of oral Gd-DTPA for MRCP, a phantom study was performed followed by clinical trial in 15 cases undergoing MRCP before and after oral Gd-DTPA (in a total volume of 250 ml 1∶5 diluted Gd-DTPA, 1.488 g/L). MRCP images were acquired using two-dimensional single slice fast spin-echo (SSTSE) sequence and half-Fourier acquisition single slice fast spin-echo (HASTE) sequence. Results: The phantom study showed that the 1∶5 diluted oral Gd-DTPA was best in decreasing the signal intensity both in T2-weighted imaging (59.5%) and in HASTE sequence (82.45%). The high signal intensity of the stomach and intestinal fluid was completely suppressed in all the cases. The depictions of the common bile duct and pancreatic duct were markedly improved by using the oral contrast agent (P<0.05). Conclusion: Oral Gd-DTPA is effective and safe for eliminating the high signal of the gastrointestinal tract to improve the depiction of the biliary system by MRCP.

Liver metastases:The role of magnetic resonance imaging

The liver is one of the organs most commonly involved in metastatic disease,especially due to its unique vascularization.It’s well known that liver metastases represent the most common hepatic malignant tumors.From a practical point of view,it’s of utmost importance to evaluate the presence of liver metastases when staging oncologic patients,to select the best treatment possible,and finally to predict the overall prognosis.In the past few years,imaging techniques have gained a central role in identifying liver metastases,thanks to ultrasonography,contrast-enhanced computed tomography(CT),and magnetic resonance imaging(MRI).All these techniques,especially CT and MRI,can be considered the noninvasive reference standard techniques for the assessment of liver involvement by metastases.On the other hand,the liver can be affected by different focal lesions,sometimes benign,and sometimes malignant.On these bases,radiologists should face the differential diagnosis between benign and secondary lesions to correctly allocate patients to the best management.Considering the above-mentioned principles,it’s extremely important to underline and refresh the broad spectrum of liver metastases features that can occur in everyday clinical practice.This review aims to summarize the most common imaging features of liver metastases,with a special focus on typical and atypical appearance,by using MRI.

Effects of iodinated contrast on various magnetic resonance imaging sequences and field strength: Implications for characterization of hemorrhagic transformation in acute stroke therapy

AIM: To characterize the effects of iodinated contrast material(ICM) on magnetic resonance imaging(MRI) comparing different sequences and magnetic fields, with emphasis to similarities/differences with well-known signal characteristics of hemorrhage in the brain. METHODS: Aliquots of iopamidol and iodixanol mixed with normal saline were scanned at 1.5T and 3T. Signal intensity(SI) was measured using similar spin-echo(SE)-T1, SE-T2, gradient-echo(GRE) and fluid-attenuationinversion-recovery(FLAIR) sequences at both magnets. Contrast to noise ratio(CNR)(SI contrast-SI saline/SD noise) for each aliquot were calculated and Kruskall-wallis test and graphic analysis was used to compare different pulse sequences and ICMs. RESULTS: Both ICM showed increased SI on SE-T1 and decreased SI on SE-T2, GRE and FLAIR at both 1.5T and 3T, as the concentration was increased. By CNR measurements, SE-T2 had the greatest conspicuity at 3T with undiluted iopamidol(92.6 ± 0.3, P < 0.00) followed by iodixanol(77.5 ± 0.9, P < 0.00) as compared with other sequences(CNR range: 15-40). While SE-T2 had greatest conspicuity at 1.5T with iopamidol(49.3 ± 1, P < 0.01), SE-T1 showed similar or slightly better conspicuity(20.8 ± 4) than SE-T2 with iodixanol(23 ± 1.7). In all cases, hypo-intensity on GRE was less conspicuous than on SE-T2.CONCLUSION: Iodixanol and iopamidol shorten T1 and T2 relaxation times at both 1.5T and 3T. Hypo-intensity due to shortened T2 relaxation time is significantly more conspicuous than signal changes on T1-WI, FLAIR or GRE. Variations in signal conspicuity according to pulse sequence and to type of ICM are exaggerated at 3T. We postulate T2 hypointensity with less GRE conspicuity differentiates ICM from hemorrhage; given the wellknown GRE hypointensity of hemorrhage. Described signal changes may be relevant in the setting of recent intra-arterial or intravenous ICM administration in translational research and/or human stroke therapy.

Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma

AIM: To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma(HCC). METHODS: From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant(K_(trans)), plasma flow(F_p), permeability surface area product(PS), efflux rate constant(k_(ep)), extravascular extracellular space volume ratio(V_e), blood plasma volume ratio(V_p), and hepatic perfusion index(HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model(2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student's t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis. RESULTS: The F_p value was greater than the PS value(F_P = 1.07 m L/m L per minute, PS = 0.19 m L/m L per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dualinput 2CXM, respectively. There were no significant differences in the K_(ep), V_p, or HPI between the dual-input extended Tofts model and the dual-input 2CXM(P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for V_e, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dualinput 2CXM were correlated with K_(trans) derived from the dual-input extended Tofts model(P = 0.002, r = 0.566; P = 0.002, r = 0.570); K_(ep), V_p, and HPI between the two kinetic models were positively correlated(P = 0.001, r = 0.594; P = 0.0001, r = 0.686; P = 0.04, r = 0.391, respectively). In the dual input extended Tofts model, V_e was significantly less than that in the dual input 2CXM(P = 0.004), and no significant correlation was seen between the two tracer kinetic models(P = 0.156, r = 0.276). Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models(P > 0.05).CONCLUSION: A dual-input two-compartment pharmacokinetic model(a dual-input extended Tofts model and a dual-input 2CXM) can be used in assessing the microvascular physiopathological properties before the treatment of advanced HCC. The dual-input extended Tofts model may be more stable in measuring the V_e; however, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.

Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer

AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma(HNSCC). METHODS: In this retrospective study,19 HNSCC patients underwent pre- and intra-treatment DCEMRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images,generating maps of volume transfer rate(Ktrans) and volume fraction of the extravascular extracellular space(ve). Image texture analysis was then employed on maps of Ktrans and ve,generating two texture measures: Energy(E) and homogeneity.RESULTS: No significant changes were found for the mean and standard deviation for Ktrans and ve between pre- and intra-treatment(P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans,relative to pretreatment scans(P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.

Evaluation of tumor response to antiangiogenic therapy in patients with recurrent gliomas using contrast-enhanced perfusion-weighted magnetic resonance imaging techniques:A meta-analysis

BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.

Perfusion magnetic resonance imaging of the liver

Perfusion magnetic resonance imaging (MRI) studies quantify the microcirculatory status of liver parenchyma and liver lesions, and can be used for the detection of liver metastases, assessing the effectiveness of antiangiogenic therapy, evaluating tumor viability after anticancer therapy or ablation, and diagnosis of liver cirrhosis and its severity. In this review, we discuss the basic concepts of perfusion MRI using tracer kinetic modeling, the common kinetic models applied for analyses, the MR scanning techniques, methods of data processing, and evidence that supports its use from published clinical and research studies. Technical standardization and further studies will help to establish and validate perfusion MRI as a clinical imaging modality.