Detection of cancer-associated cachexia in lung cancer patients using whole-body [18F]FDG-PET/CT imaging: A multi-centre study.

BACKGROUND: Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. METHODS: This multi-centre study included 345 LCP who underwent WB [18F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N = 158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N = 90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake () and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [18F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. RESULTS: The three CAC categories displayed multi-organ differences in . In all target organs, was higher in the 'CAC' cohort compared with 'No CAC' (P < 0.01), except for liver and kidneys, where in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ = -0.8) was identified between and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'. CONCLUSIONS: WB [18F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi-centre study has been initiated to address the limitations of the present retrospective analysis.

Non-Invasive Glucose Metabolism Quantification Method Based on Unilateral ICA Image Derived Input Function by Hybrid PET/MR in Ischemic Cerebrovascular Disease.

The non-invasive quantification of the cerebral metabolic rate for glucose (CMRGlc) and the characterization of cerebral metabolism in the cerebrovascular territories are helpful in understanding ischemic cerebrovascular disease (ICVD). Firstly, we investigated a non-invasive quantification approach based on an image-derived input function (IDIF) in ICVD. Second, we studied the metabolic changes in CMRGlc after surgical intervention. We evaluated the hypothesis that the IDIF method based on the unilateral internal carotid artery could address challenges in ICVD quantification. The CMRGlc and standardized uptake value ratio (SUVR) were used to measure glucose metabolism activity. Healthy controls showed no significant differences in CMRGlc values between bilateral and unilateral IDIF measurements (intraclass correlation coefficient [ICC]: 0.91-0.98). Patients with ICVD showed significantly increased CMRGlc values after surgical intervention for all territories (percentage changes: 7.4%-22.5%). In contrast, SUVR showed minor differences between postoperative and preoperative patients, indicating that it was a poor biomarker for the diagnosis of ICVD. A significant association between CMRGlc and the National Institutes of Health Stroke Scale (NIHSS) scores was observed (r=-0.54). Our findings suggested that IDIF could be a valuable tool for CMRGlc quantification in patients with ICVD and may advance personalized precision interventions.

Standard MRI-based attenuation correction for PET/MRI phantoms: a novel concept using MRI-visible polymer.

BACKGROUND: PET/MRI phantom studies are challenged by the need of phantom-specific attenuation templates to account for attenuation properties of the phantom material. We present a PET/MRI phantom built from MRI-visible material for which attenuation correction (AC) can be performed using the standard MRI-based AC. METHODS: A water-fillable phantom was 3D-printed with a commercially available MRI-visible polymer. The phantom had a cylindrical shape and the fillable compartment consisted of a homogeneous region and a region containing solid rods of different diameters. The phantom was filled with a solution of water and [18F]FDG. A 30 min PET/MRI acquisition including the standard Dixon-based MR-AC method was performed. In addition, a CT scan of the phantom was acquired on a PET/CT system. From the Dixon in-phase, opposed-phase and fat images, a phantom-specific AC map (Phantom MR-AC) was produced by separating the phantom material from the water compartment using a thresholding-based method and assigning fixed attenuation coefficients to the individual compartments. The PET data was reconstructed using the Phantom MR-AC, the original Dixon MR-AC, and an MR-AC just containing the water compartment (NoWall-AC) to estimate the error of ignoring the phantom walls. CT-based AC was employed as the reference standard. Average %-differences in measured activity between the CT corrected PET and the PET corrected with the other AC methods were calculated. RESULTS: The phantom housing and the liquid compartment were both visible and distinguishable from each other in the Dixon images and allowed the segmentation of a phantom-specific MR-based AC. Compared to the CT-AC PET, average differences in measured activity in the whole water compartment in the phantom of -0.3%, 9.4%, and -24.1% were found for Dixon phantom MR-AC, MR-AC, and NoWall-AC based PET, respectively. Average differences near the phantom wall in the homogeneous region were -0.3%, 6.6%, and -34.3%, respectively. Around the rods, activity differed from the CT-AC PET by 0.7%, 8.9%, and -45.5%, respectively. CONCLUSION: The presented phantom material is visible using standard MR sequences, and thus, supports the use of standard, phantom-independent MR measurements for MR-AC in PET/MRI phantom studies.

Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI.

INTRODUCTION: Inhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI. METHODS: PET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls. RESULTS: MTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p<0.001). The higher the GRP value in kidneys of T2DMSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation. CONCLUSION: MTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy. TRIAL REGISTRATION NUMBER: NCT03557138.

Utility of Absolute Quantification in Non-lesional Extratemporal Lobe Epilepsy Using FDG PET/MR Imaging.

The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [18F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (µmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention.

Assessment of the kidney function parameters split function, mean transit time, and outflow efficiency using dynamic FDG-PET/MRI in healthy subjects.

BACKGROUND: Traditionally, isotope nephrography is considered as the method of choice to assess kidney function parameters in nuclear medicine. We propose a novel approach to determine the split function (SF), mean transit time (MTT), and outflow efficiency (OE) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) dynamic positron emission tomography (PET). MATERIALS AND METHODS: Healthy adult subjects underwent dynamic simultaneous FDG-PET and magnetic resonance imaging (PET/MRI). Time-activity curves (TACs) of total kidneys, renal cortices, and the aorta were prospectively obtained from dynamic PET series. MRI images were used for anatomical correlation. The same individuals were subjected to dynamic renal Technetium-99 m-mercaptoacetyltriglycine (MAG3) scintigraphy and TACs of kidneys; the perirenal background and the left ventricle were determined. SF was calculated on the basis of integrals over the TACs, MTT was determined from renal retention functions after deconvolution analysis, and OE was determined from MTT. Values obtained from PET series were compared with scintigraphic parameters, which served as the reference. RESULTS: Twenty-four subjects underwent both examinations. Total kidney SF, MTT, and OE as estimated by dynamic PET/MRI correlated to their reference values by r = 0.75, r = 0.74 and r = 0.81, respectively, with significant difference (p < 0.0001) between the means of MTT and OE. No correlations were found for cortex FDG values. CONCLUSIONS: The study proofs the concept that SF, MTT, and OE can be estimated with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients receiving a routine PET/MRI scan, as kidney parameters can be estimated simultaneously to functional and morphological imaging with high accuracy.

Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects.

BACKGROUND: A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. RESULTS: Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. CONCLUSIONS: The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.