Can DKI-MRI predict recurrence and invasion of peritumoral zone of hepatocellular carcinoma after transcatheter arterial chemoembolization?

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Transcatheter arterial chemoembolization (TACE) has been performed as a palliative treatment for patients with HCC. However, HCC is easy to recur after TACE. Magnetic resonance imaging (MRI) has clinical potential in evaluating the TACE treatment effect for patients with liver cancer. However, traditional MRI has some limitations. AIM: To explore the clinical potential of diffusion kurtosis imaging (DKI) in predicting recurrence and cellular invasion of the peritumoral liver zone of HCC after TACE. METHODS: Seventy-six patients with 82 HCC nodules were recruited in this study and underwent DKI after TACE. According to pathological examinations or the overall modified response evaluation criteria in solid tumors (mRECIST) criterion, 48 and 34 nodules were divided into true progression and pseudo-progression groups, respectively. The TACE-treated area, peritumoral liver zone, and far-tumoral zone were evaluated on DKI-derived metric maps. Non-parametric U test and receiver operating characteristic curve (ROC) analysis were used to evaluate the prediction performance of each DKI metric between the two groups. The independent t-test was used to compare each DKI metric between the peritumoral and far-tumoral zones of the true progression group. RESULTS: DKI metrics, including mean diffusivity (MD), axial diffusivity (DA), radial diffusivity (DR), axial kurtosis (KA), and anisotropy fraction of kurtosis (Fak), showed statistically different values between the true progression and pseudo-progression groups (P < 0.05). Among these, MD, DA, and DR values were higher in pseudo-progression lesions than in true progression lesions, whereas KA and FAk values were higher in true progression lesions than in pseudo-progression lesions. Moreover, for the true progression group, the peritumoral zone showed significantly different DA, DR, KA, and FAk values from the far-tumoral zone. Furthermore, MD values of the liver parenchyma (peritumoral and far-tumoral zones) were significantly lower in the true progression group than in the pseudo-progression group (P < 0.05). CONCLUSION: DKI has been demonstrated with robust performance in predicting the therapeutic response of HCC to TACE. Moreover, DKI might reveal cellular invasion of the peritumoral zone by molecular diffusion-restricted change.

Imaging findings of immunoglobin G4-related hypophysitis: A case report.

BACKGROUND: Immunoglobin G4 (IgG4)-related hypophysitis (IgG4-RH) is a rare form of IgG4-related disease (IgG4-RD), which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically and by imaging. There are few reports of imaging findings of IgG4-RH. Therefore, we describe a case of IgG4-RH, which mimicked a pituitary macroadenoma, that was detected by computed tomography (CT) and magnetic resonance imaging (MRI), and review the previous literature in order to further the understanding of IgG4-RH. CASE SUMMARY: A 47-year-old man presented with a history of blurred vision for more than 2 mo, without other symptoms. A preoperative unenhanced CT scan revealed a slightly hyperdense mass in the sellar region measuring 2.5 cm × 2.3 cm × 1.8 cm, with a CT value of 45 HU. T1-weighted imaging (T1WI) and T2-weighted imaging showed iso-hypointensity, and gadolinium contrast-enhanced T1WI showed obvious homogeneous enhancement. The MRI revealed involvement of the pituitary gland and stalk. Preoperative laboratory tests revealed abnormal pituitary hormone levels, including an increased prolactin level, and decreased levels of insulin-like growth factor, dehydroepiandrosterone, and testosterone. The lesion was surgically resected. Postoperative histopathological examination of a tissue sample and an elevated serum IgG4 level confirmed the diagnosis of IgG4-RH. The patient was treated with cortisone acetate postoperatively and made a good recovery without developing any neurological deficit. CONCLUSION: An elevated serum IgG4 concentration is the main clue for diagnosis of IgG4-RD. Imaging combined with laboratory testing is useful for preoperative diagnosis of IgG4-RH.

Application of an Improved U2-Net Model in Ultrasound Median Neural Image Segmentation.

To investigate whether an improved U2-Net model could be used to segment the median nerve and improve segmentation performance, we performed a retrospective study with 402 nerve images from patients who visited Huashan Hospital from October 2018 to July 2020; 249 images were from patients with carpal tunnel syndrome, and 153 were from healthy volunteers. From these, 320 cases were selected as training sets, and 82 cases were selected as test sets. The improved U2-Net model was used to segment each image. Dice coefficients (Dice), pixel accuracy (PA), mean intersection over union (MIoU) and average Hausdorff distance (AVD) were used to evaluate segmentation performance. Results revealed that the Dice, MIoU, PA and AVD values of our improved U2-Net were 72.85%, 79.66%, 95.92% and 51.37 mm, respectively, which were comparable to the actual ground truth; the ground truth came from the labeling of clinicians. However, the Dice, MIoU, PA and AVD values of U-Net were 43.19%, 65.57%, 86.22% and 74.82 mm, and those of Res-U-Net were 58.65%, 72.53%, 88.98% and 57.30 mm. Overall, our data suggest our improved U2-Net model might be used for segmentation of ultrasound median neural images.

Radiomics for the detection of microvascular invasion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for about 90% of liver cancer cases. It is currently the fifth most common cancer in the world and the third leading cause of cancer-related mortality. Moreover, recurrence of HCC is common. Microvascular invasion (MVI) is a major factor associated with recurrence in postoperative HCC. It is difficult to evaluate MVI using traditional imaging modalities. Currently, MVI is assessed primarily through pathological and immunohistochemical analyses of postoperative tissue samples. Needle biopsy is the primary method used to confirm MVI diagnosis before surgery. As the puncture specimens represent just a small part of the tumor, and given the heterogeneity of HCC, biopsy samples may yield false-negative results. Radiomics, an emerging, powerful, and non-invasive tool based on various imaging modalities, such as computed tomography, magnetic resonance imaging, ultrasound, and positron emission tomography, can predict the HCC-MVI status preoperatively by delineating the tumor and/or the regions at a certain distance from the surface of the tumor to extract the image features. Although positive results have been reported for radiomics, its drawbacks have limited its clinical translation. This article reviews the application of radiomics, based on various imaging modalities, in preoperative evaluation of HCC-MVI and explores future research directions that facilitate its clinical translation.

Clinical and angiographic outcomes of stent-assisted coiling of paraclinoid aneurysms: Comparison of LVIS and Neuroform stents.

Paraclinoid aneurysms are mainly intradural, and are associated with a potential risk of subarachnoid hemorrhage (SAH). The application of stent-assisted coiling has been widely used in endovascular treatment of intracranial aneurysms. Here we aimed to compare clinical outcomes between low-profile visualized intraluminal support stents (LVIS) and Neuroform (NU) stents. Between January 2013 and December 2017, a total of 101 patients with 118 unruptured paraclinoid aneurysms were embolized by LVIS or NU stents. Procedure-related complications, angiography, and follow-up results were retrospectively analyzed. A total of 45 patients with 54 aneurysms received LVIS stents, and 56 patients with 64 aneurysms received NU stents. Procedure-related complication rate was 6.7% in the LVIS group and 5.4% in the NU group, with no statistical differences between groups (P = 0.511). Compared with the NU group, greater initial complete or near-complete aneurysm obliteration was achieved in the LVIS group (79.6% vs 59.4%, P = 0.0192). DSA angiography follow-up imaging of the 118 aneurysms showed that the LVIS group increased in Raymond-Roy Grade Scale I (RRGS I), however there is no statistical difference (P = 0.32). Compared with NU stents, LVIS stents may achieve greater complete or near-complete occlusion rate immediately post-operation. However, there was no difference in procedural-related complications and follow-up outcomes between LVIS and NU stent groups.

MRI Features of Intracranial Anaplastic Ependymomas: A Comparison of Supratentorial and Infratentorial Lesions.

Background: Several previous reports of anaplastic ependymomas have described their imaging features, and most of these studies were case reports. However, no studies have compared the magnetic resonance imaging (MRI) features between the infratentorial and supratentorial anaplastic ependymomas. Objective: The goal of this study was to explore MRI characteristics for intracranial anaplastic ependymomas. Material and Methods: We retrospectively reviewed the demographics of 165 patients and MRI findings of 60 patients with supratentorial (SAEs) and infratentorial anaplastic ependymomas (IAEs) before surgery. The demographics and MRI features for SAEs and IAEs were compared and evaluated. Results: Among the 60 patients, most SAEs (91.7%) were extraventricular, whereas most IAEs (91.7%) were intraventricular. Of sixty intracranial anaplastic ependymomas, most lesions were well-defined (n = 45) and round-like (n = 36). On T1-weighted imaging, compared with the gray matter, the SAEs exhibited heterogeneous signal intensity, whereas IAEs exhibited iso-hypointense signals. T2 signals exhibited greater associations with hyperintense signals in IAEs; however, SAEs showed hyperintense or hypointense-hyperintense. On diffusion-weighted imaging (DWI), almost all solid tissues of SAEs appeared as hyperintense, whereas IAEs exhibited iso-hypointense signals. Peritumoral edema and intratumoral hemorrhage occurred more frequently in SAEs. Almost all anaplastic ependymomas exhibited heterogeneous enhancement. Cysts or necrosis was associated with 56 anaplastic ependymomas; however, large cysts were more prevalent in SAEs. On magnetic resonance spectroscopy (MRS), the mean choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratio of anaplastic ependymomas were (6.58 ± 4.26) and (8.84 ± 6.34), respectively, representing typical high-grade tumors. Conclusion: We demonstrate the conventional and functional MRI features of intracranial anaplastic ependymomas, including DWI and MRS. MRI characteristics, such as location, cyst, diffusion restriction, and peritumoral edema, differed between supratentorial and infratentorial locations. Cho/Cr and Cho/ NAA ratios of anaplastic ependymomas are increased.

Short-echo-time magnitude image derived from quantitative susceptibility mapping could resemble neuromelanin-sensitive MRI image in substantia nigra.

BACKGROUND: In this study, we explored whether the proposed short-echo-time magnitude (setMag) image derived from quantitative susceptibility mapping (QSM) could resemble NM-MRI image in substantia nigra (SN), by quantitatively comparing the spatial similarity and diagnosis performances for Parkinson's disease (PD). METHODS: QSM and NM-MRI were performed in 18 PD patients and 15 healthy controls (HCs). The setMag images were calculated using the short-echo-time magnitude images. Bilateral hyperintensity areas of SN (SNhyper) were manually segmented on setMag and NM-MRI images by two raters in a blinded manner. The inter-rater reliability was evaluated by the intraclass correlation coefficients (ICC) and the Dice similarity coefficient (DSC). Then the inter-modality (i.e. setMag and NM-MRI) spatial similarity was quantitatively assessed using DSC and volume of the consensual voxels identified by both of two raters. The performances of mean SNhyper volume for PD diagnosis on setMag and NM-MRI images were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The SNhyper segmented by two raters showed substantial to excellent inter-rater reliability for both setMag and NM-MRI images. The DSCs of SNhyper between setMag and NM-MRI images showed substantial to excellent voxel-wise overlap in HCs (0.80 ~ 0.83) and PD (0.73 ~ 0.76), and no significant difference was found between the SNhyper volumes of setMag and NM-MRI images in either HCs or PD (p > 0.05). The mean SNhyper volume was significantly decreased in PD patients in comparison with HCs on both setMag images (77.61 mm3 vs 95.99 mm3, p < 0.0001) and NM-MRI images (79.06 mm3 vs 96.00 mm3, p < 0.0001). Areas under the curve (AUCs) of mean SNhyper volume for PD diagnosis were 0.904 on setMag and 0.906 on NM-MRI images. No significant difference was found between the two curves (p = 0.96). CONCLUSIONS: SNhyper on setMag derived from QSM demonstrated substantial spatial overlap with that on NM-MRI and provided comparable PD diagnostic performance, providing a new QSM-based multi-contrast imaging strategy for future PD studies.

Multi-parameters of Magnetic Resonance Imaging to Estimate Ischemia-Reperfusion Injury after Stroke in Hyperglycemic Rats.

The aim of the study is to verify the effect of hyperglycemia on ischemia-reperfusion injury and to explore the feasibility of noninvasive observation of ischemic-reperfusion injury in hyperglycemic ischemic stroke by MRI technique. According to the duration of ischemia and blood glucose levels, 40 rats were divided into hyperglycemic ischemic 2-hr (H-I2h), hyperglycemic ischemic 6-hr (H-I6h), non- hyperglycemic ischemic 2-hr (NH-I2h), and non- hyperglycemic ischemic 6-hr (NH-I6h) groups. T2W imaging, DW imaging, T2 mapping, T2* mapping, DCE, and T1 mapping after enhancement sequences were acquired before reperfusion and approximately 3-hr after reperfusion. ADC, T1, T2, T2*, and Ktrans values of ischemic lesion were obtained in different groups. After reperfusion, the variation of ADC values showed no significant difference between groups with diabetes and groups without diabetes and between different recanalization time-points (2-hr vs 6-hr). After reperfusion, T2, T2*, and Ktrans values increased in different degrees in all four groups. Only the T1 value decreased in all groups. The change of all parameters in groups with hyperglycemia was more obvious than that in groups without hyperglycemia and was more obvious in groups with H-I6h versus those with H-I2h. This study confirms that hyperglycemia aggravates ischemia-reperfusion injury and may be an important risk factor for the prognosis of ischemic stroke. The Ktrans values should be noninvasive imaging indicators to monitor blood brain barrier permeability and ischemic-reperfusion injury in ischemic stroke.

MR imaging features of spinal pilocytic astrocytoma.

BACKGROUND: The purpose of this retrospective review is to determine the MR imaging features of pilocytic astrocytoma (PA) in the spinal cord to help neuroradiologists preoperatively differentiate PA from other intramedullary tumors. METHODS: Neuro-oncology database review revealed 13 consecutive patients with a pathological spinal PA diagnosis and availability of preoperative MR imaging. Three patients had preoperative diffusion-weighted MR imaging. Demographics and conventional and diffusion MR imaging records were retrospectively evaluated. RESULTS: Among 13 cases of spinal PA, six PAs were located in the cervical region, 4 in the cervical-thoracic region, and 3 in the thoracic region. The average length of vertebral segments involved for the tumors were 4.7 ± 4.6 segments. Six tumors had associated syringomyelia. Eight PAs were located eccentrically in the spinal cord, and eleven had well-defined margins. Eight tumors (61.5%) were intermixed cystic and solid. All were contrast-enhanced, and 53.8% of all PAs showed focal nodule enhancement of the solid components. Two PAs showed intratumoral hemorrhages, and only one demonstrated cap sign. The ADC values (n = 3) of the tumors were 1.40 ± 0.28 × 10- 3 mm2/s (min-max: 1.17-1.71 × 10- 3 mm2/s). CONCLUSIONS: PA should be considered in the differential diagnosis of intramedullary tumors that occur in the cervical and thoracic regions. Eccentric growth pattern, well-defined margin, intermixed cystic and solid appearance, focal nodular enhancement of solid components and syringomyelia are relatively frequent features. Relatively high ADC values compared with normal-appearing spinal cord parenchyma are common in spinal PA.

Evaluation of patients with relapsing-remitting multiple sclerosis using tract-based spatial statistics analysis: diffusion kurtosis imaging.

BACKGROUND: Diffusion kurtosis imaging (DKI) has the potential to provide microstructural insights into myelin and axonal pathology with additional kurtosis parameters. To our knowledge, few studies are available in the current literature using DKI by tract-based spatial statistics (TBSS) analysis in patients with multiple sclerosis (MS). The aim of this study is to assess the performance of commonly used parameters derived from DKI and diffusion tensor imaging (DTI) in detecting microstructural changes and associated pathology in relapsing remitting MS (RRMS). METHODS: Thirty-six patients with RRMS and 49 age and sex matched healthy controls underwent DKI. The brain tissue integrity was assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr) of DKI and FA, MD, Da and Dr of DTI. Group differences in these parameters were compared using TBSS (P < 0.01, corrected). To compare the sensitivity of these parameters in detecting white matter (WM) damage, the percentage of the abnormal voxels based on TBSS analysis, relative to the whole skeleton voxels for each parameter was calculated. RESULTS: The sensitivities in detecting WM abnormality in RRMS were MK (78.2%) > Kr (76.7%) > Ka (53.5%) and Dr (78.8%) > MD (76.7%) > FA (74.1%) > Da (28.3%) for DKI, and Dr (79.8%) > MD (79.5%) > FA (68.6%) > Da (40.1%) for DTI. DKI-derived diffusion parameters (FA, MD, and Dr) were sensitive for detecting abnormality in WM regions with coherent fiber arrangement; however, the kurtosis parameters (MK and Kr) were sensitive to discern abnormalities in WM regions with complex fiber arrangement. CONCLUSIONS: The diffusion and kurtosis parameters could provide complementary information for revealing brain microstructural damage in RRMS. Dr and DKI_Kr may be regarded as useful surrogate markers for reflecting pathological changes in RRMS.

Differentiating Primary Central Nervous System Lymphomas From Glioblastomas and Inflammatory Demyelinating Pseudotumor Using Relative Minimum Apparent Diffusion Coefficients.

OBJECTIVE: Our purpose was to evaluate the diagnostic performance of diffusion-weighted imaging, the relative minimum apparent diffusion coefficient (rADCmin) in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastomas (GBMs) and inflammatory demyelinating pseudotumors (IDPs). MATERIALS AND METHODS: Magnetic resonance images were reviewed retrospectively in 82 patients including 39 PCNSLs, 35 GBMs, and 8 IDPs. Regions of interest were drawn around the tumor on contrast-enhanced axial images; these images were transferred onto coregistered ADC maps to obtain the ADCmin, and the normalized ADCmin ratios (rADCmin) were calculated using the formula rADCmin = ADCmin of the lesion / ADCmin of the normal white matter. The rADCmin values were compared between PCNSLs, GBMs, and IDPs using the analysis of variance test. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of rADCmin values and to determine the optimum thresholds. Simple logistic regression was analyzed to evaluate the relationship between ADCs and tumor cellularity. RESULTS: The rADCmin value was significantly lower in PCNSLs (0.675 ± 0.113) than GBMs (0.765 ± 0.059) and IDPs (0.834 ± 0.067) (PCNSL vs GBM, P < 0.001; PCNSL vs IDP, P < 0.001). Relative ADCmin was a significant assessor for differentiating PCNSLs from non-PCNCLs (P < 0.001). The optimal cutoff value was 0.722 (sensitivity, 74.5%; specificity, 74.1%; area under the curve, 0.803) on receiver operating characteristic analysis. A stronger negative correlation (r = -0.755, P = 0.000) was obtained between the cytoplasm and rADCmin. CONCLUSIONS: Relative ADCmin value is helpful in differentiating PCNSL from GBM and IDP. Thus, ADC values may provide a useful supplement to the information obtained from conventional contrast-enhanced magnetic resonance imaging and assist in future treatment planning.

Computed tomography perfusion and computed tomography angiography for prediction of clinical outcomes in ischemic stroke patients after thrombolysis.

Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis. At present, the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment, with less attention to predictions of outcomes after thrombolysis. Thus, in the present study, we assessed the efficacy of combined computed tomography (CT) perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients. The study included 52 patients who received both CT perfusion and CT angiography. Patients were grouped based on the following criteria to compare clinical outcomes: (1) thrombolytic and non-thrombolytic patients, (2) thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis, (3) thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch, and (4) different CT angiography and CT perfusion results. Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change. Long-term outcome was assessed by the 3-month modified Rankin Scale score. Of 52 ischemic stroke patients, 29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment (23 patients). Patients with both vascular stenosis and blood flow mismatch (13 patients) exhibited the best short-term outcome, while there was no correlation of long-term outcome with CT angiography or CT perfusion findings. These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome, but not long-term outcome, after thrombolysis.

Changes of T2 Relaxation Time From Neoadjuvant Chemotherapy in Breast Cancer Lesions.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is generally an effective method of reducing locally advanced malignant breast lesions before surgery; assessing the tumor response to NAC is crucial for patient management. T2 relaxation times can reflect biological state of lesions, may prove useful to assess the response to NAC. OBJECTIVES: To investigate the lesion T2 relaxation times change in breast cancer neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: In total, 26 patients underwent NAC. Magnetic resonance imaging (MRI) T2 mapping was performed before and after NAC. The T2 relaxation times were obtained by using Functool software on an AW 43 workstation. The treatment response was assessed according to the pathological response classification. We aimed to analyze the changes in the T2 relaxation times before and after NAC as well as to study the relationship between the response and the lesion T2 relaxation times after NAC. RESULTS: In 26 cases with NAC, the mean lesion T2 relaxation time before NAC was 81.34 ± 13.68 ms, compared with 64.50 ± 8.71 ms after NAC. Significant differences in the lesion T2 relaxation times existed between the pre- and post-NAC (P < 0.001) ; based on the pathology results, the mean lesion T2 relaxation times in 23 of the 26 responders (63.18 ± 8.37 ms) was shorter than in 3 of the 26 nonresponders (74.62 ± 2.32 ms) after NAC (P = 0.029). CONCLUSION: In breast cancer after NAC, the lesion T2 relaxation time was reduced in the responders, and this finding is potentially useful to assess the response to NAC.

Early prediction of functional outcome using dynamic contrast enhanced magnetic resonance imaging in experimental stroke.

BACKGROUND AND PURPOSE: Early prediction of functional outcome in cerebral ischemia stroke using MRI remains a challenge. The aim of this study was to evaluate the predictive value of dynamic contrast-enhanced (DCE) MRI in terms of functional outcome of ischemia stroke. METHODS: Right middle cerebral artery occlusion (MCAO) was performed in male SD rats (n=50), followed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10) or 7 (n = 10) h to establish ischemia and reperfusion stroke. DCE and conventional MRI were performed in each animal 60 ± 15 min before and after reperfusion. The outcome was assessed by the modified Neurological Severity Scores (mNSS) (before reperfusion and at 72 h after reperfusion) and the infarct volume. Comparisons of functional prognosis and DCE parameters (K(trans), Ve and Kep) were performed using binary logistic regression and operating characteristic (ROC) analysis. RESULTS: DCE parameters results indicated that blood brain barrier (BBB) permeability increased with prolonged reperfusion timing. Using binary logistic regression analysis on stroke characteristics (reperfusion timing, infarct volume) and BBB permeability parameters (drK(trans)subcortex, drK(trans)cortex, drVesubcortex, drVecortex, drKepsubcortex and drKepcortex) as covariates , the results demonstrated that reperfusion timing, infarct volume, drK(trans)subcortex and drKepsubcortex were independent factors that were associated with prognosis (OR=0.01, OR=0.23, OR=245.23, OR=1.29). ROC analysis indicated that a drK(trans)subcortex threshold of 0.88 with a sensitivity of 95.7% and a specificity of 85.2% and a drKepsubcortex threshold of -0.25 with a sensitivity of 69.6% and a specificity of 70.4% for differentiation between favourable and unfavourable prognosis. CONCLUSIONS: Quantitative DCE-MRI can be used to predict the functional outcomes of cerebral ischemia injury.

Detecting isocitrate dehydrogenase gene mutations in oligodendroglial tumors using diffusion tensor imaging metrics and their correlations with proliferation and microvascular density.

PURPOSE: Isocitrate dehydrogenase (IDH) mutations are frequently present in oligodendroglial tumors (OTs) and have prognostic value. We assessed whether diffusion tensor imaging (DTI) metrics could aid the noninvasive detection of IDH mutations and their correlations with tumor proliferation and microvascular density (MVD) in OTs. MATERIALS AND METHODS: Ninety patients with OTs who underwent conventional magnetic resonance imaging (MRI) and DTI were retrospectively reviewed (3T). IDH mutations were determined by immunohistochemical staining or direct sequencing. MVD and cell proliferation were evaluated by immunohistochemical staining with anti-CD31 and Ki-67, respectively. The Mann-Whitney U-test was applied to each of the imaging parameters. Spearman correlation analysis and receiver operating characteristic curve analysis were performed. RESULTS: The maximal fractional anisotropy (FA), ratio of maximal FA (rmFA), minimal ADC, and ratio of minimal (rmADC) values were demonstrated to be significantly different between the OTs with IDH1/2 mutations and those without mutations (P < 0.05). The areas under the curve (AUCs) for the maximal FA, rmFA, minimal ADC, and rmADC were 0.79, 0.82, 0.77, and 0.80, respectively. A combination rmFA and rmADC for the diagnosis of IDH1/2 mutations led to sensitivity, specificity, and AUC of 91.5%, 76.5%, and 0.86, respectively. The Ki-67 and MVD levels in the IDH-mutated samples were lower than those in the IDH wildtype cases (P < 0.05). CONCLUSION: DTI metrics may provide a noninvasive method for assessing the IDH statuses of OTs. Significantly higher minimal ADC and lower maximal FA in OTs with IDH mutations may suggest that IDH mutations lead to proliferation inhibition and an angiogenesis decrease.

Prediction of Reperfusion-Associated Hemorrhagic Transformation Using Dynamic Contrast-Enhanced Imaging in a Rat Stroke Model.

BACKGROUND AND PURPOSE: Reperfusion-associated hemorrhagic transformation (HT) is an important complication of recanalization therapy. A method to identify stroke victims that may undergo HT will improve the patient selection and safety of this treatment. In this study, we determined the relationship between timing of reperfusion and the frequency and severity of HT, and whether very early dynamic contrast-enhanced (DCE) imaging predicts the occurrence of reperfusion-associated HT in a model of experimental stroke. METHODS: Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Sprague Dawley rats (n = 50). Reperfusion was performed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10), or 7 (n = 10) hours. Magnetic resonance imaging studies were performed before reperfusion using DCE, susceptibility-weighted imaging, diffusion-weighted imaging, and T2- and T1-weighted imaging. Follow-up magnetic resonance imaging and histological studies were performed at 24 hours. RESULTS: Hemorrhagic transformation occurred by 24 hours after injury in 8 of 50 animals. The HT rate increased with prolonged ischemic duration. All animals exhibiting acute blood-brain barrier (BBB) perturbation subsequently developed HT by 24 hours. Statistically significant differences in the BBB permeability parameters (P < 0.05) between the HT group and non-HT group were detected by DCE imaging. There were also statistically significant differences (P < 0.05) between the HT area and adjacent HT area. Among the permeability parameters, subcortex rK was the most sensitive and specific predictor of HT. CONCLUSIONS: The results suggest that the use of quantitative BBB measurements may further improve early prediction and identification of HT. The DCE parameters were the sensitive early independent predictor of reperfusion-associated HT.

Recurrent gain-of-function USP8 mutations in Cushing's disease.

Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease.

Magnetic resonance imaging findings of intracranial papillary meningioma: a study on eight cases.

OBJECTIVES: To increase the awareness on intracranial papillary meningiomas (PMs) by presenting magnetic resonance imaging (MRI) findings on this disease. MATERIALS AND METHODS: The MRI findings and clinical presentations of nine discrete lesions in eight patients with pathologically documented PMs were retrospectively analyzed. RESULTS: Most tumors occurred in young adults. The tumors originated from the convexity meninges in five cases and from the parasagittal regions in four cases. The tumor shape was irregular in six cases, lobulated in two cases, and round in one case. By MRI, nine masses were primarily isointense (n=5) or mildly hypointense (n=4) to gray matter on T1-weighted images and inhomogeneous hyperintense (n=3) or isointense (n=6) to the cortex on T2-weighted and fluid-attenuated inversion recovery images. On diffusion-weighted imaging, the signal intensity of the tumor was increased in all lesions compared with the adjacent parenchyma. Tumor and brain interfaces were unclear in seven cases, cyst formation was observed in eight tumors, scattered hemorrhage was observed in three tumors, signal voids due to vessels were visible in four cases, and eight tumors had moderate or marked irregular peritumoral edema. Enhancement was homogeneous (n=2) or heterogeneous (n=7), an area of focal nodular enhancement was observed in three lesions, and the dural tail sign was visible in seven cases. CONCLUSION: Although PM is rare, it should be considered in the differential diagnosis when evaluating intracranial neoplasms. Younger patient age, as well as imaging features such as unclear tumor-brain interface, internal heterogeneity including cyst formation, irregular enhancement, signal voids of vessels, and marked peritumoral edema can help distinguish PM from typical benign meningiomas.