Imaging Assessment of the Efficacy of Chemotherapy in Primary Malignant Bone Tumors: Recent Advances in Qualitative and Quantitative Magnetic Resonance Imaging and Radiomics.

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Reactivity of Rare Earth Metal Alkyl Complexes with Nitriles or Isonitrile: Versatile Ways toward Multiply Functionalized ß-Diketiminato, (Iso)indolyl, and Imidazolyl Chelating Rare Earth Metal Complexes.

The reactivity of the rare earth metal alkyl complexes LRE(CH2SiMe3)(THF)2 (1RE) [RE = Y (1Y), Yb (1Yb), Lu (1Lu); L = 2,5-[(2-pyrrolyl)CPh2]2(N-methylpyrrole)] with various nitriles and isonitriles has been fully developed. Treatment of the yttrium monoalkyl complex (1Y) with 2 equiv of aromatic nitriles afforded the symmetric trisubstituted ß-diketiminato yttrium complexes (2Y(H), 2Y(Me), and 2Y(F)) through successive cyano group insertion into the RE-C bond and 1,3-H shift or the unsymmetric trisubstituted ß-diketiminato yttrium complex (3Y) unexpectedly via a 1,3-SiMe3 shift when 4-(trifluoromethyl)benzonitrile was used in this reaction under the same conditions. By treating 1Y with 2 equiv of tolyl acetonitrile, an activation of the sp3 C-H bond occurred to form the corresponding ß-aryl keteniminato complexes 4Y(p-tol) and 4Y(m-tol). Remarkably, a heteroleptic cleavage of the CO-CN bond took place in the reaction of 1Y with benzoyl nitrile, affording the unsymmetric trinuclear yttrium complex 5Y bridged by three cyanide groups. Dinuclear ytterbium and lutetium complexes 6Yb and 6Lu containing a functionalized isoindole fragment were synthesized from the reactions of 1 with phthalonitrile by tandem insertion and cyclization. Further studies indicated that the temperature and stoichiometric ratio have a great influence on the reactivity patterns between the reactions of 1RE with benzylisonitrile: two tetrasubstituted ß-diketiminato complexes 8 and 9 were obtained at -30 °C, and tetrasubstituted imidazolyl yttrium and lutetium complexes 7 were isolated at elevated temperature, respectively. In addition, the tetrasubstituted ß-diketiminato complexes 8 and 9 could be irreversibly converted to the cyclization products 7 by elevating the reaction temperature not only on the NMR scale but also on the preparative scale. Notably, when the phenyl isonitrile instead of benzyl isonitrile was reacted with 1Yb, a 2,3-functionalized indolyl ytterbium complex 10Yb was isolated.

Advances in The Application and Research of Magnetic Resonance Diffusion Kurtosis Imaging in The Musculoskeletal System.

Magnetic resonance diffusion kurtosis imaging (DKI) is an emerging magnetic resonance imaging (MRI) technique that can reflect microstructural changes in tissue through non-Gaussian diffusion of water molecules. Compared to traditional diffusion weighted imaging (DWI), the DKI model has shown greater sensitivity for diagnosis of musculoskeletal diseases and can help formulate more reasonable treatment plans. Moreover, DKI is an important auxiliary examination for evaluation of the motor function of the musculoskeletal system. This article briefly introduces the basic principles of DKI and reviews the application and research of DKI in the evaluation of disorders of the musculoskeletal system (including bone tumors, soft tissue tumors, spinal lesions, chronic musculoskeletal diseases, musculoskeletal trauma, and developmental disorders) as well as the normal musculoskeletal tissues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: 1.

Correlation of Intravoxel Incoherent Motion and Diffusion Kurtosis MR Imaging Models With Reactive Stromal Grade in Prostate Cancer.

BACKGROUND: Reactive stroma is recognized as one of the independent prognostic factors in prostate cancer (PCa). Intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) may be useful for assessing the reactive stromal grade (RSG). PURPOSE: To investigate whether IVIM and DKI models can evaluate RSG in PCa patients. STUDY TYPE: Retrospective. SUBJECTS: A total of 56 PCa patients aged 73 years on average confirmed by MRI and transrectal ultrasound (MRI/TRUS) fusion biopsy divided into two subgroups (18 high RSG and 38 low RSG). FIELD STRENGTH/SEQUENCE: A 3 T/T1 WI-fs, T1 WI, T2 WI-fs, T2 WI, DWI, IVIM, and DKI. ASSESSMENT: Apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK) were obtained. Patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups on hematoxylin and eosin (H&E) stained sections. STATISTICAL TESTS: Spearman correlation and independent sample t-test or Wilcoxon's rank sum test was used to investigate the relationship between each imaging parameter and RSG. The combined parameters were calculated using a binary logistic regression model. Receiver operating characteristic (ROC) analysis was used to explore the value of individual and combined parameters to differentiate between high and low RSG group. Area under the ROC curves (AUC) > 0.7 were used as reference standards. RESULTS: ADC, D, f, and MD values showed positive correlation with RSG (r = 0.489, 0.619, 0.318, and 0.544, respectively); MK showed negative correlation with RSG (r = -0.444). ADC, D, f, and MD values were significantly lower in the low RSG group than in the high RSG group. The combined model showed the best diagnostic ability to differentiate low and high RSG groups (AUC = 0.887). DATA CONCLUSION: Parameters of IVIM and DKI may be promising methods for assessment of RSG in PCa patients. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Correlation of Apparent Diffusion Coefficient With Proliferation and Apoptotic Indexes in a Murine Model of Fibrosarcoma: Comparison of Four Methods for MRI Region of Interest Positioning.

BACKGROUND: Diffusion-weighted imaging (DWI) has demonstrated great potential in predicting the expression of tumor cell proliferation and apoptosis indexes. PURPOSE: To evaluate the impact of four region of interest (ROI) methods on interobserver variability and apparent diffusion coefficient (ADC) values and to examine the correlation of ADC values with Ki-67, Bcl-2, and P53 labeling indexes (LIs) in a murine model of fibrosarcoma. STUDY TYPE: Prospective, animal model. ANIMAL MODEL: A total of 22 female BALB/c mice bearing intramuscular fibrosarcoma xenografts. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted fast spin-echo (FSE), T2-weighted fast relaxation fast spin-echo, and DWI PROPELLER FSE sequences. ASSESSMENT: Four radiologists measured ADC values using four ROI methods (oval, freehand, small-sample, and whole-volume). Immunohistochemical assessment of Ki-67, Bcl-2, and P53 LIs was performed. STATISTICAL TESTS: Interclass correlation coefficient (ICC), one-way analysis of variance followed by LSD-t post hoc analysis, and Pearson correlation test were performed. The statistical threshold was defined as a P-value of <0.05. RESULTS: All ROI methods for ADC measurements showed excellent interobserver agreement (ICC range, 0.832-0.986). The ADC values demonstrated significant differences among the four ROI methods. The ADC values for oval, freehand, small-sample, and whole-volume ROI methods showed a moderately negative correlation with Ki-67 (r = -0.623; r = -0.629; r = -0.642, and r = -0.431) and Bcl-2 (r = -0.590; r = -0.597; r = -0.659, and r = -0.425) LIs, but no correlation with P53 LI (r = 0.364, P = 0.104; r = 0.350, P = 0.120; r = 0.379, P = 0.091; r = 0.390, P = 0.080). DATA CONCLUSION: The ADC value can be used to evaluate cell proliferation and apoptosis indexes in a murine model of fibrosarcoma, employing the small-sample ROI as a reliable method. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Correlation between IVIM parameters and microvessel architecture: direct comparison of MRI images and pathological slices in an orthotopic murine model of rhabdomyosarcoma.

OBJECTIVE: This study aimed to explore the correlation between intravoxel incoherent motion (IVIM) parameters and microvessel architecture (microvessel density (MVD), vasculogenic mimicry (VM), and pericyte coverage index (PCI)) in an orthotopic murine model of rhabdomyosarcoma. METHODS: The murine model was established by injecting rhabdomyosarcoma-derived (RD) cells into the muscle. Nude mice underwent routine magnetic resonance imaging (MRI) and IVIM examinations with ten b values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 2000 s/mm2). D, D*, and f values were calculated with the ADW4.7 workstation. MRI images and pathological slices were directly compared to ensure that radiology parameters accurately reflect pathology. MVD, VM, PCI, and cellularity were obtained by histological analysis. The correlations were assessed between IVIM parameters (D, D*, f, and fD* values) and pathological markers (MVD, VM, PCI, and cellularity). RESULTS: The average of D, D*, f, and fD* values were 0.55 ± 0.07 × 10-3 mm2/s, 5.25 ± 0.73 × 10-3 mm2/s, 13.39 ± 7.68%, and 0.73 ± 0.49 × 10-3 mm2/s, respectively. The average of MVD, VM, PCI, and cellularity were 41.91 ± 10.98, 1.16 ± 0.83, 0.49 ± 0.18, and 39.15 ± 9.00%. D*, f, and fD* values showed a positive correlation with MVD separately, while the D value did not correlate with MVD. D value negatively correlated to VM moderately, and other parameters did not associate with VM. D* and fD* values were positively correlated with PCI, but no correlation was observed between other parameters and PCI. CONCLUSIONS: IVIM may evaluate the tumor microvessel architecture. D*, f, and fD* may reflect the endothelial lining blood vessel; D could indirectly reflect the VM; D* and fD* could reflect PCI(the normal degree of the tumor blood vessel). CLINICAL RELEVANCE STATEMENT: An intravoxel incoherent motion may be useful in assessing rhabdomyosarcoma microvessel structure to predict the target and effectiveness of anti-angiogenic therapy. KEY POINTS: • IVIM may be used to evaluate the tumor microvessel architecture in the mouse rhabdomyosarcoma model. • The MRI-pathology control method achieves correspondence between MRI slices and pathology slices, which ensures the consistency of the ROI of MRI and the pathology observation region.

Rare-Earth Metal Complexes Supported by 1,3-Functionalized Indolyl-Based Ligands for Efficient Hydrosilylation of Alkenes.

Two different 1,3-functionalized indolyl-based proligands 1-(2-C4H7O)CH2-3-(2-tBuC6H5N═CH)C8H5N (HL1) and 1-Me2NCH2CH2-3-(2-iPrC6H5N═CH)C8H5N (HL2) were designed, prepared in high yields, and successfully applied to rare-earth metal chemistry showing different reactivities and different bondings with the central metals. The reactions of HL1 with RE(CH2SiMe3)3(THF)2 provided two types of rare-earth metal complexes: the pincer type mononuclear complexes κ3-(L1)RE(CH2SiMe3)2 [L1 = 1-(2-C4H7O)CH2-3-(2-tBuC6H5N═CH)C8H4N, RE = Lu(1), Yb(2)], and the dinuclear rare-earth metal alkyl (per alkyl/per metal) complexes having the ligand in novel coordination modes {(η1:(µ-η2:η1):η1-1-(2-C4H7O)CH2-3-[2-tBuC6H5NCH-(CH2SiMe3)]C8H4N)RECH2SiMe3}2 [RE = Er(3), Y(4), Dy(5), and Gd(6)]. Meanwhile, the reactions of HL2 with RE(CH2SiMe3)3(THF)2 led to the isolation and characterization of only the mononuclear rare-earth metal dialkyl complexes κ3-(L2)RE(CH2SiMe3)2 [L2 = 1-Me2NCH2CH2-3-(2-iPrC6H5N═CH)C8H4N, RE = Lu(7), Gd(8)] bearing the ligand in the pincer chelate form. The mononuclear complexes were formed through the sp2 C-H activation of the 2-indolyl moiety, while the dinuclear complexes were produced unexpectedly through the tandem 2-indolyl sp2 C-H activation and C═N insertion into the RE-CH2SiMe3 bond. These complexes were fully characterized by spectroscopic methods, elemental analyses, and single-crystal X-ray crystallography. The applications of the synthesized complexes as catalysts for the hydrosilylation of terminal alkenes with phenylsilane are described. Anti-Markovnikov addition products were produced by the hydrosilylation of aliphatic olefins, and Markovnikov addition products were isolated with aromatic olefins with high selectivity in the absence of cocatalysts. It is found that the dinuclear rare-earth alkyl complexes exhibited the best catalytic activity with the advantages of mild reaction conditions, short reaction time, low catalyst loading, and wide substrate applicability in comparison with the synthesized mononuclear complexes and the reported catalysts.

Soft tissue sarcoma: intravoxel incoherent motion and diffusion kurtosis imaging parameters correlate with the histological grade and Ki-67 expression.

BACKGROUND: Accurate prediction of the histological grade and Ki-67 expression of soft tissue sarcoma (STS) before surgery is essential for the subsequent diagnosis, treatment, and prognostic evaluation of patients. PURPOSE: To evaluate intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in predicting the histological grade and Ki-67 expression of STS. MATERIAL AND METHODS: A total of 40 patients underwent 3-T MRI, including conventional sequences; IVIM and DKI parameters were obtained. All patients were divided into a low-grade (grade 1 and grade 2) group and a high-grade (grade 3) group through pathological analysis. Ki-67 expression of each lesion was calculated. Chi-square test, independent sample t-test, Mann-Whitney U test, Pearson, Spearman, and receiver operating characteristic curve analysis were performed. RESULTS: There were 17 patients in the low-grade group and 23 in the high-grade group. Ki-67 expression was in the range of 10%-80%. D value was inversely correlated with Ki-67 expression. MK value showed a moderate positive correlation with Ki-67 expression. Regarding histological grading, only the peritumoral enhancement was statistically different between low- and high-grade STS on conventional MRI (P=0.024). The high-grade group had significantly higher MK value and lower D and MD value than the low-grade group. MK value showed the best diagnostic performance. The combination of MK and MD yielded the highest specificity (88.24%), and the combination of D, MK, and MD yielded the best area under the curve value (0.841) and sensitivity (95.65%). CONCLUSION: IVIM and DKI parameters were correlated with Ki-67 expression and could help differentiate between low- and high-grade STS.

Development of clinical and magnetic resonance imaging-based radiomics nomograms for the differentiation of nodular fasciitis from soft tissue sarcoma.

BACKGROUND: Accurate differentiation of nodular fasciitis (NF) from soft tissue sarcoma (STS) before surgery is essential for the subsequent diagnosis and treatment of patients. PURPOSE: To develop and evaluate radiomics nomograms based on clinical factors and magnetic resonance imaging (MRI) for the preoperative differentiation of NF from STS. MATERIAL AND METHODS: This retrospective study analyzed the MRI data of 27 patients with pathologically diagnosed NF and 58 patients with STS who were randomly divided into training (n = 62) and validation (n = 23) groups. Univariate and multivariate analyses were performed to identify the clinical factors and semantic features of MRI. Radiomics analysis was applied to fat-suppressed T1-weighted (T1W-FS) images, fat-suppressed T2-weighted (T2W-FS) images, and contrast-enhanced T1-weighted (CE-T1W) images. The radiomics nomograms incorporating the radiomics signatures, clinical factors, and semantic features of MRI were developed. ROC curves and AUCs were carried out to compare the performance of the clinical factors, radiomics signatures, and clinical radiomics nomograms. RESULTS: Tumor location, size, heterogeneous signal intensity on T2W-FS imaging, heterogeneous signal intensity on CE-T1W imaging, margin definitions on CE-T1W imaging, and septa were independent predictors for differentiating NF from STS (P < 0.05). The performance of the radiomics signatures based on T2W-FS imaging (AUC = 0.961) and CE-T1W imaging (AUC = 0.938) was better than that based on T1W-FS imaging (AUC = 0.833). The radiomics nomograms had AUCs of 0.949, which demonstrated good clinical utility and calibration. CONCLUSION: The non-invasive clinical radiomics nomograms exhibited good performance in the differentiation of NF from STS, and they have clinical application in the preoperative diagnosis of diseases.

Radiomics model based on intravoxel incoherent motion and diffusion kurtosis imaging for predicting histopathological grade and Ki-67 expression level of soft tissue sarcomas.

BACKGROUND: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). PURPOSE: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. MATERIAL AND METHODS: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. RESULTS: D-SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). CONCLUSION: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs.

Correlations between DWI, IVIM, and HIF-1α expression based on MRI and pathology in a murine model of rhabdomyosarcoma.

PURPOSE: To investigate the correlation between DWI, intravoxel incoherent motion (IVIM), and hypoxia-inducible factor 1-alpha (HIF-1α) expression in a nude mouse model of rhabdomyosarcoma based on imaging and pathological comparisons. METHODS: Human rhabdomyosarcoma-derived (RD) cells were inoculated into the right thigh muscle of 20 BALB/c female nude mice. Mice were imaged using 3.0 Tesla MRI system. T1 -weighted imaging, T2 -weighted imaging, DWI, and IVIM images were obtained. ADW4.7 (GE Healthcare, ChicagoAQ34, IL, USA) was used for image processing of ADC, Dslow , Dfast , and f values. All parameter values were independently analyzed by 2 observers. Immunohistochemistry of HIF-1α was performed. We used a specific image-pathology comparison method to ensure correct overlap between the image plane and the pathological section. Mann-Whitney U test or independent sample t test, Pearson or Spearman correlation test, the intragroup correlation coefficient, Kolmogorov-Smirnov test, and receiver operating characteristic curve were used. The correlation between DWI and intravoxel incoherent motion parameter values and HIF-1α expression was determined. RESULTS: There were 10 mice in the low-expression group and 7 in the high-expression group. The ADC and Dslow values were negatively correlated with HIF-1α with correlation coefficients of -0.491 and - 0.702 (P = 0.045 and 0.002). The f value positively correlated with HIF-1α expression (r = 0.485, P = 0.048). ADC, Dslow , and f were significantly different between the high-HIF-1α expression tumors and the low-HIF-1α expression tumors. ADC showed the best predictive performance among all parameters (area under the curve = 0.652, sensitivity = 83.3%, specificity = 63.6%). CONCLUSION: The parameter values of DWI and intravoxel incoherent motion can be used to evaluate the expression of HIF-1α in rhabdomyosarcoma. ADC, Dslow , and f value showed correlation with the expression of HIF-1α.

DWI and IVIM Imaging in a Murine Model of Rhabdomyosarcoma: Correlations with Quantitative Histopathologic Features.

BACKGROUND: High cellularity and abnormal interstitial structures are some of the unfavorable factors that affect the treatment outcomes and survival of rhabdomyosarcoma (RMS) patients. PURPOSE: To explore the correlation between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with quantitative histopathologic features in a murine model of RMS. STUDY TYPE: Prospective. ANIMAL MODEL: Murine model of RMS (31 female BALB/c nude mice). FIELD STRENGTH/SEQUENCE: 3.0 T; fast spin-echo (FSE) T1-weighted imaging, fast relaxation fast spin-echo (FRFSE) T2-weighted imaging, DWI PROPELLER FSE imaging sequence, and IVIM echo planar imaging sequence; 10 different b-values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 1200 s/mm2 ). ASSESSMENT: Magnetic resonance imaging (MRI) was performed after 30-45 days of implantation. The following MRI parameters were calculated: apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Histopathologic features, which contained nuclear, cytoplasmic, and stromal fractions, and the nuclear-to-cytoplasmic ratio within the tumor were measured using image-based segmentation. STATISTICAL TESTS: Pearson's correlation, multiple linear regression analysis, and receiver operating characteristic curve analysis were performed. A P < 0.05 was considered statistically significant. RESULTS: The ADC value showed moderate negative correlation with nuclear fraction (r = -0.540), and moderate positive correlation with stroma fraction (r = 0.474). The D value showed moderate negative correlation with nuclear fraction (r = -0.491), and moderate positive correlation with stroma fraction (r = 0.421). The f value showed a moderate negative correlation with stroma fraction (r = -0.423). The D value showed the best diagnostic ability. The optimal cut-off D value of 0.460 was associated with 77.8% sensitivity and 68.2% specificity (area under the curve, 0.747). DATA CONCLUSION: The ADC, D, and f values obtained from DWI and IVIM images showed moderate correlation with the quantitative histopathologic features in a murine model of RMS. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

An Update in Imaging Evaluation of Histopathological Grade of Soft Tissue Sarcomas Using Structural and Quantitative Imaging and Radiomics.

Over the past two decades, considerable efforts have been made to develop non-invasive methods for determining tumor grade or surrogates for predicting the biological behavior, aiding early treatment decisions, and providing prognostic information. The development of new imaging tools, such as diffusion-weighted imaging, diffusion kurtosis imaging, perfusion imaging, and magnetic resonance spectroscopy have provided leverage in the diagnosis of soft tissue sarcomas. Artificial intelligence is a new technology used to study and simulate human thinking and abilities, which can extract and analyze advanced and quantitative image features from medical images with high throughput for an in-depth characterization of the spatial heterogeneity of tumor tissues. This article reviews the current imaging modalities used to predict the histopathological grade of soft tissue sarcomas and highlights the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Soft tissue sarcoma: IVIM and DKI parameters correlate with Ki-67 labeling index on direct comparison of MRI and histopathological slices.

OBJECTIVES: To explore the correlation of parameters derived from intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) with Ki-67 labeling index (LI) in soft tissue sarcoma (STS). METHODS: Forty-one patients with STS underwent IVIM and DKI imaging at 3.0 MRI. The standard apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) were compared between Ki-67 low- and high-expression groups by two independent observers. A novel method was used to ensure the topographic correlation of histologic sections and magnetic resonance imaging slices. Receiver operating characteristic (ROC), intraclass correlation coefficient (ICC), and Spearman's rank correlations were performed for statistical analysis. RESULTS: The high-expression group displayed lower standard ADC, D, and MD values and a higher MK value than the low-expression group. No significant differences were found for D∗ and f values. The areas under the curve for standard ADC, D, MD, and MK when discriminating between low- and high-expression groups were 0.736, 0.745, 0.848, and 0.894, respectively. MK was positively correlated with Ki-67 LI (r = 0.809, p < 0.001). Standard ADC, D, and MD were negatively correlated with Ki-67 LI (r = -0.541, -0.556, -0.702, respectively, p < 0.001). CONCLUSIONS: IVIM and DKI parameters are correlated with Ki-67 LI. MK may be the optimal imaging biomarker for assessing the Ki-67 expression of STS. KEY POINTS: • IVIM and DKI parameters are correlated with the expression of Ki-67 in STS. • The MRI-pathology control method ensured a strong correlation between MRI slices and histologic sections, resulting in a robust radiological-pathological correlation.

Rare-Earth-Metal-Complex-Catalyzed Hydroalkoxylation and Tandem Hydroalkoxylation/Cyclohydroamination of Isocyanates: Synthesis of Carbamates and Oxazolidinones.

Novel N,N,N-tridentate ß-diketiminato rare-earth-metal dialkyl complexes LRE(CH2SiMe3)2 [RE = Y (1a), Gd (1b), Yb (1c), Lu (1d); L = MeC(NDipp)CHC(Me)N(CH2)2NC4H8, where Dipp = 2,6-iPr2C6H3] have been conveniently synthesized by one step from reactions of the rare-earth-metal trialkyl complexes RE(CH2SiMe3)3(THF)2 (THF = tetrahydrofuran) with a pyrrolidine-functionalized ß-diketiminate HL, and their catalytic behaviors toward hydroalkoxylation and tandem hydroalkoxylation/cyclohydroamination of isocyanates have been described. These rare-earth-metal catalysts exhibited high efficiency in the hydroalkoxylation of isocyanates, providing a variety of N-alkyl and N-aryl carbamate derivatives under mild reaction conditions with a rather low catalyst loading (0.04 mol %). More significantly, they can promote a tandem hydroalkoxylation/cyclohydroamination reaction between terminal and internal propargylic alcohols with substituted arylisocyanates, leading to the efficient synthesis of methylene and (Z)-selective arylidene oxazolidinones in good-to-high yields via consecutive C-O and C-N bond formation. The stoichiometric reaction of 1a with p-tolylisocyanate generated an unusual dinuclear yttrium complex, {[η2-(4-MePhNCO)(CH2SiMe3)]Y[µ-η2:η1:η1-(4-MePhNCO)CC(Me)(NDipp)C(Me)N(CH2)2NC4H8]}2 (7a), with two different amidate units, which underwent an sp2 C-H bond activation of the ß-diketiminato backbone, followed by the insertion of isocyanate.

The diagnostic accuracy of intravoxel incoherent motion and diffusion kurtosis imaging in the differentiation of malignant and benign soft-tissue masses: which is better?

BACKGROUND: It is difficult for conventional magnetic resonance imaging (MRI) to distinguish benign soft-tissue masses (STMs) from malignant masses. PURPOSE: To quantitatively compare the diagnostic value of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in STMs. MATERIAL AND METHODS: The data from 58 patients with STMs were retrospectively analyzed. The GE Discovery 3.0-T MRI scanner was used to acquire conventional MRI sequences, IVIM, and DKI images. The chi-square test, independent sample t-test, and Mann-Whitney U tests were used to compare the differences between conventional MRI features, IVIM, and DKI parameters (Dslow, Dfast, f, mean kurtosis [MK], and mean diffusivity [MD]) between the benign and malignant groups. Receiver-operating characteristic (ROC) curve analysis was also performed. RESULTS: Tumor size and depth are statistically different in STTs. Dslow, MK, and MD values in the malignant groups are significantly lower than the benign groups (P < 0.05). However, Dfast and f values are not statistically different between the two groups. The area under the curve (AUC) of Dslow value (0.859) is higher than MD (0.765) and MK (0.676) values for identifying benign and malignant STMs. The Dslow value showed the best specificity (82.93%). The sensitivity and specificity of IVIM and DKI parameters are higher than that of conventional MRI sequences. CONCLUSION: IVIM and DKI can be used to distinguish between benign and malignant STMs, with Dslow as the most meaningful parameter.

Soft tissue sarcomas: IVIM and DKI correlate with the expression of HIF-1α on direct comparison of MRI and pathological slices.

OBJECTIVE: To investigate the correlation of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters with the expression of HIF-1α in soft tissue sarcoma (STS). METHODS: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained from all patients. Forty patients with STS who underwent 3.0 T MRI, including IVIM and DKI, were included in the study. Standard apparent diffusion coefficient (ADC), true ADC (Dslow), pseudo ADC (Dfast), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) of each lesion were independently analyzed by two observers. An MRI-pathology control method was used to ensure correspondence between the MRI slices and the pathological sections. Spearman analysis, independent sample t test, Mann-Whitney U test, chi-squared test, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Dslow and MD values showed a negative correlation with HIF-1α expression (r = - 0.469, - 0.588). MK and f values showed a positive correlation with HIF-1α expression (r = 0.779, 0.572). Dslow, MD, MK, and f values showed significant differences between the high- and low-expression groups. The MK value showed the best diagnostic ability. The optimal cut-off MK value of 0.604 was associated with 78.3% sensitivity and 88.2% specificity (area under the curve, 0.867). CONCLUSIONS: This preliminary study demonstrated the association of IVIM and DKI parameters with the expression of HIF-1α in STS. KEY POINTS: • IVIM and DKI parameters are correlated with the expression of HIF-1α in STS. • The MRI-pathology control method can be used in clinical studies to ensure correspondence between MRI slices and pathology sections.

Transformation of the sp2 Carbanion to Carbene with Subsequent 1,1-Migratory Insertion and Nucleophilic Substitution in Rare-Earth Metal Chemistry.

The development of Fischer-type electrophilic carbene chemistry with early transition metals has been a great challenge due to the fact that such metals in their high oxidation states lack the d electrons to stabilize the electrophilic carbene. Herein, we disclose the first experimental and theoretical findings of in situ transformation of an sp2 carbanion to a Fischer-type electrophilic carbene with rare-earth metals in their high oxidation state with a d0 electron via electron transfer. The carbene may undergo 1,1-migratory insertion into an adjacent RE-C(sp3) bond, and an unprecedented ring opening of the indole ring of the ligand occurs when the carbenes undergo nucleophilic substitution with a special organolithium reagent o-Me2NC6H4CH2Li. The key to success is the uniquely tailored novel ligand systems featuring a suitable conjugate building block (-C═C-C═N) bearing an sp2 carbanion connected to the rare-earth metal center.

The diagnostic performance of conventional ultrasound and strain elastography in malignant soft tissue tumors.

OBJECTIVE: To investigate the diagnostic value of conventional ultrasound (US) and strain elastography (SE) in malignant soft tissue tumors. METHOD: A total of 83 soft tissue masses were included prospectively. US and SE imaging were performed at the same time. Two observers assessed the B mode, color Doppler, elastic scores (ES), strain ratio (SR), and SE size to B mode size (EI/B) ratio and compared the consistency of the data between the observers. According to the pathological diagnosis of resection, the cases were divided into malignant and nonmalignant groups. The diagnostic value of conventional US and SE in the prediction of malignant soft tissue tumors was assessed. RESULTS: The pathology results divided cases into 36 malignant lesions and 47 nonmalignant lesions. There was no statistically significant difference in gender, location, maximum diameter, echo, tail sign, cystic component, Doppler scores, or SR between the two groups (p > 0.05). However, significant differences between the two groups were found in age, depth, heterogeneity, edge, ES, and EI/B (p < 0.05). The biggest area under the receiver operating characteristics curve (0.934) was the combination model of age, heterogeneity, edge, ES, and EI/B, and the sensitivity and specificity were 0.861 and 0.957, respectively. CONCLUSIONS: Conventional US and SE are significant for the diagnosis of malignant soft tissue tumors, and SE can be used as a complementary technique to the characterization of STTs using conventional US.

DWI and IVIM are predictors of Ki67 proliferation index: direct comparison of MRI images and pathological slices in a murine model of rhabdomyosarcoma.

OBJECTIVES: The purpose of this study was to investigate the correlation of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the Ki67 proliferation index in a murine model of rhabdomyosarcoma. METHODS: The rhabdomyosarcoma model was established by injecting RD cells into the right hind flank of nude mice. The mice underwent 3.0T magnetic resonance imaging (MRI), including DWI and IVIM. The apparent diffusion coefficient (ADC), D, D*, and f were calculated with the ADW4.7 workstation. A specialized method was employed to ensure the pathological sections corresponded to the correct MRI slices. The Ki67 proliferation index was analyzed by immunohistochemistry, and any possible correlations were assessed between the DWI and IVIM parameters and Ki67 proliferation index. RESULTS: Twenty-seven rhabdomyosarcoma mice were established successfully. After 46 days, the average tumor volume reached 1094.78 ± 678.77 mm3. The average ADC, D, and D* values were 1.0470 ± 0.2036 × 10-3 mm2/s, 0.7237 ± 0.0971 × 10-3 mm2/s, and 4.8497 ± 1.6293 × 10-3 mm2/s, respectively. The range in f values was 0.102-0.229. The ADC and D values showed a moderate negative correlation with the Ki67 proliferation indexes (r = - 0.543, p = 0.003; r = - 0.491, p = 0.009, respectively). In addition, the f value showed a weak negative correlation with the Ki67 proliferation indexes (r = - 0.151, p = 0.451), while the D* value showed no association with the Ki67 proliferation indexes (r = - 0.037, p = 0.853). CONCLUSIONS: The ADC value of DWI, along with the D value of IVIM, may be reflective of Ki67 proliferation indexes in murine models of rhabdomyosarcoma. KEY POINTS: • DWI and IVIM parameters are correlated with Ki67 proliferation indexes in rhabdomyosarcoma mouse models. • A specialized method ensured a strong correlation between pathological sections and MRI slices, resulting in a robust radiological-pathological correlation.