Andrew M. Siegel

Volumetric diffuse optical tomography of brain activity

We present three-dimensional diffuse optical tomography of the hemodynamic response to somatosensory stimulation in a rat. These images show the feasibility of volumetrically imaging the functional response to brain activity with diffuse light. A combination of positional optode calibration and contrast-to-noise ratio weighting was found to improve imaging performance.

Bedside functional imaging of the premature infant brain during passive motor activation.

Abstract Background: Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. Traditional functional radiologic methods cannot provide continuous, portable measurements. Imaging methods, which use near-infrared light allow for non-invasive measurements by taking advantage of the fact that hemoglobin is a strong absorber at these wavelengths. Aims: To test the feasibility of a new optical functional imaging system in premature infants, and to obtain preliminary brain imaging of passive motor activation in this population. Methods: A new optical imaging system, the Diffuse Optical Tomography System (DOTS), was used to provide real-time, bedside assessments. Custom-made soft flexible fiberoptic probes were placed on two extremely ill, mechanically ventilated 24 week premature infants, and three healthier 32 week premature infants. Passive motor stimulation protocols were used during imaging. Results: Specific movement of the arm resulted in reproducible focal, contralateral changes in cerebral absorption. The data suggest an overall increase in blood volume to the imaged area, as well as an increase in deoxyhemoglobin concentration. These findings in premature infants differ from those expected in adults. Conclusions: In the intensive care setting, continuous non-invasive optical functional imaging could be critically important and, with further study, may provide a bedside monitoring tool for prospectively identifying patients at high risk for brain injury.

Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation

The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.

Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin

With the aim of evaluating the relative performance of hemodynamic contrasts for mapping brain activity, the spatio-temporal response of oxy-, deoxy-, and total-hemoglobin concentrations were imaged with diffuse optical tomography during electrical stimulation of the rat somatosensory cortex. For both 6-s and 30-s stimulus durations, total hemoglobin images provided smaller activation areas than oxy- or deoxy-hemoglobin images. In addition, analysis of regions of interest near the sagittal sinus vein show significantly greater contrast in both oxy- and deoxy-relative to total hemoglobin, suggesting that oximetric contrasts have larger draining vein contributions compared to total hemoglobin contrasts under the given stimulus conditions. These results indicate that total hemoglobin and cerebral blood volume may have advantages as hemodynamic mapping contrasts, particularly for large amplitude, longer duration stimulus paradigms.

Diffuse optical tomography of rat brain function

Diffuse optical tomography (DOT) can image spatial variations in highly scattering, tissue-like optical media. We have built an inexpensive and portable continuous-wave DOT system containing 32 laser sources (16 at 780nm and 16 at 830nm) and 16 detectors, which can acquire 288 independent measurements in less than 1 second. These data can then be processed using a variety of imaging algorithms. Preliminary studies have shown that this system can image brain bleeds in piglets, modulation of cerebral hemodynamics in rats, and brain function in both neonate and adult humans. The technical challenges involved in performing DOT over large optode areas is discussed. We describe the instrument and discuss a number of the technical issues which influenced its design. We then present a study of rat brain functional response to electrical forepaw stimulation measured with DOT, and compare it to functional MRI (fMRI). fMRI can separately measure blood volume, blood flow, and deoxy-hemoglobin concentration, and is thus a good benchmark for DOT. The relative performance of DOT and fMRI will be discussed. Our comparison shows similar temporal and spatial trends in blood volume and oxygen saturation following functional activation. These results clearly demonstrate the capabilities of DOT and set the stage for advancement to quantitative functional brain imaging.

Noninvasive transabdominal monitoring of fetal cerebral oxygenation using pulse oximetry

Pulse oximetry (oxygen saturation monitoring) has markedly improved medical care in many fields, including anesthesiology, intensive care, and newborn intensive care. In obstetrics, fetal heart rate monitoring remains the standard for intrapartum assessment of fetal well being. Fetal oxygen saturation monitoring is a new technique currently under development. It is potentially superior to electronic fetal heart rate monitoring (cardiotocography) because it allows direct assessment of both fetal oxygen status and fetal tissue perfusion. Here, we present feasibility studies for trans-abdominal fetal cerebral pulse oximetry. Our experiments on more than 20 patients indicate feasibility. We will present the methodology for obtaining these data, as well as a summary of our pilot clinical study.

Bedside functional imaging of the premature infant brain during passive motor activation

Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. These changes create a signal that can be imaged and quantitated using various methods, most of which do not allow for continuous bedside measurements. Imaging methods using near-infrared light, however, have been described. These allow for non-invasive measurements, and take advantage of the fact that hemoglobin is a strong absorber at these wavelengths and thus acts as a naturalO contrast agent. We have generated brain functional images of ill, premature infants during passive movement of the forearm using the Boston Diffusion Optical Tomography System (DOTS), a system which allows for near real-time bedside assessments. For these initial feasibility studies in the neonatal intensive care unit (NICU), custom-made soft flexible probes were made, and passive motor tasks were performed during imaging. We found that specific passive movements of the arm resulted in focal, reproducible changes in cerebral absorption at 830 nm, indicating an increase in regional blood flow and oxygenation. Further bedside studies have since been undertaken using 780 nm and 830 nm lasers. These studies indicate that the Boston DOTS is a safe and feasible bedside near-infrared functional imaging device, and underline the importance offurther studies in this critically ill patient group at high risk for brain injury.

Volumetric diffuse optical tomography of brain activity in rat

We present three-dimensional diffuse optical tomography (DOT) of the hemodynamic response to forepaw stimulation in a rat. DOT results agree with previous fMRI studies and demonstrate feasibility of volumetrically imaging brain activity.

Event-related FMRI of tactile stimulus detection

Introduction A variety of studies have investigated the effect of vibrotactile frequency, amplitude, and probability of detection on single-unit activity in the primate cortex (e.g., Mountcastle et al., 1969). In this study, we examined the effect of these variables on activation across human cortical regions using event-related fMRI. The event-related fMR1 approach facilitated evaluation of the response to relatively brief stimuli (1-set duration), the derivation of hemodynamic gain functions, and the correlation of correct and incorrect psychophysical responses with the pattern and amplitude of cortical activity.

Rapid multispectral cw multiplexing technique for photon migration measurements

A discussion of photon migration will introduce both some fundamental limitations and practical concerns which directly affect the design and construction of DOT instrumentation. The utility of four different multiplexing schemes will be discussed and then contrasted in light of these concerns. The relative merits of each scheme will be used to determine which measurements they are best suited for, given some of the realistic technical, legal, and practical issues common to the medical research community. Within this context, the unique advantages offered by a variant of time-division multiplexing; Pulse-TDM, will be introduced and explained.