Andreas Kjær

EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology

The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.

18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Survival of Patients with Neuroendocrine Tumors

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. Experimental Design: Ninety-eight prospectively enrolled patients with NE tumors underwent FDG-PET imaging. FDG uptake was quantified by maximal standardized uptake value (SUVmax). The prognostic value of FDG uptake, proliferation index, chromogranin A, and liver metastases were assessed. Results: During the 1-year follow-up, 14 patients died. The diagnostic sensitivity of FDG-PET was 58% (n = 57) and a positive FDG-PET result was associated with a significantly higher risk of death with a hazard ratio (HR) of 10.3 [95% confidence interval (CI), 1.3-78.9]. Thirteen of the 57 (23%) FDG-PET–positive patients died compared with 1 of 41 (2%) FDG-PET–negative patients. By univariate analysis, a SUVmax of >9 and a high Ki67 index were significant predictors of overall survival with a HR of 8.8 (95% CI, 2.7-28.7) and a HR of 2.6 (95% CI, 1.3-5.1), respectively. In a multivariate analysis including a SUVmax of >3, Ki67, and chromogranin A, SUVmax of >3 was the only predictor of progression-free survival (HR, 8.4; P < 0.001). Conclusions: This study shows a strong prognostic value of FDG-PET for NE tumors, which exceeds the prognostic value of traditional markers such as Ki67, chromogranin A, and liver metastases. FDG-PET may obtain an important role for NE tumors. Clin Cancer Res; 16(3); 978–85

Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper

BackgroundIn animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from 18F-fluorodeoxyglucose (18F-FDG) PET.MethodsSubcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined in vivo by external caliper, microCT and 18F-FDG-PET and subsequently reference volume was determined ex vivo. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation.ResultsTumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements.ConclusionMicroCT was more accurate than both caliper and 18F-FDG-PET for in vivo volumetric measurements of subcutaneous tumors in mice.18F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.

Functional Imaging of Neuroendocrine Tumors: A Head-to-Head Comparison of Somatostatin Receptor Scintigraphy, 123I-MIBG Scintigraphy, and 18F-FDG PET

Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with 111In-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with 123I-metaiodobenzylguanidine (MIBG), and 18F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123I-MIBG scintigraphy, and 18F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, 123I-MIBG scintigraphy, and 18F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18F-FDG PET-positive, of which 3 were also 123I-MIBG scintigraphy–positive, giving a combined overall sensitivity of 96%. SRS also exceeded 123I-MIBG scintigraphy and 18F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123I-MIBG scintigraphy was superior to 18F-FDG PET for ileal neuroendocrine tumors, and 18F-FDG PET was superior to 123I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18F-FDG PET (92%) exceeded that of both SRS (69%) and 123I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123I-MIBG scintigraphy and 18F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.

Serotonin receptors involved in vasopressin and oxytocin secretion

Serotonin (5‐HT), 5‐HT agonists, the 5‐HT precursor 5‐hydroxytryptophan, 5‐HT‐releasers and ‐reuptake inhibitors stimulate the release of vasopressin and oxytocin. We investigated the involvement of 5‐HT receptors in the serotonergic regulation of vasopressin and oxytocin secretion. Vasopressin and oxytocin secretion was stimulated by 5‐HT, the 5‐HT1A+1B+5A+7 agonist 5‐carboxamidotryptamine (5‐CT), the 5‐HT2A+2C agonist DOI, the 5‐HT2C+2A agonist mCPP, the 5‐HT2C agonist MK‐212, the 5‐HT3 agonist SR 57277 and the 5‐HT4 agonist RS 67506. The 5‐HT1A agonist 8‐OH‐DPAT, which had no effect on vasopressin secretion, stimulated oxytocin secretion. The 5‐HT‐induced release of vasopressin and oxytocin was inhibited by central infusion of the 5‐HT antagonists WAY 100635 (5‐HT1A), LY 53857 (5‐HT2A+2C), ICS 205‐930 (5‐HT3+4) and RS 23597 (5‐HT4). The 5‐HT2+6+7 antagonist metergoline in combination with the 5‐HT1A+2+7 antagonist methysergide inhibited the stimulatory effect of 5‐CT on both hormones, whereas the 5‐HT1A+1B antagonist cyanopindolol only inhibited the oxytocin response. The 5‐HT2A antagonist 4‐(4‐flourobenzoyl)‐1‐(4‐phenylbutyl)‐piperidine oxalate had no effect on DOI‐induced hormone response. The 5‐HT2C antagonist Y 25130 partly inhibited the stimulating effect of MK‐212. ICS 205‐930 and RS 23597 inhibited vasopressin and oxytocin secretion induced by RS 67506. WAY 100635 inhibited 8‐OH‐DPAT‐induced oxytocin secretion. We conclude that 5‐HT‐induced vasopressin secretion primarily is mediated via 5‐HT2C, 5‐HT4 and 5‐HT7 receptors, whereas 5‐HT2A, 5‐HT3 and 5‐HT5A receptors seem to be of minor importance. 5‐HT‐induced oxytocin secretion involves 5‐HT1A, 5‐HT2C and 5‐HT4 receptors; in addition an involvement of 5‐HT1B, 5‐HT5A and 5‐HT7 receptors seems likely, whereas 5‐HT2A and 5‐HT3 receptors seem to be less important.

Detection of Pulmonary Embolism with Combined Ventilation–Perfusion SPECT and Low-Dose CT: Head-to-Head Comparison with Multidetector CT Angiography

The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer testing, and imaging with either pulmonary ventilation–perfusion (V/Q) scintigraphy or pulmonary multidetector CT (MDCT) angiography. Both V/Q SPECT and MDCT angiography seem to have high diagnostic accuracy. However, only limited data directly comparing these 2 modalities are available. Hybrid γ-camera/MDCT systems have been introduced and allow simultaneous 3-dimensional lung V/Q SPECT and MDCT angiography, suitable for diagnosing PE. The aim of our study was to compare, in a prospective design, the diagnostic ability of V/Q SPECT, V/Q SPECT combined with low-dose CT, and pulmonary MDCT angiography obtained simultaneously using a combined SPECT/MDCT scanner in patients suspected of having PE. Methods: Consecutive patients from June 2006 to February 2008 suspected of having acute PE were referred to the Department of Nuclear Medicine at Rigshospitalet or Frederiksberg Hospital, Denmark, for V/Q SPECT as a first-line imaging procedure. The number of eligible patients was 196. Patients with positive D-dimer results (>0.5 mmol/mL) or a clinical assessment with a Wells score greater than 2 were included and underwent V/Q SPECT, low-dose CT, and pulmonary MDCT angiography in a single session. Patient follow-up was 6 mo. Results: A total of 81 simultaneous studies were available for analysis, of which 38% were from patients with PE. V/Q SPECT had a sensitivity of 97% and a specificity of 88%. When low-dose CT was added, the sensitivity was still 97% and the specificity increased to 100%. Perfusion SPECT with low-dose CT had a sensitivity of 93% and a specificity of 51%. MDCT angiography alone had a sensitivity of 68% and a specificity of 100%. Conclusion: We conclude that V/Q SPECT in combination with low-dose CT without contrast enhancement has an excellent diagnostic performance and should therefore probably be considered first-line imaging in the work-up of PE in most cases.

Effects of passive heating on central blood volume and ventricular dimensions in humans

Mixed findings regarding the effects of whole‐body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non‐heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium‐99m labelled autologous red blood cells and gamma camera imaging. Whole‐body heating increased internal temperature (> 1.0°C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 ± 2 to 93 ± 4 beats min−1), while reducing central venous pressure (5.5 ± 07 to 0.2 ± 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 ± 2%), heart plus central vasculature (17 ± 2%), thorax (14 ± 2%), inferior vena cava (23 ± 2%) and liver (23 ± 2%) (all P≤ 0.005 relative to time control subjects). Radionuclide multiple‐gated acquisition assessment revealed that heat stress did not significantly change left ventricular end‐diastolic volume, while ventricular end‐systolic volume was reduced by 24 ± 6% of pre‐heat stress levels (P < 0.001 relative to time control subjects). Thus, heat stress increased left ventricular ejection fraction from 60 ± 1% to 68 ± 2% (P= 0.02). We conclude that heat stress shifts blood volume from thoracic and splanchnic regions presumably to aid in heat dissipation, while simultaneously increasing heart rate and ejection fraction.

EANM/ESC guidelines for radionuclide imaging of cardiac function

Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to “prevailing or general consensus”. The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy

The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and 111In-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious/inflammatory or malignant cause of FUO. The sensitivity of granulocyte scintigraphy and FDG-PET were 71% [95% confidence interval (CI): 37–85%] and 50% (CI: 16–84%), respectively. The specificity of granulocyte scintigraphy was 92% (71–100%), which was significantly higher than that of FDG-PET, at 46% (34–62%). Positive and negative predictive values for granulocyte scintigraphy were both 85%. Positive and negative predictive values for FDG-PET were 30% and 67%, respectively. 111In-granulocyte scintigraphy has a superior diagnostic performance compared to FDG-PET for detection of a localised infectious/inflammatory or neoplastic cause of FUO. The poorer performance of FDG-PET is in particular attributable to a high percentage of false positive scans, leading to low specificity.

Combined PET/MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone☆

AIM Combined PET/MR systems have now become available for clinical use. Given the lack of integrated standard transmission (TX) sources in these systems, attenuation and scatter correction (AC) must be performed using the available MR-images. Since bone tissue cannot easily be accounted for during MR-AC, PET quantification can be biased, in particular, in the vicinity of the skull. Here, we assess PET quantification in PET/MR imaging of patients using phantoms and patient data. MATERIALS AND METHODS Nineteen patients referred to our clinic for a PET/CT exam as part of the diagnostic evaluation of suspected dementia were included in our study. The patients were injected with 200MBq [(18)F]FDG and imaged with PET/CT and PET/MR in random sequence within 1h. Both, PET/CT and PET/MR were performed as single-bed acquisitions without contrast administration. PET/CT and PET/MR data were reconstructed following CT-based and MR-based AC, respectively. MR-AC was performed based on: (A) standard Dixon-Water-Fat segmentation (DWFS), (B) DWFS with co-registered and segmented CT bone values superimposed, and (C) with co-registered full CT-based attenuation image. All PET images were reconstructed using AW-OSEM, with neither resolution recovery nor time-of-flight option employed. PET/CT (D) or PET/MR (A-C) images were decay-corrected to the start time of the first examination. PET images following AC were evaluated visually and quantitatively using 10 homeomorphic regions of interest drawn on a transaxial T1w-MR image traversing the central basal ganglia. We report the relative difference (%) of the mean ROI values for (A)-(C) in reference to PET/CT (D). In a separate phantom experiment a 2L plastic bottle was layered with approximately 12mm of Gypsum plaster to mimic skull bone. The phantom was imaged on PET/CT only and standard MR-AC was performed by replacing hyperdense CT attenuation values corresponding to bone (plaster) with attenuation values of water. PET image reconstruction was performed with CT-AC (D) and CT-AC using the modified CT images corresponding to MR-AC using DWFS (A). RESULTS PET activity values in patients following MR-AC (A) showed a substantial radial dependency when compared to PET/CT. In all patients cortical PET activity was lower than the activity in the central region of the brain (10-15%). When adding bone attenuation values to standard MR-AC (B and C) the radial gradient of PET activity values was removed. Further evaluation of PET/MR activity following MR-AC (A) relative to MR-AC (C) using the full CT for attenuation correction showed an underestimation of 25% in the cortical regions and 5-10% in the central regions of the brain. Observations in patients were replicated by observations from the phantom study. CONCLUSION Our phantom and patient data demonstrate a spatially varying bias of the PET activity in PET/MR images of the brain when bone tissue is not accounted for during attenuation correction. This has immediate implications for PET/MR imaging of the brain. Therefore, refinements to existing MR-AC methods or alternative strategies need to be found prior to adopting PET/MR imaging of the brain in clinical routine and research.