Semiautomatic algorithm for lymph node analysis corrected for partial volume effects in combined positron emission tomography-computed tomography

Positron emission tomography-computed tomography (PET-CT) is superior compared to stand-alone PET in evaluation of malignancies. Few studies have employed high-resolution structural information to correct PET. We designed a semiautomatic algorithm using CT and PET to obtain a partial volume corrected (PVC) standardized uptake value (SUV) and a combined morphologic and functional parameter (multimodal SUV) for lymph node assessment. Lesions were segmented by a semiautomatic algorithm in CT images. Lesion volume was used for PVC and for calculating the multimodal SUV. The method was applied to 47 lymph nodes (30 patients) characterized as suspicious in 18F-fluorodeoxyglucose-PET-CT. In phantoms, PVC improved significantly the measured uptake of the lesion. In patients, 36 lymph nodes could be segmented without problems; in 11 lesions, a manual interaction was necessary. SUVs before PVC (mean 1.29) increased significantly (p < .0005) after PVC (mean 2.8). If SUV 2.5 was used as a threshold value to distinguish between benign and malignant lesions, 11 of the 47 lesions changed from benign to malignant after the PVC. The mean multimodal SUV was 0.39 mL for the benign lesions and 4.47 mL for the malignant lesions. In this work we presented a method for quantitative analysis of lymph nodes in PET-CT. PVC leads to significant differences in SUV.     

Glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners

The aim of this study was to determine glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners. Positron emission tomography (PET) using 18F-fluoro-2-deoxyglucose (FDG) was performed to determine the patterns of glucose uptake in lower limbs of short-distance (SD group, n=8) and long-distance (LD group, n=8) male runners after a modified 20 min Bruce treadmill test. Magnetic resonance imaging (MRI) was used to delineate the muscle groups in lower limbs. Muscle groups from hip, knee, and ankle movers were measured. The total FDG uptake and the standard uptake value (SUV) for each muscle group were compared between the 2 groups. For the SD and LD runners, the 2 major muscle groups utilizing glucose during running were knee extensors and ankle plantarflexors, which accounted for 49.3 +/- 8.1% (25.1 +/- 4.7% and 24.2 +/- 6.0%) of overall lower extremity glucose uptake for SD group, and 51.3 +/- 8.0% (27.2 +/- 2.7% and 24.0 +/- 8.1%) for LD group. No difference in muscle glucose uptake was noted for other muscle groups. For SD runners, the SUVs for the muscle groups varied from 0.49 +/- 0.27 for the ankle plantarflexors, to 0.20 +/- 0.08 for the hip flexor. For the LD runners, the highest and lowest SUVs were 0.43 +/- 0.15 for the ankle dorsiflexors and 0.21 +/- 0.19 for the hip. For SD and LD groups, no difference in muscle SUV was noted for the muscle groups. However, the SUV ratio between the ankle dorsiflexors and plantarflexors in the LD group was significantly greater than that in the SD group. We thus conclude that the major propelling muscle groups account for approximately 50% of lower limb glucose utilization during running. Thus, the other muscle groups involving maintenance of balance, limb deceleration, and shock absorption utilize an equal amount. This result provides a new insight into glucose distribution in skeletal muscle, suggesting that propellers and supporters are both energetically important during running. Furthermore, for each unit muscle volume, movers of ankle are more glucose-demanding than those of hip.     

Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning

PurposeTo conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning.MethodsWe acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images. At each count level, patches extracted from 23 pairs of SD/SLD PET images were used to train three IQT models – global linear, single tree, and random forest regressions with cubic patch sizes of 3 and 5 voxels. The models were then used to estimate SD images from LD images at each count level for 10 unseen subjects. Lesion-detection task was carried out on matched lesion-present and lesion-absent images.ResultsLD PET-CT protocol yielded lesion detectability with sensitivity of 0.98 and specificity of 1. Random forest algorithm with cubic patch size of 5 allowed further 11.7% reduction in the effective PETCT dose without compromising lesion detectability, but underestimated SUV by 30%.ConclusionLD PET-CT protocol was validated for lesion detection using ALD PET scans. Substantial image quality improvement or additional dose reduction while preserving clinical values can be achieved using machine learning methods though SUV quantification may be biased and adjustment of our research protocol is required for clinical use.     

Confirmation of histology of PET positive lymph nodes recovered by hand-video-assisted thoracoscopy surgery

PET/CT (Positron Emission Tomography-Computed Tomography) is an advanced diagnostic imaging device that combines both PET and an X-ray CT. This study evaluates the effects of PET/CT on detecting primary tumors and metastases, and looks at the therapeutic effect of minimally invasive surgery on esophageal cancer patients. Eighty patients with esophageal cancer were enrolled in the study between January, 2004 and December, 2007, who were randomly divided into two groups of 40, one of which was treated with hand-video-assisted thoracoscopy surgery (HVATS) esophagectomy and one of which was treated with conventional surgery. All patients underwent a PET/CT scan 2-3weeks before their operation, and their cervical, thoracic and upper abdominal lymph nodes were biopsied. All the primary esophageal lesions showed high FDG uptake. The maximum standardized uptake value (SUV) was 3.78-25.64 (11.73±5.32), while the mean SUV was 3.65=16.92 (9.12±4.37). Using 2.5 as the SUV standard, all esophageal lesions were detected by PET/CT image. Of the 80 patients, 53 had lymph nodal metastases, with a total of 142 metastatic lymph nodes, which showed high FDG uptake. The maximum SUV was 2.77-14.63 (7.98±3.25), and the mean SUV was 2.31-12.84 (5.34±3.19). The visual analysis from the PET/CT scan showed a sensitivity of 86.62%, a specificity of 95.85%, a positive predictive value of 93.89%, a negative predictive value of 90.69% and an accuracy of 91.94%. The PET/CT scan showed a high sensitivity and specificity in detecting primary esophageal cancer and lymph nodal metastases. The mean post-surgery life expectancies for patients undergoing HVATS and conventional surgery are 27.93months and 28.05months, respectively. The two groups showed no statistically significant difference. We thus conclude that PET/CT combined with HVATS is a new choice for esophageal carcinoma patients.     

3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts from patients with mevalonate kinase deficiency: differential response to lipid supplied by fetal bovine serum in tissue culture medium

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was measured in extracts of cultured fibroblasts derived from patients with mevalonate kinase deficiency (MKD). For six patients studied, the mean activity of 63.3 +/- 41.1 pmol/min-mg protein (+/- 1 SD, range 37.7-146.2) was significantly higher than the mean value in three control fibroblast lines of 11.1 +/- 3.5 (+/- 1 SD, range 8.0-14.9). These values were obtained using cells subcultured in medium supplemented with 10% fetal bovine serum (FBS) 21 h prior to assay. When cells were deprived of cholesterol by subculturing for 21 h in delipidated FBS, the mean value for patient cells was increased to 230.8 +/- 78.5 pmol/min-mg protein (range 130.9-333.8) as compared to 109.5 +/- 47.1 (range 78.0-163.6) for controls. The activity of HMG-CoA synthase in extracts of fibroblasts derived from the patients was not elevated. The mevalonic acid concentration in the surrounding culture medium was assessed by stable isotope dilution assay. For five patients, the mean concentration in medium containing FBS was 0.92 +/- 0.37 microM (+/- 1 SD, range 0.46-1.48) in contrast to 1.24 +/- 0.83 microM (range 0.46-2.54) for cells subcultured in delipidated FBS. The mean value for three control fibroblast lines was 0.22 +/- 0.12 microM (+/- 1 SD, range 0.11-0.35) for cells subcultured in FBS as compared to 0.01 +/- 0.01 microM (range 0.0-0.01 microM) for cells sucultured in delipidated FBS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digital Imaging and Communications in Medicine (DICOM) information conversion procedure for SUV calculation of PET scanners with different DICOM header information

PurposeIn nuclear medicine, the standardized uptake value (SUV) obtained using positron emission tomography with 2-deoxy-2-fluoro-D-glucose (FDG-PET) is widely used as a semi-quantitative diagnosis factor. We found that the header file of the Philips Allegro PET scanner using the Digital Imaging and Communications in Medicine (DICOM) standard was stored differently than with other scanners. Thus, the purpose of this study was to develop a DICOM header information conversion program to ensure compatibility between Allegro and other equipment.Methods and resultsThe NEMA IEC Body phantom was scanned using the Allegro PET scanner. We conducted measurements and performed calculations by using commercial software and the proposed self-developed program, respectively, to compare the SUVs by using conversion data. The program consists of three parts: an input part that can load data regardless of the number of DICOM images, and conversion and output parts that can be used to convert the DICOM header information and store it in the order of slices. The results of the calculation are in good agreement with the data measured at 12 circular regions of interest. The percent difference was lower than the 20%.ConclusionIn conclusion, this study suggested a simple and convenient method to solve the incompatibility through conversion of the DICOM header information. This study thus provides physicians more accurate information for diagnosis and treatment.     

Biases in Multicenter Longitudinal PET Standardized Uptake Value Measurements

This study investigates measurement biases in longitudinal positron-emission tomography/computed tomography (PET/CT) studies that are due to instrumentation variability including human error. Improved estimation of variability between patient scans is of particular importance for assessing response to therapy and multicenter trials. We used National Institute of Standards and Technology-traceable calibration methodology for solid germanium-68/gallium-68 (⁶⁸Ge/⁶⁸Ga) sources used as surrogates for fluorine-18 (¹⁸F) in radionuclide activity calibrators. One cross-calibration kit was constructed for both dose calibrators and PET scanners using the same 9-month half-life batch of ⁶⁸Ge/⁶⁸Ga in epoxy. Repeat measurements occurred in a local network of PET imaging sites to assess standardized uptake value (SUV) errors over time for six dose calibrators from two major manufacturers and for six PET/CT scanners from three major manufacturers. Bias in activity measures by dose calibrators ranged from -50% to 9% and was relatively stable over time except at one site that modified settings between measurements. Bias in activity concentration measures by PET scanners ranged from -27% to 13% with a median of 174 days between the six repeat scans (range, 29 to 226 days). Corresponding errors in SUV measurements ranged from -20% to 47%. SUV biases were not stable over time with longitudinal differences for individual scanners ranging from -11% to 59%. Bias in SUV measurements varied over time and between scanner sites. These results suggest that attention should be paid to PET scanner calibration for longitudinal studies and use of dose calibrator and scanner cross-calibration kits could be helpful for quality assurance and control.     

A Virtual Clinical Trial of FDG-PET Imaging of Breast Cancer: Effect of Variability on Response Assessment

INTRODUCTION: There is growing interest in using positron emission tomography (PET) standardized uptake values (SUVs) to assess tumor response to therapy. However, many error sources compromise the ability to detect SUV changes. We explore relationships between these errors and overall SUV variability. METHODS: We used simulations in a virtual clinical trial framework to study impacts of error sources from scanning and analysis effects on assessment of SUV changes. We varied tumor diameter, scan duration, pretherapy SUV, magnitude of change in SUV, image reconstruction filter, and SUV metric. Poisson noise was added to the raw data before image reconstruction. Variance from global sources of error, e.g., scanner calibration, was incorporated. Two thousand independent noisy sinograms per scenario were generated and reconstructed. We used SUVs to create receiver operating characteristic (ROC) curves to quantify ability to assess response. Integrating area under the ROC curve summarized ability to detect SUV changes. RESULTS: Scan duration and image reconstruction method had relatively little impact on ability to measure response. SUV_MAX is nearly as effective as SUV_MEAN, especially with increased image smoothing and despite size-matched region of interest placement. For an effective variability of 15%, we found the Positron Emission Tomography Response Criteria in Solid Tumors criteria for measuring response (±30%) similar to the European Organization for Research and Treatment of Cancer criteria (±25%). CONCLUSIONS: For typical PET variance levels, tumor response must be 30% to 40% to be reliably determined using SUVs. PET scan duration and image reconstruction method had relatively little effect.     

Normal SUV Values Measured from NaF18- PET/CT Bone Scan Studies

Objectives

Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans.

Methods

A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past history of cancer and metabolic bone diseases including but not limited to osteoporosis, osteopenia and Paget’s disease. Eleven studies met all the criteria.

Results

The average normal SUV_max values from 11 patients were: cervical vertebrae 6.84 (range 4.38–8.64), thoracic vertebrae 7.36 (range 6.99–7.66), lumbar vertebrae 7.27 (range 7.04–7.72), femoral head 2.22 (range 1.1–4.3), humeral head 1.82 (range 1.2–2.9), mid sternum 5.51 (range 2.6–8.1), parietal bone 1.71 (range 1.3–2.4).

Conclusion

According to our study, various skeletal sites have different normal SUV values. SUV values can be different between the normal bones and bones with tumor or metabolic bone disease. SUV can be used to quantify NaF-18 PET/CT studies. If the SUV values of the normal skeleton are known, they can be used in the characterization of bone lesions and in the assessment of treatment response to bone diseases.     

Multicenter study of quantitative PET system harmonization using NIST-traceable 68Ge/68Ga cross-calibration kit

PurposeThe present study aimed to define the errors in SUV and demonstrate the feasibility of SUV harmonization among contemporary PET/CT scanners using a novel National Institute of Standards and Technology (NIST)-traceable ⁶⁸Ge/⁶⁸Ga source as the reference standard.MethodsWe used ⁶⁸Ge/⁶⁸Ga dose calibrator and PET sources made with same batch of ⁶⁸Ge/⁶⁸Ga embedded in epoxy that is traceable to the NIST standard. Bias in the amount of radioactivity and the radioactive concentrations measured by the dose calibrators and PET/CT scanners, respectively, was determined at five Japanese sites. We adjusted optimal dial setting of the dose calibrators and PET reconstruction parameters to close the actual amount of radioactivity and the radioactive concentration, respectively, of the NIST-traceable ⁶⁸Ge/⁶⁸Ga sources to harmonize SUV. Errors in SUV before and after harmonization were then calculated at each site.ResultsThe average bias in the amount of radioactivity and the radioactive concentrations measured by dose calibrator and PET scanner was −4.94% and −12.22%, respectively, before, and −0.14% and −4.81%, respectively, after harmonization. Corresponding averaged errors in SUV measured under clinical conditions were underestimated by 7.66%, but improved by −4.70% under optimal conditions.ConclusionOur proposed method using an NIST-traceable ⁶⁸Ge/⁶⁸Ga source identified bias in values obtained using dose calibrators and PET scanners, and reduced SUV variability to within 5% across different models of PET scanners at five sites. Our protocol using a standard source has considerable potential for harmonizing the SUV when contemporary PET scanners are involved in multicenter studies.     

Novel positron emission tomography/computed tomography of diffuse parenchymal lung disease combining a labeled somatostatin receptor analogue and 2-deoxy-2[18F]fluoro-D-glucose

We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue ??Ga-DOTATATE and 2-deoxy-2[1?F]fluoro-D-glucose (1?F-FDG) in diffuse parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for ??Ga-DOTATATE and 1?F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value [SUV(max)]) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with ??Ga-DOTATATE and 1?F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUV(max) was 2.2 ± 0.7 for ??Ga-DOTATATE and 2.8 ± 1.0 (t-test, p = .018) for 1?F-FDG. The mean ??Ga-DOTATATE SUV(max) in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p = .235) in NSIP patients. The correlation between ??Ga-DOTATATE SUV(max) and gas transfer (transfer factor of the lung for carbon monoxide [TLCO]) was r = -.34 (p = .127) and r = -.49 (p = .028) between 1?F-FDG SUV(max) and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of 1?F-FDG on PET.     

Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia.

Thermolability of 5,10-methylenetetrahydrofolate reductase (MTHFR) was examined as a possible cause of mild hyperhomocysteinemia in patients with premature vascular disease. Control subjects and vascular patients with mild hyperhomocysteinemia and with normohomocysteinemia were studied. The mean (+/- SD) specific MTHFR activity in lymphocytes of 22 control subjects was 15.6 (+/- 4.7) nmol CH2O/mg protein/h (range: 9.1-26.6), and the residual activity (+/- SD) after heat inactivation for 5 min at 46 degrees C was 55.3 (+/- 12.0)% (range: 35.9-78.3). By measurement of MTHFR activity, two distinct subgroups of hyperhomocysteinemic patients became evident. One group (n = 11) had thermolabile MTHFR with a mean (+/- SD) specific activity of 8.7 (+/- 2.1) nmol CH2O/mg protein/h (range: 5.5-12.7) and a residual activity, after heat inactivation, ranging from 0% to 33%. The other group (n = 28) had normal specific activity (+/- SD) of 21.5 (+/- 7.2) nmol CH2O/mg protein/h (range: 10.0-39.0) and a normal residual activity (+/- SD) of 53.8 (+/- 9.2)% (range: 33.1-71.5) after heat inactivation. The mean (+/- SD) specific activity of 29 normohomocysteinemic patients was 20.7 (+/- 6.5) nmol CH2O/mg protein/h (range: 9.4-33.8), and the mean (+/- SD) residual activity after heat inactivation was 58.2 (+/- 10.2)% (range: 43.0-82.0). Thus, in 28% of the hyperhomocysteinemic patients with premature vascular disease, abnormal homocysteine metabolism could be attributed to thermolabile MTHFR.     

Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes

This study aimed to investigate the influence of the preparation conditions on the performance of an ethosomal formulation for topical delivery of the local anesthetic agent, benzocaine (BZC). Ethosomes were prepared with different techniques, such as thin-layer evaporation, freezing and thawing, reverse-phase evaporation, extrusion and sonication, obtaining, respectively, multilayer vesicles (MLVs), frozen and thawed MLV (FATMLV), large unilamellar vesicles (LUVs), and small unilamellar vesicles (SUVs). The obtained vesicles were characterized for morphology, size, zeta potential, and entrapment efficiency (EE%), and their stability was monitored during storage at 4°C. In vitro permeation properties from gels incorporating drug ethosomal dispersions were evaluated in vitro by using artificial lipophilic membranes, while their anesthetic effect was determined in vivo on rabbits. The results suggested that the vesicle preparation method plays an important role in affecting the properties and effectiveness of ethosomal formulations. MLVs and LUVs exhibited higher drug EE% and better stability than FATMLV and SUV vesicles. The In vitro drug permeation rate was directly related to the vesicle EE% and varied in the order MLV>LUV≈FATMLV>SUV. The therapeutic efficacy of BZC ethosomal formulations was significantly improved with respect to the corresponding BZC solution. The best results, in terms of enhanced intensity of anesthetic effect, were given by formulations containing MLVs and LUVs, and the order of effectiveness was MLV≈LUV>FATMLV≈SUV, rather similar to that found in permeation studies. On the contrary, unexpectedly, the effectiveness order in increasing the duration of drug action was SUV≥MLV>LUV≈FATMLV. The highest efficacy of SUVs was probably due to the more intimate contact with the epithelium due to their greatest surface area, which allowed the longest extension of drug therapeutic action. The overall results suggest that a suitably developed ethosomal formulation of BZC can be of actual value for improving its clinical effectiveness in topical anesthesia.     

Antibody directed targeting of methotrexate-containing small unilamellar vesicles

Summary The potential of antibody-linked SUVs containing MTX in anticancer therapy was investigated. The SUVs, mean diameter 50±20 nm, were prepared by probe sonication of MTX-containing MLVs and were covalently linked either to a RAMG or NRG. After incubation with M21 melanoma cells for 2 h, RAMG-linked SUVs showed 2 and 4 times more binding than NRG-linked MTX-containing SUVs or MTX-containing SUVs unlinked to any Ig. Furthermore, on incubating M21 melanoma cells with RAMG-linked ³H MTX-containing SUVs for 2, 4, and 8 h at 4° C or 37° C, a higher radioactivity was associated with cells at 37° C than at 4° C. Membrane immunofluorescence revealed aggregation of and cap formation by RAMG-linked SUVs after 2 h (37° C) and endocytosis at 4 and 8 h at 37° C. Electron microscopic and autoradiographic studies confirmed aggregation of ³H MTX-containing SUVs around and on the surface of M21 cells. Electron microscopy also revealed these SUVs inside invaginations of and under the plasma membrane of melanoma cells. A colony inhibition assay showed that RAMG-linked, MTX-containing SUVs were 60 times, 8 times, and 4.5 times more growth inhibitory than free MTX, NRG-linked MTX-containing SUV, and MTX-containing SUVs unlinked to any Ig, but not toxic to a human kidney cancer line (that did not react with RAMG). Abbreviations used: DPPC, DL- -dipalmitoyl phosphatidylcholine; DTT, dithiothreitol; MTX, methotrexate; (MTX)SUV or MLV, MTX-containing SUV or MLV; MLV, multilamellar vesicle; NRG, normal rabbit immunoglobulin G; RAMG, rabbit antimelanoma IgG; SA, stearylamine; SPDP, N-succinimidy1-3-(2-pyridyldithio)propionate; SUV, small unilamellar vesicle; CHOL, cholesterol; LUV, large unilamellar vesicle; Ig, immunoglobulin; PDP-SA, N-[3-(2-pyridyldithio)-propinyl]stearylamine     

Fine needle aspiration outcomes of masses detected by positron emission tomography: correlation with standard uptake value

OBJECTIVES: To characterize the cytopathologic outcome of lesions detected on positron emission tomography (PET) scan. STUDY DESIGN: Cases with fine needle aspiration (FNA) performed because of a PET-positive lesion over an 18-month period were reviewed. Correlation with the standard uptake value (SUV) (using 2.5 as a cutoff value) was carried out. RESULTS: A total of 112 FNAs were found, of which 83 had adequate tissue for evaluation and available corresponding SUVs to be included in the final study. Fisher's exact test was carried out for correlation between FNA diagnosis and SUV Sixty-one (73.5%) lesions had an SUV > or = 2.5, 53 (87%) ofwhich were malignant and 8 (13%) benign on cytology. Twenty-two (26.5%) lesions had an SUV < 2.5, of which 12 (54.5%) showed benign and 10 (45.5%) showed malignant cytology. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of SUV were 84%, 60%, 87%, 56% and 78%, respectively. CONCLUSION: Our data show that FNA procedures performed for PET-positive lesions have high PPV, but low NPV. Therefore interpretation of PET SUV values < 2.5 as benign should be made with extreme caution.     

Les limites du SUV

The standardized uptake value (SUV) is the most used index to characterize the Fluorine-18-fluorodeoxyglucose (FDG) uptake in Positron Emission Tomography (PET). To better understand the potential of this index and its limitations, this article starts from the SUV definition, explains the different steps used to calculate the SUV, and shows the relationship between the SUV and the glucose metabolic rate. This analysis demonstrates the approximations and the sources of errors explaining why the SUV does not accurately represent the glucose metabolic rate. We also discuss why, despite the limitations of the SUV, it is useful in clinical routine and is currently the reference index used to roughly characterize the glucose metabolic rate. Finally, some ideas are presented that could facilitate the accurate characterization of the glucose metabolic rate from FDG PET scans in the future.     

Variation de la captation hépatique de 18-FDG dans l’évaluation intermédiaire des lymphomes B diffus à grandes cellules en TEP/TDM

IntroductionThe aim of this study was to evaluate the variability of 18F-FDG liver uptake at interim PET/CT among patients with high-grade lymphomas.MethodsForty-six patients with diffuse large B-cell lymphomas (DLBCL) who underwent 18F-FDG PET/CT at baseline (PET1) and after a few cycles of therapy (PET2) were included retrospectively. SUV mean normalized for body weight (SUVmean) and for lean body mass (SULmean) were obtained from 2-dimensional regions of interest (ROI) in the right lobe of the liver.ResultsLiver SUVmean values for the 46 patients were not different before and after the courses of chemotherapy. On univariate and multivariate analysis, liver SUVmean values increased with BMI (P = 0.0031). No significant correlation was found between delay post-injection, blood glucose level, age, gender and liver SUVmean. We found no statistically significant correlation between the liver SULmean or mediastinum SUVmean and studied variables. No factors affecting intrapatient hepatic uptake variation between PET1 and PET2 were found on correlation analysis.ConclusionAt interim PET in diffuse large B-cell lymphomas, liver SUVmean depends on BMI, but not liver SULmean. Caution is required when using liver SUV as reference in patients with high BMI.     

Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase,SUV39H1

Heterochromatin protein 1 (HP1) binds to the nucleosome via a methylated lysine residue 9 of histone H3 which is catalyzed by a histone methyltransferase such as SUV39H1. Although co-localization of HP1 and SUV39H1 has been evident in immunostaining and immunoprecipitation experiments, direct protein-protein interactions have remained to be characterized. We examined interactions between mouse HP1 alpha (mHP1 alpha) and SUV39H1 in yeast and in vitro. A yeast two-hybrid and a glutathione S-transferase pull-down study indicated that the chromo shadow domain of mHP1 alpha directly interacts with the N-terminal 39 amino acid stretch of SUV39H1. The IY165/168EE mutation in the chromo shadow domain of mHP1 alpha abrogated a self-interaction and this mutant did not interact with SUV39H1. The 13-mer peptide containing a consensus sequence for binding to the dimer surface formed by the chromo shadow domains inhibited interaction between mHP1 alpha and SUV39H1. It seems that self-interaction through the chromo shadow domain of HP1 is crucial for recruitment of SUV39H1 onto nucleosomes.     

Estimation of Noise-Free Variance to Measure Heterogeneity

Variance is a statistical parameter used to characterize heterogeneity or variability in data sets. However, measurements commonly include noise, as random errors superimposed to the actual value, which may substantially increase the variance compared to a noise-free data set. Our aim was to develop and validate a method to estimate noise-free spatial heterogeneity of pulmonary perfusion using dynamic positron emission tomography (PET) scans. On theoretical grounds, we demonstrate a linear relationship between the total variance of a data set derived from averages of n multiple measurements, and the reciprocal of n. Using multiple measurements with varying n yields estimates of the linear relationship including the noise-free variance as the constant parameter. In PET images, n is proportional to the number of registered decay events, and the variance of the image is typically normalized by the square of its mean value yielding a coefficient of variation squared (CV ²). The method was evaluated with a Jaszczak phantom as reference spatial heterogeneity (CV_r ²) for comparison with our estimate of noise-free or ‘true’ heterogeneity (CV _t ²). We found that CV _t ² was only 5.4% higher than CV _r ². Additional evaluations were conducted on 38 PET scans of pulmonary perfusion using ¹³NN-saline injection. The mean CV _t ² was 0.10 (range: 0.03–0.30), while the mean CV ² including noise was 0.24 (range: 0.10–0.59). CV _t ² was in average 41.5% of the CV ² measured including noise (range: 17.8–71.2%). The reproducibility of CV _t ² was evaluated using three repeated PET scans from five subjects. Individual CV _t ² were within 16% of each subject''s mean and paired t-tests revealed no difference among the results from the three consecutive PET scans. In conclusion, our method provides reliable noise-free estimates of CV _t ² in PET scans, and may be useful for similar statistical problems in experimental data.     

The effect of liposome size on the final lipid/DNA ratio of cationic lipoplexes

Several studies have demonstrated that lipoplexes are two-phase systems over most mixing lipid/DNA charge ratios. Because these studies have focused on small unilamellar vesicles (SUV), they leave open the question as to whether a similar pattern is followed by other liposome types. The main purpose of this work is to examine the question further by characterizing the assembly of cationic lipoplexes prepared from 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM)/dioleoylphosphatidylethanolamine (DOPE) (1:1) liposomes of various types. Sedimentation in sucrose density gradients reveals that large unilamellar vesicles (LUV) and sedimented multilamellar vesicles (sMLV), as opposed to SUV, form lipoplexes that exist as a single phase over a relatively broad range of mixing (+/-) ratios. This is indicated by observing that most of the LUV and sMLV become involved in the assembly reaction up to mixing (+/-) ratios of 4 and 9, respectively, while only a small and constant fraction of SUV associates with DNA at all mixing (+/-) ratios tested. Consequently, while maximal (+/-) ratios of approximately 4.5 and 9 are found in LUV and sMLV lipoplexes, respectively, a final (+/-) ratio of only approximately 2 is determined in SUV lipoplexes. Isothermal titration calorimetry shows that this is the lowest possible charge ratio achieved when liposomes are titrated with DNA. Based on these observations and on the size differences of the liposomes used, a model of lipoplex formation is proposed.