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.