Absorption spectra of early stool from preterm infants need to be considered in abdominal NIRS oximetry.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of the preterm infant. Low abdominal tissue oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) oximetry may be an early sign of NEC relevant for treating or even preventing NEC. However, current commercial NIRS oximeters provide inaccurate StO2 readings because they neglect stool as an abdominal absorber. To tackle this problem, we determined the optical properties of faeces of preterm infants to enable a correct abdominal StO2 measurement. In 25 preterm born infants (median age 31 0/7 ± 2 1/7 weeks, weight 1478 ± 511 g), we measured their first five stool probes with a VIS/NIR spectrometer and calculated the optical properties using the Inverse Adding Doubling (IAD) method. We obtained two absorption spectra representing meconium and transitional stool. Probabilistic cluster analysis correctly classified 96 out of 107 stool probes. The faeces spectra need to be considered to enable correct abdominal StO2 measurements with NIRS oximetry.

Spectral correction for handheld optoacoustic imaging by means of near-infrared optical tomography in reflection mode.

In vivo imaging of tissue/vasculature oxygen saturation levels is of prime interest in many clinical applications. To this end, the feasibility of combining two distinct and complementary imaging modalities is investigated: optoacoustics (OA) and near-infrared optical tomography (NIROT), both operating noninvasively in reflection mode. Experiments were conducted on two optically heterogeneous phantoms mimicking tissue before and after the occurrence of a perturbation. OA imaging was used to resolve submillimetric vessel-like optical absorbers at depths up to 25 mm, but with a spectral distortion in the OA signals. NIROT measurements were utilized to image perturbations in the background and to estimate the light fluence inside the phantoms at the wavelength pair (760 nm, 830 nm). This enabled the spectral correction of the vessel-like absorbers' OA signals: the error in the ratio of the absorption coefficient at 830 nm to that at 760 nm was reduced from 60%-150% to 10%-20%. The results suggest that oxygen saturation (SO 2 ) levels in arteries can be determined with <10% error and furthermore, that relative changes in vessels' SO 2 can be monitored with even better accuracy. The outcome relies on a proper identification of the OA signals emanating from the studied vessels.

Characterization of the optical properties of color pastes for the design of optical phantoms mimicking biological tissue.

Clinicians need a way to rapidly and reliably test the correct functioning of near-infrared spectroscopy (NIRS)-based oximeters. Therefore, optical phantoms for quality assessment of NIRS oximeters are needed. The fabrication of such phantoms that mimic the optical properties of biological tissue in the NIR range represents a challenge. To enable their development, the aim was to characterize the absorption and scattering spectra of different dyes. The optical properties of silicone SILPURAN 2420 with 11 color pastes of type ELASTOSIL were measured in the 500 to 1000 nm range by a spectrometer with an integrating sphere. In addition, two commercial frequency-domain NIRS devices, the ISS OxiplexTS and the ISS Imagent, were used to assess the optical properties at specific wavelengths. The evaluated colors present mostly features in the visible range below 650 nm, but two colors include peaks in the near-infrared region, simulating low tissue oxygenation values. These colors were used to create an optical phantom, which matched the designed StO2 value within an error of only 4%. This set of dyes already enables simulating many different spectra, thus achieving a first step on the way to a long-term stable comparison and validation method.

Discrimination of Complex Activation Patterns in Near Infrared Optical Tomography with Artificial Neural Networks.

Near-infrared optical tomography (NIROT) has great promise for many clinical problems. Here we focus on the study of brain function. During NIROT image reconstruction of brain activity, an inverse problem has to be solved that is sensitive to small superficial perturbations on the head such as e.g. birthmarks on the skin and hair. To consider these perturbations, standard physical modeling is unpractical, since it requires the implementation of detailed information that is generally unavailable. The aim here was to test whether artificial neural networks (ANN) are able to handle such perturbations and thus detect brain activity correctly. For simplicity, we created a virtual test model, where we simulated a pattern of activated and resting brain regions, which was covered by skin features like hair or melanin. We compared the performance of this ANN approach with that of an inverse problem based on a Monte Carlo (MC) model for light propagation. We conclude that ANNs tolerate substantially higher levels of skin perturbations than MC models and consequently are more suitable for detecting brain activity.

A New Method Based on Virtual Fluence Detectors and Software Toolbox for Handheld Spectral Optoacoustic Tomography.

A minimal setup for optoacoustic (OA) imaging requires an ultrasound probe and a pulsed laser. Such a system is capable of imaging small blood vessels and is sensitive to variations in their oxygen saturation. However, absolute oxygenation values cannot be obtained without a proper correction for the varying light fluence resulting from the optical attenuation in the surrounding tissue. Other techniques, such as near-infrared optical tomography (NIROT) can be employed to assist OA imaging for fluence compensation. In this paper, we propose using blood vessels as virtual fluence detectors (VD), which serve as light detectors for NIROT image reconstructions. By avoiding the use of real photon detectors, a simpler system could be implemented in a hand-held device comparable in size with conventional ultrasound probes. Even for a low number of VDs it provides increased informational value which, in combination with a large number of light sources, results in precise reconstructions. We define a tomographic inverse problem based on ratios of OA signals measured at several wavelengths where optical properties of VDs, tumor and normal tissue can be reconstructed simultaneously. The use of ratio data effectively removes light source skin coupling errors for the case of emission in a single point, which is required for clinical applications. We have defined the mathematical structure of an inverse problem where chromophore concentrations for normal, tumor and embedded VDs are obtained simultaneously from this ratio data. To test the performance of our approach we show an image reconstruction on a virtual phantom with an embedded tumor in the vicinity of eight blood vessels. We conclude that this limited number of VDs, located in areas of maximum sensitivity result in high quality reconstructions. For the simplest case of a single blood vessel located in a homogeneous tissue, we present a graphical user interface based toolbox for conducting virtual experiments. The toolbox can be used to assist in the design and optimization of suitable hardware for different applications, among which imaging tumor oxygenation and ischemic lesions in the brain of preterm infants are of great clinical value.

Optical properties of mice's stool in 550 to 1000 nm wavelength range.

The aim of this work was to measure optical properties of stool of mice to provide this relevant wavelength-dependent behavior for optical imaging modalities such as fluorescent molecular tomography and near-infrared optical tomography. BALB/c nude female mice were studied and optical properties of the stool were determined by employing the inverse adding-doubling approach. The animals were kept on chlorophyll-free diet. Nine stool samples were measured. The wavelength-dependent behavior of absorption and scattering in 550 to 1000 nm range is presented. The reduced scattering spectrum is fitted to the Mie scattering approximation in the near-infrared (NIR) wavelength range and to the Mie + Rayleigh approximation in visible/NIR range with the fitting coefficients presented. The study revealed that the absorption spectrum of stool can lead to crosstalk with the spectrum of hemoglobin in the NIR range.

Development and Validation of a Sensor Prototype for Near-Infrared Imaging of the Newborn Brain.

Imaging brain oxygenation is crucial for preventing brain lesions in preterm infants. Our aim is to build and validate a near-infrared optical tomography (NIROT) sensor for the head of neonates. This sensor, combined with an optoacoustic device, will enable quantitative monitoring of the structural and functional information of the brain. Since the head of preterm infants is small and fragile great care must be taken to produce a comfortable and compact device in which a sufficient number of light sources and detectors can be implemented. Here we demonstrate our first prototype. Heterogeneous silicone phantoms were produced to validate the prototype's data acquisition, data processing, and image reconstruction. Reconstructed optical properties agree well with the target values. The mechanical performance of the new NIROT sensor prototype confirms its suitability for the clinical application.

A New Method Based on Graphics Processing Units for Fast Near-Infrared Optical Tomography.

The accuracy of images obtained by Diffuse Optical Tomography (DOT) could be substantially increased by the newly developed time resolved (TR) cameras. These devices result in unprecedented data volumes, which present a challenge to conventional image reconstruction techniques. In addition, many clinical applications require taking photons in air regions like the trachea into account, where the diffusion model fails. Image reconstruction techniques based on photon tracking are mandatory in those cases but have not been implemented so far due to computing demands. We aimed at designing an inversion algorithm which could be implemented on commercial graphics processing units (GPUs) by making use of information obtained with other imaging modalities. The method requires a segmented volume and an approximately uniform value for the reduced scattering coefficient in the volume under study. The complex photon path is reduced to a small number of partial path lengths within each segment resulting in drastically reduced memory usage and computation time. Our approach takes advantage of wavelength normalized data which renders it robust against instrumental biases and skin irregularities which is critical for realistic clinical applications. The accuracy of this method has been assessed with both simulated and experimental inhomogeneous phantoms showing good agreement with target values. The simulation study analyzed a phantom containing a tumor next to an air region. For the experimental test, a segmented cuboid phantom was illuminated by a supercontinuum laser and data were gathered by a state of the art TR camera. Reconstructions were obtained on a GPU-installed computer in less than 2 h. To our knowledge, it is the first time Monte Carlo methods have been successfully used for DOT based on TR cameras. This opens the door to applications such as accurate measurements of oxygenation in neck tumors where the presence of air regions is a problem for conventional approaches.

Clinical evaluation of an anatomy-based patient specific quality assurance system.

The Delta(4DVH) Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta(4DVH) Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta(4DVH) Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta(4DVH) Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta(4DVH) Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta(4PT) QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta(4PT) GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta(4DVH) Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse).