TMU Translational Imaging Research Center 台北醫學大學轉譯影像研究中心 anoxia definicion

The relation between thalamocortical dysrhythmia (TCD) and post-concussive syndrome (PCS) in mild traumatic brain

Injury (mtbi) patients has recently been recognized in several studies; however the potential imaging biomarkers to

Evaluate neurological functional deficits and to localize TCD, in particular the thalamocortical circuits, have not

Been established. Based on the current understanding of the mtbi, network dysfunction of thalamocortical circuits is

The one of main points of investigation which is characterized by microstructural injuries, disrupted functional

Connectivity, and the altered interplay between excitatory and inhibitory neurotransmitters.


The elevated synaptic

Glutamate levels after mtbi can further exacerbate the post-traumatic cellular injury.Anoxia definicion recent studies have indicated

That mtbi patients can benefit from N-acetylcysteine (NAC) treatment by effectively improving the behavioral deficits

Which had a significant impact on neuropsychological test results.

Though the cognitive

Tests outcome after administration of NAC is promising, the neuroimaging evidence of NAC treatment efficacy on mtbi

And its prevention of subsequent brain atrophy had not been well explored. The purpose of this study is to propose a

TCD model in mtbi by simultaneous measurements of MRI and MR-compatible EEG on human participants followed by a

Pre-clinical experiment using animal mtbi model to evaluate the therapeutic effect of NAC on mtbi. Through the

Characterization of the neural network dysfunction from the perspectives of neural electrophysiology, microstructure

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Integrity, and hemodynamic synchrony, we will be able to have a complete vision on the pathophysiological mechanism

In mtbi. In addition, this study can help provide the neuroimaging evidence of the NAC efficacy in treating mtbi.

Glioblastoma is the most common malignant tumor of the central nervous system. Over 90% of diagnosed glioblastoma

Are primary cases, originating from glial cells and making up 80% of malignant brain tumors through multi-step

Oncogenesis. Despite the advances of treatment, the cure of malignant GBM remains elusive and the prognosis appears

Poor, partly due to under-sampling and mis-grading that influence the therapeutic strategy. Moreover, intra-tumoral

And individual genetic heterogeneity remains another important issue.Anoxia definicion therefore, an accurate grading of glioma by

Advanced imaging biomarkers that can address the heterogeneity of glioblastoma cannot be overemphasized. In addition

To the heterogeneity at the histology level, primary glioblastoma are also characterized by heterogeneous alterations

Of gene expression, which consist of EGFR amplification, loss of PTEN, and loss of cyclin-dependent kinase

Inhibitors. The incorporation of oncogenomics to the imaging biomarkers, the radiogenomic, has recently emerged for

Cancer management. The key pathological features of glioblastoma, including cellularity, invasiveness, mitotic

Activity, angiogenesis, and necrosis can be evaluated with advanced MR imaging which can be used as glioma genomic

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Signatures. By linking specific imaging biomarkers with specific gene expression profile could allow for more

Accurate diagnosis, prognosis prediction and better therapeutic guidance. In this three-year translational glioma

Project, we aim to investigate the advanced MR imaging biomarkers, the phonotypical expression, of gliomas with

Respect to their gene expression in preclinical animal model at 7T MRI and human subjects at 3T. To study

Intra-tumoral and inter-tumoral heterogeneity of glioblastomas, advanced MR imaging biomarkers such as

Perfusion-weighted imaging (PWI), CBF measurements by arterial spin labeling (ASL), high resolution diffusion tensor

Imaging (DTI), MR spectroscopy (MRS), amide proton transfer (APT) image and vessel size image will be used to depict

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The physiological as well as molecular events within the tumor. Genomic information will be acquired from microarray

Analysis. In addition to the frequently affected pathway including proliferation and angiogenesis, we will also focus

On the DNA damage/repair genes, as radiation response of glioblastomas in taiwanese is uniquely different from that

Caucasian glioblastoma population. With the combined application of genomic information and multiparametric MRI, the

Tumor extent can be accurately defined, the therapeutic response can be better monitored and the prognosis can be

Well predicted. In summary, with the establishment of tumor radiogenomic platform, we will be able to unveil the

Genomic modification of glioblastoma from the perspective of molecular MRI through a bedside-to-bench translational

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Research.

Brain compliance is a parameter introduced very early to describe brain homeostasis with an intracranial

Pressure–volume relationship based on the monro-kellie doctrine. The intracranial constituents (blood,

Cerebrospinal fluid (CSF), and brain parenchyma) create a state of volume equilibrium to maintain a normal range of

Intracranial pressure (ICP) for a limited change in compartmental volume. Once the inter-compartmental volume

Compensation fails, the intracranial hypertension occurs and the brain compliances decreases. The measurement of

Brain compliance therefore provides comprehensive information about compensatory volume reserve and the risk of

Developing high ICP.

Previous studies have used various techniques to assess brain compliance either in an invasive manner,the

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Spiegelberg compliance monitor, or with an over-simplified model of cerebral flow system. At present, a non-invasive

And accurate method to monitoring the brain compliance is demanded in clinical routines for intensive care units,

Cerebrovascular diseases, or traumatic brain injuries. Superior to the conventional invasive monitoring, magnetic

Resonance (MR) motion-sensitive imaging shows strength on in-vivo and non-invasive measurements of volume arterial

Inflow, venous blood outflow, and CSF movement method during a cardiac cycle, and therefore allows the

Compartmentalization of brain compliance. The technique of cine displacement-encoded MRI further enables the

Visualization of pulsatile brain motion in a scale of sub-millimeter within a cardiac cycle.Anoxia definicion

In this three-year study, the advanced motion-sensitive MR techniques will be employed using a 3T scanner for

Human and a 7T scanner for rat imaging. We aim to establish the dynamic relation between 4 main intracranial

Compartments, i.E., the arterial inflow, venous outflow, CSF movement, and brain motion, within a cardiac cycle to

Reveal the underlying physiological mechanism. We also aim to propose a modified computational model to improve the

Accuracy and repeatability of MR-based measurement of brain compliance to promote its clinical impact. A norm of

MR-based brain compliance for healthy controls will be established through the proposed model and tested in

Variability in the first year. Based on the current understanding, both CSF and venous blood are considered to be the

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Key buffers for maintaining the brain parenchyma and sufficient cerebral perfusion. We hypothesize that when the

Deficits of cerebral venous system occur, such as the cerebral venous hypertension (CVH), the brain compliance may

Reduce, reflecting the altered state of brain homeostasis. The CVH can cause an elevated ICP and therefore decreased

Cerebral perfusion pressure (CPP), resulting in the ischemic brain injury and cytotoxic edema, followed by breakdown

Of blood vessel walls.

To test our hypothesis, we will use a rat venous hypertension model with the arteriovenous anastomosis in the

Second year to investigate the induced alterations of brain compliance. The motion-sensitive MRI, MR techniques in

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Imaging edema (ADC), venous dilation (SWI), oxygen extraction fraction (OEF), and invasive measurements of CPP and

Draining vein pressure (DVP) will be collected at day 2, 7, 28 after operation to reveal the time evolution of brain

Compliance. Finally, the constructed MR-based measurement of brain compliance will be applied to patients with CVH in

The third year of this study. The outcomes of this study can facilitate the clinical applications of MRI in

Monitoring brain homeostasis and assisting disease diagnosis.

Thalamocortical oscillation, the coherent rhythm modulated by the intrinsic membrane potential of thalamic neurons

And then propagated between the thalamus and the cortex, is not only critical for the processing of sensory

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Information but also related to the emergence of multiple brain functions including awake and sleep, conscious

Awareness, cognitive functions, etc. T-type ca2+ channels play a pivotal role in regulating thalamic firing patterns

And have been implicated as the pacemaker in thalamocortical oscillation. It was lately shown that neurological

Disease may alter the thalamocortical oscillation likely due to excessive inhibition of thalamic relay neurons, and

Inactivation of T-type ca2+ channels would ameliorate functional impairment. However, spatiotemporal features of

Thalamocortical oscillation remain to be characterized and how mtbi progression impacts on thalamocortical

Connectivity is largely unexplored.Anoxia definicion

In this study, we will probe thalamocortical connectivity using magnetic resonance imaging (MRI) and address

An important question whether restoration of thalamocortical oscillation can be a potential therapeutic strategy of

MTBI. In this 3-year project, we propose to characterize thalamocortical oscillation following mtbi in the

Modified controlled cortical injury (CCI) model, which mimics the pathophysiology of concussive injury caused by

Motorcycle accidents in taiwan. We will use state-of-the-art tools for the observation of thalamocortical

Connectivity in functional and structural aspects by using resting state functional MRI (rsfmri) and diffusion tensor

Image (DTI), respectively.

In aim 1 (year 1), our goal is to develop a validate model showing significant functional deficit

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Rather than structure injury in the early phase of mtbi. Longitudinal MRI and behavioral tests will help us establish

The mtbi induction parameters based on imaging features and functional outcomes.

In aim 2 (year 2), we will specifically verify how thalamocortical connectivity changes after mtbi

Using rsfmri and DTI. We will comprehensively establish functional outcome correlations to functional and structural

Image features after CCI.

In aim 3 (year 3), our major goal is to investigate whether inhibition of burst firing mode in

Thalamic relay neurons by a T-type ca2+ channel antagonist, TTA-P2, could mitigate mtbi outcomes. We will test TTA-P2

In mtbi model with different degree of CCI. Together with longitudinal multi-parametric MRI and behavioral

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Assessments, we hypothesize that TTA-P2 will restore thalamocortical oscillation and improve outcomes of mtbi.

This project will bring up a novel platform that allows early diagnosis and evaluation of new therapeutic

Strategies for mtbi with MRI. We will prove the concept that non-invasive MR mapping of internal oscillation and

Microstructural stabilization among brain nuclei may serve as a novel diagnostic tool for neuropsychological

Disorders.

Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor. Current aggressive

Treatments consist of surgical resection followed by radiation therapy, and chemotherapy still result in a poor

Prognosis with a median survival of 14 months after diagnosis.Anoxia definicion though the resistance mechanism of GBM to temozolomide

(TMZ), the standard prescription of chemotherapy, has been well-documented by several studies, reliable image

Biomarkers for predicting TMZ outcome and personalized medicine were less explored. In next year project, a

Translational radiogenomic study combining the genomic profile and advanced MRI techniques in both human and animal

GBM model will be performed to unravel the links between image phenotypes and underlying gene alterations. Advanced

MR imaging is capable to define biological features of GBM in vivo and therefore provides a possibility to assess the

Potential TMZ resistant pathway for the purpose of predicting treatment effect and applying personalized medicine.Anoxia definicion

Imaging core is served as a platform of magnetic resonance imaging (MRI) and computed tomography (CT) to support

The four cancer programs in CECR. This imaging research platform can provide the measurements of tumor structure and

Physiological status in vivo, and therefore facilitate the early diagnosis of tumor, longitudinal monitoring, new

Drug development, and clinical trial. In next year project, the service and research directions of imaging core will

Focus on three subjects including (1) imaging service and consultation, (2) research team collaboration, and (3)

Development of advanced imaging and analysis techniques. For the imaging service and consultation to the four cancer

Programs, the in-vivo imaging of cell, small animal, and human by the 7T MRI at taipei medical university, 3T human

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MRI (service will start from dec. 2015), and dual-source computed tomography at taipei medical university hospital

Will be provided. The imaging core team, including two radiologists, two assistant professors, two assistant research

Fellows, and one medical physicist, will assist investigators to resolve the issues of imaging parameters, sequence

Selection, and image analysis. Regarding the research team collaboration, the collaborations will start from the

Studies of glioblastoma and extend to all four programs in the perspective of both basic and clinical researches and

New drug development. The initial collaborations with four research teams include (a) radiogenomic study of intra-

And inter-tumor heterogeneity with prof.Anoxia definicion yung-hsioa chiang, (b) imaging of permeability and histologic section to

Assess the dynamics of blood tumor barrier with prof. Ruei-ming chen, (c) prediction of treatment efficacy of

Temozolomide-resistant glioblastoma by MR image phenotypes with prof. Jian-ying chuang, and (d) preclinical animal

Experiments of a new drug, MPT0B291, for chemical therapy with prof. Chia-yi wang. In the development of advanced

Imaging and analysis techniques, imaging core will keep adjusting and developing the imaging protocols and analysis

Methods at 7T animal and 3T human MRI, including the ktrans permeability map for assessing the integrity of blood

Tumor barrier, diffusion kurtosis imaging (DKI) for elevating the sensitivity in malignant tumor detection, and

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Chemical exchange saturation transfer (CEST) for measuring tumor metabolism. With the achievements of all three

Subjects, imaging core will be able to expedite the progression of cancer researches.