A systematic review for the evidence of recommendations and guidelines in hybrid nuclear cardiovascular imaging.

OBJECTIVES: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging. METHODS: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed. RESULTS: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines. CONCLUSION: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures.

Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study.

BACKGROUND: The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS: Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS: Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS: The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.

PET FDG CT is useful for giant-cell arteritis with isolated cough.

Giant cell arteritis (GCA) is a chronic vasculitis of large- and medium-sized vessels. The most frequent symptoms are temporal headaches, scalp tenderness, jaw claudication and polymyalgia rheumatica in 35% of patients. Atypical presentation with dry cough is very rare and could be isolated making the diagnosis difficult. Initial imaging including PET-CT could be helpful. Literature review yielded 13 case reports with available data and one case series which focused on cough and which were all be included in this study. Most of the cases included males (n = 8), with mostly isolated cough or associated to fever and weight loss. Angio-CT of aortic wall was mostly normal, whereas FDG PET-CT showed in all available cases abnormal arterial thoracic uptake. Temporal artery biopsy was almost suggestive of GCA in all available cases. Cough was steroid responsive usually within few days in all cases without any need of combined therapy. Giant cell arteritis is the most common large-vessel vasculitis over the age of 50 in western countries. Isolated dry cough is extremely rare and encountered in less than 5% of cases.

Features of non-Hodgkin's lymphoma diagnosed in minor salivary gland biopsies from primary Sjögren's syndrome patients.

OBJECTIVE: To evaluate the contribution of minor salivary gland biopsy (mSGB) histology in diagnosing primary SS (pSS)-associated non-Hodgkin B-cell lymphoma (NHL). METHODS: pSS patients with mSGB at NHL diagnosis were included. RESULTS: Among the 24 patients (92.3% female, mean age 61.3 years) with an mSGB at NHL diagnosis, 13 (54.2%) had mSGB histology-revealed NHL (mSGB+); it was the only site enabling NHL diagnosis in 10/13 (76.9%) patients. Mucosa-associated lymphoid tissue (MALT) lymphoma was found in 23/24 (95.8%) patients; 100% of mSGB+ identified MALT lymphomas. pSS and lymphoma characteristics were comparable for mSGB+ and mSGB- patients. Eight (61.5%) of the 13 mSGB+ patients and all 11 mSGB- patients were treated for lymphoma. Between diagnosis and 1 year of follow-up, the ESSDAI without the NHL item remained stable (7.4 vs 5.0; P = 0.33) for the five untreated patients, while it decreased significantly for the 19 treated patients (15.8 vs 5.1; P = 0.004). CONCLUSION: For pSS patients with suspected NHL, mSGB histology enabled NHL diagnosis in half of them, MALT was found in 95.8% and all mSGB+ were MALT lymphomas, thereby avoiding more invasive biopsy. Our results suggest that mSGB should be obtained at pSS diagnosis and repeated during follow-up when NHL is suspected.

AZTEK: Adaptive zero TE k-space trajectories.

PURPOSE: Because of short signal lifetimes and respiratory motion, 3D lung MRI is still challenging today. Zero-TE (ZTE) pulse sequences offer promising solutions as they overcome the issue of short T2∗ . Nevertheless, as they rely on continuous readout gradients, the trajectories they follow in k-space are not adapted to retrospective gating and inferred motion correction. THEORY AND METHODS: We propose AZTEK (adaptive ZTE k-space trajectories), a set of 3D radial trajectories featuring three tuning parameters, to adapt the acquisition to any moving organ while keeping seamless transitions between consecutive spokes. Standard ZTE and AZTEK trajectories were compared for static and moving phantom acquisitions as well as for human thoracic imaging performed on 3 volunteers (1 healthy and 2 patients with lung cancer). RESULTS: For the static phantom, we observe comparable image qualities with standard and AZTEK trajectories. For the moving phantom, spatially coherent undersampling artifacts observed on gated images with the standard trajectory are alleviated with AZTEK. The same improvement in image quality is obtained in human, so details are more delineated in the lung with the use of the adaptive trajectory. CONCLUSION: The AZTEK technique opens the possibility for 3D dynamic ZTE lung imaging with retrospective gating. It enables us to uniformly sample the k-space for any arbitrary respiratory motion gate, while preserving static image quality, improving dynamic image quality and guaranteeing continuous readout gradient transitions between spokes, which makes it appropriate to ZTE.

PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology.

PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level.

Diffusion-weighted Imaging Voxelwise-matched Analyses of Lung Cancer at 3.0-T PET/MRI: Reverse Phase Encoding Approach for Echo-planar Imaging Distortion Correction.

Background PET/MRI has drawn increasing interest in thoracic oncology due to the simultaneous acquisition of PET and MRI data. Geometric distortions related to diffusion-weighted imaging (DWI) limit the evaluation of voxelwise multimodal analyses. Purpose To assess the effectiveness of reverse phase encoding in correcting DWI geometric distortion for multimodal PET/MRI voxelwise lung tumor analyses. Materials and Methods In this prospective study, reverse phase encoding method was implemented with 3.0-T PET/MRI to correct geometric distortions related to DWI. The method was validated in dedicated phantom and then applied to 12 consecutive patients (mean age, 66 years ± 13 [standard deviation]; 10 men) suspected of having lung cancer who underwent fluorodeoxyglucose PET/MRI between October 2018 and April 2019. The effects on DWI-related image matching and apparent diffusion coefficient (ADC) regional map computation were assessed. Consequences on multimodal PET/MRI voxelwise lung tumor analyses were evaluated. Spearman correlation coefficients (rs) between the standardized uptake value (SUV) and ADC data corrected for distortion were computed from optimal realigned DWI PET data, along with bootstrap confidence intervals. Results Phantom results showed that in highly distorted areas, correcting the distortion significantly reduced the mean error against the ground truth (-25% ± 10.6 to -18.4% ± 12.6; P < .001) and the number of voxels with more than 20% error (from 85.3% to 31.4%). In the 12 patients, the coregistration of multimodal PET/MRI tumor data was improved by using the reverse phase encoding method (0.4%-44%). In all tumors, voxelwise correlations (rs) between ADC and SUV revealed null or weak monotonic relationships (mean rs of 0.016 ± 0.24 with none above 0.5). Conclusion Reverse phase encoding is a simple-to-implement method for improved diffusion-weighted multimodal PET/MRI voxelwise-matched analyses in lung cancer. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Colletti in this issue.

Rapid Contour-based Segmentation for 18F-FDG PET Imaging of Lung Tumors by Using ITK-SNAP: Comparison to Expert-based Segmentation.

Purpose To assess the performance of the ITK-SNAP software for fluorodeoxyglucose (FDG) positron emission tomography (PET) segmentation of complex-shaped lung tumors compared with an optimized, expert-based manual reference standard. Materials and Methods Seventy-six FDG PET images of thoracic lesions were retrospectively segmented by using ITK-SNAP software. Each tumor was manually segmented by six raters to generate an optimized reference standard by using the simultaneous truth and performance level estimate algorithm. Four raters segmented 76 FDG PET images of lung tumors twice by using ITK-SNAP active contour algorithm. Accuracy of ITK-SNAP procedure was assessed by using Dice coefficient and Hausdorff metric. Interrater and intrarater reliability were estimated by using intraclass correlation coefficients of output volumes. Finally, the ITK-SNAP procedure was compared with currently recommended PET tumor delineation methods on the basis of thresholding at 41% volume of interest (VOI; VOI41) and 50% VOI (VOI50) of the tumor's maximal metabolism intensity. Results Accuracy estimates for the ITK-SNAP procedure indicated a Dice coefficient of 0.83 (95% confidence interval: 0.77, 0.89) and a Hausdorff distance of 12.6 mm (95% confidence interval: 9.82, 15.32). Interrater reliability was an intraclass correlation coefficient of 0.94 (95% confidence interval: 0.91, 0.96). The intrarater reliabilities were intraclass correlation coefficients above 0.97. Finally, VOI41 and VOI50 accuracy metrics were as follows: Dice coefficient, 0.48 (95% confidence interval: 0.44, 0.51) and 0.34 (95% confidence interval: 0.30, 0.38), respectively, and Hausdorff distance, 25.6 mm (95% confidence interval: 21.7, 31.4) and 31.3 mm (95% confidence interval: 26.8, 38.4), respectively. Conclusion ITK-SNAP is accurate and reliable for active-contour-based segmentation of heterogeneous thoracic PET tumors. ITK-SNAP surpassed the recommended PET methods compared with ground truth manual segmentation.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.

Effect of CRP value on 18F-FDG PET vascular positivity in Takayasu arteritis: a systematic review and per-patient based meta-analysis.

PURPOSE: The aim of this study was to quantify the association between the CRP value and 18F-FDG PET vascular positivity in Takayasu arteritis (TAK) through a structured dedicated systematic review and meta-analysis. METHODS: From January 2000 to December 2016, the PubMed/MEDLINE database was searched for articles specifically dealing with the assessment of vascular inflammation using 18F-FDG PET and CRP biomarkers in TAK. Inclusion criteria for the qualitative analysis were (1) 18F-FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available. For the meta-analysis, PET-positive and PET-negative subgroups with the corresponding CRP concentrations were generated based on per patient data. The standard mean difference, which represents the effect of the CRP concentrations on the 18F-FDG PET vascular uptake, was computed for all studies, and then the results were pooled together. RESULTS: Among the 33 initial citations, nine complete articles including 210 patients fulfilled the inclusion criteria. Five studies found a significant correlation between the 18F-FDG PET and CRP concentration, one provided a trend towards association and three did not find any association between the two biomarkers. Six studies found a significant association between 18F-FDG PET and clinical disease activity, one found a trend towards association and the last two studies did not evaluate this correlation. The meta-analysis (121 patients) provided the following results: Standard Mean Deviation = 0.54 [0.15;0.92]; Chi2 = 3.35; I2 = 0%; Test for overall effect: Z = 2.70 (P = 0.007). CONCLUSION: The CRP concentration only moderately reflects the 18F-FDG PET vascular positivity in TAK, suggesting dissociated information. Standardized longitudinal prospective studies are necessary to assess the value of 18F-FDG PET as an independent biomarker for subtle vascular wall inflammation detection.

Cognitive and Brain Profiles Associated with Current Neuroimaging Biomarkers of Preclinical Alzheimer's Disease.

Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical ß-amyloid (Aß) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age = 65.8 ± 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE ε4 carriers compared with the amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with Aß deposition such that those with neurodegeneration tended to show less Aß deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or Aß deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Significance statement: Neuroimaging biomarkers are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers should be used in combination, offering an additive contribution instead of reflecting the same process of neurodegeneration. Moreover, the present study also challenges the hierarchical use of the neuroimaging biomarkers in preclinical AD because it suggests that the neurodegeneration observed in this population is not due to ß-amyloid deposition. Rather, our results suggest that ß-amyloid- and tau-related pathological processes may interact but not necessarily appear in a systematic sequence.

Contribution of (18)F-FDG PET in the diagnostic assessment of fever of unknown origin (FUO): a stratification-based meta-analysis.

PURPOSE: The aim of this study was to quantify the contribution of FDG PET to the diagnostic assessment of fever of unknown origin (FUO), taking into account the diagnostic limitations resulting from the composite nature of this entity. METHODS: The PubMed/MEDLINE database was searched from 2000 to September 2015. Original articles fulfilling the following criteria were included: (1) FUO as the initial diagnosis, (2) no immunosuppressed or nosocomial condition, (3) final diagnosis not based on PET, (4) a follow-up period specified, (5) adult population, and (6) availability of adapted data for calculation of odds ratios (ORs). ORs were computed for each study and then pooled using a random effects model. Stratification-based sensitivity analyses were finally performed using the following prespecified criteria: (a) study design, (b) PET device, (c) geographic area, and (d) follow-up period. RESULTS: A meta-analysis of the 14 included studies showed that normal PET findings led to an increase in the absolute final diagnostic rate of 36 % abnormal PET findings to an increase of 83 %, corresponding to a pooled OR of 8.94 (95 % CI 4.18 - 19.12, Z = 5.65; p < 0.00001). The design of the studies influenced the results (OR 2.92, 95 % CI 1.00 - 8.53 for prospective studies; OR 18,57, 95 % CI 7.57 - 45.59 for retrospective studies; p = 0.01), whereas devices (dedicated or hybrid), geographic area and follow-up period did not. CONCLUSION: Abnormal PET findings are associated with a substantially increased final diagnostic rate in FUO. Consequently, FDG PET could be considered for inclusion in the first-line diagnostic work-up of FUO. Further randomized prospective studies with standardized FDG PET procedures are warranted to confirm this first-line position.

Imaging brain effects of APOE4 in cognitively normal individuals across the lifespan.

The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer's disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aß) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aß deposition as most studies report significantly higher cortical Aß load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aß over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aß-dependent and Aß-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers.

Towards an optimal semiquantitative approach in giant cell arteritis: an (18)F-FDG PET/CT case-control study.

PURPOSE: Giant cell arteritis (GCA) is the most common form of vasculitis in western countries. (18)F-FDG PET has been shown to be a valuable tool for the diagnosis of extracranial GCA, but results of studies are inconsistent due to a lack of standardized (18)F-FDG PET criteria. In this study, we compared different semiquantitative approaches using a controlled design to define the most efficient method. METHODS: All patients with biopsy-proven GCA who had undergone an (18)F-FDG PET/CT scan in our PET unit were reviewed and matched with a control group based on age and sex. Different semiquantitative arterial (ascending and descending thoracic aorta and aortic arch) to background (liver, lung and venous blood pool) SUV ratios were blindly compared between GCA patients and matched controls. RESULTS: We included 11 patients with biopsy-proven GCA cases and 11 matched controls. There were no differences between the groups with regard to body weight, injected radioactivity, blood glucose level or CRP. The arterial to venous blood pool ratios discriminated the two groups better than other methods when applied to the aortic arch and the descending thoracic aorta (p<0.015). In particular, the highest aortic to highest blood pool SUVmax ratio, when applied to the aortic arch, provided optimal diagnostic performance (sensitivity 81.8 %, specificity 91 %, AUC 0.87; p<0.0001) using a cut-off value of 1.53. CONCLUSION: Among all tested (18)F-FDG PET/CT methods, the aortic to blood pool SUVmax ratio outperformed the liver and lung ratios. We suggest the use of this ratio for the assessment of aortic inflammation in GCA patients.

Myocardial innervation and perfusion imaging during LVAD implantation: a nuclear imaging approach.

In recent years, heart failure has been recognized as a major and increasing public health issue. In the context of the shortage of heart donors and increasing waiting time on the transplantation list, nonpulsatile left ventricular assist devices (LVAD) have shown their efficiency in reducing mortality and improving quality of life in patients with end-stage heart failure. Among LVAD recipients, a minority of patients will recover a normal cardiac function, allowing pump weaning. However, the evaluation of intrinsic cardiac function is particularly challenging and still a matter of debate in LVAD recipients.