Patterns of cortical oxygenation may predict the response to stenting in subjects with renal artery stenosis: A radiomics-based model.

BACKGROUND: Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS. MATERIALS AND METHODS: Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling. RESULTS: Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function. CONCLUSIONS: Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting.

Correlation between surgical booking by a PA and surgical procedure performed.

OBJECTIVE: This study evaluated the concordance between clinical evaluation and diagnosis by a physician associate/assistant (PA) and the preoperative and intraoperative evaluations by a pediatric urologic surgeon. METHODS: A retrospective chart review was performed for patients independently evaluated and scheduled for surgery by a single PA between 2017 and 2020. Concordance was measured by comparing the PA's office note with the surgeon's preoperative note and operative report. RESULTS: Of the 242 patients scheduled for surgery, 11 underwent an operative report procedure change and 11 others underwent a preoperative note procedure change. Concordance increased from 89.09% in 2017 to 92.31% in 2020; this was not statistically significant ( P = .230). Urologic conditions evaluated demonstrated an increase in the variety and complexity of conditions. CONCLUSIONS: A supervisory/collaborative model involving a well-trained PA yields excellent outcomes in terms of concordance with surgical scheduling and procedure performed.

Obesity blunts amelioration of cardiac hypertrophy and fibrosis by human mesenchymal stem/stromal cell-derived extracellular vesicles.

Renovascular hypertension (RVH) can induce cardiac damage that is reversible using adipose tissue-derived mesenchymal stromal/stem cells (A-MSCs). However, A-MSCs isolated from patients with obesity are less effective than lean-A-MSC in blunting hypertensive cardiomyopathy in mice with RVH. We tested the hypothesis that this impairment extends to their obese A-MSC-extracellular vesicles (EVs) progeny. MSCs were harvested from the subcutaneous fat of obese and lean human subjects, and their EVs were collected and injected into the aorta of mice 2 wk after renal artery stenosis or sham surgery. Cardiac left ventricular (LV) function was studied with MRI 2 wk later, and myocardial tissue ex vivo. Blood pressure, LV myocardial wall thickness, mass, and fibrosis that were elevated in RVH mice were suppressed only by lean EVs. Hence, human A-MSC-derived lean EVs are more effective than obese EVs in blunting hypertensive cardiac injury in RVH mice. These observations highlight impaired paracrine repair potency of endogenous MSCs in patients with obesity.NEW & NOTEWORTHY Injection of A-MSC-derived EVs harvested from patients who are lean can resolve myocardial injury in mice with experimental renovascular hypertension more effectively than A-MSC-derived EVs from patients with obesity. These observations underscore and might have important ramifications for the self-healing capacity of patients with obesity and for the use of autologous EVs as a regenerative tool.

Liver T1 Relaxation Quantification Using a 3-Dimensional Interleaved Look-Locker Acquisition With T2 Preparation Pulse Sequence (3D-QALAS): Comparison With Conventional 2-Dimensional MOLLI.

BACKGROUND: Changes in liver magnetic resonance imaging T1 relaxation times are associated with histologic inflammation and fibrosis. OBJECTIVE: To compare liver T1 measurements obtained using a novel single-breath-hold 3-dimensional (3D) whole-liver T1 estimation method (3D-QALAS) to standard-of-care 2-dimensional (2D) modified Look-Locker (2D-MOLLI) measurements. METHODS: With institutional review board approval, research magnetic resonance imaging examinations were performed in 19 participants at 1.5 T. T1 relaxometry of the liver was performed using a novel 3D whole-liver T1 estimation method (3D-QALAS) as well as a 2D modified Look-Locker (2D-MOLLI) method. The 3D method covered the entire liver in a single breath hold, whereas 2D imaging was performed at 4 anatomic levels in 4 consecutive breath holds. T1 measurements from parametric maps were obtained by a single operator, and region-of-interest area-weighted mean T1 values were calculated. Pearson correlation ( r ) was used to assess correlation between T1 estimation methods, and the paired t test and Bland-Altman analysis were used to compare agreement in T1 measurements. RESULTS: In 18 participants (1 participant was excluded from analysis because of respiratory motion artifacts on 3D-QALAS images), 2D-MOLLI and 3D-QALAS mean T1 measurements were strongly correlated ( r = 0.95, [95% CI: 0.87-0.98]; P < 0.0001). 2D-MOLLI T1 values were significantly longer than 3D-QALAS values (647.2 ± 87.3 milliseconds vs. 554.7 ± 75.8 milliseconds; P < 0.0001) with mean bias = 92.5 milliseconds (95% limits of agreement, 36.8, 148.2 milliseconds). CONCLUSION: Whole-liver T1 measurements obtained using a novel single-breath-hold 3D T1 estimation method correlate with a standard-of-care multiple consecutive-breath-hold 2D single-slice method but demonstrate systematic bias that should be considered or corrected when used in a clinical or research setting.

Performance of C-SENSE Accelerated Rapid Liver Shear Stiffness Measurement Using Displacement Wave Polarity-Inversion Motion Encoding: An Evaluation Study.

BACKGROUND: Liver shear stiffness measurement using magnetic resonance elastography (MRE) aids in the noninvasive diagnosis and staging of liver fibrosis. Inadequate breath-holds can lead to inaccurate stiffness estimation and/or failed MRE exams. PURPOSE: To prospectively evaluate the performance of compressed sensitivity encoding (C-SENSE) accelerated rapid MRE measurement of liver shear stiffness using displacement wave polarity-inversion motion encoding. STUDY TYPE: Retrospective. SUBJECTS: Eleven with liver disease and 10 asymptomatic subjects. FIELD STRENGTH/SEQUENCE: 1.5 T; gradient-recalled-echo (GRE) MRE. ASSESSMENT: All participants underwent: 1) two-dimensional (2D) GRE MRE with inflow saturation using SENSE acceleration factor (R) of 2 (standard of care [SC]); 2) 2D rapid MRE with (RwS); and 3) without (RnS) inflow saturation using C-SENSE R = 3; and 4) spatial three-dimensional (3D) rapid MRE with inflow saturation (R3D) using C-SENSE R = 4; with nominally identical spatial resolution and coverage. Image analyst (D.G., 2 years of experience) drew identical and maximal regions of interest (ROIs) in right hepatic lobe. STATISTICAL TESTS: Linear regression, intra-class correlation coefficients (ICC), Bland-Altman analyses, and the Wilcoxon signed-rank test were used to assess consistency and agreement of liver stiffness measurements for manually drawn identical and maximal ROIs. RESULTS: In 21 participants (37 ± 14 years) with liver stiffness (2.3 ± 0.7 kPa), body mass index (BMI 27 ± 7 kg/m2 ), proton density fat fraction (PDFF 9 ± 9%), and T2 * (27 ± 4 msec); rapid MRE sequences showed excellent agreement (ICC > 0.95) with SC MRE and no correlation (r2 < 0.1) of the differences (mean difference <0.2 kPa, <6%; limits of agreement <0.4 kPa, <16%) with BMI, PDFF, and T2 *. Breath-hold times were: 14 seconds (SC), 5 seconds (RnS), 7 seconds (RwS) per slice, and 16 seconds for the R3D acquisition. DATA CONCLUSIONS: C-SENSE accelerated GRE MRE sequences, using displacement wave polarity-inversion motion encoding, produce equivalent measurements of liver stiffness and have potential clinical benefit in patients with limited breath-holding capacity. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Agreement Between Automated and Clinically Reported Manual ROI-Based MR Elastography Liver Stiffness Measurements in Children and Young Adults.

MR elastography (MRE) typically requires manual ROI placement to generate liver shear stiffness measurements. Among 419 patients (primarily children and young adults), a computer-based automated MRE processing tool and clinically reported manual ROI-based measurements generated similar results (mean bias = 0.13 kPa). The intraclass correlation coefficient was 0.94 and was at least 0.90 across common indications in male and female patients and in patients with and without elevated liver fat fraction. Automated analysis may promote postprocessing standardization and decrease reporting variability.

Velocity-Encoded Phase-Contrast MRI for Measuring Mesenteric Blood Flow in Patients With Newly Diagnosed Small-Bowel Crohn Disease.

BACKGROUND. Intestinal inflammation is associated with radiologic and histologic hyperemia. A paucity of studies have used MRI to measure mesenteric blood flow in patients with Crohn disease. OBJECTIVE. The purpose of this study was to evaluate the application of velocity-encoded phase-contrast MRI for measuring mesenteric blood flow in patients with newly diagnosed small-bowel Crohn disease. METHODS. This prospective study included 20 patients with ileal Crohn disease newly diagnosed between December 2018 and October 2021 (eight female participants, 12 male participants; median age, 14.0 years), and 15 healthy control participants (eight female participants, seven male participants; median age, 17.0 years). Patients with Crohn disease underwent investigational MRI and laboratory assessments at diagnosis and at 6 weeks and 6 months after initiating anti-tumor necrosis factor-α medical therapy; control participants underwent a single investigational MRI examination. All MRI examinations included a velocity-encoded phase-contrast acquisition, which was used to measure blood flow in the abdominal aorta, superior mesenteric artery (SMA), and superior mesenteric vein (SMV). Mann-Whitney U test was used to compare blood flow measurements (ratios of SMA and SMV blood flow to aorta blood flow [hereafter, SMA-to-aorta and SMV-to-aorta blood flow, respectively]) between groups; Friedman test was used to evaluate temporal changes in blood flow. Spearman correlation was used to assess relationships between blood flow measurements and laboratory markers of intestinal inflammation. Diagnostic performance was assessed by ROC analysis. RESULTS. At baseline, SMA-to-aorta blood flow in patients versus control participants was 0.44 versus 0.30 (p = .003), and SMV-to-aorta blood flow was 0.36 versus 0.21 (p = .002). At 6 weeks and 6 months, SMA-to-aorta blood flow in patients decreased to 0.30 and 0.27 (p < .001), and SMV-to-aorta blood flow decreased to 0.27 and 0.21 (p = .02), respectively. SMA-to-aorta and SMV-to-aorta blood flow were positively correlated with C-reactive protein (rho, 0.34 [p = .01] and 0.35 [p = .008], respectively) and fecal calprotectin (rho, 0.34 [p = .01] vs 0.47 [p < .001]). AUCs for differentiating patients from controls were 0.79 for SMA-to-aorta (sensitivity, 60%; specificity, 100%) and 0.82 for SMV-to-aorta (sensitivity, 75%; specificity, 87%) blood flow. CONCLUSION. Mesenteric blood flow is quantifiable using velocity-encoded phase-contrast MRI. The measurements differ between patients with ileal Crohn disease and healthy control participants and change in response to medical therapy. CLINICAL IMPACT. MRI-based mesenteric blood flow measurements provide a potential novel marker of intestinal inflammation.

Varicocele is underdiagnosed in men evaluated for infertility: Examination of multi-center large-scale electronic health record data.

Varicocele is the most common reversible cause of male infertility, affecting up to 20% of healthy men and 40% of men with primary infertility. The objective of this study was to investigate the prevalence of varicocele in men evaluated for infertility, and to determine rates of subsequent varicocele repair. Since reproductive endocrinologists are the first specialists seen for male infertility care in North America, we hypothesized that varicocele would be underdiagnosed when compared to its reported prevalence among men with infertility. TriNetX, a large, multicenter electronic health record (EHR) database was queried to establish a cohort of all men (above 18 years of age) with a diagnosis of male infertility. This cohort was used to identify those with ensuing varicocele diagnosis. Men who received varicocelectomy or venous embolization after a diagnosis of varicocele were then identified. Out of 101,309 men with a diagnosis of male infertility in the network, only 9768 (9.6%) had a diagnosis of varicocele. Mean age of men with varicocele was 34. Varicocelectomy or venous embolization was performed in 1699 (20.2%) and 69 (0.76%) of men with varicocele, respectively. In this cross-sectional EHR study, varicocele was underdiagnosed in men evaluated for infertility when compared with prior epidemiological studies.

COVID-19 vaccination not associated with increased risk of erectile dysfunction.

Although mRNA COVID-19 vaccines have proven to be safe and effective against SARS-CoV-2, vaccination rates have slowed, with some individuals citing impotence as a concern. Therefore, we conducted a survey of the US males to evaluate the impact of COVID-19 vaccination on erectile function. We hypothesized that vaccinated men would not have a higher risk of ED compared to unvaccinated men. Amazon Mechanical Turk (MTurk) was utilized to survey the US adult male population between August 26 and September 2, 2021. Survey participation was open to 1000 males over the age of 18 and currently living in the United States regardless of vaccination status or the past medical history of COVID-19. Selection criteria included respondents ≥45 years old, no history of physician-diagnosed ED, biologically born, and identify as male. Participants completed an anonymous 16-question survey that included a multidimensional scale used to evaluate ED, the International Index of Erectile Function (IIEF-5). Among vaccinated men, the median IIEF-5 score was 20 [16-24] compared to 22 [17.5-25] in the unvaccinated group (p = 0.195). The multivariable-adjusted analysis demonstrated that vaccination against COVID-19 was not associated with increased risk of ED. Overall, this cross-sectional survey showed that COVID-19 vaccination was not associated with an increased risk of erectile dysfunction in males 45 years and older.

Magnetic resonance elastography-derived stiffness of the kidneys and its correlation with water perfusion.

Stiffness plays an important role in diagnosing renal fibrosis. However, kidney stiffness is altered by perfusion changes in many kidney diseases. Therefore, the aim of the current study is to determine the correlation of kidney stiffness with water intake. We hypothesize that kidney stiffness will increase with 1 L of water intake due to increased water perfusion to the kidneys. Additionally, stiffness of the kidneys will correlate with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values before and after water intake. A 3 T MRI scanner was used to perform magnetic resonance elastography and diffusion tensor imaging of the kidneys on 24 healthy subjects (age range: 22-66 years) before and after water intake of 1 L. A 3D T1-weighted bladder scan was also performed to measure bladder volume before and after water intake. A paired t-test was performed to evaluate the effect of water intake on the stiffness of kidneys, in addition to bladder volume. A Spearman correlation test was performed to determine the association between stiffness, bladder volume, ADC and FA values of both kidneys before and after water intake. The results show a significant increase in stiffness in different regions of the kidney (ie, percentage increase ranged from 3.6% to 7.5%) and bladder volume after water intake (all P < 0.05). A moderate significant negative correlation was observed between change in kidney stiffness and bladder volume (concordance correlation coefficient = -0.468, P < 0.05). No significant correlation was observed between stiffness and ADC or FA values before and after water intake in both kidneys (P > 0.05). Water intake caused a significant increase in the stiffness of the kidneys. The negative correlation between the change in kidney stiffness and bladder volume, before and after water intake, indicates higher perfusion pressure in the kidneys, leading to increased stiffness.

Magnetic Resonance Elastography of kidneys: SE-EPI MRE reproducibility and its comparison to GRE MRE.

The purpose of this study is 1) to demonstrate reproducibility of spin echo-echo planar imaging (SE-EPI) magnetic resonance elastography (MRE) to estimate kidney stiffness; and 2) to compare SE-EPI MRE and gradient recalled echo (GRE) MRE-derived stiffness estimations in various anatomical regions of the kidney. Kidney MRE was performed on 33 healthy subjects (8 for SE-EPI MRE reproducibility and 25 for comparison with GRE MRE; age range: 22-66 years) in a 3 T MRI scanner. To demonstrate SE-EPI MRE reproducibility, subjects were scanned for the first scan and then asked to leave the scan room and repositioned again for the second (repeat) scan. Similar set-up was used for GRE MRE as well. The displacement data was then processed to obtain overall stiffness estimates of the kidney. Concordance correlation analyses were performed to determine SE-EPI MRE reproducibility and agreement between GRE MRE and SE-EPI MRE derived stiffness. A high concordance correlation (ρc  = 0.95; p-value<0.0001) was obtained for SE-EPI MRE reproducibility. Good concordance correlation was observed (ρc  = 0.84; p < 0.0001 for both kidneys, ρc  = 0.91; p < 0.0001 for right kidney and ρc  = 0.78; p < 0.0001 for left kidney) between GRE MRE and SE-EPI MRE derived stiffness measurements. Paired t-test results showed that stiffness value of medulla was significantly (p < 0.0001) greater than cortex using SE-EPI MRE as well as GRE MRE. SE-EPI MRE was reproducible and good agreement was observed in MRE-derived stiffness measurements obtained using SE-EPI and GRE sequences. Therefore, SE-EPI can be used for kidney MRE applications.

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration.

BACKGROUND: Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria. QUESTIONS/PURPOSES: We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate. METHODS: In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation. RESULTS: IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation. In vitro immunomodulatory activity of IDR-1018 included inducing production of MCP-1 in the absence of other inflammatory stimuli and to potently blunt excess production of proinflammatory cytokines and MCP-1 induced by lipopolysaccharide. Higher concentrations of IDR-1018 were required to blunt production of proinflammatory cytokines and MCP-1 in the presence S aureus. The largest in vivo immunomodulatory effect of IDR-1018 was to reduce tumor necrosis factor-α levels induced by S aureus by 60% (p = 0.006). Most importantly, IDR-1018 reduced S aureus-induced failures of osseointegration by threefold (p = 0.022) and increased osseointegration as measured by ultimate force (5.4-fold, p = 0.033) and average stiffness (4.3-fold, p = 0.049). CONCLUSIONS: IDR-1018 is potentially useful to reduce orthopaedic infections by directly killing bacteria and by recruiting macrophages to the infection site. CLINICAL RELEVANCE: These findings make IDR-1018 an attractive candidate to explore in larger animal models to ascertain whether its effects in our in vitro and mouse experiments can be replicated in more clinically relevant settings.

Emerging Medical Technologies and Their Use in Bionic Repair and Human Augmentation.

As both the proportion of older people and the length of life increases globally, a rise in age-related degenerative diseases, disability, and prolonged dependency is projected. However, more sophisticated biomedical materials, as well as an improved understanding of human disease, is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease as well as impact disease prevention. Another, albeit quieter, revolution is also taking place within society: human augmentation. In this context, humans seek to improve themselves, metamorphosing through self-discipline or more recently, through use of emerging medical technologies, with the goal of transcending aging and mortality. In this review, and in the pursuit of improved medical care following aging, disease, disability, or injury, we first highlight cutting-edge and emerging materials-based neuroprosthetic technologies designed to restore limb or organ function. We highlight the potential for these technologies to be utilized to augment human performance beyond the range of natural performance. We discuss and explore the growing social movement of human augmentation and the idea that it is possible and desirable to use emerging technologies to push the boundaries of what it means to be a healthy human into the realm of superhuman performance and intelligence. This potential future capability is contrasted with limitations in the right-to-repair legislation, which may create challenges for patients. Now is the time for continued discussion of the ethical strategies for research, implementation, and long-term device sustainability or repair.

Comparison of weighting algorithms to mitigate respiratory motion in free-breathing neonatal pulmonary radial UTE-MRI.

Background. Thoracoabdominal MRI is limited by respiratory motion, especially in populations who cannot perform breath-holds. One approach for reducing motion blurring in radially-acquired MRI is respiratory gating. Straightforward 'hard-gating' uses only data from a specified respiratory window and suffers from reduced SNR. Proposed 'soft-gating' reconstructions may improve scan efficiency but reduce motion correction by incorporating data with nonzero weight acquired outside the specified window. However, previous studies report conflicting benefits, and importantly the choice of soft-gated weighting algorithm and effect on image quality has not previously been explored. The purpose of this study is to map how variable soft-gated weighting functions and parameters affect signal and motion blurring in respiratory-gated reconstructions of radial lung MRI, using neonates as a model population.Methods. Ten neonatal inpatients with respiratory abnormalities were imaged using a 1.5 T neonatal-sized scanner and 3D radial ultrashort echo-time (UTE) sequence. Images were reconstructed using ungated, hard-gated, and several soft-gating weighting algorithms (exponential, sigmoid, inverse, and linear weighting decay outside the period of interest), with %Nprojrepresenting the relative amount of data included. The apparent SNR (aSNR) and motion blurring (measured by the maximum derivative of image intensity at the diaphragm, MDD) were compared between reconstructions.Results. Soft-gating functions produced higher aSNR and lower MDD than hard-gated images using equivalent %Nproj, as expected. aSNR was not identical between different gating schemes for given %Nproj. While aSNR was approximately linear with %Nprojfor each algorithm, MDD performance diverged between functions as %Nprojdecreased. Algorithm performance was relatively consistent between subjects, except in images with high noise.Conclusion. The algorithm selection for soft-gating has a notable effect on image quality of respiratory-gated MRI; the timing of included data across the respiratory phase, and not simply the amount of data, plays an important role in aSNR. The specific soft-gating function and parameters should be considered for a given imaging application's requirements of signal and sharpness.

Training and Comparison of nnU-Net and DeepMedic Methods for Autosegmentation of Pediatric Brain Tumors.

BACKGROUND AND PURPOSE: Tumor segmentation is essential in surgical and treatment planning and response assessment and monitoring in pediatric brain tumors, the leading cause of cancer-related death among children. However, manual segmentation is time-consuming and has high interoperator variability, underscoring the need for more efficient methods. After training, we compared 2 deep-learning-based 3D segmentation models, DeepMedic and nnU-Net, with pediatric-specific multi-institutional brain tumor data based on multiparametric MR images. MATERIALS AND METHODS: Multiparametric preoperative MR imaging scans of 339 pediatric patients (n = 293 internal and n = 46 external cohorts) with a variety of tumor subtypes were preprocessed and manually segmented into 4 tumor subregions, ie, enhancing tumor, nonenhancing tumor, cystic components, and peritumoral edema. After training, performances of the 2 models on internal and external test sets were evaluated with reference to ground truth manual segmentations. Additionally, concordance was assessed by comparing the volume of the subregions as a percentage of the whole tumor between model predictions and ground truth segmentations using the Pearson or Spearman correlation coefficients and the Bland-Altman method. RESULTS: The mean Dice score for nnU-Net internal test set was 0.9 (SD, 0.07) (median, 0.94) for whole tumor; 0.77 (SD, 0.29) for enhancing tumor; 0.66 (SD, 0.32) for nonenhancing tumor; 0.71 (SD, 0.33) for cystic components, and 0.71 (SD, 0.40) for peritumoral edema, respectively. For DeepMedic, the mean Dice scores were 0.82 (SD, 0.16) for whole tumor; 0.66 (SD, 0.32) for enhancing tumor; 0.48 (SD, 0.27) for nonenhancing tumor; 0.48 (SD, 0.36) for cystic components, and 0.19 (SD, 0.33) for peritumoral edema, respectively. Dice scores were significantly higher for nnU-Net (P ≤ .01). Correlation coefficients for tumor subregion percentage volumes were higher (0.98 versus 0.91 for enhancing tumor, 0.97 versus 0.75 for nonenhancing tumor, 0.98 versus 0.80 for cystic components, 0.95 versus 0.33 for peritumoral edema in the internal test set). Bland-Altman plots were better for nnU-Net compared with DeepMedic. External validation of the trained nnU-Net model on the multi-institutional Brain Tumor Segmentation Challenge in Pediatrics (BraTS-PEDs) 2023 data set revealed high generalization capability in the segmentation of whole tumor, tumor core (a combination of enhancing tumor, nonenhancing tumor, and cystic components), and enhancing tumor with mean Dice scores of 0.87 (SD, 0.13) (median, 0.91), 0.83 (SD, 0.18) (median, 0.89), and 0.48 (SD, 0.38) (median, 0.58), respectively. CONCLUSIONS: The pediatric-specific data-trained nnU-Net model is superior to DeepMedic for whole tumor and subregion segmentation of pediatric brain tumors.

Improving disease prevention, diagnosis, and treatment using novel bionic technologies.

Increased human life expectancy, due in part to improvements in infant and childhood survival, more active lifestyles, in combination with higher patient expectations for better health outcomes, is leading to an extensive change in the number, type and manner in which health conditions are treated. Over the next decades as the global population rapidly progresses toward a super-aging society, meeting the long-term quality of care needs is forecast to present a major healthcare challenge. The goal is to ensure longer periods of good health, a sustained sense of well-being, with extended periods of activity, social engagement, and productivity. To accomplish these goals, multifunctionalized interfaces are an indispensable component of next generation medical technologies. The development of more sophisticated materials and devices as well as an improved understanding of human disease is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease and will impact disease prevention. This review examines emerging cutting-edge bionic materials, devices and technologies developed to advance disease prevention, and medical care and treatment in our elderly population including developments in smart bandages, cochlear implants, and the increasing role of artificial intelligence and nanorobotics in medicine.

Evaluation of Renal Fibrosis Using Magnetization Transfer Imaging at 1.5T and 3T in a Porcine Model of Renal Artery Stenosis.

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T.

Obesity Blunts the Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Introduction: Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) are paracrine vectors with therapeutic functions comparable to their parent cells. However, it remains unclear if donor obesity affects their therapeutic functions. We tested the hypothesis that the curative effect of human adipose tissue-derived MSC-EVs (A-MSC-EVs) is blunted by obesity. Methods: MSC-EVs were isolated by ultracentrifugation from mesenchymal stem/stromal cells (MSCs) collected from abdominal subcutaneous fat of obese and lean human subjects (obese and lean-MSC-EVs, respectively) and injected into the aorta of mice 2 weeks after renal artery stenosis (RAS) induction. Magnetic resonance imaging studies were conducted 2 weeks after MSC-EVs delivery to determine renal function. The effect of MSC-EVs on tissue injury was assessed by histology and gene expression of inflammatory factors, including interleukin (IL)-1ß, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Oxidative damage, macrophage infiltration, plasma renin, and hypoxia inducible factor-1α (HIF-1α) were also assessed. Results: Tracking showed that MSC-EVs localized in the kidney tissue, including glomeruli and tubules. All MSC-EVs decreased systolic blood pressure (SBP) and plasma renin and improved the poststenotic kidney (STK) volume, but obese-MSC-EVs were less effective than lean-MSC-EVs in improving medullary hypoxia, fibrosis, and tubular injury. Lean-MSC-EVs decreased inflammation, whereas obesity attenuated this effect. Only lean-MSC-EVs decreased STK cortical HIF-1α expression. Conclusion: Obesity attenuates the antihypoxia, antifibrosis, antiinflammation, and tubular repair functions of human MSC-EVs in chronic ischemic kidney disease. These observations may have implications for the self-repair potency of obese subjects and for the use of autologous MSC-EVs in regenerative medicine.

Multiparametric quantitative renal MRI in children and young adults: comparison between healthy individuals and patients with chronic kidney disease.

PURPOSE: Multiparametric quantitative renal MRI may provide noninvasive radiologic biomarkers of chronic kidney disease (CKD) based on investigations in animal models and adults. We aimed to (1) obtain normative multiparametric quantitative MRI data from the kidneys of healthy children and young adults, (2) compare MRI measurements between healthy control participants and patients with CKD, and (3) determine if MRI measurements correlate with clinical and laboratory data as well as histology. METHODS: This was a prospective, case-control study of 20 healthy controls and 12 CKD patients who underwent percutaneous renal biopsy ranging from 12 to 23 years of age between October 2018 and March 2020. Kidney function was documented and pathology assessed for fibrosis/inflammation. Utilizing a field strength of 1.5T, we examined renal T1, T2, and T2* relaxation mapping, MR elastography (MRE), and diffusion-weighted imaging (DWI). A single analyst made all manual measurements for quantitative MRI pulse sequences. Independent measurements from cortex, medulla, and whole kidney were obtained by drawing regions of interest on single slices from the upper, mid, and lower kidney. A weighted average was calculated for each kidney; if two kidneys, the right and left were averaged. Continuous variables were compared with Mann-Whitney U test; bivariate relationships were assessed using Spearman rank-order correlation. RESULTS: Median estimated glomerular filtration rate (eGFR) was 112.3 ml/min/1.73 m2 in controls (n = 20, 10 females) and 55.0 ml/min/m2 in CKD patients (n = 12, 2 females) (p < 0.0001). Whole kidney (1333 vs. 1291 ms; p = 0.018) and cortical (1212 vs 1137 ms; p < 0.0001) T1 values were higher in CKD patients. Cortical T1 values correlated with eGFR (rho = - 0.62; p = 0.0003) and cystatin C (rho = 0.58; p = 0.0007). Whole kidney (1.87 vs. 2.02 10-3 mm2/s; p = 0.007), cortical (1.89 vs. 2.04 10-3 mm2/s; p = 0.008), and medullary (1.87 vs. 1.98 10-3 mm2/s; p = 0.0095) DWI apparent diffusion coefficients (ADC) were lower in CKD patients. Whole kidney ADC correlated with eGFR (rho = 0.45; p = 0.012) and cystatin C (rho = - 0.46; p = 0.009). Cortical histologic inflammation correlated with DWI ADC (rho = - 0.71; p = 0.011). CONCLUSION: Renal T1 relaxation and DWI ADC measurements differ between pediatric healthy controls and CKD patients, correlate with laboratory markers of CKD, and may have histologic correlates.