New objective simple evaluation methods of amyloid PET/CT using whole-brain histogram and Top20%-Map.

OBJECTIVE: This study aims to assess the utility of newly developed objective methods for the evaluation of intracranial abnormal amyloid deposition using PET/CT histogram without use of cortical ROI analyses. METHODS: Twenty-five healthy volunteers (HV) and 38 patients with diagnosed or suspected dementia who had undergone 18F-FPYBF-2 PET/CT were retrospectively included in this study. Out of them, 11C-PiB PET/CT had been also performed in 13 subjects. In addition to the conventional methods, namely visual judgment and quantitative analyses using composed standardized uptake value ratio (comSUVR), the PET images were also evaluated by the following new parameters: the skewness and the mode-to-mean ratio (MMR) obtained from the histogram of the brain parenchyma; Top20%-map highlights the areas with high tracer accumulation occupying 20% volume of the total brain parenchymal on the individual's CT images. We evaluated the utility of the new methods using histogram compared with the visual assessment and comSUVR. The results of these new methods between 18F-FPYBF-2 and 11C-PiB were also compared in 13 subjects. RESULTS: In visual analysis, 32, 9, and 22 subjects showed negative, border, and positive results, and composed SUVR in each group were 1.11 ± 0.06, 1.20 ± 0.13, and 1.48 ± 0.18 (p < 0.0001), respectively. Visually positive subjects showed significantly low skewness and high MMR (p < 0.0001), and the Top20%-Map showed the presence or absence of abnormal deposits clearly. In comparison between the two tracers, visual evaluation was all consistent, and the ComSUVR, the skewness, the MMR showed significant good correlation. The Top20%-Maps showed similar pattern. CONCLUSIONS: Our new methods using the histogram of the brain parenchymal accumulation are simple and suitable for clinical practice of amyloid PET, and Top20%-Map on the individual's brain CT can be of great help for the visual assessment.

18 F-FDG PET/CT Findings of Surgically Transposed Ovaries After Radical Hysterectomy in a Young Adult Patient.

ABSTRACT: A 35-year-old woman underwent 18 F-FDG PET/CT 2 months after a radical hysterectomy for uterine cervical cancer. An apparent FDG uptake was observed in an oval-shaped mass with an attached surgical clip in the right paracolic gutter. A similar non-FDG-avid mass with a clip was observed in the left. In this case, ovarian transposition had also been performed with metallic clips placed on both sides of the paracolic gutters. The increased FDG uptake in the right paracolic gutter was interpreted as physiological uptake in the right transposed ovary, not metastasis. Recognizing the possibility of FDG uptake in transposed ovaries is important.

Characteristic Muscular FDG Uptake Patterns Related to the Transportation Means Used by Patients to Visit the Hospital.

ABSTRACT: It is well-known that physiological FDG uptake in the skeletal muscles is affected by serum insulin levels and the extent to which the muscles contract before the examination. Patients are instructed to refrain from strenuous exercise, talking too much, and taking meals at least 4 hours before the administration of the tracer. Even if the patient does not intend to exercise, muscular accumulation related to specific behaviors can still be visualized in the images. In this manuscript, we present FDG PET/CT images from 4 cases reflecting the mode of transportation used by the patients to visit the hospital.

Radiation dosimetry and pharmacokinetics of the tau PET tracer florzolotau (18F) in healthy Japanese subjects.

OBJECTIVE: Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. Florzolotau (18F) (florzolotau, APN-1607, PM-PBB3) has been shown to be a probe for tau fibrils in an animal model and patients with Alzheimer's disease and those with non-Alzheimer's disease tauopathies. The objective of this study is to evaluate the safety, pharmacokinetics, and radiation dose following a single intravenous administration of florzolotau in healthy Japanese subjects. METHODS: Three healthy male Japanese subjects aged between 20 and 64 were enrolled in this study. Subjects were determined to be eligible based on the screening assessments at the study site. Subjects received a single intravenous dose of 195.0 ± 0.5 MBq of florzolotau and underwent the whole-body PET scan 10 times in total to calculate absorbed doses to major organs/tissues and effective dose. Radioactivities in whole blood and urine were also measured for pharmacokinetic evaluation. Absorbed doses to major organs/tissues and effective dose were estimated using the medical internal radiation dose (MIRD) method. Vital signs, electrocardiography (ECG), and blood tests were done for safety evaluation. RESULTS: The intravenous injection of florzolotau was well tolerated. There were no adverse events or clinically detectable pharmacologic effects related to the tracer in any subjects. No significant changes in vital signs and ECG were observed. The highest mean initial uptake at 15 min after injection was in the liver (29.0 ± 4.0%ID), intestine (4.69 ± 1.65%ID), and brain (2.13 ± 0.18%ID). The highest absorbed dose was 508 µGy/MBq of the gallbladder wall, followed by the liver of 79.4 µGy/MBq, the pancreas of 42.5 µGy/MBq, and the upper large intestine of 34.2 µGy/MBq. The effective dose was calculated as 19.7 µSv/MBq according to the tissue weighting factor reported by ICRP-103. CONCLUSION: Florzolotau intravenous injection was well tolerated in healthy male Japanese subjects. The effective dose was determined as 3.61 mSv when 185 MBq florzolotau was given.

FDG-PET findings associated with various medical procedures and treatments.

[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established modality with high sensitivity for the diagnosis and staging of oncologic patients. FDG is taken up by the glucose transporter of the cell membrane and becomes trapped within the cell. In addition to malignant neoplasms, active inflammatory lesions and some kinds of benign tumors also accumulate FDG. Moreover, the degree of uptake into normal organs and tissues depends on various physiological conditions, which is affected by various medical procedures, treatments, and drugs. To avoid misleading interpretations, it is important to recognize possible situations of unexpected abnormal accumulation that mimic tumor lesions. In this review, we present various FDG findings associated with surgical or medical procedures and treatments. Some findings reflect the expected physiological reaction to treatment, and some show inflammation due to prior procedures. Occasionally, FDG-PET visualizes other disorders that are unrelated to the malignancy, which may be associated with the adverse effects of certain drugs that the patient is taking. Careful review of medical records and detailed interviews of patients are thus necessary.

Misery Perfusion and Tau Deposition in Atherosclerotic Major Cerebral Artery Disease: A 18F-Florzolotau Positron Emission Tomography Study.

BACKGROUND: Studies using animal models have shown that cerebral hypoperfusion causes hyperphosphorylation of tau protein, leading to neuronal damage. However, the relationship between hypoperfusion and tau deposition in humans is unclear. Hence, we aimed to determine whether cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increased tau deposition in patients with atherosclerotic internal carotid artery or middle cerebral artery disease. METHODS: We prospectively evaluated the distribution of tau aggregate deposition using positron emission tomography and 18F-florzolotau (PMPBB3 [1-fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol)]) in 8 patients with atherosclerotic disease of the internal carotid artery or middle cerebral artery. The standardized uptake value ratio of 18F-florzolotau at 100 to 110 minutes after injection was calculated using the cerebellar cortex as a reference region and was correlated with OEF obtained from 15O-gas positron emission tomography in the middle cerebral artery distributions. RESULTS: Significant decreases in cerebral blood flow and cerebral metabolic rate of oxygen and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion. 18F-florzolotau standardized uptake value ratio in this region was also greater than that in the contralateral hemisphere. In the ipsilateral hemisphere, 18F-florzolotau standardized uptake value ratio positively correlated with OEF values. CONCLUSIONS: This pilot study with a small sample size suggests that increases in OEF-misery perfusion-may be associated with increased tau aggregates deposition in atherosclerotic internal carotid artery or middle cerebral artery disease.

Neuronal Alterations in Secondary Thalamic Degeneration Due to Cerebral Infarction: A 11C-Flumazenil Positron Emission Tomography Study.

BACKGROUND: Studies using animal experiments have shown secondary neuronal degeneration in the thalamus after cerebral infarction. Neuroimaging studies in humans have revealed changes in imaging parameters in the thalamus, remote to the infarction. However, few studies have directly demonstrated neuronal changes in the thalamus in vivo. The purpose of this study was to determine whether secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease. METHODS: We retrospectively analyzed the data of 140 patients with unilateral cerebral infarction ipsilateral to internal carotid artery or middle cerebral artery disease. All patients had quantitative measurements of 11C-flumazenil binding potential (FMZ-BP), cerebral blood flow, and cerebral metabolic rate of oxygen using positron emission tomography in the chronic stage. Region of interest analysis was performed using NeuroFlexer-an automated region of interest analysis software using NEUROSTAT. RESULTS: In the thalamus ipsilateral to the infarcts, the values of FMZ-BP, cerebral blood flow, and cerebral metabolic rate of oxygen were significantly lower than those in the contralateral thalamus. Significant correlations were found between the ipsilateral-to-contralateral ratio of FMZ-BP and the ipsilateral-to-contralateral ratio of cerebral blood flow or cerebral metabolic rate of oxygen in the thalamus. Patients with corona radiata infarcts and striatocapsular infarcts had significantly decreased ipsilateral-to-contralateral FMZ-BP ratio in the thalamus compared with those without. The ipsilateral-to-contralateral ratio of FMZ-BP in the thalamus was significantly correlated with the ipsilateral-to-contralateral cerebral metabolic rate of oxygen ratio in the frontal cortex and showed a significant negative correlation with the number of perseverative errors on the Wisconsin Card Sorting Test. CONCLUSIONS: Secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease, which may be associated with frontal lobe dysfunction.

Visit-to-Visit Blood PressureVariations and Hemodynamic Deterioration in Atherosclerotic Major Cerebral ArteryDisease.

OBJECTIVE: Visit-to-visit variations in blood pressure (BP) in patients with atherosclerotic major cerebral artery disease could impair the function of cerebral collaterals, leading to hemodynamic deterioration at follow-up. However, few studies have investigated the relationship between visit-to-visit BP variability and changes in hemodynamic parameters at follow-up. MATERIALS AND METHODS: We evaluated 35 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischemic episodes during follow-up (mean: 35 ± 20 months); these patients had a three-time visit for positron emission tomography examinations with 15O-gas. Differences in the mean hemispheric values of hemodynamic parameters in the cortical territory of the diseased artery between the first and third examinations (changes at follow-up) were correlated with the coefficient of variation (CoV) in three systolic BP (SBP) values at the three examinations (BP variability during follow-up). RESULTS: CoV values were negatively correlated with changes in oxygen metabolism or cerebral blood flow/cerebral blood volume (CBF/CBV) ratio. In 17 patients with higher CoV values (> group median, 0.072), decreases in CBF, cerebral metabolic rate of oxygen, and CBF/CBV ratio were observed at follow-up; CBV decreased in 18 patients without elevated CoV. A higher CoV was associated with a lack of statin use. CONCLUSION: In patients with atherosclerotic major cerebral artery disease, high visit-to-visit SBP variations during follow-up may be associated with deterioration in cerebral hemodynamics and metabolism.

Physiologically decreased F-18 fluorodeoxyglucose uptake in the lower vertebrae associated with daily drinking habit in Japanese men with alcohol flushing reaction.

Alcohol flushing reaction (AFR) is known as one of the risks for esophageal squamous cell cancer, and scientists have been elucidating this issue. However, little attention has been given to relevant imaging features. This study aims to investigate whether physiological 18F-fluorodeoxyglucose (FDG) uptake patterns in vertebrae are associated with drinking habits or AFR. Japanese male patients who underwent FDG positron emission computed tomography for evaluation of their known or suspected malignancies or inflammatory diseases were asked about their drinking habits and AFR. Altogether, 192 patients, 139 every-day drinkers and 53 non-drinkers were evaluated. Comparing the FDG uptake between that in the thoracic region and that in the lumbar region, vertebral uptake was visually classified into four patterns: Ld, dominant in lumbar region; TL, almost equal in both regions; BL, slightly higher in thoracic region (borderline pattern); Td, dominant in thoracic region. The uptake patterns were evaluated according to drinking habit (every-day drinker or non-drinker), AFR (flusher or non-flusher), and the combination of these two factors (habit/reaction: every-day drinker/flusher, every-day drinker/non-flusher, non-drinker/flusher, or non-drinker/non-flusher). There were 95 flushers (51 every-day drinkers and 44 non-drinkers) and 97 non-flushers (88 every-day drinkers and 9 non-drinkers). Ld, TL, BL, and Td patterns were observed in 0, 109 (56.8%), 31 (16.1%), and 52 (27.1%) patients, respectively. Td and BL patterns were more frequently observed in every-day drinkers compared with non-drinkers (p = 0.0467). Though the uptake patterns did not differ between flushers and non-flushers (p = 0.116), the Td pattern was more frequently observed in every-day drinkers/flushers (51%) compared with every-day drinkers/non-flushers (20.5%), non-drinkers/flushers (13.6%), and non-drinkers/non-flushers (22.2%) (p = 0.0014). The Td pattern was observed in patients with various diseases, with higher frequency in esophageal cancer, head and neck cancer, and lung cancer compared with other diseases. In conclusion, drinking habits and AFR were related to the vertebral uptake pattern with decreased uptake in the lumbar region in Japanese male patients.

Spatial Patterns of Amyloid Deposition in Patients with Chronic Focal or Diffuse Traumatic Brain Injury Using 18F-FPYBF-2 PET.

AIM: Amyloid-ß (Aß) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aß dynamics because of TBI's complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) positron emission tomography (PET). METHODS: Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent 18F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either 18F-FPYBF-2 PET (n=30) or structural MRI (n=20). RESULTS: Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI. CONCLUSION: Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.

FDG Uptake in Brown Adipose Tissue Activated by a ß3-Adrenergic Receptor Agonist Prescribed for Overactive Bladder.

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a ß3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.

Complete Spontaneous Regression of Hepatosplenic T-Cell Lymphoma After Surgical Biopsy.

F-FDG PET/CT for a 74-year-old man with elevated serum soluble interleukin 2 receptor showed multiple intense uptake in the liver, spleen, and bone. A surgical biopsy from 2 of liver tumors confirmed hepatosplenic αß T-cell lymphoma. One and a half months after biopsy, FDG PET scan was performed again for staging before starting chemotherapy, and it showed the complete disappearance of all of the lesions. The excisional biopsy could be a possible trigger of his spontaneous regression.

Predominance and homogeneity patterns of physiological FDG accumulation in thoracic and lumbar vertebrae: suspected mechanism of "bone pseudometastasis" on FDG-PET in Japanese patients with esophageal cancer.

OBJECTIVE: False-positive bone lesions (bone pseudometastases) have been often reported in patients with esophageal cancer (EsoC). This study aimed to evaluate the vertebral 2-deoxy-2-[18F] fluoro-D-glucose (FDG) accumulation pattern in patients with newly diagnosed esophageal cancers and other malignancies (OtherT) to elucidate the possible mechanism that causes bone pseudometastasis. METHODS: FDG positron emission tomography/computed tomography performed for 90 patients with EsoC, and 112 patients with OtherT was retrospectively evaluated. The uptake pattern in the thoracic (Th) and lumbar (L) vertebrae was visually assessed regarding predominance (TL, Th ≒ L; Td, Th > L; Ld, L > Th), main intensity compared with the uptake in the blood pool (BP) (Grade 1 < BP, Grade 2 ≒ BP, or Grade 3 > BP), and homogeneity (homogeneous, heterogeneous, marginal, or spotty). The patterns between EsoC and OtherT and between Th and L were compared. RESULTS: TL, Td, and Ld patterns were observed in 51.1%, 48.9%, and 0% in EsoC and 79.7%, 20.3%, and 0% in OtherT. Though Grade 2 was most frequently observed in both groups, the ratio of Grade 3 in Th and Grade 1 in L was significantly higher in EsoC than in OtherT. Heterogeneous and spotty patterns were more frequently observed in L and in EsoC, and these were strongly associated with Td pattern. CONCLUSION: Td pattern was frequently seen, especially in EsoC, and was strongly associated with a heterogeneous or marginal pattern in the L. Heterogeneous marrow distribution with declined lumbar uptake is suspected as the mechanism of bone pseudometastasis.

[Report in 2017 April ～ 2018 March].

Women physicians, scientists and nurses are addressing many problems encountered in the practice of their chosen fields. We carried out a survey of the women working in the nuclear medicine field. Two hundred and six professionals answered this questionnaire. The findings of our survey were that we have many female bosses (experts), a low number of sexual harassment issues and enough parental leave. Many members work very hard to practice in this field, but they do not have enough support from their hospitals or research centers, to join medical conferences. And almost a quarter of those surveyed thought it is hard to improve their careers after taking parental leave. A change of perception in how their male colleagues and counterparts regard women in the field of nuclear medicine is required. This change, along with women having a clear and realistic career plan are fundamental answers to the issues faced by women in nuclear medicine.

Significantly Increased Accumulation of 18F-FDG Throughout the Left Middle Cerebral Artery Territory Corresponding to Acute-Phase Infarction.

A 70-year-old woman had spontaneous resolution of an embolism in her right middle cerebral artery (MCA) (day 1); another embolism occurred in her left MCA (day 3), which was promptly removed. On day 5, F-FDG PET/CT performed for staging mediastinal lymphoma showed marked FDG accumulation in the left MCA territory, whereas a defect was seen in the right insular region. Eventually, bilateral lesions developed irreversible infarction. Anaerobic metabolism and/or inflammation in acute-phase infarction were the supposed mechanism for the increased accumulation of FDG in her left MCA territory.

Diffusely Decreased Liver Uptake on FDG PET and Cancer-Associated Cachexia With Reduced Survival.

OBJECTIVES: We investigated clinical characteristics of patients with extremely increased or decreased physiologic F-FDG uptake of the liver and their prognosis. METHODS: One thousand four hundred eighty-seven PET/CT scans of patients with known or suspected malignancy were retrospectively analyzed. A spherical volume of interest (3 cm in diameter) was set on the right lobe of the liver to calculate the SUVmean. Scans with extremely high (SUVmean >97.5th percentile) and low (SUVmean <2.5th percentile) FDG uptake in the liver were evaluated. Physical and laboratory data among a control group (n = 30), the extremely high liver uptake group (HG, n = 36), and the extremely low liver uptake group (LG, n = 36) were compared. Overall survival (OS) of the 3 groups was also compared. RESULTS: Body weight and body mass index in the HG (SUVmean ≥3.04) were significantly higher than those in the control group. The LG cases (SUVmean ≤1.78) had anemia, impaired liver function, and systemic inflammation. They were also in a poor nutritional state. The characteristics of LG cases had many things in common with those of cachectic patients. Indeed, 36.1% of LG cases met the diagnostic criteria for cachexia. Moreover, in LG cases with viable and/or recurrent malignant lesions on FDG PET, the proportion of cachexia increased by 52.6%. The OS of LG cases (median, 33 months) was significantly worse than that of controls and HG cases. CONCLUSIONS: Our data indicate that cancer patients with extremely decreased liver FDG uptake were likely to have cancer cachexia and a lower OS.

The difference of risk factors predicting cardiac events in patients with chronic kidney disease between with and without diabetes.

OBJECTIVE: Chronic kidney disease (CKD) and diabetes are both associated with cardiovascular disease, but the effects of diabetes in patients with CKD remain unknown. This study aimed to compare the risk factors of cardiac events between patients with CKD accompanied and not by diabetes using myocardial perfusion imaging. METHODS: We initially classified 529 patients with CKD from the Japanese Assessment of Cardiac Events and Survival Study-3 (J-ACCESS-3) study who had been assessed by gated single-photon emission-computed tomography based on whether they had diabetes (n = 220) or not (n = 309) and then separated them into four subgroups based on the ejection fraction (EF) calculated by quantitative gated SPECT. After 3-year follow-up, the incidence of major cardiac events (cardiac death, sudden death, non-fatal myocardial infarction, and heart failure requiring hospitalization), risk factors among each group, and the ability of myocardial perfusion image to predict prognosis were evaluated. RESULTS: Major cardiac events occurred in 12.7% and 10.3% of patients with and without diabetes (not significant), and heart failure requiring hospitalization was the most frequent (75% and 78%, respectively) in both groups. Event-free survival rates were lower in the subgroups with low EF and high summed stress scores (SSS). Independent risk factors comprised currently smoking and a higher SSS, among patients with diabetes, while higher left ventricular end diastolic volumes and serum C-reactive protein values among those without diabetes. CONCLUSIONS: In patients with CKD, while the risk factors of major cardiac events differ between in patients with and without diabetes, quantitation with gated MPI could be used effectively in both groups.

Bone Pseudometastasis on 18F-FDG PET in Japanese Patients With Esophageal Cancer.

PURPOSE OF THE REPORT: False-positive bone lesions mimicking bone metastases (bone pseudometastasis) on F-FDG PET/CT have often been reported in patients with esophageal cancer. We aimed to evaluate the prevalence and features of these lesions in Japanese patients with esophageal cancer. METHODS: In this retrospective study, we analyzed 83 FDG PET/CT studies for initial staging of esophageal cancer, and extracted patients with 1 or more localized high uptake sites with no subsequent progression, which were therefore judged to be bone pseudometastasis. The FDG PET/CT imaging features of the bone pseudometastasis were evaluated, and other available imaging and clinical features reviewed. RESULTS: Of the 83 patients, 7 had bone pseudometastasis. All 7 were males diagnosed with squamous cell cancer, of which 5 had T1a tumors. Bone pseudometastasis showed normal or ill-defined hyperdense (nonosteolytic) sites compared with the surrounding area on the CT. Additionally, accumulation in the upper vertebral levels of each case was contiguously high compared with the lumbar spines (we named this finding "contiguous accumulation"). On MRI, these findings were visualized as low signals on T1-weighted imaging (T1WI) and T2WI images but were unclear on fat-suppressed T2WI images. CONCLUSIONS: Among all PET/CT performed for staging of esophageal cancer, 8.3% demonstrated bone pseudometastasis characterized by heterogeneous distribution with severe fatty degeneration of bone marrow accompanied by contiguous accumulation. Caution is required during diagnoses of bone lesions in esophageal cancer patients in Japan to prevent inappropriate therapeutic choices.