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Objectives: To evaluate a training program for non-specialist health care providers in a brief coaching intervention to improve positive airway pressure (PAP) usage in Veterans with sleep apnea. Methods: We conducted a national webinar training designed for non-specialist providers to implement a brief telephone coaching intervention to improve PAP adherence. The curriculum was crafted by experts in sleep medicine and behavioral sleep medicine based on principles of PAP desensitization. Providers who participated in this training were asked to complete evaluations at 30 days and 1 year. Results: Provider surveys indicated that most respondents had incorporated the intervention into their clinical practice and felt comfortable counseling patients about sleep apnea and adherence to PAP. Provider feedback suggested that future training programs should include refresher trainings, more training on PAP equipment specifics, and facilitated collaboration with local sleep medicine staff. Conclusions: This pilot training program demonstrated that a webinar format was a feasible method to increase training in PAP adherence among non-specialist health care providers. Innovation: Non-specialists can be trained as PAP coaches in webinar format, improving patients' access to effective strategies and support to be successful with PAP therapy.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features. Method A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm. Results A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz’s model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature. Conclusion Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients.

Obstructive sleep apnea (OSA) and diabetes has been known to be closely related to each other and both diseases impact highly on the public health. There are many evidence of reports that OSA is associated with diabetes with a bidirectional correlation. A possible causal mechanism of OSA to diabetes is intermittent hypoxemia and diabetes to OSA is microvascular complication. However, OSA and diabetes have a high prevalence rate in public and shares the common overlap characteristic and risk factors such as age, obesity, and metabolic syndrome that make it difficult to establish the exact pathophysiologic mechanism between them. In addition, studies demonstrating that treatment of OSA may help prevent diabetes or improve glycemic control have not shown convincing result but have become a great field of interest research. This review outlines the bidirectional correlation between OSA and diabetes and explore the pathophysiologic mechanisms by approaching their basic etiologies.

Introduction The prevalence of sleep-disordered breathing is increasing, and there are insufficient sleep medicine specialists to meet the clinical demand of caring for these patients. One way to meet this clinical need is to train primary care and internal medicine physicians to provide some of the care. However, trainees in these specialties often receive very little training on practical aspects of the management of obstructive sleep apnea (OSA). We developed an experiential workshop to address this need at our institution. Methods For approximately 60 internal medicine residents, we ran a 2.5-hour workshop consisting of two 20-minute didactic presentations to the whole audience and two 40-minute breakout sessions, led by eight facilitators. During the breakout sessions, the residents interacted with equipment such as positive airway pressure (PAP) devices and interfaces, reviewed sleep testing and PAP download reports, and participated in guided small-group discussions. Results We received 40 evaluation surveys with at least partial responses. Only 50% of respondents had received prior formal instruction on PAP devices. Both subjective and objective knowledge scores improved on the postworkshop questions compared to the preworkshop questions. Trainee comments were extremely positive, indicating that they enjoyed the format of the session. Discussion This curriculum provides an interactive educational session focused on practical aspects of OSA management relevant to primary care physicians and internists. It was well received and could be adapted to suit other time frames and other groups of learners.

Summary: Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. Methods: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. Findings: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70–0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65–0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68–0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. Interpretation: These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. Funding: Novartis.

Abstract Purpose Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT). Methods AIT patients with pathological thyroid uptake on [68Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[18F]FDG PET in terms of SUVmax/SUVpeak/SUVmean/tissue-to-background ratio (TBR), and with a healthy control group. Results Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [68Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([68Ga]Ga-FAPI (SUVpeak): 7.0 vs. 1.7; p = 0.004/(TBRbloodpool): 6.8 vs. 1.7; p = 0.002; 2-[18F]FDG (SUVpeak): 3.9 vs. 1.4; p = 0.004/(TBRbloodpool): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [68Ga]Ga-FAPI and 2-[18F]FDG PET (SUVpeak: 7.3 vs. 5.6; p = 0.104). Conclusion Patients with AIT show higher thyroid uptake on [68Ga]Ga-FAPI and 2-[18F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [68Ga]Ga-FAPI PET and should prompt a clinical work-up.

Objective: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis. Methods: We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma gene expression classifier (GEC), Afirma gene sequencing classifier (GSC), ThyroSeq v2 (TSv2), or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata. Results: Seventy-one samples (GEC, n = 38; GSC, n = 16; TSv2, n = 9; TSv3, n = 8) in 53 studies, involving 6490 fine needle aspirations (FNAs) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, or TSv3), were included in the study. The meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI: 0.94–0.97), specificity 0.35 (0.28–0.43), positive likelihood ratio (LR+) 1.5 (1.3–1.6), and negative likelihood ratio (LR−) 0.13 (0.09–0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93–0.96), followed by TSv2 (0.90 (0.87–0.92)), GSC (0.86 (0.82–0.88)), and GEC (0.82 (0.78–0.85)); the best rule-out property was observed for GSC (LR−, 0.07 (0.02–0.19)), followed by TSv3 (0.11 (0.05–0.24)) and GEC (0.16 (0.10–0.28), and the best rule-in was observed for TSv2 (LR+, 2,9 (1.4–4.6)), followed by GSC (1.9 (1.6–2.4)). A meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors. Conclusion: We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. As regards rule-out malignancy, GSC, and rule-in, TSV2 is superior to other tests.

BackgroundFHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. ObjectiveThis study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. MethodsA Python package for the use of multimodal FHIR data (FHIRPACK [FHIR Python Analysis Conversion Kit]) was developed and pioneered in 5 real-world clinical use cases, that is, myocardial infarction, stroke, diabetes, sepsis, and prostate cancer. Patients were identified based on the ICD-10 (International Classification of Diseases, Tenth Revision) codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. ResultsFor 2022, a total of 1,302,988 patient encounters were analyzed. (1) Myocardial infarction: in 72.7% (261/359) of cases, medication regimens fulfilled guideline recommendations. (2) Stroke: out of 1277 patients, 165 received thrombolysis and 108 thrombectomy. (3) Diabetes: in 443,866 serum glucose and 16,180 glycated hemoglobin A1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (13,887/35,494). Among those with dysglycemia, diagnosis was coded in 44.2% (6138/13,887) of the patients. (4) Sepsis: In 1803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (773/2672, 28.9%) and piperacillin and tazobactam was the primarily prescribed antibiotic (593/1593, 37.2%). (5) PC: out of 54, three patients who received radical prostatectomy were identified as cases with prostate-specific antigen persistence or biochemical recurrence. ConclusionsLeveraging FHIR data through large-scale analytics can enhance health care quality and improve patient outcomes across 5 clinical specialties. We identified (1) patients with sepsis requiring less broad antibiotic therapy, (2) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, (3) patients who had a stroke with longer than recommended times to intervention, (4) patients with hyperglycemia who could benefit from specialist referral, and (5) patients with PC with early increases in cancer markers.

Abstract Aim Positron emission tomography (PET) using 124I-mIBG has been established for imaging and pretherapeutic dosimetry. Here, we report the first systematic analysis of the biodistribution and radiation dosimetry of 124I-mIBG in patients with neural crest tumours and project the results to paediatric patient models. Methods Adult patients with neural crest tumours who underwent sequential 124I-mIBG PET were included in this retrospective single-center analysis. PET data were acquired 4, 24, 48, and/or 120 h after administration of a mean of 43 MBq 124I-mIBG. Whole-body counting and blood sampling were performed at 2, 4, 24, 48 and 120 h after administration. Absorbed organ dose and effective dose coefficients were estimated in OLINDA/EXM 2.2 according to the MIRD formalism. Extrapolation to paediatric models was performed based on mass-fraction scaling of the organ-specific residence times. Biodistribution data for adults were also projected to 123I-mIBG and 131I-mIBG. Results Twenty-one patients (11 females, 10 males) were evaluated. For adults, the organs exposed to the highest dose per unit administered activity were urinary bladder (1.54 ± 0.40 mGy/MBq), salivary glands (0.77 ± 0.28 mGy/MBq) and liver (0.65 ± 0.22 mGy/MBq). Mean effective dose coefficient for adults was 0.25 ± 0.04 mSv/MBq (male: 0.24 ± 0.03 mSv/MBq, female: 0.26 ± 0.06 mSv/MBq), and increased gradually to 0.29, 0.44, 0.69, 1.21, and 2.94 mSv/MBq for the 15-, 10-, 5-, 1-years-old, and newborn paediatric reference patients. Projected mean effective dose coefficients for 123I-mIBG and 131I-mIBG for adults were 0.014 ± 0.002 mSv/MBq and 0.18 ± 0.04 mSv/MBq, respectively. Conclusion PET-based derived radiation dosimetry data for 124I-mIBG from this study agreed well with historical projected data from ICRP 53. The effective dose coefficients presented here may aid in guidance for establishing weight-based activity administration protocols.

In this prospective two-center feasibility study, we evaluate the diagnostic value of intraoperative ex vivo specimenPET/CT imaging of radical prostatectomy (RP) and lymphadenectomy specimens. Ten patients with high-risk prostate cancer underwent clinical prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) preoperatively on the day of surgery. Six patients received 68Ga-PSMA-11 and four 18F-PSMA-1007. Radioactivity of the resected specimen was measured again using a novel specimenPET/CT device (AURA10; XEOS Medical, Gent, Belgium) developed for intraoperative margin assessment. All index lesions of staging multiparametric magnetic resonance imaging could be visualized. Overall, specimenPET/CT correlated well with conventional PET/CT regarding detection of suspicious tracer foci (Pearson coefficient 0.935). In addition, specimenPET/CT demonstrated all lymph node metastases detected on conventional PET/CT (n = 3), as well as three previously undetected lymph node metastases. Importantly, all positive or close (

Purpose of the Report: Combined cardiac 68Ga-Fibroblast-Activation Protein-alpha inhibitor (FAPI) positron-emission tomography (PET) and cardiac magnetic resonance imaging (MRI) constitute a novel diagnostic tool in patients for the assessment of myocardial damage after an acute myocardial infarction (AMI). Purpose of this pilot study was to evaluate simultaneous Ga-68-FAPI-46-PET/MR imaging in the delayed phase after AMI. Material and Methods: Eleven patients underwent hybrid 68Ga-FAPI-46 PET/MRI post AMI. Standardized uptake values and fibroblast activation volume (FAV) were calculated and correlated with serum biomarkers and MRI parameters. Results: Significant 68Ga-FAPI-46 uptake could be demonstrated in 11 (100 %) patients after a mean period of 30.9 ± 22.0 days. FAV significantly exceeded the infarction size in MRI and showed a good correlation to MRI parameters as well as to serum biomarkers of myocardial damage. Conclusions: 68Ga-FAPI-46 PET/MRI offers molecular and morphological imaging of affected myocardium after AMI. This study demonstrates ongoing fibroblast activation in a delayed phase after AMI and generates hypotheses for future studies while aiming for a better understanding of myocardial remodeling following ischemic tissue damage.

Objective: Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life, and therefore, early identification of patients at risk is urgently needed. Here we investigated the predictive power of various cut-off val ues of single stimulated thyroglobulin (s-Tg) and single highly sensitive measured, unstimulated thyroglobulin (u-hsTg) measurements close to the end of primary therapy for recurrence-free survival (RFS) in long-term follow-up (>10 years) of patients with DTC. Methods: In DTC patients with adjuvant radioiodine therapy, we assessed retrospectively u-hsTg (6 ± 3 months before s-Tg measurement) and s-Tg measurements (≤24 months after last radioiodine therapy). Positive predictive (PPV)/negative predictive values (NPV) of various cut-off values (s-Tg: 0.5/1.0 ng/mL; u-hsTg: 0. 09/0.2 ng/mL) for patient outcomes as well as additional factors associated with disease development were analyzed. Results: In total, 175 patients were retrospectively reviewed (tumor rec urrence: n = 14/ complete remission: n = 161). Examined cut-off values for s-Tg and u-hsTg showed significant predictive power for RFS (log-rank: all P < 0.001). NPV/PPV for s-Tg were 98.6%/36.4%, respectively (0.5 ng/mL cut-off) and 96.7%/42.9%, r espectively (1.0 ng/ mL cut-off); those for u-hsTg were 97.3%/35.7%, respectively (0. 09 ng/mL cut-off) and 95.2%/85.7%, respectively (0.2 ng/mL cut-off). U-hsTg (P < 0.001) and patient age (P < 0.05) were significantly associated with tumor recurrence. On e-third of patients with tumor recurrence in the course initially showed undetectable u- hsTg after completion of primary therapy. Conclusion: With >10 years of follow-up, both s-Tg and u-hsTg have a compar ably high predictive power for RFS, while only u-hsTg was significantly as sociated with a recurrence event. Serial u-hsTg measurements seem warranted since patients with tumor recurrence during follow-up may have an undetectable tumor marker at basel ine.

Abstract In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a “curative intention” treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.

Rationale 177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination regimes of programmed death-ligand 1 (PD-L1) inhibition and concomitant 177Lu-PSMA therapy have been proposed to increase the response rate. However, the interplay of immune landscape and 177Lu-PSMA therapy efficacy is poorly understood.Methods Between March 2018 and December 2021, a total of 168 patients were referred to 177Lu-PSMA therapy in our department and received a mean total dose of 21.9 GBq (three cycles in mean). All patients received baseline PSMA positron emission tomography to assess the PSMA uptake. The histopathological specimen of the primary prostate tumor was available with sufficient RNA passing quality control steps for genomic analysis in n=23 patients. In this subset of patients, tumor RNA transcriptomic analyses assessed 74 immune-related features in total, out of which n=24 signatures were not co-correlated and investigated further for outcome prognostication.Results In the subset of patients who received 177Lu-PSMA therapy, PD-L1 was not significantly associated with OS (HR per SD change (95% CI) 0.74 (0.42 to 1.30); SD: 0.18; p=0.29). In contrast, PD-L2 signature was positively associated with longer OS (HR per SD change 0.46 (95% CI 0.29 to 0.74); SD: 0.24; p=0.001; median OS 17.2 vs 5.7 months in higher vs lower PD-L2 patients). In addition, PD-L2 signature correlated with PSA-response (ϱ=−0.46; p=0.04). The PD-L2 signature association with OS was significantly moderated by L-Lactatdehydrogenase (LDH) levels (Cox model interaction p=0.01).Conclusion Higher PD-L2 signature might be associated with a better response to 177Lu-PSMA therapy and warrants further studies investigating additional immunotherapy. In contrast, PD-L1 was not associated with outcome. The protective effect of PD-L2 signature might be present only in men with lower LDH levels.

Abstract Accurate determination of lymph-node (LN) metastases is a prerequisite for high precision radiotherapy. The primary aim is to characterise the performance of PET/CT-based machine-learning classifiers to predict LN-involvement by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage-III NSCLC. Prediction models for LN-positivity based on [18F]FDG-PET/CT features were built using logistic regression and machine-learning models random forest (RF) and multilayer perceptron neural network (MLP) for stage-III NSCLC before radiochemotherapy. A total of 675 LN-stations were sampled in 180 patients. The logistic and RF models identified SUVmax, the short-axis LN-diameter and the echelon of the considered LN among the most important parameters for EBUS-positivity. Adjusting the sensitivity of machine-learning classifiers to that of the expert-rater of 94.5%, MLP (P = 0.0061) and RF models (P = 0.038) showed lower misclassification rates (MCR) than the standard-report, weighting false positives and false negatives equally. Increasing the sensitivity of classifiers from 94.5 to 99.3% resulted in increase of MCR from 13.3/14.5 to 29.8/34.2% for MLP/RF, respectively. PET/CT-based machine-learning classifiers can achieve a high sensitivity (94.5%) to detect EBUS-positive LNs at a low misclassification rate. As the specificity decreases rapidly above that level, a combined test of a PET/CT-based MLP/RF classifier and EBUS-TBNA is recommended for radiation target volume definition.

Abstract Biliary-tract-carcinomas (BTC), pancreatic-ductal-adenocarcinomas (PDAC) and adenoidcystic-carcinomas (AC) have in common that they are traditionally treated with large clinical-target-volumes (CTV). The aim of this study is to examine the impact of pretreatment-[68Ga]FAPI-PET/CT on target-volume-definition and posttreatment-[68Ga]FAPI-PET/CT-response-assessment for BTC-, PDAC- and AC-patients referred to radiation-therapy. All consecutive BTC-, PDAC-, and AC-patients who received pretreatment-[68Ga]FAPI-PET/CT±[18F]FDG-PET/CT were included from 01.01.2020 to 01.03.2022. MTV and SUVmax were separately generated based on [68Ga]FAPI- and [18F]FDG-PET/CT-images. A [68Ga]FAPI- and [18F]FDG-based-CTV was defined. Treatment-plans were compared. Treatment-response was reassessed by a second [68Ga]FAPI-PET/CT and [18F]FDG-PET/CT after treatment-completion. Intermodality comparison of lesion-to-background-ratios [SUVmax_lesion/SUVmean_background] for individual timepoints t 1 and t 2 revealed significant higher values for [68Ga]FAPI compared to [18F]FDG (t 1 , p = 0.008; t 2 , p = 0.005). Intermodality comparison of radiation-therapy-plans showed that [68Ga]FAPI-based planning resulted in D100% = 97.2% and V95% = 98.8% for the [18F]FDG-MTV. [18F]FDG-based-planning resulted in D100% = 35.9% and V95% = 78.1% for [68Ga]FAPI-MTV. [18F]FDG-based-planning resulted only in 2 patients in V95% > 95% for [68Ga]FAPI-MTV, and in 1 patient in D100% > 97% for [68Ga]FAPI-MTV. GTV-coverage in terms of V95% was 76.4% by [18F]FDG-based-planning and 99.5% by [68Ga]FAPI-based-planning. Pretreatment [68Ga]FAPI-PET/CT enhances radiation-treatment-planning in this particular group of patients. While perilesional and tumoral follow-up [18F]FDG-uptake behaved uniformly, perilesional and tumoral reaction may differ in follow-up [68Ga]FAPI-imaging. Complementary [68Ga]FAPI- and [18F]FDG-imaging enhance treatment-response-assessment.

Abstract 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.

Abstract Objective Light chain (AL) amyloidosis is a life‐threatening disorder characterised by extracellular deposition of amyloid leading to dysfunction of multiple organs. Peripheral nerve involvement, particularly small fibre neuropathy, may be associated with poorer survival. Corneal confocal microscopy (CCM) is a rapid and non‐invasive imaging technique to quantify corneal small nerve fibres and immune cells in vivo. We aimed to evaluate CCM as a tool for early diagnosis of peripheral nerve involvement in AL amyloidosis. Methods CCM and nerve conduction studies (NCS) were undertaken in 21 newly diagnosed, treatment‐naïve AL amyloidosis patients and 21 age‐ and sex‐matched healthy controls. Corneal nerve fibre density (CNFD), corneal nerve branch density and fibre length, and cell infiltrates were quantified in the sub‐basal layer of the cornea. Results There was a significant reduction in CNFD and nerve fibre length, even without large fibre affection and an increase in cell density, particularly around corneal nerve fibres in patients with AL amyloidosis compared to controls. Additionally, cell infiltration correlated with reduced nerve fibre density in patients with AL amyloidosis, but reduced CNFD did not correlate with laboratory parameters of organ dysfunction. Interpretation Our study is the first to show that CCM allows rapid non‐invasive identification of early small nerve fibre damage associated with immune cell infiltration in patients with AL amyloidosis. CCM detects peripheral nerve involvement more sensitively than NCS.