Name: cerebral blood flow-based resting state functional connectivity of the human brain using optical diffuse correlation spectroscopy
Uploaded: 2020-05-27T13:30:00
Description: Watch this Scientific Journal Video about Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy at JoVE.com

The authors would like to acknowledge financial support from the Ohio Third Frontier to the Ohio Imaging Research and Innovation Network (OIRAIN, 667750), and the National Natural Science Foundation of China (No. 81771876).

The protocol was approved by the Institutional Review Board at Wright State University, and informed consent was obtained from each participant prior to the experiment.
1. Subject preparation
<ol>
	<li>Power up the FD-fNIRS and DCS system to warm up for at least 10 min (see sections 2 and 3 for more details) before starting any measurements of the subject. An example of subject measurement with the compact DCS instrument is shown in Figure 1.</li>
	<li>First, us...

To determine whether CBF as measured by DCS accurately detected RSFC, two areas of the brain with known RSFC properties were examined. Functional connectivity between DLFC regions and between DLFC and IFC is assumed to exist57,58,59. Connectivity between two sites within the left and right DLFC was chosen, because the intra-regional connectivity is usually higher. Also, connectivity between the IFC and the DLFC was chosen, as th...

When the brain is in a resting state, it demonstrates a high synchronization of spontaneous activity in functionally related regions, which can be located close in proximity or from a distance. These in-sync regions are known as functional networks1,2,3,4,5,6,7,8,9. This phenomenon was first uncovered by a functional magnetic resonance imaging (fMRI) study using blood oxygen level-dependent (BOLD) signals that indicate oxygenation levels of the cerebral blood5,10, also known as resting state functional connectivity (RSFC). Abnormalities in RSFC have been associated with brain disorders such as autism11, Alzheimer&#8217;s12, and depression13. Thus, RSFC is a valuable tool for studying patients with disorders who have trouble performaning task-based assessments. However, many patients, such as young autistic children, are poor candidates for assessment by fMRI, as it requires remaining still inside of a confined space for extended periods of time14,15. Optical imaging is fast and wearable; thus, it is suitable for a majority of patients, particularly the pediatric population16,17,18,19,20,21,22,23,24. Utilizing these advantages, functional near-infrared spectroscopy (fNIRS), which can quantify hemoglobin concentration and oxygen saturation parameters in the brain, is used to measure RSFC in humans (including the pediatric population4,8,25 and patients with autism11).
Optical diffuse correlation spectroscopy (DCS), a relatively new optical technique, can quantify cerebral blood flow, which is an important parameter that associates oxygen supply with metabolism6,17,26,27,28,29. Optical flow contrast quantified by DCS has been shown to have higher sensitivity in the brain compared to oxygenation contrast30. Thus, utilizing DCS-derived CBF parameters for assessing RSFC is advantageous.
DCS is sensitive to moving blood cells. When diffusing photons scatter from moving blood cells, this causes the intensity of detected light to fluctuate over time. DCS measures a time-based intensity autocorrelation function and its decay rate are dependent on the optical parameters and blood flow. These values are ultimately used to obtain the cerebral blood flow index (CBFi). With faster moving blood cells, the intensity autocorrelation function decays faster. Therefore, information about motion deep beneath the tissue surface can be derived (e.g., in the brain) from measurements of diffusing light fluctuations over time27,31,32,33,34,35. DCS is a technique complementary to the widely known fNIRS that measures blood oxygenation17,36. Since both fNIRS and DCS are optical brain imaging techniques with high temporal resolution in the range of milliseconds, the optical imaging set-ups are far less sensitive to motion artifacts than fMRI. They have also been successfully used for functional brain imaging in pediatric populations, including very young infants16. Previously, superficial blood flow measurements have been used to assess RSFC in preclinical studies in mice37. Here, blood flow parameters are used to quantify RSFC in nine healthy adults as a proof-of-concept study38,39.
In this study, a commercial FD-fNIRS system and custom DCS system is used (see Table of Materials). The DCS that was built in-house is comprised of two 785 nm, 100 mW, long coherence length continuous-wave lasers that are coupled to an FC connector and eight single-photon counting machines (SPCM) connected to an auto-correlator. A custom software graphical user interface (GUI) was also made specifically for this system to display and save the photon counts, autocorrelation curves, and semi-quantitative blood flow of each SPCM channel in real-time. The parts in this system are commonly used for DCS16,17,31,32,40,42,43,44, and the results obtained have also been verified in-house and used in a recent study39.

<table border="0" cellpadding="0" cellspacing="0" style="width:1012px;" width="1011">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">3D Printed Probe</td>
			<td style="width:121px;">In-house</td>
			<td style="width:272px;">N/A</td>
			<td style="width:339px;">3D printed PLA probe (Craftbot, Craft unique)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">785nm, 100mW, CW, FC coupled Laser</td>
			<td style="width:121px;">CrystaLaser</td>
			<td style="width:272px;">DL785-100-S</td>
			<td>DCS component (light source)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Auto-correlator</td>
			<td style="width:121px;">Correlator.com</td>
			<td style="width:272px;">Flex05-8ch</td>
			<td>DCS component (output g2 curve to PC)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Data Acquisition GUI</td>
			<td>In-house</td>
			<td>N/A</td>
			<td>GUI coded in LabVIEW to run the DCS system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Data analysis software</td>
			<td>In-house</td>
			<td>N/A</td>
			<td>Matlab code used for obtaining RSFC results</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">EEG Electrode Cap</td>
			<td>OpenBCI</td>
			<td>N/A</td>
			<td>EEG mesh cap with standard 10/20 positions</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Multi-mode fiber</td>
			<td style="width:121px;">OZ Optics</td>
			<td style="width:272px;">QMMJ-3,2.5-IRVIS-600/630-3PCBK-3</td>
			<td>DCS component (source fiber)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Oxiplex calibration phantom</td>
			<td>ISS</td>
			<td>75019, 75020</td>
			<td>Set of 2 PDMS Calibration Phantom</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Oxiplex muscle probe</td>
			<td style="width:121px;">ISS</td>
			<td>86010</td>
			<td>4 channel muscle probe</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Oxiplex Oximeter</td>
			<td style="width:121px;">ISS</td>
			<td>95205</td>
			<td>FD-fNIRS (690nm, 830nm)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Power meter</td>
			<td style="width:121px;">Thorlabs</td>
			<td style="width:272px;">PM100D</td>
			<td>Laser light power adjuster</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Sensor card</td>
			<td style="width:121px;">Thorlabs</td>
			<td style="width:272px;">F-IRC1-S</td>
			<td>laser IR beam viewer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:280px;">Single-mode fiber</td>
			<td style="width:121px;">OZ Optics</td>
			<td style="width:272px;">SMJ-3S2.5-780-5/125-3PCBK-3</td>
			<td>DCS component (detector fiber)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Single-Photon Counting Machine</td>
			<td>Excelitas</td>
			<td>SPMC-NIR-1x2-FC</td>
			<td>DCS component (detector)</td>
		</tr>
	</tbody>
</table>

cerebral blood flow-based resting state functional connectivity of the human brain using optical diffuse correlation spectroscopy

To obtain a comprehensive understanding of the human brain, utilization of cerebral blood flow (CBF) as a source of contrast is desired because it is a key hemodynamic parameter related to cerebral oxygen supply. Resting state low frequency fluctuations based on oxygenation contrast have been shown to provide correlations between functionally connected regions. The presented protocol uses optical diffuse correlation spectroscopy (DCS) to assess blood flow-based resting state functional connectivity (RSFC) in the human brain. Results of CBF-based RSFC in human frontal cortex indicate that intra-regional RSFC is significantly higher in the left and right cortices compared to inter-regional RSFC in both cortices. This protocol should be of interest to researchers who employ multi-modal imaging techniques to study human brain function, especially in the pediatric population.

The feasibility of using DCS to measure functional connectivity was successfully demostrated39. The resting state functional connectivity in the prefrontal cortices of nine subjects was measured. The results (mean &#177; SD) indicated a higher correlation in the intra-regional region of the left (0.64 &#177; 0.25) and right (0.62 &#177; 0.23) cortices, compared to the inter-regional region of the left (0.32 &#177; 0.32), (0.34 &#177; 0.27) and right (0.34 &#177; 0.29), (0.34 &#177; 0.26) cortices....

Watch this Scientific Journal Video about Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy at JoVE.com

Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy

This protocol demonstrates how to measure resting state functional connectivity in the human prefrontal cortex using a custom-made diffuse correlation spectroscopy instrument. The report also discuss practical aspects of the experiment as well as detailed steps for analyzing the data.

To obtain a comprehensive understanding of the human brain, utilization of cerebral blood flow (CBF) as a source of contrast is desired because it is a ...

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