Simplified Assessment of Radioiodine Biokinetics for Thyroid Cancer Patients: A Practical Approach Using Continuous External Radiation Monitoring.

INTRODUCTION: The biokinetics of radioiodine (RAI) in thyroid cancer patients are complex. This study aims to develop a practical approach for assessing RAI biokinetics to predict patient discharge time and estimate radiation exposure to caregivers. METHODS: We retrospectively reviewed data from patients with differentiated thyroid carcinoma undergoing RAI treatment. Serial radiation dose rates were dynamically collected during hospitalization and fitted to a biexponential model to assess the biokinetic features: RAI uptake fraction of thyroid tissue (Ft) and effective half-life of extra-thyroid tissue (Tet). Correlations with 99mTc thyroid uptake ratio (TcUR), radiation retention ratio (RR), renal function, and body mass index (BMI) were analyzed. RESULTS: Thirty-five patients were enrolled. The derived Ft was 0.08 ± 0.06 and Tet was 7.57 ± 1.45 h. Pearson's correlation analysis revealed a significant association between Ft and both TcUR and RR (p < 0.05), while Tet correlated with renal function and BMI (p < 0.05). CONCLUSION: This novel and practical method assessing RAI biokinetics demonstrates consistency with other parameters and related studies, enhancing the model reliability. It shows promise in predicting an appropriate discharge time and estimating radiation exposure to caregivers, allowing for modifications to radiation protection precautions to follow ALARA principle and minimize the potential risks from radiation exposure.

The Titrated Mannitol Improved Central [99mTc] Tc TRODAT-1 Uptake in an Animal Model-A Clinically Feasible Application.

[99mTc]Tc TRODAT-1 is a widely used single photon emission tomography (SPECT) radiopharmaceutical in Asian practice for early detection of central dopaminergic disorders. However, its imaging quality remains sub-optimal. To overcome this problem, mannitol, an osmotic agent was used to observe its effect on improving striatal [99mTc]Tc TRODAT-1 uptake in rat brain by titrated human dosages to investigate a clinically feasible way to improve human imaging quality. [99mTc]Tc TRODAT-1 synthesis and quality control were performed as described. Sprague-Dawley rats were used for this study. The animal in vivo nanoSPECT/CT and ex vivo autoradiography were employed to observe and verify the striatal [99mTc]Tc TRODAT-1 uptake in rat brains using clinically equivalent doses (i.e., 0, 1 and 2 mL groups, each n = 5) of mannitol (20% w/v, equivalent to 200 mg/mL) by an intravenous administration. Specific binding ratios (SBRs) were calculated to express the central striatal uptake in different experimental groups. In the NanoSPECT/CT imaging, the highest SBRs of striatal [99mTc]Tc TRODAT-1 were reached at 75-90 min post-injection. The averaged striatal SBRs were 0.85 ± 0.13 (2 mL normal saline, the control group), 0.94 ± 0.26 (1 mL mannitol group) and 1.36 ± 0.12 (2 mL mannitol group, p < 0.01 which were significantly different than the control as well as 1 mL mannitol groups (p < 0.05). The SBRs from ex vivo autoradiography also showed a comparable trend of the striatal [99mTc]Tc TRODAT-1 uptake in the 2 mL, 1 mL mannitol and the control groups (1.76 ± 0.52, 0.91 ± 0.29, and 0.21 ± 0.03, respectively, p < 0.05). No remarkable changes of vital signs were found in the mannitol groups and the controls. Pre-treated mannitol revealed a significant increase of the central striatal [99mTc]Tc TRODAT-1 uptake in a rat model which not only enabled us to perform pre-clinical studies of dopaminergic related disorders but also provided a potential way to further optimize image quality in clinical practice.

Very-Low-Dose Radiation and Clinical Molecular Nuclear Medicine.

Emerging molecular and precision medicine makes nuclear medicine a de facto choice of imaging, especially in the era of target-oriented medical care. Nuclear medicine is minimally invasive, four-dimensional (space and time or dynamic space), and functional imaging using radioactive biochemical tracers in evaluating human diseases on an anatomically configured image. Many radiopharmaceuticals are also used in therapies. However, there have been concerns over the emission of radiation from the radionuclides, resulting in wrongly neglecting the potential benefits against little or any risks at all of imaging to the patients. The sound concepts of radiation and radiation protection are critical for promoting the optimal use of radiopharmaceuticals to patients, and alleviating concerns from caregivers, nuclear medicine staff, medical colleagues, and the public alike.

Fully Automated Delineation of Gross Tumor Volume for Head and Neck Cancer on PET-CT Using Deep Learning: A Dual-Center Study.

Purpose: In this study, we proposed an automated deep learning (DL) method for head and neck cancer (HNC) gross tumor volume (GTV) contouring on positron emission tomography-computed tomography (PET-CT) images. Materials and Methods: PET-CT images were collected from 22 newly diagnosed HNC patients, of whom 17 (Database 1) and 5 (Database 2) were from two centers, respectively. An oncologist and a radiologist decided the gold standard of GTV manually by consensus. We developed a deep convolutional neural network (DCNN) and trained the network based on the two-dimensional PET-CT images and the gold standard of GTV in the training dataset. We did two experiments: Experiment 1, with Database 1 only, and Experiment 2, with both Databases 1 and 2. In both Experiment 1 and Experiment 2, we evaluated the proposed method using a leave-one-out cross-validation strategy. We compared the median results in Experiment 2 (GTVa) with the performance of other methods in the literature and with the gold standard (GTVm). Results: A tumor segmentation task for a patient on coregistered PET-CT images took less than one minute. The dice similarity coefficient (DSC) of the proposed method in Experiment 1 and Experiment 2 was 0.481∼0.872 and 0.482∼0.868, respectively. The DSC of GTVa was better than that in previous studies. A high correlation was found between GTVa and GTVm (R = 0.99, P < 0.001). The median volume difference (%) between GTVm and GTVa was 10.9%. The median values of DSC, sensitivity, and precision of GTVa were 0.785, 0.764, and 0.789, respectively. Conclusion: A fully automatic GTV contouring method for HNC based on DCNN and PET-CT from dual centers has been successfully proposed with high accuracy and efficiency. Our proposed method is of help to the clinicians in HNC management.

Optimizing 18F-FDG Uptake Time Before Imaging Improves the Accuracy of PET/CT in Liver Lesions.

UNLABELLED: (18)F-FDG PET/CT has emerged as one of the fastest-growing imaging modalities. A shorter protocol results in a lower target-to-background ratio, which can increase the challenge of identifying mildly (18)F-FDG-avid lesions and differentiating inflammatory or physiologic activity from malignant activity. The purpose of this study was to determine the delay between radiotracer injection and imaging that optimizes target-to-background ratio while maintaining counts high enough to ensure scan sensitivity. METHODS: The study included 140 patients (66 male and 74 female; age range, 42-95 y) with suspected hepatic lesions as seen on an (18)F-FDG PET scan. SUV was determined as region-of-interest activity/(dose/total body weight). RESULTS: The mean injected dose was 610 ± 66.6 MBq (16.5 ±1.8 mCi), with a mean glucose level of 107 ± 26.6 mg/dL (standardized to 90 mg/dL). The uptake time before imaging ranged from 61 to 158 min, with a mean of 108.8 ± 24.8 min. The P values for the correlation of SUV to time were 0.004, 0.003, and 0.0001 for malignant lesions, benign lesions, and background hepatic tissue, respectively. CONCLUSION: An approximately 90-min time window from (18)F-FDG injection to PET imaging would significantly improve target-to-background ratio and, thus, quantitation and visual interpretation. This benefit outweighs the minimal loss in patient throughput.

Liver Fibrosis Can Be Induced by High Salt Intake through Excess Reactive Oxygen Species (ROS) Production.

High salt intake has been known to cause hypertension and other side effects. However, it is still unclear whether it also affects fibrosis in the mature or developing liver. This study demonstrates that high salt exposure in mice (4% NaCl in drinking water) and chick embryo (calculated final osmolality of the egg was 300 mosm/L) could lead to derangement of the hepatic cords and liver fibrosis using H&E, PAS, Masson, and Sirius red staining. Meanwhile, Desmin immunofluorescent staining of mouse and chick embryo livers indicated that hepatic stellate cells were activated after the high salt exposure. pHIS3 and BrdU immunohistological staining of mouse and chick embryo livers indicated that cell proliferation decreased; as well, TUNEL analyses indicated that cell apoptosis increased in the presence of high salt exposure. Next, dihydroethidium staining on the cultured chick hepatocytes indicated the excess ROS was generated following high salt exposure. Furthermore, AAPH (a known inducer of ROS production) treatment also induced the liver fibrosis in chick embryo. Positive Nrf2 and Keap1 immunohistological staining on mouse liver suggested that Nrf2/Keap1 signaling was involved in high salt induced ROS production. Finally, the CCK8 assay was used to determine whether or not the growth inhibitory effect induced by high salt exposure can be rescued by antioxidant vitamin C. Meanwhile, the RT-PCR result indicated that the Nrf2/Keap1 downsteam genes including HO-1, NQO-1, and SOD2 were involved in this process. In sum, these experiments suggest that high salt intake would lead to high risk of liver damage and fibrosis in both adults and developing embryos. The pathological mechanism may be the result from an imbalance between oxidative stress and the antioxidant system.

The Evaluation of Cardiac Sarcoidosis with 18F-FDG PET.

Cardiac involvement in sarcoidosis is associated with poor prognosis. (18)F-FDG PET can detect the presence of cardiac sarcoidosis, assess disease activity, and serve as a means to monitor treatment response in patients with cardiac sarcoidosis.

Percutaneous Cryoablation vs Partial Nephrectomy: Cost Comparison of T1a Tumors.

PURPOSE: To compare cost of percutaneous cryoablation vs open and robot-assisted partial nephrectomy of T1a renal masses from the hospital perspective. MATERIALS AND METHODS: We retrospectively compared cost, clinical and tumor data of 37 percutaneous cryoablations to 26 open and 102 robot-assisted partial nephrectomies. Total cost was the sum of direct and indirect cost of procedural and periprocedural variables. Clinical data included demographics, Charlson Comorbidity Index (CCI), hospitalization time, complication rate, ICU admission rate, and 30-day readmission rates. Tumor data included size, RENAL nephrometry score, and malignancy rate. Student's t-test was used for continuous variables and Fisher's exact or chi-square tests for categorical data. RESULTS: Mean total cost was lower for percutaneous cryoablation than open or robot-assisted partial nephrectomy: $6067 vs $11392 or $11830 (p<0.0001) with lower cost of procedure room: $1516 vs $3272 or $3254 (p<0.0001), room and board: $95 vs $1907 or $1106 (p<0.0001), anesthesia: $684 vs $1223 or $1468 (p<0.0001), and laboratory/pathology fees: $205 vs $804 or $720 (p<0.0001). Supply and device cost was higher than open: $2596 vs $1352 (p<0.0001), but lower than robot-assisted partial nephrectomy: $3207 (p=0.002). Mean hospitalization times were lower for percutaneous cryoablation (p<0.0001), while age and CCI were higher (p<0.0001). No differences in tumor size, nephrometry score, malignancy rate complication, ICU, or 30-day readmission rates were observed. CONCLUSION: Percutaneous cryoablation can be performed at significantly lower cost than open and robotic partial nephrectomies for similar masses.

Yttrium-90 Infusion: Incidence and Outcome of Delivery System Occlusions during 885 Deliveries.

PURPOSE: To evaluate the incidence, cause, and management of delivery system occlusions during yttrium-90 (90Y) microsphere infusions and to identify techniques to prevent occlusions. MATERIALS AND METHODS: A retrospective review was conducted of 885 consecutive radioembolization deliveries during 820 procedures (some with multiple deliveries) in 503 patients (mean age, 65 y; 293 male) performed between June 2001 and July 2013 at a single academic tertiary care hospital. Occlusions were reported prospectively, and procedural details were reviewed. Statistical analysis assessed associations between catheter occlusions and patient and procedural characteristics. RESULTS: Of 885 90Y microsphere deliveries, 11 resulted in occlusion (1.2%). Five occlusions were associated with contained leakage of radioactive material, and one was associated with a spill. Treatment was completed in the same day in 10 patients; repeat catheterization was required in five patients. One patient returned 1 week later to complete treatment. Occlusions were more frequent with deliveries of resin (11/492; 2.2%) versus glass (0/393; 0%) microspheres (P = .002). Occlusions were more likely to occur within the proximal portion of the delivery apparatus (P = .002). There was no significant relationship with any patient characteristics, and there was no improvement with operator experience. The most common cause of occlusion was resin microsphere delivery device failure. CONCLUSIONS: (90)Y microsphere delivery device occlusion is uncommon but does occur with resin microspheres. Understanding causes and how to troubleshoot can limit the incidence and detrimental effects.

Primary tumour standardised uptake value is prognostic in nonsmall cell lung cancer: a multivariate pooled analysis of individual data.

(18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I-II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22-1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I-III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27-1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I-III NSCLC, for squamous cell carcinoma and for adenocarcinoma.

Prognostic Value of (18)F-FDG PET-CT in Nasopharyngeal Carcinoma: Is Dynamic Scanning Helpful?

OBJECTIVES: To evaluate the differences in prognostic values of static and dynamic PET-CT in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS: Forty-five patients who had static scan were recruited. Sixteen had dynamic scan. The primary lesions were delineated from standardized uptake value (SUV) maps from static scan and K i maps from dynamic scan. The average follow-up lasted for 34 months. The patients who died or those with recurrence/residual disease were considered "poor outcome"; otherwise they were considered "good outcome." Fisher's exact test and ROC analysis were used to evaluate the prognostic value of various factors. RESULTS: Tumor volume thresholded by 40% of maximal SUV (VOLSUV40) significantly predicted treatment outcome (p = 0.024) in the whole cohort. In 16 patients with dynamic scan, all parameters by dynamic scan were insignificant in predicting the outcome. The combination of maximal SUV, maximal K i , VOLSUV40, and VOL K i 37 (the tumor volume thresholded by 37% maximal K i ) achieved the highest predicting accuracy for treatment outcome with sensitivity, specificity, and accuracy of 100% in these 16 patients; however this improvement compared to VOLSUV40 was insignificant. CONCLUSION: Tumor volume from static scan is useful in NPC prognosis. However, the role of dynamic scanning was not justified in this small cohort.

Systemic mastocytosis: a rare cause of single vertebral body uptake on bone scan.

Systemic Mastocytosis is a rare condition characterized by the abnormal proliferation of Mast Cells. Presentation as a solitary vertebral body lesion is extremely uncommon and may be confused with more ominous conditions such as metastasis. Familiarity with the condition can heighten clinical suspicion, direct tissue diagnosis, guide management and indicate appropriate follow up. We present a case of a 64-year-old woman undergoing staging for recently diagnosed breast cancer who was found to have Systemic Mastocytosis of a single vertebral body.

Detection of Aberrant Right Subclavian Artery by PET/CT.

An aberrant right subclavian artery can be diagnosed by PET/CT, as demonstrated in this case of a 70-y-old man undergoing PET/CT for staging of squamous cell carcinoma of the right lung. It is important to report this finding during the evaluation of oncologic patients, to prevent severe complications that may arise from various oncologic interventions.

The appearance of congenitally corrected transposition of the great arteries on myocardial perfusion imaging.

We present a case of incidentally discovered congenitally corrected transposition of the great arteries (ccTGA), initially seen on stress-rest myocardial perfusion imaging (MPI). ccTGA has a characteristic appearance on MPI, which reflects the functional alterations associated with this condition.

Glucose metabolism gene expression patterns and tumor uptake of ¹8F-fluorodeoxyglucose after radiation treatment.

PURPOSE: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). METHODS AND MATERIALS: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm(3) they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. RESULTS: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport-related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. CONCLUSION: (18)F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

18F-FDG PET assessment of Lewy body dementia with cerebellar diaschisis.

Alzheimer disease and Lewy body dementia are the 2 most common causes of dementia. Each disease has distinctive regional metabolic reduction patterns on (18)F-FDG PET. In this report, we present a rare case of an elderly man with dementia whereby (18)F-FDG PET clearly showed Lewy body disease with crossed cerebellar diaschisis.

Time sensitivity-corrected retention index: an enhanced metabolic index from 18F-FDG PET to differentiate between benign and malignant pulmonary nodules.

The aim of the study was to evaluate pulmonary nodules (PNs) by incorporating time sensitivity (S) factor in the retention index (RI) and compare with the traditional fixed interval method. After obtaining approval from the Human Investigations Committee, 97 PNs from 81 patients (age=70±11) referred for dual-time fluorine-18 fluorodeoxyglucose PET (16.1±1.9 mCi) with definite pathological diagnosis or 1-year computed tomography follow-up were retrospectively studied. S=d{ln[SUV]]/d{ln[T]} was obtained by logarithmic regression using scan times, T (0, 1, 2), and standard uptake value (SUV) (0, 1, 2). This time-corrected RI, RIs=[(T2/T1)-1]×100%, was compared with traditional fixed time interval RI, RIx=[(SUV2/SUV1)-1]×100%, by means of receiver operating characteristic curve analysis. The mean±SD of T1 and T2 (72.3±14.0 and 134.9±17.6 min, respectively) skewed markedly from the intended time of PET scans (skewness=2.076 and 1.356, respectively). There were 27 benign tumors, 37 cases of non-small-cell lung cancer, 15 other types of cancer, and 18 stable lesions by 1-year computed tomography follow-up. There were significant differences between the nonmalignant group (NM, n=45) and the cancer group (CA, n=52) in time sensitivity (0.186±0.161 vs. 0.483±0.180, P<0.0005) and RIs (12.7±12.5 vs. 37.4±17.5%, P<0.0005). The RIx showed wider variation than RIs, although the difference between NM and CA was also significant (18.0±28.8 vs. 37.8±32.0%, P=0.002). The RIs and RIx were only weakly correlated (r=0.257, P=0.011). Receiver operating characteristic curve analysis performed for the CA or NM groups revealed a significant improvement in the diagnostic accuracy for malignancy by RIs (area under the curve=0.880±0.035, P<0.0005) compared with RIx (area under the curve=0.694±0.054, P=0.001). Incorporating the time sensitivity factor improves the diagnostic performance of RI for malignant PNs by using additional biologic information from the variation in fluorine-18 fluorodeoxyglucose uptake times and rates.

The use of 99mTc-MDP bone scanning to assess facial bone growth.

Bone scanning is an important technique to detect mandibular growth, and its quantitation aids in deciding the optimal timing for surgery. Here, we will discuss a case of abnormal mandibular growth and use of bone scanning to evaluate the facial bone growth.

Implications of Ambient Glucose Variation on the Target-to-Background Ratio of Hepatic Tumors By (18)FDG-PET Imaging.

OBJECTIVES: To investigate the effects of ambient glucose on quantitative analysis of hepatic tumors on 2-deoxy-2-((18)F)-fluoro-D-glucose ((18)FDG) positron emission tomography (PET) and to establish a method for glucose correction. PATIENTS AND METHODS: Eighty-six patients with hepatic lesions identified on (18)FDG PET/computed tomography (CT) were analyzed. The serum glucose level (Glc) was recorded prior to imaging, and the maximum standardized uptake value (SUV) in the hepatic tumors and the average SUV in normal liver were determined. The inverse relationship of SUV to glucose can be defined as d (SUV)/d (Glc) = g*SUV/(Glc), where g is the glucose sensitivity. Simulations using glucose level from 70 to 250 mg/dl were performed to evaluate the effects of Glc on the maximum SUV of malignant hepatic lesions and normal liver. RESULTS: By logarithmic transformation and linear regression, g for metastasis was significantly higher than that for normal liver (-0.636 ± 0.144 vs. -0.0536 ± 0.0583; P = 0.00092). Simulation studies showed that the SUV in malignant lesions will decrease rapidly when Glc level is >120 mg/dl, while background liver remains relatively constant up to 250 mg/dl. CONCLUSION: The tumor FDG uptake is much more sensitive to ambient glucose level variation than the background liver. Therefore, correction by the glucose sensitivity factor will result in more accurate SUV measurements and make semi-quantitative analysis of (18)FDG PET scans more reliable.