BOSS™ – Brillouin Optical Scanner System

BOSS™ stands for Brillouin Optical Scattering System. It is a non-contact, confocal, high-resolution optical-scanning diagnostic platform targeted at identifying intrinsic biomechanical properties of transparent or opaque ocular tissues - such as the cornea, sclera or lens.

BRILLOUIN SCATTERING

Brillouin scattering is a phenomenon that arises from the interaction between incident light (e.g. a laser beam) and acoustic phonons* intrinsically present within the illuminated specimen (i.e., material or tissue). Acoustically induced inelastic light scattering, first reported in 1922 by Brillouin, allows non-contact, direct readout of the viscoelastic properties of a material and has widely been investigated for material characterization, structural monitoring and environmental sensing.

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The undisturbed part of the interaction is elastic scattered light (green), which needs to be eliminated in order to reveal the much weaker inelastically scattered Brillouin components (blue and orange). This is done in a spectrometer, where the frequency shift component ∆vB is measured. The resulting frequency shift of the incident and the scattered light (e.g., laser beams) define the Brillouin spectrum, which directly relate to the longitudinal elastic modulus at the probed location in the tissue.

Extending the Brillouin technique from point sampling light spectroscopy to a scanned imaging modality allows new possibilities for biomechanical imaging. BOSS™ makes use of this spontaneous Brillouin scattering effect by recording this frequency shift in dependence of its location. A technology that has proven challenging in the past due to the need of rapid spectrum acquisition, is now made available with BOSS™ for clinical use, and Intelon is poised to bring this in-vivo real-time biomechanical imaging methodology to eyecare practitioners around the world.

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* A "phonon" is a quantum of vibrational mechanical energy, just as a "photon" is a quantum of light energy. Acoustic phonons refer to in-phase vibration of neighboring atoms in a material. 

Elastic Modulus of Ocular TissueS

The material properties of the cornea are responsible for its functionality. The shape of the cornea relies on the equilibrium between its mechanical stiffness (resistance to deformation) and the forces acting upon it. The mechanical stiffness of the cornea depends on its geometry (thickness and topography) and material properties, which in-turn relies on the microstructure of its main layer: the stroma.

Viscoelastic materials exhibit characteristics of both viscosity and elasticity. In other words, the response of the cornea to a force such as the intraocular pressure (IOP) is dependent not only on the deformation in that moment at that specific location, but also at all previous times at the same location.

 Biomechanics Imaging with BOSS will address a large range of ophthalmic indications.

Biomechanics Imaging with BOSS will address a large range of ophthalmic indications.

Brillouin Spectroscopy used in a confocal setup allows to potentially probe biomechanical tissue properties from more posterior structures such as the lens or the vitreous and even the retina. Individually probed locations can then be joined to build spatially resolved profile or map images of stiffness in-vivo.

The Cornea

 Schematic view of a cut through a human cornea.

Schematic view of a cut through a human cornea.

For most ocular soft-tissues, collagen is often considered the primary biomechanical element as it provides tensile strength through its long and dense fibrous bundle organization. The ground substance matrix, wherein collagen fibers are embedded, contains the elastin fibers, proteoglycans, fibroblasts, tissue fluid and all other tissue constituents, except collagen.

The stroma comprises over 200 lamellae, which are formed of a proteoglycan-rich matrix containing tightly packed and ordered collagen fibrils. The arrangement and the density of collagen fibrils in the stroma are the primary contributors to the biomechanical stiffness of corneal tissue.

It is well documented in the literature that corneal tissue does not have a constant modulus of elasticity. Its modulus is non-linear and depends on the degree of deformation at the specific location. This means the more the cornea is deformed, the stiffer it becomes.

Responsible for this behavior is the organization (distribution and orientation) of collagen fibrils within the cellular matrix. The collagen fibrils distribution in the cornea is inhomogeneous, as it varies between the center of the cornea, and the periphery. Furthermore, the anterior section of the cornea has a different fiber structure than the deeper layers on the posterior cornea. Currently, there are no established non-invasive methods to measure the elastic properties of the cornea in-vivo. BOSS™ is here to change that.

 Biomechanics and Morphology. (a) Normal subjects. (b) Mild Keratoconus, (c) Advanced Keratoconus.  All: Top images are pachymetry (thickness) and topography (elevation and steepness) images recorded with the Oculus Pentacam; Below are measurements of BOSS™ stiffness with morphologically-matched regions of interest.

Biomechanics and Morphology. (a) Normal subjects. (b) Mild Keratoconus, (c) Advanced Keratoconus.

All: Top images are pachymetry (thickness) and topography (elevation and steepness) images recorded with the Oculus Pentacam; Below are measurements of BOSS™ stiffness with morphologically-matched regions of interest.

The Lens

 Schematic cut through a human crystalline lens.

Schematic cut through a human crystalline lens.

Increasing stiffness of the crystalline lens with age has since long been recognized as one of the major factors causing presbyopia - a failure of the eye to accommodate and focus on a nearby object. More recent studies indicate that lens stiffening alone can be responsible for the inability of the lens to change its refractive power at older age. BOSS™ can provide critical information on the progression of presbyopia and potential surgical or therapeutic interventions.

In experiments, stiffness of the lens center (nucleus) was found to depend on the type of cataract (clouding), and the age of the patient. Nuclear cataract lenses (clouding in the nucleus) were generally stiffer than those extracted from patients with predominantly cortical cataract (clouding in the cortex), with some in the latter group appearing not to differ significantly from age‐matched normals. At age 40‐50, the nuclear region of advanced nuclear cataract lenses was found to be approximately 46 times harder than that of normal lenses of the same age. By age 70‐80 the stiffness of advanced nuclear cataract lenses had doubled, however by this age, normal lenses had also increased significantly in stiffness so that the difference between cataract and normal lenses was much less pronounced; being a factor of approximately 2.5.

BOSS™ can provide new identification possibilities of the clouding process in cataract in different parts of the lens, and will potentially be useful in guidance and control of lens extraction surgery and therapeutic lens-softening procedures. 

 Age-related crystalline lens thickening. a) Model of thickening, b) Crystalline lens stiffness profiles measured with BOSS™ in 19-, 31-, 43-, and 61-year-old human showing the aqueous humor (A.H.), the vitreous humor (V.H.), the lens cortex, and lens nucleus plateau.

Age-related crystalline lens thickening. a) Model of thickening, b) Crystalline lens stiffness profiles measured with BOSS™ in 19-, 31-, 43-, and 61-year-old human showing the aqueous humor (A.H.), the vitreous humor (V.H.), the lens cortex, and lens nucleus plateau.


Publications

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The Ophthalmologist - March 2017

The Hubble Telescope of the Eye - the quest for truly non-invasive ocular biomechanical measurements.

IOVS - October 2016

In vivo Brillouin analysis of the aging human crystalline lens.

JAMA Ophthalmology – January 2015

In vivo Brillouin biomechanical mapping of normal and keratoconus corneas.

IOVS - February 2013

Brillouin microscopy of collagen crosslinking: non-contact depth-dependent analysis of corneal elastic modulus.

Optics Express – April 2012

In vivo Brillouin optical microscopy in the human eye.

Nature Photonics – January 2008

Confocal Brillouin microscopy for three-dimensional mechanical imaging. Fundamental report in Nature Photonics paper — authored by Intelon’s scientific founder, S.H. Andy Yun, Ph.D. — describing the core Intelon BOSS spectrometer technology, which enables safe and rapid biomechanical measurements in the human body.

And many more...