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Papers - Iwabuchi, Yu

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A diagnostic strategy for Parkinsonian syndromes using quantitative indices of DAT SPECT and MIBG scintigraphy: an investigation using the classification and regression tree analysis

Iwabuchi Y., Kameyama M., Matsusaka Y., Narimatsu H., Hashimoto M., Seki M., Ito D., Tabuchi H., Yamada Y., Jinzaki M.

European Journal of Nuclear Medicine and Molecular Imaging (European Journal of Nuclear Medicine and Molecular Imaging) 48 ( 6 ) 1833 - 1841 2021

ISSN 16197070

Purpose: We aimed to evaluate the diagnostic performances of quantitative indices obtained from dopamine transporter (DAT) single-photon emission computed tomography (SPECT) and I-metaiodobenzylguanidine (MIBG) scintigraphy for Parkinsonian syndromes (PS) using the classification and regression tree (CART) analysis. Methods: We retrospectively enrolled 216 patients with or without PS, including 80 without PS (NPS) and 136 with PS [90 Parkinson’s disease (PD), 21 dementia with Lewy bodies (DLB), 16 progressive supranuclear palsy (PSP), and 9 multiple system atrophy (MSA). The striatal binding ratio (SBR), putamen-to-caudate ratio (PCR), and asymmetry index (AI) were calculated using DAT SPECT. The heart-to-mediastinum uptake ratio (H/M) based on the early (H/M [Early]) and delayed (H/M [Delay]) images and cardiac washout rate (WR) were calculated from MIBG scintigraphy. The CART analysis was used to establish a diagnostic decision tree model for differentiating PS based on these quantitative indices. Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.5, 96.3, 93.3, 92.9, and 93.1 for NPS; 91.1, 78.6, 75.2, 92.5, and 83.8 for PD; 57.1, 95.9, 60.0, 95.4, and 92.1 for DLB; and 50.0, 98.0, 66.7, 96.1, and 94.4 for PSP, respectively. The PCR, WR, H/M (Delay), and SBR indices played important roles in the optimal decision tree model, and their feature importance was 0.61, 0.22, 0.11, and 0.05, respectively. Conclusion: The quantitative indices showed high diagnostic performances in differentiating NPS, PD, DLB, and PSP, but not MSA. Our findings provide useful guidance on how to apply these quantitative indices in clinical practice. 123

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[123I]-IMP single-photon emission computed tomography imaging in visual snow syndrome: A case series

Shibata M., Tsutsumi K., Iwabuchi Y., Kameyama M., Takizawa T., Nakahara T., Fujiwara H., Jinzaki M., Nakahara J., Dodick D.W.

Cephalalgia (Cephalalgia) 40 ( 14 ) 1671 - 1675 2020.12

ISSN 03331024

© International Headache Society 2020. Background: Visual snow syndrome (VSS) is a neurological condition characterized by persistent flickering dots in the visual fields, palinopsia, enhanced entoptic phenomenon, photophobia, and nyctalopia. Neuroimaging evidence supports the role of the visual association cortex in visual snow syndrome. Case series: We provided clinical care to three patients with visual snow syndrome, in whom [123I]-IMP single-photon emission computed tomography (SPECT) imaging was performed. Case 1 was a 21-year-old male with a past history of migraine with aura who exhibited visual snow and entoptic phenomenon. In this patient, [123I]-IMP SPECT imaging revealed right occipital and temporal hypoperfusion with a distribution matching the ventral visual stream. [123I]-IMP SPECT imaging detected only mild bilateral frontal hypoperfusion in Case 2 and no overt abnormalities in Case 3. Conclusion: Although visual snow syndrome seems to be a heterogenous condition, our observations indicate that abnormal visual processing within the ventral visual stream may play a role in the pathogenesis of this condition.

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Development of 68Ga-labeled tin colloids for evaluating phagocytic function of Kupffer cells using preclinical PET imaging

Matsusaka Y., Nakahara T., Takahashi K., Iwabuchi Y., Nakamura S., Jinzaki M.

Annals of Nuclear Medicine (Annals of Nuclear Medicine) 34 ( 11 ) 807 - 814 2020.11

ISSN 09147187

© 2020, The Japanese Society of Nuclear Medicine. Objective: This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. Methods: 68Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to 68Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000 nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60 min. PET scanning was performed for 30 min after intravenous administration of 68Ga-tin colloid solution (4 MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. Results: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). Conclusions: 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.

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Egested Feces Revealed Massive Protein Loss in 99mTc-HSA-D Scintigraphy

Matsusaka Y., Nakahara T., Iwabuchi Y., Owaki Y., Narimatsu H., Jinzaki M.

Clinical Nuclear Medicine (Clinical Nuclear Medicine) 45 ( 7 ) e329 - e330 2020.07

ISSN 03639762

© 2020 Wolters Kluwer Health, Inc. All rights reserved. A 66-year-old man with severe diarrhea and severe hypoproteinemia was referred for 99mTc-DTPA-human serum albumin (HSA-D) scintigraphy. The scintigraphy at 24 hours postinjection showed strong accumulation of 99mTc-HSA-D in not only the colon but also all his diapers containing his egested feces. The ratio of the diapers counts to the total counts was 17.0%, and a considerable amount of protein loss was confirmed. 99mTc-HSA-D scintigraphy has an important role in diagnosing protein-losing enteropathy, but the abdomen is the only routinely scanned area. Additional scanning of egested radiotracer and the whole body can be useful for evaluating the disease severity.

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Usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for predicting the prognosis and treatment response of neoadjuvant therapy for pancreatic ductal adenocarcinoma

Yokose T., Kitago M., Matsusaka Y., Masugi Y., Shinoda M., Yagi H., Abe Y., Oshima G., Hori S., Endo Y., Toyama K., Iwabuchi Y., Takemura R., Ishii R., Nakahara T., Okuda S., Jinzaki M., Kitagawa Y.

Cancer Medicine (Cancer Medicine) 9 ( 12 ) 4059 - 4068 2020.06

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Background: The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC. Methods: Forty-two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors. Results: Twenty-two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P =.017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut-off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse-free survival (hazard ratio [HR], 3.92; P =.044) and overall survival (HR, 14.08; P =.023). Conclusions: PERCIST was more accurate in determining NAT’s therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC.

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Focal 123I-MIBG Uptake in the Medial Segment of the Normal Liver

Matsusaka Y., Nakahara T., Iwabuchi Y., Minami Y., Jinzaki M.

Clinical Nuclear Medicine (Clinical Nuclear Medicine) 44 ( 3 ) e170 - e171 2019.03

ISSN 03639762

© 2019 Wolters Kluwer Health, Inc. All rights reserved. An 84-year-old man with parkinsonism was referred for 123 I-MIBG scintigraphy. Abnormal uptake in the right upper abdomen was incidentally seen in planar image, and SPECT revealed focal uptake in the medial segment (S4) of the liver. Subsequent triple-phase contrast-enhanced CT showed no evidence of hepatic tumors, although in the arterial phase, there were an enhanced region corresponding to the uptake area and the enhanced vein of Sappey that flowed into S4. In this case, the focal 123 I-MIBG uptake would be attributable to hemodynamic change in the liver.

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Impact of a combination of quantitative indices representing uptake intensity, shape, and asymmetry in DAT SPECT using machine learning: comparison of different volume of interest settings

Iwabuchi Y., Nakahara T., Kameyama M., Yamada Y., Hashimoto M., Matsusaka Y., Osada T., Ito D., Tabuchi H., Jinzaki M.

EJNMMI Research (EJNMMI Research) 9 2019

© 2019, The Author(s). Background: We sought to assess the machine learning-based combined diagnostic accuracy of three types of quantitative indices obtained using dopamine transporter single-photon emission computed tomography (DAT SPECT)—specific binding ratio (SBR), putamen-to-caudate ratio (PCR)/fractal dimension (FD), and asymmetry index (AI)—for parkinsonian syndrome (PS). We also aimed to compare the effect of two different types of volume of interest (VOI) settings from commercially available software packages DaTQUANT (Q) and DaTView (V) on diagnostic accuracy. Methods: Seventy-one patients with PS and 40 without PS (NPS) were enrolled. Using SPECT images obtained from these patients, three quantitative indices were calculated at two different VOI settings each. SBR-Q, PCR-Q, and AI-Q were derived using the VOI settings from DaTQUANT, whereas SBR-V, FD-V, and AI-V were derived using those from DaTView. We compared the diagnostic value of these six indices for PS. We incorporated a support vector machine (SVM) classifier for assessing the combined accuracy of the three indices (SVM-Q: combination of SBR-Q, PCR-Q, and AI-Q; SVM-V: combination of SBR-V, FD-V, and AI-V). A Mann-Whitney U test and receiver-operating characteristics (ROC) analysis were used for statistical analyses. Results: ROC analyses demonstrated that the areas under the curve (AUC) for SBR-Q, PCR-Q, AI-Q, SBR-V, FD-V, and AI-V were 0.978, 0.837, 0.802, 0.906, 0.972, and 0.829, respectively. On comparing the corresponding quantitative indices between the two types of VOI settings, SBR-Q performed better than SBR-V (p = 0.006), whereas FD-V performed better than PCR-Q (p = 0.0003). No significant difference was observed between AI-Q and AI-V (p = 0.56). The AUCs for SVM-Q and SVM-V were 0.988 and 0.994, respectively; the two different VOI settings displayed no significant differences in terms of diagnostic accuracy (p = 0.48). Conclusion: The combination of the three indices obtained using the SVM classifier improved the diagnostic performance for PS; this performance did not differ based on the VOI settings and software used.

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Impact of the cerebrospinal fluid-mask algorithm on the diagnostic performance of 123I-Ioflupane SPECT: an investigation of parkinsonian syndromes

Iwabuchi Y., Nakahara T., Kameyama M., Matsusaka Y., Minami Y., Ito D., Tabuchi H., Yamada Y., Jinzaki M.

EJNMMI Research (EJNMMI Research) 9 ( 1 ) 2019

© 2019, The Author(s). Background: A cerebrospinal fluid (CSF)-mask algorithm has been developed to reduce the adverse influence of CSF-low-counts on the diagnostic utility of the specific binding ratio (SBR) index calculated with Southampton method. We assessed the effect of the CSF-mask algorithm on the diagnostic performance of the SBR index for parkinsonian syndromes (PS), including Parkinson’s disease, and the influence of cerebral ventricle dilatation on the CSF-mask algorithm. Methods: We enrolled 163 and 158 patients with and without PS, respectively. Both the conventional SBR (non-CSF-mask) and SBR corrected with the CSF-mask algorithm (CSF-mask) were calculated from 123I-Ioflupane single-photon emission computed tomography (SPECT) images of these patients. We compared the diagnostic performance of the corresponding indices and evaluated whether the effect of the CSF-mask algorithm varied according to the extent of ventricle dilatation, as assessed with the Evans index (EI). A receiver-operating characteristics (ROC) analysis was used for statistical analyses. Results: ROC analyses demonstrated that the CSF-mask algorithm performed better than the non-CSF-mask (no correction, area under the curve [AUC] = 0.917 [95% confidence interval (CI) 0.887–0.947] vs. 0.895 [95% CI 0.861–0.929], p < 0.001; attenuation correction, AUC = 0.930 [95% CI 0.902–0.957] vs. 0.903 [95% CI 0.870–0.936], p < 0.001). When not corrected for attenuation, no significant difference in the AUC was observed in the low EI group between the non-CSF-mask and CSF-mask algorithms (0.927 [95% CI 0.877–0.978] vs. 0.942 [95% CI 0.898–0.986], p = 0.11); in the middle and high EI groups, the CSF-mask algorithm performed better than the non-CSF-mask algorithm (middle EI group, AUC = 0.894 [95% CI 0.825–0.963] vs. 0.872 [95% CI 0.798–0.947], p < 0.05; high EI group, AUC = 0.931 [95% CI 0.883–0.978] vs. 0.900 [95% CI 0.840–0.961], p < 0.01). When corrected for attenuation, significant differences in the AUC were observed in all three EI groups (low EI group, AUC = 0.961 [95% CI 0.924–0.998] vs. 0.942 [95% CI 0.895–0.988], p < 0.05; middle EI group, AUC = 0.905 [95% CI 0.843–0.968] vs. 0.872 [95% CI 0.800–0.944], p < 0.005; high EI group, AUC = 0.954 [95% CI 0.917–0.991] vs. 0.917 [95% CI 0.862–0.973], p < 0.005). Conclusion: The CSF-mask algorithm improved the performance of the SBR index in informing the diagnosis of PS, especially in cases with ventricle dilatation.

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Bilateral Adrenal Hyperplasia Due to Adrenocorticotropic Hormone-Secreting Esthesioneuroblastoma on FDG PET and 111In-Pentetreotide Scintigraphy

Matsusaka Y., Nakahara T., Kurihara I., Iwabuchi Y., Jinzaki M.

Clinical Nuclear Medicine (Clinical Nuclear Medicine) 43 ( 6 ) 452 - 453 2018.06

ISSN 03639762

© 2018 Wolters Kluwer Health, Inc. All rights reserved. A 53-year-old woman with metastatic esthesioneuroblastoma was referred for FDG PET/CT imaging. FDG PET/CT showed symmetrical uptake in bilaterally enlarged adrenal glands, in addition to abnormal uptake in bone and lymph node metastases. 111In-pentetreotide scintigraphy was further performed and revealed the lack of adrenal uptake. The patient's serum adrenocorticotropic hormone (ACTH) level was extremely high, suggesting that hyperplastic condition in the adrenal glands due to ACTH stimulation from the metastatic esthesioneuroblastoma was responsible for increased FDG uptake. The combination of FDG PET and 111In-pentetreotide scintigraphy was useful for the pathophysiological evaluation of ACTH-secreting esthesioneuroblastoma.

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Quantitative evaluation of the tracer distribution in dopamine transporter SPECT for objective interpretation

Iwabuchi Y., Nakahara T., Kameyama M., Yamada Y., Hashimoto M., Ogata Y., Matsusaka Y., Katagiri M., Itoh K., Osada T., Ito D., Tabuchi H., Jinzaki M.

Annals of Nuclear Medicine (Annals of Nuclear Medicine) 32 ( 5 ) 363 - 371 2018.06

ISSN 09147187

© 2018, The Japanese Society of Nuclear Medicine. Purpose: Quantification of the tracer distribution would add objectivity to the visual assessments of dopamine transporter (DAT) single photon emission computed tomography (SPECT) data. Our study aimed to evaluate the diagnostic utility of fractal dimension (FD) as a quantitative indicator of tracer distribution and compared with the conventional quantitative value: specific binding ratio (SBR). We also evaluated the utility of the combined index SBR/FD (SBR divided by FD). Materials and methods: We conducted both clinical and phantom studies. In the clinical study, 150 patients including 110 patients with Parkinsonian syndrome (PS) and 40 without PS were enrolled. In the phantom study, we used a striatal phantom with the striatum chamber divided into two spaces, representing the caudate nucleus and putamen. The SBR, FD, and SBR/FD were calculated and compared between datasets for evaluating the diagnostic utility. Mann–Whitney test and receiver-operating characteristics (ROC) analysis were used for analysis. Results: ROC analysis revealed that the FD value had high diagnostic performance [the areas under the curve (AUC) = 0.943] and the combined use of SBR and FD (SBR/FD) delivered better results than the SBR alone (AUC, 0.964 vs 0.899; p < 0.001). The sensitivity, specificity, and accuracy, respectively, were 79.1, 85.0, and 80.7% with SBR, 84.5, 97.5, and 88.0% with FD, and 92.7, 87.5, and 91.3% with SBR/FD. Conclusion: Our results confirmed that the FD value is a useful diagnostic index, which reflects the tracer distribution in DAT SPECT images. The combined use of SBR and FD was more useful than either used alone.

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Preclinical evaluation of heat-denatured [ 18 F]FDG-labeled red blood cells for detecting splenic tissues with PET in rats

Matsusaka Y., Nakahara T., Takahashi K., Iwabuchi Y., Ogata Y., Nishime C., Kajimura M., Jinzaki M.

Nuclear Medicine and Biology (Nuclear Medicine and Biology) 56 26 - 30 2018.01

ISSN 09698051

© 2017 Elsevier Inc. Introduction Heat-denatured 99m Tc-labeled red blood cells (RBCs) are used for detecting splenic tissues with scintigraphy. The present study aimed to evaluate the feasibility of using heat-denatured [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)-labeled RBCs in detecting splenic tissues using positron emission tomography (PET) in rats. Methods RBCs were washed with phosphate buffered saline, labeled with [ 18 F]FDG at 38°C, and heat-denatured at 50°C for 15 min. In vitro stability was assessed by measuring extracellular radioactivity during the 0–180 min incubation at 37°C. Thin layer chromatography (TLC) of the extracellular fluid was performed. The autologous RBCs were intravenously injected in four rats and PET scanning was simultaneously performed for 30 min. Time-activity curves of several organs, including the spleen, were analyzed on the PET images. Results Labeling efficiency was 92%. Low levels of radioactivity were released from the labeled RBCs for 180 min. TLC revealed that 80% of the released radioactivity was due to [ 18 F]FDG-6-phosphate. Whole body images showed strong uptake of heat-denatured [ 18 F]FDG-labeled RBCs in the spleen soon after injection in all four rats. Time-activity curves revealed that the splenic uptake continued to increase for 30 min and the amount of radioactivity in the other organs, except the urinary bladder, decreased after the initial surge. Conclusions Heat-denatured [ 18 F]FDG-labeled RBCs are suitable spleen-specific agents for PET. This method is clinically relevant as an alternative for heat-denatured 99m Tc-labeled RBC scintigraphy.

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Diagnostic imaging of bladder cancer

Akita H., Iwabuchi Y., Jinzaki M.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 72 ( 7 ) 514 - 525 2018

ISSN 03852393

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