Matteo Caffini

Time domain functional NIRS imaging for human brain mapping

This review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community.

Validating atlas-guided DOT: A comparison of diffuse optical tomography informed by atlas and subject-specific anatomies

We describe the validation of an anatomical brain atlas approach to the analysis of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare the diffuse optical images of simulated cortical activation reconstructed using a registered atlas with those obtained using a subjects true anatomy. The error in localization of the simulated cortical activations when using a registered atlas is due to a combination of imperfect registration, anatomical differences between atlas and subject anatomies and the localization error associated with diffuse optical image reconstruction. When using a subject-specific MRI, any localization error is due to diffuse optical image reconstruction only. In this study we determine that using a registered anatomical brain atlas results in an average localization error of approximately 18 mm in Euclidean space. The corresponding error when the subjects own MRI is employed is 9.1 mm. In general, the cost of using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling of the localization error. Our results show that despite this increase in error, reasonable anatomical localization is achievable even in cases where the subject-specific anatomy is unavailable.

Review: Brain and muscle near infrared spectroscopy/imaging techniques

This review is an introduction to functional near infrared spectroscopy techniques and instrumentation which are commonly used for the estimation of haemoglobin concentration in muscle and brain cortex. Three approaches are considered: continuous wave, frequency domain and time domain near infrared spectroscopy. The different techniques are briefly analysed from a theoretical point of view in order to understand their capabilities and drawbacks. Some of the instrumentation commonly used is considered, presenting the main characteristics of the different techniques, their similarities and principal differences.

Load-dependent brain activation assessed by time-domain functional near-infrared spectroscopy during a working memory task with graded levels of difficulty

We evaluated frontal brain activation during a mixed attentional/working memory task with graded levels of difficulty in a group of 19 healthy subjects, by means of time-domain functional near-infrared spectroscopy (fNIRS). Brain activation was assessed, and load-related oxy- and deoxy-hemoglobin changes were studied. Generalized linear model (GLM) was applied to the data to explore the metabolic processes occurring during the mental effort and, possibly, their involvement in short-term memorization. GLM was applied to the data twice: for modeling the task as a whole and for specifically investigating brain activation at each cognitive load. This twofold employment of GLM allowed (1) the extraction and isolation of different information from the same signals, obtained through the modeling of different cognitive categories (sustained attention and working memory), and (2) the evaluation of model fitness, by inspection and comparison of residuals (i.e., unmodeled part of the signal) obtained in the two different cases. Results attest to the presence of a persistent attentional-related metabolic activity, superimposed to a task-related mnemonic contribution. Some hemispherical differences have also been highlighted frontally: deoxy-hemoglobin changes manifested a strong right lateralization, whereas modifications in oxy- and total hemoglobin showed a medial localization. The present work successfully explored the capability of fNIRS to detect the two neurophysiological categories under investigation and distinguish their activation patterns.

Multi-channel medical device for time domain functional near infrared spectroscopy based on wavelength space multiplexing

We have designed a compact dual wavelength (687 nm, 826 nm) multi-channel (16 sources, 8 detectors) medical device for muscle and brain imaging based on time domain functional near infrared spectroscopy. The system employs the wavelength space multiplexing approach to reduce wavelength cross-talk and increase signal-to-noise ratio. System performances have been tested on homogeneous and heterogeneous tissue phantoms following specifically designed protocols for photon migration instruments. Preliminary in vivo measurements have been performed to validate the instrument capability to monitor hemodynamic parameters changes in the arm muscle during arterial occlusion and in the adult head during a motor task experiment.

A compact time-resolved system for near infrared spectroscopy based on wavelength space multiplexing

We designed and developed a compact dual-wavelength and dual-channel time-resolved system for near-infrared spectroscopy studies of muscle and brain. The system employs pulsed diode lasers as sources, compact photomultipliers, and time-correlated single photon counting boards for detection. To exploit the full temporal and dynamic range of the acquisition technique, we implemented an approach based on wavelength space multiplexing: laser pulses at the two wavelengths are alternatively injected into the two channels by means of an optical 2×2 switch. In each detection line (i.e., in each temporal window), the distribution of photon time-of-flights at one wavelength is acquired. The proposed approach increases the signal-to-noise ratio and avoids wavelength cross-talk with respect to the typical approach based on time multiplexing. The instrument was characterized on tissue phantoms to assess its properties in terms of linearity, stability, noise, and reproducibility. Finally, it was successfully tested in preliminary in vivo measurements on muscle during standard cuff occlusion and on the brain during a motor cortex response due to hand movements.

Corticospinal tract integrity is related to primary motor cortex thinning in relapsing–remitting multiple sclerosis

Background: The relationship between white matter injury and cortical atrophy development in relapsing–remitting multiple sclerosis (RRMS) remains unclear. Objectives: To investigate the associations between corticospinal tract integrity and cortical morphology measures of the primary motor cortex in RRMS patients and healthy controls. Methods: 51 RRMS patients and 30 healthy controls underwent MRI examination for cortical reconstruction and assessment of corticospinal tract integrity. Partial correlation and multiple linear regression analyses were used to investigate the associations of focal and normal appearing white matter (NAWM) injury of the corticospinal tract with thickness and surface area measures of the primary motor cortex. Relationships between MRI measures and clinical disability as assessed by the Expanded Disability Status Scale and disease duration were also investigated. Results: In patients only, decreased cortical thickness was related to increased corticospinal tract NAWM mean, axial and radial diffusivities in addition to corticospinal tract lesion volume. The final multiple linear regression model for PMC thickness retained only NAWM axial diffusivity as a significant predictor (adjusted R2= 0.270, p= 0.001). Clinical measures were associated with NAWM corticospinal tract integrity measures. Conclusions: Primary motor cortex thinning in RRMS is related to alterations in connected white matter and is best explained by decreased NAWM integrity.

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Computer-aided cephalometric landmark annotation for CBCT data

PurposeNowadays, with the increased diffusion of Cone Beam Computerized Tomography (CBCT) scanners in dental and maxillo-facial practice, 3D cephalometric analysis is emerging. Maxillofacial surgeons and dentists make wide use of cephalometric analysis in diagnosis, surgery and treatment planning. Accuracy and repeatability of the manual approach, the most common approach in clinical practice, are limited by intra- and inter-subject variability in landmark identification. So, we propose a computer-aided landmark annotation approach that estimates the three-dimensional (3D) positions of 21 selected landmarks.MethodsThe procedure involves an adaptive cluster-based segmentation of bone tissues followed by an intensity-based registration of an annotated reference volume onto a patient Cone Beam CT (CBCT) head volume. The outcomes of the annotation process are presented to the clinician as a 3D surface of the patient skull with the estimate landmark displayed on it. Moreover, each landmark is centered into a spherical confidence region that can help the clinician in a subsequent manual refinement of the annotation. The algorithm was validated onto 18 CBCT images.ResultsAutomatic segmentation shows a high accuracy level with no significant difference between automatically and manually determined threshold values. The overall median value of the localization error was equal to 1.99 mm with an interquartile range (IQR) of 1.22–2.89 mm.ConclusionThe obtained results are promising, segmentation was proved to be very robust and the achieved accuracy level in landmark annotation was acceptable for most of landmarks and comparable with other available methods.

From neurovascular coupling to neurovascular cascade: a study on neural, autonomic and vascular transients in attention

Mental processes bring about neural, vascular and autonomic changes in the brain cortex. Due to the different nature of these modifications, their onsets show no synchrony and time dynamics is often strongly dissimilar. After acquiring data from a group of 16 subjects, we estimated temporal correlation between task and signals in order to assess possible influences induced by an attentive task on electroencephalographic (EEG), heart rate variability (HRV), oxy- and deoxy-haemoglobin concentration signals. We also investigated correlations and time delays between couples of different biological signals. This allowed for the isolation of a subgroup of subjects showing similar tracks. Cardiac frequency and deoxy-haemoglobin signals displayed a strong positive correlation with the task design, while EEG alpha rhythm and oxygenation showed a negative correlation. Neural electrical response was nearly instantaneous with respect to the task progression, and autonomic response showed a mean delay of about 15 s and a slower hemodynamic response (mean delay above 20 s) was finally induced. Globally, the task elicited a cascade of responses, in which delays can be quantified.