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New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Optics and Lasers".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 64252

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Prof. Dr. Yoko Hoshi

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Department of Biomedical Optics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Interests: diffuse optics; time-resolved spectroscopy; pediatric neurology; cognitive neuroscience; oxygen metabolism
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Dear Colleagues,

In 1977, Jöbsis first described the in vivo application of near-infrared spectroscopy (NIRS), which is also called diffuse optical spectroscopy. NIRS was originally designed for clinical monitoring of tissue oxygenation, and it has also become a useful tool for neuroimaging studies (functional near-infrared spectroscopy, fNIRS). A wide range of NIRS instruments have been developed, including commonly commercially available instruments for continuous wave (CW) measurement based on the modified Beer–Lambert law (steady-state domain measurement). During the past 40 years, difficulties in selective and quantitative measurements of tissue hemoglobin have been central issues in the NIRS field. To overcome the problems with quantification, time-domain (TD) and frequency-domain (FD) measurements have been developed. TD measurement is the most promising approach, whereas compared with CW and FD measurements, TD measurement has been less frequently used due to large and expensive instruments with poor temporal resolution and limited dynamic range. Recently, however, the technology has advanced, and TD measurement is now increasingly implemented in research and practice in various clinical settings. This upcoming Special Issue aims to demonstrate the cutting edge of TD diffuse optical spectroscopy and imaging. It covers all aspects of TD measurement, including advances in hardware and instrumentation, methodology, theory of light propagation, and practical implementation.

Prof. Dr. Yoko Hoshi
Guest Editor

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Keywords

time-domain diffuse optical spectroscopy
time-domain diffuse optical imaging
time-domain fluorescence imaging
optical properties of biological tissue
quantification
time-domain radiative transfer equation
time-domain photon diffusion equation

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Published Papers (13 papers)

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Editorial

Jump to: Research, Review

4 pages, 161 KiB

Open AccessEditorial

Special Issue on New Horizons in Time Domain Diffuse Optical Spectroscopy and Imaging

by Yoko Hoshi

Appl. Sci. 2020, 10(8), 2752; https://doi.org/10.3390/app10082752 - 16 Apr 2020

Viewed by 1641

Abstract

In 1977, Jöbsis first described the in vivo application of near-infrared spectroscopy (NIRS) [...] Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

Research

Jump to: Editorial, Review

16 pages, 959 KiB

Open AccessArticle

Characteristic Length and Time Scales of the Highly Forward Scattering of Photons in Random Media

by Hiroyuki Fujii, Moegi Ueno, Kazumichi Kobayashi and Masao Watanabe

Appl. Sci. 2020, 10(1), 93; https://doi.org/10.3390/app10010093 - 20 Dec 2019

Cited by 7 | Viewed by 3138

Abstract

Background: Elucidation of the highly forward scattering of photons in random media such as biological tissue is crucial for further developments of optical imaging using photon transport models. We evaluated length and time scales of the photon scattering in three-dimensional media. Methods: We employed analytical solutions of the time-dependent radiative transfer, M-th order delta-Eddington, and photon diffusion equations (RTE, dEM, and PDE). We calculated the fluence rates at different source-detector distances and optical properties. Results: We found that the zeroth order dEM and PDE, which approximate the highly forward scattering to the isotropic scattering, are valid in longer length and time scales than approximately

10 / μ_{t}^{'}

and

40 / μ_{t}^{'} v

, respectively, where

μ_{t}^{'}

is the reduced transport coefficient and v the speed of light in a medium. The first and second order dEM, which approximate the highly forward-peaked phase function by the first two and three Legendre moments, are valid in the longer scales than approximately

4.0 / μ_{t}^{'}

and

6.3 / μ_{t}^{'} v

;

2.8 / μ_{t}^{'}

and

3.5 / μ_{t}^{'} v

, respectively. The boundary conditions less influence the length scales, while they reduce the times scales from those for bulk at the longer length scale than approximately

4.0 / μ_{t}^{'}

. Conclusion: Our findings are useful for constructions of accurate and efficient photon transport models. We evaluated length and time scales of the highly forward scattering of photons in various kinds of three-dimensional random media by analytical solutions of the radiative transfer, M-th order delta-Eddington, and photon diffusion equations. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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27 pages, 4958 KiB

Open AccessArticle

Improving Localization of Deep Inclusions in Time-Resolved Diffuse Optical Tomography

by David Orive-Miguel, Lionel Hervé, Laurent Condat and Jérôme Mars

Appl. Sci. 2019, 9(24), 5468; https://doi.org/10.3390/app9245468 - 12 Dec 2019

Cited by 5 | Viewed by 2506

Abstract

Time-resolved diffuse optical tomography is a technique used to recover the optical properties of an unknown diffusive medium by solving an ill-posed inverse problem. In time-domain, reconstructions based on datatypes are used for their computational efficiency. In practice, most used datatypes are temporal windows and Fourier transform. Nevertheless, neither theoretical nor numerical studies assessing different datatypes have been clearly expressed. In this paper, we propose an overview and a new process to compute efficiently a long set of temporal windows in order to perform diffuse optical tomography. We did a theoretical comparison of these large set of temporal windows. We also did simulations in a reflectance geometry with a spherical inclusion at different depths. The results are presented in terms of inclusion localization and its absorption coefficient recovery. We show that (1) the new windows computed with the developed method improve inclusion localization for inclusions at deep layers, (2) inclusion absorption quantification is improved at all depths and, (3) in some cases these windows can be equivalent to frequency based reconstruction at GHz order. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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17 pages, 449 KiB

Open AccessFeature PaperArticle

A Hybrid Inversion Scheme Combining Markov Chain Monte Carlo and Iterative Methods for Determining Optical Properties of Random Media

by Yu Jiang, Yoko Hoshi, Manabu Machida and Gen Nakamura

Appl. Sci. 2019, 9(17), 3500; https://doi.org/10.3390/app9173500 - 24 Aug 2019

Cited by 4 | Viewed by 2857

Abstract

Near-infrared spectroscopy (NIRS) including diffuse optical tomography is an imaging modality which makes use of diffuse light propagation in random media. When optical properties of a random medium are investigated from boundary measurements of reflected or transmitted light, iterative inversion schemes such as the Levenberg–Marquardt algorithm are known to fail when initial guesses are not close enough to the true value of the coefficient to be reconstructed. In this paper, we investigate how this weakness of iterative schemes is overcome using Markov chain Monte Carlo. Using time-resolved measurements performed against a polyurethane-based phantom, we present a case that the Levenberg–Marquardt algorithm fails to work but the proposed hybrid method works well. Then, with a toy model of diffuse optical tomography we illustrate that the Levenberg–Marquardt method fails when it is trapped by a local minimum but the hybrid method can escape from local minima by using the Metropolis–Hastings Markov chain Monte Carlo algorithm until it reaches the valley of the global minimum. The proposed hybrid scheme can be applied to different inverse problems in NIRS which are solved iteratively. We find that for both numerical and phantom experiments, optical properties such as the absorption and reduced scattering coefficients can be retrieved without being trapped by a local minimum when Monte Carlo simulation is run only about 100 steps before switching to an iterative method. The hybrid method is compared with simulated annealing. Although the Metropolis–Hastings MCMC arrives at the steady state at about 10,000 Monte Carlo steps, in the hybrid method the Monte Carlo simulation can be stopped way before the burn-in time. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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9 pages, 903 KiB

Open AccessArticle

Relationship of Total Hemoglobin in Subcutaneous Adipose Tissue with Whole-Body and Visceral Adiposity in Humans

by Miyuki Kuroiwa, Sayuri Fuse, Shiho Amagasa, Ryotaro Kime, Tasuki Endo, Yuko Kurosawa and Takafumi Hamaoka

Appl. Sci. 2019, 9(12), 2442; https://doi.org/10.3390/app9122442 - 14 Jun 2019

Cited by 6 | Viewed by 4005

Abstract

High whole-body and visceral adiposity are risk factors that can cause metabolic diseases. We hypothesized that the total hemoglobin concentration (total-Hb) in abdominal subcutaneous adipose tissue (SAT_ab), an indicator of white adipose tissue (WAT) vascularity, correlates negatively with risk factors for developing metabolic diseases, such as whole-body and visceral adiposity. We tested the optical characteristics of abdominal tissue in 140 participants (45 men and 95 women) who were apparently healthy individuals with a median age of 39 years. They also had a median body fat percentage of 25.4%, a visceral fat area of 50.4 cm², and a SAT_ab thickness of 1.05 cm. These tests were conducted using near-infrared time-resolved spectroscopy (NIR_TRS) with a 2-cm optode separation. To distinguish the segments of SAT_ab (Seg_SAT) and the mixture of muscle and SAT_ab (Seg_SAT+Mus), the threshold was analyzed using the slopes of (total-Hb) against the thickness of SAT_ab using the least-squares mean method. According to the results from the logistic regression analysis, the percentage of body fat and visceral fat area remained significant predictors of the (total-Hb) (p = 0.005 and p = 0.043, respectively) in the data for Seg_SAT (no influence from the SAT_ab thickness). We conclude that simple, rapid, and noninvasive NIR_TRS-determined (total-Hb) in WAT could be a useful parameter for evaluating risk factors for metabolic diseases. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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11 pages, 1813 KiB

Open AccessArticle

A Versatile Setup for Time-Resolved Functional Near Infrared Spectroscopy Based on Fast-Gated Single-Photon Avalanche Diode and on Four-Wave Mixing Laser

by Laura Di Sieno, Alberto Dalla Mora, Alessandro Torricelli, Lorenzo Spinelli, Rebecca Re, Antonio Pifferi and Davide Contini

Appl. Sci. 2019, 9(11), 2366; https://doi.org/10.3390/app9112366 - 10 Jun 2019

Cited by 8 | Viewed by 3635

Abstract

In this paper, a time-domain fast gated near-infrared spectroscopy system is presented. The system is composed of a fiber-based laser providing two pulsed sources and two fast gated detectors. The system is characterized on phantoms and was tested in vivo, showing how the gating approach can improve the contrast and contrast-to-noise-ratio for detection of absorption perturbation inside a diffusive medium, regardless of source-detector separation. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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11 pages, 1009 KiB

Open AccessArticle

Effects of Aging, Cognitive Dysfunction, Brain Atrophy on Hemoglobin Concentrations and Optical Pathlength at Rest in the Prefrontal Cortex: A Time-Resolved Spectroscopy Study

by Kaoru Sakatani, Lizhen Hu, Katsunori Oyama and Yukio Yamada

Appl. Sci. 2019, 9(11), 2209; https://doi.org/10.3390/app9112209 - 29 May 2019

Cited by 2 | Viewed by 6534

Abstract

Background: In order to evaluate usefulness of a time-resolved spectroscopy (TRS) in screening test of cognitive dysfunction, we studied the effects of aging, cognitive dysfunction, brain atrophy on hemoglobin (Hb) concentrations and optical pathlengths (OPLs) in the prefrontal cortex (PFC) at rest, using TRS. Methods: Employing TRS, we measured Hb concentrations and OPLs at rest in the PFC, and evaluated the relationship between the TRS parameters and cognitive function assessed by Mini-Mental State Examination (MMSE). In addition, we evaluated the relationship between the TRS parameters and the brain atrophy assessed by MRI. Results: We found positive correlations between MMSE scores and oxygen saturation (SO₂), oxy-Hb in the PFC, suggesting that the greater the degree of PFC activity, the higher the cognitive function. In addition, we found the negative correlation between the subject’s age and SO₂ and oxy-Hb in the PFC, suggesting that the older the subject, the lower the PFC activity at rest. Moreover, the OPLs in the right PFC negatively correlated with degree of brain atrophy evaluated by MRI, indicating that the shorter the OPL, greater degree of brain atrophy. Conclusions: TRS allowed us to evaluate the relation between the cerebral blood oxygenation (CBO) in the PFC at rest and cognitive function. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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9 pages, 1332 KiB

Open AccessArticle

Measurement of the Absolute Value of Cerebral Blood Volume and Optical Properties in Term Neonates Immediately after Birth Using Near-Infrared Time-Resolved Spectroscopy: A Preliminary Observation Study

by Aya Morimoto, Shinji Nakamura, Masashiro Sugino, Kosuke Koyano, Yinmon Htun, Makoto Arioka, Noriko Fuke, Ami Mizuo, Takayuki Yokota, Ikuko Kato, Yukihiko Konishi, Sonoko Kondo, Takashi Iwase, Saneyuki Yasuda and Takashi Kusaka

Appl. Sci. 2019, 9(10), 2172; https://doi.org/10.3390/app9102172 - 27 May 2019

Cited by 7 | Viewed by 3521

Abstract

The aim of this study was to use near-infrared time-resolved spectroscopy (TRS) to determine the absolute values of cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO₂) during the immediate transition period in term neonates and the changes in optical properties such as the differential pathlength factor (DPF) and reduced scattering coefficient (μ_s’). CBV and ScO₂ were measured using TRS during the first 15 min after birth by vaginal delivery in term neonates who did not need resuscitation. Within 2–3 min after birth, CBV showed various changes such as increases or decreases, followed by a gradual decrease until 15 min and then stability (mean (SD) mL/100 g brain: 2 min, 3.09 (0.74); 3 min, 3.01 (0.77); 5 min, 2.69 (0.77); 10 min, 2.40 (0.61), 15 min, 2.08 (0.47)). ScO₂ showed a gradual increase, then kept increasing or became a stable reading. The DPF and μ_s’ values (mean (SD) at 762, 800, and 836 nm) were stable during the first 15 min after birth (DPF: 4.47 (0.38), 4.41 (0.32), and 4.06 (0.28)/cm; μ_s’: 6.54 (0.67), 5.82 (0.84), and 5.43 (0.95)/cm). Accordingly, we proved that TRS can stably measure cerebral hemodynamics, despite the dramatic physiological changes occurring at this time in the labor room. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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12 pages, 1321 KiB

Open AccessArticle

Compression Stockings Suppressed Reduced Muscle Blood Volume and Oxygenation Levels Induced by Persistent Sitting

by Misato Kinoshita, Yuko Kurosawa, Sayuri Fuse, Riki Tanaka, Nobuko Tano, Ryota Kobayashi, Ryotaro Kime and Takafumi Hamaoka

Appl. Sci. 2019, 9(9), 1800; https://doi.org/10.3390/app9091800 - 30 Apr 2019

Cited by 5 | Viewed by 4385

Abstract

This study quantitatively analyzed the effects of 3 h of constant sitting on skeletal muscle oxygenation in the lower extremities, using near-infrared time-resolved spectroscopy (NIR_TRS). The effects of compression stockings were also evaluated. Eleven healthy men (age, 30.0 ± 6.7 years) maintained their knee joints at 90° flexion during 3 h of constant sitting and wore a compression stocking on either the right or left leg. The side the stocking was worn was chosen randomly. Subsequently, leg circumference and extracellular water were measured. After 3 h of sitting, both factors increased significantly in uncompressed limbs. Furthermore, intracellular water and muscle oxygenation had significantly decreased. In contrast, extracellular water had not increased in the limbs wearing compression stockings. Furthermore, the increased circumference of compressed limbs was significantly smaller than that of uncompressed limbs. Decreases in oxygenated hemoglobin and total hemoglobin were significantly smaller in compressed limbs than in uncompressed limbs (oxy-Hb; p = 0.021, total-Hb; p = 0.013). Three hours of sitting resulted in decreased intracellular water and increased extracellular water in the lower extremities, leading to reduced blood volume and oxygenation levels in skeletal muscle. Compression stockings successfully suppressed these negative effects. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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13 pages, 2586 KiB

Open AccessArticle

Comparison of Lipid and Water Contents by Time-domain Diffuse Optical Spectroscopy and Dual-energy Computed Tomography in Breast Cancer Patients

by Etsuko Ohmae, Nobuko Yoshizawa, Kenji Yoshimoto, Maho Hayashi, Hiroko Wada, Tetsuya Mimura, Yuko Asano, Hiroyuki Ogura, Yutaka Yamashita, Harumi Sakahara and Yukio Ueda

Appl. Sci. 2019, 9(7), 1482; https://doi.org/10.3390/app9071482 - 9 Apr 2019

Cited by 12 | Viewed by 4002

Abstract

We previously compared time-domain diffuse optical spectroscopy (TD-DOS) with magnetic resonance imaging (MRI) using various water/lipid phantoms. However, it is difficult to conduct similar comparisons in the breast, because of measurement differences due to modality-dependent differences in posture. Dual-energy computed tomography (DECT) examination is performed in the same supine position as a TD-DOS measurement. Therefore, we first verified the accuracy of the measured fat fraction of fibroglandular tissue in the normal breast on DECT by comparing it with MRI in breast cancer patients (n = 28). Then, we compared lipid and water signals obtained in TD-DOS and DECT from normal and tumor-tissue regions (n = 16). The TD-DOS breast measurements were carried out using reflectance geometry with a source–detector separation of 3 cm. A semicircular region of interest (ROI), with a transverse diameter of 3 cm and a depth of 2 cm that included the breast surface, was set on the DECT image. Although the measurement area differed between the modalities, the correlation coefficients of lipid and water signals between TD-DOS and DECT were rs = 0.58 (p < 0.01) and rs = 0.90 (p < 0.01), respectively. These results indicate that TD-DOS captures the characteristics of the lipid and water contents of the breast. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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13 pages, 2955 KiB

Open AccessFeature PaperArticle

Early Therapeutic Prediction Based on Tumor Hemodynamic Response Imaging: Clinical Studies in Breast Cancer with Time-Resolved Diffuse Optical Spectroscopy

by Shigeto Ueda and Toshiaki Saeki

Appl. Sci. 2019, 9(1), 3; https://doi.org/10.3390/app9010003 - 20 Dec 2018

Cited by 3 | Viewed by 3033

Abstract

This study reports data from three clinical studies using the time-resolved diffuse optical spectroscopy (TRS) system among breast cancer patients. The parameters of oxy-hemoglobin (O₂Hb), deoxy-hemoglobin (HHb), total hemoglobin (tHb), and oxygen saturation (SO₂) were evaluated using TRS, and its efficacy was tested in three trials. In trial 1, we recruited 118 patients with primary breast cancer to estimate the tumor detection rate. The cumulative detection rate was 62.7%, while that in T stage 0 was 31.3% and in T stage 1 was 44.7%. These were lower than those of T stage 2 (78.9%) and T stage 3 (100%). Next, we used TRS to monitor tumor hemodynamic response to neoadjuvant chemotherapy (n = 100) and found that pathological complete response (pCR) tumors had significantly lower tumor tHb than non-pCR tumors; a similar result was observed in estrogen receptor (ER)-negative tumors, but not in ER-positive tumors. The third trial monitored hemodynamic response to antiangiogenic therapy, bevacizumab (n = 28), and we demonstrated that sequential optical measurement of tumor SO₂ might be useful for detecting acute hypoxia 1–3 days after bevacizumab initiation. Next, response monitoring of neoadjuvant endocrine therapy (n = 30) suggested that changes in tumor tHb during treatment can predict and distinguish between responsive and non-responsive tumors early in letrozole therapy. In conclusion, our results show that hemodynamic monitoring of tumors by TRS could pair the unique features of tumor physiology to drug therapy and contribute to patient-tailored medicine. We recently established a platform for performing TRS in patients with breast cancer. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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Review

Jump to: Editorial, Research

31 pages, 2651 KiB

Open AccessReview

Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives

by Frédéric Lange and Ilias Tachtsidis

Appl. Sci. 2019, 9(8), 1612; https://doi.org/10.3390/app9081612 - 18 Apr 2019

Cited by 90 | Viewed by 13466

Abstract

Near-infrared spectroscopy (NIRS) is an optical technique that can measure brain tissue oxygenation and haemodynamics in real-time and at the patient bedside allowing medical doctors to access important physiological information. However, despite this, the use of NIRS in a clinical environment is hindered due to limitations, such as poor reproducibility, lack of depth sensitivity and poor brain-specificity. Time domain NIRS (or TD-NIRS) can resolve these issues and offer detailed information of the optical properties of the tissue, allowing better physiological information to be retrieved. This is achieved at the cost of increased instrument complexity, operation complexity and price. In this review, we focus on brain monitoring clinical applications of TD-NIRS. A total of 52 publications were identified, spanning the fields of neonatal imaging, stroke assessment, traumatic brain injury (TBI) assessment, brain death assessment, psychiatry, peroperative care, neuronal disorders assessment and communication with patient with locked-in syndrome. In all the publications, the advantages of the TD-NIRS measurement to (1) extract absolute values of haemoglobin concentration and tissue oxygen saturation, (2) assess the reduced scattering coefficient, and (3) separate between extra-cerebral and cerebral tissues, are highlighted; and emphasize the utility of TD-NIRS in a clinical context. In the last sections of this review, we explore the recent developments of TD-NIRS, in terms of instrumentation and methodologies that might impact and broaden its use in the hospital. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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54 pages, 6669 KiB

Open AccessFeature PaperReview

Time-Domain Near-Infrared Spectroscopy and Imaging: A Review

by Yukio Yamada, Hiroaki Suzuki and Yutaka Yamashita

Appl. Sci. 2019, 9(6), 1127; https://doi.org/10.3390/app9061127 - 17 Mar 2019

Cited by 76 | Viewed by 10041

Abstract

This article reviews the past and current statuses of time-domain near-infrared spectroscopy (TD-NIRS) and imaging. Although time-domain technology is not yet widely employed due to its drawbacks of being cumbersome, bulky, and very expensive compared to commercial continuous wave (CW) and frequency-domain (FD) fNIRS systems, TD-NIRS has great advantages over CW and FD systems because time-resolved data measured by TD systems contain the richest information about optical properties inside measured objects. This article focuses on reviewing the theoretical background, advanced theories and methods, instruments, and studies on clinical applications for TD-NIRS including some clinical studies which used TD-NIRS systems. Major events in the development of TD-NIRS and imaging are identified and summarized in chronological tables and figures. Finally, prospects for TD-NIRS in the near future are briefly described. Full article

(This article belongs to the Special Issue New Horizons in Time-Domain Diffuse Optical Spectroscopy and Imaging)

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