Machine learning algorithms require a large and diverse data set for robust training. However, gathering a sufficient number is a difficult task due to time and budget constraints. Generated data sets can augment training data and provide diverse example for training. We propose a method to generate realistic diffuse optical tomography (DOT) data sets based on known physiological components of the DOT signal. We generate three dimensional models of each signal component and seed the hemodynamic response to activate targeted cortices. Our method reduces the need for a large recruitment process and increases the accuracy of machine learning algorithms.
Significance: We propose a customized animal-specific head cap and an near-infrared spectroscopy (NIRS) system to obtain NIRS signals in mobile small animals. NIRS studies in mobile small animals provide a feasible solution for comprehensive brain function studies.
Aim: We aim to develop and validate a multichannel NIRS system capable of performing functional brain imaging along with a closed-box stimulation kit for small animals in mobile conditions.
Approach: The customized NIRS system uses light-weight long optical fibers, along with a customized light-weight head cap to securely attach the optical fibers to the mouse. A customized stimulation box was designed to perform various stimuli in a controlled environment. The system performance was tested in a visual stimulation task on eight anesthetized mice and eight freely moving mice.
Results: Following the visual stimulation task, we observed a significant stimulation-related oxyhemoglobin (HbO) increase in the visual cortex of freely moving mice during the task. In contrast, HbO concentration did not change significantly in the visual cortex of anesthetized mice.
Conclusions: We demonstrate the feasibility of a wearable, multichannel NIRS system for small animals in a less confined experimental design.
Significance: Cerebral oxygenation changes in the superior, middle, and medial gyri were used to elucidate spatial impairments of autonomic hemodynamic recovery during the head-up tilt table test (HUTT) in Parkinson’s disease (PD) patients with orthostatic intolerance (OI) symptoms.
Aim: To analyze dynamic oxygenation changes during the HUTT and classify PD patients with OI symptoms using clinical and oxygenation features.
Approach: Thirty-nine PD patients with OI symptoms [10: orthostatic hypotension (PD-OH); 29: normal HUTT results (PD-NOR)] and seven healthy controls (HCs) were recruited. Prefrontal oxyhemoglobin (HbO) changes during the HUTT were reconstructed with diffuse optical tomography and segmented using the automated anatomical labeling system. Decision trees were used for classification.
Results: HCs and PD-NOR patients with positive rates of HbO change (PD-POS) showed the greatest HbO recovery in the superior frontal gyrus (SFG) during tilt. PD-OH and PD-NOR patients with negative rates of HbO change (PD-NEG) showed asymmetric reoxygenation. The classification accuracy was 89.4% for PD-POS versus PD-NEG, 71% for PD-NOR versus PD-OH, and 55.8% for PD-POS versus PD-NEG versus PD-OH. The oxygenation features were more discriminative than the clinical features.
Conclusions: PD-OH showed decreased right SFG function, which may be associated with impaired compensatory autonomic responses to orthostatic stress.
Significance: Monitoring of cerebral perfusion rather than blood pressure changes during a head-up tilt test (HUTT) is proposed to understand the pathophysiological effect of orthostatic intolerance (OI), including orthostatic hypotension (OH), in Parkinson’s disease (PD) patients.
Aim: We aim to characterize and distinguish the cerebral perfusion response to a HUTT for healthy controls (HCs) and PD patients with OI symptoms.
Approach: Thirty-nine PD patients with OI symptoms [10 PD patients with OH (PD-OH) and 29 PD patients with normal HUTT results (PD-NOR)], along with seven HCs participated. A 108-channel diffuse optical tomography (DOT) system was used to reconstruct prefrontal oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT) changes during dynamic tilt (from supine to 70-deg tilt) and static tilt (remained tilted at 70 deg).
Results: HCs showed rapid recovery of cerebral perfusion in the early stages of static tilt. PD-OH patients showed decreasing HbO and HbT during dynamic tilt, continuing into the static tilt period. The rate of HbO change from dynamic tilt to static tilt is the distinguishing feature between HCs and PD-OH patients. Accordingly, PD-NOR patients were subgrouped based on positive-rate and negative-rate of HbO change. PD patients with a negative rate of HbO change were more likely to report severe OI symptoms in the COMPASS questionnaire.
Conclusions: Our findings showcase the usability of DOT for sensitive detection and quantification of autonomic dysfunction in PD patients with OI symptoms, even those with normal HUTT results.
Childhood Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose symptoms include the inability to focus, impulsivity, and extremely active behavior. Advanced Test of Attention (ATA) is used to diagnose ADHD by measuring the patient’s impulse rate, average response rate, standard deviation rate, and omission rate during visual and auditory stimulation. However, ATA metrics are often skewed due to long task times and level of difficulty. We recruited healthy and ADHD children to monitor their performance during ATA. This work highlights diffuse optical tomography’s capability in providing cerebral perfusion changes to supplement ATA results for monitoring the cognitive effects of ADHD.
The Valsalva maneuver (VM) with beat-to-beat blood pressure and heart rate monitoring are used to evaluate orthostatic intolerance (OI). However, they lack the ability to detect cerebral hemodynamic changes, which may be a cause of OI symptoms. Therefore, we utilized near-infrared spectroscopy during VM. Patients with OI symptoms and normal healthy subjects were recruited. Patients were subgrouped according to VM results: patients with normal VM (NVM) and abnormal VM (AbVM). Oxyhemoglobin (HbO), deoxyhemoglobin, and total hemoglobin changes were measured at four different source–detector distances (SD) (15, 30, 36, and 45 mm), and latency, amplitude, duration, and integrated total signal were calculated. Those parameters were compared between a normal healthy control (HC) group and the two OI patient subgroups. We found that HbO increment latency at 30-mm SD in the HC, NVM, and AbVM groups was as follows: 0.39±0.23 s, 2.79±0.36 s, and 8.14±0.55 s, respectively (p<0.05). Among the four parameters we evaluated, latency of HbO increment was the best marker for differentiating OI.
KEYWORDS: Real time imaging, Brain mapping, Neuroimaging, Hemodynamics, Monte Carlo methods, Near infrared spectroscopy, Photon transport, Brain, Oxygen, Tissues
Accurate and efficient reconstruction of hemodynamic changes is an important step towards the implementation of NIRS as an enhanced clinical tool for understanding oxygenation changes at various depths within the brain. Depth information could provide insight on how oxygen transported to the tissue. For this work, we ran Monte Carlo simulations to develop sensitivity profiles for various source-detector separations. The source-detector separations were based on our custom built 108 channel NIRS probe and consisted of separations of 15 mm, 30 mm, 36 mm, and 45 mm. We used the mesh-based Monte Carlo program MMCLAB (Fang et al. 2010) to acquire the sensitivity profiles. The sensitivity profiles consisted of a tetrahedral mesh which was converted to a regular grid in three-dimensional space. Then, the structural tensor was calculated for each voxel and the Hamilton-Jacobi equation was solved anisotropically for the tensor volume. As the result, the distance map was in same space as the calculated tensor volume. Using this distance map, we modeled the probabilistic path of photons. We then weighted the hemodynamic changes acquired by our NIRS probe according to the probabilistic path to reconstruct hemodynamic changes in the prefrontal area of the brain.
In this work, we analyzed the clinical applicability of NIRS for use during Quantitative Autonomic Testing (QAT). QAT is a protocol consisting of deep breathing, Valsalva maneuver, and tilt table examination. It is used to diagnose a patient with disorders of the autonomic nervous system (ANS). Disorders of ANS includes orthostatic hyper/hypotension, vasovagal syncope, and postural orthostatic tachycardia syndrome. The results of QAT are typically analyzed with the use of blood pressure and heart rate data, however these metrics may be influenced by factors such as arrhythmia, making the data interpretation and diagnosis difficult for clinicians. We tested our custom built 108-channel NIRS probe on 26 elderly patients during the QAT protocol with various ANS disorders. We found that prefrontal cerebral oxygenation correlated well with blood pressure and heart rate changes for all three tasks, making it a clinically feasible tool for observing ANS functionality. During the Valsalva maneuver, we observed a longer delayed and lower amplitude response of cerebral oxygenation to the prefrontal area in orthostatic intolerant patients. During the tilt table examination, we saw a larger response in cerebral oxygenation and less equal transient cerebral oxygenation during tilt up and tilt down in tilt table examinations that were positive (unhealthy), compared to tilt table examinations that were negative (healthy). Overall, our study showcases NIRS as an enhanced tool for understanding ANS disorders.
A combined diffuse speckle contrast analysis (DSCA)–near-infrared spectroscopy (NIRS) system is proposed to simultaneously measure qualitative blood flow and blood oxygenation changes in human tissue. The system employs an optical switch to alternate two laser sources at two different wavelengths and a CCD camera to capture the speckle image. Therefore, an optical density can be measured from two wavelengths for NIRS measurements and a speckle contrast can be calculated for DSCA measurements. In order to validate the system, a flow phantom test and an arm occlusion protocol for arterial and venous occlusion were performed. Shorter exposure times (<1 ms) show a higher drop (between 50% and 66%) and recovery of 1/KS2 values after occlusion (approximately 150%), but longer exposure time (3 ms) shows more consistent hemodynamic changes. For four subjects, the 1/KS2 values dropped to an average of 82.1±4.0% during the occlusion period and the average recovery of 1/KS2 values after occlusion was 109.1±0.8%. There was also an approximately equivalent amplitude change in oxyhemoglobin (OHb) and deoxyhemoglobin (RHb) during arterial occlusion (max RHb=0.0085±0.0024 mM/DPF, min OHb=−0.0057±0.0044 mM/DPF). The sensitivity of the system makes it a suitable modality to observe qualitative hemodynamic trends during induced physiological changes.
Appropriate oxygen supply and blood flow are important in coordination of body functions and maintaining a life. To measure both oxygen supply and blood flow simultaneously, we developed a system that combined near-infrared spectroscopy (NIRS) and diffuse speckle contrast analysis (DSCA). Our system is more cost effective and compact than such combined systems as diffuse correlation spectroscopy(DCS)-NIRS or DCS flow oximeter, and also offers the same quantitative information. In this article, we present the configuration of DSCA-NIRS and preliminary data from an arm cuff occlusion and a repeated gripping exercise. With further investigation, we believe that DSCA-NIRS can be a useful tool for the field of neuroscience, muscle physiology and metabolic diseases such as diabetes.
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