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Papers by Uzay Emrah Emir

Metabolites, Jul 11, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

The main objective of this work was to evaluate the application of individual and ensemble machin... more The main objective of this work was to evaluate the application of individual and ensemble machine learning models to classify malignant and benign breast masses using features from two-dimensional (2D) correlated spectroscopy spectra extracted from five-dimensional Echo Planar-Correlated Spectroscopic Imaging (5D EP-COSI) and Diffusion-weighted imaging (DWI). Twenty-four different metabolite and lipid ratios with respect to 2D diagonal peaks at 1.4ppm and 5.4ppm, and water from one-dimensional non-water-suppressed (NWS) spectra were used as the features. Additionally, water fraction, fat fraction and water-to-fat ratios from NWS spectra and apparent diffusion coefficients (ADC) from DWI were included. Nine most important features were identified using recursive feature elimination. XGBoost (AUC:93.0%, Accuracy:85.7%, F1-score:87.6%), GradientBoost (AUC:94.4%, Accuracy:87.0%, F1-score:89.4%), CatBoost (AUC:95.2%, Accuracy:86.9%, F1-score:88.4%) and RandomForest (AUC:92.2%, Accuracy:...

Human Brain Mapping, Apr 9, 2021

Frontiers in Neurology

The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected ... more The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with1H MR spectroscopy (1H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER (TE= 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B0inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as lo...

Scientific Reports, 2017

Psychiatry Research: Neuroimaging, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

We developed a method of acquiring high-resolution MRI for the generation of Quantitative Suscept... more We developed a method of acquiring high-resolution MRI for the generation of Quantitative Susceptibility Mapping (QSM) using Ultra-short echo time (UTE) MRI with a novel 3D rosette k-space trajectory. This method was used to generate high-resolution (0.94 mm3 isotropic) magnetic susceptibility maps in an Iron-Chloride phantom and the human brain. Generated maps were then compared with the susceptibility maps reconstructed from low-resolution data acquired using multi-echo UTE acquisition. Susceptibility values were comparable with current literature demonstrating the promise of this novel method in the generation of QSM.

Feasibility of a novel, rosette trajectory UTE (70 μs) 3D 31P MRSI sequence is tested at 3T in ph... more Feasibility of a novel, rosette trajectory UTE (70 μs) 3D 31P MRSI sequence is tested at 3T in phantoms and in upper leg scan with healthy subject. Braino phantom, proton resolution phantom, and highly concentrated 31P phantom test demonstrated proper reconstruction and metabolite localization. In vivo calculations of acquired PCr and β-ATP signals showed competitive SNR across 20 voxels of interest. With further acceleration, the sequence may serve as a superior alternative to conventional weighted 3D MRSI, allowing for greater SNR or resolution in briefer times. Notably, this unprecedentedly short UTE 31P MRSI intrinsically avoids baseline and phasing issues.

Pulmonary imaging traditionally uses techniques utilizing ionizing radiation such as x-rays and C... more Pulmonary imaging traditionally uses techniques utilizing ionizing radiation such as x-rays and CT. Pediatrics, pregnant patients, and patients who will be exposed multiple times over long periods of time would benefit from a non-ionizing modality. MRI does not use ionizing radiation but suffers from low signal from the lungs and breathing motion artifact. We are proposing a novel MRI technique to combat these issues: a 3-dimensional Dual-Echo FID Ultra-short Echo Time (3D DE UTE) sequence utilizing Rosette k-space acquisition. Preliminary results demonstrated better pulmonary artery segmental branches and pleural wall definition compared to other commercially available MRI sequences.

bioRxiv (Cold Spring Harbor Laboratory), Sep 20, 2021

Purpose: This study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically ... more Purpose: This study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically for ultra-short echo time (UTE) magnetic resonance imaging (MRI) applications. The direct imaging of the myelin bilayer, which has ultra-short transverse relaxation time (uT 2), was acquired to test the performance of the proposed UTE sequence. Theory and Methods: The rosette trajectory was developed based on rotations of a 'petal-like' pattern in the k x-k y plane, with oscillated extensions in k z-direction for 3D coverage. Five healthy volunteers were recruited and underwent ten dual-echo 3D rosette UTE scans with various echo times (TEs). Dual-exponential complex model fitting was performed on the magnitude data to separate uT 2 signals, with the output of uT 2 fraction, uT 2 value, and long T 2 value. Results: The reconstructed images' signal contrast between whiate matter (WM) and grey matter (GM) increased with longer TEs. The WM regions had higher uT 2 fraction values than GM (10.9%േ1.9% vs. 5.7%േ2.4%). The uT 2 value was approximately 0.15 milliseconds in WM. Conclusion: The higher uT 2 fraction value in WM compared to GM demonstrated the ability of the proposed sequence to capture rapidly decaying signals.

Although our view of the world looks singular, it is combined from each eye’s separate retinal im... more Although our view of the world looks singular, it is combined from each eye’s separate retinal image. If the balanced input between eyes is disrupted during early childhood, visual acuity and stereoscopic depth perception are impaired. This is because one eye dominates over the other, causing a neurological condition called ‘amblyopia’ [1]. In the normal, healthy visual system, the balance between eyes can be determined using various methods to provide a measure of ‘eye dominance’. Eye dominance is the preference for using image from one eye over another [2], suggesting that the visual system applies different weights upon their input. Hence, eye dominance is relevant for understanding the mechanisms underlying binocular vision. As an investigative strategy to understand the binocular visual system in health in disease, we want to characterize eye dominance in the normal visual system. This information can then be used to serve as a baseline to compare to extreme eye dominance in ‘amblyopia’. Specifically, we ask to which degree variations in eye dominance are related to visual cortex concentrations of major excitatory neurotransmitter and metabolite glutamate (‘Glu’) and inhibitory neurotransmitter γ-aminobutyric acid (‘GABA’). Their relationship is formalised as the ‘Glu/GABA’ ratio. 13 participants took part in a 1-h psychophysical experiment to quantify eye dominance and a separate 1.5-h 7-Tesla MRI brain scan to measure hemodynamic and neurochemical responses during visual stimulation. The degree of eye dominance was predicted by the inter-ocular difference in V1 Glu/GABA balance. Stronger eye dominance correlated with an increase in inhibition during dominant relative to non-dominant eye viewing (r = −0.647, p = 0.023). In contrast the hemodynamic response, measured with functional magnetic resonance imaging, did not correlate with eye dominance. Our findings suggest that normally occurring eye dominance is associated with the balance of neurochemicals in the early visual cortex.

Tomography, Jun 1, 2016

2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumor cell isocitrate dehydrogenase mutat... more 2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumor cell isocitrate dehydrogenase mutations that may enable the differential diagnosis of patients with glioma. At 3 T, detection of 2-HG with magnetic resonance spectroscopy is challenging because of metabolite signal overlap and spectral pattern modulation by slice selection and chemical shift displacement. Using density matrix simulations and phantom experiments, an optimized semi-LASER scheme (echo time ϭ 110 milliseconds) considerably improves localization of the 2-HG spin system compared with that of an existing point-resolved spectroscopy sequence. This results in a visible 2-HG peak in the in vivo spectra at 1.9 ppm in the majority of isocitrate dehydrogenase-mutated tumors. Detected concentrations of 2-HG were similar using both sequences, although the use of semi-LASER generated narrower confidence intervals. Signal overlap with glutamate and glutamine, as measured by pairwise fitting correlation, was reduced. Lactate was readily detectable across patients with glioma using the method presented here (mean Cramér-Rao lower bound: 10% Ϯ 2%). Together with more robust 2-HG detection, long-echo time semi-LASER offers the potential to investigate tumor metabolism and stratify patients in vivo at 3 T.

Scientific Reports, Aug 23, 2021

www.nature.com/scientificreports/ 'EDI' , see "Methods" section, Eq. (1)) was calculated. The EDI... more www.nature.com/scientificreports/ 'EDI' , see "Methods" section, Eq. (1)) was calculated. The EDI measures the increase in duration of the DE phase as a percentage of the NDE phase (range 0.64-23.1%, mean: 7.9 ± 8.2%). Monocular visual stimulation protocol during combined fMRI-MRS acquisition. To measure cortical inhibition during monocular visual stimulation in the visual cortex (Fig. 2a), a 2 × 2 × 2 cm 3 MRS volume-of-interest (VOI) was symmetrically placed along the midline of the calcarine sulcus to cover the early visual cortex (EVC) using a combined fMRI-MRS sequence (see 'Supplementary Information'). We obtained high quality MRS spectra from the EVC volume (Fig. 2b), including detection of inhibitory neurotransmitter GABA. Across participants, an average of 85 ± 13.7% of the MRS VOI overlapped with the fMRI activation map (checkerboard > fixation), confirming that measurement of the neurochemical levels was measured from visually-stimulated tissue. No difference in percentage overlap was found between monocular stimulation conditions (dominant eye: 85 ± 13.7%, non-dominant eye: 86 ± 11.3%, Wilcoxon Rank Sum Test, p = 0.72).

This phantom study aimed to compare a conventional multi-gradient recalled echo (mGRE) sequence a... more This phantom study aimed to compare a conventional multi-gradient recalled echo (mGRE) sequence and an ultra-short echo (UTE) with a novel 3D rosette k-space trajectory for iron (Fe) detection and quantification. Conventional mGRE imaging may underestimate massive Fe load due to the long echo times (TEs). Advanced UTE techniques with TEs 10-200 times shorter than conventional mGRE sequences can capture fast signal decay caused by high Fe content. Our preliminary results show that both sequences yield a strong linear relationship between R2* values and Fe concentrations, with the 3D-UTE results aligning more with expected R2* values for high Fe concentrations.

The Journal of Neuroscience, Sep 9, 2022

Motor adaptation is crucial for performing accurate movements in a changing environment and relie... more Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel magnetic resonance spectroscopic imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter GABA in the human cerebellum during visuomotor adaptation. Participants (n = 17, six female) used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found that GABA in the left cerebellar nuclei and the right cerebellar nuclei diverged, although GABA change from baseline at the right cerebellar nuclei was not different from zero at the group level. Early adaptation-driven GABA fluctuations in the right cerebellar nuclei correlated with adaptation performance. Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviorally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network. Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation, and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterizing these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation.

bioRxiv (Cold Spring Harbor Laboratory), Dec 22, 2020

Scientific Reports, Nov 23, 2017

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epi... more Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE. Clinical imaging investigations in drug-resistant temporal lobe epilepsy (TLE) aim to detect seizure foci arising from surgically targetable lesions, the most common of which is hippocampal sclerosis (HS). The presence of HS on diagnostic imaging offers a prognostic marker for surgical treatment success in TLE 1,2. The complex and heterogeneous architecture of the hippocampus, however, hinders detection of cell loss that may differentially affect specific hippocampal subfields across patients 3. High-field 7T MRI provides enhanced contrast relative to standard (1.5 or 3T) clinical MRI systems, alongside exquisite spatial detail due to increased signal-to-noise yield 4. Consequently, 7T MRI offers potential to identify hippocampal lesions that go undetected in around 20% of routine TLE clinical scans. In people with focal epilepsy, initial 7T studies have demonstrated sensitivity to detect tuberous sclerosis lesions 5 , polymicrogyria 6 , focal cortical dysplasia 7-9 , and hippocampal sclerosis 9-12. Compared to clinical MRIs, 7T anatomical imaging enables improved qualitative 9,11 and quantitative 10,12 hippocampal atrophy ratings for TLE patients with known pathology. But to provide added value, 7T must show enhanced sensitivity to pathology not evidenced on clinical MRI that, furthermore, improves treatment outcome predictions in individual patients. Yet, in the only prior study of patients with normal clinical imaging, 7T hippocampal volumetry showed no association with post-operative seizure outcomes 12. Despite the predictive association between HS and surgical outcomes in TLE, the relationship between seizure activity and neuronal atrophy remains elusive 13. In 10-30% of surgically resected epileptic hippocampi, no

PurposeThis study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically fo... more PurposeThis study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically for ultra-short echo time (UTE) magnetic resonance imaging (MRI) applications. The direct imaging of the myelin bilayer, which has ultra-short transverse relaxation time (uT2), was acquired to test the performance of the proposed UTE sequence.Theory and MethodsThe rosette trajectory was developed based on rotations of a ‘petal-like’ pattern in the kx-kyplane, with oscillated extensions in kz-direction for 3D coverage. Five healthy volunteers were recruited and underwent ten dual-echo 3D rosette UTE scans with various echo times (TEs). Dual-exponential complex model fitting was performed on the magnitude data to separate uT2signals, with the output of uT2fraction, uT2value, and long T2value.ResultsThe reconstructed images’ signal contrast between whiate matter (WM) and grey matter (GM) increased with longer TEs. The WM regions had higher uT2fraction values than GM (10.9%±1.9% vs. 5.7%±2.4%)...

Zeitschrift Fur Medizinische Physik, Oct 1, 2022