This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85–11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.
The present translational study aimed to verify whether serial F-FDG PET/CT predicts doxorubicin cardiotoxicity. Fifteen athymic mice were treated intravenously with saline ( = 5) or with 5 or 7.5 mg of doxorubicin per kilogram ( = 5 each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. In mice, LV MRGlu was 17.9 ± 4.4 nmol × min × g at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min × g, < 0.05 vs. controls) and high-dose subgroups (37.2 ± 7.8 nmol × min × g, < 0.01 vs. controls, < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 ± 0.9 vs. 3.34 ± 2.54, respectively, < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Doxorubicin dose-dependently increases LV MRGlu, particularly in the presence of low baselineF-FDG uptake. These results imply that low myocardial F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis.
Objective: To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Methods: Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. Results: Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal View this article online at wileyonlinelibrary.com.
In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD.
Several studies have highlighted the role of vascular 18 F-NaF uptake as a marker of ongoing calcium deposition. However, accumulation of 18 F-NaF is often inconsistent with localization of arterial plaque. Calcification activity and thus 18 F-NaF uptake might prevail in the earlier plaque stages. To test this hypothesis, we evaluated 18 F-NaF uptake in plaque of 3 different densities, using density as a marker of calcification progression. We also tested whether attenuationweighted image reconstruction affects 18 F-NaF uptake in the different plaque stages. Methods: Sixty-four oncologic patients (14 men and 50 women; mean age, 65.3 ± 8.2 y; range, 26-81 y) underwent 18 F-NaF PET/CT. A volume of interest was drawn on each plaque within the infrarenal aorta to assess mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque was then categorized as light (,210 HU), medium (211-510 HU), or heavy (.510 HU). Standardized uptake value was normalized for blood 18 F-NaF activity to obtain the plaque target-to-background ratio (TBR). During this process, several focal, noncalcified areas of 18 F-NaF were identified (hot spots). The TBR of the hot spots was computed after isocontour thresholding. The TBR of a noncalcified control region was also calculated. In 35 patients, the TBR of nonattenuation-corrected images was calculated. Results: The average TBR was highest in light plaque (2.21 ± 0.88), significantly lower in medium plaque (1.59 ± 0.63, P , 0.001), and lower still in heavy plaque (1.14 ± 0.37, P , 0.0001 with respect to both light and medium plaque). The TBR of the control region was not significantly different from that of heavy plaque but was significantly lower than that of light and medium plaque (P , 0.01). Hot spots had the highest absolute TBR (3.89 ± 1.87, P , 0.0001 vs. light plaque). TBRs originating from non-attenuation-corrected images did not significantly differ from those originating from attenuation-corrected images. Conclusion: Our results support the concept that 18 FNaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanisms are the main determinants of calcium presence, but that retention of 18 F-NaF progressively decreases with increasing calcium deposition in the arterial wall. Our data suggest that nonattenuation-corrected reconstruction does not significantly affect evaluation of plaque of any thickness.
Because of the peculiar mechanism of action of immune checkpoint inhibitors (ICIs), evaluation of the radiologic response to them in solid tumors presents many challenges. We aimed to compare evaluation of the first response to nivolumab by means of CT-based criteria with respect to 18 F-FDG PET response criteria in non-small cell lung cancer (NSCLC) patients. Methods: Seventy-two patients with advanced NSCLC were recruited in a single-institution ancillary trial within the expanded-access program (NCT02475382) for nivolumab. Patients underwent CT and 18 F-FDG PET at baseline and after 4 cycles (the first evaluation). In cases of progressive disease, an additional evaluation was performed after 2 further cycles to confirm progression. We evaluated the treatment response on CT using RECIST 1.1 and the immune-related response criteria (irRC) and on 18 F-FDG PET using PERCIST and immunotherapy-modified PERCIST. The concordance between CT-and PET-based criteria and the capability of each method to predict overall survival were evaluated. Results: Forty-eight of 72 patients were evaluable for a first response assessment with both PET-and CT-based criteria. We observed low concordance between CT-and PET-based criteria (κ-value of 0.346 and 0.355 between PERCIST and imPERCIST and RECIST, respectively. κ-value of 0.128 and 0.198 between PERCIST and imPERCIST and irRC, respectively). Regarding overall survival, irRC could more reliably distinguish responders from nonresponders. However, thanks to the prognostic value of partial metabolic response assessed by both PERCIST and immunotherapy-modified PERCIST, PET-based response maintained prognostic significance in patients classified as having progressive disease on the basis of irRC. Conclusion: Even though the present study did not support the routine use of 18 F-FDG PET in the general population of NSCLC patients treated with ICIs, the findings suggest that metabolic response assessment has added prognostic value, potentially improving therapeutic decision making.
Purpose Coronavirus disease-19 (COVID-19) pandemic is challenging the availability of hospital resources worldwide. The Young Group of the Italian Association of Nuclear Medicine (AIMN) developed the first international survey to evaluate the impact of COVID-19 in nuclear medicine (NM). The aim of this study was to perform a preliminary report of the ongoing survey. Methods A questionnaire of thirty questions was prepared for all NM professionals addressing three main issues: (1) new scheduling praxes for NM diagnostic and therapeutic procedures, (2) assistance of patients with diagnosed or suspected COVID-19, and (3) prevention of COVID-19 spreading in the departments. An invitation to the survey was sent to the corresponding authors of NM scientific papers indexed in SCOPUS in 2019. Personal data were analysed per individual responder. Organisation data were evaluated per single department. Results Two-hundred and ninety-six individual responders from 220 departments were evaluated. Most of the responders were from Europe (199/296, 67%). Approximately, all departments already changed their scheduling praxes due to the pandemic (213/ 220, 97%). In most departments, scheduled diagnostic and therapeutic procedures were allowed but quantitatively reduced (112/ 220, 51%). A significant reduction of diagnostic and therapeutic procedures (more than 20%) affected 198/220 (90%) and 158/ 220 (72%) departments, respectively. Incidental COVID-19 signs in NM exams occurred in 106/220 departments (48%). Few departments were closed or shifted to assist patients with 16%). Most of the responders thought that pandemic would not permanently change the work of NM departments in the future (189/296, 64%). Conclusions According to this preliminary report of the first international survey, COVID-19 heavily impacted NM departments and professionals. New praxes for NM procedures, assistance, and prevention of COVID-19 have been applied during the pandemic.Keywords COVID-19 . Nuclear medicine . Survey This article is part of the Topical Collection on Infection and inflammation.
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