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Kâmil Uludağ

Publications and source records attributed to Kâmil Uludağ.

7 recordsLinked to original sources

Frontiers of brain mapping using MRI.

Over the past dozen years, the use of MRI techniques to map brain function (fMRI) has sparked a great deal of research. The ability of fMRI to image several different physiological processes concurrently (i.e., blood oxygenation, blood flow, metabolism) and noninvasively over large volumes make it the ideal choice for many different areas of neuroscience research in addition to countless applications in clinical settings. Furthermore, with the advent of high magnetic fields (and other hardware advancements, i.e., parallel imaging) for both human and animal research, spatial and temporal resolutions continue to be pushed to higher levels because of increases in the sensitivity as well as specificity of MR-detectable functional signals. fMRI methodology continues to grow and has the ability to cater to many different research applications. There seems to be no foreseeable end in sight to the advancement of fMRI techniques and its subsequent use in basic research as well as in clinical settings. In this work, fMRI techniques and the ongoing development of existing techniques are discussed with implications for the future of fMRI.

Brain Mapping↗

Investigating the post-stimulus undershoot of the BOLD signal--a simultaneous fMRI and fNIRS study.

Measuring the hemodynamic response with functional magnetic resonance imaging (fMRI) together with functional near-infrared spectroscopy (fNIRS) may overcome limitations of single-method approaches. Accordingly, we measured the event-related hemodynamic response with both imaging methods simultaneously in young subjects during visual stimulation. An intertrial interval of 60 s was chosen to include the prolonged post-stimulus undershoot of the blood oxygenation level dependent (BOLD) signal. During visual stimulation, the BOLD signal, oxy-, and total hemoglobin (Hb) increased, whereas deoxy-Hb decreased. The post-stimulus period was characterized by an undershoot of the BOLD signal, oxy-Hb, and an overshoot of deoxy-Hb. Total Hb as measured by fNIRS returned to baseline immediately after the end of stimulation. Results suggest that the post-stimulus events as measured by fNIRS are dominated by a prolonged high-level oxygen consumption in the microvasculature. The contribution of a delayed return of blood volume to the BOLD post-stimulus undershoot in post-capillary veins as suggested by the Balloon and Windkessel models remains ambiguous. Temporal changes in the BOLD signal were highly correlated with deoxy-Hb, with lower correlation values for oxy- and total Hb. Furthermore, data show that fNIRS covers the outer 1 cm of the brain cortex. These results were confirmed by simultaneous fMRI/fNIRS measurements during rest. In conclusion, multimodal imaging approaches may contribute to the understanding of neurovascular coupling.

Adult↗

Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact.

The detection of redox changes in cytochrome-c-oxidase ([Cyt-ox]) in response to cerebral activation by non-invasive NIRS is hampered by methodological spectroscopic issues related to the modification of the Beer-Lambert law. Also, the question whether a change in the enzyme's redox-state is elicited by functional stimulation is unresolved. In a previous study, we found physiological evidence in favour of an activation-induced increase in oxidation of the enzyme [J. Cereb. Blood Flow Metab. 19 (1999) 592], while in a second study on spectroscopic cross talk, we found that the [Cyt-ox] changes to potentially be an artefact of the spectroscopic approach [J. Biomed. Opt. 7 (2002) 51]. Here, we use two different stimuli which differentially activate areas either rich or poor in [Cyt-ox] content (blob/interblob in visual cortex V1 and pale/thin stripes in V2) to further clarify this apparent discrepancy. In a first experiment, two stimuli were presented in an alternating fashion for 20 s and all stimulation periods were separated by resting periods of 40 s. We observed similar changes in [Cyt-ox] for both stimuli. To become more sensitive to the potentially very small optical changes related to changes in [Cyt-ox], we tried to minimise global haemodynamic and metabolic effects in a second experiment by omitting the resting periods. Our hypothesis was that [Cyt-ox] changes could be fully explained by cross talk as it is predicted from our last study [J. Biomed. Opt. 7 (2002) 51]. However, in more than half of the experiments, we were not able to model the changes in Cyt-ox calculated from measured attenuation spectra as a cross talk artefact. We interpret this finding as an argument in favour of the existence of [Cyt-ox] changes in response to functional stimulation. This finding, however, does not lessen the liability of the [Cyt-ox] changes to cross talk and calls for great caution when [Cyt-ox] changes are derived from NIRS measurements based on the modified Beer-Lambert approach. Further (invasive) validation studies are required.

Adult↗

Towards a standard analysis for functional near-infrared imaging.

Functional near-infrared spectroscopy (fNIRS) allows the ability to monitor brain activation by measuring changes in the concentration of oxy- and deoxy-hemoglobin. Until now no standardized approach for fNIRS data analysis has been established, although this has to be regarded as a precondition for future application. Hence, we applied the well-established general linear model to optical imaging data. Further, fNIRS data were analyzed in the frequency domain. Two visual tasks were investigated with optical imaging: a checkerboard paradigm supposed to activate the primary and secondary visual cortex, and a paradigm consisting of moving colored stimuli (rotating 'L's) additionally involving the motion area V5. Analysis with the general linear model detected the activation focus in the primary and secondary visual cortex during the first paradigm. For the second paradigm, a second laterally localized activated brain region was found, most likely representing V5. Spatially resolved spectral analysis confirmed the results by showing maxima of power spectral density and coherence in the same respective brain regions. Moreover, it demonstrated a delay of the hemodynamic response in the motion area. In summary, the present study suggests that the general linear model and spatially resolved spectral analysis can be used as standard statistical approaches for optical imaging data, particularly because they are almost independent of the assumed differential path length factors.

Adult↗

Separability and cross talk: optimizing dual wavelength combinations for near-infrared spectroscopy of the adult head.

By means of noninvasive near-infrared spectroscopy (NIRS), cerebral concentration changes in oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb]) can be determined. The quality of the concentration changes' assessment critically depends on the wavelength combination used. Trying to optimize this combination, two spectroscopic effects must be taken into account: cross talk and separability. Cross talk between [oxy-Hb] and [deoxy-Hb] occurs because the assumption made in the analysis-that there is a homogeneous concentration change-does not hold true for the adult human head. Separability-to be introduced in this paper-is a measure for the degree of physical noise of the measurement that will influence the noise of the concentration changes' assessment. In other words, high separability corresponds to a low noise with respect to the concentration changes assessed. Here, we present analytical expressions for both measures and provide model-based estimates of cross talk and separability for any combination of two wavelengths between 610 and 920 nm. These theoretical considerations allow for two predictions: (a) if both wavelengths used are greater than approximately 780 nm, cross talk is high and separability is low resulting in erroneous and noisy concentration data. (b) If one wavelength is chosen below 720 nm while the other is greater than 730 nm, cross talk is low and separability is high resulting in accurate concentration changes. We show the relevance of these theoretical results for noninvasive NIRS by testing the predictions on experimental data obtained in adults undergoing visual stimulation.

Adult↗

Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI.

The physiological basis of the blood oxygenation level dependent (BOLD) signal and its dependence on baseline cerebral blood flow (CBF) were investigated by comparing responses to a visual stimulus after physiological changes of the baseline. Eight human subjects were imaged with 3 and 4 T MRI scanners, and both BOLD signal and CBF were simultaneously measured. Subjects viewed a flickering radial checkerboard in a block design experiment, alternating between eyes open or closed during the off periods. Compared to a baseline state with eyes open in a darkened room, substantial deactivation (average change: 2.9 +/- 0.3% BOLD, 22 +/- 2.1% CBF) in the occipital cortex was observed when the eyes were closed. The absolute response during stimulation (average change: 4.4 +/- 0.4% BOLD, 36.3 +/- 3.1% CBF) was independent of the preceding resting condition. We estimated the fractional change in CBF to be approximately 2.2 +/- 0.15 times greater than the fractional change in metabolic rate of oxygen (CMRO2). The changes in CBF and CMRO2 were consistently linearly coupled during activation and deactivation with CBF changes being between approximately 60% and 150% compared to baseline with eyes open. Relative to an assumed baseline oxygen extraction fraction (OEF) of 40%, the estimated OEF decreased to 33 +/- 1.4% during activation and increased to 46 +/- 1.2% during rest with eyes closed. In conclusion, we found that simply closing the eyes creates a large physiological deactivation in the visual cortex, and provides a robust paradigm for studying baseline effects in fMRI. In addition, we propose a feed-forward model for neurovascular coupling which accounts for the changes in OEF seen following baseline changes, including both the current physiological perturbations as well as previously reported pharmacologically induced changes.

Adult↗

Modeling the hemodynamic response to brain activation.

Neural activity in the brain is accompanied by changes in cerebral blood flow (CBF) and blood oxygenation that are detectable with functional magnetic resonance imaging (fMRI) techniques. In this paper, recent mathematical models of this hemodynamic response are reviewed and integrated. Models are described for: (1) the blood oxygenation level dependent (BOLD) signal as a function of changes in cerebral oxygen extraction fraction (E) and cerebral blood volume (CBV); (2) the balloon model, proposed to describe the transient dynamics of CBV and deoxy-hemoglobin (Hb) and how they affect the BOLD signal; (3) neurovascular coupling, relating the responses in CBF and cerebral metabolic rate of oxygen (CMRO(2)) to the neural activity response; and (4) a simple model for the temporal nonlinearity of the neural response itself. These models are integrated into a mathematical framework describing the steps linking a stimulus to the measured BOLD and CBF responses. Experimental results examining transient features of the BOLD response (post-stimulus undershoot and initial dip), nonlinearities of the hemodynamic response, and the role of the physiologic baseline state in altering the BOLD signal are discussed in the context of the proposed models. Quantitative modeling of the hemodynamic response, when combined with experimental data measuring both the BOLD and CBF responses, makes possible a more specific and quantitative assessment of brain physiology than is possible with standard BOLD imaging alone. This approach has the potential to enhance numerous studies of brain function in development, health, and disease.

Algorithms↗