Yunlong Sun

Noninvasive diagnosis and therapeutic effect evaluation of deep vein thrombosis in clinics by near-infrared spectroscopy

Abstract. Deep vein thrombosis (DVT) has become a severe disease with a rising incidence rate. The conventional diagnosis relies on complicated imaging modalities that may also involve invasive contrast agent injection and ionizing procedures (e.g., venography). Noninvasive near-infrared spectroscopy (NIRS) methods have been explored which required the DVT patients to follow some exercise protocols. Here, we attempt to use portable NIRS under patients’ natural state for DVT diagnosis. Nine DVT patients and seven healthy subjects participated in NIRS measurements of concentration of oxy- and deoxy-hemoglobins (Δ[HbO2] and Δ[Hb]) relative to data on a tissue mimicking phantom at six particular sites of calves. It was found that Δ[HbO2] is significantly lower in DVT patients than healthy ones, whereas Δ[Hb] is distinctly higher. Moreover, after thrombolytic therapy, both Δ[HbO2] and Δ[Hb] in DVT calves assume a gradual convergence to the curves of healthy ones. This reveals the potential of NIRS for the noninvasive, continuous, and straightforward monitoring/therapeutic effect evaluation of DVT in clinics with appropriate bedside monitoring capability.

Effect of head model on Monte Carlo modeling of spatial sensitivity distribution for functional near-infrared spectroscopy

Modeling Light propagation within human head to deduce spatial sensitivity distribution (SSD) is important for Near-infrared spectroscopy (NIRS)/imaging (NIRI) and diffuse correlation tomography. Lots of head models have been used on this issue, including layered head model, artificial simplified head model, MRI slices described head model, and visible human head model. Hereinto, visible Chinese human (VCH) head model is considered to be a most faithful presentation of anatomical structure, and has been highlighted to be employed in modeling light propagation. However, it is not practical for all researchers to use VCH head models and actually increasing number of people are using magnet resonance imaging (MRI) head models. Here, all the above head models were simulated and compared, and we focused on the effect of using different head models on predictions of SSD. Our results were in line with the previous reports on the effect of cerebral cortex folding geometry. Moreover, the influence on SSD increases with the fidelity of head models. And surprisingly, the SSD percentages in scalp and gray matter (region of interest) in MRI head model were found to be 80% and 125% higher than in VCH head model. MRI head models induced nonignorable discrepancy in SSD estimation when compared with VCH head model. This study, as we believe, is the first to focus on comparison among full serials of head model on estimating SSD, and provided quantitative evidence for MRI head model users to calibrate their SSD estimation.

Effects of wavelength, beam type and size on cerebral low-level laser therapy by a Monte Carlo study on visible Chinese human

Low-level laser therapy (LLLT) has been clinically utilized for many indications in medicine requiring protection from cell/tissue death, stimulation of healing and repair of injuries, pain reduction, swelling and inflammation. Presently, the use of LLLT to treat stroke, traumatic brain injury and cognitive dysfunction are attracting growing interest. Near-infrared light is capable of penetrating into the cerebral cortex, allowing noninvasive treatments to be carried out with few treatment-related adverse events. Optimization of LLLT treatment effect is a crucial issue of this field; however, only a few experimental tests on mice for wavelength selection have been reported. We addressed this issue by low-cost, straightforward and quantitative comparisons on light dosage distribution within visible Chinese human head by Monte Carlo modeling of near-infrared light propagation. Optimized selection in wavelength, beam type and size were given based on comparisons among frequently used setups (i.e., wavelengths: 660, 810 and 980 nm; beam type: Gaussian and flat beam; beam diameter: 2, 4 and 6 cm). This study provided an efficient way for guiding the optimization of LLLT setup and selection on wavelength, beam type and size for clinical brain LLLT.

Near-infrared spectroscopy assessment of divided visual attention task-invoked cerebral hemodynamics during prolonged true driving

Driver fatigue is one of the leading causes of traffic accidents. It is imperative to develop a technique to monitor fatigue of drivers in real situation. Near-infrared spectroscopy (fNIRS) is now capable of measuring brain functional activity noninvasively in terms of hemodynamic responses sensitively, which shed a light to us that it may be possible to detect fatigue-specified brain functional activity signal. We developed a sensitive, portable and absolute-measure fNIRS, and utilized it to monitor cerebral hemodynamics on car drivers during prolonged true driving. An odd-ball protocol was employed to trigger the drivers’ visual divided attention, which is a critical function in safe driving. We found that oxyhemoglobin concentration and blood volume in prefrontal lobe dramatically increased with driving duration (stand for fatigue degree; 2-10 hours), while deoxyhemoglobin concentration increased to the top at 4 hours then decreased slowly. The behavior performance showed clear decrement only after 6 hours. Our study showed the strong potential of fNIRS combined with divided visual attention protocol in driving fatigue degree monitoring. Our findings indicated the fNIRS-measured hemodynamic parameters were more sensitive than behavior performance evaluation.

Shed a light of wireless technology on portable mobile design of NIRS

Mobile internet is growing rapidly driven by high-tech companies including the popular Apple and Google. The wireless mini-NIRS is believed to deserve a great spread future, while there is sparse report on wireless NIRS device and even for the reported wireless NIRS, its wireless design is scarcely presented. Here we focused on the wireless design of NIRS devices. The widely-used wireless communication standards and wireless communication typical solutions were employed into our NIRS design and then compared on communication efficiency, distance, error rate, low-cost, power consumption, and stabilities, based on the requirements of NIRS applications. The properly-performed wireless communication methods matched with the characteristics of NIRS are picked out. Finally, we realized one recommended wireless communication in our NIRS, developed a test platform on wireless NIRS and tested the full properties on wireless communication. This study elaborated the wireless communication methods specified for NIRS and suggested one implementation with one example fully illustrated, which support the future mobile design on NIRS devices.

Multi-channel photon migration study in visible Chinese human muscle for optical detection of deep vein thrombosis

Deep vein thrombosis (DVT) always induced venous thrombosis. Most cases of venous thrombosis were induced by deep vein thrombosis (DVT), with high incidence rate of >60% in >60 years old people. Near-infrared spectroscopy (NIRS) were reported recently to be an intriguing and potential technique in detecting DVT in clinics. However, the photon transport is still unclear, which is crucial for the image reconstruction of the updated development called as NIRS-based DVT imager. Here we employed the Monte Carlo simulation software for 3D voxelized media (MCVM) and the Visible Chinese Human (VCH) model, which segmentation is finest in the world, to simulate multi-channel photon migration in calf muscle. And the image reconstruction of DVT hemodynamic distribution was achieved. This study, for the first time, provides the most realistic 3-D multichannel photon migration for NIRS study on DVT, and explored the image reconstruction for furtherly developing a NIRS-based DVT imager.

Reliability analysis of instrument design of noninvasive bone marrow disease detector

Bone marrow is an important hematopoietic organ, and bone marrow lesions (BMLs) may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important. But the current diagnosis methods rely on bone marrow biopsy/puncture, with significant limitations such as invasion, complex operation, high risk, and discontinuous. It is highly in need of a non-invasive, safe, easily operated, and continuous monitoring technology. So we proposed to design a device aimed for detecting bone marrow lesions, which was based on near infrared spectrum technology. Then we fully tested its reliabilities, including the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Here, we reported this sequence of reliability test experiments, the experimental results, and the following data analysis. This instrument was shown to be very sensitive, with distinguishable concentration less than 0.002 and with good linearity, stability and high SNR. Finally, these reliability-test data supported the promising clinical diagnosis and surgery guidance of our novel instrument in detection of BMLs.

Calibration of NIRS-measured hemodynamics with best-matched hemoglobin extinction coefficients and group statics on human-blood-model data

Near-infrared spectroscopy (NIRS) has been extensively developed for in-vivo measurements of tissue vascular oxygenation, breast tumor detection, and functional brain imaging, by groups of physicists, biomedical engineers, and mathematicians. To quantify concentrations of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (hemodynamics), extinction coefficients of hemoglobin (ε) have to be employed. However, it is still controversial what ε values should be used and relatively what calibration should be done in NIRS quantification to achieve the highest precision, although that the differences in ε values among published data resulted in ~20% variation in quantification of hemoglobin concentration is reported based a single human blood test. We collected 12 blood samples from 12 healthy people, and with each blood sample performed blood tissue model experiments. 4 teams of published extinction value widely used in NIRS fields were employed respectively in our quantification. Calibrations based least square analysis and regression between real and estimated hemodynamics for 12 subjects were performed with each team of ε values respectively. We found that: Moaveni’s ε values contributed to highest accuracy; Regression method produced quite effective calibration, and when it combined with Moaveni’s ε values, the calibration reduced the std/mean of estimation by two orders of magnitude. Thus Moaveni’s ε values are most recommended to use in NIRS quantification, especially with our calibration matrix based on regression analysis with a group of subjects’ blood sample.

Noninvasive optical evaluation of low frequency oscillations in prefrontal cortex hemodynamics during verbal working memory

The low frequency oscillation (LFO) around 0.1 Hz has been observed recently in cerebral hemodynamic signals during rest/sleep, enhanced breathing, and head- up-tilting, showing that cerebral autoregulation can be accessed by LFOs. However, many brain function researches require direct measurement of LFOs during specified brain function activities. This pilot study explored using near-infrared spectroscopy/imaging (NIRS) to noninvasively and simultaneously detect LFOs of prefrontal cerebral hemodynamics (i.e., oxygenated/deoxygenated/total hemoglobin concentration: △[oxy-Hb]/ △[deoxy-Hb]/ △[tot-Hb]) during N-back visual verbal working memory task. The LFOs were extracted from the measured variables using power spectral analysis. We found the brain activation sites struck clear LFOs while other sites did not. The LFO of △[deoxy-Hb] acted as a negative pike and ranged in (0.05, 0.1) Hz, while LFOs of △[oxy-Hb] and △[tot-Hb] acted as a positive pike and ranged in (0.1, 0.15) Hz. The amplitude difference and frequency lag between △[deoxy-Hb] and △[oxy-Hb]/ △[tot-Hb] produced a more focused and sensitive activation map compare to hemodynamic amplitude-quantified activation maps. This study observed LFOs in brain activities and showed strong potential of LFOs in accessing brain functions.

Wavelength, beam size and type dependences of cerebral low-level light therapy: A Monte Carlo study on visible Chinese human

Low level light therapy (LLLT) has been clinically utilized for many indications in medicine requiring protection from cell/tissue death, stimulation of healing and repair of injuries, pain reduction, swelling and inflammation. Presently, use of LLLT to treat stroke, traumatic brain injury, and cognitive dysfunction is attracting growing interest. Near-infrared light can penetrate into the brain tissue, allowing noninvasive treatment to be carried out with few treatment-related adverse events. Optimization of LLLT treatment effect is one key issue of the field; however, only a few experimental tests on mice for wavelength selection have been reported. We addressed this issue by low-cost, straightforward and quantitative comparisons on light dosage distribution in Visible Chinese human head with Monte Carlo modeling of light propagation. Optimized selection in wavelength, beam type and size were given based on comparisons among frequently-used setups (i.e., wavelengths: 660 nm, 810 nm, 980 nm; beam type: Gaussian and flat beam; beam diameter: 2 cm, 4 cm, 6cm).This study provided an efficient way to guide optimization of LLLT setup and selection on wavelength, beam type and size for clinical brain LLLT.