Kei Wagatsuma

FDG uptake heterogeneity evaluated by fractal analysis improves the differential diagnosis of pulmonary nodules

PURPOSE The present study aimed to determine whether fractal analysis of morphological complexity and intratumoral heterogeneity of FDG uptake can help to differentiate malignant from benign pulmonary nodules. MATERIALS AND METHODS We retrospectively analyzed data from 54 patients with suspected non-small cell lung cancer (NSCLC) who were examined by FDG PET/CT. Pathological assessments of biopsy specimens confirmed 35 and 19 nodules as NSCLC and inflammatory lesions, respectively. The morphological fractal dimension (m-FD), maximum standardized uptake value (SUV(max)) and density fractal dimension (d-FD) of target nodules were calculated from CT and PET images. Fractal dimension is a quantitative index of morphological complexity and tracer uptake heterogeneity; higher values indicate increased complexity and heterogeneity. RESULTS The m-FD, SUV(max) and d-FD significantly differed between malignant and benign pulmonary nodules (p<0.05). Although the diagnostic ability was better for d-FD than m-FD and SUV(max), the difference did not reach statistical significance. Tumor size correlated significantly with SUV(max) (r=0.51, p<0.05), but not with either m-FD or d-FD. Furthermore, m-FD combined with either SUV(max) or d-FD improved diagnostic accuracy to 92.6% and 94.4%, respectively. CONCLUSION The d-FD of intratumoral heterogeneity of FDG uptake can help to differentially diagnose malignant and benign pulmonary nodules. The SUV(max) and d-FD obtained from FDG-PET images provide different types of information that are equally useful for differential diagnoses. Furthermore, the morphological complexity determined by CT combined with heterogeneous FDG uptake determined by PET improved diagnostic accuracy.

Alteration of the regional cerebral glucose metabolism in healthy subjects by glucose loading.

High plasma glucose (PG) levels can reduce fluorine‐18‐labeled fluorodeoxyglucose (18F‐FDG) uptake, especially in the Alzheimers disease (AD)‐related regions. This fact is supported by studies showing that the resting‐state activity in diabetes can be altered in the default mode network (DMN)‐related regions, which considerably overlap with the AD‐related regions. In order to expand the current knowledge, we aimed to investigate the relationship between increasing PG levels and the regional cerebral metabolic rates for glucose (CMRglc) as a direct index of brain activity. We performed dynamic 18F‐FDG positron emission tomography with arterial blood sampling once each in the fasting and glucose‐loading conditions on 12 young, healthy volunteers without cognitive impairment or insulin resistance. The absolute CMRglc values were calculated for the volume‐of‐interest (VOI) analysis, and normalized CMRglc maps were generated for the voxelwise analysis. The normalized measurement is known to have smaller intersubject variability than the absolute measurement, and may, thus, lead to greater statistical power. In VOI analysis, no regional difference in the CMRglc was found between the two conditions. In exploratory voxelwise analysis, however, significant clusters were identified in the precuneus, posterior cingulate, lateral parietotemporal, and medial prefrontal regions where the CMRglc decreased upon glucose loading (P < 0.05, corrected). These regions include the representative components of both the DMN and AD pathology. Taken together with the previous knowledge on the relationships between the DMN, AD, and diabetes, it may be inferred that glucose loading induces hypometabolism in the AD‐related and DMN‐related regions. Hum Brain Mapp 37:2823–2832, 2016.

Evaluation of a revised version of computer-assisted diagnosis system, BONENAVI version 2.1.7, for bone scintigraphy in cancer patients

ObjectiveBONENAVI is a computer-assisted diagnosis system that analyzes bone scintigraphy automatically. We experienced more than a few segmentation errors with the previous BONENAVI version (2.0.5). We have since obtained a revised version (2.1.7) and evaluate it.MethodsBone scans of patients were analyzed by BONENAVI version 2.0.5 and a revised version 2.1.7 with regard to segmentation errors, sensitivity, and specificity. Patients with skeletal metastases from prostate cancer, lung cancer, breast cancer, and other cancers were included in the study as true-positive cases. Patients with no skeletal metastasis (regardless of hot spots), and patients with abnormal bone scans but no skeletal metastasis were included as negative cases. Bone-scan patients were subjected to artificial neural network (ANN) evaluation. Values equal to or above 0.5 were regarded as positive, and those below 0.5 as negative. The patients whose clinical status did not correspond to their ANN scores were assessed for any similarities.ResultsThe frequency of segmentation errors was statistically significantly reduced when using BONENAVI version 2.1.7. The differences in sensitivity and specificity for the results of version 2.0.5 versus version 2.1.7 were not different, giving a high Cohen’s kappa coefficient. In the patients who showed an increased ANN value with version 2.1.7, a few false-positive thoracic lesions were identified. Patients whose ANN value was significantly high with version 2.0.5 showed no tendencies.ConclusionRevised BONENAVI version 2.1.7 for bone scintigraphy was superior with regard to segmentation errors. However, its sensitivity and specificity were similar to those of version 2.0.5. The false-positive identification of thoracic lesions in revised version 2.1.7 might be subject to remedy.

Initial Evaluation of an Adenosine A(2A) Receptor Ligand, C-11-Preladenant, in Healthy Human Subjects

11C-preladenant is a selective antagonist for mapping of cerebral adenosine A2A receptors (A2ARs) by PET. This is a first-in-human study to examine the safety, radiation dosimetry, and brain imaging of 11C-preladenant in healthy human subjects. Methods: Dynamic 11C-preladenant PET scans (90 min) were obtained in 5 healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined. For anatomic coregistration, T1-weighted MRI was performed. The total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1T and 2T, respectively). The distribution volume ratio (DVR) was calculated from VT of target and reference region and obtained with a noninvasive Logan graphical reference tissue method (t* = 30 min). The applicability of a shortened protocol as an alternative to the 90-min PET scan was investigated. Tracer biodistribution and dosimetry were determined in 3 healthy male subjects, using serial whole-body PET scans acquired over 2 h after 11C-preladenant injection. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-preladenat readily entered the brain, with a peak uptake in the putamen and head of the caudate nucleus 30−40 min after tracer injection. Other brain regions showed rapid clearance of radioactivity. The regional distribution of 11C-preladenant was consistent with known A2AR densities in the brain. At pseudoequilibrium (reached at 40 min after injection), stable target–to–cerebellar cortex ratios of around 3.8−10.0 were obtained. The 2T fit better than the 1T in the low-density A2AR regions. In contrast, there were no significant differences between 1T and 2T in the high-A2AR-density regions. DVRs in the putamen and head of the caudate nucleus were around 3.8−10.3 when estimated using a Logan graphical reference tissue method with cerebellum as the reference region. PET scanning at 50 or 70 min can provide the stable DVR estimates within 10% or 5% differences at most, respectively. The radioactivity was mainly excreted through the hepatobiliary system after 11C-preladenant injection. As a result, the absorbed dose (μGy/MBq) was highest in the gallbladder wall (mean ± SD, 17.0 ± 2.5) and liver (11.7 ± 2.1). The estimated effective dose for 11C-preladenant was 3.7 ± 0.4 μSv/MBq. Conclusion: This initial evaluation indicated that 11C-preladenat is suitable for imaging of A2ARs in the brain.

Comparison between new-generation SiPM-based and conventional PMT-based TOF-PET/CT

PURPOSE This study aimed to determine whether the SiPM-PET/CT, Discovery MI (DMI) performs better than the PMT-PET/CT system, Discovery 710 (D710). METHODS The physical performance of both systems was evaluated using NEMA NU 2 standards. Contrast (%), uniformity and image noise (%) are criteria proposed by the Japanese Society of Nuclear Medicine (JSNM) for phantom tests and were determined in images acquired from Hoffman and uniform phantoms using the DMI and D710. Brain and whole-body [18F]FDG images were also acquired from a healthy male using the DMI and D710. RESULTS The spatial resolution at 1.0cm off-center in the DMI and D710 was 3.91 and 4.52mm, respectively. The sensitivity of the DMI and D710 was 12.62 and 7.50cps/kBq, respectively. The observed peak noise-equivalent count rates were 185.6kcps at 22.5kBq/mL and 137.0kcps at 29.0kBq/mL, and the scatter fractions were 42.1% and 37.9% in the DMI and D710, respectively. The D710 had better contrast recovery and lower background variability. Contrast, uniformity and image noise in the DMI were 61.0%, 0.0225, and 7.85%, respectively. These outcomes were better than those derived from the D710 and satisfied the JSNM criteria. Brain images acquired by the DMI had better grey-to-white matter contrast and lower image noise at the edge of axial field of view. CONCLUSIONS The DMI offers better sensitivity, performance under conditions of high count rates and image quality than the conventional PMT-PET/CT system, D710.

Evaluation of scatter limitation correction: a new method of correcting photopenic artifacts caused by patient motion during whole-body PET/CT imaging.

ObjectiveOvercorrection of scatter caused by patient motion during whole-body PET/computed tomography (CT) imaging can induce the appearance of photopenic artifacts in the PET images. The present study aimed to quantify the accuracy of scatter limitation correction (SLC) for eliminating photopenic artifacts. MethodsThis study analyzed photopenic artifacts in 18F-fluorodeoxyglucose (18F-FDG) PET/CT images acquired from 12 patients and from a National Electrical Manufacturers Association phantom with two peripheral plastic bottles that simulated the human body and arms, respectively. The phantom comprised a sphere (diameter, 10 or 37 mm) containing fluorine-18 solutions with target-to-background ratios of 2, 4, and 8. The plastic bottles were moved 10 cm posteriorly between CT and PET acquisitions. All PET data were reconstructed using model-based scatter correction (SC), no scatter correction (NSC), and SLC, and the presence or absence of artifacts on the PET images was visually evaluated. The SC and SLC images were also semiquantitatively evaluated using standardized uptake values (SUVs). ResultsPhotopenic artifacts were not recognizable in any NSC and SLC image from all 12 patients in the clinical study. The SUVmax of mismatched SLC PET/CT images were almost equal to those of matched SC and SLC PET/CT images. Applying NSC and SLC substantially eliminated the photopenic artifacts on SC PET images in the phantom study. SLC improved the activity concentration of the sphere for all target-to-background ratios. The highest %errors of the 10 and 37-mm spheres were 93.3 and 58.3%, respectively, for mismatched SC, and 73.2 and 22.0%, respectively, for mismatched SLC. ConclusionPhotopenic artifacts caused by SC error induced by CT and PET image misalignment were corrected using SLC, indicating that this method is useful and practical for clinical qualitative and quantitative PET/CT assessment.

Response of Cerebral Blood Flow and Blood Pressure to Dynamic Exercise: A Study Using PET

Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This study investigated responses in BP and CBF during cycling exercise and post-exercise hypotension (PEH) using positron emission tomography (PET). CBF was measured using oxygen-15-labeled water (H215O) and PET in 11 human subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest, regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis, sensorimotor cortex for the bilateral legs (M1Leg and S1Leg), insular cortex and brain stem, but increased at Ex2 (28~31%) only in the vermis and M1Leg and S1Leg. During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal gyrus, piriform lobe, thalamus and pons. The areas showing correlations between rCBF and mean BP during exercise and PEH were consistent with the central autonomic network, including the brain stem, cerebellum, and hypothalamus (R2=0.25-0.64). The present study suggests that higher brain regions are coordinated through reflex centers in the brain stem in order to regulate the cardiovascular response to exercise.

Effects of a novel tungsten-impregnated rubber neck shield on the quality of cerebral images acquired using 15O-labeled gas

The present study aimed to validate the effects of a novel tungsten-impregnated rubber neck shield on the quality of phantom and clinical 15O-labeled gas positron emission tomography (PET) images. Images were acquired in the presence or absence of a neck shield from a cylindrical phantom containing [15O]H2O (phantom study) and from three individuals using [15O]CO2, [15O]O2 and [15O]CO gas (clinical study). Data were acquired in three-dimensional (3D) mode using a Discovery PET/CT 710. Values for cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and cerebral metabolic rate of oxygen with and without the neck shield were calculated from 15O-labeled gas images. Arterial radioactivity and count characteristics were evaluated in the phantom and clinical studies. The coefficient of variance (CV) for the phantom study and the standard deviation (SD) for functional images were also analyzed. The neck shield decreased the random count rates by 25–59% in the phantom and clinical studies. The noise equivalent count rate (NECR) increased by 44–66% in the phantom and clinical studies. Random count rates and NECR in [15O]CO2 images significantly differed with and without the neck shield. The improvement in visual and physical image quality with the neck shield was not observed in the phantom and clinical studies. The novel neck shield reduced random count rate and improved NECR in a 3D PET study using 15O-labeled gas. The image quality with the neck shield was similar to that without the neck shield.

Multicenter study of quantitative PET system harmonization using NIST-traceable 68Ge/68Ga cross-calibration kit

PURPOSE The present study aimed to define the errors in SUV and demonstrate the feasibility of SUV harmonization among contemporary PET/CT scanners using a novel National Institute of Standards and Technology (NIST)-traceable 68Ge/68Ga source as the reference standard. METHODS We used 68Ge/68Ga dose calibrator and PET sources made with same batch of 68Ge/68Ga embedded in epoxy that is traceable to the NIST standard. Bias in the amount of radioactivity and the radioactive concentrations measured by the dose calibrators and PET/CT scanners, respectively, was determined at five Japanese sites. We adjusted optimal dial setting of the dose calibrators and PET reconstruction parameters to close the actual amount of radioactivity and the radioactive concentration, respectively, of the NIST-traceable 68Ge/68Ga sources to harmonize SUV. Errors in SUV before and after harmonization were then calculated at each site. RESULTS The average bias in the amount of radioactivity and the radioactive concentrations measured by dose calibrator and PET scanner was -4.94% and -12.22%, respectively, before, and -0.14% and -4.81%, respectively, after harmonization. Corresponding averaged errors in SUV measured under clinical conditions were underestimated by 7.66%, but improved by -4.70% under optimal conditions. CONCLUSION Our proposed method using an NIST-traceable 68Ge/68Ga source identified bias in values obtained using dose calibrators and PET scanners, and reduced SUV variability to within 5% across different models of PET scanners at five sites. Our protocol using a standard source has considerable potential for harmonizing the SUV when contemporary PET scanners are involved in multicenter studies.

Bayesian penalized-likelihood reconstruction algorithm suppresses edge artifacts in PET reconstruction based on point-spread-function

PURPOSE The Bayesian penalized-likelihood reconstruction algorithm (BPL), Q.Clear, uses relative difference penalty as a regularization function to control image noise and the degree of edge-preservation in PET images. The present study aimed to determine the effects of suppression on edge artifacts due to point-spread-function (PSF) correction using a Q.Clear. METHODS Spheres of a cylindrical phantom contained a background of 5.3 kBq/mL of [18F]FDG and sphere-to-background ratios (SBR) of 16, 8, 4 and 2. The background also contained water and spheres containing 21.2 kBq/mL of [18F]FDG as non-background. All data were acquired using a Discovery PET/CT 710 and were reconstructed using three-dimensional ordered-subset expectation maximization with time-of-flight (TOF) and PSF correction (3D-OSEM), and Q.Clear with TOF (BPL). We investigated β-values of 200-800 using BPL. The PET images were analyzed using visual assessment and profile curves, edge variability and contrast recovery coefficients were measured. RESULTS The 38- and 27-mm spheres were surrounded by higher radioactivity concentration when reconstructed with 3D-OSEM as opposed to BPL, which suppressed edge artifacts. Images of 10-mm spheres had sharper overshoot at high SBR and non-background when reconstructed with BPL. Although contrast recovery coefficients of 10-mm spheres in BPL decreased as a function of increasing β, higher penalty parameter decreased the overshoot. CONCLUSIONS BPL is a feasible method for the suppression of edge artifacts of PSF correction, although this depends on SBR and sphere size. Overshoot associated with BPL caused overestimation in small spheres at high SBR. Higher penalty parameter in BPL can suppress overshoot more effectively.