Poul-Erik Braad

18F-FDG-PET/CT in fever of unknown origin: clinical value

ObjectiveFever of unknown origin continues to be a diagnostic challenge for clinicians. The aim of this study was to confirm whether 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) is a helpful tool in patients suffering from this condition. Patients and methodsFifty-seven patients with fever of unknown origin were examined with 18F-FDG-PET/CT as part of their diagnostic workup at the clinicians’ discretion. The medical records were read retrospectively to establish the final diagnosis and evaluate the degree to which PET/CT contributed to the diagnosis. ResultsThe examination was considered helpful if it corresponded to the final diagnosis by showing uptake in an organ considered responsible for the condition, or if it was without focal findings, thereby excluding the patient from having focal infection or malignancy. It was perceived false positive if it pointed towards an organ not regarded by the clinicians as being related to the final diagnosis. It was perceived not helpful if the cause of fever was not visible on 18F-FDG-PET/CT.We found 18F-FDG-PET/CT helpful in 75% of patients, not helpful in 4%, and false positive in 21% of patients. Conclusion18F-FDG-PET/CT is a useful tool in the investigation of fever of unknown origin; it can reduce patient inconvenience and possibly costs to society if used earlier in the diagnostic process.

Renal cortical and medullary blood flow responses to altered NO availability in humans

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor N(ω)-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P < 0.05) and decreased after L-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P < 0.05). Cortical blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P < 0.05]. PET/CT scanning allows identification of a renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.

Quantitative myocardial perfusion by O-15-water PET: individualized vs. standardized vascular territories

AIMS Reporting of quantitative myocardial blood flow (MBF) is typically performed in standard coronary territories. However, coronary anatomy and myocardial vascular territories vary among individuals, and a coronary artery may erroneously be deemed stenosed or not if territorial demarcation is incorrect. So far, the diagnostic consequences of calculating individually vs. standardly assessed MBF values have not been reported. We examined whether individual reassignment of vascular territories would improve the diagnostic accuracy of MBF with regard to the detection of significant coronary artery disease (CAD). METHODS AND RESULTS Forty-four patients with suspected CAD were included prospectively and underwent coronary CT-angiography and quantitative MBF assessment with O-15-water PET followed by invasive, quantitative coronary angiography, which served as reference. MBF was calculated in the vascular territories during adenosine stress according to a standardized 17-segment American Heart Association model and an individualized model, using CT-angiography to adjust the coronary territories to their feeding vessels. Individually defined territories deviated from standard territories in 52% of patients. However, MBF in the three coronary territories defined by standard and individualized models did not differ significantly, except in one patient, in whom the MBF of an individualized coronary territory deviated sufficiently as to change the test from a false positive to a true negative result in this particular territory. CONCLUSION Disparity between standardized and individualized vascular territories was present in half of the patients, but had little clinical impact. Still, caution should be taken not always to rely on standard territories, as this may at times cause misinterpretation.

PET imaging with the non-pure positron emitters: 55Co, 86Y and 124I

PET/CT with non-pure positron emitters is a highly valuable tool in immuno-PET and for pretherapeutic dosimetry. However, imaging is complicated by prompt gamma coincidences (PGCs) that add an undesired background activity to the images. Time-of-flight (TOF) reconstruction improves lesion detectability in (18)F-PET and can potentially also improve the signal-to-noise ratio in images acquired with non-pure positron emitters. Using the GE Discovery 690 PET/CT system, we evaluated the image quality with (55)Co, (86)Y and (124)I, and the effect of PGC-correction and TOF-reconstruction on image quality and quantitation in a series of phantom studies. PET image quality and quantitation for all isotopes were significantly affected by PGCs. The effect was most severe with (86)Y, and less, but comparable, with (55)Co and (124)I. PGC-correction improved the image quality and the quantitation accuracy dramatically for all isotopes, especially when the activity was limited to a few hot lesions in a warm background. In imaging situations, where high levels of activity were present in the background, activity concentrations were overestimated. TOF-reconstruction improved image quality in isolated lesions but worsened the accuracy of quantitation and uniformity in homogeneous activity distributions. Better modelling of PGCs in the scatter correction can potentially improve the situation.

Renal cortical and medullary blood flow during modest saline loading in humans.

Renal medullary blood flow (RMBF) is considered an important element of sodium homeostasis, but the experimental evidence is incongruent. Studies in anaesthetized animals generally support the concept in contrast to measurements in conscious animals. We hypothesized that saline‐induced natriuresis is associated with changes in RMBF in humans.

Seeing the Unseen—Bioturbation in 4D: Tracing Bioirrigation in Marine Sediment Using Positron Emission Tomography and Computed Tomography

Understanding spatial and temporal patterns of bioirrigation induced by benthic fauna ventilation is critical given its significance on benthic nutrient exchange and biogeochemistry in coastal ecosystems. The quantification of this process challenges marine scientists because faunal activities and behaviors are concealed in an opaque sediment matrix. Here, we use a hybrid medical imaging technique, positron emission tomography and computed tomography (PET/CT) to provide a qualitative visual and fully quantitative description of bioirrigation in 4D (space and time). As a study case, we present images of porewater advection induced by the well-studied lugworm (Arenicola marina). Our results show that PET/CT allows more comprehensive studies on ventilation and bioirrigation than possible using techniques traditionally applied in marine ecology. We provide a dynamic three-dimensional description of bioirrigation by the lugworm at very high temporal and spatial resolution. Results obtained with the PET/CT are in agreement with literature data on lugworm ventilation and bioirrigation. Major advantages of PET/CT over methods commonly used are its non-invasive and non-destructive approach and its capacity to provide information that otherwise would require multiple methods. Furthermore, PET/CT scan is versatile as it can be used for a variety of benthic macrofauna species and sediment types and it provides information on burrow morphology or animal behavior. The lack of accessibility to the expensive equipment is its major drawback which can only be overcome through collaboration among several institutions.

Impact of high (131)I-activities on quantitative (124)I-PET.

Peri-therapeutic (124)I-PET/CT is of interest as guidance for radioiodine therapy. Unfortunately, image quality is complicated by dead time effects and increased random coincidence rates from high (131)I-activities. A series of phantom experiments with clinically relevant (124)I/(131)I-activities were performed on a clinical PET/CT-system. Noise equivalent count rate (NECR) curves and quantitation accuracy were determined from repeated scans performed over several weeks on a decaying NEMA NU-2 1994 cylinder phantom initially filled with 25 MBq (124)I and 1250 MBq (131)I. Six spherical inserts with diameters 10-37 mm were filled with (124)I (0.45 MBq ml(-1)) and (131)I (22 MBq ml(-1)) and placed inside the background of the NEMA/IEC torso phantom. Contrast recovery, background variability and the accuracy of scatter and attenuation corrections were assessed at sphere-to-background activity ratios of 20, 10 and 5. Results were compared to pure (124)I-acquisitions. The quality of (124)I-PET images in the presence of high (131)I-activities was good and image quantification unaffected except at very high count rates. Quantitation accuracy and contrast recovery were uninfluenced at (131)I-activities below 1000 MBq, whereas image noise was slightly increased. The NECR peaked at 550 MBq of (131)I, where it was 2.8 times lower than without (131)I in the phantom. Quantitative peri-therapeutic (124)I-PET is feasible.

111 Indium-transferrin for localization and quantification of gastrointestinal protein loss

Objective. To evaluate the indium-111 (111In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an 111In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of 111In during the course of 5 days. Two of the patients went through a subsequent chromium-51–trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean±SEM whole-body loss of 111In of 10.9±2.9% for 96 h, while the healthy controls lost 1.8±1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0±1.0 h in patients and 12.1±1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the 51Cr trichloride test, the loss of radio-labelled protein appeared to be in the same order of magnitude. Conclusions. Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the 111In-transferrin method comparable with the former standard using 51CrCl3–trichloride. Plasma measurements of 111In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality.

15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89–97%) versus 76% (64–88%), p = 0.0004; positive predictive value 71% (55–86%) versus 51% (37–65%), p = 0.0001; accuracy 90% (84–95%) versus 77% (69–84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.

Large bed overlap and short acquisition time or vice versa

European Journal of Nuclear Medicine and Molecular Imaging Volume 44, Supplement 2 10.1007/s00259-017-3822-1 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources DOI 10.1007/s00259-017-3822-1 S119 Eur J Nucl Med Mol Imaging (2017) 44 (Suppl 2):S119–S956