Vortioxetine improved schizophrenia-like behavioral deficits in a Poly I:C-induced maternal immune activation model of schizophrenia in rats.

BACKGROUND: Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic-polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring. OBJECTIVES: The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C-induced schizophrenia-like model in rats. METHODS: For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL-6 levels after 2 h. At postnatal days 83-86, behavioral tests were performed. RESULTS: Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open-field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69-83) caused significant improvements in these deficits. CONCLUSION: Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.

Independent and combined effects of astaxanthin and omega-3 on behavioral deficits and molecular changes in a prenatal valproic acid model of autism in rats.

Objectives: Autism is a devastating neurodevelopmental disorder and recent studies showed that omega-3 or astaxanthin might reduce autistic symptoms due to their anti-inflammatory properties. Therefore, we investigated the effects of omega-3 and astaxanthin on the VPA-induced autism model of rats.Material and Methods: Female Wistar albino pups (n = 40) were grouped as control, autistic, astaxanthin (2 mg/kg), omega-3 (200 mg/kg), and astaxanthin (2 mg/kg)+omega-3 (200 mg/kg). All groups except the control were prenatally exposed to VPA. Astaxanthin and omega-3 were orally administered from the postnatal day 41 to 68 and behavioral tests were performed between day 69 and 73. The rats were decapitated 24 h after the behavioral tests and hippocampal and prefrontal cytokines and 5-HT levels were analyzed by ELISA.Results: VPA rats have increased grooming behavior while decreased sociability (SI), social preference index (SPI), discrimination index (DI), and prepulse inhibition (PPI) compared to control. Additionally, IL-1ß, IL-6, TNF-α, and IFN-γ levels increased while IL-10 and 5-HT levels decreased in both brain regions. Astaxanthin treatment raised SI, SPI, DI, PPI, and prefrontal IL-10 levels. It also raised 5-HT levels and decreased IL-6 levels in both brain regions. Omega-3 and astaxanthin + omega-3 increased the SI, SPI, DI, and PPI and decreased grooming behavior. Moreover, they increased IL-10 and 5-HT levels whereas decreased IL-1ß, IL-6, TNF-α, IFN-γ levels in both brain regions.Conclusions: Our results showed that VPA administration mimicked the behavioral and molecular changes of autism in rats. Single and combined administration of astaxanthin and omega-3 improved the autistic-like behavioral and molecular changes in the VPA model of rats.

The long-lasting effects of aceclofenac, a COX-2 inhibitor, in a Poly I:C-Induced maternal immune activation model of schizophrenia in rats.

It is well established that rats exposed to inflammation during pregnancy or the perinatal period have an increased chance of developing schizophrenia-like symptoms and behaviors, and people with schizophrenia also have raised levels of inflammatory markers. Therefore, there is evidence supporting the idea that anti-inflammatory drugs may have therapeutic benefits. Aceclofenac is a nonsteroidal anti-inflammatory drug that has anti-inflammatory properties and is used clinically to treat inflammatory and painful processes such as osteoarthritis and rheumatoid arthritis, making it a potential candidate for preventive or adjunctive therapy in schizophrenia. This study therefore examined the effect of aceclofenac in a maternal immune activation model of schizophrenia, in which polyinosinic-polycytidylic acid (Poly I:C) (8 mg/kg, i.p.) was administered to pregnant rat dams. Young female rat pups received daily aceclofenac (5, 10, and 20 mg/kg, i.p., n = 10) between postnatal day 56 and 76. The effects of aceclofenac were compared with assessment of behavioral tests and ELISA results. During the postnatal days (PNDs) 73-76, behavioral tests were conducted in rats, and on PND 76, ELISA tests were performed to examine the changes in Tumor necrosis factor alpha (TNF-α), Interleukin-1ß (IL-1ß), Brain-derived neurotrophic factor (BDNF), and nestin levels. Aceclofenac treatment reversed deficits in prepulse inhibition, novel object recognition, social interaction, and locomotor activity tests. In addition, aceclofenac administration decreased TNF-α and IL-1ß expression in the prefrontal cortex and hippocampus. In contrast, BDNF and nestin levels did not change significantly during treatment with aceclofenac. Taken together, these results suggest that aceclofenac may be an alternative therapeutic adjunctive strategy to improve the clinical expression of schizophrenia in the further studies.

Group I mGluRs positive allosteric modulators improved schizophrenia-related behavioral and molecular deficits in the Poly I:C rat model.

RATIONALE: Maternal polyinosinic-polycytidylic acid (Poly I:C) exposure leads to an increase in various proinflammatory cytokines and causes schizophrenia-like symptoms in offspring. In recent years, group I metabotropic glutamate receptors (mGluRs) have emerged as a potential target in the pathophysiology of schizophrenia. OBJECTIVES: The aim of our study was to investigate the behavioral and molecular changes by using the mGlu1 receptor positive allosteric modulator (PAM) agent RO 67-7476, and the negative allosteric modulator (NAM) agent JNJ 16259685 and the mGlu5 receptor PAM agent VU-29, and NAM agent fenobam in the Poly I:C-induced schizophrenia model in rats. METHODS: Female Wistar albino rats were treated with Poly I:C on day 14 of gestation after mating. On the postnatal day (PND) 34-35, 56-57 and 83-84, behavioral tests were performed in the male offspring. On the PND84, brain tissue was collected and the level of proinflammatory cytokines was determined by ELISA method. RESULTS: Poly I:C caused impairments in all behavioral tests and increased the levels of proinflammatory cytokines. While PAM agents caused significant improvements in prepulse inhibition (PPI), novel object recognition (NOR), spontaneous alternation and reference memory tests, they brought the levels of proinflammatory cytokines closer to the control group. NAM agents were ineffective on behavioral tests. It was observed that PAM agents significantly improved Poly I:C-induced disruption in behavioral and molecular analyses. CONCLUSIONS: These results suggest that PAM agents, particularly the mGlu5 receptor VU-29, are also promising and could be a potential target in schizophrenia.

Vortioxetine improved negative and cognitive symptoms of schizophrenia in subchronic MK-801 model in rats.

Schizophrenia is a devastating psychiatric disorder with complex symptoms and neurobiology. Serotonergic dysregulation is known to contribute to the pathogenesis of schizophrenia although dopaminergic and glutamatergic systems are thought to have central roles in neurobiology. No significant success can be achieved in the treatment of negative and cognitive symptoms while positive symptoms can be significantly reduced with current pharmacotherapy. Vortioxetine is a new multimodal antidepressant with 5-HT1A agonism, 5-HT1B partial agonism, 5-HT3, 5-HT7, and 5-HT1D antagonism, and serotonin reuptake inhibition. A limited number of studies suggest its therapeutic effect on the negative and cognitive symptoms of schizophrenia. Therefore, we investigated the potential beneficial effects of vortioxetine on behavioral and molecular deficits in the MK-801 model of schizophrenia in rats. Female Wistar albino rats (10-12 weeks) were grouped as saline, MK-801 (0.2 mg/kg), MK-801 + vortioxetine (2.5 mg/kg), MK-801 + vortioxetine (5 mg/kg), MK-801 + vortioxetine (10 mg/kg), MK-801 + risperidone (0.3 mg/kg), MK-801 + haloperidol (1 mg/kg) (n = 8 in each group). MK-801 has been daily administered (i.p.) for 14 days. Vortioxetine and antipsychotic treatments were injected for 21 days after a washout period of MK-801 and locomotor activity (LA), social interaction (SI), novel object recognition (NOR), Y-maze and prepulse inhibition (PPI) tests were performed at the 16-20th days of treatments, respectively. ELISA test was conducted to evaluate molecular analyses. MK-801 decreased PPI (%), social behaviors, and discrimination index in NOR and alternation (%) in the Y-maze test. In NOR and Y-maze tests, especially vortioxetine 5 and 10 mg/kg increased discrimination index and alternation (%) compared to MK-801. In addition, vortioxetine administration increased social behaviors. Moreover, MK-801 decreased GAD67 and parvalbumin levels while vortioxetine increased these protein levels compared to MK-801. Herein, we first suggested a potential therapeutic effect of vortioxetine, a new multimodal antidepressant, on negative and cognitive symptoms and neurobiological deficits including GAD67 and parvalbumin low expression in the MK-801 model in rats. It would be beneficial to confirm our results in different rodent models and to shed light on the possible mechanisms underlying these effects.

Fat Juice: A Novel Approach on the Usage and Preparation of Adipose Tissue By-Products.

BACKGROUND: Adipose tissue is considered to be naturally rich in a range of bioactive substances that may be extracted directly for therapeutic use without the need for cell isolation or culture. OBJECTIVES: The aim of this study was to introduce a novel approach that utilizes stromal vascular fraction in conjunction with fat extract, termed "fat juice," and to perform a comprehensive biochemical analysis in relation to the potential clinical relevance of this new combination. METHODS: A total of 11 samples of fat juice from the abdominal lipoaspirate were extracted from 11 healthy patients and analyzed in terms of the quantity and viability of stem cells, the presence and quantification of connective tissue fibers on histopathologic examination, and the levels of interleukin-6, mannose receptor C type 1, and vascular endothelial growth factor measured by enzyme-linked immunosorbent assay. RESULTS: Total stem cell amounts ranged from 0.14 × 105 to 1.31 × 105, and cell viability rates varied between 20% and 67.9%. Interleukin-6 protein and vascular endothelial growth factor expressions were highest in Sample 3, while staining intensity was highest in Sample 4. For collagen I, collagen III, and elastin, the highest expressions were observed in Samples 4 and 8, in Sample 3, and in Samples 2 and 4, respectively. CONCLUSIONS: Fat juice provides an easy-to-inject concentration of adipocyte/preadipocytes, red blood cells, adipose-derived stem cells, endothelial-derived cells, and cell residues. Prepared through an easy isolation process enabling abundant availability, fat juice seems to be an effective skin quality enhancer with potential for widespread use in the fields of plastic surgery, dermatology, and aesthetic/regenerative medicine.

Evaluation of the Chemical Composition, Antioxidant and Antidiabetic Activity of Rhaponticoides iconiensis Flowers: Effects on Key Enzymes Linked to Type 2 Diabetes In Vitro, In Silico and on Alloxan-Induced Diabetic Rats In Vivo.

Diabetes mellitus (DM) is one of the globally worst killer diseases. In this study, the in vitro and in vivo antidiabetic activity and antioxidant capacity were determined and the phytochemical analyses were carried out on flower extract and sub-extracts of Rhaponticoides iconiensis. The in vitro antidiabetic activity was tested with α-amylase and α-glucosidase enzyme inhibition methods and an in vivo OGTT test in healthy and alloxan-induced rats. Although, the antioxidant activity was investigated with DPPH●, ABTS●+ and FRAP tests, the phytochemical composition analysis was carried out by LC-MS/MS. The highest α-glucosidase and α-amylase activity even from positive control acarbose were found in the ethyl acetate sub-extract of R. iconiensis (IC50 = 11.737 ± 0.823 µg/mL and 84.247 ± 0.721 µg/mL, respectively). This sub-extract also was active according to the results of in vivo tests. Moreover, the highest antioxidant activity on DPPH● (IC50 = 0.126 ± 0.002 mg/mL), FRAP (at a concentration of 1 mg/mL equivalent to 3112.052 ± 2.023 mmol Fe2+) and ABTS+● (at a concentration of 0.5 mg/mL equivalent to 0.608 ± 0.005 µM Trolox) tests. In addition, LC-MS/MS analyses of the active sub-extract revealed mainly the presence of patuletin, patuletin 3,7-diglucoside, naringin and 3,4-dicaffeoylquinic acid detected in the active sub-extract. In silico molecular docking and dynamics simulations studies were performed on these compounds with α-amylase and α-glucosidase enzymes for protein-ligand interactions and stability.

Probiotics and prebiotics alleviate behavioral deficits, inflammatory response, and gut dysbiosis in prenatal VPA-induced rodent model of autism.

Autism spectrum disorders are neuropsychiatric conditions characterized by social interaction and communication disorders and repetitive stereotypical behaviors. These disorders are also accompanied by an inflammatory status. Bidirectional communication between microbiome, gut, and brain has been discovered as a major mechanism influencing core symptoms and biomarkers of autism. Therefore, the modulation of the gut microbiota in autism has recently attracted interest. In this study, probiotic- and prebiotic-mediated modulation of the gut microbiota was compared in terms of different symptoms and findings in an experimental autism model. Valproic acid (VPA) (500 mg/kg) was administered to Wistar rats (on prenatal day 12.5) to induce autistic-like behaviors. Based on the supply of probiotics and prebiotics, animals were grouped as control (saline), autistic-like (prenatal VPA), probiotic (prenatal VPA + 22.5 × 109 cfu/day probiotic), prebiotic (prenatal VPA + 100 mg/day prebiotic), and combined treatment (prenatal VPA + 22.5 × 109 cfu/day probiotic + 100 mg/day prebiotic). After the treatment process, behavioral tests (social behaviors, anxiety, stereotypical behavior, sensorimotor gating, and behavioral despair) and biochemical analyses (serum and brain tissue) were conducted, and the quantities of some phyla and genera were determined in stool samples. Significant positive effects of probiotic and combined treatments were observed on the sociability, social interaction, and anxiety parameters. In addition, all three treatments had positive effects on stereotypical behavior. However, the treatments did not affect sensorimotor gating deficits and behavioral despair. Further, probiotic treatment reversed the VPA-induced increase and decrease in serum IL-6 and IL-10 levels, respectively. Combined treatment also significantly increased the IL-10 levels. Prenatal VPA exposure decreased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex of the brain; however, combined treatment reversed this decrease. Prenatal VPA exposure also caused a decrease in Bacteroidetes/Firmicutes ratio in the gut microbiota, while the probiotic treatment significantly increased this ratio. These findings indicate that probiotic- and prebiotic-mediated microbial modulation may represent a new therapeutic approach to alleviate autistic-like symptoms.

Effects of probiotic supplementation on very low dose AFB1-induced neurotoxicity in adult male rats.

AIMS: Aflatoxin B1 (AFB1) is the most toxic and common form of AF found in food and feed. Although AFB1 exposure has toxic effects on many organs, studies on the brain are limited. Moreover, to the best of our knowledge, there is no study on the effect of probiotics on AFB1-induced neurotoxicity. Therefore, we aimed to evaluate the possible effects of probiotics on AFB1-induced neurotoxicity in the brain. MAIN METHODS: Thirty-two adult male Wistar rats were divided into four groups: Vehicle (VEH), Probiotic (PRO) (2.5 × 1010 CFU/day VSL#3, orally), Aflatoxin B1 (AFB1) (25 µg/kg/week AFB1, orally), and Aflatoxin B1 + Probiotic (AFB1 + PRO) (2.5 × 1010 CFU/day VSL#3 + 25 µg/kg/week AFB1, orally). At the end of eight weeks, rats were behaviorally evaluated by the open field test, novel object recognition test, and forced swim test. Then, oxidative stress and inflammatory markers in brain tissues were analyzed. Next, brain sections were processed for Hematoxylin&Eosin staining and NeuN and GFAP immunostaining. KEY FINDINGS: Probiotic supplementation tended to decrease oxidative stress and inflammatory markers compared to the AFB1 group. Besides, brain tissues had more normal histological structures in VEH, PRO, and AFB1 + PRO groups than in the AFB1 group. Moreover, in probiotic groups, GFAP immunoreactivity intensity was decreased, while NeuN-positive cell number increased in brain tissues compared to the AFB1 group. SIGNIFICANCE: Probiotics seem to be effective at reducing the neurotoxic effects of AFB1. Thus, our study suggested that especially Bifidobacterium and Lactobacillus species can improve AFB1-induced neurotoxicity with their antioxidant and anti-inflammatory effects.

Vortioxetine suppresses epileptiform activity and cognition deficits in a chronic PTZ-induced kindling rat model.

This study aimed to examine the effects of vortioxetine, a novel antidepressant, on epileptiform activity in pentylenetetrazole (PTZ)-induced kindling model in rats. For this purpose, 20 male Wistar Albino rats were used, and epileptiform activity was induced by injection of PTZ (35 mg/kg, i.p., three times a week). In the vortioxetine groups, vortioxetine (5 mg/kg and 10 mg/kg) was administered before the kindling process. During the kindling process, the Fisher and Kittner seizure scales were used to score seizure severity. After kindling, novel object recognition (NOR) tests were performed to evaluate the cognitive performance of rats. Electrodes were implanted into the fully kindled animals for ECoG recordings. In the PTZ group, the number of total spikes was 1367±136 spikes/20 minutes. First myoclonic jerks decreased while seizure severity and total spike count increased in the PTZ group. On the other hand, the total spike number and seizure severity significantly decreased and first myoclonic jerks increased in the vortioxetine groups compared to the PTZ group. Based on the NOR test, vortioxetine administration markedly raised the discrimination index compared to the PTZ group. Electrophysiological and behavioural data from the present study suggest that vortioxetine, a novel drug, plays a critical role in controlling PTZ-induced epileptiform activity in rats. Vortioxetine may therefore be a valuable candidate to prevent seizure activity and treat cognitive deficits associated with epilepsy.

Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models.

Naproxen is a common non-steroidal anti-inflammatory drug, which is the most usually used propionic acid derivative for the treatment of many types of diseases. In this study, a series of novel (S)-Naproxen derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H-13C NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds were screened for anticancer activity against two different human breast cancer cell lines (MDA-MB-231 and MCF-7). Among them, (S)-2-(6-methoxynaphthalen-2-yl)-N'-{(E)-[2-(trifluoromethoxy)phenyl]methylidene} propanehydrazide (3a) showed the most potent anticancer activity against both cancer cell lines with a good selectivity (IC50 = 22.42 and 59.81 µM, respectively). Furthermore, the molecular modeling of these compounds was studied on Vascular Endothelial Growth Factor Receptor 2. Inhibition of VEGFR-2 and apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 3a by using Western Blotting. Apoptosis was also detected by staining with DAPI in fluorescence microscopy. Flow Cytometry analyses related to cell cycle phases showed that a dramatic increase in S and M phases was established compared to untreated control cells indicating the cancer cell cycle arrest. The anticancer activity of compound 3a was investigated in the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, in mice. Our results showed that compound 3a had anticancer activity and decreased the tumor volume in both low (60 mg/kg) and high (120 mg/kg) doses in mice.

α7 nicotinic receptor agonist and positive allosteric modulators differently improved schizophrenia-like cognitive deficits in male rats.

The majority of schizophrenia patients have cognitive deficits as a separate symptom cluster independent of positive or negative symptoms. Current medicines, unfortunately, cannot provide clear benefits for cognitive symptoms in patients. Recent findings showed decreased α7 nicotinic acetylcholine receptor (nAChR) expressions in subjects with schizophrenia. α7 nAChR full/partial agonists and positive allosteric modulators (PAMs) may be valuable drug candidates to treat cognitive deficits of disease. This study comparatively investigated the effect of α7 nAChR agonist (A-582941), type I PAM (CCMI), type II PAM (PNU-120596), and the antipsychotic drug (clozapine) on behavioral, molecular, and immunohistochemical parameters in a subchronic MK-801 model of schizophrenia in male rats. Novel object recognition (NOR) and Morris water maze (MWM) tests were performed to evaluate recognition and spatial memories, respectively. Gene and protein expressions of parvalbumin, glutamic acid decarboxylase-67 (GAD67), and α7 nAChR were examined in the rats' hippocampal tissue. The subchronic MK-801 administration produced cognitive deficits in the NOR and MWM tests. It also decreased the protein and gene expressions of parvalbumin, GAD67, and α7 nAChR in the hippocampus. Clozapine, A-582941, and PNU-120596 but not CCMI increased the parvalbumin and α7 nAChR expressions and provided benefits in recognition memory. Interestingly, clozapine and CCMI restored the MK-801 induced deficits on GAD1 expression and spatial memory while A-582941 and PNU-120596 were ineffective. These results indicated that α7 nAChR agonist, type I and type II PAMs may provide benefits in different types of cognitive deficits rather than a complete treatment in schizophrenia.

Famotidine has a neuroprotective effect on MK-801 induced toxicity via the Akt/GSK-3ß/ß-catenin signaling pathway in the SH-SY5Y cell line.

Schizophrenia cannot be treated sufficiently with existing antipsychotic drugs. Taken into account that increased Glycogen Synthase Kinase 3 Beta (GSK-3ß) activity is associated with schizophrenia pathophysiology and certain antipsychotics can be able to decrease GSK3ß activity, inhibition of GSK-3ß activity could be a novel approach for the treatment of schizophrenia. In the present study MK-801, a widely used chemical for the in vivo/in vitro modeling of schizophrenia was selected to evoke a detrimental effect on cellular survival via GSK3ß and related proteins. A limited number of studies have reported the curative effects of famotidine, an antiulcer drug, in schizophrenic patients. To the best of our knowledge, no study investigated the molecular mechanism of the beneficial effect of famotidine in the patients. A recent study based on computerized drug modeling software (docking) indicated that famotidine might inhibit the GSK3ß activity due to its chemical structure independent from histaminergic receptors. In this study, we aimed to investigate the effects of famotidine on the Akt/GSK-3ß/ß-catenin signaling pathway on SH-SY5Y neuroblastoma cells in the presence of MK-801. We investigated the effects of famotidine, olanzapine (an antipsychotic drug), and SB 415286 (specific GSK-3ß inhibitor), on the basal cellular survival and MK-801 induced neuronal death beside of Akt/GSK-3ß/ß-catenin protein and gene expressions in SH-SY5Y cells. Cell viability, protein and gene expressions were determined by the real-time cell analysis (xCELLigence) system, western blotting and real-time polymerase chain reactions (Rt-PCR), respectively. Our findings suggested that MK-801 administration decreased cell survival probably via the increasing GSK-3ß gene expression and activity in the SH-SY5Y cells. Pre-treatments with famotidine, olanzapine, and SB 415286 prevented MK-801 induced cell death via inhibitory effects on the MK-801 induced GSK-3ß activity. Overall, the present results suggest that famotidine has a neuroprotective effect against MK-801 via modulation of the Akt/GSK-3ß/ß-catenin signaling pathway, an important mechanism in schizophrenia neurobiology.

Observer Variability of the Breast Imaging Reporting and Data System (BI-RADS) Lexicon for Mammography.

AIM: We aimed to determine the inter- and intra-observer variabilities between breast radiologists and a general radiologist in categorizing mammographic lesions using the Breast Imaging Reporting and Data System (BI-RADS), and to evaluate the effects of the histopathologic results on the variability. METHODS: Mammograms from 142 women who underwent biopsy were evaluated. 3 breast radiologists (2 with >10 years experience and 1 with 1 year experience) and 1 general radiologist retrospectively reviewed mammograms twice within an 8-week interval. Inter- and intra-observer variabilities were assessed with Cohen's kappa statistic, and the positive predictive value for final assessments was calculated. RESULTS: The intra-observer variability for mass and calcification assessments was moderate to almost perfect (kappa values: 0.41-1) for breast imagers and was fair to substantial for the general radiologist (kappa values: 0.21-0.8). Inter-observer agreement between the breast imagers was higher than between the breast and general radiologists. There was no apparent difference in agreement between observers for malignant and benign subgroups. CONCLUSIONS: The differences in intra- and inter-observer agreement between the breast imagers and the general radiologist affirm the utility of the BI-RADS lexicon. The histopathologic results of the lesions do not affect the agreement. BI-RADS is a simple and adequate tool for assessing mammograms, even after only 1 year of training.

SSH-EPI diffusion-weighted MR imaging of the spine with low b values: is it useful in differentiating malignant metastatic tumor infiltration from benign fracture edema?

OBJECTIVE: Conventional MR sequences are sometimes not helpful in differentiating benign from pathologic fractures. Our aim was to evaluate the usefulness of single-shot echo-planar imaging sequences (diffusion-weighted imaging (DWI)/SSH-EPI) with low b value in differentiating malignant metastatic tumor infiltration of vertebral bone marrow from benign vertebral fracture edema. MATERIALS AND METHODS: A total of 47 patients, 20 with benign fractures and 27 with tumor infiltration, were included in this prospective study. Diffusion-weighted MR images were obtained by single-shot echo-planar imaging technique with diffusion gradient (b = 300 s/mm2; TR/TE, 1,400/100), using a 1.5 T MR scanner. T1- and T2-weighted images and short inversion time inversion-recovery images were available for all 64 lesions. The lesions on DWI/SSH-EPI were categorized as having hypo-, iso-, or hyperintense signal intensity relative to normal vertebrae by two experienced radiologists. RESULTS: We evaluated signal intensity patterns on DWI/SSH-EPI in 64 lesions, which showed low signal intensity on T1-weighted images in both benign fractures and metastasis. With the exception of sclerotic metastases in two patients, malignant metastatic tumor infiltration was hyperintense with respect to normal bone marrow on diffusion-weighted images; all but four benign vertebral fractures were isointense with respect to normal bone marrow. CONCLUSION: Single-shot echo-planar imaging sequences (DWI/SSH-EPI) with low b value provided excellent distinction between metastatic tumor infiltration and benign vertebral fracture edema. Hyperintense signal intensity on DWI/SSH-EPI was highly specific for the diagnosis of metastatic tumor infiltration of the spine.