Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Giant Cell Tumor with Secondary Aneurysmal Bone Cyst Shows Heterogeneous Metabolic Pattern on 18F-FDG PET/CT: A Case Report.

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on 18F-FDG PET/CT.

Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy.

The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.

Cavernous hemangioma of the ilium mimicking aggressive malignant bone tumor with increased activity on (18)F-FDG PET/CT.

Osseous hemangioma is a benign vascular tumor, and it usually occurs in the vertebrae and the skull. However, hemangiomas of flat bones are rare, and there are very few reports that describe the radiologic findings of osseous hemangioma of the ilium. We report a unique case of large cavernous hemangioma mimicking a chondrogenic malignant bone tumor originated from the ilium in a 22-year-old female. The mass showed stippled calcifications, heterogeneous enhancement with thick septa and enhanced soft tissue components on CT and MR, and also this mass demonstrated heterogeneous 2-fluoro [fluorine-18]-2-deoxy-D-glucose ((18)F-FDG) uptake on (18)F-FDG PET/CT.

Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis.

Vascular endothelial growth factor A (VEGF) is highly expressed in adipose tissue. Its role, however, has not been fully elucidated. Here, we reveal the metabolic role of adipose-VEGF by studying mice with deletion (VEGF(AdΔ)) or doxycycline-inducible overexpression of a VEGF transgene (VEGF(AdTg)) in the adipose tissue. VEGF(AdΔ) mice have reduced adipose vascular density and show adipose hypoxia, apoptosis, inflammation, and metabolic defects on a high-fat diet. In contrast, induction of VEGF expression in VEGF(AdTg) mice leads to increased adipose vasculature and reduced hypoxia. The latter changes are sufficient to counteract an established compromising effect of high-fat diet on the metabolism, indicating that metabolic misbalance is reversible by adipose vessel density increase. Our data clearly show the essential role of VEGF signaling for adequate adipose function. Besides revealing insights into the molecular mechanisms of obesity-related metabolic diseases, this study points to the therapeutic potential of increased adipose angiogenesis.

Medullary carcinoma of the breast: MRI findings.

OBJECTIVE: The objective of our study was to describe the MRI findings of medullary carcinoma of the breast and to correlate those findings with the histopathologic findings. MATERIALS AND METHODS: From January 2005 to June 2010, MR images of 15 patients (age range, 32-73 years; mean age, 50 years) with pathologically confirmed medullary carcinoma of the breast were retrospectively evaluated according to BI-RADS. MR images were reviewed for the following: enhancement type (mass vs nonmass), size, shape, margins, contrast enhancement, signal intensity, and time-intensity curve pattern on a dynamic study. These MR features were correlated with the histopathologic features. RESULTS: All 15 tumors were seen as a mass on MRI. The median size of the masses was 2.7 cm (range, 1.5-6.3 cm) and the most common features were an oval or lobular shape (13/15, 86.7%) and a circumscribed margin (13/15, 86.7%). Rim enhancement with enhancing internal septations was seen in seven masses (46.7%), and rim enhancement was seen in six masses (40%). A hypointense rim on T2-weighted images was seen in nine tumors (9/15, 60%). Last, the kinetics curve showed a rapid initial increase in enhancement and a washout or plateau pattern on delayed phase imaging in all 15 tumors. CONCLUSION: On MRI, medullary carcinomas of the breast appeared as masses with an oval or lobular shape and circumscribed margins. Rim enhancement with or without enhancing internal septations was frequently seen on contrast enhancement.

Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation.

Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging.

Sonographic findings of invasive cribriform carcinoma of the breast.

The purpose of this series was to evaluate the sonographic features of invasive cribriform carcinoma of the breast. Between 2004 and 2010, 3 patients had confirmed invasive cribriform carcinoma of the breast in our institution, and all of them underwent sonography. Sonograms showed masses with an oval (n = 2) or irregular (n = 1) shape, partially microlobulated (n = 2) or well-circumscribed (n = 1) margins, and a hypoechoic (n = 2) or an isoechoic (n = 1) internal echo texture. Sonographic assessments were classified as Breast Imaging Reporting and Data System category 4 in all 3 cases. Although invasive cribriform carcinoma is a rare breast malignancy, awareness of its sonographic features will be helpful for the diagnosis.

Efficacy of MRI versus arthroscopy for evaluation of sinus tarsi syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) has been used to diagnose sinus tarsi syndrome (STS) because of its non-invasiveness and accuracy. The purpose of the present study was to evaluate the diagnostic efficiency of MRI compared with subtalar arthroscopy for STS. MATERIALS AND METHODS: Twenty-eight patients (30 feet) who had undergone both MRI and subtalar arthroscopy for STS were evaluated. MRI results were compared with arthroscopic findings, which were considered the standard. Sensitivity, specificity, and positive and negative predictive values were calculated, and correlations between MRI and arthroscopic findings were investigated. RESULTS: MRI was found to detect interosseous talocalcaneal ligament (ITCL) tears, cervical ligament (CL) tears, sinus tarsi fat alterations, and synovial thickening, with sensitivities, specificities, positive and negative predictive accuracies of: 44%, 60%, 85%, 18% (ITCL tears); 73%, 89%, 80%, 86% (CL tears); 71%, 92%, 93%, 71% (sinus tarsi fat alterations); and 86%, 87%, 67%, 95% (synovial thickening). Correlations between MRI and arthroscopic findings showed full agreement in 10%, partial agreement in 50%, and no agreement in 40%. CONCLUSION: MRI is useful for detecting CL tears, sinus tarsi fat alterations, and synovial thickening, but is inadequate for correctly detecting ITCL tears.

A comparison of arthroscopic and MRI findings in staging of osteochondral lesions of the talus.

The purpose of the present study was to evaluate the accuracy of MRI compared with arthroscopy in staging of osteochondral lesions of the talus (OLTs). The authors prospectively investigated 50 patients (52 cases) who had undergone both MRI and ankle arthroscopy for OLTs. The 30 males (32 ankles) and 20 females (20 ankles) had an average age of 43 years (range 19-64 years). The correlations between MRI and arthroscopic stagings were also investigated. Preoperative MRI resulted in 7 stage I, 11 stage II, 25 stage III, and 9 stage IV lesions, and ankle arthroscopic findings in 3 stage I, 5 stage II, 35 stage III, and 9 stage IV lesions. No stage V lesion was encountered. A comparison of MRI and arthroscopic stagings revealed that MRI had an accuracy of 81% (42 of 52) for staging of OLTs. MRI correctly staged 3 of 7 stage I lesions, 5 of 11 stage II, 25 of 25 stage III, and 9 of 9 stage IV lesions. Ten mismatched cases were of arthroscopic stage III lesions, which MRI classified as four stage I lesions and six stage II lesions. Thus, MRI staging tended to understate lesion severity. We re-reviewed the ten MR images of the mismatching cases to identify reasons for these mismatches, and subchondral edema was found in six cases. The authors conclude that MRI has accuracy of 81% in staging of OLTs, however, MRI had some limitation in correct staging isolated cartilage lesions of OLTs, especially combined with subchondral edema.

Melanotic neuroectodermal tumor of infancy in the femur: a case report and review of the literature.

Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon neoplasm that most often affects the maxilla in the first year of life. MNTI occurring in the long bones is extremely rare, with only 2 cases reported in the medical literature. Here we report a case of MNTI in the right femur of a 5-month-old infant who underwent neoadjuvant chemotherapy followed by limb-salvage surgery.

Systematic discovery of in vivo phosphorylation networks.

Protein kinases control cellular decision processes by phosphorylating specific substrates. Thousands of in vivo phosphorylation sites have been identified, mostly by proteome-wide mapping. However, systematically matching these sites to specific kinases is presently infeasible, due to limited specificity of consensus motifs, and the influence of contextual factors, such as protein scaffolds, localization, and expression, on cellular substrate specificity. We have developed an approach (NetworKIN) that augments motif-based predictions with the network context of kinases and phosphoproteins. The latter provides 60%-80% of the computational capability to assign in vivo substrate specificity. NetworKIN pinpoints kinases responsible for specific phosphorylations and yields a 2.5-fold improvement in the accuracy with which phosphorylation networks can be constructed. Applying this approach to DNA damage signaling, we show that 53BP1 and Rad50 are phosphorylated by CDK1 and ATM, respectively. We describe a scalable strategy to evaluate predictions, which suggests that BCLAF1 is a GSK-3 substrate.

FDG PET/CT for the detection and evaluation of breast diseases: usefulness and limitations.

Positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) is used to diagnose, stage, and monitor breast cancer. FDG PET has the capability to depict abnormal metabolic activity before any anatomic change occurs; however, in the absence of identifiable anatomic structures on PET images, it may be impossible to identify the location of areas of increased radionuclide uptake. In such cases, the coregistration of PET images with images from computed tomography (CT) may help improve diagnostic accuracy and lead to better clinical management of patients with breast cancer. Although FDG PET/CT may have limited diagnostic value for detecting small primary breast tumors, well-differentiated breast cancer, or regional lymph node involvement, it is superior to conventional imaging modalities for detecting distant metastases and recurrences and for monitoring the response to therapy.

Imaging features of hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation.

OBJECTIVE: The purpose of this pictorial essay is to show the imaging features of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and radiofrequency thermal ablation on CT, MRI, and contrast-enhanced sonography and to describe the advantages and limitations of each imaging technique in evaluating the therapeutic effect on HCC. CONCLUSION: CT is the standard imaging technique for monitoring the effectiveness of TACE and radiofrequency ablation. Contrast-enhanced sonography and MRI can complement CT in evaluating the therapeutic response.

Transarterial embolization for postoperative hemorrhage after abdominal surgery.

The study goal was to evaluate the efficacy, safety, and clinical outcome of transarterial embolization for postoperative hemorrhage after abdominal surgery. Thirty-three patients were referred for angiography because of gastrointestinal or intra-abdominal bleeding after abdominal surgery. Urgent angiography and transarterial embolization was performed in all 33 patients. The clinical and angiographic features were retrospectively reviewed. Angiography revealed a discrete bleeding focus in 26 (79%) of 33 patients. Transarterial embolization was technically successful in 24 (92%) of 26 patients with a discrete bleeding focus. Rebleeding occurred in four (17%) of 24 patients. They were successfully managed with repeat embolization. There was no procedure-related complication during follow-up period. Angiography has a high detection rate of bleeding site in patients with postoperative hemorrhage after abdominal surgery. Transarterial embolization is considered to be an effective and safe means in the management of postoperative hemorrhage.

CT in blunt liver trauma.

Nonsurgical treatment has become the standard of care in hemodynamically stable patients with blunt liver trauma. The use of helical computed tomography (CT) in the diagnosis and management of blunt liver trauma is mainly responsible for the notable shift during the past decade from routine surgical to nonsurgical management of blunt liver injuries. CT is the diagnostic modality of choice for the evaluation of blunt liver trauma in hemodynamically stable patients and can accurately help identify hepatic parenchymal injuries, help quantify the degree of hemoperitoneum, and reveal associated injuries in other abdominal organs, retroperitoneal structures, and the gastrointestinal tract. The CT features of blunt liver trauma include lacerations, subcapsular or parenchymal hematomas, active hemorrhage, juxtahepatic venous injuries, periportal low attenuation, and a flat inferior vena cava. It is important that radiologists be familiar with the liver injury grading system based on these CT features that was established by the American Association for the Surgery of Trauma. CT is also useful in the assessment of delayed complications in blunt liver trauma, including delayed hemorrhage, hepatic or perihepatic abscess, posttraumatic pseudoaneurysm and hemobilia, and biliary complications such as biloma and bile peritonitis. Follow-up CT is needed in patients with high-grade liver injuries to identify potential complications that require early intervention.

Sacrococcygeal chordoma: MR imaging in 30 patients.

OBJECTIVE: To evaluate MR imaging of sacrococcygeal chordoma. DESIGN AND PATIENTS: Thirty patients (age range 22-80 years) underwent MR imaging for the diagnosis and preoperative evaluation of sacrococcygeal chordomas. Eight patients had follow-up MR examination after treatment. The MR images were performed with T1- and T2-weighted imaging, and gadolinium (Gd)-enhanced imaging. The MR images were analyzed for the signal intensity, enhancing pattern, tumor size, growth pattern of the soft tissue component, and tumor extension. RESULTS AND CONCLUSIONS: T1-weighted images showed low signal masses with foci of high signal intensity in 73% of cases. Tumors enhanced in a variety of patterns after the administration of Gd. Soft tissue masses extending anteriorly were seen in all cases with posterior extension in 77% of cases. The posterior masses involved the surrounding muscles and extended toward the greater sciatic notch, appearing with pseudopodia (87%). Sacroiliac joints were involved in 23% of cases. Four lesions showed intraspinal extension and involvement of the posterior spinal muscles above the level of bony involvement. In 6 patients recurrent tumors were found at or around the surgical margin of the tumor 6 months to 5 years after resection of the sacral tumor. In two of the patients, nodular metastases to the pelvic bones and femur were found 1-4 years after initial examination. In conclusion, MR imaging is useful in the diagnosis and preoperative assessment of sacrococcygeal chordoma. Characteristic findings included sacral mass with heterogeneously high signal intensity with crisscrossing septa on long-repetition-time imaging, well-encapsulated pseudopodia-like or lobulated appearance, and gluteal muscle infiltration. Follow-up MR imaging is helpful to assess for recurrent or metastatic lesions of chordomas.

Imaging findings of Kimura's disease in the soft tissue of the upper extremity.

OBJECTIVE: The objective of our study was to describe the imaging findings of Kimura's disease in the soft tissue of the upper extremity. CONCLUSION: Kimura's disease should be considered as a possible diagnosis when a partially or poorly defined subcutaneous mass of high signal intensity on T1- and T2-weighted images with homogeneous enhancement, surrounding subcutaneous edema, and internal flow voids is seen in the medial epitrochlear region in an Asian person, especially if accompanied by peripheral eosinophilia.

Uterine cervical carcinoma after therapy: CT and MR imaging findings.

Cervical carcinoma is one of the most frequent causes of death in women. Computed tomography (CT) and magnetic resonance (MR) imaging are the primary modalities for follow-up of treated cervical carcinoma. A normal vaginal cuff after hysterectomy appears as a smooth, low-signal-intensity muscular wall on T2-weighted MR images. Early (2-3 months after treatment) and significant decreases in the signal intensity and volume of the tumor at MR imaging indicate a good response to radiation therapy. Sites of recurrence are the pelvis, lymph nodes, and distant sites. Pelvic recurrence appears as a heterogeneously enhancing mass at contrast material-enhanced CT and often appears as a heterogeneous, high-signal-intensity mass at T2-weighted MR imaging. Lymph node recurrence ranges from scattered, minimally enlarged nodes to large, conglomerate nodal masses. Determination of neoplastic infiltration of lymph nodes is based on size; most researchers consider nodes greater than 1 cm in short-axis diameter to be metastatic. Distant metastases are usually due to recurrent disease and occur in the abdomen, thorax, and bone. Knowledge of the normal therapeutic changes and the spectrum of recurrent tumor in patients with cervical carcinoma is important for accurate interpretation of follow-up CT and MR images.