Impact of irregular waveforms on data-driven respiratory gated PET/CT images processed using MotionFree algorithm.

OBJECTIVES: MotionFree® (AMF) is a data-driven respiratory gating (DDG) algorithm for image processing that has recently been introduced into clinical practice. The present study aimed to verify the accuracy of respiratory waveform and the effects of normal and irregular respiratory motions using AMF with the DDG algorithm. METHODS: We used a NEMA IEC body phantom comprising six spheres (37-, 28-, 22-, 17-, 13-, and 10 mm diameter) containing 18F. The sphere-to-background ratio was 4:1 (21.2 and 5.3 kBq/mL). We acquired PET/CT images from a stationary or moving phantom placed on a custom-designed motion platform. Respiratory motions were reproduced based on normal (sinusoidal or expiratory-paused waveforms) and irregular (changed amplitude or shifted baseline waveforms) movements. The "width" parameters in AMF were set at 10-60% and extracted data during the expiratory phases of each waveform. We verified the accuracy of the derived waveforms by comparing those input from the motion platform and output determined using AMF. Quantitative accuracy was evaluated as recovery coefficients (RCs), improvement rate, and %change that were calculated based on sphere diameter or width. We evaluated statistical differences in activity concentrations of each sphere between normal and irregular waveforms. RESULTS: Respiratory waveforms derived from AMF were almost identical to the input waveforms on the motion platform. Although the RCs in each sphere for expiratory-paused and ideal stationary waveforms were almost identical, RCs except the expiratory-paused waveform were lower than those for the stationary waveform. The improvement rate decreased more for the irregular, than the normal waveforms with AMF in smaller spheres. The %change was improved by decreasing the width of waveforms with a shifted baseline. Activity concentrations significantly differed between normal waveforms and those with a shifted baseline in spheres < 28 mm. CONCLUSIONS: The PET images using AMF with the DDG algorithm provided the precise waveform of respiratory motions and the improvement of quantitative accuracy in the four types of respiratory waveforms. The improvement rate was the most obvious in expiratory-paused waveforms, and the most subtle in those with a shifted baseline. Optimizing the width parameter in irregular waveform will benefit patients who breathe like the waveform with the shifted baseline.

Promotion of ABCG2 gene expression by neolignans from Piper longum L.

We focused on Piper longum L., a herbal drug produced in Myanmar, which has a renoprotective effect. Thus, we attempted to isolate and identify compounds that enhance the expression of the ABCG2 gene from the aerial parts of the plant except for the fruit. Among the various P. longum extracts, we isolated and identified the components. Using Caco-2 cells, the hABCG2 mRNA expression-enhancing effects of the isolated compounds were compared with the positive reference compound (3-methylcholanthrene [3MC]) using real-time polymerase chain reaction. Six compounds were isolated and identified from the methanol extract of P. longum. Among the isolated compounds, licarin A and neopomatene had lower toxicity and higher hABCG2 mRNA expression-enhancing effects in Caco-2 cells. Suppression of hAhR expression by siRNA reduced the activity of licarin A and neopomatene, as well as the hAhR agonist 3MC, suggesting that these 2 compounds may act as hAhR agonists to promote hABCG2 expression.

Reproducibility of the principal component analysis (PCA)-based data-driven respiratory gating on texture features in non-small cell lung cancer patients with 18 F-FDG PET/CT.

OBJECTIVE: Texture analysis is one of the lung cancer countermeasures in the field of radiomics. Even though image quality affects texture features, the reproducibility of principal component analysis (PCA)-based data-driven respiratory gating (DDG) on texture features remains poorly understood. Hence, this study aimed to clarify the reproducibility of PCA-based DDG on texture features in non-small cell lung cancer (NSCLC) patients with 18 F-Fluorodeoxyglucose (18 F-FDG) Positron emission tomography/computed tomography (PET/CT). METHODS: Twenty patients with NSCLC who underwent 18 F-FDG PET/CT in routine clinical practice were retrospectively analyzed. Each patient's PET data were reconstructed in two PET groups of no gating (NG-PET) and PCA-based DDG gating (DDG-PET). Forty-six image features were analyzed using LIFEx software. Reproducibility was evaluated using Lin's concordance correlation coefficient ( ρ c ${\rho _c}$ ) and percentage difference (%Diff). Non-reproducibility was defined as having unacceptable strength ( ρ c $({\rho _c}$  < 0.8) and a %Diff of >10%. NG-PET and DDG-PET were compared using the Wilcoxon signed-rank test. RESULTS: A total of 3/46 (6.5%) image features had unacceptable strength, and 9/46 (19.6%) image features had a %Diff of >10%. Significant differences between the NG-PET and DDG-PET groups were confirmed in only 4/46 (8.7%) of the high %Diff image features. CONCLUSION: Although the DDG application affected several texture features, most image features had adequate reproducibility. PCA-based DDG-PET can be routinely used as interchangeable images for texture feature extraction from NSCLC patients.

Development of a new quantification method using partial volume effect correction for individual energy peaks in 111In-pentetreotide SPECT/CT.

Objectives: Somatostatin receptor scintigraphy (SRS) using 111In-pentetreotide has no established quantification method. The purpose of this study was to develop a new quantitative method to correct the partial volume effect (PVE) for individual energy peaks in 111In-pentetreotide single-photon emission computed tomography (SPECT). Methods: Phantom experiments were performed to construct a new quantitative method. In the phantom experiments, a NEMA IEC body phantom was used. Acquisition was performed using two energy peaks (171 keV and 245 keV) on the SPECT/CT system. The volume of interest was set at each hot sphere and lung insert in the SPECT images of each energy peak, and the recovery coefficient (RC) was calculated to understand the PVE. A new quantitative index, the indium uptake index (IUI), was calculated using the RC to correct the PVE. The quantitative accuracy of the IUI in the hot sphere was confirmed. Case studies were performed to clarify the quantitative accuracy. In a case study, the relationship between the IUI and the Krenning score, which is used as a visual assessment, was evaluated for each lesion. Results: The obtained RCs showed that the energy peak at 171 keV was faster in recovering the effect of PVE than that at 245 keV. The IUI in the 17-mm-diameter hot sphere was overestimated by 4.8% and 8.3% at 171 keV and 245 keV, respectively, compared to the actual IUIs. The relationship between IUI and Krenning score was rs=0.773 (p<0.005) at sum, rs=0.739 (p<0.005) at 171 keV, and rs=0.773 (p<0.005) at 245 keV. Conclusion: We have developed a new quantification method for 111In-pentetreotide SPECT/CT using RC-based PVE correction for an individual energy peak of 171 keV. The quantitative accuracy of this method was high even for accumulations of less than 20 mm, and it showed a good relationship with the Krenning score; therefore, the clinical usefulness of IUI was demonstrated.

Comparison of skeletal segmentation by deep learning-based and atlas-based segmentation in prostate cancer patients.

OBJECTIVE: We aimed to compare the deep learning-based (VSBONE BSI) and atlas-based (BONENAVI) segmentation accuracy that have been developed to measure the bone scan index based on skeletal segmentation. METHODS: We retrospectively conducted bone scans for 383 patients with prostate cancer. These patients were divided into two groups: 208 patients were injected with 99mTc-hydroxymethylene diphosphonate processed by VSBONE BSI, and 175 patients were injected with 99mTc-methylene diphosphonate processed by BONENAVI. Three observers classified the skeletal segmentations as either a "Match" or "Mismatch" in the following regions: the skull, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, pelvis, sacrum, humerus, rib, sternum, clavicle, scapula, and femur. Segmentation error was defined if two or more observers selected "Mismatch" in the same region. We calculated the segmentation error rate according to each administration group and evaluated the presence of hot spots suspected bone metastases in "Mismatch" regions. Multivariate logistic regression analysis was used to determine the association between segmentation error and variables like age, uptake time, total counts, extent of disease, and gamma cameras. RESULTS: The regions of "Mismatch" were more common in the long tube bones for VSBONE BSI and in the pelvis and axial skeletons for BONENAVI. Segmentation error was observed in 49 cases (23.6%) with VSBONE BSI and 58 cases (33.1%) with BONENAVI. VSBONE BSI tended that "Mismatch" regions contained hot spots suspected of bone metastases in patients with multiple bone metastases and showed that patients with higher extent of disease (odds ratio = 8.34) were associated with segmentation error in multivariate logistic regression analysis. CONCLUSIONS: VSBONE BSI has a potential to be higher segmentation accuracy compared with BONENAVI. However, the segmentation error in VSBONE BSI occurred dependent on bone metastases burden. We need to be careful when evaluating multiple bone metastases using VSBONE BSI.

[Effects of CT-based Attenuation Correction on PET Images Using Data-driven Respiratory Gating].

PURPOSE: We applied deviceless, positron emission tomography/computed tomography(PET/CT) data-driven respiratory gating (DDG) to validate the effects of misalignment between PET and CT at various respiratory phases. METHODS: A lung lesion was simulated using an NEMA IEC body phantom in which the background comprised hot spheres containing polystyrene foam beads. We acquired PET images as the phantom moved downwards and then stopped. Attenuation on computed tomography images acquired at the inspiratory, stationary, and expiratory phases was corrected after the phantom stopped moving. Normalized mean square error (NMSE), recovery coefficients (RCmax and RCmean) and volume were analyzed on DDG-PET images using CT-based attenuation correction. RESULTS: The NMSE was closest to 0 in PET images corrected using the expiratory CT image. The RCmax was<1.0, and the RCmean was closest to 1.0 only in PET images corrected using the expiratory CT image. Volume was either underestimated or overestimated more according to the size of the spheres when the alignment of CT and PET images was greater. CONCLUSION: We recommend using the expiratory but not the inspiratory phase when using DDG for PET/CT correction.

Effect of Compounds from Moringa oleifera Lam. on in Vitro Non-Alcoholic Fatty Liver Disease (NAFLD) Model System.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in the world, with a prevalence of 25 % in many countries. To date, no drug has been approved to treat NAFLD, therefore, the use of phytochemicals to prevent this disease is meaningful. In this study, we focused on the effects of Moringa oleifera Lam. on diabetes, attempted to isolate compounds that regulate NAFLD. Compounds 1 and 2 were isolated from the ethyl acetate fraction of M. oleifera. Spectral data revealed that they were 1-hydroxy-3-phenylpropan-2-yl benzoate (1) and benzyl benzylcarbamate (2), respectively. The three-dimensional structure of compound 1 was determined by single crystal X-ray structural analysis. Neither compound was toxic to HepG2 cells, and compound 1 was found to have a concentration-dependent inhibitory effect on intracellular lipid accumulation induced by stimulation of linoleic acid (LA). As a result of measuring the effects of compound 1 on the intracellular lipid production-related protein, it was found that compound 1 enhanced protein expression that promotes lipolysis. On the other hand, since the action of compound 1 was similar to that of PPARα agonists, it is deduced that compound 1 enhanced the activity of PPARα and further enhanced the expression of lipolytic proteins, which is related to the suppression of intracellular lipid accumulation. Furthermore, as the result of docking simulation, compound 1 had a higher binding affinity to the ligand binding site of PPARα than fenofibrate, which is a PPARα agonist, and thus compound 1 was considered to be promising as an agonist of PPARα.

Patient arm position during quantitative bone single-photon emission computed tomography/computed tomography acquisition can affect image quality and quantitative accuracy: a phantom study.

PURPOSE: The present study used a phantom to determine the effects of various arm positions on bone SPECT/computed tomography (CT) images and the optimal arm position to acquire good-quality and quantitatively accurate images. MATERIALS AND METHODS: We designed a phantom study of five simulated arm positions that are assumed during SPECT image acquisition. All SPECT data were acquired during a total of 120 projections of 10 and 100 s/view over 360° in a non-circular mode and reconstructed using Flash 3D (Siemens Healthineers). We evaluated contrast (QH,17 mm), image noise (NB,17 mm), contrast-to-noise ratios (QNRs), and visual scores according to the guidelines for bone SPECT acquisition protocols published by the Japanese Society of Nuclear Medicine Technology. The SUVmean, SUVmax, and SUVpeak were calculated and quantitative errors were evaluated using the recovery coefficient (RC) and the root means square error (RMSE). RESULTS: The spatial resolution of SPECT images was better when the arms were down than raised with simulated shoulder disorders. Raised arms with shoulder disorders significantly increased the NB,17 mm and decreased the QH,17 mm, and the QNR in each image differed over a range from 2.2 to 5.2. The visual score was >1.5 with the arms down, raised normally, and raised with moderate shoulder disorders. The SUVmax and SUVpeak were overestimated compared with 100-min data for all images, whereas SUVmean was underestimated. Raised arms with a shoulder disorder decreased RCmax, and RCmean and RCpeak suppressed differences among arm positions. In addition, RMSE with the arms down and raised normally were close to that for 100-min data. CONCLUSION: Bone SPECT images with good quality and quantitative accuracy can be acquired with patients holding their arms down by their sides. This will help patients with shoulder pain who have difficulties raising their arms.

Evaluation of bone metastasis burden as an imaging biomarker by quantitative single-photon emission computed tomography/computed tomography for assessing prostate cancer with bone metastasis: a phantom and clinical study.

Metabolic bone volume (MBV), standardized uptake value (SUV), and total bone uptake (TBU) are new imaging biomarkers for quantitative bone single-photon emission computed tomography/computed tomography. The purpose of this study was to validate the quantitative accuracy and utility of MBV, SUVmean, and TBU for the assessment of bone metastases in prostate cancer. We used a bone-specific phantom with four hot spheres (φ = 13, 17, 22, 28 mm) filled with different Tc-99 m activities to simulate uptake ratios of 3 and 7, corresponding to normal and metastatic values. We calculated the error ratio (%Error) by comparing MBV, SUVmean, and TBU with true values for various parameters, including bone lesion size, uptake ratio, and SUV cut-off level. Differences for MBV, SUVmean, TBU, and bone scan index (BSI) were calculated to verify their utility in assessing bone metastases. Receiver-operating characteristic curve (ROC) analysis was performed to calculate the area under the curve (AUC) for each biomarker. MBV, SUVmean, and TBU were affected by lesion size, uptake ratio, and SUV cut-off level; however, TBU demonstrated the most stable %Error. The TBU %Error was within 15% in spheres 17 mm or larger when the SUV cut-off level was 7, regardless of the uptake ratio. The ROC analyses revealed the AUCs of BSI (0.977) and TBU (0.968). Additionally, TBU was able to assess bone metastasis when BSI provided false-negative results, but TBU also provided false-positive results by degenerative changes. The synergy between TBU and BSI could potentially improve diagnostic accuracy.

Technical Note: Development of an ischemic defect model insert attachable to a commercially available myocardial phantom.

OBJECTIVE: The purpose of this study was to develop a novel myocardial phantom insert model that attaches to commercially available myocardial phantoms and simulates an ischemic area, using three-dimensional printing technology. METHODS: Ischemic inserts were designed to give four levels of absolute percent contrast (Low; 10%, Medium; 20%, High; 35%, and Defect; 100%) using CT images and computer-aided design software. The ischemic insert was composed of multiple slit structures to replicate myocardial ischemia. Myocardial phantom images with developed ischemic inserts were acquired using a SPECT/CT system and were then reconstructed using filtered back projection (FBP) and iterative reconstruction (IR) with various cutoff frequencies of a Butterworth filter. The performance and utility of ischemic inserts were evaluated according to percent contrast and 5-point scoring. RESULTS: The percent contrast and scoring results changed according to the ischemic insert type, cutoff frequency, and reconstruction method. The percent contrast of each insert obtained by FBP with 0.4 cycles/cm was 4.1% (Low), 15.7% (Medium), 17.4% (High), and 36.1% (Defect). Similarly, the percent contrast of each insert obtained by IR with 0.4 cycles/cm was 5.0% (Low), 17.0% (Medium), 21.9% (High), and 47.7% (Defect). CONCLUSIONS: We successfully developed an ischemic insert that attaches to a commercially available myocardial phantom by using CT imaging and 3D printing technology. Our proposed ischemic insert provided several abnormal perfusion patterns on myocardial SPECT images and may be useful for evaluating SPECT image quality.

Diagnostic performance of a computer-assisted diagnostic system: sensitivity of BONENAVI for bone scintigraphy in patients with disseminated skeletal metastasis is not so high.

PURPOSE: Bone scintigraphy (BS) of disseminated skeletal metastasis is sometimes misinterpreted as normal. The use of computer-assisted diagnosis (CAD) may resolve this problem. We investigated the performance of a CAD system, BONENAVI, in the diagnosis of disseminated skeletal metastasis. METHODS: Cases of disseminated skeletal metastasis were selected from a BS log. These patients' BSs were analyzed by BONENAVI to obtain an artificial neural network (ANN) and bone scan index (BSI). Clinical features (type of primary cancer, CT type, and BS type) were compared with the BONENAVI (ANN and BSI) results. The BS findings (diffuse increased axial skeleton uptake, inhomogeneity of uptake, proximal extremity contrast, and degree of renal uptake) and ANN or BSI were evaluated. Then, negative ANN patients were presented. RESULTS: Fifty-four patients were diagnosed as having disseminated skeletal metastasis. Regarding the primary cancers, 12 had prostate cancer, 16 gastric cancers, 16 breast cancers, and 10 miscellaneous cancers. Total sensitivity of ANN (≥ 0.5) was 76% (41/54). ANN values correlated with the BS type among clinical features. Diffuse increased axial skeleton uptake was mostly correlated with ANN of the BS findings. CONCLUSION: The BONENAVI CAD system was partially helpful in diagnosing disseminated skeletal metastasis, but the sensitivity of BONENAVI was not sufficient and underestimated the disseminated skeletal metastasis. Further improvement of this CAD system is necessary to improve the detectability of disseminated skeletal metastasis.

A novel biomarker, active whole skeletal total lesion glycolysis (WS-TLG), as a quantitative method to measure bone metastatic activity in breast cancer patients.

OBJECTIVE: There is no good response evaluation method for skeletal metastasis. We aimed to develop a novel quantitative method to evaluate the response of skeletal metastasis, especially lytic lesions, for treatment. METHODS: A method to measure active bone metastatic burden quantitatively using F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) in breast cancer patients, whole skeletal total lesion glycolysis (WS-TLG), a summation of each skeletal lesion's TLG, was developed. To identify active bone lesions, a tentative cutoff value was decided using FDG-PET/CT in 85 breast cancer patients without skeletal metastasis and 35 with skeletal metastasis by changing the cutoff value. Then, the WS-TLG method was evaluated by comparing to PET Response Criteria in Solid Tumor (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria for only bone in 15 breast cancer patients with skeletal metastasis who were treated. RESULTS: A cutoff value of the standardized uptake value (SUV) = 4.0 gave 91% (77/85) specificity and 97% (34/35) sensitivity. We decided on SUV = 4.0 as a tentative cutoff value. Skeletal metastases of lytic and mixed types showed higher WS-TLG values than those of blastic or intertrabecular types, although statistical significance was not tested. All 15 patients showed agreement with PERCIST or EORTC in the therapeutic bone response. CONCLUSION: This quantitative WS-TLG method appears to be a good biomarker to evaluate skeletal metastasis in breast cancer patients, especially lytic or mixed types. Further clinical studies are warranted to assess the clinical values of this new WS-TLG method.

[Administration Accuracy of Automated Infusion Device for PET Using Improved Disposable Kit].

PURPOSE: The AI-300 automated infusion device (Sumitomo Heavy Industries, Ltd., Tokyo, Japan) is subject to administration error as a function of smaller volumes of 18F-FDG dispensed via a three-way cock supplied with a disposable kit. The present study aimed to validate the administration accuracy of the AI-300 using an improved disposable kit for quantitative positron emission tomography (PET) assessment. METHODS: We determined administration accuracy between the improved and previous disposable kits by measuring variations in dispensed volumes and radioactive concentrations of 18F-FDG according to the criteria of the Japanese Society of Nuclear Medicine. A reference value was generated by measuring radioactivity using a standard dose calibrator. RESULTS: The values obtained using the previous kit deviated from the reference values by a maximum of -10.6%, and the deviation depended on dispensed volumes of 18F-FDG<0.25 mL. In contrast, the values were relatively stable when using the improved kit with dispensed 18F-FDG volumes < 0.25 mL. Variations in radioactive concentrations were relatively stable using the improved kit, whereas that of the previous kit was slightly unstable at high radioactive concentrations. CONCLUSION: The administration accuracy of the AI-300 using the previous kit varied considerably according to smaller dispensed volumes, but the improved kit might alleviate this problem. The present results indicated that the improved disposal kit should be immediately implemented to eliminate uncertainty surrounding quantitative PET findings.

Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients.

OBJECTIVES: To establish a new three-dimensional quantitative evaluation method for bone metastasis, we applied bone single photon emission tomography with computed tomography (SPECT/CT). The total bone uptake (TBU), which measures active bone metastatic burden, was calculated as the sum of [mean uptake obtained as standardized uptake value (SUV) above a cut-off level] × (the volume of the lesion) in the trunk using bone SPECT/CT. We studied the threshold value and utility of TBU in prostate cancer patients treated with radium-223 (Ra-223) therapy. METHODS: To establish the threshold value of TBU, we compared bone metastatic and non-metastatic regions in 61 prostate cancer patients with bone metastasis and 69 without. Five fixed sites in each patient were selected as evaluation points and divided into bone metastatic and non-metastatic sites. Sensitivity and specificity analysis was applied to establish the threshold level. Using the obtained threshold value, we then calculated the TBU in nine prostate cancer patients who received Ra-223 therapy, and compared the results with the bone scan index (BSI) by BONENAVI® and visual evaluation of bone scintigraphy. RESULTS: Uptake was significantly lower in non-metastatic sites in patients with bone metastasis than in patients without metastasis. Sensitivity and specificity analysis revealed SUV = 7.0 as the threshold level. There was a discrepancy between TBU and BSI change in two of the nine patients, in whom TBU change correlated with visual judgement, but BSI change did not. In two patients, BSI was nearly 0 throughout the course, but the TBU was positive and changed, although the change was not large. These results suggest that TBU may be more accurate and sensitive than BSI for quantitative evaluation of active bone metastatic burden. CONCLUSION: We established a threshold value (SUV > 7.0) for three-dimensional TBU for evaluating active bone metastatic burden in prostate cancer patients using bone SPECT/CT. Despite the small number of patients, we expect the change in TBU could be more accurate and sensitive than the change in BSI among patients who received Ra-223.

[A Comparison of Planar Sensitivity and Spatial Resolution among Different Collimators and Energy Windows on 223Ra Imaging].

OBJECTIVE: The present study aimed to reveal the influence of combination of different collimators and energy windows on the planar sensitivity and the spatial resolution during experimental 223Ra imaging, and to determine optimal imaging parameters. METHODS: A vial type source containing 223Ra solution (4.55 MBq / 5.6 ml) was placed in the air at 100 mm away from the collimator surface. Planar images were acquired with LEHR, LMEGP, ELEGP and MEGP collimators on two dual-head gamma cameras (Symbia intevo (Siemens) and Infinia 3 (GE)). We compared three energy window combinations: 1) single window at 82 keV, 2) double window at 82+154 keV, 3) triple window at 82+154+270 keV. The energy spectrum, the sensitivity and the spatial resolution, such as full-width at half-maximum (FWHM) and full-width at tenth-maximum (FWTM), of each collimator were assessed. RESULTS: Five energy spectra (at around 82, 154, 270, 351 and 405 keV) were essentially observed among four collimators. The sensitivity was high for LEHR collimator, then ELEGP and LMEGP collimator was 3-4 fold, which is greater than MEGP collimator. The 82 keV energy window of four collimators has best spatial resolution. Moreover, the spatial resolution of the 82 keV energy window with LMEGP and ELEGP collimator was almost equal to that of the triple window with MEGP collimator. CONCLUSIONS: Optimal imaging parameters were single energy window using LMEGP or ELEGP, and then triple energy window using MEGP collimator.

Optimization of a shorter variable-acquisition time for legs to achieve true whole-body PET/CT images.

The present study aimed to qualitatively and quantitatively evaluate PET images as a function of acquisition time for various leg sizes, and to optimize a shorter variable-acquisition time protocol for legs to achieve better qualitative and quantitative accuracy of true whole-body PET/CT images. The diameters of legs to be modeled as phantoms were defined based on data derived from 53 patients. This study analyzed PET images of a NEMA phantom and three plastic bottle phantoms (diameter, 5.68, 8.54 and 10.7 cm) that simulated the human body and legs, respectively. The phantoms comprised two spheres (diameters, 10 and 17 mm) containing fluorine-18 fluorodeoxyglucose solution with sphere-to-background ratios of 4 at a background radioactivity level of 2.65 kBq/mL. All PET data were reconstructed with acquisition times ranging from 10 to 180, and 1200 s. We visually evaluated image quality and determined the coefficient of variance (CV) of the background, contrast and the quantitative %error of the hot spheres, and then determined two shorter variable-acquisition protocols for legs. Lesion detectability and quantitative accuracy determined based on maximum standardized uptake values (SUVmax) in PET images of a patient using the proposed protocols were also evaluated. A larger phantom and a shorter acquisition time resulted in increased background noise on images and decreased the contrast in hot spheres. A visual score of ≥ 1.5 was obtained when the acquisition time was ≥ 30 s for three leg phantoms, and ≥ 120 s for the NEMA phantom. The quantitative %errors of the 10- and 17-mm spheres in the leg phantoms were ± 15 and ± 10%, respectively, in PET images with a high CV (scan < 30 s). The mean SUVmax of three lesions using the current fixed-acquisition and two proposed variable-acquisition time protocols in the clinical study were 3.1, 3.1 and 3.2, respectively, which did not significantly differ. Leg acquisition time per bed position of even 30-90 s allows axial equalization, uniform image noise and a maximum ± 15% quantitative accuracy for the smallest lesion. The overall acquisition time was reduced by 23-42% using the proposed shorter variable than the current fixed-acquisition time for imaging legs, indicating that this is a useful and practical protocol for routine qualitative and quantitative PET/CT assessment in the clinical setting.

Calculation Accuracy of Gross Tumor Volume at the Diaphragm Boundary Evaluated Using Respiratory-gated PET/CT.

OBJECTIVE: The present study aimed to clarify gross tumor volume (GTV) contouring accuracy at the diaphragm boundary using respiratory-gated PET/CT. METHODS: The lung/diaphragm boundary was simulated using a phantom containing 18F solution (10.6 kBq/mL). Tumors were simulated using spheres (diameter, 11-38 mm) containing 18F and located at the positions of the lungs and liver. The tumor background ratios (TBR) were 2, 4, and 8. The phantom was moved from the superior to inferior direction with a 20-mm motion displacement at 3.6 s intervals. The recovery coefficient (RC), volume RC (VRC), and standardized uptake value (SUV) threshold were calculated using stationary, non-gated (3D), and gated (4D) PET/CT. RESULTS: In lung cancer simulation, RC and VRC in 3D PET images were, respectively, underestimated and overestimated in smaller tumors, whereas both improved in 4D PET images regardless of tumor size and TBR. The optimal SUV threshold was about 30% in 4D PET images. In liver cancer simulation, RC and VRC were, respectively, underestimated and overestimated in smaller tumors, and when the TBR was lower, but both improved in 4D PET images when tumors were >17 mm and the TBR was >4. The optimal SUV threshold tended to depend on the TBR. CONCLUSIONS: The contouring accuracy of GTV was improved by considering TBR and using an optimal SUV threshold acquired from 4D PET images.

Validation of Cross-calibration Schemes for Quantitative Bone SPECT/CT Using Different Sources under Various Geometric Conditions.

PURPOSE: Several cross-calibration schemes have been proposed to produce quantitative values in bone SPECT imaging. Differences in the radionuclide sources and geometric conditions can decrease the accuracy of cross-calibration factor (CCF). The present study aimed to validate the effects of calibration schemes using different sources under various geometric conditions. METHODS: Temporal variations as well as variations in acquisition counts and the shapes of 57Co standard and 99mTc point sources and a 99mTc disk source were determined. The effects of the geometric conditions of the source-to-camera distance (SCD) and lateral distance on the CCF were investigated by moving the camera or source away from the origin. The system planar sensitivity of NEMA incorporated into a Symbia Intevo SPECT/CT device (Siemens®) was defined as reference values. RESULTS: The temporal variation in CCF using the 57Co source was relatively stable within the range of 0.7% to 2.3%, whereas the 99mTc source ranged from 2.7% to 7.3%. In terms of source shape, the 57Co standard point source was the most stable. Both SCD and lateral distance decreased as a function of distance from the origin. Errors in the geometric condition were higher for the 57Co standard point source than the 99mTc disk source. CONCLUSIONS: Different calibration schemes influenced the reliability of quantitative values. The 57Co standard point source was stable over a long period, and this helped to maintain the quality of quantitative SPECT/CT imaging data. The CCF accuracy of the 99mTc source decreased depending on the preparative method. The method of calibration for quantitative SPECT should be immediately standardized to eliminate uncertainty.

Diagnostic performance of a computer-assisted diagnosis system for bone scintigraphy of newly developed skeletal metastasis in prostate cancer patients: search for low-sensitivity subgroups.

PURPOSE: The computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems. METHODS: An artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient's situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded. RESULTS: BONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion. CONCLUSIONS: BONENAVI with BS has good sensitivity and specificity for detecting prostate cancer's osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.