Wavelength and code-division multiplexing in diffuse optical imaging

Three-dimensional diffuse optical imaging of hand joints: System description and phantom studies

Optical imaging of fluorescent probes is an essential tool for investigation of molecular events in small animals for drug developments. In order to get localization and quantification information of fluorescent labels, CEA-LETI has developed efficient approaches in classical reflectance imaging as well as in diffuse optical tomographic imaging with continuous and temporal signals. This paper presents an overview of the different approaches investigated and their performances. High quality fluorescence reflectance imaging is obtained thanks to the development of an original "multiple wavelengths" system. The uniformity of the excitation light surface area is better than 15%. Combined with the use of adapted fluorescent probes, this system enables an accurate detection of pathological tissues, such as nodules, beneath the animal's observed area. Performances for the detection of ovarian nodules on a nude mouse are shown. In order to investigate deeper inside animals and get 3D localization, diffuse optical tomography systems are being developed for both slab and cylindrical geometries. For these two geometries, our reconstruction algorithms are based on analytical expression of light diffusion. Thanks to an accurate introduction of light/matter interaction process in the algorithms, high quality reconstructions of tumors in mice have been obtained. Reconstruction of lung tumors on mice are presented. By the use of temporal diffuse optical imaging, localization and quantification performances can be improved at the price of a more sophisticated acquisition system and more elaborate information processing methods. Such a system based on a pulsed laser diode and a time correlated single photon counting system has been set up. Performances of this system for localization and quantification of fluorescent probes are presented.

The accuracy and clinical utility of diffuse optical imaging systems rely on continuous advancements in instrumentation, theoretical modeling, and computational methods, alongside strategies to overcome persistent barriers to clinical translation. A key challenge in diffuse optical imaging research is the development of computationally efficient numerical models that accurately describe light-tissue interactions in complex anatomical domains, along with the validation of these models and novel instrumentation using realistic tissue-mimicking phantoms. Although diffuse optical imaging remains a promising area of research for applications such as cancer detection and functional brain activity assessment, progress has been limited by the lack of anatomically complex optical phantoms and the high computational cost of Monte Carlo simulations required to model light propagation. This dissertation addresses these challenges through two key innovations. First, we designed a multi-filament-mixing 3-D printing platform which enables spatially varying absorption, scattering, and luminescent optical properties by dynamically blending multiple commercially available filaments. This platform facilitates the design and fabrication of anatomically accurate phantoms with precise control over optical absorbance and scattering parameters, while also incorporating tunable luminescence intensity through the embedding of phosphorescent materials. We printed several benchmark phantoms showcasing our method's capability of generating complex anatomical shapes with continuously varying optical properties. This method should therefore allow for the design and easy fabrication of highly complex, anatomically accurate phantoms for benchmarking, calibration, and training across a wide range of diffuse optical imaging applications. Second, we introduce a memory-efficient parametric modeling approach to address the computational challenges in capturing detected photon partial path length (PPL) distributions in Monte Carlo simulations. This method utilizes numerical stochastic estimation techniques, such as the Box-Cox transformation, skew-normal distribution modeling, and rejection sampling, to efficiently approximate the PPL distribution with a small set of statistical parameters. This approach significantly reduces the memory footprint of large-scale Monte Carlo simulations, while remaining generalizable to anatomically accurate domains. Furthermore, the ability to regenerate an arbitrary number of detected photon PPLs using the recorded parametric PPL models demonstrates significant computational savings while retaining high levels of accuracy. Together, these findings enable more accessible and accurate diffuse optical imaging modeling by substantially reducing the computational costs typically associated with simulating light transport in complex anatomical domains. In summary, this dissertation presents experimental and computational advancements that are broadly applicable to diffuse optical imaging research. Both innovations are generalizable to complex tissue-like domains, enhancing their relevance across a wide range of applications. These contributions support the continued development of diffuse optical imaging technologies and promote their clinical translation, helping to enable more accessible, cost-effective, and practical imaging systems.--Author's abstract

Functional neuroimaging is a vital element of neuroscience and cognitive research and, increasingly, is an important clinical tool. Diffuse optical imaging is an emerging, noninvasive technique with unique portability and hemodynamic contrast capabilities for mapping brain function in young subjects and subjects in enriched or clinical environments. We have developed a high-performance, high-density diffuse optical tomography (DOT) system that overcomes previous limitations and enables superior image quality. We show herein the utility of the DOT system by presenting functional hemodynamic maps of the adult human visual cortex. The functional brain images have a high contrast-to-noise ratio, allowing visualization of individual activations and highly repeatable mapping within and across subjects. With the improved spatial resolution and localization, we were able to image functional responses of 1.7 cm in extent and shifts of <1 cm. Cortical maps of angle and eccentricity in the visual field are consistent with retinotopic studies using functional MRI and positron-emission tomography. These results demonstrate that high-density DOT is a practical and powerful tool for mapping function in the human cortex.

Optical techniques based on photon migration are rapidly emerging as a promising alternative and/or augmentation of existing medical imaging modalities. For example, real time studies of hemodynamic changes in brain tissue are possible as a step towards optical functional brain imaging. Time-resolved implementations of these techniques allow for discrimination between scattering and absorption and for depth resolution. They require sub-nanosecond pulsed light sources with high repetition rate and sufficient power for deep enough tissue penetration. Picosecond diode lasers satisfy the clinical demands of economy, compact size, and reliability almost perfectly. Today multi-channel diode laser devices are commercially available and are widely used in diffuse optical imaging and spectroscopy, in particular in optical tomography and breast cancer detection. However, the output powers of these devices are just about sufficient for moderate tissue penetration depths. An improvement that does not compromise the advantages of the diode laser sources is amplification of the diode laser output by means of solid state tapered amplifiers. We present an amplified light source for use in NIR diffuse optical spectroscopy and imaging, providing pulse widths as short as 100 ps, adjustable repetition rates up to 80 MHz, and peak power levels as high as 7 Watts, corresponding to average power levels exceeding 100 mW. In combination with time-resolved photon counting electronics matching the high throughput demands in conjunction with the new source, state-of-the-art systems for diffuse optical imaging can be built. System design features and possible application examples are presented.

In this paper, we present a high performance time-resolved diffuse optical tomography (DOT) system whose working principle and implementation are very different from the conventional methods and features near real-time data acquisition. Dual-wavelength near-infrared light at 784 nm and 808 nm are used as light source. A high bit rate pseudo-random bit sequence (2.488 GB/s) modulates both continuous lights when they go through the external intensity modulator. The diffuse photon density waves responding to such modulated light are detected by array of high sensitivity, high speed silicon avalanche photodetectors (APD). The temporal point spread function can be retrieved very quickly by using hardware auto-/cross-correlation. Our system implementation has achieved system impulse with rise time approaching 0.5 ns which is highly desirable for time-domain DOT application to penetrate depth in few centimeters. The temporal resolution is mainly limited by the photodetectors. System performance is stabilized with accurate temperature control over key components. Experiment results based on tissue-like phantoms verify our design is potential for breast cancer imaging.

Pseudo random bit sequence (PRBS) generation is important for a wide range of applications including communication systems, pattern generation and encryption. All optical pseudo random bit sequence (PRBS) generation using both regular and quantum dot (QD) semiconductor optical amplifier (SOA) based Mach-Zehnder interferometer have been studied. The speed of operation is limited by the gain and phase recovery times in the SOA. A key element in the fabrication of a PRBS generator is an all optical XOR. All optical XOR functionality has been demonstrated experimentally using regular semiconductor optical amplifier (SOA) based Mach-Zehnder interferometer at 80 Gb/s. The performance of the XOR operation has been analyzed by solving the rate equation of the SOA for SOAs with both regular and QD active region. QD-SOAs should result in significantly higher speed operation. The paper shows that QD-SOA based devices can be used to produce PRBS generators that operate near 250 Gb/s.

This article demonstrates a spectroscopic diffuse optical tomography (DOT) system for the noninvasive continuous imaging of tissue. The system was built on an embedded system architecture along with an algorithm that performs entire system control, data acquisition, noise-free lock-in detection, and wireless data transmission to a host computer, equipped with a graphics processing unit (GPU). The GPU system executes a fast 3-D DOT spectroscopic image reconstruction algorithm. The algorithm computes Jacobians and solves four different depth-sensitive inverse problems of image reconstruction. The host computer sends commands to the DOT server system and collects data, and simultaneously performs high-speed 3-D spectroscopic image reconstruction to display images in real-time. We designed a configurable optical fiber patch to collect depth-resolved diffused light exiting the imaging media by placing the patch on the surface. The simulation and experimental results from two setups showed the spectroscopic imaging capability of the system to map the concentration of oxyhemoglobin, deoxyhemoglobin, and water, and to characterize the tumor located deep inside the tissue. The proposed system uses low-cost LEDs, photodiode detectors, embedded system, and algorithms to perform high-speed 3-D functional imaging and can be further miniaturized. Our promising results pave the way for the development of a low-cost hand-held spectroscopic DOT system for the real-time onsite functional imaging of biological tissue.

Advances in epilepsy studies have shown that specific changes in hemodynamics precede and accompany seizure onset and propagation. However, it has been challenging to noninvasively detect these changes in real time and in humans, due to the lack of fast functional neuroimaging tools. In this study, we present a functional diffuse optical tomography (DOT) method with the guidance of an anatomical human head atlas for 3-dimensionally mapping the brain in real time. Central to our DOT system is a human head interface coupled with a technique that can incorporate topological information of the brain surface into the DOT image reconstruction. The performance of the DOT system was tested by imaging motor tasks-involved brain activities on N = 6 subjects (3 epilepsy patients and 3 healthy controls). We observed diffuse areas of activations from the reconstructed [HbT] images of patients, relative to more focal activations for healthy subjects. Moreover, significant pretask hemodynamic activations were also seen in the motor cortex of patients, which indicated abnormal activities persistent in the brain of an epilepsy patient. This work demonstrates that fast functional DOT is a valuable tool for noninvasive 3-dimensional mapping of brain hemodynamics.

Diffuse optical imaging (DOI) is a label-free, safe, inexpensive, and quantitative imaging modality that provides metabolic and molecular contrast in tissue using visible or near-infrared light. DOI modalities can image up to several centimeters deep in tissue, providing access to a wide range of human tissues and organ sites. DOI technologies have benefitted from several decades of academic research, which has provided a variety of platforms that prioritize imaging depth, resolution, field-of-view, spectral content, and other application-specific criteria. Until recently, however, acquisition and processing speeds have represented a stubborn barrier to further clinical exploration and implementation. Over the last several years, advances in high-speed data acquisition enabled by high-speed digital electronics, newly available sources and detectors, and innovative new scanning methods have led to major improvements in DOI rates. These advances are now being coupled with new data processing algorithms that utilize deep learning and other computationally efficient methods to provide rapid or real-time feedback in the clinic. Together, these improvements have the potential to help advance DOI technologies to the point where major impacts can be made in clinical care. Here, we review recent advances in acquisition and processing speed for several important DOI modalities.

In this paper, we study the mechanical interface between a hard-disk drive (HDD) head and magnetic recording tape to enable the use of HDD heads to investigate future tape operating points. Tape surface height measurements were obtained using an interferometer microscope for varying wrap angle configurations, tape velocities, and tape tensions. Simultaneously, the readback signal from the read element of the HDD head was captured to study the quality of the contact between the tape and the head. The signal-to-noise ratio (SNR) and bit-error rate (BER) performance of pseudorandom bit sequence (PRBS) data readback experiments are presented. An analytical model is described for estimating the magnetic spacing from the PRBS readback spectrum. In contrast to current commercial tape heads, the HDD head surface has a pronounced topography containing cavities. When tape passes in close proximity, subambient pressures are formed inside these cavities and the resulting pressure differences force the tape toward the head and deform the tape into remarkable shapes. For the topography of the HDD head used, the shape of tape is predominantly determined by the leading and trailing wrap angles. Readback was obtained only in the backward direction (i.e., opposite to the direction of operation in an HDD), with positive leading but negative trailing wrap angles. Better readback is obtained for shallow wrap angles, lower tape velocity, and higher tape tension. Good readback is obtained for leading and trailing wrap angles ~0.3° and -0.2°, respectively. Fits of the analytical model to the spectrum of the readback signal of PRBS data lead to a magnetic spacing estimate of ~30 nm. At 600 kb/in linear density, we measured 11 dB SNR and 7 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> BER for PRBS data on perpendicularly oriented particulate barium-ferrite tape.

INTRODUCTIONDelirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three‐dimensional capabilities.METHODSTwenty‐five delirious and matched non‐delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium.RESULTSTotal hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post‐resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls.DISCUSSIONThese findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias.HighlightsWe developed a portable diffuse optical tomography (DOT) system for bedside three‐dimensional functional neuroimaging to study delirium in the hospital.We implemented a novel DOT task‐focused seed‐based correlation analysis.DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

In Diffuse Optical Tomography (DOT), data processing and reconstruction stages are crucial to obtain high-quality images. Thus, choosing suitable algorithms for the system is a critical choice. This study aims to determine an appropriate reconstruction algorithm for DOT imaging. There are several reconstruction algorithms used in DOT systems. Some algorithms have been improved for solving specific cases, and some still need to be improved. In this study, we used three algorithms for the reconstruction process: Singular Value Decomposition (SVD), Bi-Conjugated Gradient (Bi-CG), and Transpose Free Quasi Minimal Residual (TFQMR). In testing the algorithms, data of the simulation experiments have been used. The simulation experiments model the tumoral tissue within the breast. All three algorithms were produced correct images while the tumor close to the surface. In the case of the tumor that is not close to the breast surface, the tumor location on the images created by Bi-CG and SVD algorithms was not its actual location. However, the tumor location in the image created by the TFQMR algorithm was close to its actual location. Outcomes of the reconstruction algorithms were evaluated based on correctly defining the location of the tumors by using Mean Percentage Error (MPE), Mean Squared Error (MSE), and Mean Absolute Error (MAE) metrics. We have demonstrated the TFQMR algorithm is a more appropriate reconstruction technique for DOT systems. Thus, we have concluded that TFQMR can have the potential to be used in medical imaging systems.

We present a photoacoustic tomography-guided diffuse optical tomography approach using a hand-held probe for detection and characterization of deeply-seated targets embedded in a turbid medium. Diffuse optical tomography guided by coregistered ultrasound, MRI, and x ray has demonstrated a great clinical potential to overcome lesion location uncertainty and to improve light quantification accuracy. However, due to the different contrast mechanisms, some lesions may not be detectable by a nonoptical modality but yet have high optical contrast. Photoacoustic tomography utilizes a short-pulsed laser beam to diffusively penetrate into tissue. Upon absorption of the light by the target, photoacoustic waves are generated and used to reconstruct, at ultrasound resolution, the optical absorption distribution that reveals optical contrast. However, the robustness of optical property quantification of targets by photoacoustic tomography is complicated because of the wide range of ultrasound transducer sensitivity, the orientation and shape of the targets relative to the ultrasound array, and the uniformity of the laser beam. We show in this paper that the relative optical absorption map provided by photoacoustic tomography can potentially guide the diffuse optical tomography to accurately reconstruct target absorption maps.

The ability to perform all-optical digital information processing is one of the key requirements for future photonic networks. Recently, the use of semiconductor optical amplifier based all-optical interferometric switches [1] has allowed practical demonstrations of advanced functionality to be demonstrated. These have included a bit-serial regenerative optical memory which is capable of long term storage [2] and has the ability to restore the optical logic level [3]. Here we describe a further advance in all-optical digital functionality with a demonstration of an all-optical pseudorandom bit sequence (PRBS) generator. The all-optical PRBS comprises two coupled regenerative memories [2] which act as a time-of-flight shift register for optical pulses. A digital PRBS can be generated by applying the logical XOR function between the output of the register and a tap point and feeding the logical result back into the start of the register [4]. We use two TOAD all-optical switching gates [5] to create the all-optical PRBS architecture. One TOAD is used for the XOR function and the other acts as a wavelength converter and all-optical regenerator. The PRBS output depends on the number of pulses m in the shift register and the tap position n (n&lt;m). At present, the experimental latency is several hundred bits at a IGHz clock rate and so we use multiples of lower length sequences in order to measure the performance of the design. We have experimentally demonstrated a maximal length 231-1 PRBS ({m,n}={713,552} ≡ 23 x {m,n}={31,24}) and also sub-maximal sequences. The figure below shows a digitally sampled part of the maximal 231-1 PRBS. The apparent amplitude modulation of the pulses is an artefact of the relatively low sampling rate (400Msamples/s). We were only able to record short temporal sequences since the repeat period of the PRBS is ~50s.