Aria Tzika

• PhD
• Managing Director at Massachusetts General Hospital

Although the relationship between corticospinal tract (CST) fiber degeneration and motor outcome after stroke has been established, the relationship of sensorimotor cortical areas with CST fibers has not been clarified. Also limited research has been conducted on how abnormalities in brain structural networks are related to motor recovery. To addre...

Macrophages utilize metabolic pathways to generate energy and metabolites that may be vulnerable to pathogen hijacking to favor pathogen survival and persistence. It is unclear how bacterial pathogens alter metabolic pathways in immune cells for their benefit and persistence in the infected host. We have shown that the Pseudomonas aeruginosa quorum...

Background Ischemic stroke is the most common cause of complex chronic disability and the third leading cause of death worldwide. In recovering stroke patients, peak activation within the ipsilesional primary motor cortex (M1) during the performance of a simple motor task has been shown to exhibit an anterior shift in many studies and a posterior s...

New rehabilitation strategies enabled by technological developments are challenging the prevailing concept of there being a limited window for functional recovery after stroke. In this study, we examined the utility of a robot-assisted therapy used in combination with a serious game as a rehabilitation and motor assessment tool in patients with chr...

Therapies based on stem cell transplants offer significant potential in the field of regenerative medicine. Monitoring the fate of the transplanted stem cells in a timely manner is considered one of the main limitations for long-standing success of stem cell transplants. Imaging methods that visualize and track stem cells in vivo non-invasively in...

Pseudomonas aeruginosa , a bacterium that is resistant to treatment, causes serious acute, persistent, and relapsing infections in humans. There is increasing evidence that bacterial excreted small molecules play a critical role during infection. We have shown that a quorum sensing (QS)-regulated excreted small molecule, 2-AA, which is abundantly p...

Green fluorescent protein (GFP) is a widely utilized molecular reporter of gene expression. However, its use in in vivo imaging has been restricted to transparent tissue mainly due to the tissue penetrance limitation of optical imaging. Magnetization transfer contrast (MTC) is a magnetic resonance imaging (MRI) methodology currently utilized to det...

In the present study, high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy was applied to live Pseudomonas aeruginosa (PA) bacterial cells to determine the metabolome of this opportunistic Gram-negative human pathogen, and in particular, its response to the volatile aromatic low molecular weight signaling molec...

Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence...

Background: Obesity and type 2 diabetes are major risk factors for peripheral arterial disease in humans, which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularizati...

Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial...

Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of genes in Drosophila melanogaster, a useful model for investigating genetics and physiology. After trauma was induced by a non-let...

Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR...

A novel approach was developed that combines biomarkers detected with magnetic resonance spectroscopy (MRS) and molecular genomics to improve the typing and prog-nostication of biospecimens in clinical medicine. Metabolite and genome wide profi les from 55 biopsies from subjects with brain tumors were analyzed with a classifi cation algorithm that...

In vivo nuclear magnetic resonance spectroscopy (NMR), a non-destructive biochemical tool used for investigating live organisms, has recently been performed in studies of the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We used a novel high-resolution magic angle-spinning (HRMAS) NMR method t...

Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochon-drial uncoupling in skeletal muscle. We subjected...

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tiss...

Pseudomonas aeruginosa (PA) is a pathogenic gram-negative bacterium that is widespread in nature, inhabiting soil, water, plants and animals. PA is a prevalent cause of deleterious human infections, particularly in patients whose host defense mechanisms have been compromised. Metabolomics is an important tool used to study host-pathogen interaction...

Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post‑stroke therapy may improve rehabilitation and reduce long‑term disability; however, objective methods for evaluating the specific...

Previous brain imaging studies suggest that stroke alters functional connectivity in motor execution networks. Moreover, current understanding of brain plasticity has led to new approaches in stroke rehabilitation. Recent studies showed a significant role of effective coupling of neuronal activity in the SMA (supplementary motor area) and M1 (prima...

Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected...

Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy to...

Aim. This paper reports a systematic review and critical appraisal of the evidence on the effectiveness of behavioral therapies such as yoga and mindfulness practices for stroke rehabilitation. Background. The experience of stroke can have a negative impact on both psychological and physical health and on quality of life. Yoga and relevant practice...

MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Althoug...

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease...

The number of individuals suffering from stroke is increasing daily, and its consequences are a major contributor to invalidity in today's society. Stroke rehabilitation is relatively new, having been hampered from the longstanding view that lost functions were not recoverable. Nowadays, robotic devices, which aid by stimulating brain plasticity, c...

Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in viv...

Recent advents in magnetic resonance spectroscopy (MRS) techniques permit subsequent microarray analysis over the entire human transcriptome in the same tissue biopsies. However, extracting information from such immense quantities of data is limited by difficulties in recognizing and evaluating the relevant patterns of apparent gene expression in t...

To develop novel magnetic resonance (MR) imaging methods to monitor accumulation of macrophages in inflammation and infection. Positive-contrast MR imaging provides an alternative to negative-contrast MRI, exploiting the chemical shift induced by ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles to nearby water molecules. We introduce...

Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce metabolic changes in the host that lead to massive loss in skeletal muscle mass. Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant expression in skeletal musc...

In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live...

High-Resolution Magic Angle Spinning (HRMAS) proton magnetic resonance spectroscopy ((1)H-MRS) is a novel non-destructive technique that improves spectral line-widths and allows high-resolution spectra to be obtained from extracts, intact cells, cell cultures, and more importantly intact tissue to investigate relationships between metabolites and c...

The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer]...

The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glio-blastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer...

We describe a novel solid-state nuclear magnetic resonance (NMR) method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS), relative conventional liquid-state NMR approaches, when applied to intact biopsies of skeletal muscle specimens collected from burn trauma patients. This novel method, termed optimized adiabatic TOta...

Introduction− Stroke is one of the main causes of morbidity and invalidity in modern society. Approximately 400 persons per 100,000 over the age of 45 years have their first stroke each year in the United States, Europe, and Australia. About 80–90% of stroke survivors exhibit motor weakness [1]. Robot-assisted therapy has been shown to result in si...

We compared GRAPPA parallel MRI (pMRI) to regular MRI (non-GRAPPA) for BOLD fMRI while keeping all other parameters fixed. We acquired both GRAPPA and non-GRAPPA images using a high resolution as well as a low resolution EPI matrix. We found significantly larger values of percent BOLD signal when comparing higher resolution acquisitions to lower re...

Burn injuries to extensive areas of the body are complicated by muscle catabolism. Elucidating the molecular mechanisms that mediate this catabolism may facilitate the development of a medical intervention. Here, we assessed the functional classification of genes that were differentially expressed in skeletal muscle following burn injury in 19 chil...

Burn injuries to extensive areas of the body are complicated by muscle catabolism. Elucidating the molecular mechanisms that mediate this catabolism may facilitate the development of a medical intervention. Here, we assessed the functional classification of genes that were differentially expressed in skeletal muscle following burn injury in 19 chil...

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease...

The aim of this study was to investigate functional reorganization of motor systems by probing connectivity between motor related areas in chronic stroke patients using functional magnetic resonance imaging (fMRI) in conjunction with a novel MR-compatible hand-induced, robotic device (MR_CHIROD). We evaluated data sets obtained from healthy volunte...

PURPOSE To monitor brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible hand-induced robotic device (MR_CHIROD). METHOD AND MATERIALS We evaluated 60 fMRI datasets at 3T from five right-hand-dominant patients (mean age: 65 years) with first-ever left-sided stroke ≥6 months prior...

Brain tumors are one of the leading causes of death in adults with cancer; however, molecular classification of these tumors with in vivo magnetic resonance spectroscopy (MRS) is limited because of the small number of metabolites detected. In vitro MRS provides highly informative biomarker profiles at higher fields, but also consumes the sample so...

Using a mouse model, we tested the hypotheses that severe burn trauma causes metabolic disturbances in skeletal muscle, and that these can be measured and repeatedly followed by in vivo electron paramagnetic resonance (EPR). We used a 1.2-GHz (L-band) EPR spectrometer to measure partial pressure of oxygen (pO(2)) levels, redox status and oxidative...

This paper evaluates the use of electrorheological fluids (ERFs) within a magnetic resonance imaging (MRI) environment. ERF is a semiactive variable impedance material, which could be used as an alternative type of resistive force/torque generation or in combination with other actuators as a damper/clutch to modulate the output force/torque of the...

It has been suggested that intramyocellular lipids (IMCLs) may serve as biomarkers of insulin resistance and mitochondrial dysfunction. Using a hind-limb mouse model of burn trauma, we tested the hypothesis that severe localized burn trauma involving 5% of the total body surface area causes a local increase in IMCLs in the leg skeletal muscle. We q...

We propose a solid-state NMR method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS) applied to intact biopsies when compared to more conventional liquid-state NMR approaches. Theoretical treatment, numerical simulations and experimental results on intact human brain biopsies are presented. Experimentally, it is proven...

Magnetic resonance (MR) techniques offer a non-invasive, non-irradiating yet sensitive approach to diagnose and monitor cancer, which encompasses diverse processes affecting various aspects of pathophysiology. Techniques such as MR spectroscopy (MRS) have been developed and applied to monitor the metabolic aspects of cancer. Given that cancer is su...

This paper presents the design, fabrication, and testing of a novel, one degree-of-freedom, magnetic resonance compatible smart hand interfaced rehabilitation device (MR_CHIROD v.2), which may be used in brain magnetic resonance (MR) imaging during handgrip rehabilitation. A key feature of the device is the use of electrorheological fluids (ERFs) t...

Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in vivo 31P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characteriz...

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke >/=6 months prior and mild to moderate hemiparesis. Patients traine...

Using a mouse model, we tested the hypotheses that severe burn trauma causes metabolic disturbances in skeletal muscle, and that these can be measured and repeatedly followed by in vivo electron paramagnetic resonance (EPR). We used a 1.2-GHz (L-band) EPR spectrometer to measure partial pressure of oxygen (pO 2) levels, redox status and oxidative s...

Author Summary Current treatments of human bacterial infections depend on antibiotics, whose long-term effectiveness is limited as they select for multidrug-resistant pathogens. An alternative approach that is likely to limit the development of bacterial super pathogens is to selectively disrupt bacterial virulence mechanisms without affecting bac...

Growth Kinetics of PA14 in Response to 6FABA, 6CABA, 4CABA, or MA (89 KB PDF)

The AA Analogs 6FABA, 6CABA, and 4CABA Inhibit (A) Transcription from pqsA-E Promoter, (B) Pyocyanin, and (C) Elastase Production Data are average of triplicate experiments ± SD. Three independent experiments were performed. (171 KB PDF)

The 600-MHz HRMAS 1H NMR Spectra of PA14 Cell Samples Grown in the Presence or Absence of 1.5 mM 4CABA The 1H chemical shift assignments are labeled as 0, TSP; 1, lipids/macromolecules; 2, lactate; 3, alanine; 4, acetate; 5, glutamate; 6, glutamine; 7, lysine; 8, histidine; 9, choline; 10, betaine aldehyde; 11, glycine; 12, amino acid; 13, betaine...

Levels of Prominent 1H HRMAS MR Spectra Metabolite Peaks in PA14 Cells Minus or Plus 4CABA Treatment (50 KB DOC)

Tryptophan Deficiency Does Not Contribute to the Analog-Mediated Decreased P. aeruginosa Virulence in Mice (A) Growth kinetics of PA14 in minimal medium in the presence or absence of 6 mM 6FABA, 6 mM 6CABA, or 1.5 mM 4CABA plus or minus 1 mM tryptophan. (B) Virulence of PA14 wild-type, and trpE−, and trpC− mutants in the B+I model. (165 KB PDF)

Differential Expression Ratios of Genes that Are Positively and Negatively Regulated in Response to 6FABA, 6CABA, and 4CABA (484 KB DOC)

Differential Expression Levels of MvfR Positively and Negatively Regulated Genes in Response to 6FABA, 6CABA, or 4CABA (297 KB DOC)

Advancements in the diagnosis and prognosis of brain tumor patients, and thus in their survival and quality of life, can be achieved using biomarkers that facilitate improved tumor typing. We introduce and implement a combinatorial metabolic and molecular approach that applies state-of-the-art, high-resolution magic angle spinning (HRMAS) proton (1...

This paper presents the design, fabrication and testing of a novel, one degree of freedom (DOF) magnetic resonance compatible smart hand interfaced rehabilitation device (MR_CHIROD v.2), which may be used in brain magnetic resonance (MR) imaging during handgrip rehabilitation. The device consists of three major subsystems: a) an ERF based resistive...

Using brain proton magnetic resonance spectroscopic imaging (MRSI) in children with central nervous system (CNS) tumors, we tested the hypothesis that combining information from biologically important metabolites, at diagnosis and prior to treatment, would improve prediction of survival. We evaluated brain proton MRSI exams in 76 children (median a...

Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e...

PURPOSE Here, we used one and two-dimensional high-resolution Magic Angle Spinning (HRMAS) Proton MRS metabolomics and subsequently genomics to analyze intact biopsies and detect significant biomarkers from patients anaplastic ganglioglioma which account for 1% of all central nervous system tumors in children. METHOD AND MATERIALS HRMAS Proton MRS...

Severe burn trauma mediates immune dysfunction, infection, and multiple organ dysfunction syndrome. We are investigating the immuno-inflammatory response by characterizing gene expression changes in skeletal muscle after local and distant burn injury. Male CD1 mice in three experimental groups, control (unburned), hind limb (local burn), and 30% to...

Functional magnetic resonance imaging (fMRI) has been widely used in studying human brain functions and neurorehabilitation. In order to develop complex and well-controlled fMRI paradigms, interfaces that can precisely control and measure output force and kinematics of the movements in human subjects are needed. Optimized state-of-the-art fMRI meth...

Current developments in medical information technologies provide the clinical researcher with overwhelming amounts of data that need to be retrieved, organized, analyzed, and shared using secure, efficient, and robust protocols. The development of a local research database can provide an infrastructure for improved data management and detailed data...

PURPOSE The objective of this study was to test the hypothesis that combining information from biologically important intracellular molecules, obtained by proton MR spectroscopic imaging (MRSI) and histology, will increase the probability of predicting survival in children with pediatric CNS tumors. METHOD AND MATERIALS Proton MRSI was performed u...

Burn trauma triggers hypermetabolism and muscle wasting via increased cellular protein degradation and apoptosis. Proton nuclear magnetic resonance (1H NMR) spectroscopy can detect mobile lipids in vivo. To examine the local effects of burn in skeletal muscle, we performed in vivo 1H NMR on mice 3 days after burn trauma; and ex vivo, high-resolutio...

Severe burn trauma is generally followed by a catabolic response that leads to muscle wasting and weakness affecting skeletal musculature. Here, we perform whole-genome expression and in vivo NMR spectroscopy studies to define respectively the full set of burn-induced changes in skeletal muscle gene expression and the role of mitochondria in the al...

This paper presents the design, fabrication and testing of a novel, one degree of freedom, magnetic resonance (MR) compatible, computer controlled, variable resistance hand device that will be used in fMRI studies of the brain and motor performance during rehabilitation after stroke. The device consists of four major subsystems: a) the Electro-Rheo...

This paper presents the design, fabrication and preliminary tests of a novel, one degree of freedom, MR compatible, computer controlled, variable resistance hand device that will be used in fMRI studies of the brain and motor performance during rehabilitation after stroke. The device consists of four major subsystems: a) the electro-rheological flu...

The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive...

In vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors. MR spec...

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clin...

HTML Purpose: We sought to test the hypothesis that biologically important intracellular molecules detected by proton magnetic resonance spectroscopic imaging (MRSI) can predict clinical grades of central nervous system (CNS) tumors in children. Methods and Materials: We evaluated proton MRSI exams on 76 children with CNS tumors of childhood. Intra...

HTML Purpose: To assess whether quantitative cerebral lactate and apparent diffusion coefficient (ADC) obtained from the white matter regions of infants with perinatal asphyxia can differentiate clinical outcome. Methods and Materials: Seventeen full-term infants were examined with diffusion-weighted MR imaging. Proton MR spectroscopic imaging exam...

Introduction Recent studies following burn injury have indicated apoptotic changes, together with increased expression of proapoptotic proteins in skeletal muscles at sites immediately proximal and distant from burn injury (1,2). Apoptosis or programmed cell death is a fundamental homeostatic mechanism but also a primary factor in disease i.e., isc...

MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with...

To compare the predictive value for adverse outcome of quantitative cerebral lactate level and of apparent diffusion coefficient (ADC) in infants with perinatal asphyxia in the early postnatal period. Lactate-choline ratios determined with proton magnetic resonance (MR) spectroscopy and ADC determined with diffusion MR imaging in basal ganglia and...