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OBJECTIVES: Significant variability exists in the contrast phases applied during computed tomography (CT) studies when assessing morphometric measurements of muscle area (CT-assessed sarcopenia) and density (CT-assessed myosteatosis) and visceral adipose tissue area (CT-assessed visceral obesity). This study explored the impact of contrast phase timing on changes in morphometric measurements of body composition. METHODS: This single-center retrospective cohort study included 459 patients undergoing a multiphase CT scan. Morphometric measurements were obtained at the third lumbar vertebra level. Patients were classified as sarcopenic, myosteatotic, or visceral obese using predefined cutoff values. The intraclass correlation coefficient was used to assess correlations across different enhancement phases, and Cohen's κ measured the inter-enhancement agreement for sarcopenia, myosteatosis, and visceral obesity. RESULTS: Significant differences were observed in mean visceral adipose tissue area, muscle density, and muscle area (P < 0.001). The intraclass correlation coefficient between unenhanced and arterial phases was 0.987 (95% confidence interval [CI], 0.759-0.996) for adipose tissue, 0.995 (95% CI, 0.989-0.997) for muscle area, and 0.850 (95% CI, 0.000-0.956) for muscle density. However, when morphometric measurements were categorized using predefined cutoffs, the κ agreement was considerably lower, particularly for CT-assessed myosteatosis, ranging from 0.635 (unenhanced to arterial) to 0.331 (unenhanced to late venous phase). CONCLUSIONS: Different CT contrast phases induce small but clinically significant alterations in the measurements of muscle area and density and visceral fat. Such minor changes can result in misclassification issues when fixed cutoff values are used to diagnose myosteatosis with CT. This underscores the importance of reporting absolute values and the specific contrast phase used in future studies.
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PURPOSE: To determine how much timesaving and reduction of interruptions reading room assistants can provide by taking over non-image interpretation tasks (NITs) from radiology residents during on-call hours. METHODS: Reading room assistants are medical students who were trained to take over NITs from radiology residents (e.g. answering telephone calls, administrative tasks and logistics) to reduce residents' workload during on-call hours. Reading room assistants' and residents' activities were tracked during 6 weekend dayshifts in a tertiary care academic center (with more than 2.5 million inhabitants in its catchment area) between 10 a.m. and 5p.m. (7-hour shift, 420 min), and time spent on each activity was recorded. RESULTS: Reading room assistants spent the most time on the following timesaving activities for residents: answering incoming (41 min, 19%) and outgoing telephone calls (35 min, 16%), ultrasound machine related activities (19 min, 9%) and paramedical assistance such as supporting residents during ultrasound guided procedures and with patients (17 min, 8%). Reading room assistants saved 132 min of residents' time by taking over NITs while also spending circa 31 min consulting the resident, resulting in a net timesaving of 101 min (24%) during a 7-hour shift. The reading room assistants also prevented residents from being interrupted, at a mean of 18 times during the 7-hour shift. CONCLUSION: This study shows that the implementation of reading room assistants to radiology on-call hours could provide a timesaving for residents and also reduce the number of times residents are being interrupted during their work.
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Internato e Residência , Radiologia , Humanos , Carga de Trabalho , Radiologia/educação , Radiografia , TempoRESUMO
Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aimed to assess the use of the internal carotids for quantifying brain glucose metabolism before and after partial-volume correction. Methods: Dynamic [18F]FDG images were acquired on a 106-cm-long PET scanner, and quantification was performed with a 2-tissue-compartment model and Patlak analysis using an IDIF extracted from the internal carotids. An IDIF extracted from the ascending aorta was used as ground truth. Results: The internal carotid IDIF underestimated the area under the curve by 37% compared with the ascending aorta IDIF, leading to Ki values approximately 17% higher. After partial-volume correction, the mean relative Ki differences calculated with the ascending aorta and internal carotid IDIFs dropped to 7.5% and 0.05%, when using a 2-tissue-compartment model and Patlak analysis, respectively. However, microparameters (K 1, k 2, k 3) derived from the corrected internal carotid curve differed significantly from those obtained using the ascending aorta. Conclusion: These results suggest that partial-volume-corrected internal carotids may be used to estimate Ki but not kinetic microparameters. Further validation in a larger patient cohort with more variable kinetics is needed for more definitive conclusions.
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Artéria Carótida Interna , Tomografia por Emissão de Pósitrons , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/metabolismo , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Artérias Carótidas/diagnóstico por imagemRESUMO
Adenosine A2A-receptors (A2AR) and dopamine D2-receptors (D2R) are known to work together in a synergistic manner. Inhibiting A2ARs by genetic or pharmacological means can relief symptoms and have neuroprotective effects in certain conditions. We applied PET imaging to evaluate the impact of the A2AR antagonist KW6002 on D2R availability and neuroinflammation in an animal model of Parkinson's disease. Male Wistar rats with 6-hydroxydopamine-induced damage to the right striatum were given 3 mg/kg of KW6002 daily for 20 days. Motor function was assessed using the rotarod and cylinder tests, and neuroinflammation and dopamine receptor availability were measured using PET scans with the tracers [11C]PBR28 and [11C]raclopride, respectively. On day 7 and 22 following 6-OHDA injection, rats were sacrificed for postmortem analysis. PET scans revealed a peak in neuroinflammation on day 7. Chronic treatment with KW6002 significantly reduced [11C]PBR28 uptake in the ipsilateral striatum [normalized to contralateral striatum] and [11C]raclopride binding in both striata when compared to the vehicle group. These imaging findings were accompanied by an improvement in motor function. Postmortem analysis showed an 84% decrease in the number of Iba-1+ cells in the ipsilateral striatum [normalized to contralateral striatum] of KW6002-treated rats compared to vehicle rats on day 22 (p = 0.007), corroborating the PET findings. Analysis of tyrosine hydroxylase levels showed less dopaminergic neuron loss in the ipsilateral striatum of KW6002-treated rats compared to controls on day 7. These findings suggest that KW6002 reduces inflammation and dopaminergic neuron loss, leading to less motor symptoms in this animal model of Parkinson's disease.
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Doença de Parkinson , Purinas , Ratos , Masculino , Animais , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Dopamina , Receptor A2A de Adenosina/metabolismo , Doenças Neuroinflamatórias , Adenosina/metabolismo , Racloprida , Ratos Wistar , Oxidopamina/toxicidadeRESUMO
PURPOSE: Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[18F]-fluoro-17ß-estradiol ([18F]FES) positron emission tomography (PET). PROCEDURES: Seven postmenopausal women underwent a dynamic [18F]FES PET scan with arterial blood sampling. A T1-weighted MRI was acquired for anatomical information. After one week, four subjects received a selective ER degrader (SERD), four hours before the PET scan. Pharmacokinetic analysis was performed using a metabolite-corrected plasma curve as the input function. The optimal kinetic model was selected based on the Akaike information criterion and standard error of estimated parameters. Accuracy of Logan graphical analysis and standardized uptake value (SUV) was determined via correlational analyses. RESULTS: The reversible two-tissue compartment model (2T4k) model with fixed K1/k2 was preferred. The total volume of distribution (VT) could be more reliably estimated than the binding potential (BPND). A high correlation of VT with Logan graphical analysis was observed, but only a moderate correlation with SUV. SERD administration resulted in a reduced VT in the pituitary gland, but not in other regions. CONCLUSIONS: The optimal quantification method for [18F]FES was the 2T4k with fixed K1/k2 or Logan graphical analysis, but specific binding was only observed in the pituitary gland.
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Encéfalo , Tomografia por Emissão de Pósitrons , Humanos , Feminino , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/metabolismo , Estradiol , Receptores de Estrogênio/metabolismo , Hipófise/metabolismoRESUMO
Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing. Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox. Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group. Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.
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Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([18F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn, Shank3, Igf1r, Cck, Apba2, Foxp2); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869, Itga11, Arhgap5, Cd47, Dlg1, Gas6, Cml5, Mef2c). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development.
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Desoxicitidina/análogos & derivados , Compostos Orgânicos de Estanho , Tionucleosídeos , Gravidez , Feminino , Ratos , Masculino , Animais , Compostos Orgânicos de Estanho/toxicidade , Encéfalo , Proteínas de Transporte , Proteínas do Tecido Nervoso , CaderinasRESUMO
PURPOSE: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [11C]methionine PET/CT, [11C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan. METHODS: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT. RESULTS: A total of 32 patients were included in the study. With blinded evaluation, [11C]choline PET/CT was positive in 28 patients (88%), [11C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively). CONCLUSION: In the setting of pHPT with negative first-line imaging, [11C]choline PET/CT is superior to [11C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.
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Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Humanos , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Metionina , Colina , Estudos de Coortes , Estudos Prospectivos , Glândulas Paratireoides , Tecnécio Tc 99m Sestamibi , RacemetioninaRESUMO
This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure.
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Artéria Hepática , Transplante de Fígado , Trombose , Criança , Humanos , Hepatopatias , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Trombose/etiologiaAssuntos
Inteligência Artificial , Medicina Nuclear , Humanos , Informática , Cintilografia , CogniçãoRESUMO
BACKGROUND: The use of computed tomography (CT) for attenuation correction (AC) in whole-body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose. PURPOSE: The purpose of this study was to investigate the ultra-low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC-CT and how it affects PET image quality. METHODS: The study evaluated a range of ultra-low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDIVol reported by the scanner. Several voxel-based and volumes of interest (VOI)-based comparisons were performed to compare the ultra-low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra-low dose CT settings. RESULTS: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU-60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel-based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%. CONCLUSIONS: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Tomógrafos Computadorizados , Tomografia por Emissão de Pósitrons/métodos , Imagens de FantasmasRESUMO
PURPOSE: To determine the association between workload and diagnostic errors on 18F-FDG-PET/CT. MATERIALS AND METHODS: This study included 103 18F-FDG-PET/CT scans with a diagnostic error that was corrected with an addendum between March 2018 and July 2023. All scans were performed at a tertiary care center. The workload of each nuclear medicine physician or radiologist who authorized the 18F-FDG-PET/CT report was determined on the day the diagnostic error was made and normalized for his or her own average daily production (workloadnormalized). A workloadnormalized of more than 100% indicates that the nuclear medicine physician or radiologist had a relative work overload, while a value of less than 100% indicates a relative work underload on the day the diagnostic error was made. The time of the day the diagnostic error was made was also recorded. Workloadnormalized was compared to 100% using a signed rank sum test, with the hypothesis that it would significantly exceed 100%. A Mann-Kendall test was performed to test the hypothesis that diagnostic errors would increase over the course of the day. RESULTS: Workloadnormalized (median of 121%, interquartile range: 71 to 146%) on the days the diagnostic errors were made was significantly higher than 100% (P = 0.014). There was no significant upward trend in the frequency of diagnostic errors over the course of the day (Mann-Kendall tau = 0.05, P = 0.7294). CONCLUSION: Work overload seems to be associated with diagnostic errors on 18F-FDG-PET/CT. Diagnostic errors were encountered throughout the entire working day, without any upward trend towards the end of the day.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Feminino , Tomografia por Emissão de Pósitrons , Erros de Diagnóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the current job market for medical specialists in radiology and nuclear medicine (NM) in the Netherlands. METHODS: Vacancies posted for radiologists and nuclear medicine physicians in the Netherlands between December 2020 and February 2022 were collected and analyzed. RESULTS: A total of 157 vacancies (146 for radiologist and 11 for nuclear medicine physicians) were included. The most sought-after subspecialties were all-round (22%), abdominal (19%), and interventional radiology (14%), and 30% of vacancies preferred applicants with additional non-clinical skills (research, teaching, management, information and communications technology (ICT)/artificial intelligence (AI)). Non-academic hospitals significantly more frequently requested all-round radiologists (n = 31) than academic hospitals (n = 1) (p = 0.001), while the distribution of other requested subspecialties was not significantly different between non-academic and academic vacancies. Non-academic hospitals also significantly more frequently requested additional research tasks in their vacancies (n = 35) compared to academic hospitals (n = 4) (p = 0.011). There were non-significant trends for non-academic hospitals more frequently requesting teaching tasks in their vacancies (n =18) than academic hospitals (n = 1) (p = 0.051), and for non-academic hospitals more frequently asking for management skills (n = 11) than academic hospitals (n = 0) (p = 0.075). CONCLUSION: All-round, abdominal, and interventional radiologists are most in demand on the job market in the Netherlands. All-round radiologists are particularly sought after by non-academic hospitals, whereas nuclear radiologists who completed the Dutch integrated NM and radiology residency seem to be welcomed by hospitals searching for a nuclear medicine specialist. Finally, non-clinical skills (research, teaching, management, ICT/AI) are commonly requested. These data can be useful for residents and developers of training curricula. CLINICAL RELEVANCE STATEMENT: An overview of the radiology job market and the requested skills is important for residents, for those who seek work as a radiologist, and for those who are involved in the design and revision of residency programs. KEY POINTS: Review of job vacancies over an extended period of time provides valuable information to residents and feedback to potentially improve radiology and nuclear medicine (NM) residency programs. All-round radiologists are wanted in non-academic hospitals and nuclear radiologists (those who have completed an integrated NM-radiology curriculum) are welcomed by hospitals searching for nuclear medicine specialists in the Netherlands. There is a need to train residents in important non-clinical skills, such as research and teaching, but also management and communications technology/artificial intelligence.
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Internato e Residência , Medicina Nuclear , Humanos , Países Baixos , Inteligência Artificial , Recursos Humanos , Radiografia , RadiologistasRESUMO
BACKGROUND: The apolipoprotein E-deficient (apoE-/-) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE-/- rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE-/- rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging. RESULTS: ApoE-/- rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE-/- rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE-/- rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE-/- rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE-/- rats. CONCLUSION: These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE-/- rats. Therefore, this model shows promise for atherosclerosis imaging studies.
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The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.
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MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty (p = 0.021) but did not influence treatment consequences (p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.
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The molecular imaging of biomarkers plays an increasing role in medical diagnostics. In particular, the imaging of enzyme activity is a promising approach, as it enables the use of its inherent catalytic activity for the amplification of an imaging signal. The increased activity of a sulfatase enzyme has been observed in several types of cancers. We describe the development and in vitro evaluation of molecular imaging agents that allow for the detection of sulfatase activity using the whole-body, non-invasive MRI and CEST imaging methods. This approach relies on a responsive ligand that features a sulfate ester moiety, which upon sulfatase-catalyzed hydrolysis undergoes an elimination process that changes the functional group, coordinating with the metal ion. When Gd3+ is used as the metal, the complex can be used for MRI, showing a 25% decrease at 0.23T and a 42% decrease at 4.7T in magnetic relaxivity after enzymatic conversion, thus providing a "switch-off" contrast agent. Conversely, the use of Yb3+ as the metal leads to a "switch-on" effect in the CEST imaging of sulfatase activity. Altogether, the results presented here provide a molecular basis and a proof-of-principle for the magnetic imaging of the activity of a key cancer biomarker.
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BACKGROUND: Early detection of recurrent or progressive HCC remains the strongest prognostic factor for survival. Dual tracer PET/CT imaging with [11C]CH and [18F]FDG can further increase detection rates as both tracers entail different metabolic pathways involved in HCC development. We investigated dual-tracer PET/CT in clinical decision making in patients suspected of recurrent or progressive HCC. All HCC patients who underwent both [11C]CH and [18F]FDG PET/CT in our institute from February 2018 to December 2021 were included. Both tracer PET/CT were within 4 weeks of each other with at least 6-month follow-up. Patients underwent dual tracer PET/CT because of unexplained and suspicious CT/MRI or sudden rise of serum tumour markers. A detected lesion was considered critical when the finding had prognostic consequences leading to treatment changes. RESULTS: Nineteen patients who underwent [11C]CH and [18F]FDG PET/CT were included of which all but six patients were previously treated for HCC. Dual-tracer critical finding detection rate was 95%, with [18F]FDG 68%, and [11C]CH 84%. Intrahepatic HCC recurrence finding rate was 65% for both tracers. [18F]FDG found more ablation site recurrences (4/5) compared to [11C]CH (2/5). Only [11C]CH found two needle tract metastases. Both tracers found 75% of the positive lymph nodes. Two new primary tumours were found, one by [18F]FDG and both by [11C]CH. CONCLUSIONS: Our study favours a dual-tracer approach in HCC staging in high-risk patients or when conventional imaging is non-conclusive.
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INTRODUCTION: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[11C]verapamil PET. (R)-[11C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [18F]MC225 was developed to measure both increases and decreases in P-gp function. AIM: The aim of this study was (1) to identify the pharmacokinetic model that best describes [18F]MC225 kinetics in the human brain and (2) to determine test-retest variability. METHODS: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [18F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility. RESULTS: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model. CONCLUSION: [18F]MC225 VT, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%. TRIAL REGISTRATION: EudraCT 2020-001564-28 . Registered 25 May 2020.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Barreira Hematoencefálica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Tomografia por Emissão de Pósitrons , Verapamil , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.