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Sridhar S Kannurpatti

Publications and source records attributed to Sridhar S Kannurpatti.

7 recordsLinked to original sources

Spatial extent of CBF response during whisker stimulation using trial averaged laser Doppler imaging.

The spatial pattern of activation in response to multiple whisker stimulation was studied using high-resolution laser Doppler (LD) imaging in urethane-anesthetized rats. LD flux change representing cerebral blood flow (CBF) responses were analyzed from a single trial or after averaging a number of similar trials. CBF change in a single trial was observed predominantly over pixels having low baseline flux values (microvessels), which included diffuse circular patterns of activation 400-800 microm in diameter similar to the histological dimensions of individual barrels established in the layer IV of the rat somatosensory cortex. The overall activation pattern varied considerably between each trial (only about 9-10% overlap); however, the diffuse circular pattern of activation was reproducible in every single trial within and across all rats. With trial averaging, no significant increase was observed in the outer boundary of activation, but the number of activated pixels increased within the diffuse circular patterns of activation. Emergence of further active pixels primarily within the diffuse circular regions of activity with trial averaging indicates distinct CBF responses in the septal and barrel regions, with a lesser LD signal to noise ratio in the barrel core.

Afferent Pathways↗

Bootstrap resampling method to estimate confidence intervals of activation-induced CBF changes using laser Doppler imaging.

Laser Doppler imaging (LDI) signal and noise characteristics can vary significantly depending upon the underlying vascular caliber. Further, noise characteristics are not constant over time (non-stationary) and can vary during resting and activated conditions in a typical experiment. Since only a limited number of images can be acquired in a single run, concatenation of data from similar experimental trials becomes necessary which can induce further variation in temporal noise due to instrumental response. In conventional statistical analysis methods such as cross-correlation, a fixed significance threshold is generally used (for the entire image) to detect activation assuming constant noise over time and a normal distribution. As a consequence, statistical significance can become strong or weak due to temporal differences in baseline LD noise, which can possibly deviate from a normal distribution. The main emphasis of this study was the application of bootstrap resampling in conjunction with cross-correlation to estimate the confidence intervals on a pixel-by-pixel basis to avoid distributional specifications on the additive measurement error leading to reliable whisker activation-induced CBF changes. At a 95% confidence level, bootstrap resampling followed by confidence intervals for the correlation coefficient distribution increased the number of active pixels by almost 45% when compared to conventional cross-correlation. These pixels were mostly confined to areas with intermediate and large baseline LD flux with considerable deviation from normality. It is suggested that confidence intervals of the bootstrap estimates can lead to unbiased detection of CBF change in the cerebral cortex, particularly in regions with large temporal variation in noise and low CNR.

Afferent Pathways↗

Effect of anesthesia on CBF, MAP and fMRI-BOLD signal in response to apnea.

Systemic effects of anesthesia on the dynamics of the apnea-induced Blood Oxygen Level Dependent (BOLD) signal is still not clear. In the present study, the dynamics of the fMRI-BOLD signal and blood flow using laser Doppler flowmetry (LDF) was studied in rats in response to apnea. Two anesthetics namely pentobarbital and urethane, hypothesized to have distinct effects on the mean arterial blood pressure (MAP) were used. During normoxic baseline conditions, MAP decreased in response to apnea in rats anesthetized with pentobarbital but increased with urethane. However, MAP did not change significantly in response to apnea during hyperoxic or hypercapnic baseline conditions with both anesthetics. LDF increased in response to apnea during normoxia, hyperoxia or hypercapnia and was influenced by MAP during normoxia. Apnea-induced BOLD signal dynamics was similar with both anesthetics, dominated by an alteration in arterial blood oxygenation and independent of changes in MAP. Our results suggest that anesthesia-dependent MAP change modulates the apnea-induced cerebral blood flow (CBF) response but has a minimal effect on the fMRI-BOLD signal probably due to uncoupling of CBF and oxygen consumption.

Anesthesia↗

Negative functional response to sensory stimulation and its origins.

Functional imaging studies typically give prominence to positive responses. However, negative changes that accompany activation-induced positive responses are not yet clearly understood. The authors investigated the origin of sustained negative CBF responses that accompanied positive CBF changes. Measurements were made in the rat somatosensory cortex in response to whisker stimulation using laser-Doppler imaging. Flux images indicative of CBF were obtained at rest and during whisker stimulation with a spatial resolution of 200 microm. Large and intermediate blood vessels in the cortical surface exhibiting high flux values were clearly resolved. This greatly reduced the contamination of the tissue pixel volume with macroscopic blood vessels. Regions that responded positively to whisker stimulation were from areas with intermediate to low baseline flux and distinctly away from high flux areas. Stimulation-induced change in signal intensity was the largest in pixels with low baseline flux, presumably from tissue and microvessels. Simultaneously, a sustained decrease in signal intensity was observed in regions with high baseline flux values. The temporal coherence, macrovascular origin, lesser trial-to trial variability, and complete absence of the negative CBF response in the microvascular regions suggest that it may be purely hemodynamic in nature.

Animals↗

Regional dynamics of the fMRI-BOLD signal response to hypoxia-hypercapnia in the rat brain.

PURPOSE: To examine the regional blood oxygenation level-dependent (BOLD) signal response to rapid changes in arterial oxygen tension. MATERIALS AND METHODS: Functional MR imaging (fMRI) was carried out in five male Sprague-Dawley rats anesthetized with Sodium Pentobarbital. Rats were subjected to different durations of apnea as a rapid, graded, and reversible hypoxic-hypercapnic stimulus. Dynamics of the BOLD signal response were studied on a pixel-by-pixel basis in the cerebral cortex, hippocampus, third ventricle, and thalamus in the rat brain. RESULTS: Apnea induced a BOLD signal drop in all the brain regions studied, the magnitude of which increased with longer durations of the stimulus. The signal recovered to preapnic baseline levels after resumption of normal ventilation. Regional variation in the BOLD signal dynamics was observed with the magnitude of the BOLD signal change in the hippocampus being the least, followed by a relatively larger change in the thalamus, cerebral cortex, and third ventricle. The time (t(0)) for the signal change after the onset of the stimulus was estimated for every pixel. Time delay maps generated show the highest onset time values in the hippocampus followed by the thalamus, cerebral cortex, and third ventricle. CONCLUSION: The regional dynamics of the BOLD signal in the brain in response to apnea may vary depending on the rate of oxygen metabolism in addition to cerebral blood flow (CBF).

Animals↗

Baseline physiological state and the fMRI-BOLD signal response to apnea in anesthetized rats.

To decipher the biophysical mechanism behind the fMRI-BOLD response to apnea and its dependence on the baseline cerebral blood flow and oxygenation, fMRI and laser Doppler flow (LDF) studies were carried out in anesthetized rats. Baseline cerebral blood flow (CBF) and PaO2 were modulated by ventilating with different gas mixtures namely, room air (21% O2), 100% O2, carbogen (95% O2+5% CO2), 2% CO2 in air or 5% CO2 in air, respectively. A decrease in BOLD signal intensity was observed after the onset of apnea with either room air, 2% CO2 or 5% CO2 ventilation. PaO2 and cerebral tissue PO2 decreased during apnea under these conditions. However, the apnea-induced BOLD signal intensity was unaffected with carbogen ventilation and increased with 100% O2 ventilation, during which PaO2 remained constant and cerebral tissue PO2 increased. When baseline CBF was high during hypercapnia, a faster decrease occurred in the apnea-induced BOLD signal. Apnea induced the largest increase in CBF of 85 +/- 25% when ventilated with 2% CO2 while a 44 +/- 8% increase was observed with room air. During the other ventilatory conditions, minimal or no significant change in CBF was observed during apnea. These results show a significant correlation between the BOLD signal change and tissue PO2 in response to apnea under different physiological conditions. Apnea-induced increase in CBF affects the magnitude of the BOLD signal response when PaO2 remains constant or changes minimally.

Anesthesia↗

Differential fMRI-BOLD signal response to apnea in humans and anesthetized rats.

Blood oxygenation level dependent (BOLD) signal intensity (SI) and regional cerebral blood flow (CBF) during a 20-s apnea stimulus in awake humans and pentobarbital-anesthetized rats were measured to assess the usefulness of apnea in estimating cerebral vasodilatory capacity for functional MRI (fMRI) experiments. Rats were ventilated with either room air or 100% O(2.) While breathing room air, apnea for 20 s increased the BOLD SI in humans but decreased it in rats. However, in rats ventilated with 100% O(2), BOLD SI increased upon apnea for 20 s. CBF measurements in rats using laser Doppler flowmetry (LDF) showed a 45% +/- 8% increase during apnea with room air ventilation, and a 10% +/- 3% increase with 100% O(2). Arterial blood oxygen saturation fell from 96% +/- 1% to 29% +/- 5%, and cerebral tissue PO(2) decreased from 15 +/- 3 mmHg to 6 +/- 2 mmHg by the end of 20-s apnea in rats breathing room air. However, with 100% O(2) respiration, apnea produced no change in the arterial blood oxygen saturation, which remained at 99%, but increased tissue PO(2) from 35 +/- 9 mmHg to 39 +/- 10 mmHg. From the results obtained in rats ventilated with room air, it is concluded that apnea induces hypoxia that results in a decrease in fMRI-BOLD signal. The signal decrease occurred despite an increase in P(a)CO(2) and CBF. This BOLD response is the opposite of that observed in humans, who presumably do not develop hypoxia within the applied apnea period. These studies highlight the importance of the choice of ventilating gas mixture on the outcome of BOLD experiments during systemic perturbations.

Animals↗