A Convolutional Neural Network Model for Distinguishing Hemangioblastomas From Other Cerebellar-and-Brainstem Tumors Using Contrast-Enhanced MRI.

BACKGROUND: Hemangioblastoma (HB) is a highly vascularized tumor most commonly occurring in the posterior cranial fossa, requiring accurate preoperative diagnosis to avoid accidental intraoperative hemorrhage and even death. PURPOSE: To accurately distinguish HBs from other cerebellar-and-brainstem tumors using a convolutional neural network model based on a contrast-enhanced brain MRI dataset. STUDY TYPE: Retrospective. POPULATION: Four hundred five patients (182 = HBs; 223 = other cerebellar-and brainstem tumors): 305 cases for model training, and 100 for evaluation. FIELD STRENGTH/SEQUENCE: 3 T/contrast-enhanced T1-weighted imaging (T1WI + C). ASSESSMENT: A CNN-based 2D classification network was trained by using sliced data along the z-axis. To improve the performance of the network, we introduced demographic information, various data-augmentation methods and an auxiliary task to segment tumor region. Then, this method was compared with the evaluations performed by experienced and intermediate-level neuroradiologists, and the heatmap of deep feature, which indicates the contribution of each pixel to model prediction, was visualized by Grad-CAM for analyzing the misclassified cases. STATISTICAL TESTS: The Pearson chi-square test and an independent t-test were used to test for distribution difference in age and sex. And the independent t-test was exploited to evaluate the performance between experts and our proposed method. P value <0.05 was considered significant. RESULTS: The trained network showed a higher accuracy for identifying HBs (accuracy = 0.902 ± 0.031, F1 = 0.891 ± 0.035, AUC = 0.926 ± 0.040) than experienced (accuracy = 0.887 ± 0.013, F1 = 0.868 ± 0.011, AUC = 0.881 ± 0.008) and intermediate-level (accuracy = 0.827 ± 0.037, F1 = 0.768 ± 0.068, AUC = 0.810 ± 0.047) neuroradiologists. The recall values were 0.910 ± 0.050, 0.659 ± 0.084, and 0.828 ± 0.019 for the trained network, intermediate and experienced neuroradiologists, respectively. Additional ablation experiments verified the utility of the introduced demographic information, data augmentation, and the auxiliary-segmentation task. DATA CONCLUSION: Our proposed method can successfully distinguish HBs from other cerebellar-and-brainstem tumors and showed diagnostic efficiency comparable to that of experienced neuroradiologists. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats.

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire-mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy on esophageal squamous cell cancers. © RSNA, 2016.

Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma.

PURPOSE: To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in vitro confirmation and in vivo validation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology. RESULTS: In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29 ± 6% vs. 56 ± 9%, 93 ± 4%, and 100 ± 5%, p < .05). Ultrasound imaging of treated animal xenografts showed smaller relative tumour volume in combination therapy group than those in three control groups (0.74 ± 0.19 vs. 1.79 ± 0.24, 3.14 ± 0.49 and 3.22 ± 0.52, p < .05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumours in the combination therapy group, compared to those in three control groups (1.2 ± 0.1 vs. 1.9 ± 0.2% vs. 3.3 ± 0.6% vs. 3.5 ± 0.4%, p < .05). These imaging findings were correlated well with histologic confirmation. CONCLUSION: RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy.

Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins.

PURPOSE: To investigate the possibility of using motexafin gadolinium (MGd)-enhanced molecular magnetic resonance (MR) imaging and optical imaging to identify the true margins of gliomas. MATERIALS AND METHODS: The animal protocol was approved by the institutional animal care and use committee. Thirty-six Sprague-Dawley rats with gliomas were randomized into six groups of six rats. Five groups were euthanized 15, 30, 60, 120, and 240 minutes after intravenous administration of 6 mg/kg of MGd, while one group received only saline solution as a control group. After craniotomy, optical imaging and T1-weighted MR imaging were performed to identify the tumor margins. One-way analysis of variance was used to compare optical photon intensity and MR imaging signal-to-noise ratios. Histologic analysis was performed to confirm the intracellular uptake of MGd by tumor cells and to correlate the tumor margins delineated on both optical and MR images. RESULTS: Both optical imaging and T1-weighted MR imaging showed tumor margins. The highest optical photon intensity (2.6 × 10(8) photons per second per mm(2) ± 2.3 × 10(7); analysis of variance, P < .001) and MR signal-to-noise ratio (77.61 ± 2.52; analysis of variance, P = .006) were reached at 15-30 minutes after administration of MGd, with continued tumor visibility at 2-4 hours. Examination with confocal microscopy allowed confirmation that the fluorescence of optical images and MR imaging T1 enhancement exclusively originated from MGd that accumulated in the cytoplasm of tumor cells. CONCLUSION: MGd-enhanced optical and MR imaging can allow determination of glioma tumor margins at the optimal time of 15-120 minutes after administration of MGd. Clinical application of these results may allow complete removal of gliomas in a hybrid surgical setting in which intraoperative optical and MR imaging are available.

Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.

PURPOSE: To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model. MATERIALS AND METHODS: Four liposome preparations, including nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio-MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step pretargeting imaging, were formulated. All animal experiments were carried out with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR. T1 -weighted MRI was performed before and dynamically repeated after different contrast agents were injected. The enhancement features of the tumors were compared. RESULTS: The signal enhancement of the tumor in the two-step pretargeting group increased by 117.9 ± 5.3% at the periphery and 109.2 ± 3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs injection. Ring-like enhancement margins were demonstrated at the periphery of the tumor in the two-step targeted group. The specificity of the targeted liposomes was supported by the competitive study. The signal of peak enhancement using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly higher than the non-targeted groups. CONCLUSION: The two-step endoglin-targeted imaging using biotin-streptavidin interaction was demonstrated to induce intense enhancement of the tumor periphery, which implies that this advanced MR molecular contrast agent may be suitable for accurately delineating glioma tumor margins. J. Magn. Reson. Imaging 2015;41:1056-1064. © 2014 Wiley Periodicals, Inc.

Monitoring Rotator Cuff Muscle Fatty Infiltration Progression by Magnetic Resonance Imaging T1 Mapping: Correlation With Direct Evaluation Findings in Rats.

BACKGROUND: Monitoring the fatty infiltration (FI) process in rotator cuff muscles is of value in establishing a treatment plan and predicting the postoperative prognosis. Quantitative T1 mapping shows promise for evaluating muscle degeneration, while its validity in monitoring rotator cuff muscle FI progression needs further investigation. PURPOSE: To determine the validity of T1 mapping in monitoring FI progression of rotator cuff muscles. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague-Dawley rats (N = 108) underwent left supraspinatus (SS) and infraspinatus (IS) tenotomy only (TT), suprascapular nerve transection only (NT), or SS and IS tenotomy plus suprascapular nerve transection (TT+NT). Sham surgery on the right shoulder served as the control. The magnetic resonance imaging examination included T1 mapping performed at 12, 16, and 20 weeks postoperation. SS and IS muscles were harvested to quantitatively evaluate FI via direct evaluation (triglyceride quantification assay and histological analysis) at the same predetermined intervals. The correlation of the imaging data with direct evaluation of rotator cuff muscles was analyzed. RESULTS: T1 values were significantly lower in left SS and IS muscles at 12, 16, and 20 weeks postoperation as compared with those on the right side. T1 values of the left SS and IS muscles were continuously decreased in all groups. The TT+NT group had a greater decrease in T1 value than did the TT and NT groups. Triglyceride quantification assay and histological analysis demonstrated significant and progressive FI of the left SS and IS muscles in the 3 groups. The most serious FI changes were observed in the TT+NT group. T1 values were also well correlated with triglyceride contents and area fractions of fat. CONCLUSION: T1 mapping can be an effective imaging modality for sensitive and quantitative monitoring of FI progression in rotator cuff muscles. CLINICAL RELEVANCE: The findings of this study provide a tool for researchers to noninvasively and quantitatively monitor the process of muscle degeneration, contributing to the evaluation of surgical indication and postoperative prognosis.

Intratumoral radiofrequency hyperthermia-enhanced direct chemotherapy of pancreatic cancer.

PURPOSE: To investigate the technical feasibility of using ultrasound-guided intratumoral radiofrequency hyperthermia (RFH) to enhance local chemotherapy of rat orthotopic pancreatic cancers. MATERIALS AND METHODS: Orthotopic pancreatic cancer masses were established by inoculating luciferase/mCherry labeled-pancreatic cancer cells into the pancreatic tails of Lewis model rats via a laparotomy approach. Twenty-four rats with pancreatic cancer and 24 mice with subcutaneous pancreatic cancer xenografts in four study groups (n = 6/group) received various treatments: i) combination therapy of intratumoral MR imaging-heating-guidewire-mediated RFH (42oC) plus local chemotherapy (gemcitabine); ii) intratumoral chemotherapy alone; iii) RFH alone; and (iv)phosphate-buffered saline (PBS). Transcutaneous ultrasound imaging was used to guide the treatment and subsequently follow changes in tumor sizes. Bioluminescence optical imaging was performed to follow photon signal changes. Sonographic and optical findings were correlated with histology at 14 days. RESULTS: Optical imaging demonstrated a significantly decreased bioluminescence signal in mice with combination therapy group, compared with the other control groups (0.51±0.18 VS 1.6±0.4 VS 3.18±0.9 VS 3.5±0.96, p < 0.05). Ultrasound imaging showed the smallest tumor volumes of both mice and rat group with the combination therapy, compared with other control groups (0.62±0.16 VS 1.25±0.19 VS 2.28±0.25 VS 2.64±0.26, p < 0.05) and (0.75±0.18 VS 1.31±0.30 VS 1.61±0.28 VS 1.72±0.28, p < 0.05). Both imaging findings were confirmed by histologic correlation. CONCLUSION: Intratumoral RFH can augment the chemotherapeutic effect in an orthotopic pancreatic cancer model.

Multi-modality imaging-monitored creation of rat orthotopic pancreatic head cancer with obstructive jaundice.

PURPOSE: To investigate the feasibility of using multi-modality imaging to monitor the creation of rat models with orthotopic pancreatic head cancer with obstructive jaundice. RESULTS: 27 of 52 rats (51.92%) developed pancreatic head cancer. The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]. Both ultrasound imaging and MRI clearly characterized the orthotopic tumors. Laboratory biochemistry test for those rats with obstructive jaundice showed elevated levels of bilirubin, aspartate transaminase (AST), alkaline phosphatase (ALT) and gamma-glutamyl transpeptidase (λ-GGT), compared with those rats without jaundice (P < 0.05). Correlative pathology confirmed that all tumors were ductal adenocarcinomas, and located in pancreatic head regions. MATERIALS AND METHODS: Rat pancreatic adenocarcinoma cells (DSL-6A/C1) were first transfected with lentivirus/mCherry-luciferase genes, and then subcutaneously implanted into flanks of donor immunocompetent Lewis rats, to create pancreatic tumor tissues. The tumor tissues from donor rats with either bioluminescence signal or without the signal were then transplanted into the pancreatic heads of 52 recipient Lewis rats. Bioluminescence optical and ultrasound imaging, as well as magnetic resonance imaging (MRI), were performed to follow up the tumor formation and growth in these tumor-transplanted rats. Physical examination and biochemistry test were used to discern the rats with obstructive jaundice. The rats were euthanized for subsequent histologic correlation and confirmation. CONCLUSIONS: We successfully created a new rat model with orthotopic pancreatic head cancer, which can be accurately monitored and visualized by different imaging modalities.

Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of esophageal squamous cancers.

Despite recent advances in surgical technique and treatment strategies for esophageal cancer (EC), to effectively manage the advanced (metastatic or disseminated) and recurrent EC still remain a great challenge. The aim of this study was to determine the feasibility of using intra-esophagus radiofrequency hyperthermia to enhance local HSV-TK/ganciclovir-mediated suicide gene therapy of an innovative animal models with orthotopic esophageal squamous cancers. Human esophageal squamous cancer (ESCa) cells were labeled with lentivirus/luciferase. ESCa cells and nude rats with orthotopic ESCa were divided into in four groups (n = 6/group) and treated with: i) combination therapy of MR imaging-heating-guidewire-mediated radiofrequency hyperthermia ((RFH, 42°C) plus local HSV-TK/GCV; ii) HSV-TK/GCV alone; iii) RFH alone; and (iv) phosphate-buffered saline (PBS). Bioluminescence optical imaging and transcutaneous ultrasound imaging were used to follow up bioluminescence signal and size changes of tumors among different groups over two weeks, which were correlated with subsequent histology. We demonstrated that combination therapy of RFH with gene therapy resulted in the lowest cell proliferation (37.5±8.6%, P<0.0001), rendered the smallest relative tumor volume (0.90±0.15, P<0.01), and relative bioluminescence optical imaging photon signal intensity (0.81±0.17, P<0.01) of orthotopic esophageal cancers, compared with groups treated with gene therapy alone, RFH alone and PBS. Our study indicated that intra-esophageal radiofrequency hyperthermia could enhance the HSV-TK-mediated effect on esophageal squamous cancers.

Imaging characteristics of Rosai-Dorfman disease in the central nervous system.

BACKGROUND AND PURPOSE: Rosai-Dorfman disease (RDD) is a rare, lymphoproliferative disorder of uncertain etiology. The Central Nervous System (CNS) is a very rare site for RDD and only a few imaging appearances have been described. The purpose of this study is to present the largest series of cases in the CNS imaging literature to increase familiarity with this entity and further identify features that may distinguish RDD from meningioma. MATERIALS AND METHODS: Findings from imaging examinations in 10 patients with pathologically confirmed RDD were retrospectively reviewed. Two radiologists evaluated the lesion location, shape, size, number, edge, cerebral edema, homogeneous or heterogeneous appearance, attenuation and signal intensity, degree of enhancement, and the relation between lesions and meninges. RESULTS: RDD in CNS showed similar features in imaging: an extra-axial, well-circumscribed, dura-based mass, isodense or hyperdense on CT, isointensity on T1-weighted imaging and isointensity with hypointensity on T2-weighted imaging. The mass enhanced markedly and homogeneously after the administration of contrast agent and demonstrated dural tail sign in all cases. Significant perifocal edema was associated with the masses. Remarkably, seven patients (77.8%) showed strong hypointensity within isointensity on T2-weighted or FLAIR images and no calcification was observed in CT images or pathologic specimens. CONCLUSIONS: Although RDD in the CNS is a rare process, it should be considered in the differential diagnoses for meningioma. We believe that a typical representation of hypointensity irrelevant to calcification on T2-weighted or FLAIR images can suggest the diagnosis of RDD.

Imaging Findings of Follicular Dendritic Cell Sarcoma: Report of Four Cases

Follicular dendritic cell sarcoma is a rare malignant neoplasm and little is known about its radiological features. We present here four cases of follicular dendritic cell sarcomas and we provide the image characteristics of these tumors to help radiologists recognize this entity when making a diagnosis.