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Background: Treatment of patients with low-grade and high-grade gliomas is highly variable due to the large difference in survival expectancy. New non-invasive tools are needed for risk stratification prior to treatment. The urokinase plasminogen activator receptor (uPAR) is expressed in several cancers, associated with poor prognosis and may be non-invasively imaged using uPAR-PET. We aimed to investigate the uptake of the uPAR-PET tracer [68Ga]Ga-NOTA-AE105 in primary gliomas and establish its prognostic value regarding overall survival (OS), and progression-free survival (PFS). Additionally, we analyzed the proportion of uPAR-PET positive tumors to estimate the potential number of candidates for future uPAR-PRRT. Methods: In a prospective phase II clinical trial, 24 patients suspected of primary glioma underwent a dynamic 60-min PET/MRI following the administration of approximately 200 MBq (range: 83–222 MBq) [68Ga]Ga-NOTA-AE105. Lesions were considered uPAR positive if the tumor-to-background ratio, calculated as the ratio of TumorSUVmax-to-Normal-BrainSUVmean tumor-SUVmax-to-background-SUVmean, was ≥ 2.0. The patients were followed over time to assess OS and PFS and stratified into high and low uPAR expression groups based on TumorSUVmax. Results: Of the 24 patients, 16 (67%) were diagnosed with WHO grade 4 gliomas, 6 (25%) with grade 3, and 2 (8%) with grade 2. Two-thirds of all patients (67%) presented with uPAR positive lesions and 94% grade 4 gliomas. At median follow up of 18.8 (2.1–45.6) months, 19 patients had disease progression and 14 had died. uPAR expression dichotomized into high and low, revealed significant worse prognosis for the high uPAR group for OS and PFS with HR of 14.3 (95% CI, 1.8-112.3; P = 0.011), and HR of 26.5 (95% CI, 3.3–214.0; P = 0.0021), respectively. uPAR expression as a continuous variable was associated with worse prognosis for OS and PFS with HR of 2.7 (95% CI, 1.5–4.8; P = 0.0012), and HR of 2.5 (95% CI, 1.5–4.2; P = 0.00073), respectively. Conclusions: The majority of glioma patients and almost all with grade 4 gliomas displayed uPAR positive lesions underlining the feasibility of 68Ga-NOTA-AE105 PET/MRI in gliomas. High uPAR expression is significantly correlated with worse survival outcomes for patients. Additionally, the high proportion of uPAR positive gliomas underscores the potential of uPAR-targeted radionuclide therapy in these patients. Trail Registration: EudraCT No: 2016-002417-21; the Scientific Ethics Committee: H-16,035,303; the Danish Data Protection Agency: 2012-58-0004; clinical trials registry: NCT02945826, 26Oct2016, URL: https://classic.clinicaltrials.gov/ct2/show/NCT02945826. [ABSTRACT FROM AUTHOR]

Background: The outstanding capabilities of modern Positron Emission Tomography (PET) to highlight small tumor lesions and provide pathological function assessment are at peril from image quality degradation caused by respiratory and cardiac motion. However, the advent of the long axial field-of-view (LAFOV) scanners with increased sensitivity, alongside the precise time-of-flight (TOF) of modern PET systems, enables the acquisition of ultrafast time resolution images, which can be used for estimating and correcting the cyclic motion. Methods: 0.25 s so-called [18F]FDG PET histo image series were generated in the scope of for detecting respiratory and cardiac frequency estimates applicable for performing device-less data-driven gated image reconstructions. The frequencies of the cardiac and respiratory motion were estimated for 18 patients using Short Time Fourier Transform (STFT) with 20 s and 30 s window segments, respectively. Results: The Fourier analysis provided time points usable as input to the gated reconstruction based on eight equally spaced time gates. The cardiac investigations showed estimates in accordance with the measured pulse oximeter references (p = 0.97) and a mean absolute difference of 0.4 ± 0.3 beats per minute (bpm). The respiratory frequencies were within the expected range of 10–20 respirations per minute (rpm) in 16 out of 18 patients. Using this setup, the analysis of three patients with visible lung tumors showed an increase in tumor SUVmax and a decrease in tumor volume compared to the non-gated reconstructed image. Conclusions: The method can provide signals that were applicable for gated reconstruction of both cardiac and respiratory motion, providing a potential increased diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Stress is a ubiquitous challenge in modern societies. Symptoms range from mood swings and cognitive impairment to autonomic symptoms. This study explores the link between work-related stress and the neurobiological element of brain processing, testing the hypothesis that patients with occupational stress have altered cerebral glucose consumption compared to healthy controls. The participants' present conditions were evaluated using an adapted WHO SCAN interview. Neural activity at rest was assessed by positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose. Participants were genotyped for the Val158Met polymorphism of the COMT gene, believed to influence stress resilience. This study included 11 women with work-related stress and 11 demographically comparable healthy controls aged 28–62 years, with an average of 46.2 years. The PET scans indicated clusters of decreased glucose consumption primarily located in the white matter of frontal lobe sub-gyral areas in stress patients. COMT Val158Met polymorphism detection indicated no immediate relation of the homozygous alleles and stress resilience; however, healthy controls mainly had the heterozygous allele. In conclusion, the results support that work-related stress does affect the brain in the form of altered glucose metabolism, suggesting neurobiological effects could be related to white matter abnormalities rather than gray matter deterioration. Genotyping indicates a more complex picture than just that of the one type being more resilient to stress. Further studies recruiting a larger number of participants are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

The accurate estimation of the tracer arterial blood concentration is crucial for reliable quantitative kinetic analysis in PET. In the current work, we demonstrate the automatic extraction of an image-derived input function (IDIF) from a CT AI-based aorta segmentation subsequently resliced to a dynamic PET series acquired on a Siemens Vision Quadra long-axial field of view scanner in 10 human subjects scanned with [15O]H2O. We demonstrate that the extracted IDIF is quantitative and in excellent agreement with a delay- and dispersion-corrected sampled arterial input function (AIF). Perfusion maps in the brain are calculated and compared from the IDIF and AIF, respectively, showed a high degree of correlation. The results demonstrate the possibility of defining a quantitatively correct IDIF compared with AIFs from the new-generation high-sensitivity and high-time-resolution long-axial field-of-view PET/CT scanners. [ABSTRACT FROM AUTHOR]

Purpose: Conventional magnetic resonance imaging (MRI) can for glioma assessment be supplemented by positron emission tomography (PET) imaging with radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), which provides additional information on metabolic properties. In neurooncology, patients often undergo brain and skull altering treatment, which is known to challenge MRI-based attenuation correction (MR-AC) methods and thereby impact the simplified semi-quantitative measures such as tumor-to-brain ratio (TBR) used in clinical routine. The aim of the present study was to examine the applicability of our deep learning method, DeepDixon, for MR-AC in [18F]FET PET/MRI scans of a post-surgery glioma cohort with metal implants. Methods: The MR-AC maps were assessed for all 194 included post-surgery glioma patients (318 studies). The subgroup of 147 patients (222 studies, 200 MBq [18F]FET PET/MRI) with tracer uptake above 1 ml were subsequently reconstructed with DeepDixon, vendor-default atlas-based method, and a low-dose computed tomography (CT) used as reference. The biological tumor volume (BTV) was delineated on each patient by isocontouring tracer uptake above a TBR threshold of 1.6.We evaluated the MR-AC methods using the recommended clinical metrics BTV and mean and maximum TBR on a patient-by-patient basis against the reference with CT-AC. Results: Ninety-seven percent of the studies (310/318) did not have any major artifacts using DeepDixon, which resulted in a Dice coefficient of 0.89/0.83 for tissue/bone, respectively, compared to 0.84/0.57 when using atlas. The average difference between DeepDixon and CT-AC was within 0.2% across all clinical metrics, and no statistically significant difference was found. When using DeepDixon, only 3 out of 222 studies (1%) exceeded our acceptance criteria compared to 72 of the 222 studies (32%) with the atlas method. Conclusion: We evaluated the performance of a state-of-the-art MR-AC method on the largest post-surgical glioma patient cohort to date. We found that DeepDixon could overcome most of the issues arising from irregular anatomy and metal artifacts present in the cohort resulting in clinical metrics within acceptable limits of the reference CT-AC in almost all cases. This is a significant improvement over the vendor-provided atlas method and of particular importance in response assessment. [ABSTRACT FROM AUTHOR]

Editorial for "Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade" Echo-planar spectroscopic imaging[6] and echo-planar imaging[7] sequences have been used as a faster alternative to chemical shift imaging and for combined spatial and temporal coverage, respectively. The research interest and clinical potential of hyperpolarized magnetic resonance imaging (MRI) are substantial, as evidenced by the increasing number of registered clinical trials in recent years. [Extracted from the article]

Angiogenesis is crucial in tissue repair and prevents scar tissue formation following an ischemic event such as myocardial infarction. The ischemia induces formation of new capillaries, which have high expression of integrin αvβ3. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 ([68Ga]Ga-RGD) is a promising PET-radiotracer reflecting angiogenesis by binding to integrin αvβ3. A Göttingen mini-pig underwent transient catheter-induced left anterior descending artery (LAD) occlusion for 120 min, and after 8 weeks was imaged on a Siemens mMR 3T PET/MR system. A large antero-septal infarction was evident by late gadolinium enhancement (LGE) on the short axis and 2–4 chamber views. The infarcted area corresponded to the area with high [68Ga]Ga-RGD uptake on the fused PET/MR images, with no uptake in the healthy myocardium. To support the hypothesis that [68Ga]Ga-RGD uptake reflects angiogenesis, biopsies were sampled from the infarct border and healthy myocardium. Expression of αvβ3 was evaluated using immunohistochemistry. The staining showed higher αvβ3 expression in the capillaries of the infarct border compared to those in the healthy myocardium. These initial data confirm in vivo detection of angiogenesis using [68Ga]Ga-RGD PET in a translational model, which overall support the method applicability when evaluating novel cardio-protective therapies. [ABSTRACT FROM AUTHOR]

Cross‐sectional imaging supplements endoscopy in detecting disease manifestations in inflammatory bowel diseases (IBD). This study aimed to evaluate the accuracy of PET/MRI in a paediatric population suspected of IBD. This prospective study consecutively included patients aged 8–17 years under diagnostic evaluation for IBD. Forty‐three patients underwent a PET/MRI scan and subsequent ileocolonoscopy, of whom 26 patients diagnosed with IBD participated in a follow‐up scan, hereof 19 with Crohn's disease (CD), five with Ulcerative colitis and two with unclassified IBD. The results of PET alone, MRI alone, and PET/MRI combined were compared to a reference standard of endoscopy and histopathology. Of the 208 intestinal segments analysed, 109 showed inflammation, and 99 had no inflammation. In the per‐segment analysis PET had a sensitivity of 0.83 (95% CI 0.73–0.93), specificity of 0.59 (95% CI 0.47–0.71), and area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI 0.67–0.80). MRI had a sensitivity of 0.52 (95% CI 0.41–0.64), specificity 0.89 (95% CI 0.82–0.96), and AUROC of 0.72 (95% CI 0.66–0.77). PET/MRI had a sensitivity of 0.83 (95% CI 0.74–0.94), specificity of 0.57 (95% CI 0.44–0.69), and AUROC of 0.77 (95% CI 0.71–0.84). At follow‐up, PET and MRI scores decreased, and the change in MRI was able to identify patients with a clinical response. The accuracy of the PET/MRI scan in detecting inflammation in the terminal ileum and colon was moderate and not superior to either modality alone. With technological advances and combined reading, PET/MRI may still be valuable in selected cases. [ABSTRACT FROM AUTHOR]

Objective: We present an algorithm to estimate the delay between a tissue time-activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics., Methods: Whole-body scans of 15 patients divided equally among three tracers, namely [ 15 O]H 2 O, [ 18 F]FDG and [ 64 Cu]Cu-DOTATATE, which were used in development and testing of the algorithm. Delay times were estimated by fitting the cumulatively summed input function and tissue time-activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation: name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time-activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution., Results: Our proposed model performs better for low signal-to-noise ratio time-activity curves compared to both cross-correlation and the one-tissue compartment models for non-[ 15 O]H 2 O tracers. Testing on synthetically produced time-activity curves showed only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays., Conclusion: The algorithm is robust to noise and proves applicable on a range of tracers as tested on [ 15 O]H 2 O, [ 18 F]FDG and [ 64 Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Nielsen, Lindberg, Bordallo, Johnbeck, Law, Fischer, Andersen and Andersen.)

The diagnosis of a malignant brain tumour is often associated with a poor prognosis. Current treatment is surgical resection followed by radio-chemotherapy. Surgical resection is most favourable in relation to survival time. Unfortunately, many patients are not suitable for surgical resection, due to inoperable tumour location or the patients' poor state. Minimally invasive thermal ablation may pose an interesting new treatment alternative. In this review, we describe the evolution, the underlying physiology and the clinical applications of cryo- and laser-induced thermal therapy of primary and secondary brain tumours.