• ⽣存期間の短縮 • 癌死亡 Nakajima K. et al. International Journal of Urology (2017) 24, 668-73.（⼀部改変） 0.0 0.2 0.4 AUC EB: 0.94 BN1: 0.95 BN2: 0.96 AUC EB: 0.86 BN1: 0.91 BN2: 0.92 0.0 0.2 0.4 1-Specificity 0.6 0.8 1.0 0.0 0.2 0.4 1-Specificity 0.6 0.8 1.0 Sens 0.0 0.2 0.4 Sen with (a) prostate and (b) breast cancer. The artificial neural network of the software was trained using databases in Sweden (EXINI bone; EB), Japan (BONENAVI 1; BN1) and revised in Japan (BN2). The area under the receiver operating characteristic curve (AUC) is equally high in patients with prostate cancer, but improved with BN2 in patients with breast cancer.12 Table 1 Application of BSI in patients with prostate cancer Author and reference number Year No. patients Patients or study setting BSI cut-off and prognosis Sabbatini et al.13 1999 191 Androgen independent prostate cancer from a randomized trial BSI of <1.4%, 1.4–5.1% and >5.1% (median survivals of 18.3, 15.5 and 8.1 months, respectively) Meirelles et al.23 2010 43 Progressing prostate cancer with bone metastasis BSI >1.27 and <1.27 (median survival of 14.7 and 28.2 months, respectively) Dennis et al.17 2012 81 Metastatic CRPC in four clinical trials Doubling in BSI, 1.9-fold increase in risk of death; change in BSI, prognostic at 3 and 6 months on treatment Mitsui et al.18 2012 42 CRPC patients with taxane-based chemotherapy Reduction in BSI showing longer overall survival Ulmert et al.14 2012 384 Prostate cancer cases in two large population-based cohorts BSI groups of 0, 0.01–1.00 and >1.00 correlated prostate cancer death Kaboteh et al.19 2013 130 High-risk prostate cancer patients receiving primary hormonal therapy 5-year probability of survival: 55% for patients without metastases, 42% for BSI <1, 31% for BSI 1–5 and 0% for BSI >5 Kaboteh et al.24 2013 266 Prostate cancer patients with chemotherapy 2-year survival for patients with increasing and decreasing BSI from baseline to follow-up scans: 18% and 57%, respectively Reza et al.25 2014 146 Prostate cancer patients during androgen deprivation therapy BSI groups of 0, 0.01–1.00 and >1.00 correlated prostate cancer death (5-year survival rates of 80%, 60% and 25%, respectively) Armstrong et al.26 2014 201 Randomized double-blind trial of tasquinimod in men with metastatic CRPC BSI worsening at 12 weeks, prognostic for progression-free survival; patients with BSI >1.0 showing reduced survival Uemura et al.27 2016 41 Patients with metastatic CRPC treated with docetaxel Patients with BSI >1 showing shorter overall survival than patients with BSI ≤1 Miyoshi et al.28 2016 60 Hormone-naive prostate cancer patients with bone metastases Median OS: not reached in patients with BSI ≤1.9, 34.8 months in patients with BSI >1.9 Poulsen et al.29 2016 88 Patients with prostate cancer awaiting initiation of androgen-deprivation therapy Patients with BSI ≥1, significantly shorter overall survival than patients with BSI <1 52% 予後評価においては転移の数 よりもEODが重要 Armstrong AJ . et al. JAMA Oncol. 2018;4(7):944-51
ൠతʹ༻͍ΒΕΔࢹ֮తʹೝΊΔߴूੵ෦Ґͱศٓ ɽ݁ɹՌ 2-1 શͰͷධՁ ɹݪը૾͓Αͼॲཧը૾ͷ BONENAVI ղੳ݁ ۉΛ Table 1 ʹɼࢄਤΛ Fig. 1 ʹࣔ͢ɽࠎస Table 1 Comparison of ANN value, BSI, and number of hotspots for raw and processed images ANN BSI No. of hotspots Bone metastases (n=10) Raw image 0.72±0.30 3.201±4.015 10.2±7.7 Processed image 0.70±0.31 3.193±4.084 9.9±7.5 P value 0.161 0.859 0.317 No bone metastases (n=47) Raw image 0.14±0.19 0.083±0.288 1.5±3.8 Processed image 0.12±0.19 0.070±0.272 1.0±2.5 P value 0.024 0.031 0.006 mean±standard deviation 市川 肇 他. ⽇放技学誌 70(5);2014 461-6. Planar processing Original 投与量の適正化（低投与量化）に伴って有⽤性はさらに⾼まる!? 前⽴腺癌患者57例︓全例 740MBq投与 16%
of tumor bone with a reference part for di erent acquisition times in the Swi Scan planar image. (a) Contrat to noise ratio (CNR), (b) the percent of the coe cient of variance (% CV). LEHR low-energy high-resolution, LEHRS low-energy high-resolution and sensitivity. Shibutani T. et al. Scientific Reports 2021; 11:2644 25%収集時間の短縮が可能 m/scientificreports/ Figure 5. e phantom image of Swi Scan planar processing. Upper, middle and lower rows show the 100%, 75% and 50% acquisition time, respectively. e 100% acquisition corresponds to the clinical condition. LEHR
Res Int. 2017; 2017:7039406. Threshold A: ⾻転移(+) Threshold B: ⾻転移(-) Metastatic Total Whole-body SPECT/CT ndings Final diagnosis Nonmetastatic Equivocal Metastatic Total A; nonmetastatic; B equivocal; C metastatic. T : Sensitivity and speci city % con dence intervals (CI) of planar with targeted SPECT/CT versus whole-body SPECT/CT. reshold A reshold B Sensitivity Speci city Sensitivity Speci city WB SPECT/CT ( . ; ) . ( . ; . ) . ( . ; . ) ( . ; ) Targeted SPECT/CT . ( . ; . ) . ( . ; . ) . ( . ; . ) . ( . ; . ) Di erence and exact % CI . [ . – . ] . [− . – . ] . [ . – . ] . [− . – . ] value . . . . T : Repartition of extra-axial scintigraphic ndings on targeted SPECT/CT and whole-body SPECT/CT in relation to nal diagnosis. A B C Total Targeted SPECT/CT ndings Final diagnosis Nonmetastatic
be maps to ECT im- e the ex- the CT mage fu- rrection ons of e the re- ed near c lesion images. itfalls in lesions. tions on efully in- ntigrams d on CT ive fol- able image fusion in the thorax region in kere E, Bombardieri E. Bone scintigraphy Figure 6 Figure 6: Graphs show ROC curves representing findings of scintigraphic image (dashed line), separate datasetsofscintigraphicandCTimages(thinsolidline),andfusedimages(thicksolidline).(a)ROCcurve forreviewer1;(b)ROCcurveforreviewer2.FPFϭfalse-positivefraction,Sϭbonescintigraphicimages alone,andTPFϭtrue-positivefraction. spectedBoneMetastasis Utsunomiyaetal Utsunomiya D. et al. Radiology: 2006 238(1); 264-71. Figure 2 Figure 2: Diagnostic confidence scores of three reviews each for reviewers (a) 1 and (b) 2. (1 ϭ definitely not metastasis, 2 ϭ probably not metastasis, 3 ϭ indeter- minate,4ϭprobablymetastasis,5ϭdefinitelymetastasis.)FusedϭfusedbonescintigraphicandCTimages,Negativeϭactuallynegativecases,Non-fusedϭsepa- NUCLEARMEDICINE:SPECT/CTofSuspectedBoneMetastasis Utsunomiyaetal 89% (18％)
equivocal reading was categorized as malignant (P , TABLE 3 Detection of Bone Metastases in 24 Study Patients Who Had Multi-FOV Axial-Body SPECT Final diagnosis Spread of metastases (n 5 13) No metastases (n 5 11) Interpretation* Modality M E B/N M E B/N Sensitivity (%) Specificity (%) PPV (%) NPV (%) Planar BS 6 3 4 0 4 7 69 (46) 64 (100) 69 (100) 64 (61) SPECTy 6 6 1 0 2 9 92 (46) 82 (100) 86 (100) 90 (61) 18F-Fluoride PET 6 7 0 0 2 9 100 (46) 82 (100) 87 (100) 100 (61) 18F-Fluoride PET/CT 11 2 0 0 0 11 100 (85) 100 (100) 100 (100) 100 (85) *Analysis considering equivocal results as positive for malignancy. In parentheses, analysis considering equivocal results as negative for malignancy. yMulti-FOV SPECT composed of 3 or 4 FOVs covering the axial skeleton. M 5 malignant; E 5 equivocal; B/N 5 benign or normal. by on November 13, 2018. For personal use only. jnm.snmjournals.org Downloaded from Even-Sapir E., et al. J Nucl Med 2006;47(2): 287−297. 前立腺癌患者において18F-NaF PET/CTには及ばないが， プラナー全身像と比較してSPECTの感度・特異度は高い
1800-4. (一部改変) after intravenous eight gadolinium y typical contrast 18F PET, and 2 S complemented PECT by 2 other readers of BS, gs of each other. vailable to the 2 lts. ere classified as sed tracer uptake disk spaces was located at joints d endplates were interpreted as equivocal with SPECT, BS, and 18F PET. The results of planar BS, BS complemented with SPECT, and 18F PET are summarized in Table 1. TABLE 1 Results of Planar BS With and Without SPECT and 18F PET Finding BS BS ϩ SPECT 18F PET True-positive 5 9 11 False-positive 2 0 0 Equivocal 5 (2 BM, 3 benign) 2 (2 BM) 1 (BM) True-negative 35 41 41 False-negative 6 1 0 Total 53 53 53 NaF ＊撮像時間2〜2.5h
Mol Imaging (2014) 41:59–67 rate of 29.5 % (13/44 patients). No patient was upstaged. ROC analysis The changes in sensitivity and specificity in relation to the applied cut-off values are shown in Fig. 4. In the total patient CT was possible in 32.1 % of breast cancer patients, and in 29. (Table 7). Upstaging of prev Table 6 Sensitivity, specificity, and negative and positive predictive values of whole-body scintigraphy, SPECT and SPECT/CT analysed on a per-patient basis in patients with prostate cancer Modality Sensitivity Specificity Negative predictive value Positive predictive value Whole-body scintigraphy 96.4 % 75.3 % 98.1 % 61.4 % 27/28 52/69 52/53 27/44 SPECT 96.4 % 63.7 % 97.8 % 51.9 % 27/28 44/69 44/45 27/52 SPECT/CT 96.4 % 94.2 % 98.5 % 87.1 % 27/28 65/69 65/66 27/31 Fig. 4 ROC analysis for whole-bod SPECT/CT for different cut-off value static and nonmetastatic patients in th
Imaging 2016;6(5):262-268 Kuji et al. European Journal of Hybrid Imaging (2017) 1:2 Table 2 Summary of SUV measurements in the DC and BM groups Total DC BM n mean sd n mean sd n mean sd p T 100 75 25 SUVmax 7.58 2.42 7.52 2.63 7.76 1.69 0.242 SUVpeak 6.51 2.12 6.49 2.30 6.59 1.48 0.399 SUVave 4.62 1.68 4.61 1.86 4.67 0.93 0.292 L 140 101 39 SUVmax 8.12 2.24 7.95 2.37 8.56 1.80 0.020* SUVpeak 6.68 1.93 6.57 2.01 6.97 1.72 0.083 SUVave 4.54 1.38 4.46 1.47 4.76 1.06 0.017* Lesions 240 114 126 SUVmax 29.42 27.45 16.73 6.74 40.90 33.46 <0.001*** SUVpeak 24.50 24.14 13.74 4.52 34.24 29.91 <0.001*** SUVave 17.41 17.30 9.47 3.94 24.59 21.19 <0.001*** MV 23.99 26.16 26.27 26.21 21.92 26.04 0.009** n number, sd standard deviation, T thoracic vertebral body, L lumbar vertebral body, BM bone metastases, DC degenerative changes, ***p < 0.001; **p < 0.01; *p < 0.05 Kuji et al. European Journal of Hybrid Imaging (2017) 1:2 SUV of bone using SPECT/CT Figure 2. Box-and-whisker plots of SUVmax (A), SUVpeak (B) and SUVmean (C), showing a quantitative distribution of 5 standard statistics: Smallest val- Data analysis From the vertebral bodies scanned, all vertebrae exhib- iting any focal SPECT or CT pathology, such as osteoph- yte, metastasis, and compre- ssion fracture, were exclud- ed from the analysis based RQ WKH GLDJQRVLV GHÀQHG E\ D ERDUGFHUWLÀHG UDGLRORJLVW Overall, SUVs of 189 verte- brae were calculated for anal- yses based on the criteria SUHYLRXVO\GHÀQHG The delineation of the vol- umes of interest (VOIs) was performed by a board-certi- ÀHGUDGLRORJLVWXVLQJDQHZO\ released software “G-I bone” provided by Nihon Medi-Ph- ysics Co., Ltd. (Tokyo, Japan), which reports the statistics for the various SUVs, such as max, peak, min, and mean SUV. Cylinder-shaped VOIs th- at covered the complete ver- 59% xSPECT Bone Flash3D
トレーニング︓40例 テスト︓10例 current bone scan, a comparison with the previous scan, and pain or injury reported by the patient. The criteria are applied only to patients with known or suspected malignant disease who are undergoing routine bone scanning for screening or follow-up. For other indications, the nuclear medicine physician makes the decision regarding SPECT/CT (Table 1). between August and October 2011 at Ska ˚ne University Hospital, Malmo ¨, Sweden. Patients with known malignant disease who were undergoing routine bone scanning for screening or follow-up were included in the study. The mean age was 69 6 11 y. According to Swedish law, a study regarded as quality-improvement work does not need formal approval from a local research ethics committee. TABLE 1 Criteria for Performing SPECT/CT After Whole-Body Bone Scan Section Description A Indications for not performing SPECT/CT after bone scan Patient cannot participate in SPECT/CT examination Widespread metastatic disease is present A previous whole-body bone scan is available and no new lesions are present B Indications for performing SPECT/CT after bone scan Focal lesions in spine or pelvis are present Patient reports newly developed pain from spine or pelvis Prostate cancer patients have prostate-specific antigen that is increasing or . 20 ng/mL even though no metastatic lesions are present (SPECT/CT of lumbar spine and pelvis) Large urinary bladder is covering sacrum and patient has reported symptoms from this area C Indications for not performing SPECT/CT Whole-body bone scan has normal results and no criteria from section B to perform SPECT/CT are fulfilled D If technologist is unsure whether SPECT/CT should be performed, technologist calls physician These criteria apply to patients suspected of having metastatic disease. For other indications, nuclear medicine physician makes decision. TECHNOLOGISTS DECIDE ABOUT SPECT/CT • Shafi et al. 29 ・ ・ ・ ・
25 35 A B C D E Ref 0.00 2.00 4.00 6.00 5 15 25 35 A B C D E Ref SUVmax SUVmean 0.00 2.00 4.00 6.00 8.00 5 15 25 35 A B C D E Ref SUVpeak A B C D E Ref Width (cm) Height (cm) A：両手体側 22 5 B：挙上伸展 22 3 C：軽度下垂 26 6 D：中度下垂 18 12 E：補助台使用 26 10 Miyaji N. et al. Nucl Med Commun. 2021;42(3):267-275.（⼀部改変）
was chosen diagnostic misclassification [17]; we encourage the inclu- Fig. 2 Illustrative examples of the M1 category (bone metastases); in this example, tracer uptake was increased in the os sacrum and proximal right femur corresponding to osteosclerotic lesions on low-dose CT. Additionally, tracer uptake was increased in the left side of L3 and L5 corresponding to benign changes seen on low-dose CT. a Posterior view of a maximum intensity projection (MIP) from ultra-fast acquisition SPECT. b Posterior view of a MIP from standard acquisition SPECT Zacho et al. EJNMMI Research (2017) 7:1 Page 5 of 7 3-min 11-min Zacho HD. et al. EJNMMI Research (2017) 7:1 全⾝プラナー像に3-min SPECT/CTを追加することで診断能はルーチン条件と同等
were set as a reference to CT images of the bone window to measure SUVs and SDs from the first thoracic to the fifth lumbar vertebrae in clinical xB images using the Syngo Via software (Siemens Healthcare, Erlangen, Germany). Each of the 17 spherical VOIs was set at the center of the vertebral body as much as possible without abnormal accumulation and degenerative changes. The FWHM was also measured by drawing a profile curve on the spinous process of the fifth lumbar vertebra. time. The 13-mm sphere and intervertebral space were observable in xB but were undetectable in F3D. The noise and background of the spinous process were improved by increasing the acquisition time in F3D images. Radioactiv- ity concentrations of the cortical and spongious bones in the first vertebra were almost similar, whereas those of the cortical bone with high HU were decidedly higher than those of the spongious bone in xB images. In F3D image, the high- est value was observed at the center of the homogeneous Fig. 2 Sagittal image of the custom-designed xSPECT bone-specific (xSB) phantom. Flash3D images (top row) and xSPECT bone images (bot- tom row). The acquisition times are 3, 6, 9, 12, and 30 min from left to right 3 6 9 12 30 (min) xSPECT Bone Flash 3D Ichikawa H. et al. Ann Nucl Med. 2022;36(2):183-190.
vertebra covered by the cortical egion of the 13-mm sphere. The %CV wer values of xB than F3D, except that 13-mm sphere (Fig. 3c, d). No reduc- erved with prolonged acquisition time ion method. 12.6 ± 0.2 mm at 3-, 6-, 9-, 12-, and 30-min acquisition times, respectively. The FWHM of xB was lower than that of F3D at all acquisition times; moreover, the FWHM decreased with increasing acquisition time and exhibited almost the same value at 12 and 30 min for both recon- struction methods. centra- ent of econ- ous nificant n the 1 3 Fig. 4 Measured profiles of the first lumbar vertebra at various acquisition times for Flash3D (a) and xSPECT bone (b). The dashed line shows the actual radioactivity concentration Ichikawa H. et al. Ann Nucl Med. 2022;36(2):183-190. Ultra-high-speed xSPECT Bone撮像
whole-body planar images, general SPECT/CT images, and xB images, as increased accumu- lation due to bone metastases in the left iliac bone and left fifth rib, decreased accumulation in the right greater bar vertebrae for std-xB and UHS-xB were 0.90 ± 0.26 and 0.66 ± 0.21, respectively, which were significantly lower for UHS-xB than for std-xB. The FWHM of the fifth lumbar vertebra in the std-xB and UHS-xB images were 10.3 mm and 10.8 mm, respectively. Fig. 5 Clinical images are shown from left to right; maximum inten- sity projections (MIP) images of xSPECT bone (a, e), MIP images of Flash3D (b, f), anterior (c, g), and posterior (d, h) whole-body planar images. Upper row: standard acquisition time; lower row: ultra-high- speed acquisit images is equa standardized u 9 min/Bed xSPECT Bone Flash 3D 3 min/Bed (3m after) xSPECT Bone Flash 3D Ultra-high-speed xSPECT Bone撮像
variance l 定量値（Bq/mL, SUV） l Line profile (FWHMも含む) l 検出能 l etc. ファントムを用いた骨SPECTの画質評価 ROI（VOI）の設定 1) Zeintl J, et al. J Nucl Med. 2010; 51(6). 2) Nakahara T, et al. EJNMMI Res. 2017; 7(53). 3) Zhang R, et al. EJNMMI Phys. 2021;8(66). 4) 市川 肇 他. 日放技学誌. 2015;71(12). 5) 市川 肇 他. 核医学技術. 2017;37(3). 6) 三輪 建太 他.核医学技術. 2017;37(4). 7) 佐越 美香 他．日放技学誌. 2018;74(5). 8) Miyaji N, et al. EJNMMI Res. 2020;10(71). 9) Motegi K et al. Rad Phys Tech. 2020. 10) Ichikawa H, et al. Ann Nucl Med. 2021;35(8). 11) Ichikawa H, et al. Nucl Med comm. 2021;35(8). 12) Ito T, et al. Rad Phys Tech. 2021 13) Fukami M, et al. J Nucl Med Tech. 2021;49(2). 14) Shibutani T, et al. scientificreports. 2021; 11:2644 15) Ichikawa H, et al. Ann Nucl Med. 2022; 36(2).
(green) and non-detected (red) In general, the PET/CT showed slightly increased CRC and CNR for the OSEM+PSF(+TOF) reconstructions compared to PET/MRI. CRC and CNR in- creased when PSF was incorporated in the reconstruction, and a further increase was found when both PSF and TOF were included. Improvements by PSF and TOF have also been demonstrated previously [4, 13, 15–17, 19, 20], and this indi- cates that these algorithms should be used to increase the possibility of detecting small lesions. PSF is a geometry correction that provides higher and more uniform spatial resolution over the transaxial FOV and will therefore have the most impact at the outer edges of the FOV [32]. The inclusion of TOF increases the signal-to- Fig. 7 Histograms of contrast-to-noise ratio (CNR) for detected (green) and non-detected (red) spheres for a PET/MRI and b PET/CT for all the reconstructions with similar number of true counts for the two systems. The black line represents CNR = 5 (Rose criterion). There are twice as many reconstructions for the PET/CT than for the PET/MRI due to the TOF option Oen SK, et al. Fig. 2 Spherical VOIs placed over the hot spheres in OSEM with PSF and TOF with activity concentration of 8:1 (3 iterations, 2 mm voxel size) (purple: d = 20 mm, cyan: d = 12 mm, green: d = 8 mm, pink: d = 6 mm, orange: d = 5 mm, red: d = 4 mm) and seven spherical background VOIs (yellow: d = 20 mm) (a) (b) Øen et al. EJNMMI Physics (2019) 6:16 Page 7 of 16 Rose A. Vision. 1ed: Springer US; 1973. Oen SK, et al. EJNMMI Phys. 2019;6(1):16. 病変の検出
RC ¼ a A ð2Þ Volumes of interest (VOIs) for each sphere were determined with a region growing algorithm for which the cut-off threshold was calculated by [41]: VVthresh ¼ 0:5∙ VV max;sphere þ VVmean;bg À Á ð3Þ where VVthresh is the threshold voxel value, VVmax,sphere is the maximum voxel coefficients at 140 keV Scatter Correction DEW* (120 keV ± 10%) Kernel based DEW* (119 keV ± 7.5%) DEW* (119 keV ± 10%) Monte Carlo-based Monte Carlo-based Image voxel size 2.21 × 2.21 × 2.21 mm3† 4.7 × 4.7 × 4.7 mm3 2.54 × 2.54 × 2.54 mm3 4.8 × 4.8 × 4.8 mm3 4.8 × 4.8 × 4.8 mm3 4.8 × 4.8 × 4.8 mm3 * OSEM ordered subset expectation maximization, PSF point spread function, DEW dual energy window † Initial acquisition was performed with 128 × 128 matrix size and corresponding voxel size of 4.42 × 4.42 × 4.42 mm3. For quantification purposes this was interpolated to a 256 × 256 matrix size and corresponding voxel size of 2.21 × 2.21 × 2.21 mm3, as recommended by the vendor. Peters et al. EJNMMI Physics (2019) 6:29 三輪建太, 他.核医学技術. 2017; 37(4): 517-530 Miyaji N. et al. Nucl Med Commun. 2021;42(3):267-275. ü Bone GL tool ü Hone Graph 0 50000 100000 150000 200000 VVmax,sphere VVmean,bg VVthresh Ichikawa H. et al. Ann Nucl Med. 2021;35(8): 937–46.
mm 22 mm 28 mm ᑜಥى ٿঢ়ٖපม ମ ԣಥى ഏʢλϑϥϯάϑΝϯτϜʣ όοΫάϥϯυ NN Target-to-normal bone ratio 6: i6 protocol Ichikawa H. et al. Ann Nucl Med. 2021;35(8): 937–46. (⼀部改変)
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