Yihao Yao

Bio: Yihao Yao is an academic researcher from Huazhong University of Science and Technology. The author has contributed to research in topics: Quantitative susceptibility mapping & Diffusion MRI. The author has an hindex of 11, co-authored 23 publications receiving 627 citations. Previous affiliations of Yihao Yao include Cornell University.

Clinical Quantitative Susceptibility Mapping (QSM): Biometal Imaging and Its Emerging Roles in Patient Care

Abstract: Quantitative susceptibility mapping (QSM) has enabled magnetic resonance imaging (MRI) of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols. Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:951–971.

MEDI+0: Morphology enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference for quantitative susceptibility mapping

Abstract: Purpose To develop a quantitative susceptibility mapping (QSM) method with a consistent zero reference using minimal variation in cerebrospinal fluid (CSF) susceptibility. Theory and methods The ventricular CSF was automatically segmented on the R2* map. An L2 -regularization was used to enforce CSF susceptibility homogeneity within the segmented region, with the averaged CSF susceptibility as the zero reference. This regularization for CSF homogeneity was added to the model used in a prior QSM method (morphology enabled dipole inversion [MEDI]). Therefore, the proposed method was referred to as MEDI+0 and compared with MEDI in a numerical simulation, in multiple sclerosis (MS) lesions, and in a reproducibility study in healthy subjects. Results In both the numerical simulations and in vivo experiments, MEDI+0 not only decreased the susceptibility variation within the ventricular CSF, but also suppressed the artifact near the lateral ventricles. In the simulation, MEDI+0 also provided more accurate quantification compared to MEDI in the globus pallidus, substantia nigra, corpus callosum, and internal capsule. MEDI+0 measurements of MS lesion susceptibility were in good agreement with those obtained by MEDI. Finally, both MEDI+0 and MEDI showed good and similar intrasubject reproducibility. Conclusion QSM with a minimal variation in ventricular CSF is viable to provide a consistent zero reference while improving image quality. Magn Reson Med 79:2795-2803, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative Susceptibility Mapping Identifies Inflammation in a Subset of Chronic Multiple Sclerosis Lesions

Abstract: Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.

Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation

Abstract: Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non-Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologically confirmed glioma. The kurtosis and conventional diffusion metric values of the tumor were semi-automatically obtained. The relationships of these metrics with the glioma grade and Ki-67 expression were evaluated. The diagnostic efficiency of these metrics in grading was further compared. It was demonstrated that compared with the conventional diffusion metrics, the kurtosis metrics were more promising imaging markers in distinguishing high-grade from low-grade gliomas and distinguishing among grade II, III and IV gliomas; the kurtosis metrics also showed great potential in the prediction of Ki-67 expression. To our best knowledge, we are the first to reveal the ability of DKI to assess the cellular proliferation of gliomas, and to employ the semi-automatic method for the accurate measurement of gliomas. These results could have a significant impact on the diagnosis and subsequent therapy of glioma.

Altered Intranetwork and Internetwork Functional Connectivity in Type 2 Diabetes Mellitus With and Without Cognitive Impairment.

Abstract: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. We investigated whether alterations of intranetwork and internetwork functional connectivity with T2DM progression exist, by using resting-state functional MRI. MRI data were analysed from 19 T2DM patients with normal cognition (DMCN) and 19 T2DM patients with cognitive impairment (DMCI), 19 healthy controls (HC). Functional connectivity among 36 previously well-defined brain regions which consisted of 5 resting-state network (RSN) systems [default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL) and sensorimotor network (SMN)] was investigated at 3 levels (integrity, network and connectivity). Impaired intranetwork and internetwork connectivity were found in T2DM, especially in DMCI, on the basis of the three levels of analysis. The bilateral posterior cerebellum, the right insula, the DMN and the CON were mainly involved in these changes. The functional connectivity strength of specific brain architectures in T2DM was found to be associated with haemoglobin A1c (HbA1c), cognitive score and illness duration. These network alterations in intergroup differences, which were associated with brain functional impairment due to T2DM, indicate that network organizations might be potential biomarkers for predicting the clinical progression, evaluating the cognitive impairment, and further understanding the pathophysiology of T2DM.

Magnetic Resonance Imaging Physical Principles And Sequence Design

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Networks of the Brain

Abstract: Models of Network Growth All networks, whether they are social, technological, or biological, are the result of a growth process. Many of these networks continue to grow for prolonged periods of time, continually modifying their connectivity structure throughout their entire existence. For example, the World Wide Web has grown from a small number of cross-linked documents in the early 1 990s to an estimated 30 billion indexed web pages in 2009.3 The extraordinary growth of the Web continues unabated and has occurred without any top-down design, yet the topology of its hyperlink structure exhibits characteristic statistical patterns (Pastor-Satorras and Vespig­ nani, 2004). Other technological networks such as the power grid, global transportation networks, or mobile communication networks continue to grow and evolve, each displaying characteristic patterns of expansion and elaboration. Growth and change in social and organizational

Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data.

Abstract: The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.

Superparamagnetic Iron Oxide Nanoparticles—Current and Prospective Medical Applications

Abstract: The recent, fast development of nanotechnology is reflected in the medical sciences. Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are an excellent example. Thanks to their superparamagnetic properties, SPIONs have found application in Magnetic Resonance Imaging (MRI) and magnetic hyperthermia. Unlike bulk iron, SPIONs do not have remnant magnetization in the absence of the external magnetic field; therefore, a precise remote control over their action is possible. This makes them also useful as a component of the advanced drug delivery systems. Due to their easy synthesis, biocompatibility, multifunctionality, and possibility of further surface modification with various chemical agents, SPIONs could support many fields of medicine. SPIONs have also some disadvantages, such as their high uptake by macrophages. Nevertheless, based on the ongoing studies, they seem to be very promising in oncological therapy (especially in the brain, breast, prostate, and pancreatic tumors). The main goal of our paper is, therefore, to present the basic properties of SPIONs, to discuss their current role in medicine, and to review their applications in order to inspire future developments of new, improved SPION systems.