A Clinical Quantitative Evaluation of Hepatobiliary Transport of [11C]Dehydropravastatin in Humans Using Positron Emission Tomography.

Various positron emission tomography (PET) probes have been developed to assess in vivo activities in humans of drug transporters, which aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, sodium (3R, 5R)-3, 5-dihydroxy-7-((1S, 2S, 6S, 8S)-6-hydroxy-2-methyl-8- ((1-[11C]-(E)-2-methyl-but-2-enoyl) oxy) -1, 2, 6, 7, 8, 8a-hexahydronaphthalen-1-yl) heptanoate ([11C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps (gene symbol SLCO) and Mrp2 (gene symbol ABCC2) in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [11C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion. After intravenous injection, [11C]DPV rapidly distributed to the liver and kidney followed by secretion into the bile and urine. Rifampicin significantly reduced the liver distribution of [11C]DPV 3-fold, resulting in a 7.5-fold reduced amount of excretion into the bile and the delayed elimination of [11C]DPV from the blood circulation. The hepatic uptake clearance (CLuptake, liver) and canalicular efflux clearance (CLint, bile) of [11C]DPV (544 ± 204 and 10.2 ± 3.5 µl/min per gram liver, respectively) in humans were lower than the previously reported corresponding parameters in rats (1800 and 298 µl/min per gram liver, respectively) (Shingaki et al., 2013). Furthermore, rifampicin treatment significantly reduced CLuptake, liver and CLint, bile by 58% and 44%, respectively. These results suggest that PET imaging with [11C]DPV is an effective tool for quantitatively characterizing the OATP1Bs and MRP2 functions in the human hepatobiliary transport system.

[Using Super Resolution to Denoise on PET Images].

A high-resolution display panel comes to practical use, but the resolution of the indicated contents does not change. The up-sampling processing is applied to indication of the low-resolution contents. In the up-sampling process, the super resolution enables an up-sampling process which estimates information of high frequency components lost by sampling while analyzing input images is noticed. In this paper, we aimed at reconstructing an image of normal resolution in which the influence of statistical noise is reduced by applying super resolution after down-sampling processing is applied to positron emission tomography (PET) image with many statistical noises. To evaluate the noise reduction effect, we compared it with the Gaussian filter which is frequently used to reduce the influence of the statistical noise of the PET image. A 3D Hoffman brain phantom was used to evaluate objectively by peak signal-to-noise ratio and power spectral density. The objective index of the PET image applying super resolution is positive results, suggesting the possibility of being useful as compared with the conventional method.

Scatter Correction of Septal Penetration for 123I-IMP Cerebral Blood Flow SPECT Adding Radioactivity from the Outside of Field of View-Comparison between Simulation-based and Multi-window Scatter Corrections.

PURPOSE: The N-Isopropyl-p-[123I] Iodoamphetamine (123I-IMP) SPECT imaging reduces the image quality and quantitative accuracy due to scatter and septal penetration occurred by radioactive uptake from outside of the field of view such as the lungs. We evaluated the influence of scatter and septal penetration using phantom-simulated radioactivity from outside of the field of view, and subsequently compared the effect of scatter and septal penetration corrections between the simulation-based effective scatter source estimation (ESSE) method and the multi-window method (ellipse approximation method). METHODS: We used the phantom filled with 10 and 25 kBq/mL for the brain and lung parts corresponding to radioactive concentration in the clinical study. The SPECT images were acquired with and without lung phantom using low-energy high-resolution (LEHR) and cardiac high-resolution (CHR) collimators. We quantitatively evaluated a brain phantom by count analysis and coefficient of variation as reference data without lung phantom simulated the radioactivity from outside of the field of view, and compared between two scatter corrections by each collimator. RESULTS: The brain count in cerebral base with the ESSE method using LEHR collimator was higher than that of the ellipse approximation method. The whole brain count with the ellipse approximation method using CHR collimator shows 28.8% lower than the ESSE method, so that it suggests that the ellipse approximation method for LEHR collimator and the ESSE method for CHR collimator was close to reference counts. The coefficient of variation of the ESSE method was lower than that of the ellipse approximation method for both two collimators. CONCLUSIONS: It was possible to correct the scatter and penetration from outside the field of view with high accuracy, by using the ellipse approximation method with LEHR collimator and the ESSE method with CHR collimator.

Diagnostic ability of (99m)Tc-HSA-DTPA scintigraphy in combination with SPECT/CT for gastrointestinal bleeding.

PURPOSE: Gastrointestinal (GI) bleeding scintigraphy in combination with single-photon emission computed tomography/computed tomography (SPECT/CT) remains to be studied in detail. This study aimed to examine the diagnostic ability of this tool. METHODS: GI bleeding scintigraphy using (99m)Tc-human serum albumin-diethylenetriaminepentaacetic acid was performed for 38 patients with suspected GI bleeding. Twenty-four patients were diagnosed using planar images alone (planar group) and 14 patients were diagnosed using planar images and additional SPECT/CT images (planar + SPECT/CT group). The diagnostic ability of each method was analyzed. RESULTS: GI bleeding was observed in 20 of the 38 patients. For the existence of GI bleeding, planar images alone showed a sensitivity of 70%, specificity of 93%, positive predictive value (PPV) of 88%, negative predictive value (NPV) of 81%, and an overall accuracy of 83%, whereas planar images + SPECT/CT showed a sensitivity of 100%, specificity of 75%, PPV of 91%, NPV of 100%, and an overall accuracy of 93%. The source of bleeding was accurately diagnosed in 50% in the planar group and 78% in the planar + SPECT/CT group. In the planar + SPECT/CT group, 44% of the evaluable patients showed correct localization of the source of GI bleeding by additional SPECT/CT images, although planar images only showed incorrect localization. CONCLUSION: GI bleeding scintigraphy in combination with SPECT/CT is a noninvasive and useful tool for the examination of GI bleeding.

[Bilateral filter applied to bone scintigraphy].

The aim of this study is to improve the image quality using a post process rather than a correction process at acquisition time. We used a smoothing filter that is widely used on a compact digital camera. Especially for nuclear medicine, when we use a short acquisition time, we will get images that have a large increase in statistical noise. For those images, we validated the efficiency of the smoothing filter by assessing two characteristic parameters. In addition, we defined the best smoothing filter parameters to get stable images that reduced the influence of statistical noise.

[Development of Dose Management Software Using Visual Basic for Applications and Dose Evaluation in the Field of Nuclear Medicine].

PURPOSE: The purpose of this study was to develop software for smooth dose management based on the Japan diagnostic reference levels (DRLs 2020) in the field of nuclear medicine. METHOD: Using the programming language Visual Basic for Applications (VBA), we implemented a function for calculating actual doses, a function for comparing doses at one's own facility with those of DRLs 2020, a function for calculating appropriate doses for pediatric nuclear medicine examinations, and so on. In addition, we evaluated actual doses before and after the software implementation. RESULT: The software enabled easy calculation of actual doses and comparison with DRLs 2020 for smooth dose management. Furthermore, we were able to use the results of dose evaluation to determine the dosage at our facility and to use them as a reference for optimization. CONCLUSION: In the field of nuclear medicine, it is possible to manage doses in accordance with DRLs 2020 by introducing own software into our clinical practice.

Deep learning-based detection of parathyroid adenoma by 99mTc-MIBI scintigraphy in patients with primary hyperparathyroidism.

OBJECTIVE: It is important to detect parathyroid adenomas by parathyroid scintigraphy with 99m-technetium sestamibi (99mTc-MIBI) before surgery. This study aimed to develop and validate deep learning (DL)-based models to detect parathyroid adenoma in patients with primary hyperparathyroidism, from parathyroid scintigrams with 99mTc-MIBI. METHODS: DL-based models for detecting parathyroid adenoma in early- and late-phase parathyroid scintigrams were, respectively, developed and evaluated. The training dataset used to train the models was collected from 192 patients (165 adenoma cases, mean age: 64 years ± 13, 145 women) and the validation dataset used to tune the models was collected from 45 patients (30 adenoma cases, mean age: 67 years ± 12, 37 women). The images were collected from patients who were pathologically diagnosed with parathyroid adenomas or in whom no lesions could be detected by either parathyroid scintigraphy or ultrasonography at our institution from June 2010 to March 2019. The models were tested on a dataset collected from 44 patients (30 adenoma cases, mean age: 67 years ± 12, 38 women) who took scintigraphy from April 2019 to March 2020. The models' lesion-based sensitivity and mean false positive indications per image (mFPI) were assessed with the test dataset. RESULTS: The sensitivity was 82% [95% confidence interval 72-92%] with mFPI of 0.44 for the scintigrams of the early-phase model and 83% [73-92%] with mFPI of 0.31 for the scintigrams of the delayed-phase model in the test dataset, respectively. CONCLUSIONS: The DL-based models were able to detect parathyroid adenomas with a high sensitivity using parathyroid scintigraphy with 99m-technetium sestamibi.

Advantages of upright position imaging with medium-energy collimator for sentinel node lymphoscintigraphy in breast cancer patients.

OBJECTIVE: To evaluate the advantage of upright position imaging with a medium-energy collimator for the detection of sentinel lymph node (SLN). METHODS: Thirty-four patients with operable breast cancer underwent sentinel node lymphoscintigraphy with 99mTc-tin colloid. Images were obtained in 5 different positions and paired images from the same patient were compared using side-by-side interpretation. Images were compared in 3 groups: group 1 (anterior view); supine (SAV) vs. upright (UAV), group 2 (oblique view); supine (SOV) vs. upright (UOV), and group 3 (oblique view); modified supine (MOV) vs. UOV. Image quality was evaluated using a 3-grade scale of clear, faint, and equivocal depiction, and correlated to 3 parameters: distance from injection site to lymph node (hot node), counts in hot node, and image contrast. Parameters in group 1 were compared by classifying the primary tumor site into 4 subregions. RESULTS: Image quality in all 3 groups was more enhanced on the image obtained in the upright position than that in the supine position. Obtaining images in an upright position increased the mean distances by 1.5-3.2 cm, and mean contrasts were significantly increased by 0.13-0.31 (p < 0.05). It was shown that image quality was more greatly affected by image contrast than by counts in the hot node. Image contrast of 0.5 seemed an appropriate threshold level for detection of the hot node. On comparison of tumor sites, the upper outer quadrant (C) region of the 4 subregions demonstrated greater contrast enhancement on upright position images. CONCLUSION: Clinical images obtained in an upright position with a medium-energy collimator were superior to those obtained in a supine position. Use of this procedure is recommended to enhance lymph node detection on sentinel node lymphoscintigraphy.

Usefulness of medium-energy collimator for sentinel node lymphoscintigraphy imaging in breast cancer patients.

UNLABELLED: This study was performed to investigate the usefulness of a general-purpose medium-energy (ME) collimator for the accurate localization of the sentinel lymph node (SLN) in breast cancer patients. METHODS: We compared phantom images and lymphoscintigraphy images obtained under different conditions for a patient with breast cancer. Comparisons were performed between 2 cameras, between a low-energy high-resolution (LEHR) collimator and a general-purpose ME collimator, and between energy windows centered at 141 keV and at 146 keV. Profile curves and image contrast were evaluated along with the visual interpretation of images. The most suitable imaging time was selected from the relationship between contrast and the data acquisition time. RESULTS: The images obtained with the general-purpose ME collimator and the energy window centered at 141 keV were of poorer quality than those obtained with the LEHR collimator and the same energy window. However, the quality of the images obtained with the general-purpose ME collimator improved when the energy window was centered at 146 keV. The method involving the general-purpose ME collimator and the energy window centered at 146 keV showed excellent image quality similar to that obtained with the LEHR collimator. The enhancement of contrast was confirmed at more than 3 cm away from the center of the injection site. Stable contrast was obtained with a data acquisition time of 5 min, with the general-purpose ME collimator, and with the energy window centered at 146 keV. CONCLUSION: The method involving the general-purpose ME collimator and the energy window centered at 146 keV has the merit of the lymph node not being concealed by a lead shield. This new method is expected to improve the rate of detection of SLN and has the potential for shortening the acquisition time.

Usefulness of standardized uptake value normalized by individual CT-based lean body mass in application of PET response criteria in solid tumors (PERCIST).

Our aim in this study was to verify the usefulness of the standardized uptake value (SUV) normalized by individual CT-based lean body mass (LBMCT) in application of PET response criteria in solid tumors (PERCIST).We retrospectively investigated 14 patients (4 male and 10 female) with malignant lymphoma who were undergoing chemotherapy. (18)F-FDG PET/CT examinations were performed before and after chemotherapy. The LBMCT was calculated by estimation of fat weight from CT data (from skull base to pelvis). The mean ± standard deviation (SD) and the Bland-Altman plot were used for comparison among body weight, LBMCT, and LBM derived from a predictive equation (LBMPE). Indices for FDG uptake in the liver were: SUV, SUV based on LBMPE (SULPE), and SUV based on LBMCT (SULCT). Overall differences between the uptake values were analyzed by one-way ANOVA. If the ANOVA showed significance, differences between uptake values were investigated further by use of the Tukey-Kramer test. The mean values of body weight, LBMPE, and LBMCT were: 55.4 ± 14.9 (39.0-112.0), 43.0 ± 10.5 (31.3-75.2), and 35.3 ± 9.8 (23.4-75.8) kg, respectively. There was a wide dispersion between LBMPE and LBMCT (differences, 7.6 ± 3.6 kg; 95 % CI, 6.42-8.85). LBMPE was higher than LBMCT in all the cases except in Case 11. The mean uptake values significantly differed among SUV, SULPE, and SULCT (F = 68.3, p < 0.05). Whereas SULPE deviated from PERCIST criteria in seven patients, SULCT satisfied the criteria except in one case. These results suggest that liver SULCT is useful for application of PERCIST.

[Usefulness of imaging method without using lead plate for sentinel lymph node scintigraphy].

PURPOSE: In scintigraphy of the sentinel lymph node, it is common to use a lead plate as a shield to reduce star artifact and scattered radiation in the portion surrounding the injected site of radioactive colloid. We have developed an imaging method without using a lead plate, and examined its usefulness in phantom and clinical imagings. METHODS, RESULTS: Star artifact was eliminated using a medium energy collimator. Effects of scattered radiation from the injection site were reduced by setting energy window at higher level. CONCLUSIONS: Our method without using a lead plate can be applied to dynamic data acquisition and imaging of a portion where it is difficult to place a lead plate. It also seems to be a useful imaging method in that it takes patients' feelings into consideration.

Validation of threshold method for myocardial control database by use of clinical data.

A database is an important factor in the statistical analysis of myocardial scintigraphy. Our aim in this study was to verify the validity of the threshold method using phantoms and to create a clinical database using this method. Since this method involves artificially excluding a low count area on a polar map, we created a myocardial phantom with defects. Then, we applied this method to the construction of a control database (CDB) for which we used stress-rest scans of 152 male and 52 female Japanese patients. The clinical relevance of this database was investigated by comparison of the values between the CDB and a Japanese normal database. In the study evaluation, we mainly used the summed extent score (SES) and a severity map (severity). Data from the phantom with defects demonstrated that the threshold method could compensate for defective areas, enabling the use of data for the creation of the CDB. Comparison of the CDB with the Japanese normal database showed a good relationship with respect to the SES and severity (Initial post-stress: SES: r = 0.978; severity: r = 0.997, Redistribution: SES: r = 0.944; severity: r = 0.993). The threshold method facilitates the effective creation of a database by use of clinical data. This enables individual institutions to build their own databases, taking into account differences in collection and processing conditions between institutions as well as the characteristics of individual equipment.

Subcutaneous Extravasation of Sr-89: Usefulness of Bremsstrahlung Imaging in Confirming Sr-89 Extravasation and in the Decision Making for the Choice of Treatment Strategies for Local Radiation Injuries Caused by Sr-89 Extravasation.

A male patient in his 20s presented at our clinic with pain caused by bone metastases of the primitive neuroectodermal tumor, and Sr-89 was administrated to palliate the pain. After receiving the injection, the patient complained of a slight burning pain at the catheterized area. Slight reddening and small circular swelling (diameter, 0.5 cm) were observed at the catheterized area. Sr-89 extravasation was suspected. To estimate the amount of subcutaneous Sr-89 leakage, bremsstrahlung imaging was immediately performed. We speculated that the skin-absorbed dose from subcutaneous infiltration of Sr-89 was 1.78 Gy. The mildest clinical sign of local radiation injury was erythema. The received dose was higher than 3 Gy, and the time of onset was from 2 to 3 weeks. In our patient, local radiation injuries (LRIs) did not occur. Though requiring further verification, subsequent bremsstrahlung imaging and estimation of the skin-absorbed dose from the subcutaneous infiltration of Sr-89 are useful in confirming Sr-89 extravasation and in the decision making for the choice of treatment strategies for LRIs caused by Sr-89 extravasation.