Liselotte Højgaard

PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients

PurposeIf the CT scan of a combined PET/CT study is performed as a full diagnostic quality CT scan including intravenous (IV) contrast agent, the quality of the joint PET/CT procedure is improved and a separate diagnostic CT scan can be avoided. CT with IV contrast can be used for PET attenuation correction, but this may result in a bias in the attenuation factors. The clinical significance of this bias has not been established. Our aim was to perform a prospective clinical study where each patient had CT performed with and without IV contrast agent to establish whether PET/CT with IV contrast can be used for PET attenuation without reducing the clinical value of the PET scan.MethodsA uniform phantom study was used to document that the PET acquisition itself is not significantly influenced by the presence of IV contrast medium. Then, 19 patients referred to PET/CT with IV contrast underwent CT scans without, and then with contrast agent, followed by an 18F-fluorodeoxyglucose whole-body PET scan. The CT examinations were performed with identical parameters on a GE Discovery LS scanner. The PET data were reconstructed with attenuation correction based on the two CT data sets. A global comparison of standard uptake value (SUV) was performed, and SUVs in tumour, in non-tumour tissue and in the subclavian vein were calculated. Clinical evaluation of the number and location of lesions on all PET/CT scans was performed twice, blinded and in a different random order, by two independent nuclear medicine specialists.ResultsIn all patients, the measured global SUV of PET images based on CT with IV contrast agent was higher than the global activity using non-contrast correction. The overall increase in the mean SUV (for two different conversion tables tested) was 4.5±2.3% and 1.6±0.5%, respectively. In 11/19 patients, focal uptake was identified corresponding to malignant tumours. Eight out of 11 tumours showed an increased SUVmax (2.9±3.1%) on the PET images reconstructed using IV contrast. The clinical evaluation performed by the two specialists comparing contrast and non-contrast CT attenuated PET images showed weighted kappa values of 0.92 (doctor A) and 0.82 (doctor B). No contrast-introduced artefacts were found.ConclusionThis study demonstrates that CT scans with IV contrast agent can be used for attenuation correction of the PET data in combined modality PET/CT scanning, without changing the clinical diagnostic interpretation.

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

AIMnCombined 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.nnnMATERIALS AND METHODSnNineteen 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).nnnRESULTSnPET 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.nnnCONCLUSIONnOur 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.

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

Abstract.Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.

Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology

ObjectiveThe purpose of these guidelines is to offer to the nuclear medicine team a framework that could prove helpful in daily practice. These guidelines contain information related to the indications, acquisition, processing and interpretation of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in paediatric oncology. The Oncology Committee of the European Association of Nuclear Medicine (EANM) has published excellent procedure guidelines on tumour imaging with 18F-FDG PET (Bombardieri et al., Eur J Nucl Med Mol Imaging 30:BP115–24, 2003 [2]. These guidelines, published by the EANM Paediatric Committee, do not intend to compete with the existing guidelines, but rather aim at providing additional information on issues particularly relevant to PET imaging of children with cancer.ConclusionThe guidelines summarize the views of the Paediatric Committee of the European Association of Nuclear Medicine. They should be taken in the context of “good practice” of nuclear medicine and of any national rules, which may apply to nuclear medicine examinations. The recommendations of these guidelines cannot be applied to all patients in all practice settings. The guidelines should not be deemed inclusive of all proper procedures or exclusive of other procedures reasonably directed to obtaining the same results.

Clinical PET of Neuroendocrine Tumors Using 64Cu-DOTATATE: First-in-Humans Study

UNLABELLEDnThe use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of (64)Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV).nnnMETHODSnIn a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with our current routine imaging agent (111)In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of (64)Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n = 14), 3 h (n = 12), and 24 h (n = 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of (64)Cu-DOTATATE with respect to lesion detection was compared with conventional SRI.nnnRESULTSnSRI with (64)Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, (64)Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of (64)Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq).nnnCONCLUSIONnThis first-in-humans study supports the clinical use of (64)Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with (111)In-diethylenetriaminepentaacetic acid-octreotide.

Multimodality approach to mediastinal staging in non-small cell lung cancer. Faults and benefits of PET-CT: a randomised trial

Background Correct mediastinal staging is a cornerstone in the treatment of patients with non-small cell lung cancer. A large range of methods is available for this purpose, making the process of adequate staging complex. The objective of this study was to describe faults and benefits of positron emission tomography (PET)-CT in multimodality mediastinal staging. Methods A randomised clinical trial was conducted including patients with a verified diagnosis of non-small cell lung cancer, who were considered operable. Patients were assigned to staging with PET-CT (PET-CT group) followed by invasive staging (mediastinoscopy and/or endoscopic ultrasound with fine needle aspiration (EUS-FNA)) or invasive staging without prior PET-CT (conventional work up (CWU) group). Mediastinal involvement (dichotomising N stage into N0–1 versus N2–3) was described according to CT, PET-CT, mediastinoscopy, EUS-FNA and consensus (based on all available information), and compared with the final N stage as verified by thoracotomy or a conclusive invasive diagnostic procedure. Results A total of 189 patients were recruited, 98 in the PET-CT group and 91 in the CWU group. In an intention-to-treat analysis the overall accuracy of the consensus N stage was not significantly higher in the PET-CT group than in the CWU group (90% (95% confidence interval 82% to 95%) vs 85% (95% CI 77% to 91%)). Excluding the patients in whom PET-CT was not performed (n=14) the difference was significant (95% (95% CI 88% to 98%) vs 85% (95% CI 77% to 91%), p=0.034). This was mainly based on a higher sensitivity of the staging approach including PET-CT. Conclusion An approach to lung cancer staging with PET-CT improves discrimination between N0–1 and N2–3. In those without enlarged lymph nodes and a PET-negative mediastinum the patient may proceed directly to surgery. However, enlarged lymph nodes on CT needs confirmation independent of PET findings and a positive finding on PET-CT needs confirmation before a decision on surgery is made. Clinical trial number NCT00867412.

How few cancer cells can be detected by positron emission tomography? A frequent question addressed by an in vitro study

PurposePositron emission tomography (PET) has gained widespread use in cancer diagnosis and treatment, but how many malignant cells are required for a tumour to be detected by PET?MethodsThree human cancer cell lines [glioblastoma and two subtypes of small cell lung cancer (SCLC)] in concentrations from 104 to 107 were seeded on six-well plates or plastic tubes and treated with [18F]fluorodeoxy-glucose (FDG) in vitro. FDG retention was measured in a PET/CT scanner and in a calibrated well counter. The clinical situation was simulated using a cylinder phantom with a background concentration of FDG.ResultsThe theoretical detection limit was found to be around 105 malignant cells. In a cylinder phantom the detection limit was increased by a factor of 10. The FDG retention by the glioblastoma cell line was significantly higher than the activity of the SCLC cell line. FDG retention measured by PET and a gamma counter was closely correlated to the number of cells and a linear relationship was found.DiscussionThe detection limit of PET is in the magnitude of 105 to 106 malignant cells. The experimental set-up was robust and well suited as a platform for further investigations of factors influencing the detection limit of PET.

Spatial resolution of the HRRT PET scanner using 3D-OSEM PSF reconstruction

In this paper, the resolution of the Siemens high resolution research tomograph (HRRT) was centrally (r < 60 mm) homogenous with a FWHM of 1.4 mm for 18F-FDG in air. This was where the main part of the brain is located if the patient has been positioned correctly. The 1.4 mm resolution was obtained using the newly develop 3D-OSEM PSF reconstruction algorithm, which was a significant improvement over 3D-OSEM reconstruction without PSF. The algorithm uses a simple PSF model that was the same for all the pixels in the FOV and does not regulate for the circular/octagonal scanner geometry. This supports that the FWHM of the radial axis is increasing with the distance from the center for r > 60mm.

Added Diagnostic Value of 11C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis

Introduction: The added diagnostic value of 11C-PiB-PET for the assessment of the accumulation of cortical beta-amyloid in memory clinic patients with uncertain diagnosis remains undetermined. Methods: All patients who underwent PiB-PET at the Copenhagen Memory Clinic between March 2008 and November 2011 were included in this uncontrolled, retrospective study. The standard diagnostic evaluation program included physical and neurological examination, cognitive and functional assessment, a cranial CT or MRI, functional imaging and cerebrospinal fluid sampling. Based on anonymized case reports, three experienced clinicians reached a consensus diagnosis and rated their confidence in the diagnosis before and after disclosure of PiB-PET ratings. PiB-PET scans were rated as either positive or negative. Results: A total of 57 patients (17 females, 30 males; age 65.7 years, range 44.2–82.6) were included in the study. Twenty-seven had a positive PiB-PET scan. At the first diagnostic evaluation, 16 patients were given a clinical Alheimer’s disease diagnosis (14 PiB positive). Of the 57 patients, 13 (23%) were diagnostically reclassified after PiB-PET ratings were disclosed. The clinicians’ overall confidence in their diagnosis increased in 28 (49%) patients. Conclusion: PiB-PET adds to the specialist clinical evaluation and other supplemental diagnostic investigations in the diagnostic classification of patients with uncertain diagnosis in a specialized memory clinic.

Reproducibility of (18)F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR.

OBJECTIVEnTo investigate reproducibility of fluorine-18 fludeoxyglucose ((18)F-FDG) uptake on (18)F-FDG positron emission tomography (PET)/CT and (18)F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC).nnnMETHODSn30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland-Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV-volume histograms were measured and tested for reproducibility of the distribution of (18)F-FDG uptake.nnnRESULTSn24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5-7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09).nnnCONCLUSIONn(18)F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR.nnnADVANCES IN KNOWLEDGEnThis is the first report to test reproducibility of PET/CT and PET/MR.