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Research Papers

ASME J of Medical Diagnostics. 2018;1(4):041001-041001-8. doi:10.1115/1.4040498.

Treatment of vision-threating elevated intraocular pressure (IOP) for severe glaucoma may require implantation of a glaucoma drainage device (GDD) to shunt aqueous humor (AH) from the anterior chamber of the eye and lower IOP to acceptable levels between 8 and 21 mm Hg. Nonvalved GDDs (NVGDDs) cannot maintain IOP in that acceptable range during the early postoperative period and require intra-operative modifications for IOP control during the first 30 days after surgery. Other GDDs have valves to overcome this issue, but are less successful with maintaining long-term IOP. Our research goal is to improve NVGDD postoperative performance. Little rigorous research has been done to systematically analyze flow/pressure characteristics in NVGDDs. We describe an experimental system developed to assess the pressure drop for physiologic flow rates through NVGDD-like microtubes of various lengths/diameters, some with annular inserts. Experimental pressure measurements for flow through hollow microtubes are within predictive theory's limits. For instance, a 50.4 μm inner diameter microtube yields an average experimental pressure of 33.7 mm Hg, while theory predicts 31.0–64.2 mm Hg. An annular example, with 358.8 μm outside and 330.7 μm inside diameters, yields an experimental pressure of 9.6 mm Hg, within theoretical predictions of 4.2–19.2 mm Hg. These results are repeatable and consistent over 25 days, which fits the 20–35 day period needed for scar tissue formation to achieve long-term IOP control. This work introduces a novel method for controlling IOP and demonstrates an experiment to examine this over 25 days. Future efforts will study insert size and degradable inserts.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041002-041002-10. doi:10.1115/1.4040470.

Skin thermal burn wounds are classified according to subjective assessments of wound depth that indicate divergent modes of medical intervention. However, clinically discriminating superficial partial from deep partial thickness burns remains a significant challenge, where only the latter requires excision and skin grafting. Motivated by the need for and ramifications of an objective burn wound assessment tool, this paper advances hyperspectral imaging (HSI) in a porcine skin burn model to quantitatively evaluate thermal burn injuries (superficial and deep partial thickness burns). Two-dimensional (2D) principal component analysis for noise reduction is applied to images captured by HSI in the visible wavelength range. Herein, a multivariate regression analysis is used to calculate the total hemoglobin concentration (tHb) and the oxygen saturation (StO2) of the injured tissue. These perfusion profiles are spatially mapped to yield characteristic distributions corresponding to the burn wound degree validated histologically. The results demonstrate that StO2 and tHb diverge significantly for superficial partial and deep partial burns at 24 h and 1 h, respectively (p < 0.05). A StO2 burn map at 1 h post-burn yields a 2D burn contour that is registered with a burn color image. This early stage burn-specific contour has implications to guide downstream burn excision and grafting.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041003-041003-7. doi:10.1115/1.4040589.

The inability to discern between pathology and physiological variability is a key issue in cardiac electrophysiology since this prevents the use of minimally invasive acquisitions to predict early pathological behavior. The goal of this work is to demonstrate how experimentally calibrated populations of models (ePoM) may be employed to inform which cellular-level pathologies are responsible for abnormalities observed in organ-level acquisitions while accounting for intersubject variability; this will be done through an exemplary computational and experimental approach. Unipolar epicardial electrograms (EGM) were acquired during an ex vivo porcine heart experiment. A population of the Ten Tusscher 2006 model was calibrated to activation–recovery intervals (ARI), measured from the electrograms, at three representative times. The distributions of the parameters from the resulting calibrated populations were compared to reveal statistically significant pathological variations. Activation–recovery interval reduction was observed in the experiments, and the comparison of the calibrated populations of models suggested a reduced L-type calcium conductance and a high extra-cellular potassium concentration as the most probable causes for the abnormal electrograms. This behavior was consistent with a reduction in the cardiac output (CO) and was confirmed by other experimental measurements. A proof of concept method to infer cellular pathologies by means of organ-level acquisitions is presented, allowing for an earlier detection of pathology than would be possible with current methods. This novel method that uses mathematical models as a tool for formulating hypotheses regarding the cellular causes of observed organ-level behaviors, while accounting for physiological variability has been unexplored.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041004-041004-12. doi:10.1115/1.4040817.

This paper presents the design evolution, fabrication, and testing of a novel patient and organ-specific, three-dimensional (3D)-printed phantom for external beam radiation therapy (EBRT) of prostate cancer. In contrast to those found in current practice, this phantom can be used to plan and validate treatment tailored to an individual patient. It contains a model of the prostate gland with a dominant intraprostatic lesion (DIL), seminal vesicles, urethra, ejaculatory duct, neurovascular bundles, rectal wall, and penile bulb generated from a series of combined T2-weighted/dynamic contrast-enhanced magnetic resonance (MR) images. The iterative process for designing the phantom based on user interaction and evaluation is described. Using the CyberKnife System at Boston Medical Center, a treatment plan was successfully created and delivered. Dosage delivery results were validated through gamma index calculations based on radiochromic film measurements which yielded a 99.8% passing rate. This phantom is a demonstration of a methodology for incorporating high-contrast MR imaging into computed-tomography-based radiotherapy treatment planning; moreover, it can be used to perform quality assurance (QA).

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041005-041005-10. doi:10.1115/1.4041005.

The medical application of implant replacements to remedy the pain in joints has necessitated a comprehensive study of wear due to contact of implant surfaces. Excessive wear can lead to toxicity and other implant associated medical issues such as patient discomfort and decreased mobility. Since implant wear is the result of contact between surfaces of tibia and talus implant, it is important to establish a model that can address implant surface contact mechanics with roughness effects. In this research, a statistical contact model is developed for the interaction of tibia and talus including normal and lateral contact in which surface roughness effects are included. The model accounts for the elastic–plastic interaction of the implant surface with roughness. For this purpose, tibia and talus implants are considered as macroscopic surfaces containing micron-scale roughness. Approximate equations are obtained that relate the contact force to the mean surface separation explicitly. Closed-form equations are obtained for hysteretic energy loss in implant using the approximate equations. Such a function can serve as a very useful tool for implant designers and manufacturers. Natural frequencies of both adduction-abduction and planter-dorsiflexion rotations are obtained using nonlinear vibration analyses.

Commentary by Dr. Valentin Fuster

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