Non-invasive quantification of cerebral glucose metabolism using Gjedde-Patlak plot and image-derived input function from the aorta.

INTRODUCTION: We aimed at evaluating a Gjedde-Patlak plot and non-invasive image-derived input functions (IDIF) from the aorta to quantify cerebral glucose metabolic rate (CMRglc) in comparison to the reference standard based on sampling the arterial input function (AIF). METHOD: Six healthy subjects received 200 MBq [18F]FDG simultaneously with the initiation of a three-part dynamic PET recording consisting of a 15 min-recording of the aorta, a 40 min-recording of the brain and finally 2 min-recording of the aorta. Simultaneously, the arterial 18F concentration was measured via arterial cannulation. Regions of interest were drawn in the aorta and the brain and time-activity curves extracted. The IDIF was obtained by fitting a triple exponential function to the aorta time-activity curve after the initial peak including the late aorta frame, thereby interpolating the arterial blood activity concentration during the brain scan. CMRglc was calculated from Gjedde-Patlak plots using AIF and IDIF, respectively and the predictive value was examined. Results from frontal cortex, insula, hippocampus and cerebellum were compared by paired t-test and agreement between the methods was analyzed by Bland-Altman plot statistics. RESULTS: There was a strong linear relationship and an excellent agreement between the methods (mean±SD of CMRglcIDIF (µmol 100 g-1 min-1), mean difference, mean relative difference, 95% limits of agreement): frontal cortex: 30.8 ± 3.3, 0.5, 2.2%, [-1,6:2.5], insula: 25.4 ± 2.2, 0.4, 2.4%, [-1.4:2.2], hippocampus: 16.9 ± 1.2, 0.4, 3.8%, [-1.1:2.0] and cerebellum: 23.4 ± 1.9, 0.5, 3.1%, [-1.4:2.5]). CONCLUSION: We found excellent agreement between CMRglc obtained with an IDIF from the aorta and the reference standard with AIF. A non-invasive three-part dynamic [18F]FDG PET recording is feasible as a non-invasive alternative for reliable quantification of cerebral glucose metabolism in all scanner systems. This is useful in patients with presumed global cerebral changes owing to systemic disease or for the monitoring of treatment effects.

Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database.

PURPOSE: Multi-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example. METHODS: A framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device. RESULTS: A total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images. CONCLUSION: A framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database.

PURPOSE: A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved. METHODS: (123)I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the "Southampton" methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV). RESULTS: The relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69-89%, ACSC range 87-116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001). CONCLUSION: A satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.

Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy: A Randomized Controlled Trial (SUPER).

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.

An active learning approach to the physics of medical imaging.

This paper describes an experimentally oriented medical imaging course where the students record, process and analyse 3D data of an unknown piece of formalin fixed porcine tissue hidden in agar in order to estimate the tissue types present in a selected 2D slice. The recorded planar X-ray, CT, MRI, ultrasound and SPECT images show the tissue in very different ways. The students can only estimate the tissue type by studying the physical principles of the imaging modalities. The true answer is later revealed by anatomical photographs obtained from physical slicing. The paper describes the phantoms and methods used in the course. Sample images recorded with the different imaging modalities are provided. Challenges faced by the students are outlined. Results of the course show high increase in competencies as judged from graded reports, low course drop-out rate, high pass-rate at the exam, high student participation and large student satisfaction.

Curriculum for education and training of medical physicists in nuclear medicine: recommendations from the EANM Physics Committee, the EANM Dosimetry Committee and EFOMP.

PURPOSE: To provide a guideline curriculum covering theoretical and practical aspects of education and training for Medical Physicists in Nuclear Medicine within Europe. MATERIAL AND METHODS: National training programmes of Medical Physics, Radiation Physics and Nuclear Medicine physics from a range of European countries and from North America were reviewed and elements of best practice identified. An independent panel of experts was used to achieve consensus regarding the content of the curriculum. RESULTS: Guidelines have been developed for the specialist theoretical knowledge and practical experience required to practice as a Medical Physicist in Nuclear Medicine in Europe. It is assumed that the precondition for the beginning of the training is a good initial degree in Medical Physics at master level (or equivalent). The Learning Outcomes are categorised using the Knowledge, Skill and Competence approach along the lines recommended by the European Qualifications Framework. The minimum level expected in each topic in the theoretical knowledge and practical experience sections is intended to bring trainees up to the requirements expected of a Medical Physicist entering the field of Nuclear Medicine. CONCLUSIONS: This new joint EANM/EFOMP European guideline curriculum is a further step to harmonise specialist training of Medical Physicists in Nuclear Medicine within Europe. It provides a common framework for national Medical Physics societies to develop or benchmark their own curricula. The responsibility for the implementation and accreditation of these standards and guidelines resides within national training and regulatory bodies.

A positron emission tomography study of wind-up pain in chronic postherniotomy pain.

Many neuropathic pain conditions are characterized by abnormal responses to noxious or innocuous mechanical stimulation, including wind-up pain. Whereas previous brain imaging studies have explored the cerebral correlates of hyperalgesia and allodynia, no studies are available on mechanical-induced wind-up pain in neuropathic pain patients. We therefore used positron emission tomography (PET) to investigate the cerebral response pattern of mechanical wind-up pain in a homogenous group of 10 neuropathic pain patients with long-standing postherniotomy pain in the groin area. Patients were scanned in the following conditions: (1) rest; (2) wind-up pain, induced by 2 Hz von Frey stimulation in the painful area; (3) non-painful 2 Hz von Frey stimulation in the homologous contralateral area and (4) tonic pressure pain in the homologous contralateral area. A direct comparison between wind-up pain and non-painful von Frey stimulation revealed that the former more strongly activated contralateral secondary somatosensory cortex, insula, anterior cingulate cortex, right dorsolateral prefrontal cortex, thalamus and cerebellum. In addition, wind-up pain also activated the sublenticular extended amygdala (SLEA) and the brain stem. A direct comparison between wind-up pain and pressure pain revealed that both activated a largely overlapping network. Since no de novo brain areas were activated by wind-up pain, our data suggest that the processes specific to wind-up pain do not occur at the cerebral level.

Dual-modality PET/CT instrumentation-today and tomorrow.

Positron emission tomography (PET) has proven to be a clinically valuable imaging modality, particularly for oncology staging and therapy follow-up. The introduction of combined PET/CT imaging has helped address challenging imaging situations when anatomical information on PET-only was inadequate for accurate lesion localization. After a decade of PET/CT these combined systems have matured technically. Today, whole-body oncology staging is available with PET/CT in 15 min, or less. This review details recent developments in combined PET/CT instrumentation and points to implications for major applications in clinical oncology.

Association between regional cerebral blood flow during hypoglycemia and genetic and phenotypic traits of the renin-angiotensin system.

The risk of severe hypoglycemia in patients with type I diabetes and high basal activity in the renin-angiotensin system (RAS) is significantly higher than in patients with low basal RAS activity. In healthy men, we tested the hypothesis that differences in spontaneous RAS activity are associated with differences in cerebral activity responses during mild hypoglycemia. A total of 10 healthy men with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O-PET (H(2)(15)O-positron emission tomography) study was conducted with a series of six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after hypoglycemia. The mean plasma glucose concentration was similar in both the groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.: 0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral activity in the frontal area and a higher cerebral activity in the entorhinal area that expanded to include the parahippocampal gyrus after hypoglycemia. Our findings suggest that the high RAS group to a lesser extent than the low RAS group activates areas involving executive function that may explain the correlation between high basal RAS activity and risk of severe hypoglycemia in type I diabetes.