Christina Habermehl

A wearable multi-channel fNIRS system for brain imaging in freely moving subjects.

Functional near infrared spectroscopy (fNIRS) is a versatile neuroimaging tool with an increasing acceptance in the neuroimaging community. While often lauded for its portability, most of the fNIRS setups employed in neuroscientific research still impose usage in a laboratory environment. We present a wearable, multi-channel fNIRS imaging system for functional brain imaging in unrestrained settings. The system operates without optical fiber bundles, using eight dual wavelength light emitting diodes and eight electro-optical sensors, which can be placed freely on the subjects head for direct illumination and detection. Its performance is tested on N=8 subjects in a motor execution paradigm performed under three different exercising conditions: (i) during outdoor bicycle riding, (ii) while pedaling on a stationary training bicycle, and (iii) sitting still on the training bicycle. Following left hand gripping, we observe a significant decrease in the deoxyhemoglobin concentration over the contralateral motor cortex in all three conditions. A significant task-related ΔHbO2 increase was seen for the non-pedaling condition. Although the gross movements involved in pedaling and steering a bike induced more motion artifacts than carrying out the same task while sitting still, we found no significant differences in the shape or amplitude of the HbR time courses for outdoor or indoor cycling and sitting still. We demonstrate the general feasibility of using wearable multi-channel NIRS during strenuous exercise in natural, unrestrained settings and discuss the origins and effects of data artifacts. We provide quantitative guidelines for taking condition-dependent signal quality into account to allow the comparison of data across various levels of physical exercise. To the best of our knowledge, this is the first demonstration of functional NIRS brain imaging during an outdoor activity in a real life situation in humans.

Somatosensory activation of two fingers can be discriminated with ultrahigh-density diffuse optical tomography

Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools. However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays. We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI). In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.

High-resolution optical functional mapping of the human somatosensory cortex

Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation.

Contrast enhanced high-resolution diffuse optical tomography of the human brain using ICG

Non-invasive diffuse optical tomography (DOT) of the adult brain has recently been shown to improve the spatial resolution for functional brain imaging applications. Here we show that high-resolution (HR) DOT is also advantageous for clinical perfusion imaging using an optical contrast agent. We present the first HR-DOT results with a continuous wave near infrared spectroscopy setup using a dense grid of optical fibers and indocyanine green (ICG) as an exogenic contrast agent. We find an early arrival of the ICG bolus in the intracerebral tissue and a delayed arrival of the bolus in the extracerebral tissue, achieving the separation of both layers. This demonstrates the method’s potential for brain perfusion monitoring in neurointensive care patients.

Towards Whole-Body Fluorescence Imaging in Humans

Dynamic near-infrared fluorescence (DNIF) whole-body imaging of small animals has become a popular tool in experimental biomedical research. In humans, however, the field of view has been limited to body parts, such as rheumatoid hands, diabetic feet or sentinel lymph nodes. Here we present a new whole-body DNIF-system suitable for adult subjects. We explored whether this system (i) allows dynamic whole-body fluorescence imaging and (ii) can detect modulations in skin perfusion. The non-specific fluorescent probe indocyanine green (ICG) was injected intravenously into two subjects, and fluorescence images were obtained at 5 Hz. The in- and out-flow kinetics of ICG have been shown to correlate with tissue perfusion. To validate the system, skin perfusion was modulated by warming and cooling distinct areas on the chest and the abdomen. Movies of fluorescence images show a bolus passage first in the face, then in the chest, abdomen and finally in the periphery (∼10, 15, 20 and 30 seconds, respectively). When skin perfusion is augmented by warming, bolus arrives about 5 seconds earlier than when the skin is cooled and perfusion decreased. Calculating bolus arrival times and spatial fitting of basis time courses extracted from different regions of interest allowed a mapping of local differences in subcutaneous skin perfusion. This experiment is the first to demonstrate the feasibility of whole-body dynamic fluorescence imaging in humans. Since the whole-body approach demonstrates sensitivity to circumscribed alterations in skinperfusion, it may be used to target autonomous changes in polyneuropathy and to screen for peripheral vascular diseases.

Imaging of Motor Activity in Freely Moving Subjects Using a Wearable NIRS Imaging System

We present a miniaturized multi-channel NIRS imaging system for functional brain imaging in unrestrained settings suitable for any aspect of the head. Performance is demonstrated in a motor execution paradigm performed during bicycle riding.

Three-dimensional superposition of diffuse optical tomography results and subjacent anatomic structures

Near infrared spectroscopy (NIRS) and diffuse optical tomography (DOT) of the brain reveal no information about the measurements underlying anatomical structures. An independent anatomical mapping of DOT results onto the subjects brain or a generic brain model is desirable, especially when regions prone to large inter-subject variability are studied. We show two methods to match DOT data from high density fiber grids to anatomical structures. The forward model that is used to predict the light propagation is based on one generic anatomical MR scan. In both approaches we use this model MR-scan to translocate the position of the optical fiber grid from our experimental setup to the FEM model space. The first method, using fiduciary marks, achieves the spatial normalization of the subjects MR-scan (with marked corners of the fiber grid) and the models MR scan, leading to a translocation of the fiber pad position to the FEM-Model space. The second, anatomic landmark based, approach does not require the individuals MR scan. For this, 19 reference points and the position of the fiber pad corners are determined using photogrammetry software. These coordinates are translocated to the FEM model space by solving the least square problem of the subjects and the models reference points. We illustrate and compare both methods and show results from a vibrotactile stimulation experiment in humans.

Contrast-enhanced diffuse optical tomography of brain perfusion in humans using ICG

Regular monitoring of brain perfusion at the bedside in neurointensive care is desirable. Currently used imaging modalities are not suited for constant monitoring and often require a transport of the patient. Noninvasive near infrared spectroscopy (NIRS) in combination with an injection of a safe dye (indocyanine green, ICG) could serve as a quasi-continuous brain perfusion monitor. In this work, we evaluate prerequisites for the development of a brain perfusion monitor using continuous wave (cw) NIRS technique. We present results from a high-resolution diffuse optical tomography (HR-DOT) experiment in humans demonstrating the separation of signals from skin from the brain. This technique can help to monitor neurointensive care patients on a regular basis, detecting changes in cortical perfusion in time.

Whole Body Fluorescence Imaging in Humans

Whole body fluorescence imaging was performed in two adult subjects following injection of ICG. Results show that bolus tracking is very well feasible in humans and might be used for studying peripheral vascular diseases.

High-Density Optical Mapping of the Human Somatosensory Cortex

We use a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction to map the moto-somatosensory organisation of the human cortex at high resolution. Optical results are co-registered to individual anatomical brain anatomy.