Review of tracer kinetic models in evaluation of gliomas using dynamic contrast-enhanced imaging.

Glioma is the most common type of primary malignant tumor of the central nervous system (CNS), and is characterized by high malignancy, high recurrence rate and poor survival. Conventional imaging techniques only provide information regarding the anatomical location, morphological characteristics, and enhancement patterns. In contrast, advanced imaging techniques such as dynamic contrast-enhanced (DCE) MRI or DCE CT can reflect tissue microcirculation, including tumor vascular hyperplasia and vessel permeability. Although several studies have used DCE imaging to evaluate gliomas, the results of data analysis using conventional tracer kinetic models (TKMs) such as Tofts or extended-Tofts model (ETM) have been ambiguous. More advanced models such as Brix's conventional two-compartment model (Brix), tissue homogeneity model (TH) and distributed parameter (DP) model have been developed, but their application in clinical trials has been limited. This review attempts to appraise issues on glioma studies using conventional TKMs, such as Tofts or ETM model, highlight advancement of DCE imaging techniques and provides insights on the clinical value of glioma management using more advanced TKMs.

Iodine-Rich Nanoadjuvants for CT Imaging-Guided Photodynamic Immunotherapy of Breast Cancer.

Immunotherapy, which stimulates the body's own immune system to kill cancer cells, has shown great promise in the field of cancer therapy. However, the uncontrolled biodistribution of immunotherapeutic drugs may cause severe side effects. Herein, we report an iodine-rich nanoadjuvant (INA) for photo-immunotherapy. INA is prepared by encapsulating a toll-like receptor 7 agonist (R837) and a photosensitizer (phthalocyanine) into an iodine-rich amphiphilic copolymer PEG-PHEMA-I. By virtue of the enhanced permeation and retention (EPR) effect, INA can effectively accumulate into the tumor site. Under light irradiation, photodynamic therapy (PDT) triggered by INA will induce immunogenic cell death (ICD) in the tumor region to trigger the release of immune-associated cytokines. Such a process may further induce the maturation of dendritic cells which will be accelerated by R837, leading to the proliferation of effector T cells for immunotherapy. The photo-immunotherapy mediated by INA shows good anticancer efficacy both in vitro and in vivo. Meanwhile, INA is also a CT contrast agent owing to its high density of iodine, which can successfully illuminate tumors by CT imaging. Thus, our study develops a light-triggered nanoadjuvant for CT imaging-guided enhanced photo-immunotherapy.

Evaluation of apparent diffusion coefficient mappings in amnestic mild cognitive impairment using an image analysis software brain search.

BACKGROUND: The apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can quantify alterations in water diffusivity resulting from microscopic structural changes from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). PURPOSE: To investigate the ADC value for aMCI and AD using Brain Search (BS) software based on anatomical volumes of interest (AVOI). MATERIAL AND METHODS: In total, 174 aged people were screened, and 25 patients with AD, 26 patients with aMCI, and 18 normal controls (NCs) were recruited. DWI was performed at 1.5 T with a fluid-attenuated inversion recovery (FLAIR), and the independent ADC mapping was generated after imaging acquisition. Ninety regional parcellations were adopted in a Brain Search (BS) based on the automated anatomic labeling atlas. The gray scale intensities (water diffusivity) from the collected ADC mappings were analyzed with BS. The mean value of each anatomical brain region was compared among aMCI, AD, and NC. The statistically significant (P < 0.05) group differences are displayed in color. RESULTS: During the pathological process of AD, the changes of water diffusivity appeared first in the left hippocampus, then gradually progressed to the bilateral sides and eventually displayed right lateralization. The ADC values from aMCI were obviously elevated compared to the values from the NC group in the left limbic cortex. Between the AD and NC groups, the significantly different brain areas included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and the Temporal and Frontal lobes. There was a negative correlation between the ADC values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ. Additionally, the ADC values were positively correlated with the scores from CDR, ADL, and ADAS-Cog. CONCLUSION: The water diffusivity for aMCI and AD displays asymmetric anatomical lateralization. The water diffusivity alterations can be analyzed and visualized with our newly designed analytic imaging software, BS, which can be used as a good reference for examining and diagnosing aMCI and AD patients.

Non-invasive assessment of phosphate metabolism and oxidative capacity in working skeletal muscle in healthy young Chinese volunteers using (31)P Magnetic Resonance Spectroscopy.

Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent (31)P Magnetic Resonance Spectroscopy ((31)P-MRS); our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR) scanner. The (31)P-MRS coil was firmly placed under the middle of the quadriceps . (31)P-MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE), kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002) than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047), PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025), and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035) had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had higher energy transfer efficiency than females. At the post-exercise status, the recovery of PCr did not show sex difference. Conclusions. Our in-house force control and gauge system quantitatively applied force during the exercise for (31)P-MRS experiments, and a sex difference of higher energy transfer efficiency and WE was detected in males with mild loaded exercising quadriceps. This noninvasive technology allows us to further study and understand the sex difference of high energy phosphate metabolism in the future.

Correction: Cerebral Glioma Grading Using Bayesian Network with Features Extracted from Multiple Modalities of Magnetic Resonance Imaging.

[This corrects the article DOI: 10.1371/journal.pone.0153369.].

Cerebral Glioma Grading Using Bayesian Network with Features Extracted from Multiple Modalities of Magnetic Resonance Imaging.

Many modalities of magnetic resonance imaging (MRI) have been confirmed to be of great diagnostic value in glioma grading. Contrast enhanced T1-weighted imaging allows the recognition of blood-brain barrier breakdown. Perfusion weighted imaging and MR spectroscopic imaging enable the quantitative measurement of perfusion parameters and metabolic alterations respectively. These modalities can potentially improve the grading process in glioma if combined properly. In this study, Bayesian Network, which is a powerful and flexible method for probabilistic analysis under uncertainty, is used to combine features extracted from contrast enhanced T1-weighted imaging, perfusion weighted imaging and MR spectroscopic imaging. The networks were constructed using K2 algorithm along with manual determination and distribution parameters learned using maximum likelihood estimation. The grading performance was evaluated in a leave-one-out analysis, achieving an overall grading accuracy of 92.86% and an area under the curve of 0.9577 in the receiver operating characteristic analysis given all available features observed in the total 56 patients. Results and discussions show that Bayesian Network is promising in combining features from multiple modalities of MRI for improved grading performance.

Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction.

The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.

APOE genotype and age modifies the correlation between cognitive status and metabolites from hippocampus by a 2D (1)H-MRS in non-demented elders.

Purpose. To examine the associations among age, Apolipoprotein E (APOE) genotype, metabolic changes in the hippocampus detected by 2D (1)H magnetic resonance spectroscopy (MRS), and neuropsychological measures of cognition in non-demented elders. Materials and Methods. We studied a cohort of 16 cognitively normal controls (CN) and 11 amnestic mild cognitive impairment (aMCI) patients between 66 and 88 years old who were genotyped for APOE genetic polymorphism. Measurements of 2D(1)H-MRS metabolites were obtained in the hippocampus region. Adjusting by age among all subjects, the association between metabolic changes and cognitive function was measured by Spearman partial rank-order correlation. The effect of APOE status was measured by separating the subjects into APOE genotype subgroups, including the APOEε4 carriers and APOEε4 non-carriers. Results. In contrast to the CN group matched with age, gender, and education, aMCI patients showed increased myo-inositol (mI)/Creatine (Cr) ratio only in the right hippocampus. No differences were noted on N-acetylaspartate (NAA)/Cr and mI/NAA from bilateral hippocampus, and so was mI/Cr ratio in left hippocampus between aMCI and CN. The mI/Cr ratio from the right hippocampus in non-demented elders was negatively correlated with Montreal Cognitive Assessment (MoCA) scores. Whether ε4 genotype or age was added as a covariate, none of the correlation effects remained significant. Additionally, adjusting for age and APOE genotype together, there was no significant correlation between them. Conclusion. Since the higher mI/Cr from the right hippocampus of the patients with aMCI than those from CN, the mI/Cr could be a more specific predictor of general cognitive function in aMCI patients. There is an association between higher mI/Cr in right hippocampus and worse cognitive function for the non-demented older adults, and the correlation could be modified by APOE status and age. That provided a window on objectively understanding the mechanism between the brain metabolites and the influence factors in non-demented elders.

Characterizing topological patterns in amnestic mild cognitive impairment by quantitative water diffusivity.

Mean diffusivity (MD) derived from diffusion tensor imaging has shown its ability to assess the microscopic structural integrity damage of gray matter in amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease (AD). However, little is known about the small world topology networks constructed by cortical MD in cognitive disease. In this work, we measured the cortical MD in the entire brain in patients with aMCI (n = 30) and AD (n = 30) compared with cognitive-normal (CNs) controls (n = 30), and then constructed the cortical diffusivity network by using graph-theoretical analysis. Compared with CNs, patients with aMCI and AD showed abnormal small-world property of cortical diffusivity networks (higher degree of clustering and longer path length), reflecting a less optimal topological organization. Moreover, the mean degree of connections of network in aMCI patients was characterized by lower than CNs but higher than AD. In addition, 11 hub regions were identified by negative correlations between MD and the score of Montreal Cognitive Assessment after multiple regression analysis, including bilateral hippocampi and related limbic system. Among those hub regions, the connectivity of the right olfactory cortex and middle orbital gyrus to the rest of brain regions were disrupted earlier than the other 9 regions in aMCI when compared to CN. In conclusion, the change of cortical diffusivity in topological network organization, mean degree of connections, and disrupted hub regions in aMCI may serve to identify patients in the prodromal stage of AD and reflect microstructural deterioration of neurodegeneration.

A primary spinal extradural atypical teratoid/rhabdoid tumor of the cervical spine with bony involvement.

Primary spinal atypical teratoid/rhabdoid tumors are extremely rare and most commonly occur as intramedural or extramedural intradural. The location of extradural type is rarely reported. A 10-year-old girl presented with a 2-month history of nape pain. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an extradural tumor from C2-C5 with bony destruction of the C3 vertebral body. Subtotal removal of the tumor was performed and atypical teratoid/rhabdoid tumor was proven histologically. But 2 months after surgery, the neck pain became worse. There were metastasic lesions in bilateral lung fields and multiple enlarged lymph nodes around the carotid sheath. She died 8 months after the initial symptoms. The present case is the third detailed report of spinal extradural. We describe the CT and MRI findings of this case and review the literature describing this rare disease.