Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

A Multicenter Large-Sample Shear Wave Ultrasound Elastographic Study of the Achilles Tendon in Chinese Adults.

OBJECTIVES: The changes in the viscoelasticity of the Achilles tendon are related to tendinopathy. Therefore, constructing a data model in the healthy population is essential to understanding the key factors affecting the viscoelasticity of the Achilles tendon. The purpose of our research was to obtain large sample data, construct a data model, and determine parameters that affect the elastic modulus of the Achilles tendon in healthy Chinese adults. METHODS: We designed a prospective multicenter clinical trial to evaluate the viscoelasticity of the Achilles tendon by using shear wave elastography. A total of 1165 healthy adult participants from 17 Chinese hospitals were recruited for the assessment. The necessary parameters (age, height, weight, and body mass index) were recorded. The elastic modulus (Young modulus) was obtained from the middle of the Achilles tendon and calculated with feet in naturally relaxed, dorsal, and plantar positions. The thickness and perimeter of the Achilles tendon were measured via cross section on the same site. A multiple linear regression was performed to find the key factors affecting the Young modulus of the Achilles tendon. RESULTS: The Young modulus of the left Achilles tendon in the natural relaxed position followed a normal distribution (P > .05) with a mean ± SD of 374.24 ± 106.12 kPa. The regression equations showed a positive correlation between the Young modulus and weight and a negative correlation between the Young modulus and the circumference or thickness of the left Achilles tendon (P < .05). CONCLUSIONS: The Young modulus of the Achilles tendon as measured by shear wave elastography is related to body weight as well as the perimeter or thickness of the tendon.

Federated learning via multi-attention guided UNet for thyroid nodule segmentation of ultrasound images.

Accurate segmentation of thyroid nodules is essential for early screening and diagnosis, but it can be challenging due to the nodules' varying sizes and positions. To address this issue, we propose a multi-attention guided UNet (MAUNet) for thyroid nodule segmentation. We use a multi-scale cross attention (MSCA) module for initial image feature extraction. By integrating interactions between features at different scales, the impact of thyroid nodule shape and size on the segmentation results has been reduced. Additionally, we incorporate a dual attention (DA) module into the skip-connection step of the UNet network, which promotes information exchange and fusion between the encoder and decoder. To test the model's robustness and effectiveness, we conduct the extensive experiments on multi-center ultrasound images provided by 17 local hospitals. The model is trained using the federal learning mechanism to ensure privacy protection. The experimental results show that the Dice scores of the model on the data sets from the three centers are 0.908, 0.912 and 0.887, respectively. Compared to existing methods, our method demonstrates higher generalization ability on multi-center datasets and achieves better segmentation results.

Predicting malignancy in thyroid nodules based on conventional ultrasound and elastography: the value of predictive models in a multi-center study.

BACKGROUND: This study aimed to establish predictive models based on features of Conventional Ultrasound (CUS) and elastography in a multi-center study to determine appropriate preoperative diagnosis of malignancy in thyroid nodules with different risk stratification based on 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guidelines. METHODS: Five hundred forty-eight thyroid nodules from three centers pathologically confirmed by the cytology or histology were retrospectively enrolled in the study, which were examined by CUS and elastography before fine needle aspiration (FNA) and surgery. Characteristics of CUS of thyroid nodules were reviewed according to 2017 ACR TI-RADS. Binary logistic regression analysis was used to develop the prediction models based on the different risk stratification of CUS features and elastography which were statistically significant. Values of predictive models were evaluated regarding the discrimination and calibration. RESULTS: Binary logistic regression showed that patients' age, taller-than-wider, lobulated or irregular boundary, extra-thyroid extension, microcalcification and the elastic parameter of Virtual touch tissue imaging quantification (VTIQ) max were independent predictors for thyroid malignancy (p < 0.05) in the ACR model and showed the area under the curve (AUC) in training (0.912) and validation cohort (internal and external: 0.877 vs 0.935). Predictive models showed predictors in ACR TR4 and TR5 for malignancy and diagnostic performance of AUC in training, internal and external validation cohort respectively: the VTIQ max (p < 0.001) with AUC of 0.809 vs 0.842 vs 0.705 and the age, taller than wide, VTIQ max variables with AUC of 0.859 vs 0.830 vs 0.906 in validation cohort. All predictive models have better calibration capabilities (p > 0.05). CONCLUSIONS: Predictive models combined CUS and elastography features would aid clinicians to make appropriate preoperative diagnosis of thyroid nodules among different risk stratification. The elastography parameter of VTIQ max has the priority in distinguishing thyroid malignancy with moderately suspicious (ACR TR4).

Lung Ultrasound for the Diagnosis and Management of Neonatal Respiratory Distress Syndrome: A Minireview.

Lung ultrasound (LUS) is useful for diagnosis of respiratory distress syndrome in neonates. Recently, it has been proved to play an important role in the management of neonatal respiratory distress syndrome (RDS). It is feasible to grade RDS and select therapeutic modalities accordingly by LUS. The treatment also should be adjusted with the change in ultrasound images. In conclusion, LUS is valuable for the diagnosis and management of neonatal respiratory distress syndrome.

Comprehensive Quantitative Assessment of Lung Liquid Clearance by Lung Ultrasound Score in Neonates with No Lung Disease during the First 24 Hours.

OBJECTIVES: To comprehensively and quantitatively assess the process of lung liquid clearance using the lung ultrasound score. This study is to evaluate the whole healthy lungs of neonates during the first 24 h. METHODS: Lung ultrasound was performed in neonates with no respiratory symptoms within 3 h after birth, and scans were then repeated at 6 hours and 24 hours, respectively. The entire chest wall was divided into 12 regions. The lung ultrasound scores of the anterior, posterior, upper, and lower regions and sum of all regions were calculated according to the ultrasound pattern of each region examined. RESULTS: The total lung ultrasound score decreased gradually during the first 24 h, with the total lung ultrasound score at 6 h being significantly lower than that at <3 h (P < 0.05). At <3 h, B-lines were more abundant in the posterior chest than in the anterior chest (P < 0.05). At <3 h, B-lines were more abundant in the posterior chest than in the anterior chest (P < 0.05). At <3 h, B-lines were more abundant in the posterior chest than in the anterior chest (. CONCLUSION: Changes in the lung ultrasound score may quantitatively reflect the characteristics of different regions and processes of lung liquid clearance during the first 24 h.

Ultrasound-mediated microbubble destruction facilitates gene transfection in rat C6 glioma cells.

The goal of this study was to determine whether ultrasound (US) exposure combined with microbubble destruction could be used to enhance non-viral gene delivery in rat C6 glioma cells. Microbubbles were prepared and gently mixed with plasmid DNA. The mixture of the DNA and microbubbles was administered to cultured C6 cells under different US/microbubble conditions. Transfection efficiency and cell viability were assessed by FACS analysis, confocal laser scanning microscopy, and Trypan blue staining. The results demonstrate that microbubble with US exposure could significantly enhance the reporter gene expression as compared with other groups. No statistical significant difference was observed in the glioma cell viability between different groups. Our in vitro findings suggest that US-mediated microbubble destruction has the potential to promote safe and efficient gene transfer into C6 cells. This non-invasive gene transfer method may be useful for safe clinical gene therapy of brain cancer without a viral vector system.

Muscle damage responses of the elbow flexors to four maximal eccentric exercise bouts performed every 4 weeks.

Since little is known about the repeated bout effect of more than two eccentric exercise bouts, this study compared muscle damage responses among four exercise bouts. Fifteen young (21.8 +/- 1.9 years) men performed four bouts of 30 maximal isokinetic eccentric contractions of the elbow flexors every 4 weeks. Maximal voluntary elbow flexion isometric and concentric strength, range of motion at the elbow joint (ROM), upper arm circumference, blood markers of muscle damage, and muscle soreness were measured before and up to 120 h following each bout. Changes in all measures following the second to fourth bouts were significantly (P < 0.05) smaller than those after the first bout. The decreases in strength and ROM immediately after the fourth bout were significantly (P < 0.05) smaller than other bouts. It is concluded that the first bout confers the greatest adaptation, but further adaptation is induced when the exercise is repeated more than three times.

A Preliminary Study of Neonatal Cranial Venous System by Color Doppler.

AIM: To present anatomic data in the ultrasound planes for the identification of the major veins and the venous sinuses in cerebrum and to establish the sonographic normal reference values for the visualization of vein vessels and vein sinuses and blood flow velocities. METHODS: This study involved 55 healthy full-term neonates for transfontanellar color Doppler sonography. The imaging included both sagittal and coronal planes with LA332E probe, supplemented with PA240 probe as necessary. As low as reasonably achievable (ALARA) principle was obeyed, limiting Doppler exposure time and maximizing signal intensity by increasing gain rather than outputting transducer power settings. The output power was kept at a minimum level consistent with recording an adequate signal. Keeping the newborns in calm state, the total examination time which every neonate required was less than 5 min. All images were stored also in a workstation for further analysis. The description statistics and t-test for statistical analysis were used. RESULT: In all studied cases (100% cases), subependymal veins (SV), internal cerebral veins (ICV), Galen vein (GV), straight sinus (SS), superior sagittal sinus (SSS), and transverse sinuses (TS) were visualized. The visualization percentages of inferior sagittal sinus (ISS) or basal veins/Rosenthal veins (BV/RV) were lower than 100%. Based on vessel visualization percentage from high to low, the vessels were ordered as follows: SV, ICV, BV, SS, TS, ISS, and SSS. In SSS and TS, the pulsation percentage was 100%. The descending percentages of vessel pulsation were noted in SS, BV, ICV, and SV. On the basis of the mean of maximum velocities of the vessels from low to high, the vessels were ordered as follows: ISS, BV-L, BV-R, ICV-R, ICV-L, SV-L, SV-R, SSS, TS-L, TS-R, and SS. CONCLUSION: The measurements percent of visualization of cerebral deep veins was higher than the percent of cerebral venous sinuses. The pulsation percent of measurement and the velocities of cerebral venous sinuses were absolutely higher than the cerebral deep venous system. The pairs of vascular blood flow velocities were nonsignificantly different from one another.

Guidelines and recommendations on the clinical use of shear wave elastography for evaluating thyroid nodule1.

Ultrasound elastography has been introduced into clinical practice for a decade and arisen continuous increasing attention worldwide. Shear wave elastography (SWE) is a further extension of ultrasound elastography on the basis of strain elastography, providing a two-dimensional distribution map of tissue stiffness and quantitative measurement of the tissue stiffness in Young's modulus (kPa) and/or shear wave speed (m/s). The Society of Ultrasound in Medicine, Chinese Medical Association (CMA) has recently released a series of guidelines for the use of SWE, including the technique and principle of SWE, and use of SWE in liver fibrosis, breast, thyroid, and musculoskeletal system. Herein, a part of SWE in thyroid nodules is presented. In this guideline, the background, classification and technology of SWE, examination methods, diagnostic performance, prognosis evaluation, reproducibility, and limitations are discussed and recommendations are given. The recommendations are based on the published literatures with regard to SWE with different levels of evidence, particularly a mid-term result of the prospective multi-center clinical trial of SWE in thyroid, as well as the Society of Ultrasound in Medicine, CMA expert's consensus. The document provides an overall analysis of SWE in thyroid from clinical perspective, which aimed to provide recommendations to the clinicians with regard to the management of thyroid nodules by the assistance of SWE.

Ultrasound-mediated microbubble destruction enhances gene transfection in pancreatic cancer cells.

INTRODUCTION: The purpose of this study was to determine whether ultrasound exposure combined with microbubble destruction could be used to enhance non-viral gene delivery in human pancreatic carcinoma cells (PANC-1). METHODS: The study was performed with four experimental groups: Group P, plasmid alone; Group P+M, plasmid and microbubbles; Group P+U, plasmid and ultrasound; Group P+U+M, plasmid with ultrasound and microbubbles. Plasmid DNA encoding enhanced green fluorescent protein (pEGFP) was gently mixed with commercially available ultrasound microbubble contrast agents (SonoVue; Bracco Diagnostics Inc, Milan, Italy) in Group P+M and Group P+U+M. The different combinations of DNA and DNA plus microbubbles were added to cultured PANC-1 cells under different conditions. Transfection efficiency and cell viability were assessed by FACS analysis (Becton Dickinson, San Jose, CA, USA), confocal laser scanning microscopy, and trypan blue staining. RESULTS: The results demonstrated that microbubbles with ultrasound exposure could significantly enhance the reporter gene expression as compared with other groups (Group P+U+M, 21.4%+/-3.16%; Group P, 2.9%+/-0.45%; Group P+M, 3.1%+/-0.51%; Group P+U, 6.1%+/-1.27%; P<0.01). No statistically significant difference was observed in the PANC-1 cell viability between Group P+U+M and other groups (P>0.05). CONCLUSION: Our in-vitro findings suggest that ultrasound-mediated microbubble destruction has the potential to promote efficient gene transfer into PANC-1 cells without significant cell death. This non-invasive gene transfer method may be a useful tool for safe clinical gene therapy of pancreatic cancer in the future.

Low dosage of arsenic trioxide inhibits vasculogenic mimicry in hepatoblastoma without cell apoptosis.

Hepatoblastoma (HB) is the most common type of pediatric liver malignancy, which predominantly occurs in young children (aged <5 years), and continues to be a therapeutic challenge in terms of metastasis and drug resistance. As a new pattern of tumor blood supply, vasculogenic mimicry (VM) is a channel structure lined by tumor cells rather than endothelial cells, which contribute to angiogenesis. VM occurs in a variety of solid tumor types, including liver cancer, such as hepatocellular carcinoma. The aim of the present study was to elucidate the effect of arsenic trioxide (As2O3) on VM. In vitro experiments identified that HB cell line HepG2 cells form typical VM structures on Matrigel, and the structures were markedly damaged by As2O3 at a low concentration before the cell viability significantly decreased. The western blot results indicated that As2O3 downregulated the expression level of VM­associated proteins prior to the appearance of apoptotic proteins. In vivo, VM has been observed in xenografts of HB mouse models and identified by periodic acid­Schiff+/CD105­ channels lined by HepG2 cells without necrotic cells. As2O3 (2 mg/kg) markedly depresses tumor growth without causing serious adverse reactions by decreasing the number of VM channels via inhibiting the expression level of VM­associated proteins. Thus, the present data strongly indicate that low dosage As2O3 reduces the formation of VM in HB cell line HepG2 cells, independent of cell apoptosis in vivo and in vitro, and may represent as a candidate drug for HB targeting VM.

Ultrasonic Elastography Research Based on a Multicenter Study: Adding Strain Ratio after 5-Point Scoring Evaluation or Not.

BACKGROUND: This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE). MATERIALS AND METHODS: From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared. RESULTS: The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4. CONCLUSIONS: Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4.

Could ultrasonic elastography help the diagnosis of breast cancer with the usage of sonographic BI-RADS classification?

OBJECTIVES: The purpose was to evaluate whether BI-RADS (the Breast Imaging Recording and Data System) combined with UE (ultrasound elastography) could improve the differentiation and characterization of benign and malignant breast lesions by comparing with BI-RADS. METHODS: A total of 1080 patients with 1194 breast lesions were studied retrospectively at 8 different institutions from 3 geographic areas across China (North, South, and West) from June 2010 to March 2012. Each institutional ethic review board approved the study and all patients gave written informed consent. All the cases were examined by conventional US (ultrasonography) and UE prior to ultrasound-guided core biopsy. Performance of BI-RADS and BI-RADS combined with UE were compared in different size groups, age groups and area groups. RESULTS: BI-RADS combined with UE cloud improve the accuracy by 13.2% compared to BI-RADS alone for all lesions, 23.2% for <10 mm lesions, 13.3% for ≥10-20 mm lesions, 6.3% for ≥20 mm lesions, 18.4% for <50 years group, 1.7% for ≥50 years group, 13.7% for northern area group, 17.7% for southern area group and 4.4% for western area group. CONCLUSIONS: The help which UE contributed to BI-RADS was greater for breast lesions <10mm and <50 years group.

Ultrasound elastography of breast lesions in chinese women: a multicenter study in China.

PURPOSE: Through analysis, the elastograms characteristics of breast lesions of Chinese women, a suitable diagnostic standard of quasistatic ultrasound elastography (UE) for Chinese women was proposed. METHODS: From June 2010 to March 2012, 1036 consecutive female patients (mean age, 44 years old) with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All breast lesions underwent ultrasound and UE examination. Two radiologists analyzed the elastograms and separated the elastograms into 10 types. A final diagnosis was made on the basis of histologic findings. The characteristics of the elastograms were analyzed. Receiver operating characteristic curves were plotted for evaluating the diagnostic performance. Sensitivity, specificity, and accuracy were calculated. Differences in sensitivity, specificity, and accuracy were tested by using the McNemar test. RESULTS: There were 1150 lesions (593 benign, 557 malignant). There was a highly significant correlation between the elastogram color distribution and the percentage of malignant lesions, with a value of 0.92 (2P < .0001). Through analysis the different malignant percentages in different elastogram types, UE diagnostic standard was proposed, which was correlated with the blue percentage in the elastogram. The specificity, sensitivity, and accuracy of UE were 86.4%, 80.8%, and 83.5%, respectively. The specificity and accuracy of UE were higher than with ultrasound. The area under the curve was 0.86. CONCLUSION: UE could give valuable assessment in the diagnosis of breast lesions. The proposed UE diagnostic standard was suitable for Chinese women.

Impaired brachial artery flow-mediated dilation and increased carotid intima-media thickness in rheumatoid arthritis patients.

BACKGROUND: Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are common parameters used for detecting subclinical atherosclerosis. This study compared subclinical atherosclerosis of the carotid and brachial arteries in rheumatoid arthritis (RA) patients and healthy controls using high resolution ultrasonography. We also investigated their correlation with clinical factors and the association between FMD% and CIMT. METHODS: One hundred and two RA patients and 46 age-gender matched healthy controls were included in the study. FMD of the brachial artery and CIMT were measured ultrasonographically. Patients with diabetes mellitus, hypertension, renal failure, history of cardiovascular or cerebrovascular disease were excluded. Subjects who were receiving or used high dose steroids were also excluded. RESULTS: The CIMT was significantly higher in patients than that in the control group ((0.697±0.053) vs. (0.554±0.051) mm, P<0.001), whereas brachial artery FMD% was lower in patients than that in the controls ((5.454±2.653)% vs. (8.477±2.851)%, P<0.001). CIMT was related to age, disease duration, tender and swollen joint score, C-reactive protein, systolic blood pressure and high-density lipoprotein. However, FMD% was only association with systolic blood pressure. There was no significant correlation between CIMT and FMD%. CONCLUSIONS: Compared with the healthy control subjects, RA patients without clinically evident cardiovascular disease had subclinical atherosclerosis in terms of impaired FMD% and increased CIMT. FMD% and CIMT may measure a different stage of subclinical atherosclerosis in RA patients.

Potent protective effect conferred by four bouts of low-intensity eccentric exercise.

PURPOSE: It is known that submaximal eccentric exercise does not confer as strong a protective effect as maximal eccentric exercise. This study tested the hypothesis that four bouts of submaximal eccentric exercise would confer a similar protective effect to one bout maximal eccentric exercise. METHODS: Thirty untrained men were placed into 4 x 40% (40%) or control (CON) groups (n = 15 per group) by matching preexercise maximal voluntary isometric contraction strength (MVC). The 40% group performed 30 eccentric contractions with a load of 40% MVC (40% ECC) every 2 wk for four times followed 2 wk later by 30 maximal eccentric exercise (100% ECC) of the elbow flexors of the nondominant arm. The CON group performed two bouts of the 100% ECC separated by 2 wk. MVC at six angles, optimum angle (OA), concentric isokinetic strength (30 degrees x s(-1) and 300 degrees x s(-1)), range of motion, upper arm circumference, plasma creatine kinase activity and myoglobin concentration, muscle soreness, and echo intensity of B-mode ultrasound images were taken before to 5 d after each exercise. RESULTS: No significant differences in the changes in any measures were evident between the 100% ECC of the 40% group and the second 100% ECC of the CON group. Changes in all measures except for OA and upper arm circumference after the second to the fourth 40% ECC bouts were significantly smaller than those after the first 40% ECC bout. The changes in the measures after any of the 40% ECC bouts were significantly (P < 0.05) smaller than those after the first 100% ECC bout of the CON group. CONCLUSIONS: These results suggest that repeating submaximal eccentric exercise confers the same magnitude of protective effect as one bout of maximal eccentric exercise against the subsequent maximal eccentric exercise.

Changes in running economy at different intensities following downhill running.

In this study, we tested the hypothesis that running economy assessed at a high intensity [e.g. 90% maximal oxygen capacity (VO2(max))] would be affected more than at a lower intensity (e.g. 70% VO2(max)) after downhill running. Fifteen untrained young men performed level running at 70, 80, and 90% VO2(max) (5 min for each intensity) before and 2 and 5 days after a 30-min downhill run (gradient of -16%) at the intensity of their pre-determined 70% VO2(max). Oxygen consumption, minute ventilation, respiratory exchange ratio, heart rate, rating of perceived exertion, and blood lactate concentration were measured during the level runs together with kinematic measures (e.g. stride length and frequency) using high-speed video analysis. Downhill running resulted in significant (P < 0.05) decreases in maximal isometric strength of the knee extensors, the development of muscle soreness, and increases in plasma creatine kinase activity and myoglobin concentration, which lasted for 5 days after downhill running. Significant (P < 0.05) changes in all running economy and kinematic measures from baseline were evident at 2 and 5 days after downhill running at 80% and 90% VO2(max), but not at 70% VO2(max). These results suggest that running economy assessed at high intensity is affected more than at low intensity (lower than the lactate threshold).