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1.
Pediatr Infect Dis J ; 41(8): 663-665, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1948550

ABSTRACT

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.


Subject(s)
COVID-19 , Brain , COVID-19/complications , COVID-19/diagnostic imaging , Child , Fluorodeoxyglucose F18 , Frontal Lobe/diagnostic imaging , Humans , Positron-Emission Tomography/methods
2.
Eur J Nucl Med Mol Imaging ; 49(8): 2994-3004, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1844354

ABSTRACT

INTRODUCTION: Distinct physiological states arise from complex interactions among the various organs present in the human body. PET is a non-invasive modality with numerous successful applications in oncology, neurology, and cardiology. However, while PET imaging has been applied extensively in detecting focal lesions or diseases, its potential in detecting systemic abnormalities is seldom explored, mostly because total-body imaging was not possible until recently. METHODS: In this context, the present study proposes a framework capable of constructing an individual metabolic abnormality network using a subject's whole-body 18F-FDG SUV image and a normal control database. The developed framework was evaluated in the patients with lung cancer, the one discharged after suffering from Covid-19 disease, and the one that had gastrointestinal bleeding with the underlying cause unknown. RESULTS: The framework could successfully capture the deviation of these patients from healthy subjects at the level of both system and organ. The strength of the altered network edges revealed the abnormal metabolic connection between organs. The overall deviation of the network nodes was observed to be highly correlated to the organ SUV measures. Therefore, the molecular connectivity of glucose metabolism was characterized at a single subject level. CONCLUSION: The proposed framework represents a significant step toward the use of PET imaging for identifying metabolic dysfunction from a systemic perspective. A better understanding of the underlying biological mechanisms and the physiological interpretation of the interregional connections identified in the present study warrant further research.


Subject(s)
COVID-19 , Lung Neoplasms , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/pathology , Positron-Emission Tomography/methods , Whole Body Imaging
3.
Nat Commun ; 13(1): 1926, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1839522

ABSTRACT

Invasive aspergillosis is a critical complication in immunocompromised patients with hematologic malignancies or with viral pneumonia caused by influenza virus or SARS­CoV­2. Although early and accurate diagnosis of invasive aspergillosis can maximize clinical outcomes, current diagnostic methods are time-consuming and poorly sensitive. Here, we assess the ability of 2-deoxy-2-18F-fluorosorbitol (18F-FDS) positron emission tomography (PET) to specifically and noninvasively detect Aspergillus infections. We show that 18F-FDS PET can be used to visualize Aspergillus fumigatus infection of the lungs, brain, and muscles in mouse models. In particular, 18F-FDS can distinguish pulmonary aspergillosis from Staphylococcus aureus infection, both of which induce pulmonary infiltrates in immunocompromised patients. Thus, our results indicate that the combination of 18F-FDS PET and appropriate clinical information may be useful in the differential diagnosis and localization of invasive aspergillosis.


Subject(s)
Aspergillosis , COVID-19 , Invasive Fungal Infections , Animals , Aspergillosis/diagnostic imaging , Aspergillus fumigatus , Humans , Lung/diagnostic imaging , Mice , Positron-Emission Tomography/methods , SARS-CoV-2
4.
Eur J Nucl Med Mol Imaging ; 49(9): 3197-3202, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1756789

ABSTRACT

BACKGROUND: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of 18F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum. METHODS: From the beginning of August 2021 to the end of October 2021, the brain 18F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain 18F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern. RESULTS: On the 143 brain 18F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles. CONCLUSION: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.


Subject(s)
COVID-19 , Fluorodeoxyglucose F18 , Brain/diagnostic imaging , Brain/metabolism , COVID-19/complications , COVID-19/diagnostic imaging , Female , Fluorodeoxyglucose F18/metabolism , Humans , Middle Aged , Positron-Emission Tomography/methods , Radiopharmaceuticals/metabolism , Retrospective Studies , SARS-CoV-2
5.
PET Clin ; 17(2): 213-222, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1719570

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) imaging is nearly synonymous with positron emission tomography (PET) scans. Many of the nearly 60,000 newly diagnosed patients with HNSCC in the US-and 900,000 worldwide-will undergo a PET scan, if not multiple, throughout the course of their care. In this review, we describe the clinical utility of PET scans in HNSCC, emphasizing whereby their input is most impactful in improving patient outcomes as well as scenarios whereby PET/CT scans should be avoided. We also describe important considerations for capturing and processing PET scans with a special focus on the important role of tumor volume segmentation, scan timing relative to therapy, and concurrent conditions (eg, COVID-19). In addition, we will illustrate the latest innovations in the management of HNSCC. This article also will delve to exhibit novel potential biomarkers in the management of HNSCC. Finally, we describe future directions for PET imaging, including the advent of novel PET radiotracers as an alternative to 18F-fluorodeoxyglucose (18F-FDG).


Subject(s)
COVID-19 , Carcinoma, Squamous Cell , Head and Neck Neoplasms , COVID-19/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , Humans , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging
6.
Nucl Med Biol ; 106-107: 62-71, 2022.
Article in English | MEDLINE | ID: covidwho-1641554

ABSTRACT

INTRODUCTION: Neutrophils are part of the innate immune system and function as a first line of defense against invading microorganisms. Overactivity of the immune system may result in a devastating immuno-inflammation with extensive damage to tissue leading to organ damage and/or failure. The literature suggests several human diseases in which neutrophil elastase (NE) is postulated to be important in the pathophysiology including inflammatory bowel disease (IBD), chronic obstructive pulmonary disorder (COPD), abdominal aortic aneurysms (AAA), breast and lung cancer, and recently also in Sars-cov-2 virus infection (Covid-19). In particular, the lungs are affected by the destructive power of the protease neutrophil elastase (NE). In this paper, we report the pre-clinical development of a selective and specific positron emission tomography (PET) tracer, [11C]GW457427, as an in vivo biomarker for the study of NE, now available for human studies. METHODS: [11C]GW457427 was produced by methylation of GW447631 using [11C]methyl triflate and GMP validated production and quality control methods were developed. Chemical purity was high with no traces of the precursor GW611437 or other uv-absorbing compounds. A method for the determination of intact [11C]GW457427 in plasma was developed and the binding characteristics were evaluated in vitro and in vivo. An animal model for lung inflammation was used to investigate the specificity and sensitivity of the [11C]GW457427 tracer for neutrophil elastase (NE) in pulmonary inflammation, verified by blockade using two structurally different elastase inhibitors. RESULTS: [11C]GW457427 was obtained in approximately 45% radiochemical yield and with a radiochemical purity higher than 98%. Molar activity was in the range 130-360 GBq/µmol. Binding to NE was shown to be highly specific both in vitro and in vivo and a significantly higher uptake of tracer was found in a lipopolysaccharide mouse model of pulmonary inflammation compared with control animals. The uptake in lung tissue measured as standardized uptake value (SUV) strongly correlated with tissue NE content as measured by ELISA. In vitro studies also showed specific tracer binding in aortic tissue of patients with abdominal aorta aneurysm (AAA). The rate of metabolism in rats was appropriate considering the critical balance between available tracer for binding and requirement for blood clearance with about 40% and 20% intact [11C]GW457427 in plasma at 5 and 40 min, respectively. Radioactivity was cleared from blood and organs in control animals with mainly hepatobiliary excretion with distribution in the intestines and the urinary bladder; but without retention of the tracer in healthy organs of interests such as the lung, liver, kidneys or in the cardiovascular system. A dosimetry study in rat indicated that the whole-body effective dose was 2.2 µSv/MBq with bone marrow as the limiting organ. It is estimated that up to five PET-CT investigations could be performed in humans without exceeding a total dose of 10 mSv. CONCLUSION: [11C]GW457427 is a promising in vivo PET-biomarker for NE with high specific binding demonstrated both in vitro and in vivo. A GMP validated production method including quality control has been developed and a microdosing toxicity study performed with no adverse signs. [11C]GW457427 is currently being evaluated in a First-In-Man PET study.


Subject(s)
COVID-19 , Positron Emission Tomography Computed Tomography , Animals , Humans , Leukocyte Elastase , Mice , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography/methods , Rats , SARS-CoV-2
8.
Int J Mol Sci ; 22(16)2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1367845

ABSTRACT

The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αß3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. In this review article, we have discussed and evaluated the role of peptides in imaging and non-imaging diagnostics. The most popular non-imaging and imaging diagnostic platforms are discussed, categorized, and ranked, as per their scientific contribution on PUBMED. Moreover, the applicability of peptide-based diagnostics in deadly diseases, mainly COVID-19 and cancer, is also discussed in detail.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Peptides/analysis , COVID-19/virology , Databases, Factual , Enzyme-Linked Immunosorbent Assay/methods , Humans , Positron-Emission Tomography/methods , Receptors, Somatostatin , SARS-CoV-2/isolation & purification , Tandem Mass Spectrometry/methods , Tomography, Emission-Computed, Single-Photon/methods
9.
Brain ; 144(4): 1263-1276, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1313840

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/metabolism , Glucose/metabolism , Mental Status and Dementia Tests , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/psychology , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
11.
Brain ; 144(4): 1263-1276, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1169654

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/metabolism , Glucose/metabolism , Mental Status and Dementia Tests , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/psychology , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
12.
PET Clin ; 16(1): 89-97, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-938149

ABSTRACT

Total-body PET enables high-sensitivity imaging with dramatically improved signal-to-noise ratio. These enhanced performance characteristics allow for decreased PET scanning times acquiring data "total-body wide" and can be leveraged to decrease the amount of radiotracer required, thereby permitting more frequent imaging or longer imaging periods during radiotracer decay. Novel approaches to PET imaging of infectious diseases are emerging, including those that directly visualize pathogens in vivo and characterize concomitant immune responses and inflammation. Efforts to develop these imaging approaches are hampered by challenges of traditional imaging platforms, which may be overcome by novel total-body PET strategies.


Subject(s)
Communicable Diseases/diagnostic imaging , Positron-Emission Tomography/methods , Whole Body Imaging/methods , Humans , Signal-To-Noise Ratio , Time
14.
Neurosci Lett ; 742: 135529, 2021 01 18.
Article in English | MEDLINE | ID: covidwho-971460
15.
Trends Neurosci ; 43(12): 935-938, 2020 12.
Article in English | MEDLINE | ID: covidwho-885448

ABSTRACT

A substantial fraction of coronavirus disease 2019 (COVID-19) patients experience neurological manifestations. Nevertheless, brain changes caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain largely unknown. Here, we provide a brief overview of positron emission tomography (PET) applications that could advance current understanding of CNS pathophysiological alterations associated with SARS-CoV-2 infection.


Subject(s)
Brain/diagnostic imaging , COVID-19/diagnostic imaging , Neuroimaging/methods , Positron-Emission Tomography/methods , Brain/metabolism , Brain/pathology , COVID-19/complications , COVID-19/physiopathology , Humans
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