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Positron emission tomography and magnetic resonance imaging of the brain in experimental human malaria, a prospective cohort study.

ABSTRACT: Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falciparum induced blood stage malaria (IBSM) infection, and compared results to individuals with P. vivax infection, in whom coma is rare. Seven healthy, malaria-naïve participants underwent imaging at baseline, and at early symptom onset a median 9 days following inoculation (n = 4 P. falciparum, n = 3 P. vivax). Participants with P. falciparum infection demonstrated marked lability in radiotracer uptake across all regions of the brain, exceeding expected normal variation (within subject coefficient of variation (wCV): 14.4%) compared to the relatively stable uptake in participants with P. vivax infection (wCV: 3.5%). No consistent imaging changes suggestive of microvascular dysfunction were observed in either group. Neuroimaging in early IBSM studies is safe and technically feasible, with preliminary results suggesting that differences in brain tropism between P. falciparum and P. vivax may occur very early in infection.

SUBMITTER: Woodford J

PROVIDER: S-EPMC8983718 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Positron emission tomography and magnetic resonance imaging of the brain in experimental human malaria, a prospective cohort study.

Woodford John J Gillman Ashley A Jenvey Peter P Roberts Jennie J Woolley Stephen S Barber Bridget E BE Fernandez Melissa M Rose Stephen S Thomas Paul P Anstey Nicholas M NM McCarthy James S JS

Scientific reports 20220405 1

Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falcipar ...[more]

PMID: 35383257

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Project description:BackgroundPlasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life.Methods and findingsTo identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI -15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI -0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI -15.9% to +25.0%], P. falciparum: +3.2% [CI -3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI -8.7% to +21.1%], P. falciparum: -1.4% [CI -4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity.ConclusionsPET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.

Project description:BackgroundThe hybrid imaging positron emission tomography/magnetic resonance (PET/MR) is an important tool in the management of pediatric oncology patients, particularly in malignant musculoskeletal pathologies, because it combines the functional and metabolic information of tumor provided by PET with the high soft-tissue contrast and the functional information offered by magnetic resonance imaging (MRI).MethodsWe performed an observational retrospective study that included pediatric patients diagnosed with primary bone or soft-tissue sarcomas in the Pediatric Hematology and Oncology Unit at the HM Montepríncipe University Hospital, Boadilla del Monte, Madrid (Spain) who underwent whole-body 18F-fluorodeoxyglucose (18F-FDG) PET/MRI as a staging study and for follow-up evaluation for treatment response from September 2017 to January 2023. This study explores the protocols, the practical application of the PET/MRI technique and our clinical experience at our center in the diagnosis and follow-up of primary bone tumors and soft-tissue sarcomas in children.ResultsSeventy-one 18F-PET/MR studies were performed on 39 patients. Most of them (55%) were initial extension studies and (45%) were follow-up studies. Most of the patients studied were male (74.4%) with a median age of 15 years. Of the 39 cases, 51% were primary bone tumors while 18% were Langerhans cell histiocytosis and 21% soft tissue tumors. Of the 71 studies, five showed metastases at the initial diagnosis, three presented lymph node involvement, one with local infiltration, and one with pulmonary metastasis.ConclusionsPET/MR has represented a significant advancement in the evaluation of pediatric malignant neoplasms, with specific applications in musculoskeletal tumors showing clear benefits over PET/CT. The primary advantage is the reduction in ionizing radiation doses and the assessment of soft tissues, making it an excellent option for malignant musculoskeletal pathologies in pediatric patients who often require long-term follow-up. It is particularly useful for early tumor detection and functional therapy monitoring in oncology. The development of new protocols is making studies increasingly faster and better tolerated, even without the need for anesthesia. PET/MRI has shown to increase diagnostic accuracy in primary bone and soft tissue tumors, as it allows for the comprehensive evaluation of their morpho-metabolic characteristics, locoregional, and distant involvement in a single study. It is also useful in surgical planning and post-treatment follow-up.

Project description:ImportanceMyocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the development of fibrosis.ObjectivesTo characterize the burden and distribution of fluorine 18-labeled (18F) fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) in patients with degenerative MVP and ventricular ectopy.Design, setting, and participantsProspective observational study of 20 patients with MVP and significant primary degenerative MR who were referred for mitral valve repair and underwent hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Ventricular arrhythmias were categorized as either complex (n = 12) or minor (n = 8). Coregistered hybrid 18F FDG-PET and MRI LGE images were assessed and categorized. Recruitment occurred in the new patient clinic of a mitral valve repair reference center. This study was conducted from January 11, 2018, to June 26, 2019.ExposuresSimultaneous cardiac 18F FDG-PET and MRI with LGE imaging on a hybrid PET/MRI system and ambulatory rhythm monitoring.Main outcomes and measuresPatients were categorized by the presence and pattern of FDG uptake and LGE, the severity of ventricular arrhythmias, and the indication for mitral valve surgery.ResultsIn the cohort of 20 patients, the median age was 59.5 years (interquartile range, 52.5-63.2 years). Focal, or focal-on-diffuse uptake, of 18F-FDG (PET positive) was detected in 17 of 20 patients (85%). The FDG uptake coexisted with areas of LGE (PET/MRI positive) in 14 patients (70%). Of the 5 asymptomatic patients with normal ventricular indices and absence of any surgical indications, all were PET/MRI positive.Conclusions and relevanceIn this pilot study, we demonstrate a novel association between degenerative MVP and FDG uptake, a surrogate for myocardial inflammation and/or ischemia. Such evidence of myocardial injury, even in asymptomatic patients, suggests an ongoing subclinical disease process. These findings warrant further investigation into whether imaging for myocardial inflammation, ischemia, and scar has a role in arrhythmic risk stratification and whether it provides incremental prognostic value in patients with chronic severe mitral regurgitation undergoing active surveillance.

Dataset Information

Positron emission tomography and magnetic resonance imaging of the brain in experimental human malaria, a prospective cohort study.

Publications

Positron emission tomography and magnetic resonance imaging of the brain in experimental human malaria, a prospective cohort study.

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