Amino-acid PET as a prognostic tool after post Stupp protocol temozolomide therapy in high-grade glioma patients.

PURPOSE: This study aimed to evaluate the prognostic performance of amino-acid PET in high-grade gliomas (HGG) patients at the time of temozolomide (TMZ) treatment discontinuation, after the Stupp protocol. METHODS: The analysis included consecutive HGG patients with dynamic [18F]FDOPA PET imaging within 3 months of the end of TMZ therapy, post-Stupp protocol. Static and dynamic PET parameters, responses to RANO criteria for MRI and clinical and histo-molecular factors were correlated to progression-free (PFS). RESULTS: Thirty-two patients (59.4 [54.0;67.6] years old, 13 (41%) women) were included. Static PET parameters peak tumor-to-background ratio and metabolic tumor volume (respective thresholds of 1.9 and 1.5 mL) showed the best 84% accuracies for predicting PFS at 6 months (p = 0.02). These static PET parameters were also independent predictor of PFS in multivariate analysis (p ≤ 0.05). CONCLUSION: In HGG patients having undergone a Stupp protocol, the absence of significant PET uptake after TMZ constitutes a favorable prognostic factor.

Association between baseline hemodynamic indices, cardiotoxicity risk, and survival in women with breast cancer.

BACKGROUND: The outcome of breast cancer (BrCa) women monitored by low-dose equilibrium radionuclide angiography (ERNA) remains challenging to predict. AIM: This study aims to determine whether heart rate (HR)/blood pressure (BP) ratio-based indexes, previously confirmed to predict outcomes of various diseases, also predict BrCa-therapy-related cardiotoxicity and survival. METHODS: Predictors of cardiotoxicity and survival were determined among pre-therapy variables, including shock index ([SI HR/systolic BP) and age-adjusted SI (ASI), in a female BrCa cohort with normal baseline ERNA-left ventricular ejection fraction (LVEF). RESULTS: We included 274 women with a median age of 54.8 (interquartile range: 45.5-65.4) years, 271 treated with anthracyclines and 96 with trastuzumab. During a median follow-up of 25.9 (18.6-33.5) months, 31 women developed cardiotoxicity (LVEF: <50% and ≥10% drop from baseline), and 25 died. Baseline ASI was a multivariate predictor (p < 0.001) of (i) cardiotoxicity, in association with trastuzumab treatment (p = 0.010), and LV end-diastolic volume (p = 0.001) and (ii) survival, in association with metastasis (p < 0.001) and estimated glomerular filtration rate (p = 0.008). Cardiotoxicity poorly impacted survival (p = 0.064). The 36-month cardiotoxicity and mortality rates were markedly higher for patients in the upper half of baseline ASI values (ASI: >30 years min-1.mmHg-1, 16.5% and 20.7%, respectively) than in the lower half (7.6% and 4.5%, respectively, both p < 0.05). CONCLUSIONS: In BrCa women with normal baseline ERNA-LVEF, HR/BP ratio-based indexes unmask hemodynamic profiles associated with increased cardiotoxicity risk and decreased survival, highlighting the need for a comprehensive assessment of cardiac- and vascular-related risks in BrCa women monitored by ERNA. CONDENSED ABSTRACT: In a cohort of 274 women BrCa women who were monitored by ERNA for potentially cardiotoxic drugs (anthracyclines or trastuzumab) and who had no history of cardiac disease and a normal left ventricular ejection fraction before treatment, baseline indexes based on HR/BP ratios unmask hemodynamic profiles strongly associated with an increased risk of cardiotoxicity and subsequently decreased survival. Although further validations in other cohorts are needed, these findings highlight the need for a more comprehensive assessment of the cardiac- and vascular-related risk in BrCa women monitored by ERNA.

Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.

OBJECTIVES: Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. METHODS: Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. RESULTS: Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). CONCLUSION: Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. CLINICAL RELEVANCE STATEMENT: SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. KEY POINTS: • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.

Routine first-line detection of breast cancer therapy-related cardiotoxicity by serial, fast and ultra-low-dose equilibrium radionuclide angiography.

BACKGROUND: This study assesses a first-line left ventricular ejection fraction (LVEF) monitoring provided by an ultra-low-dose equilibrium radionuclide angiography (ERNA) in breast cancer women treated with potentially cardiotoxic drugs and analyzes patient outcome based on the ERNA results. METHODS: Breast cancer women treated with anthracyclines, followed or not by trastuzumab, were monitored using ERNA with a high-sensitivity CZT-camera. Calibrated LVEF measurements were obtained with an almost threefold reduction of radiation doses and 10-min recording times. RESULTS: During a mean 24 ± 6 months follow-up, 552 ERNAs with a mean effective dose of 2.3 ± 0.6 mSv were performed in 195 women, among whom 22 (11%) presented both ERNA criteria of cardiotoxicity (LVEF < 50% and > 10% drop from baseline; Tox + group), 35 (18%) only one criterion (Tox ± group), and 138 (71%) neither (Tox - group). This ERNA-based classification correlated with trastuzumab-anthracycline treatment (p = 0.001), prior cardiovascular disease (p = 0.018), and cardiac outcome, with a 30-month survival with no cardiotoxicity-driven drug regimen changes of 97 ± 2% in Tox -, 60 ± 13% in Tox ± and 36 ± 13% in Tox + (p < 0.001) groups. CONCLUSION: First-line detection of breast cancer therapy-related cardiotoxicity by ultra-low-dose ERNA provides consistent results, confirming the excellent cardiac outcome for the greatest majority of women with no ERNA cardiotoxicity criteria.

Detection of acute myocarditis by ECG-triggered PET imaging of somatostatin receptors compared to cardiac magnetic resonance: preliminary results.

Somatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered digital-PET imaging of somatostatin receptors (68Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting. METHODS: Fourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered 68Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology 68Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients. RESULTS: An increased myocardial 68Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial 68Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months. CONCLUSION: These preliminary results suggest that 68Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.

Assessment of the routine reporting of very low-dose exercise-first myocardial perfusion SPECT from a large-scale real-world cohort and correlation with the subsequent reporting of coronary stenosis at angiography.

PURPOSE: Our study assesses the routine reporting of exercise ischemia using very low-dose exercise-first myocardial perfusion SPECT in a large number of patients and under real-life conditions, by evaluating correlations with the subsequent routine reporting of coronary stenosis by angiography and with factors that predict ischemia. METHODS: Data from 13,126 routine exercise MPI reports, from 11,952 patients (31% women), using very low doses of sestamibi and a high-sensitivity cardiac CZT camera, were extracted to assess the reporting of significant MPI-ischemia (> 1 left ventricular segment), to determine the MPI normalcy rate in a group with < 5% pretest probability of coronary artery disease (CAD) (n = 378), and to assess the ability of MPI to predict a > 50% coronary stenosis in patients with available coronary angiography reports in the 3 months after the MPI (n = 713). RESULTS: The median effective patient dose was 2.51 [IQR: 1.00-4.71] mSv. The normalcy rate was 98%, and the MPI-ischemia rate was independently predicted by a known CAD, the male gender, obesity, and a < 50% LV ejection fraction, ranging from 29.5% with all these risk factors represented to 1.5% when there were no risk factors. A > 50% coronary stenosis was significantly predicted by MPI-ischemia, less significantly for mild (odds ratio [95% confidence interval]: 1.61 [1.26-1.96]) than for moderate-to-severe MPI-ischemia (4.05 [3.53-4.57]) and was also impacted by having a known CAD (2.17 [1.83-2.51]), by a submaximal exercise test (1.48 [1.15-1.81]) and being ≥ 65 years of age (1.43 [1.11-1.76]). CONCLUSION: Ischemia detected using a very low-dose exercise-first MPI protocol in a large-scale clinical cohort and under real-life routine conditions is a highly significant predictor for the subsequent reporting of coronary stenosis, although this prediction is enhanced by other variables. This weakly irradiating approach is amenable to being repeated at shorter time intervals, in target patient groups with a high probability of MPI-ischemia.

The detection of infectious endocarditis may be enhanced by a repeat FDG-PET while maintaining patients on a ketogenic diet.

BACKGROUND: This study aims to determine whether the suppression of myocardial FDG uptake and detection of infectious endocarditis (IE) may be enhanced when FDG-PET is repeated on the next day while maintaining patients on a ketogenic diet in the interim. METHODS: Seventeen patients with definite IE underwent FDG-PET investigations both after a conventional metabolic preparation (> 12-hour fast after a low-carbohydrate evening meal) and a subsequent 12-hour extension of the low-carbohydrate diet followed by an additional > 12-hour fast. RESULTS: Plasma biomarkers showed increased ketogenic metabolism between the two FDG-PET scans. A myocardial FDG uptake persisted on the 1st PET in 9 patients (53%) for whom myocardial FDG uptake decreased significantly on the 2nd PET (SUVmax: 6.05 ± 3.25 vs 4.32 ± 3.47, P = 0.021), resulting in an enhancement in the diagnostic confidence of IE in 6 cases. These enhancements were not documented in the 8 patients exhibiting a total suppression of myocardial FDG uptake on the 1st PET. CONCLUSIONS: Better suppression of myocardial uptake and enhanced detection of IE may be achieved when an FDG-PET, showing an incomplete suppression of the myocardial FDG uptake, is repeated as soon as the next day, while maintaining patients on a ketogenic diet in the interim.

Hypermetabolism of the spleen or bone marrow is an additional albeit indirect sign of infective endocarditis at FDG-PET.

PURPOSE: This study aimed at determining the diagnostic implications of indirect signs of infection at FDG-PET-i.e., hypermetabolisms of the spleen and/or bone marrow (HSBM)-when documented in patients with known or suspected infective endocarditis (IE). METHODS: HSBM were defined by higher mean standardized uptake values comparatively to that of the liver on FDG-PET images from patients with a high likelihood of IE and prospectively included in a multicenter study. RESULTS: Among the 129 included patients, IE was ultimately deemed as definite in 88 cases. HSBM was a predictor of definite IE (P = 0.014; odds ratio (OR) 3.2), independently of the criterion of an abnormal cardiac FDG uptake (P = 0.0007; OR 9.68), and a definite IE was documented in 97% (29/30) of patients showing both HSBM and abnormal cardiac uptake, 78% (7/9) of patients with only abnormal cardiac uptake, 67% (42/63) of patients with only HSBM, and 37% (10/27) of patients with neither one. CONCLUSION: In this cohort with a high likelihood of IE, HSBM is an additional albeit indirect sign of IE, independently of the criterion of an abnormal cardiac uptake, and could reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease.

Integration of dynamic parameters in the analysis of 18F-FDopa PET imaging improves the prediction of molecular features of gliomas.

PURPOSE: 18F-FDopa PET imaging of gliomas is routinely interpreted with standardized uptake value (SUV)-derived indices. This study aimed to determine the added value of dynamic 18F-FDopa PET parameters for predicting the molecular features of newly diagnosed gliomas. METHODS: We retrospectively included 58 patients having undergone an 18F-FDopa PET for establishing the initial diagnosis of gliomas, whose molecular features were additionally characterized according to the WHO 2016 classification. Dynamic parameters, involving time-to-peak (TTP) values and curve slopes, were tested for the prediction of glioma types in addition to current static parameters, i.e., tumor-to-normal brain or tumor-to-striatum SUV ratios and metabolic tumor volume (MTV). RESULTS: There were 21 IDH mutant without 1p/19q co-deletion (IDH+/1p19q-) gliomas, 16 IDH mutants with 1p/19q co-deletion (IDH+/1p19q+) gliomas, and 21 IDH wildtype (IDH-) gliomas. Dynamic parameters enabled differentiating the gliomas according to these molecular features, whereas static parameters did not. In particular, a longer TTP was the single best independent predictor for identifying (1) IDH mutation status (area under the curve (AUC) of 0.789, global accuracy of 74% for the criterion of a TTP ≥ 5.4 min) and (2) 1p/19q co-deletion status (AUC of 0.679, global accuracy of 69% for the criterion of a TTP ≥ 6.9 min). Moreover, the TTP from IDH- gliomas was significantly shorter than those from both IDH+/1p19q- and IDH+/1p19q+ (p ≤ 0.007). CONCLUSION: Prediction of the molecular features of newly diagnosed gliomas with 18F-FDopa PET and especially of the presence or not of an IDH mutation, may be obtained with dynamic but not with current static uptake parameters.

Left ventricular ejection fraction determined with the simulation of a very low-dose CZT-SPECT protocol and an additional count-calibration on planar radionuclide angiographic data.

PURPOSE: To determine whether the left ventricular ejection fractions (EFs), measured on a high-sensitivity CZT single photon emission computed tomography (SPECT)-camera with a 70% reduction in recording times and a prevention of EF overestimation through an additional count-calibration, are concordant with reference EF from planar radionuclide angiography (2D-RNA). METHODS: An additional 10-minute CZT-SPECT recording was performed in patients referred to 2D-RNA for cardiomyopathy (n = 23) or chemotherapy monitoring (n = 50) with an in vivo red blood cell labeling with 850 MBq [Formula: see text]. The EF, obtained from CZT-SPECT with 100% (SPECT100) or 30% (SPECT30) projection times and with a SPECT-count calibration on the 2D-RNA counts of corresponding cavity volumes, were compared to EF from 2D-RNA. RESULTS: Strong and equivalent relationships were documented between the EF from 2D-RNA and the calibrated EF from SPECT100 (y = 0.89x + 6.62; R2 = 0.87) and SPECT30 (y = 0.87x + 8.40; R2 = 0.85), and the mean EF from SPECT100 (54% ± 15%) and SPECT30 (53% ± 16%) were close to that from 2D-RNA (55% ± 15%). However, upward shifts in these mean values were documented in the absence of count calibration for both SPECT100 (60% ± 18%) and SPECT30 (60% ± 18%). CONCLUSION: Left ventricular EF may be determined on a high-sensitivity CZT-camera, a 70% reduction in injected activities, and an additional count-calibration for further enhancing the concordance with 2D-RNA values.

Performance of 18F-sodium fluoride positron emission tomography with computed tomography to assess inflammatory and structural sacroiliitis on magnetic resonance imaging in axial spondyloarthritis.

OBJECTIVES: To assess increased sacroiliac joint (SIJ) uptake on 18F-NaF PET/CT according to a qualitative and quantitative approach and to compare with MRI SIJ assessments for structural and inflammatory sacroiliitis in a population of 23 patients with spondyloarthritis (SpA) (IDRCB: 2012-A00568-35; ClinicalTrials.gov: NCT 02869100). METHODS: This single-center prospective study included 23 patients with active SpA according to the ASAS and/or modified NY criteria. All patients had a pelvic AP-view radiograph, MRI of the SIJ and 18F-NaF PET/CT examinations within a month, which were analysed by three blinded readers. For MRI data, the SIJs were assessed according to the ASAS criteria and SPARCC method for scoring structural lesions (erosion, sclerosis, fat metaplasia, backfill and ankylosis) and inflammation. On the 18F-NaF PET, the SIJs were scored according to a slice-by-slice approach. Abnormal uptake was assessed using a qualitative method inspired by the ASAS criteria and two quantitative approaches (the PET-activity score according to the SPARCC method and the maximum standardised uptake value (SUVmax) for each SIJ). RESULTS: Structural sacroiliitis was observed on 7 radiographs and 15 MRIs. 10 MRIs showed inflammatory sacroiliitis (mean SPARCC 18.7). Twenty patients had a positive PET with a mean PET-activity score of 18.2 (±8.7). The mean SUVmax for a positive PET was 1.78 vs. 1.45 for a negative one. The inter-reader reliability was good for the PET activity score (ICC= 0.56 [IC-95: 0.32; 0.76]) and good to excellent for the SUVmax (ICC=0.70-0.90 [IC-95: 0.41; 0.96]). According to a binary approach, a positive PET was not correlated with a positive MRI for structural sacroiliitis. The PET-activity score (r=0.61, p=0.001) and SUVmax (r=0.56, p=0.004) were correlated with the SPARCC inflammation score but not with structural sacroiliitis or for SPARCC structural lesions. CONCLUSIONS: Abnormal uptake by the SIJ on 18F-NaF PET is more frequent (87.0%) than inflammatory (43.5%) and structural sacroiliitis (65.2%) on MRI in a population of SpA patients. The PET activity score and SUVmax had good correlations with inflammatory sacroiliitis but not with structural lesions on MRI.

Low baseline and subsequent higher aortic abdominal aneurysm FDG uptake are associated with poor sac shrinkage post endovascular repair.

PURPOSE: The growth phases of medically treated abdominal aortic aneurysms (AAA) are frequently associated with an 18F-fluorodesoxyglucose positron emission tomography (FDG-PET) pattern involving low baseline and subsequent higher FDG uptake. However, the FDG-PET patterns associated with the endovascular aneurysm repair (EVAR) of larger AAA are presently unknown. This study aimed to investigate the relationship between serial AAA FDG uptake measurements, obtained before EVAR and 1 and 6 months post-intervention and subsequent sac shrinkage at 6 months, a well-recognized indicator of successful repair. METHODS: Thirty-three AAA patients referred for EVAR (maximal diameter: 55.4 ± 6.0 mm, total volume: 205.7 ± 63.0 mL) underwent FDG-PET/computed tomography (CT) before EVAR and at 1 and 6 months thereafter, with the monitoring of AAA volume and of a maximal standardized FDG uptake [SUVmax] averaged between the axial slices encompassing the AAA. RESULTS: Sac shrinkage was highly variable and could be stratified into three terciles: a first tercile in which shrinkage was absent or very limited (0-29 mL) and a third tercile with pronounced shrinkage (56-165 mL). SUVmax values were relatively low at baseline in the 1st tercile (SUVmax: 1.69 ± 0.33), but markedly increased at 6 months (2.42 ± 0.69, p = 0.02 vs. baseline). These SUV max values were by contrast much higher at baseline in the 3rd tercile (SUVmax: 2.53 ± 0.83 p = 0.009 vs. 1st tercile) and stable at 6 months (2.49 ± 0.80), while intermediate results were documented in the 2nd tercile. Lastly, the amount of sac shrinkage, expressed in absolute values or in percentages of baseline AAA volumes, was positively correlated with baseline SUVmax (p = 0.001 for both). CONCLUSION: A low pre-EVAR FDG uptake and increased AAA FDG uptake at 6 months are associated with reduced sac shrinkage. This sequential FDG-PET pattern is similar to that already shown to accompany growth phases of medically treated AAA.

Routine evaluation of left ventricular function using CZT-SPECT, with low injected activities and limited recording times.

PURPOSE: Gamma-cameras, with Cadmium-Zinc-Telluride (CZT) detectors, allow to perform myocardial perfusion imaging (MPI) with limited injected activities and recorded times. This study aimed at determining whether the routine assessment of left ventricular (LV) function with such limited counts protocols compares well with reference values from cardiac MRI. METHODS: The study included patients who have undergone cardiac MRI and an MPI routinely planned on a CZT camera with a low-dose protocol (120 MBq of Sestamibi for stress and 360 MBq at rest for 75 kg body weight), while targeting the recording of only 500 myocardial kcounts in order to limit the recording times (<10 minutes for stress, <4 minutes for rest). SPECT images were reconstructed with a method maintaining rather high spatial (8 mm) and temporal (16 frames/cycle) resolutions. RESULTS: Seventy-six patients were included, and mean effective dose was 3.5 ± 1.7 mSv for the total MPI protocol. Correlations between CZT-SPECT and MRI were good to excellent for ejection fraction (r 2 = 0.77), end-diastolic (r 2 = 0.88) and end-systolic (r 2 = 0.93) volumes, and the analysis of segmental contractility correlated well between the two techniques (kappa score = 0.72 ± 0.02). CONCLUSION: LV function, assessed on a CZT camera with low injected activities and limited recording times, correlates well with the reference assessment from cardiac MRI.

Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol.

PURPOSE OF THE REPORT: This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure. METHODS AND RESULTS: One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest-stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03). CONCLUSION: This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.

Grey-Matter Metabolism in Relation with White-Matter Lesions in Older Hypertensive Patients with Subjective Memory Complaints: A Pilot Voxel-Based Analysis Study.

BACKGROUND: This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging. METHODS: Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images. RESULTS: The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy. CONCLUSIONS: White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy.

¹8F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis.

PURPOSE: Timely identification of septic foci is critical in patients with severe sepsis or septic shock of unknown origin. This prospective pilot study aimed to assess (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), combined with whole-body computed tomographic angiography (CTA), in patients with suspected severe sepsis and for whom the prior diagnostic workup had been inconclusive. METHODS: Patients hospitalized in an intensive care unit with a suspected severe sepsis but no definite diagnosis after 48 h of extensive investigations were prospectively included and referred for a whole body FDG-PET/CTA. Results from FDG-PET/CTA were assessed according to the final diagnosis obtained after follow-up and additional diagnostic workup. RESULTS: Seventeen patients were prospectively included, all on mechanical ventilation and 14 under vasopressor drugs. The FDG-PET/CTA exam 1) was responsible for only one desaturation and one hypotension, both quickly reversible under treatment; 2) led to suspect 16 infectious sites among which 13 (81 %) could be confirmed by further diagnostic procedures; and 3) triggered beneficial changes in the medical management of 12 of the 17 study patients (71 %). The FDG-PET/CTA images showed a single or predominant infectious focus in two cases where CTA was negative and in three cases where CTA exhibited multiple possible foci. CONCLUSION: Whole-body FDG-PET/CTA appears to be feasible, relatively safe, and provides reliable and useful information, when prospectively planned in patients with suspected severe sepsis and for whom prior diagnostic workup had been inconclusive. The FDG-PET images are particularly helpful when CTA exhibits no or multiple possible sites.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

18F-FDG PET can effectively rule out conversion to dementia and the presence of CSF biomarker of neurodegeneration: a real-world data analysis.

BACKGROUND: Precisely defining the delay in onset of dementia is a particular challenge for early diagnosis. Brain [18F] fluoro-2-deoxy-2-D-glucose (18F-FDG) Positron Emission Tomography (PET) is a particularly interesting tool for the early diagnosis of neurodegenerative diseases, through the measurement of the cerebral glucose metabolic rate. There is currently a lack of longitudinal studies under real-life conditions, with sufficient patients, to accurately evaluate the predictive values of brain 18F-FDG PET scans. Here, we aimed to estimate the value of brain 18F-FDG PET for predicting the risk of dementia conversion and the risk of occurrence of a neurodegenerative pathology. METHODS: Longitudinal data for a cohort of patients with no diagnosis of dementia at the time of recruitment referred by a tertiary memory clinic for brain 18F-FDG PET were matched with (Prince M, Wimo A, Guerchet Maëlenn, Ali G-C, Wu Y-T et al. World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. [Research Report] Alzheimer's Disease International. 2015. 2015.) data from the French National Health Data System (NHDS), (Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62.) data from the National Alzheimer Bank (NAB), and (Davis M, O`Connell T, Johnson S, Cline S, Merikle E, Martenyi F, et al. Estimating Alzheimer's Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia. CAR. 2018;15(8):777-88.) lumbar puncture (LP) biomarker data. The criteria for dementia conversion were the designation, within the three years after the brain 18F-FDG PET scan, of a long-term condition for dementia in the NHDS and a dementia stage of cognitive impairment in the NAB. The criterion for the identification of a neurodegenerative disease in the medical records was the determination of LP biomarker levels. RESULTS: Among the 403 patients (69.9 ± 11.4 years old, 177 women) from the initial cohort with data matched with the NHDS data, 137 were matched with the NAB data, and 61 were matched with LP biomarker data. Within three years of the scan, a 18F-FDG PET had negative predictive values of 85% for dementia conversion (according to the NHDS and NAB datasets) and 95% for the presence of LP neurodegeneration biomarkers. CONCLUSION: A normal brain 18F-FDG PET scan can help rule out the risk of dementia conversion and the presence of cerebrospinal fluid (CSF) biomarker of neurodegeneration early with high certainty, allowing modifications to patient management regimens in the short term. TRIAL REGISTRATION: Clinical Trials database (NCT04804722). March 18, 2021. Retrospectively registered.

Factors Associated with Myocardial Uptake on Oncologic Somatostatin PET Investigations and Differentiation from Myocardial Uptake of Acute Myocarditis.

Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(ß), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(ß), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.