Abstract Purpose Differential diagnoses of primary pancreatic lesions include pancreatic ductal adenocarcinomas (PDAC) and inflammatory lesions of the pancreas (ILP). Post-pancreatic surgery, differentiation of postoperative reactive tissue (PRT) and PDAC-recurrence challenges oncological imaging. Static 68Ga-FAPI-PET/CT uptake is increased in all of these lesions with marked overlap in signal intensity, hampering their FAPI-PET-based assessment. Here, we evaluated static and parametric imaging parameters for discrimination of pancreatic lesions in primary and post-pancreatic surgery scenarios. Methods 55 Patients with pancreatic lesions (36 primary, 19 post-pancreatic surgery) underwent static and dynamic 68Ga-FAPI-46-PET/CT. Primary lesions were classified either by histology following PET/CT or follow-up (> 6 months). Post-surgery, PRT and PDAC-recurrence were classified by CT- and clinical course (> 18 months). Parametric maps (1 tissue compartment (1TC), 2TC and Logan plot (LP)) from dynamic PET-data were generated via image-based aortic input function using PMOD-software. Pancreatic lesions (PDAC, ILP, PRT, PDAC-recurrence) were then delineated using VOI-technique (30–70% isocontour) and signal intensities were analyzed. SPSS was used to detect outliers, unpaired t-tests was applied for comparison of static and parametric imaging parameters. Receiver-operating-characteristic curves for differentiating PDAC/ILP or recurrent PDAC/PRT were generated. Results 42 patients were included in the final analysis: in primary setting, 16 PDAC and 10 ILP; in post-surgery setting 9 PDAC-recurrences and 7 PRT. In the primary setting, although PDAC showed higher SUVmax/mean than ILP, no significant differences in maximum/mean signal values neither in static imaging nor in parametric maps were detected. With regard to the differentiation of PDAC-recurrences versus postoperative tissue, LPmax were significantly higher in PDAC-recurrences compared to PRT (4.74 vs. 2.40, p-value 0.020) with AUC 82.5% (95-CI 0.62-1.0) and a possible diagnostic threshold at > 3,49 (LR + 5.44), while differences in static imaging or other parametric maps were not statistically significant. Conclusion Differentiating pancreatic lesions remains challenging. While LPmax significantly distinguished PDAC-recurrence from PRT, other parametric mapping parameters yielded no significant results. Larger studies and additional dynamic data analysis methods should be explored.
Transverse plane malalignment is a deformity often encountered in patients with Cerebral Palsy (CP) and derotational osteotomy (DO) represents the gold standard for correction of this condition. Reports specifically on unilaterally involved individuals are limited and it remains unclear whether DO is capable to additionally improve hip abductor lever arm dysfunction. 20 individuals with unilateral CP matched the inclusion criteria. Pre- and postoperative (short-term after unilateral DO) 3D-instrumented gait analyses (IGA) were compared and assessed for changes in transverse plane kinematics. Pelvic/trunk kinematics as well as coronal hip kinetics were included. Most remarkable findings were an improved/reduced, yet not physiological, pelvic retraction, significantly improved internal rotation of the hip and significantly improved foot progression. Trunk obliquity worsened postoperatively in the GMFCS level I subgroup. DO effectively improves internal hip rotation and foot progression. There were no relevant changes evident concerning trunk lean, indicating that DO does not relevantly improve hip abductor lever arm dysfunction in unilateral CP at short-term.
Background The efficacy of current bone-targeting agents, notably bisphosphonates, in the treatment of bone metastases remains limited by their systemic toxicity and excessively long half-life. This study aims to develop bone-targeting agents inspired by osteotropic peptides involved in the bone mineralization process. These agents are intended to provide an innovative alternative to bisphosphonates for precision bone targeting. Results Osteotropic peptides and phosphopeptides were obtained by solid-phase synthesis and conjugated to DOTA. The peptides were radiolabeled with gallium-68 or lutetium-177, and their binding affinity to bone was tested in vivo. Osteopontin and matrix extracellular phosphoglycoprotein (MEPE) derived peptides did not show strong binding to bone. Systematic variations in oligoglutamic acid chain length, as well as the positioning and clustering of phosphorylated serine residues, enabled the identification of an optimized phosphopeptide. Clustering phosphorylated sites within the peptide sequence provided significant advantages over phosphorylated moieties scattered throughout the peptide sequence. DOTA-pS(4)E(8) showed the strongest affinity for bone, comparable to the clinically used bone targeting agent methylene bisphosphonate (MBP). Conclusions The novel phosphopeptides match the outstanding bone-targeting capabilities of bisphosphonates and show comparable pharmacokinetics. Owing to their peptidic nature and the consequently anticipated favorable toxicological profile, these agents warrant further investigation as versatile bone-targeting vectors.
Muscle synergy analysis has been explored as means to better understand changes in motor control, with the aim to improve treatment outcomes after Single Event Multilevel Surgery (SEMLS) for children with cerebral palsy (CP). In this single-group study, we assess changes between pre- and post-surgery muscle synergies at both patient specific, and cohort levels after surgical intervention for children with CP. We analysed the walking data of 11 patients between the ages of 7–18 years old, including surface electromyography, joint angles and ground reaction forces, recorded before and after surgery. Muscle synergies were extracted and assessed for changes in dimensionality and sparseness between pre- and post-surgery. Our results show that at a patient specific level, pre- and post-surgery muscle synergies were not highly similar, with only 41 r > 0.8) after surgery, and an overall mean correlation of 0.53 ± 0.25. On the other hand, synergies obtained at the cohort level were highly similar post-surgery ( r > 0.87). These findings suggest that at an individual level, pre-surgery motor control cannot be assumed to be preserved post-surgery. CP synergies obtained at the cohort level from pre-surgery data can demonstrate more reliable preservation in post-surgery motor control. We also observed sparseness increasing with the number of synergies, which provides an interesting future research direction exploring the link with more complex motor control and a more typical gait pattern.
The aim of this study was to characterize the anatomical and imaging features of adult-type diffuse gliomas across histomolecular subtypes. Clinical 3-Tesla brain MRI images from 644 patients with pathologically confirmed adult-diffuse glioma before treatment was retrospectively evaluated: 527 IDH-wildtype glioblastoma, 71 astrocytoma, and 46 oligodendroglioma. Pre- and post-contrast T1-weighted, T2-weighted and FLAIR sequences were part of the MRI protocol. Contrast-enhancing tumors and non-enhancing lesions (NEL) were automatically segmented using HD-GLIO. We used a voxel-wise Fisher-exact-test followed by random-permutation (ADIFFI) to identify regions with higher occurrence of tumor associated with IDH-mutation status or 1p/19q-codeletion status. Mann-Whitney-U-test was used to compare signal intensities in CET and NEL across the three different subtypes of adult-diffuse glioma investigated here. We observed a significant correlation of IDH-mutant gliomas with a predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles. IDH-wildtype tumors had larger NEL volumes than IDH-mutant gliomas (p < 0.0001). Signal intensity analysis demonstrated consistently lower T1w and T1-CE values and higher T2w and FLAIR values in IDH-mutant gliomas (all p < 0.0001). Oligodendrogliomas showed higher signal intensity on T1-CE images compared to astrocytomas (p = 0.035). We analyzed a large radio-genomic patient cohort consisting of glioblastoma, astrocytoma and oligodendroglioma. Our findings are in line with previously analyzed smaller patient cohorts. Our findings underline the importance of the IDH-mutation for determining tumor location and potentially point to a cell of origin along the rostral extension of the lateral ventricles. Adult-type diffuse gliomas with IDH-mutation showed a predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles. Signal intensity analysis demonstrated consistently lower T1w and T1-CE values and higher T2w and FLAIR values in IDH-mutant gliomas. Oligodendrogliomas showed higher mean signal intensity of NEL on T1-CE images than astrocytomas.
