Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

OBJECTIVE: Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15O-water. METHODS: Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500 MBq of 15O-water was infused slowly for 2 min, and the dynamic data were scanned for 6 min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated. RESULTS: In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET. CONCLUSIONS: The ECG-gated dynamic 15O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion.

Comparative study of physiological FDG uptake in small structures between silicon photomultiplier-based PET and conventional PET.

OBJECTIVE: Silicon photomultiplier-based positron emission tomography/computed tomography (SiPM-PET/CT) has the superior spatial resolution to conventional PET/CT (cPET/CT). This head-to-head comparison study compared the images of physiological 18F-fluorodeoxyglucose (FDG) accumulation in small-volume structures between SiPM-PET/CT and cPET/CT in patients scanned with both modalities, and we investigated whether the thresholds that are reported to be useful for differentiating physiological accumulations from malignant lesions can also be applied to SiPM-PET/CT. METHODS: We enrolled 21 consecutive patients with head and neck malignancies who underwent whole-body FDG-PET/CT for initial staging or a follow-up evaluation (October 2020 to March 2022). After being injected with FDG, all patients underwent PET acquisition on both Vereos PET-CT and Gemini TF64 PET-CT systems (both Philips Healthcare) in random order. For each patient, the maximum standardized uptake value (SUVmax) was measured in the pituitary gland, esophagogastric junction (EGJ), adrenal glands, lumbar enlargement of the spinal cord, and epididymis. We measured the liver SUVmean and the blood pool SUVmean to calculate the target-to-liver ratio (TLR) and the target-to-blood ratio (TBR), respectively. Between-groups differences in each variable were examined by a paired t-test. We also investigated whether there were cases of target uptake greater than the reported threshold for distinguishing pathological from physiological accumulations. RESULTS: Data were available for 19 patients. Ten patients were in Group 1, i.e., the patients who underwent SiPM-PET first, and the remaining nine patients who underwent cPET first were in Group 2. In the SiPM-PET results, the SUVmax of all targets was significantly higher than that obtained by cPET in all patients, and this tendency was also observed when the patients were divided into Groups 1/2. The TLRs of all targets were significantly higher in SiPM-PET than in cPET in all patients, and SiPM-PET also showed significantly higher TBRs for all targets except the EGJ (p = 0.052). CONCLUSIONS: The physiological uptake in the small structures studied herein showed high accumulation on SiPM-PET. Our results also suggest that the thresholds reported for cPET to distinguish pathological accumulations likely lead to false-positive findings in SIPM-PET evaluations.

Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study.

BACKGROUND: Lenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes. RESULTS: This was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078). CONCLUSIONS: The therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016.

Medical Radiation Exposure Reduction in PET via Super-Resolution Deep Learning Model.

In positron emission tomography (PET) imaging, image quality correlates with the injected [18F]-fluorodeoxyglucose (FDG) dose and acquisition time. If image quality improves from short-acquisition PET images via the super-resolution (SR) deep learning technique, it is possible to reduce the injected FDG dose. Therefore, the aim of this study was to clarify whether the SR deep learning technique could improve the image quality of the 50%-acquisition-time image to the level of that of the 100%-acquisition-time image. One-hundred-and-eight adult patients were enrolled in this retrospective observational study. The supervised data were divided into nine subsets for nested cross-validation. The mean peak signal-to-noise ratio and structural similarity in the SR-PET image were 31.3 dB and 0.931, respectively. The mean opinion scores of the 50% PET image, SR-PET image, and 100% PET image were 3.41, 3.96, and 4.23 for the lung level, 3.31, 3.80, and 4.27 for the liver level, and 3.08, 3.67, and 3.94 for the bowel level, respectively. Thus, the SR-PET image was more similar to the 100% PET image and subjectively improved the image quality, as compared to the 50% PET image. The use of the SR deep-learning technique can reduce the injected FDG dose and thus lower radiation exposure.

A Preliminary Study to Use SUVmax of FDG PET-CT as an Identifier of Lesion for Artificial Intelligence.

Background: Diagnostic reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily diagnostic reports of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) - computed tomography (CT). If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret diagnostic reports. We aimed to clarify whether the lesion can be localized using SUVmax strings. Methods: The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax = 3.14 was given, the voxels with 3.135 ≤ SUVmax < 3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that "identical detection" was achieved when only single voxel satisfied the criterion. Results: A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax < 2), 79.5% (2 ≤ SUVmax < 5), and 97.8% (5 ≤ SUVmax) of lesions. Conclusion: In this preliminary study, SUVmax of FDG PET-CT could be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax < 2 were difficult to identify. The proposed method may have potential to make use of diagnostic reports retrospectively for constructing training datasets for AI.

Preoperative Texture Analysis Using 11C-Methionine Positron Emission Tomography Predicts Survival after Surgery for Glioma.

BACKGROUND: Positron emission tomography with 11C-methionine (MET) is well established in the diagnostic work-up of malignant brain tumors. Texture analysis is a novel technique for extracting information regarding relationships among surrounding voxels, in order to quantify their inhomogeneity. This study evaluated whether the texture analysis of MET uptake has prognostic value for patients with glioma. METHODS: We retrospectively analyzed adults with glioma who had undergone preoperative metabolic imaging at a single center. Tumors were delineated using a threshold of 1.3-fold of the mean standardized uptake value for the contralateral cortex, and then processed to calculate the texture features in glioma. RESULTS: The study included 42 patients (median age: 56 years). The World Health Organization classifications were grade II (7 patients), grade III (17 patients), and grade IV (18 patients). Sixteen (16.1%) all-cause deaths were recorded during the median follow-up of 18.8 months. The univariate analyses revealed that overall survival (OS) was associated with age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.08, p = 0.0093), tumor grade (HR 3.64, 95% CI 1.63-9.63, p = 0.0010), genetic status (p < 0.0001), low gray-level run emphasis (LGRE, calculated from the gray-level run-length matrix) (HR 2.30 × 1011, 95% CI 737.11-4.23 × 1019, p = 0.0096), and correlation (calculated from the gray-level co-occurrence matrix) (HR 5.17, 95% CI 1.07-20.93, p = 0.041). The multivariate analyses revealed OS was independently associated with LGRE and correlation. The survival curves were also significantly different (both log-rank p < 0.05). CONCLUSION: Textural features obtained using preoperative MET positron emission tomography may compliment the semi-quantitative assessment for prognostication in glioma cases.

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.

BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

Halo artifacts of indwelling urinary catheter by inaccurate scatter correction in 18F-FDG PET/CT imaging: incidence, mechanism, and solutions.

BACKGROUND: Halo artifacts from urinary catheters can occur due to inaccurate scatter correction, and the artifacts affect the tumor visibility in 18F-FDG PET/CT images. We investigated the incidence rate and the mechanisms of halo-artifact generation and explored several scatter correction techniques to prevent artifacts. METHODS: We conducted patient and phantom studies. (1) We retrospectively reviewed the cases of patients who had undergone 18F-FDG PET/CT scans. To determine the frequency of halo-artifact generation, we used the patients' PET images with a standard scatter correction based on a tail-fitted single-scatter simulation (TF-SSS) using 4-mm voxel µ-maps (TFS 4-mm). (2) We performed phantom studies to evaluate the effects of a urine catheter and two scatter correction techniques, i.e., TF-SSS with 2-mm voxel µ-maps (TFS 2-mm) and a Monte Carlo-based single-scatter simulation (MC-SSS) using 4-mm voxel µ-maps (MCS 4-mm). The average standardized uptake values (SUVs) were measured for axial PET images. (3) Using the patients' data, we investigated whether TFS 2-mm and MCS 4-mm can eliminate the artifacts in the clinical images. RESULTS: (1) There were 61 patients with urinary catheters; in five (8.2%), halo artifacts were observed in the TFS 4-mm PET images. (2) The phantom study clearly reproduced the halo artifacts in the TFS 4-mm PET images. The halo artifacts were generated when urine moved in the interval between the CT and PET imaging, and when the urinary catheter was placed in a circular shape. The SUVs for the TFS 4-mm and TFS-2mm PET images were underestimated at the halo-artifact regions, whereas the SUVs for the MCS 4-mm PET images were close to the true values. (3) The halo artifacts disappeared in the TFS 2-mm PET images in 4/5 patients but not 1/5 patient, whereas the halo artifacts were completely absent in the MCS 4-mm PET images in 5/5 patients. CONCLUSIONS: These data suggest that halo artifacts are caused if the PET images do not correspond to the physical material in the µ-maps, which induces the scatter correction error. With the MC-SSS, it was possible to accurately estimate the scatter without generating halo artifacts.

Quantitative bone single photon emission computed tomography analysis of the effects of duration of bisphosphonate administration on the parietal bone.

Effects of long-term bisphosphonate (BP) administration on the metabolism of healthy bone and the concomitant changes in imaging are unclear. Hence, we aimed to retrospectively investigate the effects of long-term BP administration on the intact parietal bone using the standardised uptake value (SUV) derived from single photon emission computed tomography (SPECT). We enrolled 29 patients who had odontogenic infection, osteoporosis, bone metastasis cancer, or rheumatoid arthritis, and classified them into BP-naïve: A (14 patients) and BP-treated: B, < 4 years (7 patients) and C, ≥ 4 years (8 patients) groups. We measured the maximum bilateral SUV (SUVmax) of the parietal bone using quantitative bone SPECT software. There were significant differences in the duration of BP administration and SUVmax of the parietal bone among the diseases (P < 0.0001 and P = 0.0086, respectively). There was a positive correlation between the duration of BP administration and SUVmax of the parietal bone (rs = 0.65, P = 0.0002). The SUVmax was significantly different between A and B (P = 0.02) and between A and C (P = 0.0024) groups. This is the first report on the correlation between long-term BP administration and the SUVmax of the parietal bone using the quantitative bone SPECT analysis.

Biodistribution and internal radiation dosimetry of a novel probe for thymidine phosphorylase imaging, [123I]IIMU, in healthy volunteers.

OBJECTIVE: We evaluated the radiation dosage, biodistribution, human safety, and tolerability of the injection of a single dose of [123I] 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU), a new radiotracer targeting thymidine phosphorylase (TP), in healthy volunteers. METHODS: Potential participants were tested at our hospital to confirm their eligibility. Two healthy male adults passed the screening tests. They were injected with 56 and 111 MBq of [123I]IIMU, respectively. Safety assessments were performed before and at 1, 3, 6, 9, 24, 48 h, and 1-week post-injection. Whole-body emission scans were conducted at 1, 3, 6, 24, and 48 h post-injection. Regions of interest were manually drawn to enclose the entire body at each time point, identifying high-uptake organs to obtain the time-activity curves. Urine and blood samples were collected at 1, 2, 3, 4, 5, 6, 9, 24, and 48 h post-injection. The radiation dose for each organ and the effective doses were estimated using OLINDA/EXM 1.1 software. RESULTS: No adverse events were observed as of the follow-up visit > 1-week post-injection. In both subjects, the highest uptake of [123I]IIMU occurred in the liver, with peak injected activity (%IA) values of 17.7% and 15.1%, respectively. The second highest uptake was in the thyroid (0.35% and 0.66% IA). The %IA decreased gradually toward the end of the study (48 h) in all organs except the liver and thyroid. By the end of the study, 52.5% and 51.5% of the injected activity of [123I]IIMU had been excreted via the subjects' renal systems. The estimated mean effective doses of [123I]IIMU were 9.19 µSv/MBq and 10.1 µSv/MBq, respectively. CONCLUSION: In this preliminary study, [123I]IIMU was safely administered to healthy adults, and its potential clinical use in TP imaging was revealed.

Validation of regional myocardial blood flow quantification using three-dimensional PET with rubidium-82: repeatability and comparison with two-dimensional PET data acquisition.

INTRODUCTION: Three-dimensional (3D) data acquisition is now standard on PET/computed tomography scanners. The aim of this study was to evaluate the repeatability of myocardial blood flow (MBF) estimation with rubidium-82 (Rb) 3D PET and to validate regional MBF measurements by comparison with two-dimensional (2D) PET. PATIENTS AND METHODS: Fifteen healthy individuals (31.6 ± 11.4 years old) were enrolled for the evaluation of the short-term repeatability of rest 3D MBF quantification. Another 19 healthy individuals (35.3 ± 12.6 years old) underwent rest and pharmacological stress PET using 2D and 3D data acquisition within a 1-month interval. The injected dose was 1500 MBq for 2D and 555 MBq for 3D PET acquisition. RESULTS: MBF at rest showed good repeatability [whole left ventricular MBF; 0.54 ± 0.13 vs. 0.52 ± 0.13 mL/min/g, P = 0.98]. Rest MBF, stress MBF, and myocardial flow reserve (MFR) were not significantly different between 3D and 2D data acquisition. 3D MBF correlated well with 2D MBF over a wide flow range for both whole left ventricular (r = 0.97, P < 0.0001) and regional values (r = 0.61, P < 0.0001). CONCLUSION: MBF measured with 3D PET showed very good test-retest repeatability. Whole left ventricular and regional MBF measurements obtained using lower Rb-dose 3D PET were highly correlated over a wide range with those from 2D PET. Therefore, MBF with 3D PET can be applied using a lower Rb dosage in clinical settings with reduced radiation exposure.

Development of Combination Methods for Detecting Malignant Uptakes Based on Physiological Uptake Detection Using Object Detection With PET-CT MIP Images.

Deep learning technology is now used for medical imaging. YOLOv2 is an object detection model using deep learning. Here, we applied YOLOv2 to FDG-PET images to detect the physiological uptake on the images. We also investigated the detection precision of abnormal uptake by a combined technique with YOLOv2. Using 3,500 maximum intensity projection (MIP) images of 500 cases of whole-body FDG-PET examinations, we manually drew rectangular regions of interest with the size of each physiological uptake to create a dataset. Using YOLOv2, we performed image training as transfer learning by initial weight. We evaluated YOLOv2's physiological uptake detection by determining the intersection over union (IoU), average precision (AP), mean average precision (mAP), and frames per second (FPS). We also developed a combination method for detecting abnormal uptake by subtracting the YOLOv2-detected physiological uptake. We calculated the coverage rate, false-positive rate, and false-negative rate by comparing the combination method-generated color map with the abnormal findings identified by experienced radiologists. The APs for physiological uptakes were: brain, 0.993; liver, 0.913; and bladder, 0.879. The mAP was 0.831 for all classes with the IoU threshold value 0.5. Each subset's average FPS was 31.60 ± 4.66. The combination method's coverage rate, false-positive rate, and false-negative rate for detecting abnormal uptake were 0.9205 ± 0.0312, 0.3704 ± 0.0213, and 0.1000 ± 0.0774, respectively. The physiological uptake of FDG-PET on MIP images was quickly and precisely detected using YOLOv2. The combination method, which can be utilized the characteristics of the detector by YOLOv2, detected the radiologist-identified abnormalities with a high coverage rate. The detectability and fast response would thus be useful as a diagnostic tool.

Improved regional myocardial blood flow and flow reserve after coronary revascularization as assessed by serial 15O-water positron emission tomography/computed tomography.

AIMS: Myocardial perfusion imaging without and with quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) plays an important role in the diagnosis and risk stratification of patients with stable coronary artery disease (CAD). We aimed to quantify the effects of coronary revascularization on regional stress MBF and MFR and to determine whether the presence of subendocardial infarction was associated with these changes. METHODS AND RESULTS: Forty-seven patients with stable CAD were prospectively enrolled. They underwent 15O-water positron emission tomography at baseline and 6 months after optimal medical therapy alone (n = 16), percutaneous coronary intervention (PCI) (n = 18), or coronary artery bypass grafting (CABG) (n = 13). Stenosis of ≥50% diameter was detected in 98/141 vessels (70%). The regional MFR was significantly increased from baseline to follow-up [1.84 (interquartile range, IQR 1.28-2.17) vs. 2.12 (IQR 1.69-2.63), P < 0.001] in vessel territories following PCI or CABG due to an increase in the stress MBF [1.33 (IQR 0.97-1.67) mL/g/min vs. 1.64 (IQR 1.38-2.17) mL/g/min, P < 0.001], whereas there was no significant change in the regional stress MBF or MFR in vessel territories without revascularization. A multilevel mixed-effects models adjusted for baseline characteristics, subendocardial infarction assessed by cardiovascular magnetic resonance imaging, and intra-patient correlation showed that the degree of angiographic improvement after coronary revascularization was significantly associated with increased regional stress MBF and MFR (P < 0.05 for all). CONCLUSION: Coronary revascularization improved the regional stress MBF and MFR in patients with stable CAD. The magnitude of these changes was associated with the extent of revascularization independent of subendocardial infarction.

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h.

PURPOSE: 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO. METHODS: Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor. RESULTS: At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10-1.32 vs. 1.04, IQR 0.95-1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00-1.23 vs. 1.02, IQR 0.93-1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14-1.19) to 1.09 (IQR 1.07-1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67-3.32 at 2 h vs. 2.65, IQR 1.74-4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40-2.38 at 2 h vs. 2.34, IQR 1.67-3.60 at 4 h, p = 0.016). CONCLUSION: In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection.

Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET.

BACKGROUND: 11C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. METHODS: Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15O-H2O PET. In the controls, the relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET was linked by the Renkin-Crone model. RESULTS: The relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET from the controls' data was approximated as follows: K1  =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). CONCLUSION: 11C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.

Combination of FDG-PET and FMISO-PET as a treatment strategy for patients undergoing early-stage NSCLC stereotactic radiotherapy.

BACKGROUND: We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. RESULTS: Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). CONCLUSION: The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival.

Biodistribution and radiation dosimetry of the novel hypoxia PET probe [18F]DiFA and comparison with [18F]FMISO.

BACKGROUND: To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 µSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 µSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59). CONCLUSION: [18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.

Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer.

BACKGROUND: Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis. METHODS: Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia. RESULTS: Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p<0.001). A moderate correlation between FDG and FMISO uptake was found by a voxel-by-voxel comparison (r = 0.664 p<0.001). The average concordance rate was 25% (± 22%). Entropy was the TA parameter showing the highest correlation with hypoxia (r = 0.524 p<0.001). CONCLUSION: FDG uptake was higher in hypoxic tumour regions than in non-hypoxic regions as expected by tumour biology. A moderate correlation between FDG and FMISO PET was found by voxel-based analysis. TA yielded similar results in FDG and FMISO PET. However, it may not be possible to predict tumour hypoxia even with the help of texture analysis.

Effects of coronary revascularization on global coronary flow reserve in stable coronary artery disease.

Aims: Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD. Methods and results: In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8-24.5], 5.5 (IQR: 2.5-12.5), and 1.94 (IQR: 1.67-2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = -0.40, P < 0.001) and Leaman scores (ρ = -0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14-1.96) vs. 1.98 (IQR: 1.60-2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42-1.79) vs. 2.21 (IQR: 1.78-2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13-1.80) vs. 1.86 (IQR: 1.57-2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively). Conclusion: Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.