18F-FDG-PET/CT features of primary tumours for predicting the risk of recurrence in thyroid cancer after total thyroidectomy: potential usefulness of combination of the SUV-related, volumetric, and heterogeneous texture parameters.

OBJECTIVE:: This retrospective study examined whether the primary tumour 18F-FDG uptake features could predict the high-risk of recurrence in differentiated thyroid cancer (DTC) patients. METHODS:: The enrolled 114 DTC patients underwent preoperative 18F-FDG-PET/CT. SUVmax, SUVmean, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and 6 texture parameters were obtained. Because the texture features can be confounded by the tumour volume effects, 18F-FDG-avid tumour patients were divided into two groups (tumours with MTV ≤ 10.0 cm3 and >10.0 cm3). Diagnostic performance for predicting the high-risk was evaluated by the area under the curve (AUC) by the ROC curve analysis. RESULTS:: Eighty eight 18F-FDG-avid tumours revealed more advanced-risk classification (p = 0.015 → 0.02) than 26 18F-FDG-nonavid tumours, which yielded no high-risk patients. In the 44 MTV > 10.0 cm3 18F-FDG-avid tumour patients, 8 high-risk patients revealed significantly higher SUVmax, SUVmean, MTV, TLG, intensity variability and size-zone variability, and lower zone percentage than 36 non-high-risk patients (p < 0.001-0.016). Their AUC (diagnostic accuracy) ranged between 0.77 (66%) and 0.92 (91%). When each parameter was scored as 0 (negative for high-risk) or 1 (positive for high-risk) according to each threshold criterion, and the 7 parameter summed score ≥5 was defined as high-risk, the accuracy was 93.2% (AUC: 0.98) in the MTV > 10.0 cm3 18F-FDG-avid tumour patients. CONCLUSION:: For primary MTV > 10.0 cm3 18F-FDG-avid DTCs, the combined use of SUV-related, volumetric, and texture parameters may be more useful to identify high-risk patients than the individual parameters. ADVANCES IN KNOWLEDGE:: Combined use of SUV-related, volumetric, and texture parameters may be useful to identify high-risk DTC patients.

A Pilot Study of Texture Analysis of Primary Tumor [18F]FDG Uptake to Predict Recurrence in Surgically Treated Patients with Non-small Cell Lung Cancer.

PURPOSE: To examine whether the heterogeneous texture parameters in primary tumor can predict prognosis of patients with non-small cell lung cancer (NSCLC) received surgery after 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/X-ray computed tomography (CT). PROCEDURE: This retrospective study included 55 patients with NSCLC who underwent [18F]FDG-PET/CT before surgery from January 2011 and December 2015. SUV-related (SUVmax and SUVmean), volumetric (metabolic tumor volume [SUV ≥ 2.5], and total lesion glycolysis) and texture parameters (local parameters; entropy, homogeneity, and dissimilarity and regional parameters; intensity variability [IV], size-zone variability [SZV], and zone percentage [ZP]) were obtained. Tumor size, TNM stage, SUV-related, volumetric, and texture parameters were compared between the patients with progression and without progression using Mann-Whitney's U or χ2 test and progression-free survival (PFS) and prognostic significance were assessed by Kaplan-Meier method and Cox regression analysis, respectively. RESULTS: Nineteen patients eventually showed progression, and 36 patients were alive without progression during clinical follow-up (median follow-up PFS; 23 months [range, 1-71]). The patients with progression showed significantly larger tumor size (p < 0.001), higher IV (p = 0.010), and higher SZV (p = 0.007) than those without progression. PFS was significantly shorter in patients with large tumor size (p = 0.008), high T stage (p = 0.009), high stage (p = 0.013), high IV (p = 0.012), and high SZV (p = 0.015) at univariate analysis. At multivariate analysis, stage (hazard ratio [HR] 1.62, p = 0.035) and IV (hazard ratio 6.19, p = 0.048) were only remained independent predictors for PFS. CONCLUSIONS: The regional heterogeneity texture parameters IV and SZV can predict tumor progression, and IV has the potential to predict prognosis of surgically treated NSCLC patients.

Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated 18F-FDG PET.

In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated 18F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n = 6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, 18F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5 ± 4.2 vs. 59.4 ± 4.5%; HR: 331 ± 35 vs. 309 ± 24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1 ± 0.8 vs. 10.2 ± 1 Enddiastolic Volume/sec, P < 0.01). Investigating a diabetic rat model, ECG-gated 18F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

Precise regional quantitative assessment of renal function is limited with conventional 99mTc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2-18F-fluorosorbitol (18F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18F-FDS is available via simple reduction from routinely used 18F-FDG. We aimed to further investigate the potential of 18F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99mTc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18F-FDS and 99mTc-diethylenetriaminepentaacetic acid correlated well with each other (R = 0.84, P < 0.05). Conclusion:18F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.

Texture analysis of 18F-FDG PET/CT for grading thymic epithelial tumours: usefulness of combining SUV and texture parameters.

OBJECTIVE: To retrospectively investigate the standardized uptake value (SUV)-related and heterogeneous texture parameters individually and in combination for differentiating between low- and high-risk 18Fluorone-fludeoxyglucose (18F-FDG)-avid thymic epithelial tumours (TETs) with positron emission tomography (PET)/CT. METHODS: SUV-related and 6 texture parameters (entropy, homogeneity, dissimilarity, intensity variability, size-zone variability and zone percentage) were compared between 11 low-risk and 23 high-risk TETs (metabolic tumour volume >10.0 cm3 and SUV ≥2.5). Diagnostic performance was evaluated by receiver operating characteristic analysis. The diagnostic value of combining SUV and texture parameters was examined by a scoring system. RESULTS: High-risk TETs were significantly higher in SUVmax (p = 0.022), entropy (p = 0.038), intensity variability (p = 0.041) and size-zone variability (p = 0.045) than low-risk TETs. Diagnostic accuracies of these 4 parameters, dissimilarity and zone percentage which also showed significance in receiver operating characteristic analysis ranged between 64.7 and 73.5% without significant differences in AUC (range; 0.71 to 0.75) (p ≥ 0.05 each). Each parameter was scored as 0 (negative for high-risk) or 1 (positive for high-risk) according to each threshold criterion, then scores were summed [0 or 1 for low-risk TETs (median; 1); ≥2 for high-risk TETs (median; 4)]. The sensitivity, specificity and accuracy of detecting high-risk TETs were 100, 81.8 and 94.1%, respectively, with an AUC of 0.99. CONCLUSION: The diagnostic performances of individual SUVmax and texture parameters were relatively low. However, combining these parameters can significantly increase diagnostic performance when differentiating between relatively large low- and high-risk 18F-FDG-avid TETs. Advances in knowledge: Combined use of SUVmax and texture parameters can significantly increase the diagnostic performance when differentiating between low- and high-risk TETs.

Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus.

Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by 18F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic 18F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. 18F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased 18F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.

Texture analysis of FDG PET/CT for differentiating between FDG-avid benign and metastatic adrenal tumors: efficacy of combining SUV and texture parameters.

PURPOSE: To retrospectively investigate the SUV-related and texture parameters individually and in combination for differentiating between F-18-fluorodeoxyglucose (FDG)-avid benign and metastatic adrenal tumors with PET/CT. METHODS: Thirteen benign adrenal tumors (BATs) and 22 metastatic adrenal tumors (MATs) with a metabolic tumor volume (MTV) > 10.0 cm3 and SUV ≥ 2.5 were included. SUVmax, MTV, total lesion glycolysis, and four textural parameters [entropy, homogeneity, intensity variability (IV), and size-zone variability] were obtained. These parameters were compared between BATs and MATs using Mann-Whitney U test, and the diagnostic performance was evaluated by the area under the curve (AUC) values derived from the receiver operating characteristic analysis. The diagnostic value of combining SUV and texture parameters was examined using a scoring system. RESULTS: MATs showed significantly higher SUVmax (p = 0.004), entropy (p = 0.013), IV (p = 0.006), and lower homogeneity (p = 0.019) than BATs. The accuracies for diagnosing MATs were 82.9, 82.9, 85.7, and 71.4% for SUVmax, entropy, IV, and homogeneity, respectively. No significant differences in AUC were found among these parameters (p > 0.05 each). When each parameter was scored as 0 (negative for malignancy) and 1 (positive for malignancy) according to each threshold criterion and the four parameter summed scores 0, 1, and 2 were defined as benignity and 3 and 4 as malignancy, the sensitivity and specificity and accuracy to predict MATs were 100% (22/22), 84.6% (11/13), and 94.3% (33/35), respectively, with 0.97 of the AUC. CONCLUSION: The combined use of SUVmax and texture parameters has a potential to significantly increase the diagnostic performance to differentiate between large FDG-avid BATs and MATs.

Impact of tissue photon attenuation in small animal cardiac PET imaging.

OBJECTIVES: Tissue photon attenuation is one of the essential artifacts requiring correction in clinical cardiac positron emission tomography (PET) imaging. However, due to small body size its impact on diagnostic accuracy in small rodents is considered to be limited or even ignorable. The present cardiac PET study compares lean and obese rats to determine the influence of tissue attenuation on quantitative assessment as well as regional tracer distribution. METHODS: A dedicated small animal PET system equipped with a 57Co rotating source for transmission was used. To assess the impact of tissue attenuation in rats with different body sizes, cardiac 18F-FDG -PET studies for Zucker diabetic fatty rats (obese rats) and Zucker lean rats (lean rats) were performed. The radiotracer activity reduction by attenuation was compared between the two groups. Regional tracer distribution calculated with and without attenuation correction was also assessed. RESULTS: The chest diameter was significantly longer in obese than in lean rats (5.6±0.3cm in obese and 4.5±0.2cm in lean rats, p<0.0001). Whereas the activity reduction by attenuation was significantly greater in obese than in lean rats (44.1±2.5% and 5.1±3.1%, p<0.0001), the regional variation of tissue attenuation among the ventricular walls was minimal in both lean (p=0.73) and obese rats (p=0.65). CONCLUSION: Attenuation correction is indispensable for accurate comparison of cardiac tracer activity between animals with different body size, whereas it can be omitted for evaluation of regional tracer distribution.

Development of a simultaneous optical/PET imaging system for awake mice.

Simultaneous measurements of multiple physiological parameters are essential for the study of brain disease mechanisms and the development of suitable therapies to treat them. In this study, we developed a measurement system for simultaneous optical imaging and PET for awake mice. The key elements of this system are the OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET is our original open-type PET geometry, which can be used in combination with another device because of the easily accessible open space of the former. A small prototype of the axial shift single-ring OpenPET was used. The objective lens for optical imaging with a mounted charge-coupled device camera was placed inside the open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse was also applied. As a first application of this system, simultaneous measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and [(11)C]raclopride-PET were performed under control and 5% CO2 inhalation (hypercapnia) conditions. Our system successfully obtained the CBF and [(11)C]raclopride radioactivity concentration simultaneously. Accumulation of [(11)C]raclopride was observed in the striatum where the density of dopamine D2 receptors is high. LSI measurements could be stably performed for more than 60 minutes. Increased CBF induced by hypercapnia was observed while CBF under the control condition was stable. We concluded that our imaging system should be useful for investigating the mechanisms of brain diseases in awake animal models.

Development of a small single-ring OpenPET prototype with a novel transformable architecture.

The single-ring OpenPET (SROP), for which the detector arrangement has a cylinder shape cut by two parallel planes at a slant angle to form an open space, is our original proposal for in-beam PET. In this study, we developed a small prototype of an axial-shift type SROP (AS-SROP) with a novel transformable architecture for a proof-of-concept. In the AS-SROP, detectors originally forming a cylindrical PET are axially shifted little by little. We designed the small AS-SROP prototype for 4-layer depth-of-interaction detectors arranged in a ring diameter of 250 mm. The prototype had two modes: open and closed. The open mode formed the SROP with the open space of 139 mm and the closed mode formed a conventional cylindrical PET. The detectors were simultaneously moved by a rotation handle allowing them to be transformed between the two modes. We evaluated the basic performance of the developed prototype and carried out in-beam imaging tests in the HIMAC using (11)C radioactive beam irradiation. As a result, we found the open mode enabled in-beam PET imaging at a slight cost of imaging performance; the spatial resolution and sensitivity were 2.6 mm and 5.1% for the open mode and 2.1 mm and 7.3% for the closed mode. We concluded that the AS-SROP can minimize the decrease of resolution and sensitivity, for example, by transforming into the closed mode immediately after the irradiation while maintaining the open space only for the in-beam PET measurement.