Yuji Nakamoto

Respiratory motion artifacts on PET emission images obtained using CT attenuation correction on PET-CT

Abstract. PET-CT scanners allow generation of transmission maps from CT. The use of CT attenuation correction (CTAC) instead of germanium-68 attenuation correction (Ge AC) might be expected to cause artifacts on reconstructed emission images if differences in respiratory status exist between the two methods of attenuation correction. The aim of this study was to evaluate for possible respiratory motion artifacts (RMA) in PET images attenuation corrected with CT from PET-CT in clinical patients. PET-CT scans were performed using a Discovery LS PET-CT system in 50 consecutive patients (23 males, 27 females; mean age 58.2 years) with known or suspected malignancy. Both CTAC and Ge AC transmission data obtained during free tidal breathing were used to correct PET emission images. Cold artifacts at the interface of the lungs and diaphragm, believed to be due to respiratory motion (RMA), that were seen on CTAC images but not on the Ge AC images were evaluated qualitatively on a four-point scale (0, no artifact; 1, mild artifact; 2, moderate artifact; 3, severe artifact). RMA was also measured for height. Curvilinear cold artifacts paralleling the dome of the diaphragm at the lung/diaphragm interface were noted on 84% of PET-CT image acquisitions and were not seen on the 68Ge-corrected images; however, these artifacts were infrequently severe. In conclusion, RMA of varying magnitude were noted in most of our patients as a curvilinear cold area at the lung/diaphragm interface, but were not diagnostically problematic in these patients.

111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction

Mesenchymal stem cells (MSCs) have shown therapeutic potential if successfully delivered to the intended site of myocardial infarction. The purpose of this pilot study was to test the feasibility of 111In oxine labelling of MSCs and single photon emission computed tomography (SPECT) imaging after intravenous administration in a porcine model of myocardial infarction. Adult farm pigs (n = 2) were subjected to closed chest experimental myocardial infarction. 111In oxine labelled MSCs (1×107 to 2×107 cells) were infused intravenously, and SPECT imaging was performed initially and on days 1, 2, 7 and 14. High quality SPECT images were obtained through 2 weeks of imaging. High initial MSC localization occurred in the lungs and slow progressive accumulation occurred in the liver, spleen and bone marrow. Renal activity was mild and persistent throughout imaging. No appreciable accumulation occurred in the myocardium. It is concluded that 111In oxine radiolabelling of MSCs is feasible, and in vivo imaging with SPECT provides a non-invasive method for sequentially monitoring cell trafficking with good spatial resolution. Because intravenous administration of MSCs results in significant lung activity that obscures the assessment of myocardial cell trafficking, alternative routes of administration should be investigated for this application.

Reproducibility of Common Semi-quantitative Parameters for Evaluating Lung Cancer Glucose Metabolism with Positron Emission Tomography using 2-Deoxy-2-[18F]Fluoro-D-Glucose

PURPOSEnPositron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been used for various cancers, but reproducibility of common utilized semi-quantitative parameters, such as the maximal single pixel standardized uptake value (SUV) and effective glycolytic volume (EGV), remains unknown. Knowledge of precision is essential for applying these parameters to treatment monitoring. The purpose of this investigation was to assess the precision of PET results obtained by repeated examinations of patients with untreated lung cancer.nnnPATIENTS AND METHODSnTen patients with lung cancer underwent two PET examinations within a week with no intervening treatment. The reproducibility of three parameters:((1) maximal SUV of 1 x 1 pixel anywhere in the tumor, calculated on the basis of predicted lean body mass [SULmax]; (2) highest average SUV at 4 x 4 pixels in the tumor adjusted by predicted lean body mass [SULmean]; and (3) EGV calculated by multiplying SUL by tumor volume), using PET images obtained at 50-60 min post-injection, were examined. Plasma glucose, insulin and free fatty acid levels were also monitored.nnnRESULTSnThe SULmax, SULmean, and EGV were measured with a mean +/- S.D. difference of 11.3% +/- 8.0, 10.1% +/- 8.2, and 10.1% +/- 8.0%, respectively. By multiplying SUL by plasma glucose concentration, the mean differences were slightly reduced to 7.2% +/- 5.8, 6.7% +/- 6.2, and 9.5% +/- 8.2, respectively.nnnCONCLUSIONnThese data indicate that commonly used semi-quantitative indices of glucose metabolism on PET show high reproducibly. This supports their use in sequential quantitative analysis in PET, such as in treatment response monitoring.

Prevalence and Patterns of Bone Metastases Detected with Positron Emission Tomography Using F-18 Fdg

Purpose The aim of this retrospective study was to report the prevalence and imaging characteristics of bone metastases detected with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and, when possible, compare these findings with the performance of bone scans in the same patients. Methods The reports of 403 patients with histologically proved malignant disease who underwent a PET scan for initial or post-therapeutic staging were reviewed for the presence of possible bone metastases. Based on the final diagnosis confirmed by histopathologic analysis or clinical follow-up, the PET findings of patients with positive bone metastases were evaluated in terms of location, intensity, and patterns. When the PET scan was positive, the PET results were compared with the findings of available bone scans. Results PET studies suggested the presence of bone metastases in 38 patients (9%). No follow-up data were available for 9 patients, and the remaining 29 were evaluated further. Of these patients, 6 had false-positive findings, whereas bone metastatic involvement was clinically confirmed in 23 patients. The primary malignant findings included lung cancer (n = 9), esophageal cancer (n = 3), lymphoma (n = 2), melanoma (n = 2), thyroid cancer (n = 2), breast cancer (n = 1), colon cancer (n = 1), prostate cancer (n = 1), testicular cancer (n = 1), and nasopharyngeal cancer (n = 1). On PET, 5 patients had a solitary metastatic focus (22%), and the remaining 18 patients had multiple lesions (78%). The vertebrae were the most frequently involved bones (74%), followed by pelvic bones (70%), ribs (65%), upper extremities including the scapula (48%), sternum (43%), and lower extremities (43%). The patterns of abnormal uptake were classified into three groups: focal (15 patients, 65%), diffuse (2 patients, 9%), and a mixed pattern (6 patients, 26%). Most of the lesions showed intense abnormal uptake (18 patients, 78%); 5 patients had both intense and moderate FDG uptake. Thirteen of the 23 patients with confirmed bone metastases also had a bone scan, which revealed positive bone disease in all of these patients. However, PET consistently revealed more metastatic foci than did the bone scan on a lesion basis. Conclusions The most frequent pattern of detectable bone metastases with FDG-PET imaging was multiple foci of intense uptake. PET revealed more lesions than did bone scanning, independent of the type of cancer or location of bone involvement, in patients who were accurately diagnosed by FDG-PET imaging.

Accuracy of image fusion of normal upper abdominal organs visualized with PET/CT

Although PET/CT scanners have the potential for precise fused registration of structures visualized on both PET and CT, physiological motion during the acquisition of both studies may alter the appearance of organ shape, size or location. The degree of possible mismatch in abdominal organ size and position between PET and CT has not been evaluated. The aim of this study was to assess the consistency in location and measured size of upper abdominal organs with PET and CT using a combined PET/CT system. Forty-six consecutive inpatients who underwent clinical PET/CT scans for suspected cancer were evaluated. CT and PET images attenuation corrected by both CT and germanium-68 transmission scans were obtained, and we separately determined the location of the top and bottom (height), anterior and posterior margins (thickness), and right and left margins (width) for each organ, including liver, spleen, and bilateral kidneys, using CT and both sets of PET images. Differences between the two modalities in terms of location and measured organ size were investigated. In the upper margin of the liver and lower margin of the spleen, more than 10% of the cases showed a larger discrepancy (>20xa0mm) between CT-based and Ge-corrected PET-based measurements, although the differences in the positions of the edges were less than 10xa0mm in most cases. The center of the liver tended to be located cephalad and to the right of the body, and that of the spleen tended to be cephalad and posterior on PET, as compared with CT. Moreover, the center of both kidneys tended to be seen cephalad, posterior, and to the right on PET. The liver appeared slightly larger on PET than CT in thickness (CT vs CT-corrected PET vs Ge-corrected PET = 156xa0mm vs 162xa0mm vs 162xa0mm) and width (186xa0mm vs 189xa0mm vs 188xa0mm). By contrast, the spleen appeared slightly smaller on PET than CT in height (84xa0mm vs 77xa0mm vs 80xa0mm) and width (85xa0mm vs 81xa0mm vs 80xa0mm). A similar tendency was observed in the left kidney (105xa0mm vs 100xa0mm vs 99xa0mm in height, and 64xa0mm vs 59xa0mm vs 58xa0mm in width) and the right kidney (99xa0mm vs 93xa0mm vs 93xa0mm in height, and 64xa0mm vs 59xa0mm vs 60xa0mm in width). These differences between the two modalities were statistically significant (P<0.05). In conclusion, minor mismatches in location and organ size were found to exist between CT and PET images, in part due to physiological motion. Although these differences could potentially affect the quality of the image registrations, they were generally of a modest nature.

PET/CT: artifacts caused by bowel motion.

Background and aimIn a combined positron emission tomography (PET) and computed tomography (CT) system, the CT images can be used for attenuation correction as well as for image fusion. However, quantitative and qualitative differences have been reported between CT based attenuation corrected PET and conventional transmission scan corrected PET images. The purpose of this study was to investigate potential differences in PET/CT caused by attenuation differences in bowel due to motion. MethodsTwelve patients had PET/CT scans performed using 68Ge transmission and CT attenuation correction methods. Three emission imaging datasets were generated including CT corrected PET, Ge corrected PET, and the difference images (CT corrected PET minus Ge corrected PET). PET difference images were used to identify regions of mismatch and to quantify possible discordance between images by using standardized uptake values (SUVs). Using the Ge corrected PET as the standard, differences in emission images were classified as an overestimation (pattern A) or an underestimation (pattern B) in these difference images. ResultsOne hundred and twenty-three mismatched areas were identified. Among them, overestimated areas in CT corrected image were detected in 36 regions (pattern A), while underestimated areas were evaluated in the remaining 87 regions (pattern B). The mean value of the difference in pattern A (mean±standard deviation=0.84±0.44) was slightly higher than that in pattern B (0.60±0.23), and statistically significant. Six of 36 regions in pattern A had an SUV of greater than 2.5 in CT corrected PET but less than 2.5 in Ge corrected PET; two of 87 regions with pattern B demonstrated an SUV greater than 2.5 in Ge corrected PET and less than 2.5 in CT corrected PET. ConclusionPhysiological bowel motion may result in attenuation differences and subsequent differences in SUVs. Overestimation of fluorodeoxyglucose uptake should not be misinterpreted as disease.

PET-CT evaluation of 2-deoxy-2-[18F]fluoro-D-glucose myocardial uptake: effect of respiratory motion.

PURPOSEnUsing combined positron emission tomography (PET) and computerized tomography (CT) instrumentation, PET measurements of myocardial tracer uptake performed with CT attenuation correction may differ from estimates using 68Germanium transmission correction due to differences in respiratory motion during acquisition. The purpose of this study is to evaluate the effects of respiratory motion on the CT acquisition and emission corrected images, and to evaluate the correlation of diaphragm position with regional differences in myocardial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in clinical studies.nnnMETHODSnA canine myocardial FDG-PET study was performed with controlled ventilation. Attenuation correction was performed with CT scans acquired at end expiration and end inspiration, and throughout multiple respiratory cycles with conventional 68Germanium transmission scan. The mean myocardial FDG activity was evaluated in multiple short axis regions of interest (n=40) using each of these three AC maps. Differences in emission during CT acquisitions were identified and expressed as bias (%) compared to 68Germanium corrected data. Ten patient studies with high myocardial FDG uptake were retrospectively selected from a clinical population referred for whole body oncology studies. All subjects had both CT and 68Germanium AC. After analysis for diaphragm misregistration defined by imaging and diaphragm position, subjects were divided into two groups: Group A controls (n=5) with no or mild misregistration, and Group B (n=5) with moderate or severe diaphragm misregistration. Regional emission bias (n=400 regions) from CT correction was defined by using the 68Germanium attenuation corrected emission as the standard.nnnRESULTSnThe canine study using end-expiration CT for attenuation correction showed regional overestimation of activity (1.8%+/-0.7% for inferior; 2.0%+/-0.5% for inferolateral) compared to the 68Germanium corrected images. Conversely, the study using end-inspiration CT attenuation correction showed underestimation (-3.9%+/-0.5% for inferior; -4.0%+/-0.6% for inferolateral) of myocardial activity compared to 68Germanium corrected images. In subjects, Group B showed significant relative underestimation of FDG myocardial activity compared to Group A in the regions adjacent to the diaphragm including the inferior (P=0.0003), inferoseptal (P=0.008), and inferolateral (P<0.0001) regions.nnnCONCLUSIONSnIn canine myocardium, differences in respiration influenced CT attenuation maps and subsequent CT attenuation corrected PET images in the inferolateral and lateral regions. In clinical PET-CT studies, diaphragm misregistration is associated with relative decreased emission activity in inferior, inferoseptal, and inferolateral walls. Nonuniformity of bias in the emission data can affect quantitative accuracy, and therefore, the interpretation of myocardial viability. Further studies are required to determine if the frequency of these findings warrants the use of 68Germanium transmission attenuation correction in myocardial FDG-PET. The quantitative differences between these techniques were typically modest.

Impact of body habitus on quantitative and qualitative image quality in whole-body FDG-PET

Abstract. Obtaining consistent high image quality is desirable for clinical positron emission tomography (PET). Body morphology may impact image quality. The purpose of this study was to define the average and the range of body sizes in patients undergoing tumor PET studies in our center and to determine how the body habitus affects the statistical and visual quality of PET images. Height, weight, body surface area (BSA), and body mass index (BMI) were determined in 101 male and 101 female patients (group 1) referred for clinical PET. The summed total counts from three consecutive transaxial slices on non-attenuation-corrected (NAC) 2D fluorine-18 fluorodeoxyglucose (FDG) PET images, which included the largest liver section and no lesions, were determined and compared with body morphology and injected doses (ID) in a representative group of 30 male and 30 female patients (group 2) spanning a range of body morphologies. The visual quality of images was also evaluated using a scoring system by three readers. The average height, weight, and BSA were greater in male than in female patients, but the average BMI was not different between them in group 1. The largest value of weight or BMI was more than four times the smallest value in female patients. The total true counts were best correlated with ID/weight (mCi/kg) in group 2 (r=0.929, P<0.0001). Intermediate to high total counts (930,000 or more) corresponded to ID/weight of 0.22 or higher. The average visual score was positively correlated with the total counts (ρ=0.63, P<0.0001) and with ID/weight (ρ=0.68, P<0.0001) on NAC images. The image quality in 22 (84.6%) of 26 patients with intermediate to high total counts was adequate to good, whereas that in 21 (61.8%) of 34 patients with lower total counts was suboptimal. A wide variety of body morphologies was observed in patients referred for clinical FDG-PET tumor studies in our center. The total counts and average image visual score were negatively correlated with weight. Counts in heavy patients were as low as one-fourth those in light patients. Adjusting injected FDG dose in each patient on the basis of body weight may be more appropriate to achieve consistent PET image quality than giving a fixed injected FDG dose.

Comparison of attenuation-corrected and non-corrected FDG-PET images for axillary nodal staging in newly diagnosed breast cancer.

PURPOSEnThe aim of this work is to compare the accuracy of non-attenuation-corrected (NAC) and attenuation-corrected (AC) PET images using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in assessment of the axilla in patients with newly-diagnosed, untreated, primary breast cancers, and to determine the frequency of extra-axillary findings.nnnPATIENTS AND METHODSnFDG-PET was performed in 36 patients with breast cancer one hour following the intravenous injection of approximately 370 MBq of FDG. Patients were imaged prior to axillary dissection to prospectively confirm the presence or absence of axillary metastases. NAC and AC images were separately and independently reviewed in a blinded fashion by two readers. Imaging results were compared with final diagnoses obtained by surgery and pathology.nnnRESULTSnNinety-six positive axillary lymph nodes in 15 patients were histopathologically confirmed by surgery. The average areas under the ROC curve for NAC and AC image were 0.682 and 0.721, respectively. In patient-based analysis, the sensitivity in interpreting NAC images for the presence of metastases was low (53.3%) and comparable to that of AC images (46.7%). The specificity of NAC image was high (85.7%), but tended to be lower than that in AC (95.2%). The overall diagnostic accuracy for detecting axillary involvement in AC images (75.0%) was comparable to that of NAC images (72.2%). Extra-axillary disease was found in three patients.nnnCONCLUSIONnNAC images were comparable to AC images, although there were more false positive results with the NAC images. While AC PET has high specificity in this application, it appears insufficiently sensitive to use these methods to avoid axillary tissue sampling, when negative. Extra-axillary findings, while infrequent, may be quite important. Examination of both NAC and AC images is advised when assessing possible metastatic breast cancer to the axilla using PET.

Synthesis and biodistribution of [11C]adenosine 5'-monophosphate ([11C]AMP).

PurposeImaging purine receptors and adenylate biodistribution in vivo may be of clinical importance not only for the investigation of normal adenylate metabolism but also in pathological conditions where adenylate uptake and/or release from certain tissues and organs may be altered, such as some types of cancer. In order to develop a tracer for positron emission tomography (PET) that would not be subject to loss of its radioisotope, adenosine 5′-monophosphate (AMP) was intrinsically labeled at the C-8 position with carbon-11.Procedures[11C]AMP was synthesized by reacting 5-amino-1-β-d-ribofuranosylimidazole-4-carboxamidine-5′-phosphate with [11C]formaldehyde. The metabolism of [11C]AMP in human blood was determined in vitro both in the presence and absence of dipyridamole. The ex vivo biodistribution of [11C]AMP and its in vivo dosimetry were determined in normal mice. The effect of dipyridamole on the distribution of [11C]AMP in mice was also determined.Results[11C]AMP was reliably synthesized in 34 minutes (n = 7) with an average radiochemical yield of 2.4% and an average specific activity of 90.10xa0GBq/μmol (2435xa0mCi/μmol) at end of synthesis. In normal mice, the highest uptake of [11C]AMP was in the lungs, blood, and heart. The ex vivo mouse experiments showed that the uptake of 11C radiotracer in the lungs at 60 minutes postinjection was significantly lower for dipyridamole-treated animals than controls. Dosimetry showed that the critical organs for radiation dose burden are kidneys and bladder.ConclusionsTreatment with dipyridamole blocked the red blood cell uptake of extracellular adenosine and therefore its subsequent intracellular conversion to ATP. The biodistribution studies indicate that the tracer has substantial accumulation in the kidneys, lungs, heart, and blood. [11C]AMP is promising as a PET-imaging agent to trace adenylate biology in vivo.