Rajarsi Gupta

Noninvasive determination of the optical properties of adult brain: near-infrared spectroscopy approach

The basic parameters for physiological measurements provided by near-infrared spectroscopy are the local absorption and scattering coefficients. For the adult human head, they have been difficult to measure noninvasively because of the layered structure of the head. The results of measurements of absorption and reduced scattering coefficients through the forehead on 30 adult volunteers using a multidistance frequency domain method are reported. The optode separation distance ranged from 10 to 80 mm and measurements were recorded at 758 and 830 nm. The measured absorption and reduced scattering coefficients of the forehead were used to evaluate the hemoglobin content in the scalp and brain as well as cerebral oxygen saturation. We found that cerebral oxygenation was relatively narrowly distributed within the subject group (the standard deviation was about 3% for scalp and 6% for brain, respectively), whereas hemoglobin concentrations had a relatively broader distribution. We found that as the optode distance increased, the absorption coefficients increased and the scattering coefficients decreased, retrieving the optical values of scalp and brain for shorter and longer optode distances, respectively. We present the transition curves of the absorption and reduced scattering coefficients as functions of the optode distance. In order to verify the values for each layer, a comparison between the experimental data and a prediction based on the two-layer model of the adult head was carried out. The thicknesses of scalp and skull for the two-layer model were obtained by magnetic resonance imaging of a subjects head. The optical parameters obtained from the two-layer model agreed very well with those measured by the multidistance method.

Functional Frequency-Domain Near-Infrared Spectroscopy Detects Fast Neuronal Signal in the Motor Cortex

Millisecond changes in the optical properties of the human brain during stimulation were detected in five volunteers using noninvasive frequency-domain near-infrared spectroscopy. During a motor stimulation task we found highly significant signals, which were directly related to neuronal activity and exhibited much more localized patterns than the slow hemodynamic signals that are also detected by the near-infrared method. We considerably reduced the noise in the instrumental system and improved data analysis algorithms. With the achieved signal-to-noise ratio, single subject measurements were feasible without the requirement of particularly strong stimuli and within a reasonable period of measurement of 5 min at a mean signal-to-noise ratio of 3.6. The advantage of this noninvasive technique with respect to electrical recording is that it is able to detect neuronal activity with the relatively high spatial resolution of 8 mm.

Correlation of functional and resting state connectivity of cerebral oxy-, deoxy-, and total hemoglobin concentration changes measured by near-infrared spectrophotometry

The aim is to study cerebral vascular functional connectivity during motor tasks and resting state using multichannel frequency-domain near-infrared spectrophotometry. Maps of 5.7 × 10.8 cm size displaying changes in cerebral oxyhemoglobin (O(2)Hb), deoxyhemoglobin (HHb), and total hemoglobin (tHb) concentrations were measured in the motor cortex in 12 subjects (mean age of 28.8±12.7 yrs) during resting state and during two palm squeezing tasks with different timing. For each condition, phase plane plots, cross correlation functions, and connectivity indices were generated for O(2)Hb, HHb, and tHb. The amplitude of the concentration changes in O(2)Hb and HHb depends on the age of the subject. We found large regions of connectivity, which were similar for resting state and task conditions. This means the spatial relationships during resting state, when changes in O(2)Hb, HHb, and tHb corresponded to spontaneous oscillations, were correlated to the spatial patterns during the activation tasks, when changes in O(2)Hb, HHb, and tHb concentration were related to the alternation of stimulation and rest. Thus, the vascular functional connectivity was also present during resting state. The findings suggest that the vascular response to functional activation may be a nonlinear synchronization phenomenon and that resting state processes are more important than previously expected.

Detection of the fast neuronal signal on the motor cortex using functional frequency domain near infrared spectroscopy.

Using non-invasive near infrared spectroscopy fast changes in the range of ms in the optical properties of neurons during brain activity have been described. Since the signal is small, the system to detect it has to be highly noise optimized. We used a frequency-domain tissue oximeter, whose laser diodes were modulated at 110 MHz and the amplitude (AC), mean intensity (DC) and phase (phi) of the modulated optical signal was measured at 96 Hz sample rate. In two volunteers, 36 and 37 years old, the probe consisting of 4 crossed source detector pairs was placed above the motor cortex (C3 position), contralateral to the hand performing the tapping exercise. The tapping frequency was set at 2.5 times the heart rate of the subject to avoid the influence of harmonics on the signal. An electronic device recorded the tapping movement. Control-data were obtained from a solid medium of approximately the same optical properties as the human head. To reduce physiological noise the arterial pulsatility was removed using an adaptive filter, the data was detrended by a high pass filter and a cross correlation function between the optical data and the tapping signal was calculated. The instrumental noise of the control data was very low (AC mean 0.0015% +/- SD 0.00092%, DC 0.00037% +/- 0.00023% and phi 0.00083 degrees +/- 0.00042 degrees). On the head the noise level was AC 0.0042% +/- 0.0031%, DC 0.0021% +/- 0.0012% and phi 0.0020 degrees +/- 0.0017 degrees. In 14 DC, 5 AC and 0 phi out of 30 locations a fast signal was detected, which was higher (p<0.001) than the noise level. This signal disappeared during non-tapping periods. With the signal to noise ratio that we have achieved single subject measurements become feasible.

fMRI in patients with lumbar disc disease: a paradigm to study patients over time.

Low back pain is a common human ailment. It is estimated that over 70% of the population will experience low back pain that will require medication and/or medical attention. There are many causes for low back pain, one being herniation of the discs of the lumbar spine. Treatment options are very limited. Why patients develop chronic pain especially when there is no known organic cause or when the offending painful stimulus has been removed remains poorly understood. Functional magnetic resonance imaging (fMRI) is a technique that allows researchers to image which regions of the brain that are activated during motor, cognitive, and sensory experiences. Using fMRI to study pain has revealed new information about how the brain responds to painful stimuli and what regions of the brain are activated during pain. However, many of the paradigms used do not replicate the subject’s pain or use painful stimuli in volunteers without pain. Also, following patients from their acute phase of pain to the chronic phase with serial fMRI has not been performed. In this study we developed a paradigm that would allow studying patients with low back pain and leg pain including lumbar radiculopathy to better mimic a clinical pain syndrome and to have a method of following patients with this type of pain over time.

Study of the FMRI blood oxygen level dependent effect by near-infrared spectroscopy

In order to study the behavior of cerebral physiological parameters and to further the understanding of the fMRI blood-oxygen-level-dependent (BOLD) effect, we have recorded simultaneously multi-source frequency-domain near-infrared and BOLD fMRI signals during motor functional activation in humans. From the near-infrared data we obtained information on the changes in cerebral blood volume and oxygenation. In order to relate our observations to changes in cerebral blood flow we employed the “balloon” model of cerebral perfusion. Our data showed that the deoxyhemoglobin concentration is the major factor determining the time course of the BOLD signal.

Reduced cerebral hemodynamic response in sleep disorders: A NIRS frequency-domain study

We applied NIRS to investigate changes in cerebral oxygenation and hemodynamics in sleep-disordered breathing; namely, snoring and obstructive sleep apnea. A detected reduced brain hemodynamic response to hypoxia may be a predictor of cerebrovascular morbidity.