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Editorial

ASME J of Medical Diagnostics. 2018;1(4):040201-040201-3. doi:10.1115/1.4041422.
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Ultrasound has been one of the most widely adopted and rapidly developing diagnosis and therapy modalities because of its nondestructive and nonion radiative nature since the first published medical ultrasound paper in 1942.1 Ultrasound transducers, as key components in ultrasound instruments, have been developed from single element transducers to two-dimensional (2D) arrays with thousands of elements [1]2 toward the goal of real-time imaging with desired resolution and imaging depth or sufficient acoustic energy for spatially and temporally controlled therapies. Generally, in the field of medical imaging, high-resolution, super-resolution or super-harmonic imaging, etc., demand high frequency, broadband, or multifrequency transducers [26] in the form of single element or arrays. Arrays with a relatively large number of elements are usually preferred in real-time three-dimensional (3D) imaging including ultrafast imaging [1].2 In focused ultrasound, arrays with a large number of elements for imaging guided therapy with precise spatial control are desirable [7,8]. In recent years, in addition to imaging and focused ultrasound therapy (or high intensity focused ultrasound), pulsed ultrasound or low intensity ultrasound for particle manipulation and therapy including neural stimulation has received tremendous research attention [913]. The power intensity of pulsed ultrasound is usually higher than that of imaging ultrasound, but much lower than that of focused ultrasound or HIFU. As new medical ultrasound applications are booming, challenges for ultrasound transducers must be taken well by the community.

Commentary by Dr. Valentin Fuster

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
ASME J of Medical Diagnostics. 2018;1(4):041006-041006-8. doi:10.1115/1.4041421.

Infrared (IR) breast thermography has been associated with the early detection of breast cancer (BC). However, findings in previous studies have been inconclusive. The upright position of subjects during imaging introduces errors in interpretation, because it blocks the optical access in the inframammary fold region and alters the temperature due to contact between breast and chest wall. These errors can be avoided by imaging breasts in prone position. Although the numerical simulations provide insight into thermal characteristics of the female breast with a tumor, most simulations in the past have used cubical and hemispherical breast models. We hypothesize that a breast model with the actual breast shape will provide true thermal characteristics that are useful in tumor detection. A digital breast model in prone position is developed to generate the surface temperature profiles for breasts with tumors. The digital breast model is generated from sequential magnetic resonance imaging (MRI) images and simulations are performed using finite volume method employing Pennes bioheat equation. We investigated the effect of varying the tumor metabolic activity on the surface temperature profile. We compared the surface temperature profile for various tumor metabolic activities with a case without tumor. The resulting surface temperature rise near the location of the tumor was between 0.665 and 1.023 °C, detectable using modern IR cameras. This is the first time that numerical simulations are conducted in a model with the actual breast shape in prone position to study the surface temperature changes induced by BC.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041007-041007-9. doi:10.1115/1.4041463.

Cryotherapy is commonly used for the management of soft tissue injury. The dose effect of the applied cooling temperature has not been quantified previously. Six subjects were exposed during five different experiments to local skin temperatures of 16.6 °C, 19.8 °C, 24.7 °C, 27.3 °C, and 37.2 °C for 1 h of active heat transfer followed by 2 h of passive environmental interaction. Skin blood perfusion and temperature were measured continuously at treatment and control sites. All treatments resulted in significant changes in cutaneous vascular conductance (CVC, skin perfusion/mean arterial pressure) compared to baseline values. The drop in CVC for cooling to both 19.8 °C and 16.6 °C was significantly larger than for 27.3 °C (P < 0.05 and P < 0.0005, respectively). The depression of CVC for cooling to 16.6 °C was significantly larger than at 24.7 °C (P < 0.05). Active warming at 37.2 °C produced more than a twofold increase in CVC (P < 0.05). A simulation model was developed to describe the coupled effects of exposure time and temperature on skin perfusion. The model was applied to define an equivalent cooling dose defined by exposure time and temperature that produced equivalent changes in skin perfusion. The model was verified with data from 22 independent cryotherapy experiments. The equivalent doses were applied to develop a nomogram to identify therapeutic time and temperature combinations that would produce a targeted vascular response. The nomogram may be applied to design cryotherapy protocols that will yield a desired vascular response history that may combine the benefits of tissue temperature reduction while diminishing the risk of collateral ischemic injury.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041008-041008-6. doi:10.1115/1.4041503.

The anterior band of the ulnar collateral ligament (UCL) is commonly subjected to repetitive stress in overhead-throwing athletes, causing high subfailure strain and change in mechanical properties of the ligament. Understanding the change in UCL mechanical properties after repetitive loading can help to evaluate the health status of UCL. The objective of this study was to evaluate changes in UCL shear modulus in overhead-throwing, Division I college-level athletes over the course of a competitive season using ultrasound shear wave elastography (SWE). The proposed protocol quantified changes in shear modulus of UCL in 17 baseball players at preseason and season-end time points as well as in five football quarterbacks at preseason, midseason, and season-end time points. The highest shear modulus values were obtained in the nondominant arm at preseason time points in both groups of athletes. The average UCL shear modulus at the season-end decreased by 39.35% and 37.96% compared to the preseason values in dominant and nondominant arms, respectively. This study shows that SWE could quantify changes in the shear modulus of the UCL after repetitive loading, suggesting that it could be a useful clinical tool for evaluating the risk of UCL injury. Further research on injured overhead-throwing athletes is warranted.

Commentary by Dr. Valentin Fuster
ASME J of Medical Diagnostics. 2018;1(4):041009-041009-9. doi:10.1115/1.4041502.

Photothermal therapy (PTT) has been emerging as an effective, minimally invasive approach to treat cancers. However, a method to quantitatively evaluate the treatment effect after laser-induced thermotherapy (LITT) is needed. In this study, we used 808 nm laser radiation with three different power densities to treat the breast cancer tissue from 4T1 cell lines in a mouse model. The viscoelastic properties of the treated cancer tissues were characterized by a two-term Prony series using a ramp-hold indentation method. We observed that instantaneous shear modulus $G0$ was significantly higher for the treated cancer tissues than that of the untreated tissue when treated with a power density of 1.5 W/cm2, but significantly lower with a power density of 2.5 W/cm2. The long-term shear modulus $G∞$ was also significantly higher for the cancer tissue at 1.5 W/cm2, compared to the untreated tissue. The treatment effects were verified by estimating the cell apoptosis rate using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Our results indicate that the viscoelastic properties of the tissue could potentially be used as biomarkers for evaluating the LITT treatment effect. In addition, we also observed a strain-independent behavior of the treated cancer tissue, which provided useful information for applying in vivo imaging method such as magnetic resonance elastography (MRE) for treatment evaluation based on biomechanical properties.

Commentary by Dr. Valentin Fuster