Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study.

BACKGROUND: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. METHODS: Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. RESULTS: [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. CONCLUSION: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.

Factors affecting intrapatient liver and mediastinal blood pool ¹8F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin's lymphoma.

PURPOSE: The aim of our study was to assess the intrapatient variability of 2-deoxy-2-((18)F)-fluoro-D-glucose ((18)F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin's lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT). METHODS: The study included 68 patients (30 men, 38 women; mean age 32 ± 11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) (18)F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15 ± 5 days prior to the PET2 examination. All patients were further evaluated 15 ± 6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis. RESULTS: The main results of our study were an increased liver SUVmean in PET2 (1.76 ± 0.35) as compared with that of PET0 (1.57 ± 0.31; p < 0.0001) and PET6 (1.69 ± 0.28; p = 0.0407). The same results were obtained when considering liver SUVmax in PET2 (3.13 ± 0.67) as compared with that of PET0 (2.82 ± 0.64; p < 0.0001) and PET6 (2.96 ± 0.52; p = 0.0105). No significant differences were obtained when comparing mediastinum SUVmean and SUVmax in PET0, PET2 and PET6 (p > 0.05). Another finding is a relationship in PET0 between liver SUVmean and SUVmax with the stage, which was lower in those patients with advanced disease (r (2) = 0.1456 and p = 0.0013 for SUVmean and r (2) = 0.1277 and p = 0.0028 for SUVmax). CONCLUSION: The results of our study suggest that liver (18)F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.

Accumulation of (18)F-FDG in the liver in hepatic steatosis.

OBJECTIVE: Nonalcoholic fatty liver disease is associated with hepatic inflammation. An emerging technique to image inflammation is PET using the glucose tracer, (18)F-FDG. The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte. MATERIALS AND METHODS: Hepatic FDG uptake, as SUV = [voxel counts / administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate, SUVmax) and average SUV ( SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLV). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). RESULTS: The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUVave. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. CONCLUSION: FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake.

Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women.

UNLABELLED: The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using (18) F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. INTRODUCTION: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. METHODS: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n = 11) or RIS (n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. (18) F-fluoride plasma clearance (K(i)) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. RESULTS: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K(i) and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p = 0.028) and 24.0% (p = 0.013), respectively. CONCLUSIONS: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment.

Analogue tracers and lumped constant in capillary beds.

The lumped constant is a proportionality factor for converting a tracer analogue's metabolic rate to that of its mother substance. In a uniform system, it is expressed as the ratio of the tracer analogue's extraction fraction (E*) to the extraction fraction of its mother substance (E). Here we show that, in capillary beds perfused by unidirectional blood flow, unequal concentration gradients of the tracer analogue and of the mother substance influence extraction fractions both locally and across the organ and that the direct proportionality of E* and E must be replaced by ln(1-E*)/ln(1-E) to yield Λ, i.e. the lumped constant derived from first principles of bi-substrate enzyme and membrane kinetics. In other words, at a given capillary blood flow (F), the ratio of systemic clearances (FE*/FE), often used in compartmental kinetic analysis, must be replaced by the ratio of the intrinsic clearances, [-F ln(1-E*)]/[-F ln(1-E)]. The conclusion is supported by 2-[(18)F]fluoro-2-deoxy-D-galactose removal kinetics in pig liver in vivo from previous publications by the dependence of E*/E and the independence of Λ, on blood galactose concentration. Moreover, our corrections to the results of compartmental kinetics are quantified for comparing extraction fractions in different regions of interest (e.g. by positron emission tomography) and for calculating Λ using whole-organ E* and E measured by arteriovenous concentration differences.

Simplified [18F]FDG image-derived input function using the left ventricle, liver, and one venous blood sample.

A relatively simple, almost entirely noninvasive imaging-based method is presented for deriving arterial blood input functions for quantitative [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomographic (PET) studies in rodents. It requires only one venous blood sample at the end of the scan. MicroPET images and arterial blood time-activity curves (TACs) were downloaded from the Mouse Quantitation Program database at the University of California, Los Angeles. Three-dimensional regions of interest were drawn around the blood-pool region of the left ventricle and within the liver to derive their respective TACs. To construct the "hybrid" image-derived input function (IDIF), the initial part of the left ventricle TAC, containing the peak concentration of [(18)F]FDG in the arterial blood, was corrected for spillout (ie, partial-volume effect yielding a recovery coefficient < 1) and then joined to the liver TAC (normalized to the 60-minute arterial blood sample) immediately after it peaks. To validate our method, the [(18)F]FDG influx constant (K(i)) was estimated using a two-tissue compartment model and compared to estimates of K(i) obtained using measured arterial blood TACs. No significant difference in the K(i) estimates was obtained with the arterial blood input function and our hybrid IDIF. We conclude that the normalized hybrid IDIF can be used in practice to obtain reliable K(i) estimates.

Prognostic value of pretreatment tumor-to-blood standardized uptake ratio (SUR) in rectal cancer.

OBJECTIVES: The prognostic value of SUV on pretreatment F-18 FDG PET/CT imaging in patients with rectal cancer is a matter of debate. SUR is of prognostic value for survival in different cancers. In this study, we aimed to examine the potential prognostic value of SUR and other parameters in pretreatment F-18 FDG PET/CT for non-metastatic rectal cancer. METHODS: One hundred four non-metastatic rectal cancer patients who underwent pretreatment PET/CT between March 2012 and January 2018 were included in the study. Firstly, SUVmax, SUVmean, MTV, and TLG were calculated semi-automatically at the workstation. SUR was calculated as the ratio of tumor SUVmax to thoracic aorta blood SUVmean. Univariate Cox regression and Kaplan-Meier analysis were used to evaluate overall survival (OS), progression free survival (PFS), and local recurrence (LR). Then, multivariate Cox regression analysis, which included the parameters that were significant in the univariate analysis, was performed. RESULTS: Multivariate Cox regression analysis revealed that SUR was a prognostic factor for PFS. Age and T stage were prognostic factors for both OS and PFS. MTV was found to be independent risk factors for OS. CONCLUSIONS: In our study, SUR was the only F-18 FDG PET/CT parameter found to be significant for PFS. The development of new parameters can increase the prognostic value of F-18 FDG PET/CT.

In vivo imaging of oligonucleotidic aptamers.

In this chapter we present the methods developed in our laboratory for in vivo imaging of oligonucleotidic aptamers. These methods relate to (i) the labelling of aptamers with fluorine-18, a positron emitter, (ii) Positron Emission Tomography imaging of laboratory animals with [(18)F]aptamers and (iii) labelling with fluorescent dyes and optical imaging of aptamers in mice.

18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT effectively contribute to early diagnosis of infection of arteriovenous graft for hemodialysis.

OBJECTIVE: An arteriovenous graft (AVG) is indicated in hemodialysis patients with failed arteriovenous access. Early treatment of AVG infection is important because an advanced prosthetic infection leads to the removal of the prosthesis. The aim of this study was to evaluate the benefits of 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT in early detection of AVG infections. SUBJECTS AND METHODS: Fifty-one AVGs were evaluated. 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT studies were performed at intervals of 10, 20-30, and 40-50 weeks after AVG insertion. Agreement between the imaging methods and reference parameters (i.e. clinical presentation, C-reactive protein and microbiological findings on the hemodialysis cannula extracted after hemodialysis from AVG) was evaluated. RESULTS: The study results showed that focal accumulation of the radiopharmaceuticals can be considered a sign of AVG infection. At 10 weeks after AVG implantation, the focal 18F-FDG findings showed the best agreement with the reference parameters (agreement coefficients AC1 - clinical status: 0.693, CRP: 0.605, cannula microbiology: 0.518, respectively). At 20 to 30 weeks after AVG implantation, the diagnostic value of focal 99mTc-HMPAO-WBC accumulation increased (AC1 coefficients: 0.658, 0.658, 0.408) and was similar to that of focal 18F-FDG uptake (AC1s: 0.656, 0.570, 0.409). Between 40 and 50 weeks since AVG implantation, the diagnostic significance of focal 99mTc-HMPAO-WBC accumulation (AC1 coefficients: 0.771, 0.811, 0.611) slightly exceeded the diagnostic value of focal 18F-FDG accumulation (AC1 coefficients: 0.524, 0.456, 0.569). CONCLUSION: 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT can both serve as important tools contributing to early diagnosis of AVG infection.

Quantifying Brain [18F]FDG Uptake Noninvasively by Combining Medical Health Records and Dynamic PET Imaging Data.

Full quantification of regional cerebral metabolic rate of glucose (rCMRglu) with [18F]fluorodeoxy-glucose ([18F]FDG) positron emission tomography (PET) imaging requires measurement of an arterial input function (AIF) curve, which is obtained with an invasive arterial blood sampling procedure during the scan. We previously proposed a non-invasive simultaneous estimation (nSIME) method that quantifies binding of a PET radioligand by combining individual electronic health records information and a pharmacokinetic AIF (PK-AIF) model. Initially applied only to [11C]DASB data, in this study we validate nSIME for a different radioligand, [18F]FDG, adapting the algorithm to the specific distribution and metabolism of this radioligand. We evaluate the impact of the PK-AIF model, the number of [18F]FDG-specific soft constraints, and the type of predictive strategy. The accuracy of nSIME is then compared to a population-based approach. All analyses are conducted on 67 [18F]FDG PET scans with arterial blood data available for comparison. nSIME performance is optimal for [18F]FDG when using the PK-AIF model, two soft constraints, and an aggregate model to predict the soft constraint values. Higher correlation and lower Bland-Altman spread against gold standard rCMRglu values based on arterial blood measurements are observed for nSIME (r = 0.83, spread = 1.55) compared to the population-based approach (r = 0.77, spread = 2.12). nSIME provides a data-driven estimation of both amplitude and shape of the AIF curve at the individual level and potentially enables non-invasive quantification of PET data across radioligands, avoiding the need for arterial blood sampling.

Tissue standardized uptake value is a closer surrogate of blood fluorine-18 fluorodeoxyglucose clearance after division by blood standardized uptake value, illustrated in brain and liver.

The numerator and denominator of the left-hand side of the Gjedde-Patlak-Rutland (GPR) equation for measurement of blood fluorine-18 fluorodeoxyglucose (F-FDG) clearance into tissue (Ki) are the standardized uptake values (SUVs) of tissue and blood, respectively. The extent to which normalized time (NT) in the GPR equation exceeds real time depends on half-time of clearance of F-FDG from blood. A literature review shows that NT is fairly constant, about 100 min at 60 min postinjection of F-FDG, in keeping with our own finding of no significant difference in maximum SUV in blood 60 min postinjection of F-FDG between 39 patients with F-FDG-avid malignancy on routine PET/CT (1.74±0.31) and 21 patients with normal PET/CT (1.79±0.32), and similar blood glucose levels (BGLs). Volume of distribution (V0) in the GPR equation is ∼0.4 ml/ml for brain and ∼0.9 ml/ml for lean liver. Using these values of V0 and an NT of 100 min, we used the GPR equation to calculate Ki from our own published values of SUVliver/SUVblood and SUVbrain/SUVblood at 60 min postinjection, obtaining 0.0045 ml/min/ml for liver and 0.036 ml/min/ml for brain at BGL of 5 mmol/l. These values for Ki at this BGL are close to literature values of Ki, which for liver and brain are ∼0.0033 and ∼0.035 ml/min/ml, respectively. We conclude, therefore, that following division with blood pool SUV, tissue SUV becomes a closer surrogate of Ki. This division also eliminates the controversy over which whole body metric to use in the calculation of SUV.

Assessing the Effect of Various Blood Glucose Levels on 18F-FDG Activity in the Brain, Liver, and Blood Pool.

Studies have extensively analyzed the effect of hyperglycemia on 18F-FDG uptake in normal tissues and tumors. In this study, we measured SUV in the brain, liver, and blood pool in normoglycemia, hyperglycemia, and hypoglycemia to understand the effect of blood glucose on 18F-FDG uptake and to develop a formula to correct SUV. Methods: Whole-body 18F-FDG PET/CT images of adults were selected for analysis. Brain SUVmax, blood-pool SUVmean, and liver SUVmean were measured at blood glucose ranges of 61-70, 71-80, 81-90, 91-100, 101-110, 111-120, 121-130, 131-140, 141-150, 151-160, 161-170, 171-180, 181-190, 191-200, and 201 mg/dL and above. At each blood glucose range, 10 PET images were analyzed (total, 150). The mean (±SD) SUV of the brain, liver, and blood pool at each blood glucose range was calculated, and blood glucose and SUV curves were generated. Because brain and tumors show a high expression of glucose transporters 1 and 3, we generated an SUV correction formula based on percentage reduction in brain SUVmax with increasing blood glucose level. Results: Mean brain SUVmax gradually decreased with increasing blood glucose level, starting after a level of 110 mg/dL. The approximate percentage reduction in brain SUVmax was 20%, 35%, 50%, 60%, and 65% at blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively. In the formula we generated, measured SUVmax is multiplied by a reduction factor of 1.25, 1.5, 2, 2.5, and 2.8 for the blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively, to correct SUV. Brain SUVmax did not differ between hypoglycemic and normoglycemic patients (P > 0.05). SUVmean in the blood pool and liver was lower in hypoglycemic patients (P < 0.05) and did not differ between hyperglycemic (P > 0.05) and normoglycemic patients. Conclusion: Hyperglycemia gradually reduces brain 18F-FDG uptake, starting after a blood glucose level of 110 mg/dL. Hyperglycemia does not affect 18F-FDG activity in the liver or blood pool. Hypoglycemia does not seem to affect brain 18F-FDG uptake but appears to reduce liver and blood-pool activity. The simple formula we generated can be used to correct SUV in hyperglycemic adults in selected cases.

Variations of the liver standardized uptake value in relation to background blood metabolism: An 2-[18F]Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography study in a large population from China.

To investigate the influence of background blood metabolism on liver uptake of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) and search for an appropriate corrective method.Positron emission tomography/computed tomography (PET/CT) and common serological biochemical tests of 633 healthy people were collected retrospectively. The mean standardized uptake value (SUV) of the liver, liver artery, and portal vein (i.e., SUVL, SUVA, and SUVP) were measured. SUVL/A was calculated as SUVL/SUVA, while SUVL/P was calculated as SUVL/SUVP. SUV of liver parenchyma (SUVLP) was calculated as SUVL - .3 × (.75 × SUVP + .25 × SUVA). The coefficients of variation (CV) of SUVL, SUVL/A, SUVL/P, and SUVLP were compared to assess their interindividual variations. Univariate and multivariate analyses were performed to identify vulnerabilities of these SUV indexes to common factors assessed using serological liver functional tests.SUVLP was significantly larger than SUVL (2.19 ± .497 vs 1.88 ±â€Š.495, P < .001), while SUVL/P was significantly smaller than SUVL (1.72 ±â€Š.454 vs 1.88 ±â€Š.495, P < .001). The difference between SUVL/A and SUVL was not significant (1.83 ±â€Š.500 vs 1.88 ±â€Š.495, P = .130). The CV of SUVLP (22.7%) was significantly smaller than that of SUVL (22.7%:26.3%, P < .001), while the CVs of SUVL/A (27.2%) and SUVL/P (26.4%) were not different from that of SUVL (P = .429 and .929, respectively). Fewer variables independently influenced SUVLP than influenced SUVL, SUVL/A, and SUVL/P; Only aspartate aminotransferase, body mass index, and total cholesterol, all P-values <.05.The activity of background blood influences the variation of liver SUV. SUVLP might be an alternative corrective method to reduce this influence, as its interindividual variation and vulnerability to effects from common factors of serological liver functional tests are relatively lower than the commonly used SUVL.

Influence of scan time point and volume of intravenous contrast administration on blood-pool and liver SUVmax and SUVmean in [18F] FDG PET/CT.

AIM: To investigate the influence of scan time point and volume of intravenous contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake values (SUVmax/mean) in bloodpool and liver. METHODS: In 120 patients scheduled for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake values (SUVmax/SUVmean) in the liver and blood pool were measured after varying scan time-point (delay 0 s-140 s post injectionem) and volume of contrast material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine). Six groups of 20 patients were investigated: (1) without intravenous CM, (2-5) injection of 100 ml CM with a delay of 80 s (2), 100 s (3), 120 s (4), 140 s (5), and 80 ml CM and a delay of 100 s (6). SUVmax, SUVmean, maximum Hounsfield units (HUmax) and average Hounsfield units (HUav) were calculated with the use of manually drawn regions of interests (ROIs) over the aortic arch and healthy liver tissue. RESULTS: SUVmax in bloodpool was significantly higher in group 3, 4 and 6 compared to group 1. Groups 2 and 5 also showed higher mean values of SUVmax, but the difference was not significant. SUVmean in bloodpool was also higher in groups 2, 3, 4, 5 and 6 compared to group 1, but the differences were only statistically significant in group 3. Both SUVmax and SUVmean in healthy liver tissue did not show significant differences when compared to the non contrast-enhanced control group. CONCLUSION: SUVmax and to a lesser extent SUVmean measured in CM enhanced FDG PET/CT in blood pool could be significantly altered in high contrast CT examinations. This should be kept in mind in PET/CT protocols and evaluation relying on SUVmax and SUVmean, for example when used in the assessment of therapy response, especially in highly vascularized tumor lesions. ZIEL:: Das Ziel dieser Studie war den Einfluss von unterschiedlichen Messzeitpunkten und Volumina bei der Gabe von intravenösem Kontrastmittel in der 18F-FDG PET/CT auf SUVmax und SUVmean im Blutpool und Lebergewebe zu untersuchen. METHODEN: In 120 Patienten, geplant für eine Ganzkörper 18F-FDG -PET/CT, wurden die maximalen und durchschnittlichen standardisierten Aufnahmewerte (SUVmax/SUVmean) in der Leber und im Blutpool, jeweils nach unterschiedlichen Messzeitpunkten (Verzögerung 0 s-140 s post injectionem) und verschiedenen Volumina von Kontrastmittel (KM; 0 ml, 80 ml, 100 ml mit einer Konzentration von 300 mg/ml Jod) gemessen. Sechs Gruppen von je 20 Patienten wurden untersucht: (1) ohne intravenöses KM, (2-5) Injektion von 100 ml KM mit einer Verzögerung von 80 s (2), 100 s (3), 120 s (4), 140 s (5), und 80 ml KM mit einer Verzögerung von 100 s (6). Es wurden jeweils die SUVmax, SUVmean, die maximalen and die durchschnittlichen Hounsfield Einheiten (HUav, HUmax) anhand manuell gezeichneter Bereiche von Interesse (ROIs) im Aortenbogen und im gesunden Lebergewebe berechnet. ERGEBNISSE: Die SUVmax im Blutpool waren im Vergleich zur Gruppe 1 signifikant höher in Gruppe 3, 4 und 6. Die Gruppen 2 und 5 zeigten ebenfalls höhere Durchschnittswerte von SUVmax, der Unterschied war jedoch nicht signifikant. Die SUVmean im Blutpool waren im Vergleich zur Gruppe 1 ebenfalls höher in den Gruppen 2, 3, 4, 5 und 6, allerdings waren die Unterschiede nur in Gruppe 3 statistisch signifikant. Im Lebergewebe zeigten sowohl SUVmax, als auch SUVmean keine signifikanten Unterschiede im Vergleich zu der nativen Kontrollgruppe. SCHLUSSFOLGERUNGEN: In der Kontrastmittel-gestützten FDG PET/CT können die SUVmax und in geringerem Ausmaß auch SUVmean im Blutpool durch Hochkontrast-CT Untersuchungen signifikant beeinflusst werden. Dies sollte bei PET/CT Protokollen bzw. Auswertungen, die auf SUVmax und SUVmean beruhen, berücksichtigt werden, zum Beispiel bei der Beurteilung des Therapieansprechens insbesondere bei stark vaskularisiertem Tumorgewebe.

Estimation of the 18F-FDG input function in mice by use of dynamic small-animal PET and minimal blood sample data.

UNLABELLED: Derivation of the plasma time-activity curve in murine small-animal PET studies is a challenging task when tracers that are sequestered by the myocardium are used, because plasma time-activity curve estimation usually involves drawing a region of interest within the area of the reconstructed image that corresponds to the left ventricle (LV) of the heart. The small size of the LV relative to the resolution of the small-animal PET system, coupled with spillover effects from adjacent myocardial pixels, makes this method reliable only for the earliest frames of the scan. We sought to develop a method for plasma time-activity curve estimation based on a model of tracer kinetics in blood, muscle, and liver. METHODS: Sixteen C57BL/6 mice were injected with (18)F-FDG, and approximately 15 serial blood samples were taken from the femoral artery via a surgically inserted catheter during 60-min small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. We constructed a 5-compartment model designed to predict the plasma time-activity curve of (18)F-FDG by use of data from a minimum of 2 blood samples and the dynamic small-animal PET scan. The plasma time-activity curve (TACp) was assumed to have 4 exponential components (TAC(P)=A(1)e(lambda(1)t)+A(2)e(lambda(2)t)+A(3)e(lambda(3)t)-(A(1)+A(2)+A(3))e(lambda(4)t)) based on the serial blood samples. Using Bayesian constraints, we fitted 2-compartment submodels of muscle and liver to small-animal PET data for these organs and simultaneously fitted the input (forcing) function to early small-animal PET LV data and 2 blood samples (approximately 10 min and approximately 1 h). RESULTS: The area under the estimated plasma time-activity curve had an overall Spearman correlation of 0.99 when compared with the area under the gold standard plasma time-activity curve calculated from multiple blood samples. Calculated organ uptake rates (Patlak K(i)) based on the predicted plasma time-activity curve had a correlation of approximately 0.99 for liver, muscle, myocardium, and brain when compared with those based on the gold standard plasma time-activity curve. The model was also able to accurately predict the plasma time-activity curve under experimental conditions that resulted in different rates of clearance of the tracer from blood. CONCLUSION: We have developed a robust method for accurately estimating the plasma time-activity curve of (18)F-FDG by use of dynamic small-animal PET data and 2 blood samples.

Hybrid image and blood sampling input function for quantification of small animal dynamic PET data.

We describe and validate a hybrid image and blood sampling (HIBS) method to derive the input function for quantification of microPET mice data. The HIBS algorithm derives the peak of the input function from the image, which is corrected for recovery, while the tail is derived from 5 to 6 optimally placed blood sampling points. A Bezier interpolation algorithm is used to link the rightmost image peak data point to the leftmost blood sampling point. To assess the performance of HIBS, 4 mice underwent 60-min microPET imaging sessions following a 0.40-0.50-mCi bolus administration of 18FDG. In total, 21 blood samples (blood-sampled plasma time-activity curve, bsPTAC) were obtained throughout the imaging session to compare against the proposed HIBS method. MicroPET images were reconstructed using filtered back projection with a zoom of 2.75 on the heart. Volumetric regions of interest (ROIs) were composed by drawing circular ROIs 3 pixels in diameter on 3-4 transverse planes of the left ventricle. Performance was characterized by kinetic simulations in terms of bias in parameter estimates when bsPTAC and HIBS are used as input functions. The peak of the bsPTAC curve was distorted in comparison to the HIBS-derived curve due to temporal limitations and delay in blood sampling, which affected the rates of bidirectional exchange between plasma and tissue. The results highlight limitations in using bsPTAC. The HIBS method, however, yields consistent results, and thus, is a substitute for bsPTAC.

Test-Retest Variability in Lesion SUV and Lesion SUR in 18F-FDG PET: An Analysis of Data from Two Prospective Multicenter Trials.

Quantitative assessment of radio- and chemotherapy response with 18F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test-retest stability, thus becomes crucial. However, a recent study demonstrated substantial test-retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non-small cell lung cancer from the prospective multicenter trials ACRIN 6678 (n = 34) and MK-0646-008 (n = 39) were included in this study. All patients underwent two 18F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1-7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUVmax and SUVpeak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time-corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering RTRV (TRVSUR/TRVSUV), a ratio reflecting the reduction in the TRV in SUR relative to SUV. RTRV was correlated with the group-averaged-value difference (δ) in CFmean (δCFmean) of the quantity δCF = |CF - 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCFmin and computing δCFmean and RTRV for the remaining subgroup of patients/lesions with δCF ≥ δCFminResults: The group-averaged TRVSUV and TRVSUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an RTRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCFmin thresholds revealed a pronounced negative correlation (Spearman ρ = -0.99, P < 0.001) between RTRV and δCFmean, where RTRV ≈ 0.4 in the δCFmin = 20% subgroup, corresponding to a more than 2-fold reduction of TRVSUR compared with TRVSUVConclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context.

Minimally invasive method of determining blood input function from PET images in rodents.

UNLABELLED: For cardiovascular research on rodents, small-animal PET has limitations because of the inherent spatial resolution of the system and because of cardiac motion. A factor analysis (FA) technique for extracting the blood input function and myocardial time-activity curve from dynamic small-animal PET images of the rodent heart has been implemented to overcome these limitations. METHODS: Six Sprague-Dawley rats and 6 BALB/c mice underwent dynamic imaging with 18F-FDG (n = 6) and 1-11C-acetate (n = 6). From the dynamic images, blood input functions and myocardial time-activity curves were extracted by the FA method. The accuracy of input functions derived by the FA method was compared with that of input functions determined from serial blood samples, and the correlation coefficients were calculated. RESULTS: Factor images (right ventricle, left ventricle, and myocardium) were successfully extracted for both 18F-FDG and 1-11C-acetate in rats. The correlation coefficients for the input functions were 0.973 for 18F-FDG and 0.965 for 1-11C-acetate. In mice, the correlation coefficients for the input functions were 0.930 for 18F-FDG and 0.972 for 1-11C-acetate. CONCLUSION: The FA method enables minimally invasive extraction of accurate input functions and myocardial time-activity curves from dynamic microPET images of rodents without the need to draw regions of interest and without the possible complications of surgery and repeated blood sampling.

A method to quantify at late imaging a release rate of 18F-FDG in tissues.

This theoretical work shows that the rate constant for the (18)F-FDG release in tissues can be assessed without needing any arterial blood sampling. The method requires that the clearance of (18)F-FDG from plasma has occurred, whereas (18)F-FDG is still present in the tissue. This condition can be met dating from 3 h after (18)F-FDG injection, when hydration and/or phlorizin injection are applied after the routine static acquisition. The release rate constant can be obtained from a graphical analysis performed at the later decreasing phase of the tissue tracer activity. A two-compartment and a three-compartment model are developed, both in accordance with one another. To cite this article: E. Laffon et al., C. R. Biologies 328 (2005).