Laser speckle imaging in the spatial frequency domain

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects. First, depth sensitive speckle contrast is shown in phantoms by separating a deep source (4 mm) from a shallow source (2 mm) of speckle contrast by using a high spatial frequency of illumination (0.24 mm−1). We develop an SFD adapted correlation diffusion model and show that with high frequency (0.24 mm−1) illumination, doubling of absorption contrast results in only a 1% change in speckle contrast versus 25% change using a planar unmodulated (0 mm−1) illumination. Similar absorption change is mimicked in vivo imaging a finger occlusion and the relative speckle contrast change from baseline is 10% at 0.26 mm−1 versus 60% at 0 mm−1 during a finger occlusion. These results underscore the importance of path length and optical properties in determining speckle contrast. They provide an integrated approach for simultaneous mapping of blood flow (speckle contrast) and oxygenation (optical properties) which can be used to inform tissue metabolism

Spatial Frequency Domain Imaging of Intrinsic Optical Property Contrast in a Mouse Model of Alzheimer’s Disease

Extensive changes in neural tissue structure and function accompanying Alzheimer’s disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD appearance and progression. In this work, we report the development of a wide-field spatial frequency domain imaging (SFDI) method for non-contact, quantitative in vivo optical imaging of brain tissue composition and function in a triple transgenic mouse AD model (3xTg). SFDI was used to generate optical absorption and scattering maps at up to 17 wavelengths from 650 to 970 nm in 20-month-old 3xTg mice (n = 4) and age-matched controls (n = 6). Wavelength-dependent optical properties were used to form images of tissue hemoglobin (oxy-, deoxy-, and total), oxygen saturation, and water. Significant baseline contrast was observed with 13–26% higher average scattering values and elevated water content (52 ± 2% vs. 31 ± 1%); reduced total tissue hemoglobin content (127 ± 9 μM vs. 174 ± 6 μM); and lower tissue oxygen saturation (57 ± 2% vs. 69 ± 3%) in AD vs. control mice. Oxygen inhalation challenges (100% oxygen) resulted in increased levels of tissue oxy-hemoglobin (ctO2Hb) and commensurate reductions in deoxy-hemoglobin (ctHHb), with ~60–70% slower response times and ~7 μM vs. ~14 μM overall changes for 3xTg vs. controls, respectively. Our results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology

Commercialization of Modulated Imaging

Modulim (previously Modulated Imaging) is dedicated to bringing optical technologies to the clinical for the non-invasive and rapid assessment of tissue health. We have received 510(k) clearance for two medical devices, with an indication to determine oxygenation levels in superficial tissues for patients with potential circulatory compromise. Our devices are currently the only FDA-cleared systems that uses spatial frequency domain imaging (SFDI) as the underlying measurement method. SFDI uses structured illumination to quantify tissue optical properties over large fields of view. SFDI was developed by researchers at the Beckman Laser Institute and Medical Clinic, and a number of labs have continued to publish on the promise of this technology for assessment of tissue health. In this talk, we will share our experiences in translating technology from an academic lab, building the infrastructure to gain regulatory clearance, and the hurdles we face for going to market. Our translation challenges included finding time and money for technology validation, market evaluation, and risk mitigation. Challenges in building infrastructure included implementation of an appropriate quality system, execution of a regulatory strategy, and incorporation of scalable procedures. Of note, our regulatory work included careful choices for component-wise benchtop verification testing along with pre-clinical and clinical validation to establish substantial equivalence of our device to a predicate device. Lastly, we will cover the challenges faced for our go to market device, the Clarifi Imaging System. These challenges include product/workflow fit, reimbursement, and customer support. A common theme that has been true in all of these phases of growth: investment in individuals to enhance and compliment our team strengths

Spatial frequency domain imaging in 2019: principles, applications, and perspectives

International audienceSpatial frequency domain imaging (SFDI) has witnessed very rapid growth over the last decade, owing to its unique capabilities for imaging optical properties and chromophores over a large field-of-view and in a rapid manner. We provide a comprehensive review of the principles of this imaging method as of 2019, review the modeling of light propagation in this domain, describe acquisition methods, provide an understanding of the various implementations and their practical limitations, and finally review applications that have been published in the literature. Importantly, we also introduce a group effort by several key actors in the field for the dissemination of SFDI, including publications, advice in hardware and implementations, and processing code, all freely available online

Special Section Guest Editorial: Special Section on Spatial Frequency Domain Imaging.

This guest editorial introduces the Special Section on Spatial Frequency Domain Imaging

Quantitative optical tomography of sub-surface heterogeneities using spatially modulated structured light

We present a wide-field method for obtaining three-dimensional images of turbid media. By projecting patterns of light of varying spatial frequencies on a sample, we reconstruct quantitative, depth resolved images of absorption contrast. Images are reconstructed using a fast analytic inversion formula and a novel correction to the diffusion approximation for increased accuracy near boundaries. The method provides more accurate quantification of optical absorption and higher resolution than standard diffuse reflectance measurements. (C) 2009 Optical Society of Americ

Three-dimensional surface profile intensity correction for spatially modulated imaging.

We describe a noncontact profile correction technique for quantitative, wide-field optical measurement of tissue absorption (microa) and reduced scattering (micros) coefficients, based on geometric correction of the sample's Lambertian (diffuse) reflectance intensity. Because the projection of structured light onto an object is the basis for both phase-shifting profilometry and modulated imaging, we were able to develop a single instrument capable of performing both techniques. In so doing, the surface of the three-dimensional object could be acquired and used to extract the object's optical properties. The optical properties of flat polydimethylsiloxane (silicone) phantoms with homogenous tissue-like optical properties were extracted, with and without profilometry correction, after vertical translation and tilting of the phantoms at various angles. Objects having a complex shape, including a hemispheric silicone phantom and human fingers, were acquired and similarly processed, with vascular constriction of a finger being readily detectable through changes in its optical properties. Using profilometry correction, the accuracy of extracted absorption and reduced scattering coefficients improved from two- to ten-fold for surfaces having height variations as much as 3 cm and tilt angles as high as 40 deg. These data lay the foundation for employing structured light for quantitative imaging during surgery