68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

Comparison of diffusion-weighted MRI and [18F]FDG PET/MRI for treatment monitoring in pediatric Hodgkin and non-Hodgkin lymphoma.

OBJECTIVE: To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([18F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma. MATERIALS AND METHODS: In a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [18F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1-21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [18F]FDG PET/MRI-based response classifications with Gwet's agreement coefficient (AC). RESULTS: After induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [18F]FDG PET/MRI (Gwet's AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet's AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [18F]FDG PET/MRI response assessments (Gwet's AC = 0.97; 95% CI: 0.91, 1). CONCLUSION: Therapy response of Hodgkin lymphoma can be evaluated with either [18F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach. CLINICAL RELEVANCE STATEMENT: Hodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI. KEY POINTS: • Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation. • After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma. • At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types.

Modified PROMISE criteria for standardized interpretation of gastrin-releasing peptide receptor (GRPR)-targeted PET.

PURPOSE: There are image interpretation criteria to standardize reporting prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). As up to 10% of prostate cancer (PC) do not express PSMA, other targets such as gastrin-releasing peptide receptor (GRPR) are evaluated. Research on GRPR-targeted imaging has been slowly increasing in usage at staging and biochemical recurrence (BCR) of PC. We therefore propose a modification of the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria (mPROMISE) for GRPR-targeted PET. METHODS: [68 Ga]Ga-RM2 PET data from initially prospective studies performed at our institution were retrospectively reviewed: 44 patients were imaged for staging and 100 patients for BCR PC. Two nuclear medicine physicians independently evaluated PET according to the mPROMISE criteria. A third expert reader served as standard reference. Interreader reliability was computed for GRPR expression, prostate bed (T), lymph node (N), skeleton (Mb), organ (Mc) metastases, and final judgment of the scan. RESULTS: The interrater reliability for GRPR PET at staging was moderate for GRPR expression (0.59; 95% confidence interval [CI] 0.40, 0.78), substantial for T-stage (0.78; 95% CI 0.63, 0.94), and almost perfect for N-stage (0.97; 95% CI 0.92, 1.00) and final judgment (0.92; 95% CI 0.82, 1.00). The interreader agreement at BCR showed substantial agreement for GRPR expression (0.70; 95% CI 0.59, 0.81) and final judgment (0.65; 95% CI 0.53, 0.78), while almost perfect agreement was seen across the major categories (T, N, Mb, Mc). Acceptable performance of the mPROMISE criteria was found for all subsets when compared to the standard reference. CONCLUSION: Interpreting GRPR-targeted PET using the mPROMISE criteria showed its reliability with substantial or almost perfect interrater agreement across all major categories. The proposed modification of the PROMISE criteria will aid clinicians in decreasing the level of uncertainty, and clinical trials to achieve uniform evaluation, reporting, and comparability of GRPR-targeted PET. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03113617 and NCT02624518.

Tyrosine kinase inhibitor therapy in pediatric sarcoma: Prognostic implications of pulmonary metastatic cavitation.

PURPOSES: This study aims to ascertain the prevalence of cavitations in pulmonary metastases among pediatric and young adult patients with sarcoma undergoing tyrosine kinase inhibitor (TKI) therapy, and assess whether cavitation can predict clinical response and survival outcomes. METHODS: In a single-center retrospective analysis, we examined chest computed tomography (CT) scans of 17 patients (median age 16 years; age range: 4-25 years) with histopathologically confirmed bone (n = 10) or soft tissue (n = 7) sarcoma who underwent TKI treatment for lung metastases. The interval between TKI initiation and the onset of lung nodule cavitation and tumor regrowth were assessed. The combination of all imaging studies and clinical data served as the reference standard for clinical responses. Progression-free survival (PFS) was compared between patients with cavitating and solid nodules using Kaplan-Meier survival analysis and log-rank test. RESULTS: Five out of 17 patients (29%) exhibited cavitation of pulmonary nodules during TKI therapy. The median time from TKI initiation to the first observed cavitation was 79 days (range: 46-261 days). At the time of cavitation, all patients demonstrated stable disease. When the cavities began to fill with solid tumor, 60% (3/5) of patients exhibited progression in other pulmonary nodules. The median PFS for patients with cavitated pulmonary nodules after TKI treatment (6.7 months) was significantly longer compared to patients without cavitated nodules (3.8 months; log-rank p-value = .03). CONCLUSIONS: Cavitation of metastatic pulmonary nodules in sarcoma patients undergoing TKI treatment is indicative of non-progressive disease, and significantly correlates with PFS.

External Validation of a Five-Tiered CT Algorithm for the Diagnosis of Clear Cell Renal Cell Carcinoma: A Retrospective Five-Reader Study.

BACKGROUND. In 2022, a five-tiered CT algorithm was proposed for predicting whether a small (cT1a) solid renal mass represents clear cell renal cell carcinoma (ccRCC). OBJECTIVE. The purpose of this external validation study was to evaluate the proposed CT algorithm for diagnosis of ccRCC among small solid renal masses. METHODS. This retrospective study included 93 patients (median age, 62 years; 42 women, 51 men) with 97 small solid renal masses that were seen on corticomedullary phase contrast-enhanced CT performed between January 2012 and July 2022 and subsequently underwent surgical resection. Five readers (three attending radiologists, two clinical fellows) independently evaluated masses for the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score; these scores were used to derive the CT score by use of the previously proposed CT algorithm. The CT score's sensitivity, specificity, and PPV for ccRCC were calculated at threshold of 4 or greater, and the NPV for ccRCC was calculated at a threshold of 3 or greater (consistent with thresholds in studies of the MRI-based clear cell likelihood score and the CT algorithm's initial study). The CT score's sensitivity and specificity for papillary RCC were calculated at a threshold of 2 or less. Interreader agreement was assessed using the Gwet agreement coefficient (AC1). RESULTS. Overall, 61 of 97 masses (63%) were malignant and 43 of 97 (44%) were ccRCC. Across readers, CT score had sensitivity ranging from 47% to 95% (pooled sensitivity, 74% [95% CI, 68-80%]), specificity ranging from 19% to 83% (pooled specificity, 59% [95% CI, 52-67%]), PPV ranging from 48% to 76% (pooled PPV, 59% [95% CI, 49-71%]), and NPV ranging from 83% to 100% (pooled NPV, 90% [95% CI, 84-95%]), for ccRCC. A CT score of 2 or less had sensitivity ranging from 44% to 100% and specificity ranging from 77% to 98% for papillary RCC (representing nine of 97 masses). Interreader agreement was substantial for attenuation score (AC1 = 0.70), poor for heterogeneity score (AC1 = 0.17), fair for five-tiered CT score (AC1 = 0.32), and fair for dichotomous CT score at a threshold of 4 or greater (AC1 = 0.24 [95% CI, 0.14-0.33]). CONCLUSION. The five-tiered CT algorithm for evaluation of small solid renal masses was tested in an external sample and showed high NPV for ccRCC. CLINICAL IMPACT. The CT algorithm may be used for risk stratification and patient selection for active surveillance by identifying patients unlikely to have ccRCC.

Hepatocellular Adenoma Subtypes Based on 2017 Classification System: Exploratory Study of Gadoxetate Disodium-Enhanced MRI Features With Proposal of a Diagnostic Algorithm.

BACKGROUND. The classification of hepatocellular adenomas (HCAs) was updated in 2017 on the basis of genetic and molecular analysis. OBJECTIVE. The purpose of this article was to evaluate features on gadoxetate disodium-enhanced MRI of HCA subtypes on the basis of the 2017 classification and to propose a diagnostic algorithm for determining subtype using these features. METHODS. This retrospective study included 56 patients (49 women, seven men; mean age, 37 ± 13 [SD] years) with histologically confirmed HCA evaluated by gadoxetate disodium-enhanced MRI from January 2010 to January 2021. Subtypes were reclassified using 2017 criteria: hepatocyte nuclear factor-1α mutated HCA (HHCA), inflammatory HCA (IHCA), ß-catenin exon 3 activated HCA (ß-HCA), mixed inflammatory and ß-HCA (ß-IHCA), sonic hedgehog HCA (shHCA), and unclassified HCA (UHCA). Qualitative MRI features were assessed. Liver-to-lesion contrast enhancement ratios (LLCERs) were measured. Subtypes were compared, and a diagnostic algorithm was proposed. RESULTS. The analysis included 65 HCAs: 16 HHCAs, 31 IHCAs, six ß-HCA, four ß-IHCA, five shHCA, and three UHCAs. HHCAs showed homogeneous diffuse intralesional steatosis in 94%, whereas all other HCAs showed this finding in 0% (p < .001). IHCAs showed the "atoll" sign in 58%, whereas all other HCAs showed this finding in 12% (p < .001). IHCAs showed moderate T2 hyperintensity in 52%, whereas all other HCAs showed this finding in 12% (p < .001). The ß-HCAs and ß-IHCAs occurred in men in 63%, whereas all other HCAs occurred in men in 4% (p < .001). The ß-HCAs and ß-IHCAs had a mean size of 10.1 ± 6.8 cm, whereas all other HCAs had a mean size of 5.1 ± 2.9 cm (p = .03). The ß-HCAs and ß-IHCAs showed fluid components in 60%, whereas all other HCAs showed this finding in 5% (p < .001). Hepatobiliary phase iso- or hyperintensity was observed in 80% of ß-HCAs and ß-IHCAs versus 5% of all other HCAs (p < .001). Hepatobiliary phase LLCER was positive in nine HCAs (eight ß-HCAs and ß-IHCAs; one IHCA). The shHCA and UHCA did not show distinguishing features. The proposed diagnostic algorithm had accuracy of 98% for HHCAs, 83% for IHCAs, and 95% for ß-HCAs or ß-IHCAs. CONCLUSION. Findings on gadoxetate disodium-enhanced MRI, including hepatobiliary phase characteristics, were associated with HCA subtypes using the 2017 classification. CLINICAL IMPACT. The algorithm identified common HCA subtypes with high accuracy, including those with ß-catenin exon 3 mutations.

[Analysis of muscle synergy and muscle functional network at different walking speeds based on surface electromyographic signal].

An in-depth understanding of the mechanism of lower extremity muscle coordination during walking is the key to improving the efficacy of gait rehabilitation in patients with neuromuscular dysfunction. This paper investigates the effect of changes in walking speed on lower extremity muscle synergy patterns and muscle functional networks. Eight healthy subjects were recruited to perform walking tasks on a treadmill at three different speeds, and the surface electromyographic signals (sEMG) of eight muscles of the right lower limb were collected synchronously. The non-negative matrix factorization (NNMF) method was used to extract muscle synergy patterns, the mutual information (MI) method was used to construct the alpha frequency band (8-13 Hz), beta frequency band (14-30 Hz) and gamma frequency band (31-60 Hz) muscle functional network, and complex network analysis methods were introduced to quantify the differences between different networks. Muscle synergy analysis extracted 5 muscle synergy patterns, and changes in walking speed did not change the number of muscle synergy, but resulted in changes in muscle weights. Muscle network analysis found that at the same speed, high-frequency bands have lower global efficiency and clustering coefficients. As walking speed increased, the strength of connections between local muscles also increased. The results show that there are different muscle synergy patterns and muscle function networks in different walking speeds. This study provides a new perspective for exploring the mechanism of muscle coordination at different walking speeds, and is expected to provide theoretical support for the evaluation of gait function in patients with neuromuscular dysfunction.

Reduced Acquisition Time per Bed Position for PET/MRI Using 68Ga-RM2 or 68Ga-PSMA-11 in Patients With Prostate Cancer: A Retrospective Analysis.

BACKGROUND. Growing clinical adoption of PET/MRI for prostate cancer (PC) evaluation has increased interest in reducing PET/MRI scanning times. Reducing acquisition time per bed position below current times of at least 5 minutes would allow shorter examination lengths. OBJECTIVE. The purpose of this study was to evaluate the effect of different reduced PET acquisition times in patients with PC who underwent 68Ga-PSMA-11 or 68Ga-RM2 PET/MRI using highly sensitive silicon photomultiplier-based PET detectors. METHODS. This study involved retrospective review of men with PC who underwent PET/MRI as part of one of two prospective trials. Fifty men (mean [± SD] age, 69.9 ± 6.8 years) who underwent 68Ga-RM2 PET/MRI and 50 men (mean age, 66.6 ± 5.7 years) who underwent 68Ga-PSMA-11 PET/MRI were included. PET/MRI used a time-of-flight-enabled system with silicon photomultiplier-based detectors. The acquisition time was 4 minutes per bed position. PET data were reconstructed using acquisition times of 30 seconds, 1 minute, 2 minutes, 3 minutes, and 4 minutes. Three readers independently assessed image quality for each reconstruction using a 5-point Likert scale (with 1 denoting nondiagnostic and 5 indicating excellent quality). One reader measured SUVmax for up to six lesions per patient. Two readers independently assessed lesion conspicuity using a a 3-point Likert scale (with 1 indicating that lesions were not visualized and 3 denoting that they were definitely visualized). RESULTS. Mean image quality across readers at 30 seconds, 1 minutes, 2 minutes, 3 minutes, and 4 minutes was, for 68Ga-RM2 PET/MRI, from 1.0 ± 0.2 to 1.7 ± 0.7, 2.0 ± 0.3 to 2.6 ± 0.8, 3.1 ± 0.5 to 3.9 ± 0.8, 4.6 ± 0.6 to 4.7 ± 0.6, and 4.8 ± 0.4 to 4.8 ± 0.5, respectively, and for 68Ga-PSMA-11 PET/MRI it was from 1.2 ± 0.4 to 1.8 ± 0.6, 2.2 ± 0.4 to 2.8 ± 0.7, 3.6 ± 0.6 to 4.1± 0.8, 4.8 ± 0.4 to 4.9 ± 0.4, and 4.9 ± 0.3 to 5.0 ± 0.2, respectively. The mean lesion SUVmax for 68Ga-RM2 PET/MRI was 11.1 ± 12.4, 10.2 ± 11.7, 9.6 ± 11.3, 9.5 ± 11.6, and 9.4 ± 11.6, respectively, and for 68Ga-PSMA-11 PET/MRI it was 14.7 ± 8.2, 12.9 ± 7.4, 12.1 ± 7.8, 11.7 ± 7.9, and 11.6 ± 7.9, respectively. Mean lesion conspicuity (reader 1/reader 2) was, for 68Ga-RM2 PET/MRI, 2.4 ± 0.5/2.7 ± 0.5, 2.9 ± 0.3/2.9 ± 0.3, 3.0 ± 0.0/3.0 ± 0.0, 3.0 ± 0.0/3.0 ± 0.0, and 3.0 ± 0.0/3.0 ± 0.0, respectively, and for 68Ga-PSMA-11 PET/MRI it was 2.6 ± 0.5/2.8 ± 0.4, 3.0 ± 0.2/2.9 ± 0.3, 3.0 ± 0.1/3.0 ± 0.2, 3.0 ± 0.0/3.0 ± 0.0, and 3.0 ± 0.0/3.0 ± 0.0, respectively. CONCLUSION. Our data support routine 3-minute acquisitions, which provided results very similar to those for 4-minute acquisitions. Two-minute acquisitions, although they lowered quality somewhat, provided acceptable performance and warrant consideration. CLINICAL IMPACT. When PC is evaluated using modern PET/MRI equipment, time per bed position may be reduced compared with historically used times. TRIAL REGISTRATION. ClinicalTrials.gov NCT02624518 and NCT02678351.

[Follow control of upper limb rehabilitation training based on Kinect and NAO robot].

Gesture imitation is a common rehabilitation strategy in limb rehabilitation training. In traditional rehabilitation training, patients need to complete training actions under the guidance of rehabilitation physicians. However, due to the limited resources of the hospital, it cannot meet the training and guidance needs of all patients. In this paper, we proposed a following control method based on Kinect and NAO robot for the gesture imitation task in rehabilitation training. The method realized the joint angles mapping from Kinect coordination to NAO robot coordination through inverse kinematics algorithm. Aiming at the deflection angle estimation problem of the elbow joint, a virtual space plane was constructed and realized the accurate estimation of deflection angle. Finally, a comparative experiment for deflection angle of the elbow joint angle was conducted. The experimental results showed that the root mean square error of the angle estimation value of this method in right elbow transverse deflection and vertical deflection directions was 2.734° and 2.159°, respectively. It demonstrates that the method can follow the human movement in real time and stably using the NAO robot to show the rehabilitation training program for patients.

Identifying bidirectional total and non-linear information flow in functional corticomuscular coupling during a dorsiflexion task: a pilot study.

BACKGROUND: The key challenge to constructing functional corticomuscular coupling (FCMC) is to accurately identify the direction and strength of the information flow between scalp electroencephalography (EEG) and surface electromyography (SEMG). Traditional TE and TDMI methods have difficulty in identifying the information interaction for short time series as they tend to rely on long and stable data, so we propose a time-delayed maximal information coefficient (TDMIC) method. With this method, we aim to investigate the directional specificity of bidirectional total and nonlinear information flow on FCMC, and to explore the neural mechanisms underlying motor dysfunction in stroke patients. METHODS: We introduced a time-delayed parameter in the maximal information coefficient to capture the direction of information interaction between two time series. We employed the linear and non-linear system model based on short data to verify the validity of our algorithm. We then used the TDMIC method to study the characteristics of total and nonlinear information flow in FCMC during a dorsiflexion task for healthy controls and stroke patients. RESULTS: The simulation results showed that the TDMIC method can better detect the direction of information interaction compared with TE and TDMI methods. For healthy controls, the beta band (14-30 Hz) had higher information flow in FCMC than the gamma band (31-45 Hz). Furthermore, the beta-band total and nonlinear information flow in the descending direction (EEG to EMG) was significantly higher than that in the ascending direction (EMG to EEG), whereas in the gamma band the ascending direction had significantly higher information flow than the descending direction. Additionally, we found that the strong bidirectional information flow mainly acted on Cz, C3, CP3, P3 and CPz. Compared to controls, both the beta-and gamma-band bidirectional total and nonlinear information flows of the stroke group were significantly weaker. There is no significant difference in the direction of beta- and gamma-band information flow in stroke group. CONCLUSIONS: The proposed method could effectively identify the information interaction between short time series. According to our experiment, the beta band mainly passes downward motor control information while the gamma band features upward sensory feedback information delivery. Our observation demonstrate that the center and contralateral sensorimotor cortex play a major role in lower limb motor control. The study further demonstrates that brain damage caused by stroke disrupts the bidirectional information interaction between cortex and effector muscles in the sensorimotor system, leading to motor dysfunction.

[An improved maximal information coefficient algorithm applied in the analysis of functional corticomuscular coupling for stroke patients].

The functional coupling between motor cortex and effector muscles during autonomic movement can be quantified by calculating the coupling between electroencephalogram (EEG) signal and surface electromyography (sEMG) signal. The maximal information coefficient (MIC) algorithm has been proved to be effective in quantifying the coupling relationship between neural signals, but it also has the problem of time-consuming calculations in actual use. To solve this problem, an improved MIC algorithm was proposed based on the efficient clustering characteristics of K-means ++ algorithm to accurately detect the coupling strength between nonlinear time series. Simulation results showed that the improved MIC algorithm proposed in this paper can capture the coupling relationship between nonlinear time series quickly and accurately under different noise levels. The results of right dorsiflexion experiments in stroke patients showed that the improved method could accurately capture the coupling strength of EEG signal and sEMG signal in the specific frequency band. Compared with the healthy controls, the functional corticomuscular coupling (FCMC) in beta (14~30 Hz) and gamma band (31~45 Hz) were significantly weaker in stroke patients, and the beta-band MIC values were positively correlated with the Fugl-Meyers assessment (FMA) scale scores. The method proposed in this study is hopeful to be a new method for quantitative assessment of motor function for stroke patients.

Comparison of ferumoxytol- and gadolinium chelate-enhanced MRI for assessment of sarcomas in children and adolescents.

OBJECTIVES: We compared the value of ferumoxytol (FMX)- and gadolinium (Gd)-enhanced MRI for assessment of sarcomas in paediatric/adolescent patients and hypothesised that tumour size and morphological features can be equally well assessed with both protocols. METHODS: We conducted a retrospective study of paediatric/adolescent patients with newly diagnosed bone or soft tissue sarcomas and both pre-treatment FMX- and Gd-MRI scans, which were maximal 4 weeks apart. Both protocols included T1- and T2-weighted sequences. One reader assessed tumour volumes, signal-to-noise ratios (SNR) of the primary tumour and adjacent tissues and contrast-to-noise ratios (CNR) of FMX- and Gd-MRI scans. Additionally, four readers scored FMX- and Gd-MRI scans according to 15 diagnostic parameters, using a Likert scale. The results were pooled across readers and compared between FMX- and Gd-MRI scans. Statistical methods included multivariate analyses with different models. RESULTS: Twenty-two patients met inclusion criteria (16 males, 6 females; mean age 15.3 ± 5.0). Tumour volume was not significantly different on T1-LAVA (p = 0.721), T1-SE (p = 0.290) and T2-FSE (p = 0.609) sequences. Compared to Gd-MRI, FMX-MRI demonstrated significantly lower tumour SNR on T1-LAVA (p < 0.001), equal tumour SNR on T1-SE (p = 0.104) and T2-FSE (p = 0.305), significantly higher tumour-to-marrow CNR (p < 0.001) on T2-FSE as well as significantly higher tumour-to-liver (p = 0.021) and tumour-to-vessel (p = 0.003) CNR on T1-LAVA images. Peritumoural and marrow oedema enhanced significantly more on Gd-MRI compared to FMX-MRI (p < 0.001/p = 0.002, respectively). Tumour thrombi and neurovascular bundle involvement were assessed with a significantly higher confidence on FMX-MRI (both p < 0.001). CONCLUSIONS: FMX-MRI provides equal assessment of the extent of bone and soft tissue sarcomas compared to Gd-MRI with improved tumour delineation and improved evaluation of neurovascular involvement and tumour thrombi. Therefore, FMX-MRI is a possible alternative to Gd-MRI for tumour staging in paediatric/adolescent sarcoma patients. KEY POINTS: • Ferumoxytol can be used as an alterative to gadolinium chelates for MRI staging ofpaediatric sarcomas. • Ferumoxytol-enhanced MRI provides equal assessment of tumour size and other diagnostic parameters compared to gadolinium chelate-enhanced MRI. • Ferumoxytol-enhanced MRI provides improved delineation of sarcomas from bone marrow, liver and vessels compared to gadolinium chelate-enhanced MRI.

Comparison of Opioid Medication Use after Conventional Chemoembolization versus Drug-Eluting Embolic Chemoembolization.

PURPOSE: To assess the use of opioid analgesics and/or antiemetic drugs for pain and nausea following selective chemoembolization with doxorubicin-based conventional (c)-transarterial chemoembolization versus drug-eluting embolic (DEE)-transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From October 2014 to 2016, 283 patients underwent 393 selective chemoembolization procedures including 188 patients (48%) who underwent c-transarterial chemoembolization and 205 (52%) who underwent DEE-transarterial chemoembolization. Medical records for all patients were retrospectively reviewed. Administration of postprocedural opioid and/or antiemetic agents were collated. Time of administration was stratified as phase 1 recovery (0-6 hours) and observation (6-24 hours). Logistic regression model was used to investigate the relationship of transarterial chemoembolization type and use of intravenous and/or oral analgesic and antiemetic medications while controlling for other clinical variables. RESULTS: More patients treated with DEE-transarterial chemoembolization required intravenous analgesia in the observation (6-24 hours) phase (18.5%) than those treated with c-transarterial chemoembolization (10.6%; P = .033). Similar results were noted for oral analgesic agents (50.2% vs. 31.4%, respectively; P < .001) and antiemetics (17.1% vs. 7.5%, respectively; P = .006) during the observation period. Multivariate regression models identified DEE-transarterial chemoembolization as an independent predictor for oral analgesia (odds ratio [OR], 1.84; P = .011), for intravenous and oral analgesia in opioid-naïve patients (OR, 2.46; P = .029) and for antiemetics (OR, 2.56; P = .011). CONCLUSIONS: Compared to c-transarterial chemoembolization, DEE-transarterial chemoembolization required greater amounts of opioid analgesic and antiemetic agents 6-24 hours after the procedure. Surgical data indicate that a persistent opioid habit can develop even after minor surgeries, therefore, caution should be exercised, and a regimen of nonopiate pain medications should be considered to reduce postprocedural pain after transarterial chemoembolization.

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.

Background Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair. Purpose To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation. Results Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks. Conclusion Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sneag and Potter in this issue.

A New Approach to Fall Detection Based on Improved Dual Parallel Channels Convolutional Neural Network.

Falls are the major cause of fatal and non-fatal injury among people aged more than 65 years. Due to the grave consequences of the occurrence of falls, it is necessary to conduct thorough research on falls. This paper presents a method for the study of fall detection using surface electromyography (sEMG) based on an improved dual parallel channels convolutional neural network (IDPC-CNN). The proposed IDPC-CNN model is designed to identify falls from daily activities using the spectral features of sEMG. Firstly, the classification accuracy of time domain features and spectrograms are compared using linear discriminant analysis (LDA), k-nearest neighbor (KNN) and support vector machine (SVM). Results show that spectrograms provide a richer way to extract pattern information and better classification performance. Therefore, the spectrogram features of sEMG are selected as the input of IDPC-CNN to distinguish between daily activities and falls. Finally, The IDPC-CNN is compared with SVM and three different structure CNNs under the same conditions. Experimental results show that the proposed IDPC-CNN achieves 92.55% accuracy, 95.71% sensitivity and 91.7% specificity. Overall, The IDPC-CNN is more effective than the comparison in accuracy, efficiency, training and generalization.

Albumin-Bilirubin Score: An Accurate Predictor of Hepatic Decompensation in High-Risk Patients Undergoing Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To evaluate validity of albumin-bilirubin (ALBI) grade as a predictor of acute-on-chronic liver failure (ACLF) after transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients with baseline moderate to severe liver dysfunction. MATERIALS AND METHODS: In this retrospective study, serum albumin and bilirubin levels measured before chemoembolization were used to calculate ALBI score in 123 patients treated with 187 high-risk chemoembolizations. Procedures were considered high risk if Child-Turcotte-Pugh score before chemoembolization was ≥ 8. ACLF was objectively measured using chronic liver failure-sequential organ failure assessment score at 30 and 90 d. The 30-day mortality and morbidity from new or worsening ascites and/or hepatic encephalopathy (HE) were assessed. Univariate and multivariate analyses were used to identify clinical and procedural predictors of ACLF in this high-risk population. RESULTS: ACLF occurred after 15 (8%) high-risk chemoembolizations within 30 days and an additional 9 (5%) procedures between 30 and 90 days. Overall 30-day mortality was 2.7%. New or worsened ascites and/or HE occurred after 52 (28%) procedures within 30 days. Significant prognosticators of ACLF at 90 days revealed by univariate analysis were bilirubin (P = .004), albumin (P = .007), and ALBI score (P = .002), with ALBI score remaining statistically significant on multivariate regression analysis (OR = 3.99; 95% CI, 1.70-9.40; P = .002). CONCLUSIONS: Chemoembolization for HCC can be performed safely in patients with moderate to severe liver dysfunction. ALBI score before chemoembolization provides objective prognostication for ACLF after chemoembolization in this cohort and may be used for risk stratification.

Diagnostic Performance of Margin Features in Thyroid Nodules in Prediction of Malignancy.

OBJECTIVE: The purpose of this study was to evaluate thyroid nodule margins for specific morphologic features and determine the diagnostic performance of these features in differentiating papillary carcinoma from benign thyroid nodules. MATERIALS AND METHODS: Nodules measuring 1-3 cm in largest diameter that had been evaluated with high-resolution ultrasound (12-18 MHz) and ultrasound-guided biopsy with definitive pathologic diagnosis were analyzed. Three blinded board-certified readers evaluated high-resolution images of each nodule for jagged edges, lobulated borders, and curved borders along their margins. Reader interpretations were correlated with the pathologic diagnosis to determine the diagnostic performance of each feature. A board-certified pathologist analyzed 10 randomly selected nodules with jagged edges by slide review to evaluate for structural correlation with the imaging finding. RESULTS: The diagnostic performance of jagged edges in papillary carcinoma of the thyroid was 67.4% sensitive and 78.3% specific (odds ratio, 7.44; p < 0.001) for malignancy. Jagged edges correlated with infiltrative variant expansion at slide review. Lobulated borders had sensitivity of 76.1% and specificity of 60.9% for papillary carcinoma (odds ratio, 4.95; p = 0.001) for malignancy. Curved borders were not a significant predictor of papillary carcinoma. CONCLUSION: Jagged edges and lobulated borders of thyroid nodule margins are statistically significant predictors of papillary carcinoma of the thyroid. Jagged edges correlate with infiltrative-type expansion and may be useful predictors of more aggressive papillary carcinomas.

Flexible Graphene Electrodes for Prolonged Dynamic ECG Monitoring.

This paper describes the development of a graphene-based dry flexible electrocardiography (ECG) electrode and a portable wireless ECG measurement system. First, graphene films on polyethylene terephthalate (PET) substrates and graphene paper were used to construct the ECG electrode. Then, a graphene textile was synthesized for the fabrication of a wearable ECG monitoring system. The structure and the electrical properties of the graphene electrodes were evaluated using Raman spectroscopy, scanning electron microscopy (SEM), and alternating current impedance spectroscopy. ECG signals were then collected from healthy subjects using the developed graphene electrode and portable measurement system. The results show that the graphene electrode was able to acquire the typical characteristics and features of human ECG signals with a high signal-to-noise (SNR) ratio in different states of motion. A week-long continuous wearability test showed no degradation in the ECG signal quality over time. The graphene-based flexible electrode demonstrates comfortability, good biocompatibility, and high electrophysiological detection sensitivity. The graphene electrode also combines the potential for use in long-term wearable dynamic cardiac activity monitoring systems with convenience and comfort for use in home health care of elderly and high-risk adults.

Quantitative assessment of the association between MTHFR rs1801131 polymorphism and risk of liver cancer.

Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism which plays a key role in cell metabolism. MTHFR rs1801131 (A1298C) polymorphism can decrease in vitro MTHFR enzyme activity and has been hypothesized to be associated with liver cancer risk. This study aimed to quantify the strength of the association between MTHFR rs1801131 polymorphism and liver cancer risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies relating on the association between MTHFR rs1801131 polymorphism and risk of liver cancer. Seven studies with 2,030 cases of liver cancer and 3,096 controls were finally included into the meta-analysis. Meta-analysis of a total of seven studies showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer (for CC versus AA: odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.47-0.89, P = 0.007; for CC versus AA + AC: OR = 0.65, 95% CI 0.48-0.89, P = 0.006). Subgroup by race showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer in Asians (CC versus AA: OR = 0.64, 95% CI 0.46-0.90, P = 0.010; for CC versus AA + AC: OR = 0.63, 95% CI 0.45-0.88, P = 0.007). However, the association in Caucasians was still unclear owing to the limited data available now. Thus, Asian individuals with the homozygote genotype CC of MTHFR rs1801131 polymorphism are significantly associated with decreased risk of liver cancer. The association in Caucasians needs further studies.