Joseph L. Hollmann

Computational microscopy in embryo imaging

The growth of computing power has greatly improved our ability to extract quantitative information about complicated three-dimensional structures from microscope images. New hardware techniques are also being developed to provide suitable images for these tasks. However, a need exists for synthetic data to test these new developments. The work reported here was motivated by studies of embryo health, but similar needs exist across the field of microscopy. We report a rigorous computer model, based on Maxwells equations, that can produce the required synthetic images for bright-field, differential interference contrast, interferometric imaging, and polarimetric imaging. After a description of the algorithm, sample results are presented, followed by a discussion of future plans and applications.

Analysis and modeling of an ultrasound-modulated guide star to increase the depth of focusing in a turbid medium

Abstract. The effects of strong scattering in tissue limit the depth to which light may be focused. However, it has been shown that scattering may be reduced utilizing adaptive optics with a focused ultrasound (US) beam guidestar. The optical signal traveling through the US beam waist is frequency shifted and may be isolated with demodulation. This paper utilizes a multiphysics simulation to model the optical and US interactions in both synthetic tissue and random scattering media. The results illustrate that optical energy may be focused within a turbid medium utilizing a US guidestar. The results also suggest that optical energy travels preferentially along optical channels within a turbid medium.

Diffusion model for ultrasound-modulated light

Abstract. Researchers use ultrasound (US) to modulate diffusive light in a highly scattering medium like tissue. This paper analyzes the US–optical interaction in the scattering medium and derives an expression for the US-modulated optical radiance. The diffusion approximation to the radiative transport equation is employed to develop a Green’s function for US-modulated light. The predicted modulated fluence and flux are verified using finite-difference time-domain simulations. The Green’s function is then utilized to illustrate the modulated reflectance as the US–optical interaction increases in depth. The intent of this paper is to focus on high US frequencies necessary for high-resolution imaging because they are of interest for applications such as phase conjugation.

Imaging beyond scattering limits utilizing ARF as a guidestar

Optical imaging modalities are proved to be able to provide images with resolution required to image subcellular particles, however, imaging depth of optical imaging modalities are limited due to strong absorption and scattering. In contrast, ultrasound imaging modalities can provide images deeper in the tissue due to negligible scattering in tissue, but they suffer from poor resolution and contrast. Hybrid imaging modalities such as ultrasound modulated optical tomography (UOT) utilize advantages of both optical and ultrasound imaging modalities. UOT utilizes pressure waves to modulate light with ultrasound frequency that results in a week signal that requires expensive detection equipment. In Contrast, we propose to use acoustic radiation force (ARF) to tag the light that travels through the ultrasound focal spot and generate a stronger signal. Monitoring the changes in the speckle pattern reflects both mechanical and thermal properties of the medium. In this paper we have utilized our model with fixed-particle Monte Carlo to simulate the mean irradiance change (MIC) signal variations due to particle displacement and temperature rise. Results suggest that neglecting the temperature rise for short ultrasound exposure times, the change in the MIC signal reflects the local stiffness of the medium at the ultrasound focal spot and can be utilized to generate the stiffness image of the medium.

Near Infrared Spectroscopy for Measuring Changes in Bone Hemoglobin Content after Exercise in Individuals with Spinal Cord Injury

Bone blood perfusion has an essential role in maintaining a healthy bone. However, current methods for measuring bone blood perfusion are expensive and highly invasive. This study presents a custom built near‐infrared spectroscopy (NIRS) instrument to measure changes in bone blood perfusion. We demonstrated the efficacy of this device by monitoring oxygenated and deoxygenated hemoglobin changes in the human tibia during and after exercise in able‐bodied and in individuals with spinal cord injury (SCI), a population with known impaired peripheral blood perfusion. Nine able‐bodied individuals and six volunteers with SCI performed a 10 min rowing exercise (functional electrical stimulation rowing for those with SCI). With exercise, during rowing, able‐bodied showed an increase in deoxygenated hemoglobin in the tibia. Post rowing, able‐bodied showed an increase in total blood content, characterized by an increase in total hemoglobin content due primarily to an increase in deoxygenated hemoglobin. During rowing and post‐rowing, those with SCI showed no change in total blood content in the tibia. The current study demonstrates that NIRS can non‐invasively detect changes in hemoglobin concentration in the tibia.

Enhanced tagging of light utilizing acoustic radiation force with speckle pattern analysis.

Abstract. In optical imaging, the depth and resolution are limited due to scattering. Unlike light, scattering of ultrasound (US) waves in tissue is negligible. Hybrid imaging methods such as US-modulated optical tomography (UOT) use the advantages of both modalities. UOT tags light by inducing phase change caused by modulating the local index of refraction of the medium. The challenge in UOT is detecting the small signal. The displacement induced by the acoustic radiation force (ARF) is another US effect that can be utilized to tag the light. It induces greater phase change, resulting in a stronger signal. Moreover, the absorbed acoustic energy generates heat, resulting in change in the index of refraction and a strong phase change. The speckle pattern is governed by the phase of the interfering scattered waves; hence, speckle pattern analysis can obtain information about displacement and temperature changes. We have presented a model to simulate the insonation processes. Simulation results based on fixed-particle Monte Carlo and experimental results show that the signal acquired by utilizing ARF is stronger compared to UOT. The introduced mean irradiance change (MIC) signal reveals both thermal and mechanical effects of the focused US beam in different timescales. Simulation results suggest that variation in the MIC signal can be used to generate a displacement image of the medium.

Bone optical spectroscopy for the measurement of hemoglobin content

Osteoporosis is a common side effect of spinal cord injuries. Blood perfusion in the bone provides an indication of bone health and may help to evaluate therapies addressing bone loss. Current methods for measuring blood perfusion of bone use dyes and ionizing radiation, and yield qualitative results. We present a device capable of measuring blood oxygenation in the tibia. The device illuminates the skin directly over the tibia with a white light source and measures the diffusely reflected light in the near infrared spectrum. Multiple source-detector distances are utilized so that the blood perfusion in skin and bone may be differentiated.

A model for ultrasound modulated light in a turbid medium

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Researchers have investigated using both ultrasound (US) and light synergistically to overcome this difficulty. Ultrasound has been utilized to modulated light within tissue to create a diffusive wave at that is modulated at the US frequency. Recently, there has been interest in the modulated sidebands which reside at optical frequency plus or minus the US frequency. This paper will discuss a model for US-light interactions in a scattering medium. We will use this model to relate the radiance in the probe beam to the radiance in the diffusive wave. We will then employ the P-1 approximation to the radiative transport equation to find the fluence and flux of the modulated wave. We will use these parameters to write a diffusion equation for the modulated wave that can be described in terms of the incoming optical power, and the US intensity and geometry.

Analysis of phase conjugation in a turbid medium

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Recently, researchers have found they can concentrate light tightly despite these scattering effects by using a guidestar and optical phase conjugation to focus light to greater distances in tissue. An optical or probe signal is transmitted through a scattering medium and its resulting wavefront is detected. The wavefront is then conjugated and utilized as a new optical source or delivery wave that focuses back to the guidestars location with minimal scattering. The power in the delivery wave may be greatly increased for enhanced energy delivery at the focus. Modulation by an ultrasound (US) beam may be utilized to generate the guidestar dynamically and allow for US-resolution at depths of several millimeters. The delivery wave is successful at focusing light back at the guidestar because it creates constructive interference at the desired focus. However, if the phases of the field contributions change, we expect the delivered power at the focus to be reduced. This paper will analyze the robustness of this method when the probe beam is at one wavelength and the delivery wave is at another. This will allow us to characterize the deleterious effects of varying the phase contributions at the focus.

An innovative processing method for high resolution borehole density images

This technique has been successfully applied to wells drilled in the North Sea and North America. Figures 3 and 4 illustrate two examples processed using our technique. Images of selected energy windows, compensated bulk density, and PE are compared with conventional processing.