Elsevier

NeuroImage

Volume 59, Issue 4, 15 February 2012, Pages 3201-3211
NeuroImage

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

https://doi.org/10.1016/j.neuroimage.2011.11.062Get rights and content

Abstract

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.

Highlights

► Ultrahigh-density DOT can resolve cortical activation in the millimeter range. ► Highly focal activations can be missed by classical NIRS and conventional DOT. ► Ultrahigh-density DOT and fMRI have comparable acces to cortical activation.

Introduction

NIRS is an established method to measure cortical activation noninvasively. The usually practiced topographic approach relies on next-nearest neighbor source-detector combinations with a sparse array of optical fibers. Commonly, NIRS studies use inter-optode distances between 2 and 4 cm, covering particular regions of interest (Franceschini et al., 2003, Holper et al., 2010) or the whole head (Franceschini et al., 2006, Takeuchi et al., 2009), depending on the imaging device, the number of available optodes and the field of study.

Topographic NIRS has been widely used within the last decade, and has become an accepted tool in brain research. The method is known for having a good temporal and sufficient spatial resolution. The fields of application are wide and range from physiological (Holper et al., 2009, Miyai et al., 2001) to psychological (Hyde et al., 2010, Nakahachi et al., 2010, Wartenburger et al., 2007) and psychiatric studies (Kameyama et al., 2006, Zhu et al., 2010). Previously, resting state analysis using NIRS with a high coverage of the head identified the same functional connectivity networks as fMRI experiments (Franceschini et al., 2006, Mesquita et al., 2010). Promising, though still at the beginning of development, is the application of NIRS in brain–computer interfaces (BCI) where, additional to the use of electrophysiological signals in BCIs, researchers focus on hemodynamic signals that can be measured with NIRS (Fazli et al., 2011, Sitaram et al., 2009).

Applications of NIRS mainly focus on hemodynamic changes during task performance. However, there are promising clinical applications of NIRS such as the quantification of cerebral oxygenation and perfusion (Habermehl et al., 2011, Highton et al., 2010, Mittnacht, 2010) provided the confounding effects of extracerebral hemodynamic signals from tissue like the scalp can be accounted for. Although most of the applications are in the experimental stage and used only in research, NIRS has the potential to become a bedside monitoring tool in clinical routine and neurorehabilitation.

Beside the sensitivity to superficial signals, the spatial resolution of NIRS in its topographic approach is limited to several centimeters. A better resolution may not be required for many applications, but for clinical applications higher spatial resolution and depth discrimination are mandatory.

For example, investigation of rehabilitation induced changes of cortical function and neuroplasticity needs a higher spatial resolution than conventional topographic NIRS can provide. Unfortunately, NIRS provides only functional patterns but no anatomical information. Individual anatomic structures are however often needed, especially in cases where there is a high inter-subject variability concerning the location and characteristics of activation due to specific tasks or stimulations.

A higher spatial resolution can be provided by using the multi-distance approach (Barbour et al., 2001, Bluestone et al., 2001), which uses dense fiber arrays to yield measurements from multiple source-detector distances and combinations. The approach of diffuse optical tomography (DOT) aims at transforming the signal content from different measuring distances into depth information, thus forming three-dimensional image maps instead of the planar backprojection obtained with topographic NIRS. In the following sections we will refer only to the topographic approach using next-nearest neighbor source-detector (SD) distances as ‘NIRS.’ The tomographic approach using multiple SD distances will be denoted, ‘DOT’. In contrast to other groups, e.g. Zeff et al. (2007) that use fiber grids with a minimum SD separation of 13 mm and fibers that are separated sources and detectors (not co-located) we applied a tighter fiber arrangement (see Methods section), exceeding the sampling density of other multi-distance approaches. In the following, we refer to this strategy as ultrahigh-density DOT.

In DOT, image reconstruction of hemodynamic changes consists of two main steps. First, the forward model of light propagation in tissue is calculated with assumed optical properties in the medium. Second, the inverse problem of recovering interior optical properties from measured surface data is solved. Image reconstruction is an ill-posed and under-determined problem and many research groups have focused on one or both parts of the problem (Arridge and Hebden, 1997, Arridge and Schweiger, 1997, Boas et al., 2002, Dehghani et al., 2008, Dehghani et al., 2009, Fang, 2010, Fang and Boas, 2009, Gibson and Dehghani, 2009, Gibson et al., 2005, Xu et al., 2005).

Light propagation in tissue is usually described by solving the diffusion equation on a finite element (FE) mesh or by modeling the photon transport in the tissue with a Monte Carlo (MC) simulation. For both methods, different tools have been developed by various groups. The free available NIRFAST software (Dehghani et al., 2008) provides a toolbox to calculate forward models based on the FE method with different mesh geometries and the possibility to incorporate individually generated meshes of different tissue types like breast and head models. Other free tools that are available include fast, voxel based MC simulations for photon transport using graphics processing units based parallel computing techniques (Fang and Boas, 2009) and another one to solve MC simulations based on FE meshes (Fang, 2010). In this study we used the commercial NAVI software (NIRx Medical Technology LLC, Glen Head, NY, USA).

The calculation of the forward model leads to a sensitivity or weight matrix that contains information about the contributions of each voxel of the investigated medium to the measured surface data. Generally speaking, the image of internal optical properties can be regarded as the product of the inverted weight matrix with the measured surface data.

Three-dimensional DOT of human brain function has not been widely used so far. Published studies have focused on motor (Boas et al., 2004, Gibson et al., 2006, Joseph et al., 2006) and visual stimulation (White and Culver, 2010a, Zeff et al., 2007). Boas et al. (2004) first demonstrated 3D reconstructed DOT images of motor activation in the human cortex and compared these to topographic backprojection maps. The group demonstrated an increasing lateral resolution, when overlapping multi-distance measurements were used. Moreover, (White and Culver, 2010b) compared different optical fiber layouts and showed a significantly improved lateral resolution with a dense imaging grid compared to sparser grids.

In this study, we show that for demanding functional mapping tasks, such as demonstrated on the somatosensory system, not only does DOT in conjunction with high spatial sampling improve spatial resolution, but that it is essential to visualize and distinguish the activation patterns. In contrast to many studies focusing on the primary motor-system (Boas et al., 2004, Franceschini et al., 2003, Joseph et al., 2006) or primary/secondary visual system (Liao et al., 2010, White and Culver, 2010a, Zeff et al., 2007), we are only aware of two reports on somatosensory studies with NIRS (Custo et al., 2010, Franceschini et al., 2003), both using a median nerve stimulation procedure. Thus, it seems to be an issue to resolve a more delicate somatosensory cortical activation with the classical topographic approach.

The primary somatosensory cortex (SI) was chosen here as a model system for several reasons: The superficial location at the posterior wall of the central sulcus makes it easily accessible to DOT measurements. Activations within SI are of small extent with short distances between representational areas of the fingers of one hand, suitable to demonstrate the need for and the benefit of high spatially resolved optical imaging. Furthermore, the highly individual and variable representational distribution provides a challenge and an interesting quality assessment for the comparison between NIRS and fMRI activations. And finally, beyond pure and basic research, there may be relevant future clinical applications in neurorehabilitation and rehabilitation monitoring, e.g. in stroke patients by assessing cortical neuronal plasticity.

In previous fMRI studies, finger representations have been confirmed to be localized within the contralateral postcentral gyrus and to show a somatotopic arrangement; generally, the first finger (thumb, d1) is represented in the most lateral, anterior and inferior position, with the other finger representations following in a superior medial direction along the central sulcus (Maldjian et al., 1999, Kurth et al., 2000, Weibull et al., 2008). Repeated measurements show comparable results for individual subjects. However, there is high inter-individual variability in somatotopic arrangement as well as in hemodynamic response strength (Schweizer et al., 2008, Kurth et al., 2000).

In the present work, we extended our previously published results on vibrotactile finger stimulation (Koch et al., 2010) towards the comparison of classical topographic image generation and a three-dimensional image reconstruction. Additionally, the same subjects underwent fMRI using the same experimental design to compare the functional activations of both imaging modalities. Finally, the individual position of optical fibers in the forward model was taken into account in the current study allowing to co-register volumes of functional activation with the individual anatomy.

Optical topography is exceedingly used in brain research compared to optical tomography. In this work, we show that there are applications where a three-dimensional tomographic approach is essential to image brain activity: with a topographic setup or even with a conventionally dense tomographic setup the specific activation foci cannot be distinguished properly. Furthermore, we demonstrate that our imaging and reconstruction procedure is able to separate cortical answers to different stimuli not only laterally but also transversally, with the activation pattern being found in different tissue depths. Additionally, we show that DOT and 3T fMRI as tools of functional brain imaging in humans yield comparable results.

Section snippets

Subjects and stimulus procedure

We investigated eight healthy right-handed volunteers (mean age 26.8 ± 4.6 years, 2 female) who had no history of any neurological disease. Written consent was obtained from each volunteer prior to the experiment. Subjects were monetarily rewarded for their participation. The study was approved by the local ethic committee.

Volunteers underwent vibrotactile stimulation of the 1st (thumb, d1) and 5th finger (little finger, d5) of their right hand using a piezoelectric transducer (model PL-127.251,

Ultrahigh-density DOT reveals distinct activations for 1st and 5th finger

In five (out of eight) subjects, we found two distinct separate activation foci for the two fingers using the ultrahigh-density DOT approach as shown in Fig. 2. The volumes were reconstructed from the 900 optical data channels (816 data channels for s5) and are mapped onto the individuals’ anatomies. In these five participants, the activations projected to the postcentral gyrus, in line with the expected activation in response to the vibrotactile stimulation. However, the exact locations of the

Discussion

The aim of the current multimodal functional imaging study was two-fold. Firstly, we wanted to show that ultrahigh-density DOT allows identifying distinct activation patterns for stimuli that are known to activate cortical areas of a small extend. Secondly, we investigated the comparability of high-density optical measurements with the gold standard in functional brain imaging, fMRI.

For the optical measurement, we used an ultrahigh-density grid of optical fibers with an inter-optode distance of

Conclusions

In this study we showed that ultrahigh-density DOT leads to a significant increase in the lateral resolution and allows distinguishing activation maps of two discrete fingers in a somatotopic stimulation task. We showed that a typical topographic approach cannot resolve these activations and even DOT with a medium-dense grid does not lead to satisfying results. With a fiducial mark approach we correlated DOT results and the subjects’ neuroanatomy for a mapping of three-dimensional result

Acknowledgments

This work was supported in part under NIH Grant nos. R42NS050007 and R44NS049734 and by the National Bernstein Network Computational Neuroscience, Bernstein Focus: Neurotechnology, No. 01GQ0850, Project B3.

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