CineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel.

Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. Serial in vivo cineCT imaging provided data in hearts from control pigs (n = 3) and data from pigs (n = 5) under baseline conditions before MI induction, post-MI day 3, post-MI day 7, and one hour after intramyocardial delivery of a hyaluronic acid (HA)-based hydrogel with shear-thinning and self-healing properties to the central infarct area. Isolated, excised hearts underwent similar cineCT imaging using an ex vivo perfused heart preparation with cyclic LV pressurization. Deformations were evaluated using nonlinear image registration of cineCT volumes between end-diastole (ED) and end-systole (ES), and 3D Lagrangian strains were calculated from the displacement gradients. Post-MI day 3, radial, circumferential, maximum principal, and shear strains were reduced within the MI region (p < 0.04) but were unchanged in normal regions (p > 0.6), and LV end diastolic volume (LV EDV) increased (p = 0.004), while ejection fraction (EF) and stroke volume (SV) decreased (p < 0.02). Post-MI day 7, radial strains in MI border zones increased (p = 0.04) and dilation of LV EDV continued (p = 0.052). There was a significant negative linear correlation between regional radial and maximum principal/shear strains and percent infarcted tissue in all hearts (R2 > 0.47, p < 0.004), indicating that cineCT strain measures could predict MI location and degree of injury. Post-hydrogel day 7 post-MI, LV EDV was significantly reduced (p = 0.009), EF increased (p = 0.048), and radial (p = 0.021), maximum principal (p = 0.051), and shear strain (p = 0.047) increased within regions bordering the infarct. A smaller strain improvement within the infarct and normal regions was also noted on average along with an improvement in SV in 4 out of 5 hearts. CineCT provides a reliable method to assess regional changes in strains post-MI and the therapeutic effects of intramyocardial hydrogel delivery.

Serum vitamin D level correlates with disease activity and health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND AND OBJECTIVE: The association between vitamin D levels and disease activity has been established in patients with several autoimmune rheumatic diseases. We aimed to examine the association between vitamin D and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Fifty-four AAV patients and 50 age- and sex-matched healthy controls without vitamin D supplements were included. Clinical and laboratory data were evaluated during the assessment of vitamin D levels. Two different forms of vitamin D in the sera-25(OH)D, which is the sum of 25(OH)D2 and 25(OH)D3, and 25(OH)D3, which only includes 25(OH)D in its D3 form-were measured, and the relationship between vitamin D and the obtained data was assessed. Variations in vitamin D levels relative to the season were also evaluated. RESULTS: Patients with AAV demonstrated considerably lower 25(OH)D serum levels than healthy controls (16.0 vs. 20.4 ng/mL, p = 0.016), and the proportion of individuals with vitamin D deficiency was higher in patients with AAV than in healthy controls (68.5% vs. 48.0%, p = 0.035). Both serum 25(OH)D and 25(OH)D3 were positively associated with the 36-item Short-form Health Survey (SF-36) physical component summary and SF-36 mental component summary (MCS) scores. A negative correlation was observed between 25(OH)D and 25(OH)D3 serum levels and Birmingham vasculitis activity score (BVAS), C­reactive protein (CRP), and white blood cell count. Linear regression analysis indicated haemoglobin and 25(OH)D levels to be independently associated with BVAS and CRP and 25(OH)D levels with SF-36 MCS score. No seasonal variations were observed in vitamin D levels. CONCLUSION: The results from this study suggest that vitamin D levels could provide clinically useful information in AAV.

Preoperative MRI Evaluation of Thyroid Cartilage Invasion in Patients with Laryngohypopharyngeal Cancer: Comparison of Contrast-Enhanced 2D Spin-Echo and 3D T1-Weighted Radial Gradient Recalled-Echo Techniques.

BACKGROUND AND PURPOSE: Accurate assessment of thyroid cartilage invasion on preoperative imaging influences management in patients with laryngeal and hypopharyngeal cancers. We evaluated the clinical usefulness of contrast-enhanced 3D T1-weighted radial gradient recalled-echo for preoperative assessment of thyroid cartilage invasion in patients with laryngohypopharyngeal squamous cell carcinoma, compared with 2D spin-echo T1WI. MATERIALS AND METHODS: Preoperative MR images of 52 consecutive patients who were diagnosed with laryngeal or hypopharyngeal cancer and underwent partial or total laryngectomy were analyzed. Pathologic specimens served as reference standards. Two independent head and neck radiologists evaluated the presence of thyroid cartilage invasion in both contrast-enhanced 2D spin-echo T1WI and 3D gradient recalled-echo sequences. The sensitivity, specificity, and accuracy of the 2 modalities were compared. The area under the curve was a measure of diagnostic performance. RESULTS: Pathologic neoplastic thyroid cartilage invasion was identified in 24 (46.2%) of the 52 patients. The sensitivity (75.0%), specificity (96.4%), and accuracy (86.5%) of contrast-enhanced 3D gradient recalled-echo were significantly higher than those of 2D spin-echo T1WI (58.3%, 89.3%, and 75.0%; P = .017, .003, and .002, respectively). 3D gradient recalled-echo had significantly better diagnostic performance (area under the curve = 0.963) than 2D spin-echo T1WI (area under the curve = 0.862; P = .010). CONCLUSIONS: Contrast-enhanced 3D gradient recalled-echo was diagnostically superior in identifying neoplastic thyroid cartilage invasion compared with 2D spin-echo T1WI in patients with laryngohypopharyngeal cancer, and therefore, may provide more accurate preoperative staging.

Development and Validation of a Deep Learning-Based Model to Distinguish Glioblastoma from Solitary Brain Metastasis Using Conventional MR Images.

BACKGROUND AND PURPOSE: Differentiating glioblastoma from solitary brain metastasis preoperatively using conventional MR images is challenging. Deep learning models have shown promise in performing classification tasks. The diagnostic performance of a deep learning-based model in discriminating glioblastoma from solitary brain metastasis using preoperative conventional MR images was evaluated. MATERIALS AND METHODS: Records of 598 patients with histologically confirmed glioblastoma or solitary brain metastasis at our institution between February 2006 and December 2017 were retrospectively reviewed. Preoperative contrast-enhanced T1WI and T2WI were preprocessed and roughly segmented with rectangular regions of interest. A deep neural network was trained and validated using MR images from 498 patients. The MR images of the remaining 100 were used as an internal test set. An additional 143 patients from another tertiary hospital were used as an external test set. The classifications of ResNet-50 and 2 neuroradiologists were compared for their accuracy, precision, recall, F1 score, and area under the curve. RESULTS: The areas under the curve of ResNet-50 were 0.889 and 0.835 in the internal and external test sets, respectively. The area under the curve of neuroradiologists 1 and 2 were 0.889 and 0.768 in the internal test set and 0.857 and 0.708 in the external test set, respectively. CONCLUSIONS: A deep learning-based model may be a supportive tool for preoperative discrimination between glioblastoma and solitary brain metastasis using conventional MR images.

MRI Features May Predict Molecular Features of Glioblastoma in Isocitrate Dehydrogenase Wild-Type Lower-Grade Gliomas.

BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma. MATERIALS AND METHODS: In this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set. RESULTS: In the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P < . 001, both). When both Visually AcceSAble Rembrandt Images and radiomics were added to clinical features, the predictive performance significantly increased (areas under the curve = 0.514 versus 0.863, P < .001). CONCLUSIONS: MR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Hyperattenuating lesions after mechanical thrombectomy in acute ischaemic stroke: factors predicting symptomatic haemorrhage and clinical outcomes.

AIM: To evaluate the clinical significance of hyperattenuating lesions on CT after mechanical thrombectomy for acute ischaemic stroke, and to identify imaging factors that predict symptomatic haemorrhage and unfavourable outcomes. MATERIALS AND METHODS: Seventy-eight patients with acute ischaemic stroke in the anterior circulation who underwent mechanical thrombectomy were evaluated. All patients underwent post-interventional unenhanced computed tomography (CT) within 24 h and follow-up CT or magnetic resonance imaging (MRI) within 7 days. Baseline characteristics and clinical outcomes were compared between patients with and without hyperattenuating lesions. In patients with hyperattenuating lesions, clinical and imaging factors that predict symptomatic haemorrhage and unfavourable outcomes were determined. RESULTS: Fifty-six of 78 patients (71.8%) demonstrated hyperattenuating lesions on post-interventional CT. Patients with hyperattenuating lesions showed lower Alberta Stroke Program Early CT score (ASPECTS), persistent/symptomatic haemorrhage, and unfavourable outcomes than those without. In patients with hyperattenuating lesions, larger hyperattenuating lesion volume (>21.3 ml; OR, 55.60, p<0.001) and perilesional oedema (OR, 46.04, p=0.015) were independent factors predicting symptomatic haemorrhage. Older age (OR, 1.2, p=0.006) and lower ASPECTS (OR, 0.45, p=0.046) were independent factors predicting unfavourable outcomes in patients with hyperattenuating lesions. Adding the volume of the hyperattenuating lesion to age and ASPECTS increased the predictive performance of unfavourable outcomes (area under the curve 0.874 versus 0.934, p=0.043). CONCLUSIONS: Hyperattenuating lesions on post-interventional CT are associated with increased risk of symptomatic haemorrhage and unfavourable outcomes. Larger hyperattenuating lesion volume is an independent factor of symptomatic haemorrhage and it has added predictive value for unfavourable outcomes.

Prognostic nutritional index is correlated with disease activity in patients with systemic lupus erythematosus.

The prognostic nutritional index (PNI), which is calculated using serum albumin level and total lymphocyte count in the peripheral blood, is regarded as an index that reflects the immunonutritional status of patients. PNI was calculated in 217 systemic lupus erythematosus (SLE) patients according to the following formula: 10 × serum albumin value (g/dL) + 0.005 × peripheral lymphocyte count (/mm3). Pearson's correlation analysis was used to elucidate the correlation between continuous variables. Linear and logistic regression analyses were performed to assess the correlation between laboratory variables and SLE Disease Activity Index-2000 (SLEDAI-2 K) and to differentiate between active and inactive SLE. Ninety-three patients were classified as active SLE (SLEDAI-2 K ≥ 5) and 124 as inactive SLE. Patients with active SLE exhibited lower median PNI than those with inactive SLE (39.0 vs. 49.1, p < 0.001). Multivariable logistic regression analysis revealed PNI as an independent predictor of active SLE. Multivariable linear regression analysis revealed that PNI was significantly correlated with laboratory variables of SLEDAI-2 K, erythrocyte sedimentation rate, C-reactive protein and SLEDAI-2 K. Furthermore, in patients who switched from active to inactive SLE after treatment ( n = 55), PNI increased as disease activity improved ( p < 0.001), which suggests that PNI may be useful for estimating SLE activity.

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of IDH1-Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

BACKGROUND AND PURPOSE: Prediction of the isocitrate dehydrogenase 1 (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas. MATERIALS AND METHODS: Ninety-three patients with World Health Organization grade II gliomas with known IDH1-mutation and 1p/19q-codeletion status (18 IDH1 wild-type, 45 IDH1 mutant and no 1p/19q codeletion, 30 IDH1-mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the IDH1-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for IDH1 wild-type tumors and 1p/19q-codeletion status in IDH1-mutant subgroups were evaluated using the least absolute shrinkage and selection operator. RESULTS: Various histogram and texture parameters differed significantly according to IDH1-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an IDH1 wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in IDH1-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807. CONCLUSIONS: Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.

Renal outcome after kidney-transplantation in Korean patients with lupus nephritis.

We investigated renal outcome of kidney-transplantation in 19 Korean recipients with biopsy-proven lupus nephritis and compared it with 18 Korean age- and gender-matched recipients without lupus nephritis who were diagnosed with end-stage renal disease caused by renal diseases other than lupus nephritis in a single centre. We reviewed histological findings of kidneys and calculated cumulative dose of immunosuppressive agents. We assessed renal flare of systemic lupus erythematosus, recurrence of lupus nephritis and graft failure as prognosis. The mean age of recipients with lupus nephritis was 43.5 years and all patients were female. Six patients had class III, 10 had class IV and three had class V. There were no meaningful differences in demographic data, renal replacement modality, cumulative doses of immunosuppressants and prognosis between recipients with and without lupus nephritis. Eight patients experienced renal flare of systemic lupus erythematosus, but there were no cases of recurrence of lupus nephritis or graft failure in recipients with lupus nephritis. Kidney-recipients with class IV lupus nephritis exhibited a lower cumulative renal flare of systemic lupus erythematosus free survival rate than those with class III lupus nephritis. In conclusion, renal outcome of kidney-transplantation in patients with lupus nephritis is similar to that in those without lupus nephritis, and class IV was associated with renal flare of systemic lupus erythematosus.

Prediction of IDH1-Mutation and 1p/19q-Codeletion Status Using Preoperative MR Imaging Phenotypes in Lower Grade Gliomas.

BACKGROUND AND PURPOSE: WHO grade II gliomas are divided into three classes: isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant and no 1p/19q codeletion, and IDH-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas. MATERIALS AND METHODS: MR imaging scans of 175 patients with lower grade gliomas with known IDH1 mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set. MR imaging features were reviewed by using Visually AcceSAble Rembrandt Images (VASARI); their associations with molecular markers were assessed. The predictive power of imaging features for IDH1-wild type tumors was evaluated using the Least Absolute Shrinkage and Selection Operator. We tested the model in a validation set (40 subjects). RESULTS: Various imaging features were significantly different according to IDH1 mutation. Nonlobar location, larger proportion of enhancing tumors, multifocal/multicentric distribution, and poor definition of nonenhancing margins were independent predictors of an IDH1 wild type according to the Least Absolute Shrinkage and Selection Operator. The areas under the curve for the prediction model were 0.859 and 0.778 in the discovery and validation sets, respectively. The IDH1-mutant, 1p/19q-codeleted group frequently had mixed/restricted diffusion characteristics and showed more pial invasion compared with the IDH1-mutant, no codeletion group. CONCLUSIONS: Preoperative MR imaging phenotypes are different according to the molecular markers of lower grade gliomas, and they may be helpful in predicting the IDH1-mutation status.

Detection of clinically occult primary tumours in patients with cervical metastases of unknown primary tumours: comparison of three-dimensional THRIVE MRI, two-dimensional spin-echo MRI, and contrast-enhanced CT.

AIM: To evaluate and compare the utility of contrast-enhanced three-dimensional (3D) T1-weighted high-resolution isotropic volume examination (THRIVE), spin-echo (SE) T1-weighted magnetic resonance imaging (MRI), and computed tomography (CT) for detecting clinically occult primary tumours in patients with cervical lymph node metastases. MATERIALS AND METHODS: Seventy-three consecutive patients with tumours that went undetected during endoscopic or physical examinations underwent preoperative contrast-enhanced CT and MRI (SE and 3D THRIVE) after gadolinium injection. Guided biopsy results served as reference standards. The diagnostic performances of the imaging techniques were compared with McNemar's tests. RESULTS: Primary tumours were identified in 59 (80.8%) of the 73 patients after surgery. Of these, 36 were found in the palatine tonsil, 11 in the base of the tongue, seven in the nasopharynx, and five in the pyriform sinus. The sensitivity (72.9%) and accuracy (71.2%) of 3D THRIVE for detecting primary tumours were higher than were those of SE T1-weighted MRI (49.2% and 53.4%, p≤0.002) or CT (36.4% and 46.4%, p≤0.001). The specificities of these techniques did not differ. The diagnostic performance of 3D THRIVE (area under the curve [AUC]=0.681) for detecting tumours did not differ from that of SE T1-weighted MRI or CT (AUC=0.671 and 0.608, p>0.05). CONCLUSION: 3D THRIVE was more sensitive at detecting primary tumours than was SE T1-weighted MRI or CT in patients with cervical metastases of unknown primary tumours. This sequence may improve biopsy and therapeutic planning in these patients.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein can reflect systemic lupus erythematosus activity.

Serum Mac-2-binding protein (M2BP) is elevated in various chronic inflammatory diseases, and evidence suggests that glycosylation of M2BP induces discrete biological effects. However, the role of serum M2BP in systemic lupus erythematosus (SLE) is still unclear. Recently, a Wisteria floribunda agglutinin-positive-M2BP (WFA+-M2BP) immunoassay has shown promise in detecting highly glycosylated M2BP. In this study, by using WFA+-M2BP immunoassay, we measured serum M2BP in 203 SLE patients and evaluated its clinical significance. Eighty patients were classified as having active SLE and 123 patients as having inactive SLE. The median serum M2BP was higher in patients with active SLE than in those with inactive SLE (2.1 vs. 0.9, p < 0.001). In multivariate linear regression analysis, serum M2BP, anti-dsDNA, C3 and erythrocyte sedimentation rate (ESR) were associated with SLEDAI-2K. Serum M2BP also strongly correlated with laboratory variables related to SLEDAI-2K, ESR and C-reactive protein. Furthermore, multivariate logistic regression analysis demonstrated that serum M2BP was useful in predicting active SLE. Finally, following immunosuppressive treatment, elevated serum M2BP significantly decreased along with improvement in disease activity. These findings suggest that serum M2BP might contribute to the inflammatory process in SLE, and measuring serum M2BP might be a useful marker to assess SLE disease activity.

The Initial Area Under the Curve Derived from Dynamic Contrast-Enhanced MRI Improves Prognosis Prediction in Glioblastoma with Unmethylated MGMT Promoter.

BACKGROUND AND PURPOSE: Although perfusion and permeability MR parameters have known to have prognostic value, they have reproducibility issues. Our aim was to evaluate whether the initial area under the time-to-signal intensity curve (IAUC) derived from dynamic contrast-enhanced MR imaging can improve prognosis prediction in patients with glioblastoma with known MGMT status. MATERIALS AND METHODS: We retrospectively examined 88 patients with glioblastoma who underwent preoperative dynamic contrast-enhanced MR imaging. The means of IAUC values at 30 and 60 seconds (IAUC30mean and IAUC60mean) were extracted from enhancing tumors. The prognostic values of IAUC parameters for overall survival and progression-free survival were assessed with log-rank tests, according to the MGMT status. Multivariate overall survival and progression-free survival models before and after adding the IAUC parameters as covariates were explored by net reclassification improvement after receiver operating characteristic analysis for 1.5-year overall survival and 1-year progression-free survival and by random survival forest. RESULTS: High IAUC parameters were associated with worse overall survival and progression-free survival in the unmethylated MGMT group, but not in the methylated group. In the unmethylated MGMT group, 1.5-year overall survival and 1-year progression-free survival prediction improved significantly after adding IAUC parameters (overall survival area under the receiver operating characteristic curve, 0.86; progression-free survival area under the receiver operating characteristic curve, 0.74-0.76) to the model with other prognostic factors (overall survival area under the receiver operating characteristic curve, 0.81; progression-free survival area under the receiver operating characteristic curve, 0.69; P < .05 for all) except in the case of IAUC60mean for 1-year progression-free survival prediction (P = .059). Random survival forest models indicated that the IAUC parameters were the second or most important predictors in the unmethylated MGMT group, except in the case of the IAUC60mean for progression-free survival. CONCLUSIONS: IAUC can be a useful prognostic imaging biomarker in patients with glioblastoma with known MGMT status, improving prediction of glioblastoma prognosis with the unmethylated MGMT promoter status.

The Added Prognostic Value of Preoperative Dynamic Contrast-Enhanced MRI Histogram Analysis in Patients with Glioblastoma: Analysis of Overall and Progression-Free Survival.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging in patients with glioblastoma is controversial. We investigated the added prognostic value of dynamic contrast-enhanced MR imaging to clinical parameters and molecular biomarkers in patients with glioblastoma by using histogram analysis. MATERIALS AND METHODS: This retrospective study consisted of 61 patients who underwent preoperative dynamic contrast-enhanced MR imaging for glioblastoma. The histogram parameters of dynamic contrast-enhanced MR imaging, including volume transfer constant, extravascular extracellular volume fraction, and plasma volume fraction, were calculated from entire enhancing tumors. Univariate analyses for overall survival and progression-free survival were performed with preoperative clinical and dynamic contrast-enhanced MR imaging parameters and postoperative molecular biomarkers. Multivariate Cox regression was performed to build pre- and postoperative models for overall survival and progression-free survival. The performance of models was assessed by calculating the Harrell concordance index. RESULTS: In univariate analysis, patients with higher volume transfer constant and extravascular extracellular volume fraction values showed worse overall survival and progression-free survival, whereas plasma volume fraction showed no significant correlation. In multivariate analyses for overall survival, the fifth percentile value of volume transfer constant and kurtosis of extravascular extracellular volume fraction were independently prognostic in the preoperative model, and kurtosis of volume transfer constant and extravascular extracellular volume fraction were independently prognostic in the postoperative model. For progression-free survival, independent prognostic factors were minimum and fifth percentile values of volume transfer constant and kurtosis of extravascular extracellular volume fraction in the preoperative model and kurtosis of extravascular extracellular volume fraction in the postoperative model. The performance of preoperative models for progression-free survival was significantly improved when minimum or fifth percentile values of volume transfer constant and kurtosis of extravascular extracellular volume fraction were added. CONCLUSIONS: Higher volume transfer constant and extravascular extracellular volume fraction values are associated with worse prognosis, and dynamic contrast-enhanced MR imaging may have added prognostic value in combination with preoperative clinical parameters, especially in predicting progression-free survival.

Differentiation between Cystic Pituitary Adenomas and Rathke Cleft Cysts: A Diagnostic Model Using MRI.

BACKGROUND AND PURPOSE: Cystic pituitary adenomas may mimic Rathke cleft cysts when there is no solid enhancing component found on MR imaging, and preoperative differentiation may enable a more appropriate selection of treatment strategies. We investigated the diagnostic potential of MR imaging features to differentiate cystic pituitary adenomas from Rathke cleft cysts and to develop a diagnostic model. MATERIALS AND METHODS: This retrospective study included 54 patients with a cystic pituitary adenoma (40 women; mean age, 37.7 years) and 28 with a Rathke cleft cyst (18 women; mean age, 31.5 years) who underwent MR imaging followed by surgery. The following imaging features were assessed: the presence or absence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, an off-midline location, the presence or absence of an intracystic nodule, size change, and signal change. On the basis of the results of logistic regression analysis, a diagnostic tree model was developed to differentiate between cystic pituitary adenomas and Rathke cleft cysts. External validation was performed for an additional 16 patients with a cystic pituitary adenoma and 8 patients with a Rathke cleft cyst. RESULTS: The presence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, and an off-midline location were more common with pituitary adenomas, whereas the presence of an intracystic nodule was more common with Rathke cleft cysts. Multiple logistic regression analysis showed that cystic pituitary adenomas and Rathke cleft cysts can be distinguished on the basis of the presence of a fluid-fluid level, septation, an off-midline location, and the presence of an intracystic nodule (P = .006, .032, .001, and .023, respectively). Among 24 patients in the external validation population, 22 were classified correctly on the basis of the diagnostic tree model used in this study. CONCLUSIONS: A systematic approach using this diagnostic tree model can be helpful in distinguishing cystic pituitary adenomas from Rathke cleft cysts.

Discrimination of Tumorous Intracerebral Hemorrhage from Benign Causes Using CT Densitometry.

BACKGROUND AND PURPOSE: Differentiation of tumorous intracerebral hemorrhage from benign etiology is critical in initial treatment plan and prognosis. Our aim was to investigate the diagnostic value of CT densitometry to discriminate tumorous and nontumorous causes of acute intracerebral hemorrhage. MATERIALS AND METHODS: This retrospective study included 110 patients with acute intracerebral hemorrhage classified into 5 groups: primary intracerebral hemorrhage without (group 1) or with antithrombotics (group 2) and secondary intracerebral hemorrhage with vascular malformation (group 3), brain metastases (group 4), or primary brain tumors (group 5). The 5 groups were dichotomized into tumorous (groups 4 and 5) and nontumorous intracerebral hemorrhage (groups 1-3). Histogram parameters of hematoma attenuation on nonenhanced CT were compared among the groups and between tumorous and nontumorous intracerebral hemorrhages. With receiver operating characteristic analysis, optimal cutoffs and area under the curve were calculated for discriminating tumorous and nontumorous intracerebral hemorrhages. RESULTS: Histogram analysis of acute intracerebral hemorrhage attenuation showed that group 1 had higher mean, 5th, 25th, 50th, and 75th percentile values than groups 4 and 5 and higher minimum and 5th percentile values than group 2. Group 3 had higher 5th percentile values than groups 4 and 5. After dichotomization, all histogram parameters except maximum and kurtosis were different between tumorous and nontumorous intracerebral hemorrhages, with tumors having lower cumulative histogram parameters and positive skewness. In receiver operating characteristic analysis, 5th and 25th percentile values showed the highest diagnostic performance for discriminating tumorous and nontumorous intracerebral hemorrhages, with 0.81 area under the curve, cutoffs of 34 HU and 44 HU, sensitivities of 65.6% and 70.0%, and specificities of 85.0% and 80.0%, respectively. CONCLUSIONS: CT densitometry of intracerebral hemorrhage on nonenhanced CT might be useful for discriminating tumorous and nontumorous causes of acute intracerebral hemorrhage.

Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia.

BACKGROUND AND PURPOSE: BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. MATERIALS AND METHODS: Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. RESULTS: Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). CONCLUSIONS: In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of permeability by using dynamic contrast-enhanced MR imaging. Therefore, dynamic contrast-enhanced MR imaging may serve as a potential imaging biomarker for assessing the BBB stabilization properties of pharmacologic agents.

Preoperative imaging evaluation of head and neck cancer: comparison of 2D spin-echo and 3D THRIVE MRI techniques with resected tumours.

AIM: To evaluate the usefulness of contrast-enhanced three-dimensional (3D) T1-weighted high-resolution isotropic volume examination (THRIVE) for the preoperative assessment of head and neck cancer, by comparison with spin-echo (SE) T1-weighted sequences and the pathology specimen. MATERIALS AND METHODS: Thirty-seven consecutive patients who were diagnosed with oral cavity, oropharyngeal, and hypopharyngeal cancer and received surgical excision with preoperative magnetic resonance imaging (MRI) using both SE and 3D THRIVE sequences after gadolinium injection were studied. Tumour conspicuity, motion- and flow-related artefacts were evaluated, and the tumour size was measured based on both sequences, which were correlated with the surgical specimen. The population correlation coefficient (r(g)(2)) and Bland-Altman plots were used to assess measurement agreement. RESULTS: There was no statistical difference between SE and THRIVE in terms of tumour conspicuity and motion-related artefacts, however, flow-related artefacts significantly decreased with THRIVE. The measurement agreement of tumour size estimated on both SE and THRIVE was good (r(g)(2) = 0.87 for SE and 0.93 for THRIVE), and the difference was statistically significant. CONCLUSION: The 3D THRIVE sequence provided satisfactory image quality for the accurate measurement of tumour size with fewer artefacts and could be an acceptable alternative for SE T1-weighted images for preoperative staging in patients with head and neck cancer.

Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post-exposure mouse models.

Identification of antigens that provide protective immunity via prophylactic and therapeutic vaccination against Mycobacterium tuberculosis is critical for the development of subunit vaccines for tuberculosis (TB). In this study, we performed a head-to-head comparison of seven well-known TB antigens delivered by DNA vaccine, and evaluated their respective immunogenicities and protective efficacies in pre- and post-exposure mouse models. All TB antigens were designed as a chimeric fusion with Flt3-L to enhance antigen-specific T-cell immunity upon vaccination. Prophylactic vaccination with the Flt3L (F)-Mtb32 DNA vaccine elicited significant protection in both the spleen and lungs against M. tuberculosis challenge, comparable to the Bacillus Calmette-Guerin vaccine. F-Ag85A and F-Mtb32 DNA vaccines, in combination with chemotherapy, reduced the bacterial burden to undetectable levels in the lungs of all mice infected with M. tuberculosis. These data collectively indicate that the F-Mtb32 DNA vaccine confers the most efficient protective immunity that suppresses bacterial growth in the active or latent status of M. tuberculosis.