Tobias Greve

Accurate visualization of glioblastoma is essential for guiding biopsy, resection and radiotherapy. Contrast-enhanced MRI is routine in clinical practice, yet it can miss metabolically active tumor outside areas of blood-brain barrier disruption. In a histopathology-validated cohort with 472 tissue samples of 61 patients with IDH-wildtype glioblastoma, we show that O-(2-[¹⁸F]fluoroethyl)-L-tyrosine PET ([ ¹⁸ F]FET PET) depicts tumor tissue significantly better than contrast-enhanced MRI (CE-MRI), especially in regions that show no enhancement on MRI. [ ¹⁸ F]FET PET achieves substantially higher sensitivity for tumor detection (91.2% vs 52.6%) and maintains high reliability in non-enhancing tissue (positive predictive value 98.3%), findings that are consistent across newly diagnosed and recurrent disease and in both cohorts undergoing either resection or biopsy. These results indicate that [ ¹⁸ F]FET PET complements MRI by revealing MRI-occult tumor burden. Incorporating amino acid PET into routine planning may therefore improve the accuracy of tumor visualization and, ultimately, patient management.

OBJECTIVE: Radiofrequency thermocoagulation (RFT) of the gasserian ganglion provides rapid pain relief in trigeminal neuralgia (TN) and is minimally invasive. In multiple sclerosis (MS)–associated TN (MS-TN), recurrence may be more frequent than in idiopathic/classic TN (Id-TN), possibly due to demyelinating pathology. This study compared RFT outcomes between these etiologies. METHODS: The authors conducted a STROBE-compliant, single-center retrospective cohort study that screened 636 patients with TN treated between March 2012 and September 2021. Structured telephone interviews were completed in 350 patients, including the 5-level EQ-5D (EQ-5D-5L) for health-related quality of life (HRQOL). Of these patients, 182 received RFT as their first invasive treatment. The primary endpoint was the pain-free interval (PFI), defined as the time to recurrence (Barrow Neurological Institute Pain Intensity Scale score ≥ II or medication restart), analyzed using Kaplan-Meier curves and Cox proportional hazards regression models. Secondary outcomes included repeat interventions, permanent sensory deficits, and HRQOL. RESULTS: Of 182 eligible participants, 77 had MS-TN and 105 had Id-TN. Patients with MS-TN were younger (mean age 55.8 [SD 10.6] vs 70.5 [SD 8.6] years, p < 0.001). The median PFI was 33.9 (95% CI 15.5–52.3) months for MS-TN versus 87.0 (95% CI 43.1–130.9) months for Id-TN (p = 0.0493, log-rank test). The mean overall follow-up duration was 68.4 months. Despite earlier recurrence, repeat interventions achieved comparable adequate pain control at the last follow-up (68.8% in MS-TN vs 77.1% in Id-TN, p = 0.139). EQ-5D-5L scores improved significantly and converged at follow-up (p = 0.085). CONCLUSIONS: After the first RFT, pain control was shorter in MS-TN than in Id-TN. However, retreatment effectively restored long-term pain control and HRQOL, supporting the role of RFT in managing MS-TN. Regular follow-up is recommended to facilitate timely intervention.

Background: In glioblastoma studies, the presence of measurable disease is often required for trial eligibility. While response assessment according to RANO 2.0 relies on magnetic resonance imaging (MRI), the recently introduced positron emission tomography (PET) RANO 1.0 criteria allow standardized evaluation based on amino acid PET. This study compares the frequency of measurable disease according to PET RANO 1.0 vs RANO 2.0 criteria at key enrollment time points of clinical trials. Methods: In this retrospective, single-center study, we included patients with IDH-wildtype glioblastoma who underwent both [¹8F]FET PET and MRI, after standard first-line radiotherapy (time point T0) (defined per RANO 2.0) or at first progression (time point T1). Two independent raters evaluated measurable disease using PET RANO 1.0 and RANO 2.0 criteria. Further, tumor size, target lesions and tracer uptake metrics were analyzed. Results: In total 322 patients were included, 112 at T0 (median age: 59 years, interquartile range [IQR] 54-69), and 210 at T1 (median age: 59, IQR 53-67). On MRI, measurable disease was identified in 57/112 patients (50.9%) at T0 and in 137/210 patients (65.2%) at T1 (median sum of products of cross-sectional diameters: 143 mm2; 187 mm2). On PET, significantly more cases with measurable disease were detected: 102/112 patients, (91.1%) at T0 and 201/210 patients (95.7%) at T1 (median volumes: 9.86 cm³; 14.3 cm³) (P = .001). Conclusion: PET RANO 1.0 detects a substantially larger subset of patients with measurable disease compared to RANO 2.0. These findings warrant prospective validation of PET-based measurable disease as an inclusion criterion for clinical trials in IDH-wildtype glioblastoma, with the potential to broaden trial eligibility.

Objectives To compare caries detection using T1-based Free-breathing 3D Stack of Stars GRE (StarVIBE) and T1-weighted pointwise encoding time reduction with radial acquisition (PETRA) MRI sequences with the gold standard consisting of a combination of clinical evaluation and bitewing radiography. Materials and methods Included subjects were evaluated clinically by a dentist for the occurrence of caries. All subjects underwent bitewing radiographs and MRI of the viscerocranium, including 3D StarVIBE and 3D PETRA sequences. Caries lesions were evaluated for penetration depth (D1-D4). Signal intensity (SI) was measured in dental hard tissue, the pulp and caries lesions. Results 80 teeth were analyzed. Among these, 10 showed caries during clinical assessments and bitewing imaging, all of which were also detected on MRI. Furthermore, 5 additional lesions were identified exclusively on MRI. Overall image quality and diagnostic confidence were significantly higher in PETRA than in StarVIBE (4.7 vs. 3.9, p = 0.006). The SI for caries lesions was significantly higher in the PETRA sequence (-0.5 a.u. ± 1.5 a.u. vs. -4.2 a.u. ± 4.0 a.u., p = 0.002). Caries lesion volume was also significantly larger in PETRA (18 mm³± 14.8 mm³) compared to StarVIBE (11 mm³± 14.8 mm³, p = 0.003). Conclusion MRI identified all caries lesions that were detected both clinically and through bitewing imaging, along with additional lesions exclusive to MRI. The PETRA sequence outperformed StarVIBE in quantitative caries visualization.

Background/Objectives: Advancements in neuronavigation and intraoperative imaging have made gross-total resection of deep-seated lesions more feasible. However, in eloquently located regions, brain shift can lead to unintentional damage of functionally critical tissue during the approach. This study analyzes the feasibility and outcomes of a stereotactically guided microsurgical approach supported by intraoperative CT (iCT) for such lesions. Methods: Patients with deep-seated, eloquently located lesions treated between 03/2017 and 04/2023 at the Department of Neurosurgery, Ludwig-Maximilians-University (LMU) Munich, Germany, were included. Frame-based, image-guided stereotaxy was used for trajectory planning and catheter placement, verified by iCT. Microsurgical resection was conducted along the catheter trajectory using 2 mm conical blade retractors and continuous neurophysiological monitoring. Postoperative MRI assessed the extent of resection. Neurological outcomes were evaluated postoperatively, at 6 weeks, and at long-term follow-up in 12/2023. Results: A total of 12 patients were treated using the stereotactically guided microsurgical approach described in this study. In all cases, the implanted catheter precisely matched the preoperative trajectory, as confirmed by fused iCT data. Median durations were 23 min for stereotaxy and 3 h 7 min for microsurgery. Complete resection was achieved in all cases. One patient experienced transient hemiparesis and aphasia, both of which were fully resolved. All other patients showed neurological improvement or remained seizure-free at long-term follow-up. Conclusions: In selected cases, a stereotactically guided microsurgical approach with iCT enabled intraoperative localization of the target with high spatial accuracy and without immediate procedure-related complications in this limited cohort. Our findings support the feasibility of the technique; however, conclusions regarding clinical efficacy or broader applicability are limited by the small sample size and non-comparative study design.

Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) has been used for non-invasive assessment of regional body fat distributions. More recently, texture analysis (TA) has been proposed to reveal even more detailed information about the vertebral or muscular composition beyond PDFF. The aim of this study was to investigate associations between vertebral bone marrow and paraspinal muscle texture features derived from CSE-MRI-based PDFF maps in a cohort of healthy subjects. In this study, 44 healthy subjects (13 males, 55 ± 30 years; 31 females, 39 ± 17 years) underwent 3T MRI including a six-echo three-dimensional (3D) spoiled gradient echo sequence used for CSE-MRI at the lumbar spine and the paraspinal musculature. The erector spinae muscles (ES), the psoas muscles (PS), and the vertebral bodies L1-4 (LS) were manually segmented. Mean PDFF values and texture features were extracted for each compartment. Features were compared between males and females using logistic regression analysis adjusted for age and body mass index (BMI). All texture features of ES except for Sum Average were significantly (p < 0.05) different between men and women. The three global texture features (Variance, Skewness, Kurtosis) for PS as well as LS showed a significant difference between male and female subjects (p < 0.05). Mean PDFF measured in PS and ES was significantly higher in females, but no difference was found for the vertebral bone marrow’s PDFF. Partial correlation analysis between the texture features of the spine and the paraspinal muscles revealed a highly significant correlation for Variance(global) (r = 0.61 for ES, r = 0.62 for PS; p < 0.001 respectively). Texture analysis using PDFF maps based on CSE-MRI revealed differences between healthy male and female subjects. Global texture features in the lumbar vertebral bone marrow allowed for differentiation between men and women, when the overall PDFF was not significantly different, indicating that PDFF maps may contain detailed and subtle textural information beyond fat fraction. The observed significant correlation of Variance(global) suggests a metabolic interrelationship between vertebral bone marrow and the paraspinal muscles.

Purpose: Osteoporosis is prevalent and entails alterations of vertebral bone and marrow. Yet, the spine is also a common site of metastatic spread. Parameters that can be non-invasively measured and could capture these alterations are the volumetric bone mineral density (vBMD), proton density fat fraction (PDFF) as an estimate of relative fat content, and failure displacement and load from finite element analysis (FEA) for assessment of bone strength. This study’s purpose was to investigate if osteoporotic and osteoblastic metastatic changes in lumbar vertebrae can be differentiated based on the abovementioned parameters (vBMD, PDFF, and measures from FEA), and how these parameters correlate with each other.Materials and Methods: Seven patients (3 females, median age: 77.5 years) who received 3-Tesla magnetic resonance imaging (MRI) and multi-detector computed tomography (CT) of the lumbar spine and were diagnosed with either osteoporosis (4 patients) or diffuse osteoblastic metastases (3 patients) were included. Chemical shift encoding-based water-fat MRI (CSE-MRI) was used to extract the PDFF, while vBMD was extracted after automated vertebral body segmentation using CT. Segmentation masks were used for FEA-based failure displacement and failure load calculations. Failure displacement, failure load, and PDFF were compared between patients with osteoporotic vertebrae versus patients with osteoblastic metastases, considering non-fractured vertebrae (L1-L4). Associations between those parameters were assessed using Spearman correlation.Results: Median vBMD was 59.3 mg/cm³ in osteoporotic patients. Median PDFF was lower in the metastatic compared to the osteoporotic patients (11.9% vs. 43.8%, p=0.032). Median failure displacement and failure load were significantly higher in metastatic compared to osteoporotic patients (0.874 mm vs. 0.348 mm, 29,589 N vs. 3,095 N, p=0.034 each). A strong correlation was noted between PDFF and failure displacement (rho -0.679, p=0.094). A very strong correlation was noted between PDFF and failure load (rho -0.893, p=0.007).Conclusion: PDFF as well as failure displacement and load allowed to distinguish osteoporotic from diffuse osteoblastic vertebrae. Our findings further show strong associations between PDFF and failure displacement and load, thus may indicate complimentary pathophysiological associations derived from two non-invasive techniques (CSE-MRI and CT) that inherently measure different properties of vertebral bone and marrow.

Facial muscle corticobulbar motor evoked potentials (FMcoMEPs) are used to monitor facial nerve integrity during vestibular schwannoma resections to increase maximal safe tumor resection. Established warning criteria, based on ipsilateral amplitude reduction, have the limitation that the rate of false positive alarms is high, in part because FMcoMEP changes occur on both sides, e.g., due to brain shift or pneumocephalus. We retrospectively compared the predictive value of ipsilateral-only warning criteria and actual intraoperative warnings with a novel candidate warning criterion, based on “ipsilateral versus contralateral difference in relative stimulation threshold increase, from baseline to end of resection” (BilatMT ≥ 20%), combined with an optimistic approach in which a warning would be triggered only if all facial muscles on the affected side deteriorated. We included 60 patients who underwent resection of vestibular schwannoma. The outcome variable was postoperative facial muscle function. Retrospectively applying BilatMT, with the optimistic approach, was found to have a significantly better false positive rate, which was much lower (9% at day 90) than the traditionally used ipsilateral warning criteria (>20%) and was also lower than actual intraoperative warnings. This is the first report combining the threshold method with an optimistic approach in a bilateral multi-facial muscle setup. This method could substantially reduce the rate of false positive alarms in FMcoMEP monitoring.

In this study, the associations of cervical and lumbar paraspinal musculature based on a texture analysis of proton density fat fraction (PDFF) maps were investigated to identify gender- and anatomical location-specific structural patterns. Seventy-nine volunteers (25 men, 54 women) participated in the present study (mean age ± standard deviation: men: 43.7 ± 24.6 years; women: 37.1 ± 14.0 years). Using manual segmentations of the PDFF maps, texture analysis was performed and texture features were extracted. A significant difference in the mean PDFF between men and women was observed in the erector spinae muscle (p < 0.0001), whereas the mean PDFF did not significantly differ in the cervical musculature and the psoas muscle (p > 0.05 each). Among others, Variance(global) and Kurtosis(global) showed significantly higher values in men than in women in all included muscle groups (p < 0.001). Not only the mean PDFF values (p < 0.001) but also Variance(global) (p < 0.001), Energy (p < 0.001), Entropy (p = 0.01), Homogeneity (p < 0.001), and Correlation (p = 0.037) differed significantly between the three muscle compartments. The cervical and lumbar paraspinal musculature composition seems to be gender-specific and has anatomical location-specific structural patterns.

Background: Wasting disease entities like cachexia or sarcopenia are associated with a decreasing muscle mass and changing muscle composition. For valid and reliable disease detection and monitoring diagnostic techniques offering quantitative musculature assessment are needed. Multi-detector computed tomography (MDCT) is a broadly available imaging modality allowing for muscle composition analysis. A major disadvantage of using MDCT for muscle composition assessment is the radiation exposure. In this study we evaluated the performance of different methods of radiation dose reduction for paravertebral muscle composition assessment. Methods: MDCT scans of eighteen subjects (6 males, age: 71.5±15.9 years, and 12 females, age: 71.0±8.9 years) were retrospectively simulated as if they were acquired at 50%, 10%, 5%, and 3% of the original X-ray tube current or number of projections (i.e., sparse sampling). Images were reconstructed with a statistical iterative reconstruction (SIR) algorithm. Paraspinal muscles (psoas and erector spinae muscles) at the level of L4 were segmented in the original-dose images. Segmentations were superimposed on all low-dose scans and muscle density (MD) extracted. Results: Sparse sampling derived mean MD showed no significant changes (P=0.57 and P=0.22) down to 5% of the original projections in the erector spinae and psoas muscles, respectively. All virtually reduced tube current series showed significantly different (P>0.05) mean MD in the psoas and erector spinae muscles as compared to the original dose except for the images of 5% of the original tube current in the erector spinae muscle. Conclusions: Our findings demonstrated the possibility of considerable radiation dose reduction using MDCT scans for assessing the composition of the paravertebral musculature. The sparse sampling approach seems to be promising and a potentially superior technique for dose reduction as compared to tube current reduction.