Nontargeted Volatile Metabolite Screening and Microbial Contamination Detection in Fermentation Processes by Headspace GC-IMS.

Gas chromatography combined with ion mobility spectrometry (GC-IMS) is a powerful separation and detection technique for volatile organic compounds (VOC). This combination is characterized by exceptionally low detection limits in the low ppbv range, high 2-dimensional selectivity, and robust operation. These qualities make it an ideal tool for nontarget screening approaches. Fermentation broths contain a substantial number of VOC, either from the medium or produced by microbial metabolism, that are currently not regularly measured for process monitoring. In this study, Escherichia coli, Saccharomyces cerevisiae, Levilactobacillus brevis, and Pseudomonas fluorescens were exemplarily used as model organisms and cultivated, and the headspace was analyzed by GC-IMS. Additionally, mixed cultures for every combination of two of the microorganisms were also characterized. Multivariate data analysis of the GC-IMS data revealed that it is possible to differentiate between the microorganisms using PLS-DA with a prediction accuracy of 0.92. The mixed cultures could be separated from the pure cultures with accuracies between 0.87 and 1.00 depending on the organism. GC-IMS data correlate with the optical density and can be used to follow and model growth curves. The root mean squared errors ranged between 10 and 20% of the maximum value, depending on the organism. Peak identification with reference compounds did not reveal specific marker compounds, rather the pattern was found to be responsible for the model performance.

Changes in tumor-to-blood ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT.

BACKGROUND: Historically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin receptor scintigraphy (SRS). In recent years, somatostatin receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-blood ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin receptor expression, to a higher degree than standardized uptake value (SUV) measurements. TBR may therefore predict treatment response to PRRT. In addition, changes in semiquantitative SSTR-PET parameters have been shown to predate morphological changes, making them a suitable metric for response assessment. METHODS: The institutional database of the Department of Nuclear Medicine (University Hospital Essen) was searched for NET patients undergoing ≥ 2 PRRT cycles with available baseline and follow-up SSTR-PET. Two blinded independent readers reported the occurrence of new lesions quantified tumor uptake of up to nine lesions per patient using SUV and TBR. The association between baseline TBR and changes in uptake/occurrence of new lesions with progression-free survival (PFS) and overall survival (OS) was tested by use of a Cox regression model and log-rank test. RESULTS: Patients with baseline TBR in the 1st quartile had a shorter PFS (14.4 months) than those in the 3rd (23.7 months; p = 0.03) and 4th (24.1 months; p = 0.02) quartile. Similarly, these patients had significantly shorter OS (32.5 months) than those with baseline TBR in the 2nd (41.8 months; p = 0.03), 3rd (69.2 months; p < 0.01), and 4th (42.7 months; p = 0.03) quartile. Baseline to follow-up increases in TBR were independently associated with shorter PFS when accounting for prognostic markers, e.g., RECIST response (hazard ratio = 2.91 [95%CI = 1.54-5.50]; p = 0.01). This was confirmed with regard to OS (hazard ratio = 1.64 [95%CI = 1.03-2.62]; p = 0.04). Changes in SUVmean were not associated with PFS or OS. CONCLUSIONS: Baseline TBR as well as changes in TBR were significantly associated with PFS and OS and may improve patient selection and morphological response assessment. Future trials need to assess the role of TBR for therapy monitoring also during PRRT and prospectively explore TBR as a predictive marker for patient selection.

Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series.

OBJECTIVES: An accurate prognostic assessment is pivotal to adequately inform and individualize follow-up and management of patients with differentiated thyroid cancer (DTC). We aimed to develop a predictive model for recurrent disease in DTC patients treated by surgery and 131I by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), administered 131I activities and post-therapy whole body scintigraphy (PT-WBS) were identified as potential predictors and put into regression algorithm (conditional inference tree, c-tree) to develop a risk stratification model for predicting persistent/recurrent disease over time. RESULTS: The PT-WBS pattern identified a partition of the population into two subgroups (PT-WBS positive or negative for distant metastases). Patients with distant metastases exhibited lower disease-free survival (either structural, DFS-SD, and biochemical, DFS-BD, disease) compared to those without metastases. Meanwhile, the latter were further stratified into three risk subgroups based on their Tg values. Notably, Tg values >63.1 ng/mL predicted a shorter survival time, with increased DFS-SD for Tg values <63.1 and <8.9 ng/mL, respectively. A comparable model was generated for biochemical disease (BD), albeit different DFS were predicted by slightly different Tg cutoff values (41.2 and 8.8 ng/mL) compared to DFS-SD. CONCLUSIONS: We developed a simple, accurate and reproducible decision tree model able to provide reliable information on the probability of structurally and/or biochemically persistent/relapsed DTC after a TTA. In turn, the provided information is highly relevant to refine the initial risk stratification, identify patients at higher risk of reduced structural and biochemical DFS, and modulate additional therapies and the relative follow-up.

The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators.

In oral squamous cell carcinoma (OSCC) tissues, an immunotolerant situation triggered by immune checkpoints (ICPs) can be observed. Immune checkpoint inhibitors (ICIs) against the PD1/PD-L axis are used with impressive success. However, the response rate is low and the development of acquired resistance to ICI treatment can be observed. Therefore, new treatment strategies especially involving immunological combination therapies need to be developed. The novel negative immune checkpoint BTLA has been suggested as a potential biomarker and target for antibody-based immunotherapy. Moreover, improved response rates could be displayed for tumor patients when antibodies directed against BTLA were used in combination with anti-PD1/PD-L1 therapies. The aim of the study was to check whether the immune checkpoint BTLA is overexpressed in OSCC tissues compared to healthy oral mucosa (NOM) and could be a potential diagnostic biomarker and immunological target in OSCC. In addition, correlation analyses with the expression of other checkpoints should clarify more precisely whether combination therapies are potentially useful for the treatment of OSCC. A total of 207 tissue samples divided into 2 groups were included in the study. The test group comprised 102 tissue samples of OSCC. Oral mucosal tissue from 105 healthy volunteers (NOM) served as the control group. The expression of two isoforms of BTLA (BTLA-1/2), as well as PD1, PD-L1/2 and CD96 was analyzed by RT-qPCR. Additionally, BTLA and CD96 proteins were detected by IHC. Expression levels were compared between the two groups, the relative differences were calculated, and statistical relevance was determined. Furthermore, the expression rates of the immune checkpoints were correlated to each other. BTLA expression was significantly increased in OSCC compared to NOM (pBTLA_1 = 0.003; pBTLA_2 = 0.0001, pIHC = 0.003). The expression of PD1, its ligands PD-L1 and PD-L2, as well as CD96, were also significantly increased in OSCC (p ≤ 0.001). There was a strong positive correlation between BTLA expression and that of the other checkpoints (p < 0.001; ρ ≥ 0.5). BTLA is overexpressed in OSCC and appears to be a relevant local immune checkpoint in OSCC. Thus, antibodies directed against BTLA could be potential candidates for immunotherapies, especially in combination with ICI against the PD1/PD-L axis and CD96.

Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) in Metastatic Castration-resistant Prostate Cancer.

Background Response Evaluation Criteria in Prostate-specific Membrane Antigen (PSMA) PET/CT (RECIP 1.0) initially integrated software-based quantitative assessment of PSMA-positive total tumor volume (TTV). Clinical implementation of such software is not expected soon, limiting the use of RECIP in practice. Purpose To assess the agreement of RECIP determined using tumor segmentation software (quantitative RECIP) with RECIP determined by qualitative reads by nuclear medicine physicians (visual RECIP) for response evaluation in metastatic castration-resistant prostate cancer. Materials and Methods This multicenter retrospective study at three academic centers included men who received lutetium 177 (177Lu) PSMA treatment between December 2014 and July 2019. PSMA PET/CT images at baseline and 12 weeks were assessed qualitatively by five readers for changes in TTV and for new lesions. Quantitative changes in TTV were also measured using tumor segmentation software. The status of new lesions was combined with qualitative changes in TTV to determine visual RECIP and with quantitative changes in TTV to determine quantitative RECIP. The primary outcomes were the agreement between visual and quantitative RECIP and the interreader reliability of visual RECIP according to the Fleiss κ. The secondary outcome was the association of visual RECIP with overall survival according to Cox regression. Results A total of 124 men (median age, 73 years [IQR, 67-76 years]) were included. Forty (32%) and 84 (68%) men had quantitative RECIP progressive disease (PD) and non-PD, respectively. Agreement between visual versus quantitative RECIP was excellent (κ = 0.89; 118 of 124 men [95%]). Agreement among readers in classifying visual RECIP PD versus non-PD was excellent (κ = 0.81; 103 of 124 men [83%]). RECIP PD was associated with significantly shorter overall survival compared with non-PD (hazard ratio, 2.6 [95% CI: 1.7, 3.8]; P < .001). Conclusion Qualitatively assessed RECIP demonstrated excellent agreement with quantitative RECIP and excellent interreader reliability and can be readily implemented in clinical practice for response evaluation in men with metastatic castration-resistant prostate cancer undergoing 177Lu-PSMA therapy. © RSNA, 2023 Supplemental material is available for this article.

SU(2)-Symmetric Spin-Boson Model: Quantum Criticality, Fixed-Point Annihilation, and Duality.

The annihilation of two intermediate-coupling renormalization-group (RG) fixed points is of interest in diverse fields from statistical mechanics to high-energy physics, but has so far only been studied using perturbative techniques. Here we present high-accuracy quantum Monte Carlo results for the SU(2)-symmetric S=1/2 spin-boson (or Bose-Kondo) model. We study the model with a power-law bath spectrum ∝ω^{s} where, in addition to a critical phase predicted by perturbative RG, a stable strong-coupling phase is present. Using a detailed scaling analysis, we provide direct numerical evidence for the collision and annihilation of two RG fixed points at s^{*}=0.6540(2), causing the critical phase to disappear for s

Electronic Mechanism that Quenches Field-Driven Heating as Illustrated with the Static Holstein Model.

Time-dependent driving of quantum systems has emerged as a powerful tool to engineer exotic phases far from thermal equilibrium, but in the presence of many-body interactions it also leads to runaway heating, so that generic systems are believed to heat up until they reach a featureless infinite-temperature state. Understanding the mechanisms by which such a heat death can be slowed down or even avoided is a major goal-one such mechanism is to drive toward an even distribution of electrons in momentum space. Here we show how such a mechanism avoids runaway heating for an interacting charge-density-wave chain with a macroscopic number of conserved quantities when driven by a strong dc electric field; minibands with nontrivial distribution functions develop as the current is prematurely driven to zero. Moreover, when approaching a zero-temperature resonance, the field strength can tune between positive, negative, or close-to-infinite effective temperatures for each miniband. Our results suggest that nontrivial metastable distribution functions should be realized in the prethermal regime of quantum systems coupled to slow bosonic modes.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.

Reduction of emission time for [68Ga]Ga-PSMA PET/CT using the digital biograph vision: a phantom study.

BACKGROUND: The aim of this phantom study was to optimize the [68Ga]Ga-PSMA PET/CT examination in terms of scan time duration and image reconstruction parameters, in combination with PSF and TOF modelling, in a digital Biograph Vision PET/CT scanner. METHODS: Three types of phantoms were used: 1) soft-tissue tumor phantom consisting of six spheres mounted in a torso phantom; 2) bone-lung tumor phantom; 3) resolution phantom. Phantom inserts were filled with activity concentrations (ACs) that were derived from clinical data. Phantom data were acquired in list-mode at one bed position. Images with emission data ranging from 30 to 210 s in 30-s increments were reconstructed from a reference image acquired with 3.5-min emission. Iterative image reconstruction (OSEM), point-spread-function (PSF) and time-of-flight (TOF) options were applied using different iterations, Gaussian filters, and voxel sizes. The criteria for image quality was lesion detectability and lesion quantification, evaluated as contrast-to-noise ratio (CNR) and maximum AC (peak AC), respectively. A threshold value of CNR above 6 and percentage maximum AC (peak AC) deviation range of ±20% of the reference image were considered acceptable. The proposed single-bed scan time reduction was projected to a whole-body examination (patient validation scan) using the continuous-bed-motion mode. RESULTS: Sphere and background ACs of 20 kBq/mL and 1 kBq/mL were selected, respectively. The optimized single-bed scan time was approximately 60 s using OSEM-TOF or OSEM-TOF+PSF (four iterations, 4.0-mm Gaussian filter and almost isotropic voxel size of 3.0-mm side length), resulting in a PET spatial resolution of 6.3 mm for OSEM-TOF and 5.5 mm for OSEM-TOF+PSF. In the patient validation, the maximum percentage difference in lesion quantification between standard and optimized protocol (whole-body scan time of 15 vs. 5 min) was below 19%. CONCLUSIONS: A reduction of single-bed and whole-body scan time for [68Ga]Ga-PSMA PET/CT compared to current recommended clinical acquisition protocols is postulated. Clinical studies are warranted to validate the applicability of this protocol.

Quantitative 99mTc-DPD-SPECT/CT assessment of cardiac amyloidosis.

INTRODUCTION: Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring. METHODS AND MATERIALS: 136 patients received 99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest. RESULTS: Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%. CONCLUSION: We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

An ex vivo model for education and training of unilateral cleft lip surgery.

BACKGROUND: Unilateral cleft lip surgery is a complex procedure, and the outcome depends highly on the surgeon's experience. Digital simulations and low-fidelity models seem inadequate for effective surgical education and training. There are only few realistic models for haptic simulation of cleft surgery, which are all based on synthetic materials that are costly and complex to produce. Hence, they are not fully available to train and educate surgical trainees. This study aims to develop an inexpensive, widely available, high-fidelity, ex vivo model of a unilateral cleft lip using a porcine snout disc. METHODS: A foil template was manufactured combining anatomical landmarks of the porcine snout disc and the anatomical situation of a child with a unilateral cleft. This template was used to create an ex vivo model of a unilateral cleft lip from the snout disc. Millard II technique was applied on the model to proof its suitability. The individual steps of the surgical cleft closure were photo-documented and three-dimensional scans of the model were analysed digitally. Sixteen surgical trainees were instructed to create a unilateral cleft model and perform a unilateral lip plasty. Their self-assessment was evaluated by means of a questionnaire. RESULTS: The porcine snout disc proved highly suitable to serve as a simulation model for unilateral cleft lip surgery. Millard II technique was successfully performed as we were able to perform all steps of unilateral cleft surgery, including muscle suturing. The developed foil-template is reusable on any porcine snout disc. The creation of the ex vivo model is simple and inexpensive. Self-assessment of the participants showed a strong increase in comprehension and an eagerness to use the model for surgical training. CONCLUSIONS: A porcine snout disc ex vivo model of unilateral cleft lips was developed successfully. It shows many advantages, including a haptic close to human tissue, multiple layers, low cost, and wide and rapid availability. It is therefore very suitable for teaching and training beginners in cleft surgery and subsequently improving surgical skills and knowledge. Further research is needed to finally assess the ex vivo model's value in different stages of the curriculum of surgical residency.

An ex vivo model for education and training of bilateral cleft lip surgery.

BACKGROUND: Bilateral cleft lip surgery is very challenging and requires a high level of skill, knowledge and experience. Existing high-fidelity simulation models that can be used by novice cleft surgeons to gain experience and expand their knowledge are rare and expensive. In this study, we developed a bilateral cleft lip model using porcine snout discs, which are available anywhere and inexpensive. METHODS: Anatomic reference points of a patient with a bilateral cleft lip were superimposed with landmarks of the porcine snout disc on a foil template. The template was used to construct an ex vivo bilateral cleft lip model. Surgery was performed on the model according to Millard and the surgical steps were photodocumented analogous to two clinical cases of bilateral cleft lip surgery. The suitability of the model was further tested by twelve participants and evaluated using self-assessment questionnaires. RESULTS: The bilateral cleft lip ex vivo model made of a porcine snout disc proved to be a suitable model with very low cost and ease of fabrication, as the template is reusable on any snout disc. The Millard procedure was successfully performed and the surgical steps of the lip plasty were simulated close to the clinical situation. Regarding the nasal reconstruction, the model lacks three-dimensionality. As a training model, it enhanced the participants comprehension of cleft surgery as well as their surgical skills. All participants rated the model as valuable for teaching and training. CONCLUSIONS: The porcine snout discs can be used as a useful ex vivo model for bilateral cleft lip surgery with limitations in the construction of the nose, which cannot be realistically performed with the model due to anatomical differences with humans. Benefits include a realistic tissue feel, the simulation of a multi-layered lip construction, a wide and rapid availability and low cost. This allows the model to be used by novice surgeons also in low-income countries. It is therefore useful as a training model for gaining experience, but also as a model for refining, testing and evaluating surgical techniques for bilateral lip plasty.

Prevalence of carotid artery calcification detected by different dental imaging techniques and their relationship with cardiovascular risk factors, age and gender.

BACKGROUND: Atherosclerosis and its secondary diseases display a major threat to patient's health. Sequelae, like carotid artery calcification (CAC), usually develop over decades and remain asymptomatic for a long time, making preventive measures to reduce mortality and morbidity extremely important. Through panoramic radiography (PR) and cone beam computed tomography (CBCT), dentists may have helpful tools in aiding the holistic care of patients. In this context, the correlation of atherosclerotic risk factors and CAC development have not yet been sufficiently investigated. Thus, the aim of this observational radiological study was to evaluate the diagnostic value of PR compared with CBCT for the detection of CAC in patients older than 60 years. The radiological findings were correlated with gender, age, and cardiac risk factors. METHODS: PRs and CBCTs of N = 607 patients were used for the qualitative analysis and compared. Basic patient information such as age, gender, body mass index (BMI), smoking history as well as patient's detailed medical history, including heart disease and cardiovascular risk factors such as hypercholesterolemia, arterial hypertension and diabetes mellitus type II were documented and their relation to CAC provided by radiological data was estimated in the form of odds ratios (OR), which were calculated using logistic regression models. Proportions of CAC in different risk groups were compared using Fisher's exact test, the significance level was set to α ≤ 0.05. The interrater reliability of two physicians was estimated using Cohen's kappa. RESULTS: With an accuracy of 90.6%, a sensitivity of 67.5% and a specificity of 99.5% compared to CBCT, PR was a reliable method for the diagnosis of CAC. The overall detection rate for CAC was 27.8% across all age groups. Age (OR: 1.351; p = 0.021), the male sex (OR: 1.645; p = 0.006), arterial hypertension (OR: 2.217; p = < 0.001), heart disease (OR: 1.675; p = 0.006), hypercholesterolemia (OR: 1.904; p = 0.003) and chronic obstructive pulmonary disease (OR: 2.016; p = 0.036) were statistically significant risk factors. When correlated, neither history of stroke nor nicotine abuse showed any statistical significance. CONCLUSIONS: Due to the capabilities of PR in the diagnosis of CAC, dentists can play a vital role in the early diagnosis of vascular disease. Awareness should therefore be raised among dentists regarding the detection of CAC in patients over 60 years of age, with a particular focus on those with arterial hypertension and hypercholesterolaemia.

Dissipation-Induced Order: The S=1/2 Quantum Spin Chain Coupled to an Ohmic Bath.

We consider an S=1/2 antiferromagnetic quantum Heisenberg chain where each site is coupled to an independent bosonic bath with ohmic dissipation. The coupling to the bath preserves the global SO(3) spin symmetry. Using large-scale, approximation-free quantum Monte Carlo simulations, we show that any finite coupling to the bath suffices to stabilize long-range antiferromagnetic order. This is in stark contrast to the isolated Heisenberg chain where spontaneous breaking of the SO(3) symmetry is forbidden by the Mermin-Wagner theorem. A linear spin-wave theory analysis confirms that the memory of the bath and the concomitant retarded interaction stabilize the order. For the Heisenberg chain, the ohmic bath is a marginal perturbation so that exponentially large system sizes are required to observe long-range order at small couplings. Below this length scale, our numerics is dominated by a crossover regime where spin correlations show different power-law behaviors in space and time. We discuss the experimental relevance of this crossover phenomena.

Measuring response in metastatic castration-resistant prostate cancer using PSMA PET/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria.

PURPOSE: To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the adapted Prostate Cancer Working Group Criteria 3 (aPCWG3), the adapted Positron Emission Tomography Response Criteria in Solid Tumors (aPERCIST), the PSMA PET Progression (PPP), and the Response Evaluation Criteria In PSMA-Imaging (RECIP) 1.0 for response evaluation using prostate-specific membrane antigen (PSMA)-PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA radioligand therapy. METHODS: A total of 124 patients were included in this multicenter retrospective study. All patients received 177Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Imaging responses according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 were interpreted by consensus among three blinded readers. Changes in total tumor burden were obtained using the semi-automatic qPSMA software. The response according to each criterion was classified to progressive disease (PD) vs no-PD. Primary outcome measure was the prognostic value (by Cox regression analysis) for overall survival (OS). Secondary outcome measure was the inter-reader reliability (by Cohen's κ coefficient). RESULTS: A total of 43 (35%) of patients had non-measurable disease according to RECIST 1.1. Sixteen (13%), 66 (52%), 72 (58%), 69 (56%), and 39 (32%) of 124 patients had PD according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP, respectively. PD vs no-PD had significantly higher risk of death according to aPCWG3 (HR = 2.37; 95%CI, 1.62-3.48; p < 0.001), aPERCIST (HR = 2.48; 95%CI, 1.68-3.66; p < 0.001), PPP (HR = 2.72; 95%CI, 1.85-4.01; p < 0.001), RECIP 1.0 (HR = 4.33; 95%CI, 2.80-6.70; p < 0.001), but not according to RECIST 1.1 (HR = 1.29; 95%CI, 0.73-2.27; p = 0.38). The κ index of RECIST 1.1, aPCWG3, aPERCIST 1.0, PPP, and RECIP 1.0 for identifying PD vs no-PD were 0.50 (95%CI, 0.32-0.76), 0.72 (95%CI, 0.63-0.82), 0.68 (95%CI, 0.63-0.73), 0.73 (95%CI, 0.63-0.83), and 0.83 (95%CI, 0.77-0.88), respectively. CONCLUSION: PSMA-PET-specific criteria for early response evaluation in men with mCRPC treated with 177Lu-PSMA achieved higher prognostic values and inter-reader reliabilities in comparison to conventional CT assessment or to criteria adapted to PSMA-PET from other imaging modalities. RECIP 1.0 identified the fewest patients with PD and achieved the highest risk of death for PD vs. no-PD, suggesting that other classification methods tend to overcall progression. Prospective validation of our findings on an independent patient cohort is warranted.

Visualization of thermal damage using 68 Ga-FAPI-PET/CT after pulmonary vein isolation.

PURPOSE: 68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage. METHODS: Twelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated. RESULTS: Focal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02). CONCLUSION: We demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.

Artificial intelligence guided enhancement of digital PET: scans as fast as CT?

PURPOSE: Both digital positron emission tomography (PET) detector technologies and artificial intelligence based image post-reconstruction methods allow to reduce the PET acquisition time while maintaining diagnostic quality. The aim of this study was to acquire ultra-low-count fluorodeoxyglucose (FDG) ExtremePET images on a digital PET/computed tomography (CT) scanner at an acquisition time comparable to a CT scan and to generate synthetic full-dose PET images using an artificial neural network. METHODS: This is a prospective, single-arm, single-center phase I/II imaging study. A total of 587 patients were included. For each patient, a standard and an ultra-low-count FDG PET/CT scan (whole-body acquisition time about 30 s) were acquired. A modified pix2pixHD deep-learning network was trained employing 387 data sets as training and 200 as test cohort. Three models (PET-only and PET/CT with or without group convolution) were compared. Detectability and quantification were evaluated. RESULTS: The PET/CT input model with group convolution performed best regarding lesion signal recovery and was selected for detailed evaluation. Synthetic PET images were of high visual image quality; mean absolute lesion SUVmax (maximum standardized uptake value) difference was 1.5. Patient-based sensitivity and specificity for lesion detection were 79% and 100%, respectively. Not-detected lesions were of lower tracer uptake and lesion volume. In a matched-pair comparison, patient-based (lesion-based) detection rate was 89% (78%) for PERCIST (PET response criteria in solid tumors)-measurable and 36% (22%) for non PERCIST-measurable lesions. CONCLUSION: Lesion detectability and lesion quantification were promising in the context of extremely fast acquisition times. Possible application scenarios might include re-staging of late-stage cancer patients, in whom assessment of total tumor burden can be of higher relevance than detailed evaluation of small and low-uptake lesions.

Phantom-based acquisition time and image reconstruction parameter optimisation for oncologic FDG PET/CT examinations using a digital system.

BACKGROUND: New-generation silicon-photomultiplier (SiPM)-based PET/CT systems exhibit an improved lesion detectability and image quality due to a higher detector sensitivity. Consequently, the acquisition time can be reduced while maintaining diagnostic quality. The aim of this study was to determine the lowest 18F-FDG PET acquisition time without loss of diagnostic information and to optimise image reconstruction parameters (image reconstruction algorithm, number of iterations, voxel size, Gaussian filter) by phantom imaging. Moreover, patient data are evaluated to confirm the phantom results. METHODS: Three phantoms were used: a soft-tissue tumour phantom, a bone-lung tumour phantom, and a resolution phantom. Phantom conditions (lesion sizes from 6.5 mm to 28.8 mm in diameter, lesion activity concentration of 15 kBq/mL, and signal-to-background ratio of 5:1) were derived from patient data. PET data were acquired on an SiPM-based Biograph Vision PET/CT system for 10 min in list-mode format and resampled into time frames from 30 to 300 s in 30-s increments to simulate different acquisition times. Different image reconstructions with varying iterations, voxel sizes, and Gaussian filters were probed. Contrast-to-noise-ratio (CNR), maximum, and peak signal were evaluated using the 10-min acquisition time image as reference. A threshold CNR value ≥ 5 and a maximum (peak) deviation of ± 20% were considered acceptable. 20 patient data sets were evaluated regarding lesion quantification as well as agreement and correlation between reduced and full acquisition time standard uptake values (assessed by Pearson correlation coefficient, intraclass correlation coefficient, Bland-Altman analyses, and Krippendorff's alpha). RESULTS: An acquisition time of 60 s per bed position yielded acceptable detectability and quantification results for clinically relevant phantom lesions ≥ 9.7 mm in diameter using OSEM-TOF or OSEM-TOF+PSF image reconstruction, a 4-mm Gaussian filter, and a 1.65 × 1.65 x 2.00-mm3 or 3.30 × 3.30 x 3.00-mm3 voxel size. Correlation and agreement of patient lesion quantification between full and reduced acquisition times were excellent. CONCLUSION: A threefold reduction in acquisition time is possible. Patients might benefit from more comfortable examinations or reduced radiation exposure, if instead of the acquisition time the applied activity is reduced.

Frequency of the necessity of dentoalveolar surgery or conservative treatment in patients before kidney transplantation depending on the duration of dialysis and causative nephrological disease.

OBJECTIVES: This retrospective study evaluates intraoral surgical and conservative treatment need in patients with a chronic kidney end-stage disease, depending on the duration of dialysis treatment and the causative nephrological disease. MATERIAL AND METHODS: This study is based on data of patients referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Erlangen, Germany, prior to kidney transplantation between January 2015 and March 2020. The necessity for oral surgical or dental therapy was determined by clinical and radiological examinations. Data on renal replacement therapy, cause of underlying renal disease, lifestyle, and general health were collected. RESULTS: Data of N = 89 patients demonstrated that surgical treatment need depends on dialysis duration (p = 0.042). Patients, who had been dialyzing for 2 to 3 years showed the highest need for surgical intervention (80.0%; p = 0.024), followed by dialysis patients with a dialysis time of more than 3 years (48.1%). Similarly, dialysis patients in the second or third year of dialysis had the highest need for conservative treatment (73.3%; p > 0.05), followed by 55.6% of dialysis patients in the third year of dialysis. CONCLUSIONS: Operative and conservative treatment is essential to optimize subsequent kidney transplantation. The greatest necessity could be detected for patients in the second and third years of dialysis. CLINICAL RELEVANCE: Oral health addressing surgical and conservative treatment need depends on the duration of dialysis in patients with a chronic kidney end-stage disease.