Bryan Nowroozi

THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10 × higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

THz and mm-Wave Sensing of Corneal Tissue Water Content: Electromagnetic Modeling and Analysis

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.

Active THz medical imaging using broadband direct detection

Research in THz imaging is generally focused on three primary application areas: medical, security, and nondestructive evaluation (NDE). While work in THz security imaging and personnel screening is populated by a number of different active and passive system architectures, research in medical imaging in is generally performed with THz time-domain systems. These systems typically employ photoconductive or electro-optic source/detector pairs and can acquire depth resolved data or spectrally resolved pixels by synchronously sampling the electric field of the transmitted/reflected waveform. While time-domain is a very powerful scientific technique, results reported in the literature suggest that desired THz contrast in medical imaging may not require the volume of data accessible from time-resolved measurements and that a simpler direct detection, active technique may be sufficient for specific applications. In this talk we discuss an active direct detection reflectometer system architecture operating at a center frequency of ~ 525 GHz that uses a photoconductive source and schottky diode detector. This design takes advantage or radar-like pulse rectification and novel reflective optical design to achieve high target imaging contrast with significant potential for high speed acquisition time. Results in spatially resolved hydration mapping of burn wounds are presented and future outlooks discussed.

Importance of mechanics and kinematics in determining the stiffness contribution of the vertebral column during body-caudal-fin swimming in fishes ☆

Whole-body stiffness in fishes has important consequences for swimming mode, speed and efficiency, but the contribution of vertebral column stiffness to whole-body stiffness is unclear. In our opinion, this lack of clarity is due in part to the lack of studies that have measured both in vitro mechanical properties of the vertebral column as well as in vivo vertebral kinematics in the same species. Some lack of clarity may also come from real variation in the mechanical role of the vertebral column across species. Previous studies, based on either mechanics or kinematics alone, suggest species-specific variation in vertebral column locomotor function that ranges from highly stiff regimes that contribute greatly to whole-body stiffness, and potentially act as a spring, to highly compliant regimes that only prohibit excessive flexion of the intervertebral joints. We review data collected in combined investigations of both mechanics and kinematics of three species, Myxine glutinosa, Acipenser transmontanus, and Morone saxatilis, to illustrate how mechanical testing within the context of the in vivo kinematics more clearly distinguishes the role of the vertebral column in each species. In addition, we identify species for which kinematic data are available, but mechanical data are lacking. We encourage further investigation of these species to fill these mechanical data gaps. Finally, we hope these future combined analyses will identify certain morphological, mechanical, or kinematic parameters that might be associated with certain vertebral column functional regimes with respect to body stiffness.

Analysis of flexible substrates for clinical translation of laser-generated shockwave therapy

Bacteria biofilms in chronically infected wounds significantly increase the burden of healthcare costs and resources for patients and clinics. Because biofilms are such an effective barrier to standard antibiotic treatment, new methods of therapy need to be developed to combat these infections. Our group has demonstrated the potential of using Laser Generated Shockwaves as a potential therapy to mechanically disrupt the bacterial biofilms covering the wound. Previous studies have used rigid silica glass as the shockwave propagation medium, which is not compatible with the intended clinical application. This paper describes the exploration of five candidate flexible plastic films to replace the glass substrate. Each material measured 0.254 mm thick and was used to generate shockwaves of varying intensities. Shockwave characterization was performed using a high-speed Michelson displacement interferometer and peak stress values obtained in the flexible substrates were compared to glass using one-way nested Analysis of Variance and Tukey HSD post-hoc analysis. Results demonstrate statistically significant differences between substrate material and indicate that polycarbonate achieves the highest peak stress for a given laser fluence suggesting that it is optimal for clinical applications.

Pilot evaluation of wearable tactile biofeedback system for gait rehabilitation in peripheral neuropathy

Peripheral neuropathy (PN) is a significant public health concern, giving rise to abnormal gait biomechanics, diminished postural stability, and increased risk of falls. A wearable tactile feedback system previously developed for sensory augmentation of prosthetic limbs has been adapted for individuals with PN and evaluated in a pilot group of four subjects with idiopathic bilateral PN. Subjects were assessed both for their abilities to perceive and distinguish tactile stimuli, and for the effect of tactile biofeedback on gait, using optical motion capture and embedded force plate technology. Preliminary data indicate that participants could adequately perceive and localize tactile stimuli, as well as make meaningful modifications to their gait in real time, with minimal training. Observed gait modifications with feedback active included increases in walking speed, step cadence, step length, and peak joint powers. However, the variability of biofeedbacks effect on gait from subject to subject demands further investigation with the peripheral neuropathy patient population.

Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast generation to support the translation of this technology to clinical application. The hydration contrast sensing capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H), are well established and provide measures of mobile water content, lending MRI as a suitable method to validate hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.

Effect of laser generated shockwaves 1 on ex-vivo pigskin.

Persistent bacterial infection prolongs hospitalizations, leading to increased healthcare costs. Treatment of these infections costs several billion dollars annually. Biofilm production is one mechanism by which bacteria become resistant. With the help of biofilms, bacteria withstand the host immune response and are much less susceptible to antibiotics. Currently, there is interest in the use of laser‐generated shockwaves (LGS) to delaminate biofilm from infected wound surfaces; however, the safety of such an approach has not yet been established. Of particular concern are the thermal and mechanical effects of the shockwave treatment on the epidermis and the underlying collagen structure of the dermis. The present study is a preliminary investigation of the effect of LGS on freshly harvested ex vivo porcine skin tissue samples.

Fast-scanning THz medical imaging system for clinical application

Applications for terahertz (THz) medical imaging have proliferated over the past few years due to advancements in source/detector technology and vigorous application development. While considerable effort has been applied to improving source output power and detector sensitivity, significantly less work has been devoted to improving image acquisition method and time. The majority of THz medical imaging systems in the literature typically acquire pixels by translating the target of interest beneath a fixed illumination beam. While this single-pixel whiskbroom methodology is appropriate for in vitro models, it is unsuitable for in vivo large animal and patient imaging due to practical constraints. This paper presents a scanned beam imaging system based on prior work that enables for reduced image acquisition time while allowing the source, target and detector to remain stationary. The system employs a spinning polygonal mirror and a set of high-density polyethylene (HDPE) objective lenses, and operates at a center illumination frequency of 525GHz with ~125GHz of 3dB bandwidth. The system achieves a focused beam diameter of 1.66mm and a large depth of field of <25 mm. Images of characterization targets and ex vivo tissue samples are presented and compared to results obtained with conventional fixed beam scanning systems.

Acoustic characterization of low intensity focused ultrasound system through skull

Low Intensity Focused Ultrasound (LIFU) continues to gain traction in the field of non-invasive neuromodulation. Recent in vivo rat studies suggest that LIFU can be used to modulate region-specific brain activity in the motor cortex, leading investigators to conclude that LIFU may be a better alternative to more prominent, and more invasive, mechanisms of neuromodulation for conditions such as Parkinson’s disease, Epilepsy, and applications such as drug delivery applications. Despite these recent successes, a comprehensive understanding of beam patterns within the skull remains elusive.