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Abstract In this prospective, multi-reader, multi-vendor study, we evaluated the performance of a commercially available deep neural network (DNN)–based MR image reconstruction in enabling accelerated 2D fast spin-echo (FSE) knee imaging. Forty-five subjects were prospectively enrolled and randomly divided into three 3T MRIs. Conventional 2D FSE and accelerated 2D FSE sequences were acquired for each subject, and the accelerated FSE images were reconstructed and enhanced with DNN–based reconstruction software (FSE-DNN). Quantitative assessments and diagnostic performances were independently evaluated by three musculoskeletal radiologists. For statistical analyses, paired t-tests, and Pearson’s correlation were used for image quality comparison and inter-reader agreements. Accelerated FSE-DNN reduced scan times by 41.0% on average. FSE-DNN showed better SNR and CNR (p 0.05), and diagnostic performances of FSE-DNN showed comparable lesion detection. Two of cartilage lesions were under-graded or over-graded (n = 2) while there was no significant difference in other image sets (n = 43). Overall inter-reader agreement between FSE-conventional and FSE-DNN showed good agreement (R2 = 0.76; p

Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis with characteristic involvement of the spine and sacroiliac joints. MRI may be the only indicator of disease activity or response. This study aimed to use a novel water fraction measurement technique on MRI as a biomarker to predict disease activity in patients with AS. Methods: We enrolled 39 patients (18 men [mean age, 38.6 years; range, 18–59 years] and 21 women [mean age, 39.3 years; range, 23–61 years]) who were clinically diagnosed with AS and underwent MRI, including mDixon sequences. Water fraction values of sacroiliac joint subchondral bone marrow were derived from the mDixon sequences. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was recorded using clinical information and laboratory values from medical records. Multiple linear regression, Firth logistic regression, and intraclass correlation coefficients were used for the statistical analysis. Results: In multiple linear regression, water fraction, subchondral bone marrow edema, subchondral bone erosion, and subchondral bone marrow enhancements were significantly associated with ASDAS with C-reactive protein (ASDAS-CRP). The water fraction parameters showed a good linear correlation with ASDAS-CRP and ASDAS with erythrocyte sedimentation rate (ASDAS-ESR) (beta coefficient = 1.98, p < 0.001 and beta coefficient = 1.60, p = 0.003). Firth logistic regression showed that water fraction was a significant predictor of ASDAS-CRP but not ASDAS-ESR. The intraclass correlation coefficient showed excellent repeatability for the three repeated measures of the water fraction. Conclusion: Water fraction parameter could be a good imaging biomarker of disease activity status. The sacroiliac joint evaluated by mDixon MRI may be a promising biomarker of disease progression in patients with spondyloarthritis.

Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system.

Abstract Increasing evidence suggests there is a relationship between cognitive impairment and metabolic dysfunction. Diabetes is a chronic disease, and metabolic factors affecting brain metabolisms, such as serum glucose, insulin, and glucagon, are altered according to disease progression. In our previous study, we applied hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy in prediabetic mice after feeding them a 60% high-fat diet (HFD) for 6 months. Ultimately, we detected significantly increased [1-13C]lactate conversion in the whole brain and an almost five-fold increased [1-13C]lactate/pyruvate ratio in the hippocampal region. In the present study, we induced diabetes in mice by injecting streptozotocin and feeding them an HFD for 6 months. Unlike in prediabetic mice, [1-13C]lactate conversion in the diabetic mice did not differ from that in the control group, but [1-13C]lactate/total 13C ratio showed an almost 1.4-fold increase in the hippocampal region. We measured the amount of the lactate and mRNA levels of glucose transporters from isolated hippocampus and cortex samples. In the hippocampus, significantly decreased GLUT1 mRNA levels and increased lactate were detected, suggesting an inconsistency between glucose and pyruvate metabolism. Pyruvate can be produced from oxaloacetate as well as glucose. We investigated ATP citrate lyase (ACLY) because it cleaves citrate into oxaloacetate and acetyl CoA. Phosphorylated ACLY (Ser455), the active form, was increased in both hippocampus and cortex samples of mice injected with streptozotocin and fed an HFD. Also, phosphorylated ACLY/total ACLY showed a positive correlation with lactate amount in the hippocampus. Our results suggest that the brain has different responses to diabetic progression, but, in the hippocampus, maintains metabolic alteration toward increasing lactate production from the prediabetic to the diabetic stage. We suggest that ACLY-mediated pyruvate be used to support lactate levels in the hippocampus in cases of limited glucose availability.

Abstract Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer’s disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p

Abstract Reliable and reproducible assessment of animal learning and behavior is a central aim of basic and translational neuroscience research. Recent developments in automated operant chamber technology have led to the possibility of universal standard protocols, in addition to increased translational potential, reliability and accuracy. However, the impact of regional and national differences in the supplies of available reinforcers in this system on behavioural performance and inter-laboratory variability is an unknown and at present uncontrolled variable. Therefore, we aimed to identify which constituent(s) of the reward determines reinforcer strength to enable improved standardization of this parameter across laboratories. Male C57BL/6 mice were examined in the touchscreen-based fixed ratio (FR) and progressive ratio (PR) schedules, reinforced with different kinds of milk-based reinforcers to directly compare the incentive values of plain milk (PM, high-calorie: high-fat/low-sugar), strawberry-flavored milk (SM, high-calorie: low-fat/high-sugar), and semi-skimmed low-fat milk (LM, low-calorie: low-fat/low-sugar) on the basis of differences in caloric content, sugar/fat content, and flavor. Use of a higher caloric content reward was effective in increasing operant training acquisition rate. Total trial number completed in FR and breakpoint in PR were higher using the two isocaloric milk products (PM and SM) than the lower caloric LM, with comparable outcomes between PM and SM conditions, suggesting that total caloric content determines reward strength. Analysis of within-session changes in response rate revealed that overall outputs in FR and PR primarily depend on the response rate at the initial phase of a session, which itself was dependent on reinforcer caloric content. Interestingly, the rate of satiation, indicated by decay in response rate within a FR session, was highest when reinforced with SM, suggesting a rapid satiating effect of sugar. The key contribution of reward caloric content to operant performance was confirmed in a multi-laboratory study using the touchscreen 5-choice serial reaction time task (5-CSRTT) reinforced by two isocaloric milk-based liquid rewards with different countries of origin, which yielded consistent performance parameters across sites. Our results indicate that milk-based liquid reinforcer standardization can be facilitated by matching caloric content across laboratories despite regional or national differences in other non-caloric aspects of the reinforcers.

The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects. Among these mechanisms of action, ATO has been shown to cause acute vascular shutdown and massive tumor necrosis in a murine solid tumor model like vascular disrupting agent (VDA). However, relatively little is understood about this VDA-like property and its potential utility in developing clinical regimens. We focused on this VDA-like action of ATO. On the basis of the endothelial cell cytotoxicity assay and tubulin polymerization assay, we observed that higher concentrations and longer treatment with ATO reduced the level of α- and β-tubulin and inhibited the polymerization of tubulin. The antitumor action and quantitative tumor perfusion studies were carried out with locally advanced murine CT26 colon carcinoma grown in female BALB/c mice. A single injection of ATO intraperitoneally displayed central necrosis of the tumor tissue by 24 hours. T1-weighted dynamic contrast-enhanced magnetic resonance image revealed a significant decrease in tumor enhancement in the ATO-treated group. Similar to other VDAs, ATO treatment alone did not delay the progression of tumor growth; however, ATO treatment after injection of other cytotoxic agent (irinotecan) showed significant additive antitumor effect compared to control and irinotecan alone therapy. In summary, our data demonstrated that ATO acts as a VDA by means of microtubule depolymerization. It exhibits significant vascular shutdown activity in CT26 allograft model and enhances antitumor activity when used in combination with another cytotoxic chemotherapeutic agent.

KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant K(ep) value representing capillary permeability was significantly decreased (p

Purpose: Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer's disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1-13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism. Materials and Methods: ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1-13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells. Results: As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1-13C]pyruvate to [1-13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ ratio and lactate generation. Conclusion: Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1-13C]pyruvate to HP [1-13C]lactate. [ABSTRACT FROM AUTHOR]

The development of a highly efficient and cancer-specific magnetic nanocrystal probe system for in vivo magnetic resonance (MR) diagnosis of cancer is presented. Well-defined material properties, such as small size, improved magnetism, and also targeting moiety, are critical for the target-selective in vivo cancer detections.

The article explains a newly devised core-shell design concept, which can be used for the fabrication of the dual mode nanoparticle contrast agents (DMCAs). These agents are shown to be extremely beneficial for the enhancement of the accuracy of MR imaging.

A surface-modulated and highly biocompatible magnetic iron oxide nanocrystal probe that could be used for efficient intracellular labeling and their magnetic resonance imaging applications is presented. The preparation of these probes and the results from studies exploring their transport into various cell types and magnetic resonance contrast effect, cytotoxicity, and application in vivo monitoring of neural stem cell migration in rat spinal cord is described.

The use of iron oxide nanoparticle encapsulated with peptide conjugated poly(D,L lactide-co-glycolide) (PLGA) as a potent intracellular carrier for diagnosis agent was reported. It was found that the gamma-Fe2O3-PLGA-Arg-FITC nanoparticle was effectively adsorbed onto the membrane of stem cells and delivered into the nuclei without cytotoxicity.

A report is presented on the development of a synthetically controlled magnetic nanocrystal model system that correlates the nanoscale tunabilities in terms of size, magnetism, and an induced nuclear spin relaxation processes. The magnetic model system further leads to the development of high-performance magnetic nanocrytsal probe systems for diagnosis of breast cancer lines.

Ischemic stroke results in diverse pathophysiologies, including cerebral inflammation, neuronal loss, cognitive dysfunction, and depression. Studies aimed at identifying therapeutic solutions to alleviate these outcomes are important due to the increase in the number of stroke patients annually. Recently, many studies have reported that orexin, commonly known as a neuropeptide regulator of sleep/wakefulness and appetite, is associated with neuronal cell apoptosis, memory function, and depressive symptoms. Here, we briefly summarize recent studies regarding the role and future perspectives of orexin in post-ischemic stroke. This review advances our understanding of the role of orexin in post-stroke pathologies, focusing on its possible function as a therapeutic regulator in the post-ischemic brain. Ultimately, we suggest the clinical potential of orexin to regulate post-stroke pathologies. [ABSTRACT FROM AUTHOR]

PURPOSE: To validate the feasibility of real time kinematography with four-dimensional (4D) dynamic functional wrist joint imaging using dual source CT. MATERIALS AND METHODS: Two healthy volunteers performed radioulnar deviation and pronation- supination wrist motions for 10 s and 4 s per cycle in a dual source CT scanner. Scan and reconstruction protocols were set to optimize temporal resolution. Cine images of the reconstructed carpal bone of the moving wrist were recorded. The quality of the images and radiation dosage were evaluated. RESULTS: The 4D cine images obtained during 4 s and 10 s of radioulnar motion showed a smooth stream of movement with good quality and little noise or artifact. Images from the pronation-supination motion showed noise with a masked surface contour. The temporal resolution was optimized at 0.28 s. CONCLUSION: Using dual source CT, 4D cine images of in vivo kinematics of wrist joint movement were obtained and found to have a shorter scan time, improved temporal resolution and lower radiation dosages compared with those previously reported. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (Ktrans, Kep and Ve), early changes in parameters (Ktrans, tumor volume), and heterogeneity (standard deviation of Ktrans) for radiation therapy responses via a human colorectal cancer xenograft model. Materials and Methods: A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (Ktrans, Kep and Ve) were calculated based on the Tofts model. Early changes in Ktrans, standard deviation (SD) of Ktrans, and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted. Results: The good response group (mice #1 and 2) exhibited higher pretreatment Ktrans than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment Kep, higher pretreatment Ve, and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in Ktrans and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy. Conclusion: The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment Ktrans and showed an early reduction in Ktrans, demonstrating a more homogenous distribution. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate meniscofibular ligament (MFibL) at the posterolateral corner of the knee joint on the magnetic resonance arthrography (MRA) with 70° knee flexion. MATERIALS AND METHODS: The MRA of the knee joint was performed at 70° knee flexion. Eighteen patients (19 knee joints) underwent scanning of sagittal, coronal, and axial fat-suppressed T1 weighted images (T1FS), and coronal fat-suppressed T2 weighted images. Sagittal three-dimensional (3D) gradient echo (GRE) images were also obtained. Retrospective review of 19 knee MRA studies was independently performed by two musculoskeletal radiologists. The statistical significance was proved by chi-square test. RESULTS: The MFibL ligament was optimally demonstrated on the far lateral sagittal 3D GRE and T1FS MRA images. The MFibL appeared as a curvilinear or straight hypointense band of variable thickness, extended from the posterolateral meniscus to upper anteromedial aspect of the fibular head. The MFibL was demonstrated with scale 2 (more than a half length of the ligament) by both reviewers in 73.68% (n=14/19) of the knee 3D GRE images and 89.47% (n=17/19) of the knee T1FS images. The visualization on T1FS and that on GRE were not statistically different from each other (p>0.05). The interobserver agreements were significantly good on both 3D GRE and T1FS images in detecting the ligament (kappa values, 0.642 and 0.683, respectively). CONCLUSION: The MFibL is well visualized on the far lateral sagittal MRA at 70° knee flexion, which could potentially be useful in recognizing structures in the posterolateral corner of the knee, including the MFibL. [ABSTRACT FROM AUTHOR]

Abstract??Current progress integrating stem cell biology and tissue engineering techniques has been invaluable to clinical applications. Prior to the application of celluar transplantation technique to patients, we need to establish techniques that can monitor their tissue biodistribution non-invasively. In this study, we proposed an imaging modality using MRI to not only monitor implanted scaffoldin vivo, but also to track transplanted cells and behavior around the implant. For this purpose, human bone marrow-derived mesenchymal stem cells (hMSCs) were labeled with superparamagnetic iron oxide (Feridex) and then labeled hMSCs were cultured in a gelatin sponge used as a scaffold to support cell growth and proliferation. Histological assessment and MTT assay showed that cell labeling with MR contrast agent did not harm cell viability. Also, Feridex-labeled hMSCs showed a significant decrease in T2 signal intensity, even within the gelatin spongein vitro. After implanting the sponge/cell complexin vivo, we could visualize cellular behavior around the implant over time using a noninvasive MRI modality and this finding was correlated with histological study, which illustrates the potential of a new approach proposed here forin vivomonitoring of implanted cell-based tissue-engineered product. [ABSTRACT FROM AUTHOR]

To assess soft tissue impingement as well as synovitis of the ankle associated with trauma by using contrast-enhanced (CE), fat-suppressed, three-dimensional, fast gradient-recalled acquisition in the steady state with radiofrequency spoiling (FSPGR) magnetic resonance (MR) imaging. A total of 36 patients who had had chronic ankle pain associated with a traumatic injury undertook fat-suppressed CE three-dimensional FSPGR MR imaging and then arthroscopy of the ankle. The ankle joint was divided into four compartments by anatomic details: the anterolateral gutter, anteromedial gutter, anterior recess, and posterior recess. Synovial enhancement was graded as follows: grade I, no enhancement; grade II, linear enhancement; grade III, focal nodular enhancement; and grade IV, irregular nodular enhancement. MR grading of the synovial enhancement (synovitis, grade III or IV; soft tissue impingement, grade III or IV with its intrusion from the capsular reflection) was compared with arthroscopic findings. A control study of twenty asymptomatic ankles was done for determining enhancement. Arthroscopy confirmed synovitis in 47 compartments of 27 patients. Of the 27 patients, 15 revealed soft tissue impingement in 17 compartments. For the assessment of synovitis, fat-suppressed CE three-dimensional FSPGR MR imaging had an accuracy of 72.9%, sensitivity of 91.5%, and specificity of 63.9%; whereas for that of soft tissue impingement it had an accuracy of 94.4%, sensitivity of 76.5%, and specificity of 96.9%. All of the asymptomatic subjects showed grade I (81%) or II (19%) synovial enhancement. Fat-suppressed CE three-dimensional FSPGR MR imaging was sensitive for the evaluation of synovitis of the ankle associated with trauma, whereas it was specific for soft tissue impingement evaluation. J. Magn. Reson. Imaging 2004;19:108–116. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The unique properties of magnetic nanocrystals provide them with high potential as key probes and vectors in the next generation of biomedical applications. Although superparamagnetic iron oxide nanocrystals have been extensively studied as excellent magnetic resonance imaging (MRI) probes for various cell trafficking, gene expression, and cancer diagnosis, further development of in vivo MRI applications has been very limited. Here, we describe in vivo diagnosis of cancer, utilizing a well-defined magnetic nanocrystal probe system with multiple capabilities, such as small size, strong magnetism, high biocompatibility, and the possession of active functionality for desired receptors. Our magnetic nanocrystals are conjugated to a cancer-targeting antibody, Herceptin, and subsequent utilization of these conjugates as MRI probes has been successfully demonstrated for the monitoring of in vivo selective targeting events of human cancer cells implanted in live mice. Further conjugation of these nanocrystal probes with fluorescent dye-labeled antibodies enables both in vitro and ex vivo optical detection of cancer as well as in vivo MRI, which are potentially applicable for an advanced multimodal detection system. Our study finds that high performance in vivo MR diagnosis of cancer is achievable by utilizing improved and multifunctional material properties of iron oxide nanocrystal probes. [ABSTRACT FROM AUTHOR]