Comprehensive characterization of tumor therapeutic response with simultaneous mapping cell size, density, and transcytolemmal water exchange.

Early assessment of tumor therapeutic response is an important topic in precision medicine to optimize personalized treatment regimens and reduce unnecessary toxicity, cost, and delay. Although diffusion MRI (dMRI) has shown potential to address this need, its predictive accuracy is limited, likely due to its unspecific sensitivity to overall pathological changes. In this work, we propose a new quantitative dMRI-based method dubbed EXCHANGE (MRI of water Exchange, Confined and Hindered diffusion under Arbitrary Gradient waveform Encodings) for simultaneous mapping of cell size, cell density, and transcytolemmal water exchange. Such rich microstructural information comprehensively evaluates tumor pathologies at the cellular level. Validations using numerical simulations and in vitro cell experiments confirmed that the EXCHANGE method can accurately estimate mean cell size, density, and water exchange rate constants. The results from in vivo animal experiments show the potential of EXCHANGE for monitoring tumor treatment response. Finally, the EXCHANGE method was implemented in breast cancer patients with neoadjuvant chemotherapy, demonstrating its feasibility in assessing tumor therapeutic response in clinics. In summary, a new, quantitative dMRI-based EXCHANGE method was proposed to comprehensively characterize tumor microstructural properties at the cellular level, suggesting a unique means to monitor tumor treatment response in clinical practice.

Differentiation of retroperitoneal paragangliomas and schwannomas based on computed tomography radiomics.

The purpose of this study was to differentiate the retroperitoneal paragangliomas and schwannomas using computed tomography (CT) radiomics. This study included 112 patients from two centers who pathologically confirmed retroperitoneal pheochromocytomas and schwannomas and underwent preoperative CT examinations. Radiomics features of the entire primary tumor were extracted from non-contrast enhancement (NC), arterial phase (AP) and venous phase (VP) CT images. The least absolute shrinkage and selection operator method was used to screen out key radiomics signatures. Radiomics, clinical and clinical-radiomics combined models were built to differentiate the retroperitoneal paragangliomas and schwannomas. Model performance and clinical usefulness were evaluated by receiver operating characteristic curve, calibration curve and decision curve. In addition, we compared the diagnostic accuracy of radiomics, clinical and clinical-radiomics combined models with radiologists for pheochromocytomas and schwannomas in the same set of data. Three NC, 4 AP, and 3 VP radiomics features were retained as the final radiomics signatures for differentiating the paragangliomas and schwannomas. The CT characteristics CT attenuation value of NC and the enhancement magnitude at AP and VP were found to be significantly different statistically (P < 0.05). The NC, AP, VP, Radiomics and clinical models had encouraging discriminative performance. The clinical-radiomics combined model that combined radiomics signatures and clinical characteristics showed excellent performance, with an area under curve (AUC) values were 0.984 (95% CI 0.952-1.000) in the training cohort, 0.955 (95% CI 0.864-1.000) in the internal validation cohort and 0.871 (95% CI 0.710-1.000) in the external validation cohort. The accuracy, sensitivity and specificity were 0.984, 0.970 and 1.000 in the training cohort, 0.960, 1.000 and 0.917 in the internal validation cohort and 0.917, 0.923 and 0.818 in the external validation cohort, respectively. Additionally, AP, VP, Radiomics, clinical and clinical-radiomics combined models had a higher diagnostic accuracy for pheochromocytomas and schwannomas than the two radiologists. Our study demonstrated the CT-based radiomics models has promising performance in differentiating the paragangliomas and schwannomas.

7T Small Animal MRI Research for Hepatic Alveolar Echinococcosis.

OBJECTIVES: 7T small animal magnetic resonance imaging (MRI) was used to analyze the growth characteristics of hepatic alveolar echinococcosis (HAE). METHODS: A mouse model of HAE was established by intraperitoneal injection of alveolar Echinococcus tissue suspension. Ten mouse models successfully inoculated by ultrasound screening were selected. The mouse model was scanned with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) sequence by 7T small animal MRI. Size, morphology, boundary, signal, and relationship with surrounding tissues of the lesions were recorded as characteristic alterations. Mice were killed at the end of the experiment, and the pathological specimens were taken for routine hematoxylin and eosin staining. RESULTS: Lesions were mainly located in the right lobe of the liver. The multivesicular structure is the characteristic manifestation of this disease. In the liver, lesions invaded the portal vein and were mainly distributed at the hepatic hilum. The left branch of the portal vein was mainly invaded. The mean diameter of the lesions in the left lobe of the liver was larger than in other parts of the liver. The mean diameter of the cystic solid lesions was greater than the multilocular cystic lesions. HAE showed hypointense on T1WI, hyperintense on T2WI, and hypointense on DWI; the marginal zone of the lesion showed hyperintensity on DWI and grew toward the hilum. The MRI features of intraperitoneal lesions were similar to those of intrahepatic lesions. Intraperitoneal lesions increased faster than intrahepatic lesions in the same period. CONCLUSION: Polyvesicular structure is a characteristic manifestation of hepatic alveolar echinococcosis in mice. The noninvasive monitoring of liver HAE in mice by 7T small animal MRI provides a visual basis for the diagnosis and treatment integration of HAE.

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase.

Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.

Magnetic resonance imaging study of normal cranial bone marrow conversion at high altitude.

Background: To use conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to investigate the effects of long-term hypoxia on cranial bone marrow conversion in healthy people at high altitudes. Methods: A total of 1,130 individuals were selected from altitudinal areas of 2,000-3,000, 3,100-4,000, and >4,100 m. Each altitude range was divided into 5 age groups: 0-5, 6-14, 15-29, 30-49, and ≥50 years. Firstly, cranial bone marrow typing of the participants in each altitude range was performed on sagittal T1-weighted images (T1WI) according to the average diploe thickness and signal intensity of the normal skull, and the relationship between bone marrow conversion and age was analyzed. Secondly, the apparent diffusion coefficient (ADC) values of the frontal bone, parietal bone, occipital bone, and temporal bone were measured in the DWI post-processing workstation and statistical methods were used to analyze whether different altitudinal gradients and long-term hypoxic environment had any effect on cranial bone marrow conversion. Results: There was a positive correlation between bone marrow type and age in the healthy populations at all 3 levels of altitude (P<0.05). The average thickness of the cranial diploe also positively correlated with age (P<0.05); in the age ranges of 30-49 and ≥50 years, the ADC values of the occipital and temporal bone marrow positively correlated with increasing altitude (P<0.05). Conclusions: The cranial bone marrow of normal people at high altitudes changes from Type I to Type IV with increasing age and under the influence of long-term chronic hypoxia. The bone marrow of the occipital and temporal bones of healthy people aged 30-49 and ≥50 years showed erythromedularization during the process of Type III and IV bone marrow conversion.

One-tube nested MGB Probe Real-time PCR assay for detection of Echinococcus multilocularis infection in plasma cell free DNA.

INTRODUCTION: The main objective of this study was to develop a One-tube nested MGB probe real-time PCR Assay for detecting Echinococcus multilocularis infection in human plasma cell free DNA (cfDNA). METHODS: cfDNA was extracted from 10 E.m.-infected patients using a NucleoSnap DNA Plasma Kit and characterized by genomic sequencing. We designed nested PCR primers and MGB probe for Echinococcus multilocularis detection. The specificity, sensitivity and reproducibility of this assay were analyzed, and its validity was confirmed in 13 early stage clinical samples. RESULTS: Several Echinococcus multilocularis-specific sequences were detected in the cfDNA of E.m.-infected patients, and CBLO020001206.1 was selected as the candidate sequence. We designed the primers and probe for the one tube nested real-time PCR. No cross-reactions with E.g. were observed. The detection limit was as low as 1 copy for Echinococcus multilocularis. The coefficients of variation were lower than 5% in intra- and inter-assays. 11 out of 13 patients were positive with nested MGB Probe PCR Assay and 3 patients were positive without outer primer in early stage Alveolar Echinococcosis pateints. CONCLUSION: The one-tube nested MGB probe real-time PCR assay is a simple, rapid, and cost-effective method for detection of Echinococcus multilocularis infection in patients' Plasma DNA.

Development of a Nomogram Combining Clinical Risk Factors and Dual-Energy Spectral CT Parameters for the Preoperative Prediction of Lymph Node Metastasis in Patients With Colorectal Cancer.

OBJECTIVE: This study aimed to develop a dual-energy spectral computed tomography (DESCT) nomogram that incorporated both clinical factors and DESCT parameters for individual preoperative prediction of lymph node metastasis (LNM) in patients with colorectal cancer (CRC). MATERIAL AND METHODS: We retrospectively reviewed 167 pathologically confirmed patients with CRC who underwent enhanced DESCT preoperatively, and these patients were categorized into training (n = 117) and validation cohorts (n = 50). The monochromatic CT value, iodine concentration value (IC), and effective atomic number (Eff-Z) of the primary tumors were measured independently in the arterial phase (AP) and venous phase (VP) by two radiologists. DESCT parameters together with clinical factors were input into the prediction model for predicting LNM in patients with CRC. Logistic regression analyses were performed to screen for significant predictors of LNM, and these predictors were presented as an easy-to-use nomogram. The receiver operating characteristic curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram. RESULTS: The logistic regression analysis showed that carcinoembryonic antigen, carbohydrate antigen 199, pericolorectal fat invasion, ICAP, ICVP, and Eff-ZVP were independent predictors in the predictive model. Based on these predictors, a quantitative nomogram was developed to predict individual LNM probability. The area under the curve (AUC) values of the nomogram were 0.876 in the training cohort and 0.852 in the validation cohort, respectively. DCA showed that our nomogram has outstanding clinical utility. CONCLUSIONS: This study presents a clinical nomogram that incorporates clinical factors and DESCT parameters and can potentially be used as a clinical tool for individual preoperative prediction of LNM in patients with CRC.

Kodama-XUUB: an informative classification for alveolar echinococcosis hepatic lesions on magnetic resonance imaging.

OBJECTIVE: To propose a modification of the Kodama classification to classify type III lesions of alveolar echinococcosis (AE) that do not have microcysts. MATERIALS AND METHODS: 200 magnetic resonance imaging (MRI) images of AE liver lesions from four endemic regions of the world were classified according to Kodama, distinguishing within type III those with microcysts from those without. Each center included 50 MRIs of patients with unoperated AA liver lesions. The first 50 cases were classified by a first reader in the presence of four second-line readers from each region. Then each second-line reader classified his or her 50 cases. RESULTS: In all centers, type III lesions were predominant: 58% of the total lesions and 23% of them were without microcysts. The average age of the patients was 47 years. In China, the patients were on average younger and the lesions larger. German patients had more lesions within the liver. Type I and II lesions, synonymous with earlier diagnosis, were more common in Europe. CONCLUSION: The Kodama classification needed to be modified because of the existence of a significant proportion of unclassifiable lesions. This is especially true since the presence of microcysts is an informative element of parasite activity. Therefore, this study proposes a Kodama-XUUB classification with type IIIa lesions having microcysts and type IIIb lesions not having microcysts.

TITLE: Kodama-XUUB : une classification informative des lésions hépatiques de l'échinococcose alvéolaire à l'Imagerie par Résonance Magnétique. ABSTRACT: Objectif : Proposer une modification de la classification de Kodama permettant de classer les lésions de type III qui ne présentent pas de microkystes. Matériels et Méthodes : 200 IRM de lésions hépatiques d'EA en provenance de quatre régions d'endémie dans le monde ont été classées selon Kodama, en distinguant au sein du type III celles qui présentaient des microkystes de celle qui n'en présentaient pas. Chaque centre a inclus 50 IRM de patients avec lésions hépatiques d'EA non opérées. Les 50 premiers cas ont été classés par un premier lecteur en présence des quatre seconds lecteurs issus de chacune des régions. Puis chaque second lecteur a classé ses 50 cas. Résultats : Dans tous les centres, les lésions de type III étaient largement prédominantes : 58 % du total des lésions et 23 % d'entre elles ne présentaient pas de microkystes. La moyenne d'âge des patients était de 47 ans. En Chine, les patients étaient en moyenne plus jeunes et les lésions plus larges. Les patients allemands présentaient plus de lésions au sein du foie. Les lésions de type I et II, synonymes de diagnostic plus précoce étaient plus fréquentes en Europe. Conclusion : La classification de Kodama nécessitait d'être modifiée du fait de l'existence d'une proportion non négligeable de lésions non classifiables. Ce d'autant que la présence de microkystes est un élément informatif de l'activité du parasite. C'est pourquoi cette étude propose une classification Kodama-XUUB avec un type IIIa de lésions avec microkystes et un type IIIb sans microkystes.

Predicting Microsatellite Instability Status in Colorectal Cancer Based on Triphasic Enhanced Computed Tomography Radiomics Signatures: A Multicenter Study.

BACKGROUND: This study aimed to develop and validate a computed tomography (CT)-based radiomics model to predict microsatellite instability (MSI) status in colorectal cancer patients and to identify the radiomics signature with the most robust and high performance from one of the three phases of triphasic enhanced CT. METHODS: In total, 502 colorectal cancer patients with preoperative contrast-enhanced CT images and available MSI status (441 in the training cohort and 61 in the external validation cohort) were enrolled from two centers in our retrospective study. Radiomics features of the entire primary tumor were extracted from arterial-, delayed-, and venous-phase CT images. The least absolute shrinkage and selection operator method was used to retain the features closely associated with MSI status. Radiomics, clinical, and combined Clinical Radiomics models were built to predict MSI status. Model performance was evaluated by receiver operating characteristic curve analysis. RESULTS: Thirty-two radiomics features showed significant correlation with MSI status. Delayed-phase models showed superior predictive performance compared to arterial- or venous-phase models. Additionally, age, location, and carcinoembryonic antigen were considered useful predictors of MSI status. The Clinical Radiomics nomogram that incorporated both clinical risk factors and radiomics parameters showed excellent performance, with an AUC, accuracy, and sensitivity of 0.898, 0.837, and 0.821 in the training cohort and 0.964, 0.918, and 1.000 in the validation cohort, respectively. CONCLUSIONS: The proposed CT-based radiomics signature has excellent performance in predicting MSI status and could potentially guide individualized therapy.

Development of a dual-energy spectral computed tomography-based nomogram for the preoperative discrimination of histological grade in colorectal adenocarcinoma patients.

BACKGROUND: The usefulness of a dual-energy spectral computed tomography (DESCT)-based nomogram in discriminating between histological grades of colorectal adenocarcinoma (CRAC) is unclear. This study aimed to develop such a nomogram and assess its ability to preoperatively discriminate between histological grades in CRAC patients. METHODS: Primary tumors monochromatic CT value, iodine concentration (IC) value, and effective atomic number (Eff-Z) in the arterial (AP) and venous phases (VP) were retrospectively compared between patients with high-grade (n=65) and low-grade (n=108) CRAC who underwent preoperative abdominal DESCT. Univariate analysis was used to compare the DESCT parameters and clinical factors between these two patient groups. Statistically significant features in the univariate analysis were included in the multivariate logistic regression model to identify the indicators for building a nomogram that could discriminate between histological grades in CRAC patients. The clinical usefulness of the nomogram and its value for predicting overall survival were statistically evaluated. RESULTS: The logistic regression analysis showed that age, clinical T stage, clinical N stage, and IC values in AP and VP were significant independent predictors for high-grade CRAC. A quantitative nomogram developed based on these predictors showed excellent performance for discriminating between the histological grades, with an area under the curve (AUC) of 0.886 and excellent agreement in the calibration curve. The Kaplan-Meier curve for overall survival showed that our nomogram identified a significant difference between the high- and low-risk groups [hazard ratio (HR), 2.188; 95% CI, 1.072-4.465; P=0.027). CONCLUSIONS: This study presents a nomogram that incorporates DESCT parameters and clinical factors and can potentially be used as a clinical tool for individual preoperative prediction of CRAC histological grade.

Development of a dual-energy spectral CT based nomogram for the preoperative discrimination of mutated and wild-type KRAS in patients with colorectal cancer.

PURPOSE: To develop a dual-energy spectral CT (DESCT) nomogram for the preoperative identification of KRAS mutation in patients with colorectal cancer (CRC). METHOD: One hundred and twenty-four patients who underwent energy spectrum CT pre-operatively were recruited and split into mutated KRAS group (n = 50) and wild-type KRAS group (n = 74). DESCT parameters, including monochromatic CT value, iodine concentration, water concentration, and effective atomic number were measured independently by two reviewers in the arterial, venous, and delayed phases. Normalized iodine concentration (NIC) and slope k of the spectral HU curve were calculated. Evaluate other imaging features such as ATL/LTL ratio, tumor gross pattern, pericolorectal fat invasion (PFI) was also performed by these reviewers. Independent predictors for KRAS mutation were screened out using logistic regression, and these predictors were presented as a nomogram. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram. RESULTS: The slope k in the arterial phase, effective atomic number in the arterial phase, NIC in the venous phase, ATL/LTL ratio and PFI were significant independent predictors for KRAS mutation. Based on these independent predictors, a quantitative nomogram was developed to predict individual KRAS mutation probability. The nomogram had excellent performance with an AUC of 0.848 and excellent calibration. DCA showed that our nomogram has outstanding clinical utility. CONCLUSIONS: This study demonstrates that a DESCT based nomogram has potential value for individual preoperative identification of KRAS mutation in CRC patients.

Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE. PURPOSE: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China. MATERIAL AND METHODS: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion. RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P=0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ2 = 11.92; P = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P<0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations. CONCLUSION: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Parasite Circulating Cell-free DNA in the Blood of Alveolar Echinococcosis Patients as a Diagnostic and Treatment-Status Indicator.

BACKGROUND: Alveolar echinococcosis (AE) is a serious parasitic disease caused by the larvae of Echinococcus multilocularis. It is the less common but substantially more deadly of the 2 major echinococcosis diseases that can occur globally but are concentrated in central Asia. METHODS: We analyzed parasite circulating cell-free DNA (cfDNA) in 149 plasma samples using a DNA sequencing-based method (105 AE, 16 cystic echinococcosis, 4 liver cancer, 4 gallstones, and 20 healthy volunteers). After identifying the Echinococcus-specific cfDNA (Em-cfDNA) sequences in the samples, we determined whether Em-cfDNA could be used for AE diagnosis and as a potential indicator of the effectiveness of surgical treatment. We also examined potential associations between Em-cfDNA levels and clinical features of AE patients. RESULTS: Our work demonstrates that varying reads of Em-cfDNA were detectable in the plasma of 100% of preoperative AE patients and that all of the non-AE patients and healthy volunteers were negative. Em-cfDNA has good sensitivity and specificity for the diagnosis of AE. We also found that Em-cfDNA levels apparently have reference value for evaluating the therapeutic efficacy of surgery interventions for AE lesions. Finally, our analysis revealed that Em-cfDNA levels can reflect meaningful information about lesion size in preoperative AE patients. CONCLUSIONS: We demonstrate that sequencing-based monitoring of Em-cfDNA can be used in the clinic as a powerful diagnostic indicator for AE. We also note that there is a strong potential for use of this liquid-biopsy method to monitor ongoing disease status in postintervention AE patients.

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE. AIM: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim. METHODS: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States). RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III. CONCLUSION: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.

Worldwide literature on epidemiology of human alveolar echinococcosis: a systematic review of research published in the twenty-first century.

PURPOSE: Human alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this systematic review is to establish a comprehensive global AE literature overview taking into account the epidemiologically relevant AE research of the twenty-first century. METHODS: We systematically searched the global literature published from 2001 through 2018 via MEDLINE, EMBASE, the Russian databases eLIBRARY.RU, CyberLeninka, the Chinese databases CNKI, VIP, Journals. RESEARCH: ac.ir (Farsi language-based), Jordan E-Library (Arab language-based) and supplementary Google Scholar, in accordance with the PRISMA guidelines. QGIS software was used for the mapping of the affected countries. RESULTS: We have listed 154 relevant publications in the final literature synopsis in consideration of our quality assessment. Including non-autochthonous cases, human AE was reported in 36 countries within the northern hemisphere from 2001 to 2018. The first publication of AE in Tajikistan, Pakistan, South Korea, Belgium, the Netherlands, Slovakia, Hungary, Lithuania, Latvia, Slovenia and Morocco occurred in this century; further first cases in Taiwan, Thailand, and Denmark were considered to be non-autochthonous by the authors. The highest total case numbers (n ≥ 100 in a single article) were reported in France, Germany, Switzerland, Poland, and Lithuania, including China and Kyrgyzstan with by far the highest prevalence figures. CONCLUSIONS: Our paper emphasises the increasing spread of reported cases and the rise in its numbers in the literature of the twenty-first century, especially in western, northern and eastern Europe, as well as in central Asia. Epidemiological studies on human infections are lacking in many parts of the world.

Magnetic resonance imaging evaluation of characteristics of vascular invasion in intermediate and advanced hepatic alveolar echinococcosis.

The objective of the present study was to provide a basis for the personalized treatment of intermediate and advanced hepatic alveolar echinococcosis (HAE) by elucidating the characteristics of vascular invasion and lesion growth. A total of 160 patients with intermediate and advanced HAE who were subjected to plain as well as contrast-enhanced 3.0-T magnetic resonance imaging prior to surgery were analyzed. Pathological and intra-operative observations of the subjects were also considered. The size and location of HAE lesions, vascular invasion characteristics and growth patterns were assessed. A total of 78 patients (48.75%) had lesions involving the S5-8 segment/partial right liver lobe, 21 (13.13%) had involvement in the S2-4 segment/partial left liver lobe and 61 (38.13%) had lesions that transcended the left and right liver lobes. Pathological examination revealed that the vascular invasion rates of the hepatic portal veins, intrahepatic veins (left, central and right vein, and inferior vena cava) and hepatic arteries were 51.88, 43.28 and 26.87%, respectively. Liver hilum invasion was observed in 128 patients (80.00%), 71 of which (44.38%) presented with invasion of the primary porta hepatis, 11 (6.88%) with invasion of the secondary porta hepatis and 46 (28.75%) with invasion of the primary as well as the secondary porta hepatis. In conclusion, the growth pattern of intermediate and advanced HAE is determined by the site, blood supply and activity of the lesion. The current study demonstrated that lesions tend to invade the intrahepatic venous system and porta hepatis, and to target veins rather than arteries.

Polycystic kidney disease evaluation by magnetic resonance imaging in ischemia-reperfusion injured PKD1 knockout mouse model: comparison of T2-weighted FSE and true-FISP.

OBJECTIVE: To investigate the efficacy of true fast imaging with steady state precession (true-FISP) compared with T2-weighted fast spin echo (T2W-FSE) in monitoring changes in cyst volume and renal expansion in an ischemia reperfusion (IR) injured PKD1 knockout (IKO) mouse model. MATERIALS AND METHODS: The animal study was approved by the local institutional authority. A total of 24 mice (14 PKD1 IKO mice and 10 control mice) were sequentially scanned on a 4.7-T scanner from 4 to 12 weeks after IR injury and the cysts and kidney volumes were measured from true-FISP and T2W-FSE MR images. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for the images generated from both methods. RESULTS: Cyst SNR and CNR in true-FISP images were significantly higher than in images employing the T2W-FSE sequence (P < 0.05). Both methods demonstrated kidney volume increase as well as cyst growth after IR injury in the mouse model. The kidney and cysts volume at different time points were strongly correlated between true-FISP and T2W-FSE measurements (r(kidney) = 0.99, r(cysts) = 0.97). CONCLUSION: The true-FISP method offers shorter scan times and higher cyst SNR and cyst to kidney tissue contrast than T2W-FSE. Both sequences have identical accuracy in measuring the cysts and kidney volume changes in mice with PKD.

Magnetic resonance imaging of the response of a mouse model of non-small cell lung cancer to tyrosine kinase inhibitor treatment.

Mutational activation of the gene for epidermal growth factor receptor (EGFR) is 1 of the main ways by which this receptor induces non-small cell lung cancers (NSCLC). Variant III EGFR (EGFRvIII) is a potential therapeutic target in NSCLC treatment because of the high frequency of deletion mutations in this protein. This study used noninvasive magnetic resonance imaging (MRI) to investigate the role of an EGFRvIII mutant in lung tumorigenesis and tumor maintenance as well as its response to the EGFR small molecule inhibitor erlotinib (Tarceva) on bitransgenic mice. Both spin-echo and gradient-echo sequences with and without cardiac and respiratory gating were performed to image the invasive mouse lung tumor driven by EGFRvIII mutation. Tumor volumes were measured based on 2-dimensional axial MRI; 3-dimensional rendering of the images were obtained to demonstrate the spatial location and distribution of the tumor in the lung. The MRI results indicated that the tumor driven by the EGFRvIII mutation was generated and maintained in the bitransgenic mice with the use of doxycycline. Tumor monitoring via MRI showed that Erlotinib can significantly inhibit the growth of tumor in vivo. MRI has the ability to image mouse lung tumor with different sequences focusing on tissue contrasts between tumor and surroundings. The MRI approaches in this work can be applied on other antitumor drug treatment evaluation in vivo when appropriate sequences are chosen.