18F-FDG PET/CT versus Diagnostic Contrast-Enhanced CT for Follow-Up of Stage IV Melanoma Patients Treated by Immune Checkpoint Inhibitors: Frequency and Management of Discordances over a 3-Year Period in a University Hospital.

AIM: To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. MATERIALS AND METHODS: We conducted a retrospective monocentric observational study over a 3-year period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint (ICIs) as of January 2017. Imaging reports were analyzed by two physicians in consensus. The anatomical site responsible for discordances, as well as induced changes in treatment were noted. RESULTS: Eighty patients were included and 195 pairs of scans analyzed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient's management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients' management in 2/13 cases (15%). The most frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. CONCLUSIONS: Treatment monitoring with 18F-FDG PET/CT is more efficient than ceCT and has a greater impact in patient's management.

Quantification of myocardial blood flow by CZT-SPECT with motion correction and comparison with 15O-water PET.

BACKGROUND: We compared quantification of MBF and myocardial flow reserve (MFR) with a 99mTc-sestamibi CZT-SPECT to 15O-water PET. METHODS: SPECT MBF for thirty patients in the WATERDAY study was re-analyzed by QPET software with motion correction and optimal placement of the arterial input function. 15O-water PET MBF was re-quantified using dedicated software. Inter-operator variability was assessed using repeatability coefficients (RPC). RESULTS: Significant correlations were observed between global (r = 0.91, P < 0.001) and regional MBF (r = 0.86, P < 0.001) with SPECT compared to PET. Global MBF (rest 0.95 vs 1.05 ml/min/g, P = 0.07; stress 2.62 vs 2.68 mL/min/g, P = 0.17) and MFR (2.65 vs 2.75, P = 0.86) were similar between SPECT and PET. Rest (0.81 vs 0.98 mL/min/g, P = 0.03) and stress MBF (1.98 vs 2.61 mL/min/g, P = 0.01) in right coronary artery (RCA) were lower with SPECT compared to PET. However, MFR in the RCA territory was similar (2.54 vs 2.77, P = 0.21). The SPECT-PET RPC for global MBFs and MFR were 0.95 mL/min/g and 0.94, with inter-observer RPC of 0.59 mL/min/g and 0.74, respectively. CONCLUSIONS: MBF and MFR derived from CZT-SPECT with motion correction and optimal placement of the arterial input function showed good agreement with 15O-water PET, as well as low inter-operator variability.

How fast can we scan patients with modern (digital) PET/CT systems?

PURPOSE: To seek for the minimal duration per bed position with a digital PET system without compromising image quality and lesion detection in patients requiring fast 18F-FDG PET imaging. MATERIALS AND METHODS: 19 cancer patients experiencing pain or dyspnea and 9 pediatric patients were scanned on a Vereos system. List mode data were reconstructed with decreasing time frame down to 10 s per bed position. Noise was evaluated in the liver, blood pool and muscle, and using target-to-background ratios. Five PET readers recorded image quality, number of clinically relevant foci and of involved anatomical sites in reconstructions ranging from 60 to 10 s per bed position, compared to the standard 90 s reconstruction. RESULTS: The following reconstructions, which harboured a noise not significantly higher than that of the standard reconstruction, were selected for clinical evaluation: 1iterations/10 subsets/20sec (1i10 s20sec), 1i10 s30sec, and 2i10 sPSF60sec. Only the 60 s per bed acquisition displayed similar target-to-background ratios compared to the standard reconstruction, but mean ratios were still higher than 2.0 for the 30 s reconstruction. Inter-rater agreement for the number of involved anatomical sites and detected lesion was good or almost perfect (Kappa: 0.64-0.91) for all acquisitions. In particular, kappa for the 30 s per bed acquisition was 0.78 and 0.91 for lesion and anatomical sites number, respectively. Intra-rater agreement was also excellent for the 30 s reconstruction (kappa = 0.72). Median estimated total PET acquisition time for the 1i10 s30sec, and the standard reconstruction were 4 and 12 min, respectively. CONCLUSIONS: Fast imaging is feasible with state-of-the-art PET systems. Acquisitions of 30 s per bed position are feasible with the Vereos system, requiring optimization of reconstruction parameters.

Baseline 18F-FDG PET radiomic features as predictors of 2-year event-free survival in diffuse large B cell lymphomas treated with immunochemotherapy.

OBJECTIVES: To explore the prognostic value of positron emission tomography (PET) radiomic features in the field of diffuse large B cell lymphoma (DLBCL) treated with a first-line immunochemotherapy. METHODS: One-hundred thirty-two patients newly diagnosed with DLBCL were retrospectively included. PET studies were reconstructed using an ordered subset expectation maximisation algorithm with point spread function modelling. The total metabolic tumour volume (MTV) was recorded for each patient, and the volume of interest structure of the largest target lesion was used to compute 18F-FDG textural parameters. Data was randomly split into training and validation datasets. Optimal cutoff values were determined by means of 2-year event-free survival (EFS) ROC analyses. Two-year EFS analyses were performed using Kaplan-Meier survival analyses and univariable and multivariable Cox regression models. RESULTS: The median follow-up was 27 months, and the 2-year event-free survival (2y-EFS) was 77.3% in the entire population. ROC analyses for the 2y-EFS reached statistical significance for total MTV as well as four second-order metrics (homogeneity, contrast, correlation, dissimilarity) and five third-order metrics (LZE (Long-Zone Emphasis), LZLGE (Long-Zone Low-Grey Level Emphasis), LZHGE (Long-Zone High-Grey Level Emphasis), GLNU (Grey-Level Non-Uniformity) and ZP (Zone Percentage)). LZHGE displayed the highest ROC analysis accuracy (acc. = 0.76) and the best discriminant value on univariable Kaplan-Meier analysis (p < 0.0001, HR = 4.54). On multivariable analysis, including IPIaa, total MTV and LZHGE, LZHGE was the only independent predictor of 2y-EFS. These results were confirmed on the validation dataset. CONCLUSIONS: Baseline 18F-FDG PET heterogeneity of the largest lymphoma lesion is a promising predictor of 2y-EFS in newly diagnosed DLBCL treated with immunochemotherapy. KEY POINTS: •18F-FDG metabolic heterogeneity emerges as a new tool for survival prognostication of patients and has been explored in many solid tumours with promising results. • Baseline18F-FDG PET heterogeneity of the largest lymphoma lesion is an independent predictor of 2y-EFS in newly diagnosed DLBCL treated with immunochemotherapy. • DLBCL patients presenting with a heterogeneous tumour displayed a worse prognosis.

Evaluation of a new multipurpose whole-body CzT-based camera: comparison with a dual-head Anger camera and first clinical images.

BACKGROUND: Evaluate the physical performance of the VERITON CzT camera (Spectrum Dynamics, Caesarea, Israel) that benefits from new detection architecture enabling whole-body imaging compared to that of a conventional dual-head Anger camera. METHODS: Different line sources and phantom measurements were performed on each system to evaluate spatial resolution, sensitivity, energy resolution and image quality with acquisition and reconstruction parameters similar to those used in clinical routine. Extrinsic resolution was assessed using 99mTc capillary sources placed successively in air, in a head and in a body phantom filled with background activity. Spectral acquisitions for various radioelements used in nuclear medicine (99mTc, 123I, 201Tl, 111In) were performed to evaluate energy resolution by computing the FWHM of the measured photoelectric peak. Tomographic sensitivity was calculated by recording the total number of counts detected during tomographic acquisition for a set of source geometries representative of different clinical situations. Sensitivity was also evaluated in focus mode for the CzT camera, which consisted of forcing detectors to collect data in a reduced field-of-view. Image quality was assessed with a Jaszczak phantom filled with 350 MBq of 99mTc and scanned on each system with 30-,20-,10- and 5-min acquisition times. RESULTS: Extrinsic and tomographic resolution in the brain and body phantoms at the centre of the FOV was estimated at 3.55, 7.72 and 6.66 mm for the CzT system and 2.47, 7.75 and 7.72 mm for the conventional system, respectively. The energy resolution measured at 140 keV was 5.46% versus 9.21% for the Anger camera and was higher in a same manner for all energy peaks tested. Tomographic sensitivity for a point source in air was estimated at 236 counts·s-1·MBq-1 and increased to 1159 counts·s-1·MBq-1 using focus mode, which was 1.6 times and 8 times greater than the sensitivity measured on the scintillation camera (144 counts·s-1·MBq-1). Head and body measurements also showed higher sensitivity for the CzT camera in particular with focus mode. The Jaszczak phantom showed high image contrast uniformity and a high signal-to-noise ratio on the CzT system, even when decreasing acquisition time by 6-fold. Representative clinical cases are shown to illustrate these results. CONCLUSION: The CzT camera has a superior sensitivity, higher energy resolution and better image contrast than the conventional SPECT camera, whereas spatial resolution remains similar. Introduction of this new technology may change current practices in nuclear medicine such as decreasing acquisition time and activity injected to patient.

Comprehensive analysis of the influence of G-CSF on the biodistribution of 18F-FDG in lymphoma patients: insights for PET/CT scheduling.

AIMS: (1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring. MATERIALS AND METHODS: Retrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed. RESULTS: Mean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation_BONE), liver (%Variation_LIVER) and spleen (%Variation_SPLEEN) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation_LIVER and %Variation_SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation_BONE, %Variation_LIVER, and %Variation_SPLEEN. On the contrary, %Variation_BONE and %Variation_SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = - 0.342 (p = 0.010) and ρ = - 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmaxEARL. %Variation_LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmaxEARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk. CONCLUSIONS: Neither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring.

Comparative Performances of Dipyridamole and Regadenoson to Detect Myocardial Ischemia using Cardiac Cadmium-Zinc-Telluride Single-Photon Emission Computerized Tomography.

OBJECTIVE: We evaluated the relative performances of dipyridamole (Dip) and regadenoson (Reg) in a cohort of patients referred for coronary artery disease diagnosis or follow-up using myocardial perfusion imaging. MATERIALS AND METHODS: We retrospectively included 515 consecutive patients referred for 99mTc-sestamibi myocardial perfusion single-photon emission computerized tomography (SPECT) on a cadmium-zinc-telluride (CZT) camera after pharmacologic stress. About three quarters (n = 391, 76%) received Dip. Reg was administrated to patients with chronical respiratory disease or with body mass index (BMI) over 38 kg/m2 (n = 124, 24%). Patients with an abnormal stress scan (92%) underwent a rest imaging on the same day. Qualitative interpretation of perfusion images was achieved using QPS software, and the ischemic area was assessed using the 17-segment model. In patients undergoing a stress-rest protocol, perfusion polar plots were postprocessed using automated in-house software to quantify the extension, intensity, and location of the reversible perfusion defect. Statistical comparison between groups was performed using univariate and multivariate analysis. RESULTS: Qualitative analysis concluded to myocardial ischemia in 70% of the patients (69% in the Dip group, 76% in the Reg group, P = ns). In those patients, the number of involved segments (Dip 2.5 ± 1.6, Reg 2.7 ± 1.6, P = ns) and the proportion of patients with an ischemic area larger than two segments (Dip 30%, Reg 37%, P = ns) were comparable. Automated quantification of the reversible perfusion defect demonstrated similar defect extension, intensity, and severity in the two groups. Defect location was identical at the myocardial segment and vascular territory scales. CONCLUSIONS: Reg and Dip showed equal performances for ischemic burden characterization using myocardial CZT SPECT.

First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study.

PURPOSE: We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15O-water PET and fractional flow reserve (FFR). METHODS: Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99mTc-sestamibi CZT-SPECT and 15O-water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively. RESULTS: CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8). CONCLUSIONS: Dynamic 99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15O-water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

Assessment of alteration in liver 18F-FDG uptake due to steatosis in lymphoma patients and its impact on the Deauville score.

AIM: Our aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on 18F-FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders. METHODS: Over a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n = 143), interim (n = 79) and end-of-treatment (EoT, n = 136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SULmax were recorded on the liver and the tumour target lesion. DS were then computed. RESULTS: Prevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p = 0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SULmax values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66 ± 0.36 versus 2.15 ± 0.27) and EoT (1.67 ± 0.29 versus 2.17 ± 0.30) PET. CT density was found to be an independent factor that correlated with liver SULmax, while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SULmax, all DS4 steatotic patients on interim (n = 1) and EoT (n = 2) PET moved to DS3. CONCLUSIONS: Steatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%.