Patellar tendon biomechanical and morphologic properties and their relationship to serum clinical variables in persons with prediabetes and type 2 diabetes.

Tendon biomechanical properties and fibril organization are altered in patients with diabetes compared to healthy individuals, yet few biomarkers have been associated with in vivo tendon properties. We investigated the relationships between in vivo imaging-based tendon properties, serum variables, and patient characteristics across healthy controls (n = 14, age: 45 ± 5 years, body mass index [BMI]: 24 ± 1, hemoglobin A1c [HbA1c]: 5.3 ± 0.1%), prediabetes (n = 14, age: 54 ± 5 years, BMI: 29 ± 2; HbA1c: 5.7 ± 0.1), and type 2 diabetes (n = 13, age: 55 ± 3 years, BMI: 33 ± 2, HbA1c: 6.7 ± 0.3). We used ultrasound speckle-tracking and measurements from magnetic resonance imaging (MRI) to estimate the patellar tendon in vivo tangent modulus. Analysis of plasma c-peptide, interleukin-1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor-α (TNF-α), adiponectin, leptin, insulin-like growth factor 1 (IGF-1), and C-reactive protein (CRP) was completed. We built regression models incorporating statistically significant covariates and indicators for the clinically defined groups. We found that tendon cross-sectional area normalized to body weight (BWN CSA) and modulus were lower in patients with type 2 diabetes than in healthy controls (p < 0.05). Our regression analysis revealed that a model that included BMI, leptin, high-density lipoprotein (HDL), low-density lipoprotein (LDL), age, and group explained ~70% of the variability in BWN CSA (R2 = 0.70, p < 0.001). For modulus, including the main effects LDL, groups, HbA1c, age, BMI, cholesterol, IGF-1, c-peptide, leptin, and IL-6, accounted for ~54% of the variability in modulus (R2 = 0.54, p < 0.05). While BWN CSA and modulus were lower in those with diabetes, group was a poor predicter of tendon properties when considering the selected covariates. These data highlight the multifactorial nature of tendon changes with diabetes and suggest that blood variables could be reliable predictors of tendon properties.

Stretchable receive coil for 7T small animal MRI.

Receive coils used in small animal MRI are rigid, inflexible surface loops that do not conform to the anatomy being imaged. The recent trend toward design of stretchable coils that are tailored to fit any anatomical curvature has been focused on human imaging. This work demonstrates the application of stretchable coils for small animal imaging at 7T. A stretchable coil measuring 3.5 × 3.5 cm was developed for acquisition of rat brain and spine images. The SNR maps of the stretchable coil were compared with those of a traditional flexible PCB coil and a commercial surface coil. Stretch and conformance testing of the coil was performed. Ex vivo images of rat brain and spine from the stretchable a coil was acquired using T1 FLASH and T2 Turbo RARE sequences. The axial phantom SNR maps showed that the stretchable coil provided 48.5% and 42.8% higher SNR than the commercial coil for T1-w and T2-w images within the defined ROI. A 33% increase in average penetration depth was observed within the ROI using the stretchable coil when compared to the commercial coil. The ex-vivo rat brain and spine images showed distinguishable anatomical details. Stretching the coil reduced the resonant frequency with reduction in SNR, while the conformance to varying sample volumes increased the resonant frequency with decreased SNR. This study also features an open-source plug-and-play system with preamplifiers that can be used to interface surface coils with the 7T Bruker scanner.

Mechanistic Computational Modeling of Implantable, Bioresorbable Drug Release Systems.

Implantable, bioresorbable drug delivery systems offer an alternative to current drug administration techniques; allowing for patient-tailored drug dosage, while also increasing patient compliance. Mechanistic mathematical modeling allows for the acceleration of the design of the release systems, and for prediction of physical anomalies that are not intuitive and may otherwise elude discovery. This study investigates short-term drug release as a function of water-mediated polymer phase inversion into a solid depot within hours to days, as well as long-term hydrolysis-mediated degradation and erosion of the implant over the next few weeks. Finite difference methods are used to model spatial and temporal changes in polymer phase inversion, solidification, and hydrolysis. Modeling reveals the impact of non-uniform drug distribution, production and transport of H+ ions, and localized polymer degradation on the diffusion of water, drug, and hydrolyzed polymer byproducts. Compared to experimental data, the computational model accurately predicts the drug release during the solidification of implants over days and drug release profiles over weeks from microspheres and implants. This work offers new insight into the impact of various parameters on drug release profiles, and is a new tool to accelerate the design process for release systems to meet a patient specific clinical need.

Parametric Design of a 3D-Printed Removable Common-Mode Trap for Magnetic Resonance Imaging.

Radiofrequency coils are utilized during transmit and receive of MRI signals. Cable traps remove common-mode current from the coaxial cable shield, which helps improve the image quality and reduces risks of burns to the patient. Traditional cable traps use wounded coaxial cables that limit the flexibility in the design process. Floating cable traps were introduced which eliminated any physical connection between the trap and coaxial cable, allowing complete flexibility in design and placement. However, the design process of floating cable traps is iterative and may take several rounds of 3D modeling. This work seeks to optimize the design process through the use of parametric design methodologies. The proposed methodology allows for 3D printing the floating cable trap after inputting the design parameters. The cable trap was able to attenuate currents in the coaxial shields to -48 dB, highlighting its performance and design robustness.

American Football Position-Specific Neurometabolic Changes in High School Athletes: A Magnetic Resonance Spectroscopic Study.

Reports estimate between 1.6-3.8 million sports-related concussions occur annually, with 30% occurring in youth male American football athletes. Many studies report neurophysiological changes in these athletes, but the exact reasons for these changes remain elusive. Investigation of injury mechanics highlights a need to address how player position might impact these changes. Here, 55 high school American football athletes (20 linemen; 35 non-linemen) underwent magnetic resonance spectroscopy four times over the course of a football season-once prior to the season (Pre), twice during (In1, In2), and once following (Post) to quantify metabolites (N-acetyl aspartate, choline, creatine, myo-inositol, and glutamate/glutamine) in the dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1). Head acceleration events (HAEs) were monitored at each practice and game. Spectroscopic and HAE data were analyzed by imaging session and player position. Linear regression analyses were conducted between metabolite levels and HAEs, and metabolite levels in football athletes were compared with age-and gender-matched non-contact athletes. Across-season (i.e., between Pre and In1, In2, Post), different DLPFC and M1 metabolites decreased (p < 0.05) according to player position (i.e., linemen vs. non-linemen). The majority of regression results involved DLPFC metabolites in linemen, where metabolite levels were higher from Pre to Post, with increasing HAE load. Comparisons with control athletes revealed higher metabolite levels in football athletes both before and after the season. This study highlights the importance of player position when conducting analyses on American football athletes and demonstrates elevated DLPFC and M1 brain metabolites in football athletes compared with control athletes at both Pre and Post, suggesting potential HAE-related neurocompensatory mechanisms.

Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone.

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or ß-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/ß-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

Development of brain atlases for early-to-middle adolescent collision-sport athletes.

Human brains develop across the life span and largely vary in morphology. Adolescent collision-sport athletes undergo repetitive head impacts over years of practices and competitions, and therefore may exhibit a neuroanatomical trajectory different from healthy adolescents in general. However, an unbiased brain atlas targeting these individuals does not exist. Although standardized brain atlases facilitate spatial normalization and voxel-wise analysis at the group level, when the underlying neuroanatomy does not represent the study population, greater biases and errors can be introduced during spatial normalization, confounding subsequent voxel-wise analysis and statistical findings. In this work, targeting early-to-middle adolescent (EMA, ages 13-19) collision-sport athletes, we developed population-specific brain atlases that include templates (T1-weighted and diffusion tensor magnetic resonance imaging) and semantic labels (cortical and white matter parcellations). Compared to standardized adult or age-appropriate templates, our templates better characterized the neuroanatomy of the EMA collision-sport athletes, reduced biases introduced during spatial normalization, and exhibited higher sensitivity in diffusion tensor imaging analysis. In summary, these results suggest the population-specific brain atlases are more appropriate towards reproducible and meaningful statistical results, which better clarify mechanisms of traumatic brain injury and monitor brain health for EMA collision-sport athletes.

3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research.

The discovery that the stiffness of the tumor microenvironment (TME) changes during cancer progression motivated the development of cell culture involving extracellular mechanostimuli, with the intent of identifying mechanotransduction mechanisms that influence cell phenotypes. Collagen I is a main extracellular matrix (ECM) component used to study mechanotransduction in three-dimensional (3D) cell culture. There are also models with interstitial fluid stress that have been mostly focusing on the migration of invasive cells. We argue that a major step for the culture of tumors is to integrate increased ECM stiffness and fluid movement characteristic of the TME. Mechanotransduction is based on the principles of tensegrity and dynamic reciprocity, which requires measuring not only biochemical changes, but also physical changes in cytoplasmic and nuclear compartments. Most techniques available for cellular rheology were developed for a 2D, flat cell culture world, hence hampering studies requiring proper cellular architecture that, itself, depends on 3D tissue organization. New and adapted measuring techniques for 3D cell culture will be worthwhile to study the apparent increase in physical plasticity of cancer cells with disease progression. Finally, evidence of the physical heterogeneity of the TME, in terms of ECM composition and stiffness and of fluid flow, calls for the investigation of its impact on the cellular heterogeneity proposed to control tumor phenotypes. Reproducing, measuring and controlling TME heterogeneity should stimulate collaborative efforts between biologists and engineers. Studying cancers in well-tuned 3D cell culture platforms is paramount to bring mechanomedicine into the realm of oncology.

Electromagnetic simulation of a 16-channel head transceiver at 7 T using circuit-spatial optimization.

PURPOSE: With increased interest in parallel transmission in ultrahigh-field MRI, methods are needed to correctly calculate the S-parameters and complex field maps of the parallel transmission coil. We present S-parameters paired with spatial field optimization to fully simulate a double-row 16-element transceiver array for brain MRI at 7 T. METHODS: We implemented a closed-form equation of the coil S-parameters and overall spatial B1+ field. We minimized a cost function, consisting of coil S-parameters and the B1+ homogeneity in brain tissue, by optimizing transceiver components, including matching, decoupling circuits, and lumped capacitors. With this, we are able to compare the in silico results determined with and without B1+ homogeneity weighting. Using the known voltage range from the host console, we reconstructed the B1+ maps of the array and performed RF shimming with four realistic head models. RESULTS: As performed with B1+ homogeneity weighting, the optimized coil circuit components were highly consistent over the four heads, producing well-tuned, matched, and decoupled coils. The mean peak forward powers and B1+ statistics for the head models are consistent with in vivo human results (N = 8). There are systematic differences in the transceiver components as optimized with or without B1+ homogeneity weighting, resulting in an improvement of 28.4 ± 7.5% in B1+ homogeneity with a small 1.9 ± 1.5% decline in power efficiency. CONCLUSION: This co-simulation methodology accurately simulates the transceiver, predicting consistent S-parameters, component values, and B1+ field. The RF shimming of the calculated field maps match the in vivo performance.

Global and peak local specific absorption rate control on parallel transmit systems using k-means SAR compression model.

PURPOSE: To improve the specific absorption rate (SAR) compression model capability in parallel transmission (pTx) MRI systems. METHODS: A k-means clustering method is proposed to group voxels with similar SAR behaviors in the scanned object, providing a controlled upper-bounded estimation of peak local SARs. This k-means compression model and the conventional virtual observation point (VOP) model were tested in a pTx MRI framework. The pTx pulse design with different SAR controlling schemes was simulated using a numerical human head model and an eight-channel 7T coil array. Multiple criteria (including RF power, global and peak local SARs, and excitation accuracy) were compared for the performance testing. RESULTS: The k-means compression model generated a narrower overestimation bound, leading to a more accurate local SAR estimation. Among different pTx pulse design approaches, the k-means compression model showed the best trade-off between the SAR and excitation accuracy. CONCLUSIONS: The developed SAR compression model is advantageous for pTx framework given the narrower overestimation bound and control over the compression ratio. Results also illustrate that a moderate increase of maximum RF power can be useful for reducing the maximum local SAR deposition.

Characterizing near-infrared spectroscopy signal under hypercapnia.

Vasoactive stress tests (i.e. hypercapnia, elevated partial pressure of arterial CO2 [PaCO2 ]) are commonly used in functional MRI (fMRI), to induce cerebral blood flow changes and expose hidden perfusion deficits in the brain. Compared with fMRI, near-infrared spectroscopy (NIRS) is an alternative low-cost, real-time, and non-invasive tool, which can be applied in out-of-hospital settings. To develop and optimize vasoactive stress tests for NIRS, several hypercapnia-induced tasks were tested using concurrent-NIRS/fMRI on healthy subjects. The results indicated that the cerebral and extracerebral reactivity to elevated PaCO2 depended on the rate of the CO2 increase. A steep increase resulted in different cerebral and extracerebral reactivities, leading to unpredictable NIRS measurements compared with fMRI. However, a ramped increase, induced by ramped-CO2 inhalation or breath-holding tasks, induced synchronized cerebral, and extracerebral reactivities, resulting in consistent NIRS and fMRI measurements. These results demonstrate that only tasks that increase PaCO2 gradually can produce reliable NIRS results.

Current and Emerging Magnetic Resonance-Based Techniques for Breast Cancer.

Breast cancer is the most commonly diagnosed cancer among women worldwide, and early detection remains a principal factor for improved patient outcomes and reduced mortality. Clinically, magnetic resonance imaging (MRI) techniques are routinely used in determining benign and malignant tumor phenotypes and for monitoring treatment outcomes. Static MRI techniques enable superior structural contrast between adipose and fibroglandular tissues, while dynamic MRI techniques can elucidate functional characteristics of malignant tumors. The preferred clinical procedure-dynamic contrast-enhanced MRI-illuminates the hypervascularity of breast tumors through a gadolinium-based contrast agent; however, accumulation of the potentially toxic contrast agent remains a major limitation of the technique, propelling MRI research toward finding an alternative, noninvasive method. Three such techniques are magnetic resonance spectroscopy, chemical exchange saturation transfer, and non-contrast diffusion weighted imaging. These methods shed light on underlying chemical composition, provide snapshots of tissue metabolism, and more pronouncedly characterize microstructural heterogeneity. This review article outlines the present state of clinical MRI for breast cancer and examines several research techniques that demonstrate capacity for clinical translation. Ultimately, multi-parametric MRI-incorporating one or more of these emerging methods-presently holds the best potential to afford improved specificity and deliver excellent accuracy to clinics for the prediction, detection, and monitoring of breast cancer.

Conductive Thread-Based Stretchable and Flexible Radiofrequency Coils for Magnetic Resonance Imaging.

OBJECTIVE: We propose a novel flexible and entirely stretchable radiofrequency coil for magnetic resonance imaging. This coil design aims at increasing patient comfort during imaging while maintaining or improving image quality. METHODS: Conductive silver-coated thread was zigzag stitched onto stretchable athletic fabric to create a single-loop receive coil. The stitched coil was mounted in draped and stretched fashions and compared to a coil fabricated on flexible printed circuit board. Match/tune circuits, detuning circuits, and baluns were incorporated into the final setup for bench measurements and imaging on a 3T MR scanner. A fast spin echo sequence was used to obtain images for comparison. RESULTS: The fabricated coil presents multi-directional stretchability and flexibility while maintaining conductivity and stitch integrity. SNR calculations show that this stretchable coil design is comparable to a flexible, standard PCB coil with a 13-30% decrease in SNR depending on stretch degree and direction. In vivo human wrist images were obtained using the stitched coil. CONCLUSION: Despite the reduction in SNR for this combination of materials, there is a reduced percentage of SNR drop as compared to existing stretch coil designs. These imaging results and calculations support further experimentation into more complex coil geometries. SIGNIFICANCE: This coil is uniquely stretchable in all directions, allowing for joint imaging at various degrees of flexion, while offering the closest proximity of placement to the skin. The materials provide a similar level of comfort to athletic wear and could be incorporated into coils for a variety of anatomies.

Multiple-Input Multiple-Output (MIMO) MRI: Combining Parallel Excitation and Parallel Reception for Enhanced Imaging.

Magnetic resonance imaging (MRI) plays a critical role in visualizing the structure and functions of the human body. In order to accelerate imaging time and improve image quality, radio-frequency (RF) coil receive arrays are commonly employed to acquire the magnetic resonance (MR) signal. Similarly, multiple transmit coils have been shown to accelerate and refine RF excitation. In this work, we investigate the optimization of total imaging time and image accuracy when considering both the transmit and receive coil arrays; we term this strategy multiple-input multiple-output (MIMO) MRI. Our RF pulse design method is modeled by minimizing the excitation errors while simultaneously maximizing the signal-to-noise ratio (SNR) of the reconstructed MR image. It further allows a key tradeoff between the two optimizers. Additionally, multiple acceleration factors, varying numbers of receive coils used, maximum excitation error tolerance, and different excitation patterns are simulated and analyzed in this model. For a given excitation pattern, our method is shown to improve the SNR by 18-130% under certain acceleration schemes, as compared to conventional parallel transmission methods, while simultaneously controlling the excitation error within a desired scope (NRMSE ≤ 0.12).

Noninvasive characterization of in situ forming implant diffusivity using diffusion-weighted MRI.

In situ forming implants (ISFIs) form a solid drug-eluting depot, releasing drug for an extended period of time after a minimally-invasive injection. Clinical use of ISFIs has been limited because many factors affect drug release kinetics. The aim of this study was to use diffusion-weighted MRI (DWI) to noninvasively quantify spatial-temporal changes in implant diffusivity in situ. ISFIs were formed using poly(lactic-co-glycolic) acid, with a molecular weight of either 15 kDa or 52 kDa, and fluorescein as the mock drug. Drug release, polymer erosion, polymer degradation, and implant diffusivity were analyzed in vitro over 21 days. DWI was also performed in vivo over 5 days. Spatial diffusivity maps of the implant were generated using DWI data. Results showed constant diffusivity at the implant shell ((1.17 ±â€¯0.13) × 10-3 mm2/s) and increasing diffusivity within the interior over time (from (0.268 ±â€¯0.081) × 10-3 mm2/s during day 1 to (1.88 ±â€¯0.04) × 10-3 mm2/s at 14 d), which correlated with increasing porosity of the implant microstructure. Implants formed in vivo followed the same diffusivity trend as those in vitro. This study validates the use of DWI to provide novel functional information about implant behavior through its ability to noninvasively characterize transport properties within the implant both in vitro and in vivo.

Dependence on subconcussive impacts of brain metabolism in collision sport athletes: an MR spectroscopic study.

Long term neurological impairments due to repetitive head trauma are a growing concern for collision sport athletes. American Football has the highest rate of reported concussions among male high school athletes, a position held by soccer for female high school athletes. Recent research has shown that subconcussive events experienced by collision sport athletes can be a further significant source of accrued damage. Collision sport athletes experience hundreds of subconcussive events in a single season, and these largely go uninvestigated as they produce no overt clinical symptoms. Continued participation by these seemingly uninjured athletes is hypothesized to increase susceptibility to diagnoseable brain injury. This study paired magnetic resonance spectroscopy with head impact monitoring to quantify the relationship between metabolic changes and head acceleration event characteristics in high school-aged male football and female soccer collision sport athletes. During the period of exposure to subconcussive events, asymptomatic male (football) collision sport athletes exhibited statistically significant changes in concentrations of glutamate+glutamine (Glx) and total choline containing compounds (tCho) in dorsolateral prefrontal cortex, and female (soccer) collision sport athletes exhibited changes in glutamate+glutamine (Glx) in primary motor cortex. Neurometabolic alterations observed in football athletes during the second half of the season were found to be significantly associated with the average acceleration per head acceleration events, being best predicted by the accumulation of events exceeding 50 g. These marked deviations in neurometabolism, in the absence of overt symptoms, raise concern about the neural health of adolescent collision-sport athletes and suggest limiting exposure to head acceleration events may help to ameliorate the risk of subsequent cognitive impairment.

Toward 7T breast MRI clinical study: safety assessment using simulation of heterogeneous breast models in RF exposure.

PURPOSE: To facilitate assessment of RF power deposition and temperature rise within the breast, we present a method to seamlessly join heterogeneous breast models with standard whole-body models and demonstrate simulations at 7 T. METHODS: Finite-difference time-domain electromagnetic and bioheat simulations are performed to analyze the specific absorption rate (SAR) and temperature rise distributions in 36 Breast Imaging Reporting and Data System (BI-RADS) categorized breast models fused to 2 female whole-body models while transmitting from a 7T breast volume coil. The breast models are uncompressed in the prone position and feature heterogeneous tissue contents; fusion with human models uses affine transformation and the level-set method. RESULTS: The fusion method produces a continuous transient from the chest region to the posterior portion of breast models while preserving the original volume and shape of breast models. Simulation results of both Ella and Hanako models indicate that the maximum local SAR, partial body SAR, and local tissue temperature rise are positively correlated with both breast density and the highest BI-RADS density classification. Additionally, maximum local tissue temperature rise is positively correlated with maximum 10-g SAR values. CONCLUSION: Fibroglandular tissue content plays an important role in the distribution of SAR and temperature rise within breast tissue. The combined body-breast models preserve the integrity of breast models while concurrently exhibiting the loading of whole-body human models. The procedures presented in this simulation study facilitate safety assessments for breast MRI across the population at both clinical and ultrahigh field strengths.