Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: a retrospective cross-sectional study.

OBJECTIVES: We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer's disease (AD) using biomarkers. DESIGN: Retrospective cross-sectional study. SETTING: Neuropsychology clinic of Osaka University Hospital in Japan. PARTICIPANTS: Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP-AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI-P+AD) participants. MEASUREMENTS: Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics. RESULTS: Those in both VLOSLP-AD and +AD groups scored higher than those in aMCI-P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP-AD participants scoring significantly higher than aMCI-P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP-AD and +AD participants. Four VLOSLP-AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP-AD patients and five VLOSLP+AD patients. CONCLUSION: Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.

Usefulness of 18F-FPP-RGD2 PET in pathophysiological evaluation of lung fibrosis using a bleomycin-induced rat model.

PURPOSE: Integrins αv are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin αvß3 imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an 18F-FPP-RGD2 PET probe in a rat model of bleomycin-induced lung fibrosis. METHODS: Pulmonary fibrosis was induced by single intratracheal instillation of bleomycin (3 mg/rat). Positron emission tomography (PET)/computerized tomography scans were performed 4 weeks after bleomycin administration using 18F-FPP-RGD2. Total distribution volume (VT) was estimated using one-tissue/two-compartment, two-tissue/three-compartment models, and Logan graphical analysis (Logan plot; t* = 30 min). Plasma-free fractions were estimated from images of the left ventricle. Correlation between Logan VT and lung pathology was assessed by Spearman's rank correlation. RESULTS: Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin αv protein expression and lung radioactivity were higher in IPF-model group compared with control group. The lung radioactivity of 18F-FPP-RGD2 rapidly reached the peak after administration and then gradually decreased, whereas left ventricular radioactivity rapidly disappeared. Logan graphical analysis was found to be suitable for 18F-FPP-RGD2 kinetic analysis in the IPF-model lung. Logan VT values for 18F-FPP-RGD2 were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin αv protein expression, and oxygen partial pressure. CONCLUSION: Our findings demonstrate that the integrin αvß3 PET probe 18F-FPP-RGD2 can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin αv of IPF-model rats. These findings support the utility of 18F-FPP-RGD2 PET imaging for the pathophysiological evaluation of pulmonary fibrosis.

Volumetric and texture analysis on FDG PET in evaluating and predicting treatment response and recurrence after chemotherapy in follicular lymphoma.

PURPOSE: The purpose of this study was to determine if quantitative SUV-related, volumetric FDG PET parameters, and texture features (SPs, VPs, and TFs, respectively) were useful to evaluate and predict response and recurrence after chemotherapy in follicular lymphoma (FL). METHODS: Pre- and posttreatment FDG PET examinations in 45 FL patients were analyzed retrospectively. In addition to SPs in the representative lesion, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated as VPs for the representative and whole-body lesions. Six TFs were calculated in the pretreatment representative lesion. Response results with reduction of SPs or VPs after treatment (Δ) were compared to the Lugano classification based on visual assessment. SPs, VPs, and Δ of them as well as TFs were also evaluated if they allow prediction of response and recurrence after chemotherapy. RESULTS: Quantitative assessment with SPs and VPs provided 89% and 93-96% concordant results, respectively, with Lugano classification. Among pretreatment PET parameters, low gray-level zone emphasis (LGZE) in TFs solely showed statistical significance to predict complete response. All of posttreatment and Δ of SPs and VPs were considered as the predictors of progression free survival in the univariate Cox regression analysis, but none of them was the predictor in the multivariate analysis. CONCLUSION: This study demonstrated that quantitative PET parameters were applicable to evaluate treatment response in FL. Texture analysis showed promise in predicting treatment response. Although posttreatment and Δ of PET parameters were the candidates, all of them proved to have limited value in predicting recurrence after chemotherapy.

Value of 18F-FDG PET/CT in discrimination between indolent and aggressive non-Hodgkin's lymphoma: A study of 328 patients.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) cases with inconclusive biopsy findings are not infrequently referred for fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). We searched for maximum standardized uptake value (SUVmax) cut-off values that could discriminate between indolent and aggressive NHL in conventional non-time of flight (non-TOF) 18F-FDG PET/CT and TOF 18F-FDG PET/CT. SUBJECTS AND METHODS: Retrospectively, 328 patients were selected by the following inclusion criteria: biopsy-proven NHL with no more than one histopathological type; new cases with less than 90 days between obtaining biopsy and 18F-FDG PET/CT scanning; recurrent cases with time interval more than six months since the last therapy with no history of transformation; and blood glucose less than 150mg/dL. Two hundred forty six (246) selected patients were scanned with non-TOF PET/CT, and 82 patients were scanned with TOF 18F-FDG PET/CT. RESULTS: The SUVmax of NHL tends to be higher in TOF 18F-FDG PET/CT than non-TOF 18F-FDG PET/CT. New aggressive NHL had significantly higher SUVmax than new indolent NHL in both, non-TOF 18F-FDG PET/CT (13.6±7.7g/mL vs. 5.3±3.4g/mL, P<0.0001) and TOF 18F-FDG PET/CT (20.5±9.8g/mL vs. 6.6±4.7g/mL, P<0.0001). A receiver operating characteristic curve analysis for new cases in non-TOF 18F-FDG PET/CT (n=204), demonstrated SUVmax of 10g/mL as the most balanced cut-off between aggressive and indolent NHL, with the area under the curve (AUC) of 86%, specificity of 94%, and sensitivity of 71%. While SUVmax of 13g/mL was the most balanced cut-off for new cases in TOF 18F-FDG PET/CT (n=57), with AUC of 91%, specificity of 95.5%, and sensitivity of 77%. CONCLUSION: Both SUVmax>10g/mL in non-TOF 18F-FDG PET/CT and >13g/mL in TOF 18F-FDG PET/CT were highly suggestive of an aggressive nature of NHL, while there was an overlap between indolent and aggressive NHL in the lower SUVmax levels.

Phlebectasia of the external jugular vein with thrombosis: report of a case.

An 81-year-old male presented with a soft mass on his neck noted in the supine position. After undergoing an operation for an inguinal hernia, the mass was noted to persist regardless of the patient's position. Computed tomography and magnetic resonance imaging revealed phlebectasia of the external jugular vein with an associated thrombosis. Under general anesthesia, the external jugular vein was ligated and removed, along with the thrombus. A histological section revealed that the tunica media of the external jugular vein was absent, and the smooth muscle layer and elastic fibers were attenuated in the fusiform area of the vein. Due to the risk of propagation of the clot and pulmonary embolism, resection of the external jugular vein is advised in cases of phlebectasia of the external jugular vein.

Effect of scan-time shortening on the 11C-PHNO binding potential to dopamine D3 receptor in humans and test-retest reliability.

OBJECTIVE: 11C-PHNO is a PET radioligand most specific to dopamine D3 receptor (D3R). The long scan duration of 120 min used in quantification of 11C-PHNO binding to D3R in previous studies is challenging to subjects. The main objective of this study was to investigate the effects of shorter scan times on the binding of 11C-PHNO to D3R and test-retest reliability using the latest digital whole-body PET system. METHODS: Two 120-min 11C-PHNO brain scans were performed in 7 healthy subjects using a digital whole-body PET/CT. The binding potential relative to non-displaceable tracer in the tissue (BPND) of D3R-rich regions: the pallidum, ventral striatum (VST), substantia nigra (SN) and hypothalamus, were quantified using the simplified reference tissue model. The bias, correlation, and test-retest reliability of BPND, which includes the test-retest variability (TRV) and intraclass correlation coefficient (ICC), were evaluated and compared between scans of shorter durations (40-110 min post-injection) and the original 120-min scan acquisitions. RESULTS: Progressively, shorter scan durations were associated with underestimation of BPND, slightly decreased correlation with 120-min derived BPND, and decrease in test-retest reliability. The BPND values of the pallidum, VST and SN from the shortened 90-min scans showed excellent correlation with those derived from the 120-min scans (determination coefficients > 0.98), and the bias within 5%. The test-retest reliability of BPND in these regions derived from 90-min scan (TRV of 3% in the VST and pallidum, 7% in the SN and the ICC exceeded 0.88) was comparable to those obtained in previous 120-min studies using brain-dedicated PET scanners. In the hypothalamus, the BPND values obtained from scan-time less than 110 min showed bias larger than 5% and the TRV more than 9%. CONCLUSION: The scan-time shortening causes bias and decreasing test-retest reliability of 11C-PHNO BPND. However, in the whole-body PET system, 90-min scan duration was sufficient for estimating the 11C-PHNO BPND in the D3R-rich striatum and SN with small bias and at the test-retest reliability comparable to those derived from 120-min scans using the brain-dedicated PET systems.

Evaluation of an Integrin αvß3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver.

Purpose: Integrin αv is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin αvß3 positron emission tomography (PET) radiotracer, 18F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([18F]F-FPP-RGD2), for detecting hepatic integrin αv and function in nonalcoholic steatohepatitis (NASH) model rats using integrin αv siRNA. Methods: NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin αv protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin αv siRNA. Results: Integrin αv siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin αv protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [18F]F-FPP-RGD2 was decreased dose-dependently by integrin αv siRNA. The mean standard uptake value was positively correlated with integrin αv protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin αv protein expression levels in NASH model rats. Conclusion: This study suggests that [18F]F-FPP-RGD2 PET imaging is a promising radiotracer for monitoring hepatic integrin αv protein levels and hepatic function in NASH pathology.

Semiquantitative analysis using whole-body dynamic F-18 fluoro-2-deoxy-glucose-positron emission tomography to differentiate between benign and malignant lesions.

OBJECTIVES: To investigate whether whole-body dynamic positron emission tomography (PET) is useful for differentiating benign and malignant lesions. METHODS: In this retrospective study, data from a cohort of 146 lesions from 187 patients who consecutively underwent whole-body dynamic PET scans at our hospital for suspected lesions in the lung, lymph nodes, liver, bone, esophagus, and colon were analyzed. Patients with malignant lymphomas, accumulations > 5 cm in length along the long axis of the esophagus, or lesions in the colon in which the site of accumulation moved during the imaging period were excluded. Patients were administered 3.7 MBq/kg of fluorine-18-fluorodeoxyglucose (F-18 FDG), and dynamic imaging was initiated 60 min after administration. We defined the 60-65, 65-70, 70-75, and 75-80 min time mark as the first, second, third, and fourth pass, respectively. The static image is the summed average of all the four pass images. We measured the accumulation in the mean image of the whole-body dynamic PET scan, which was arithmetically similar to the maximum standardized uptake value (SUVmax) throughout the whole-body static images obtained during 20 min of imaging (S-SUVmax). The ratio of SUVmax in the dynamic first pass(60-65 min after FDG administration) and fourth pass(75-80 min after FDG administration) was calculated as R-SUVmax. RESULTS: The S-SUVmax in the lung, lymph nodes, and bone did not differ significantly between the benign and malignant groups. However, there was a significant difference in R-SUVmax, which was > 1 in most malignant lesions indicating an increase in accumulation during routine scan time. Significant differences were observed between benign and malignant lesions of the liver in both S-SUVmax and R-SUVmax values, with the latter being > 1 in most malignant lesions. CONCLUSIONS: Whole-body dynamic PET for 20 min starting 1 h after FDG administration improved the accuracy of malignant lesion detection in the liver, lymph nodes, lung, and bone. The incremental improvement was small, and the FDG dynamics in the distribution of values between benign and malignant overlapped. Additional information from whole-body dynamic imaging can help detect malignant lesions in these sites without increasing patient burden or prolonging imaging time.

Multi-modal 3D imaging of radionuclides using multiple hybrid Compton cameras.

For radiological diagnosis and radionuclide therapy, X-ray and gamma-ray imaging technologies are essential. Single-photon emission tomography (SPECT) and positron emission tomography (PET) play essential roles in radiological diagnosis, such as the early detection of tumors. Radionuclide therapy is also rapidly developing with the use of these modalities. Nevertheless, a limited number of radioactive tracers are imaged owing to the limitations of the imaging devices. In a previous study, we developed a hybrid Compton camera that conducts simultaneous Compton and pinhole imaging within a single system. In this study, we developed a system that simultaneously realizes three modalities: Compton, pinhole, and PET imaging in 3D space using multiple hybrid Compton cameras. We achieved the simultaneous imaging of Cs-137 (Compton mode targeting 662 keV), Na-22 (PET mode targeting 511 keV), and Am-241 (pinhole mode targeting 60 keV) within the same field of view. In addition, the imaging of Ga-67 and In-111, which are used in various diagnostic scenarios, was conducted. We also verified that the 3D distribution of the At-211 tracer inside a mouse could be imaged using the pinhole mode.

Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: a cross-sectional study.

BACKGROUND: This study aimed to identify cases of potential prodromal DLB in very late-onset schizophrenia-like psychosis (VLOSLP), using indicative biomarkers of dementia with Lewy bodies (DLB), and to evaluate the characteristics of psychosis as prodromal DLB. METHODS: Data of patients with VLOSLP without dementia and Parkinsonism, who underwent testing for at least one indicative biomarker of DLB, were retrospectively collected from the database of the psychiatry clinic at the Osaka University Hospital. Patients were divided into two groups based on the positive (VLOSLP+LB) and negative (VLOSLP-LB) results of the indicative biomarkers of DLB. Age, gender, cognitive battery scores, prevalence of each type of delusions and hallucinations, cerebral volume, and cerebral perfusion were compared between the two groups. RESULTS: Eleven VLOSLP+LB and 23 VLOSLP-LB participants were enrolled. There were no significant differences in age, proportion of females, and MMSE scores between the two groups. The standardized score of the digit symbol substitution test was significantly lower in the VLOSLP+LB than in VLOSLP-LB group (6.9 [3.1] vs. 10.0 [2.7], p = 0.005). The prevalence of visual hallucinations was significantly higher in the VLOSLP+LB group than in the VLOSLP-LB group (81.8% vs. 26.1%, p = 0.003). Auditory hallucinations were prevalent in both groups (43.5% in VLOSLP-LB, and 45.5% in VLOSLP+LB). Among patients with auditory hallucinations, auditory hallucinations without coexistent visual hallucinations tended to be more prevalent in VLOSLP-LB (7 out of 10) than in VLOSLP+LB patients (1 out of 5). Although cerebral volume was not different in any region, cerebral perfusion in the posterior region, including the occipital lobe, was significantly lower in the VLOSLP+LB group. CONCLUSIONS: Psychomotor slowing, visual hallucinations, and reduced perfusion in the occipital lobe may be suggestive of prodromal DLB in VLOSLP patients, even though the clinical manifestations were similar in many respects between VLOSLP+LB and VLOSLP-LB. Although auditory hallucinations were prevalent in both groups, most patients in VLOSLP+LB complained of auditory hallucinations along with visual hallucinations. Future studies with a larger number of patients without selection bias are desirable.

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease: a multicenter study.

OBJECTIVE: Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. METHODS: Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. RESULTS: Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. CONCLUSION: Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

[Subjective relaxing effect of a hospital's rooftop forest on elderly patients requiring care].

OBJECTIVES: To clarify the relaxing effects of a 5-min stay in a hospital's rooftop forest on elderly patients requiring care. METHODS: This was a within-subject, cross-sectional study. The participants were 30 elderly female patients requiring help in walking, aged 81.2±6.4 (mean±SD). A simplified emotional 7-point rating scale from -3 to 3 for 5 pairs of emotions, which was derived from the two-question Whooley Depression Screen, was used as a subjective indicator. The experimental areas were the rooftop forest that covered an area of 122 m(2) on the rooftop of a four-story health service facility and an outdoor car park area (as the control area). The participants were instructed to sit still in a wheelchair and view the scenery for 5 min in each experimental area and were then assessed. Data from the participants during exposure to the rooftop forest were compared with those during exposure to the control area. First, 15 participants moved to the rooftop forest from the preroom, and the other 15 moved to the outdoor car park area, and then they moved to the other site to eliminate any order effect. RESULTS: In the rooftop forest, the mean scores of the simplified emotional rating were 1.70 (1.17 for control) for "hopeful", 1.70 (1.17) for "interest in doing things", 1.53 (1.10) for "enjoyment", 1.67 (1.17) for "calm", and 2.03 (1.30) for "secure". The scores were all significantly higher than those in the control (p<0.01). CONCLUSION: It was demonstrated that a visit to the rooftop forest induced a significant subjective relaxing effect in elderly female patients requiring care.

[Preventive medical effects of nature therapy].

Five million years has passed since a subset of primates recognizably became human. Because we have already spent more than 99.99% of our evolutionary history in natural environments, it is thought that we are essentially adaptive to nature. However, we live in a society characterized by urbanization and artificiality, despite our physiological functions still being adapted to nature. We conducted experiments involving 420 subjects at 35 different forests throughout Japan. As a result, these subjects sitting in natural surroundings showed decreases in the following physiological indices compared with the urban control group: 12.4% decrease in cortisol level, 7.0% decrease in sympathetic nervous activity, 1.4% decrease in systolic blood pressure, and 5.8% decrease in heart rate. This shows that stressful states can be relieved by forest therapy. It should also be noted that parasympathetic nerve activity increased by 55.0%, indicating a relaxed state. The results of walking experiments were also similar. Li et al. demonstrated that immune functions are enhanced by forest therapy. Middle-aged employees volunteered to participate in these experiments. NK (natural killer cells) activity, as an indicator of immune function, increased by 56% on the second day and returned to normal levels. A significant increase of 23% was maintained for 1 month even after these subjects returned to urban life, clearly illustrating the preventive medical effects of nature therapy. We expect nature therapy to play an increasingly important role in preventive medicine in the future.

Case Report: Usefulness of Biomarkers for Alzheimer's Disease in Two Cases With Very-Late-Onset Schizophrenia-Like Psychosis.

The association between primary psychotic disorders emerging in later life and neurodegenerative diseases, including Alzheimer's disease (AD), is controversial. We present two female non-demented cases of psychosis with onset above the age of 60 years. Cases 1 and 2 were aged was 68 and 81 years, respectively. They suffered from persecutory delusions and scored 28 on the Mini-Mental State Examination (MMSE) at the first examination. Although detailed neuropsychological tests detected amnesia, they had preserved daily life function. Brain magnetic resonance imaging, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography, and cardiac [123I]-metaiodobenzylguanidine (123I-MIBG) scintigraphy showed no specific abnormalities in either case. We diagnosed them with very-late-onset schizophrenia-like psychosis (VLOSLP) because there was no evidence that their psychoses were derived from organic diseases or affective disorders. Upon close inspection, the AD biomarkers, cerebrospinal fluid (CSF) testing and Florbetapir F 18 positron emission tomography (PET), were positive in Case 1 and negative in Case 2. Case 1 scored 25 1 year later and 23 2 years later on the MMSE and was finally diagnosed as AD dementia. These two cases suggest that some clinically diagnosed VLOSLPs may be a prodromal AD. Although VLOSLP is a disease entity supposed to be a primary psychotic disorder, some are probably secondary psychosis with insidious neurodegeneration. Advanced biomarkers such as amyloid PET and CSF may contribute to the detection of secondary psychosis from clinically diagnosed VLOSLP.

Effects of New Bayesian Penalized Likelihood Reconstruction Algorithm on Visualization and Quantification of Upper Abdominal Malignant Tumors in Clinical FDG PET/CT Examinations.

PURPOSE: This study evaluated the effects of new Bayesian penalized likelihood (BPL) reconstruction algorithm on visualization and quantification of upper abdominal malignant tumors in clinical FDG PET/CT examinations, comparing the results to those obtained by an ordered subset expectation maximization (OSEM) reconstruction algorithm. Metabolic tumor volume (MTV) and texture features (TFs), as well as SUV-related metrics, were evaluated to clarify the BPL effects on quantification. MATERIALS AND METHODS: A total of 153 upper abdominal lesions (82 liver metastatic and 71 pancreatic cancers) were included in this study. FDG PET/CT images were acquired with a GE Discovery 710 scanner equipped with a time-of-flight system. Images were reconstructed using OSEM and BPL (beta 700) algorithms. In 58 lesions <1.5 cm in greatest diameter (small-lesion group), visual image quality of each lesion was evaluated using a four-point scale. SUVmax was obtained for quantitative metrics. Visual scores and SUVmax were compared between OSEM and BPL images. In 95 lesions >2.0 cm in greatest diameter (larger-lesion group), SUVmax, SUVpeak, MTV, and six TFs were compared between OSEM and BPL images. In addition to the size-based analyses, an increase of SUVmax with BPL was evaluated according to the original SUVmax in OSEM images. RESULTS: In the small-lesion group, both visual score and SUVmax were significantly higher in the BPL than OSEM images. The increase in visual score was observed in 20 (34%) of all 58 lesions. In the larger-lesion group, no statistical difference was observed in SUVmax, SUVpeak, or MTV between OSEM and BPL images. BPL increased high gray-level zone emphasis and decreased low gray-level zone emphasis among six TFs compared to OSEM with statistical significance. No statistical differences were observed in other TFs. SUVmax-based analysis demonstrated that BPL increased and decreased SUVmax in lesions with low (<5) and high (>10) SUVmax in original OSEM images, respectively. CONCLUSION: This study demonstrated that BPL improved conspicuity of small or low-count upper abdominal malignant lesions in clinical FDG PET/CT examinations. Only two TFs represented significant differences between OSEM and BPL images of all quantitative metrics in larger lesions.

Greater reductions in blood flow after anti-angiogenic treatment in non-small cell lung cancer patients are associated with shorter progression-free survival.

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS.

Quantitative evaluation of hepatic integrin αvß3 expression by positron emission tomography imaging using 18F-FPP-RGD2 in rats with non-alcoholic steatohepatitis.

BACKGROUND: Integrin αvß3, which are expressed by activated hepatic stellate cells in non-alcoholic steatohepatitis (NASH), play an important role in the fibrosis. Recently, we reported that an RGD peptide positron emission tomography (PET) probe is useful as a predictor of hepatic fibrosis. Kinetic analysis of the RGD PET probe has been performed in tumours, but not in hepatic fibrosis. Therefore, we aimed to quantify hepatic integrin αvß3 in a model of NASH by kinetic analysis using 18F-FPP-RGD2, an integrin αvß3 PET probe. METHODS: 18F-FPP-RGD2 PET/CT scans were performed in control and NASH rats. Tissue kinetic analyses were performed using a one-tissue, two-compartment (1T2C) and a two-tissue, three-compartment (2T3C) model using an image-derived input function (IDIF) for the left ventricle. We then conducted correlation analysis between standard uptake values (SUVs) or volume of distribution (VT), evaluated using compartment kinetic analysis and integrin αv or ß3 protein expression. RESULTS: Biochemical and histological evaluation confirmed the development of NASH rats. Integrin αvß3 protein expression and hepatic SUV were higher in NASH- than normal rats. The hepatic activity of 18F-FPP-RGD2 peaked rapidly after administration and then gradually decreased, whereas left ventricular activity rapidly disappeared. The 2T3C model was found to be preferable for 18F-FPP-RGD2 kinetic analysis in the liver. The VT (IDIF) for 18F-FPP-RGD2, calculated using the 2T3C model, was significantly higher in NASH- than normal rats and correlated strongly with hepatic integrin αv and ß3 protein expression. The strengths of these correlations were similar to those between SUV60-90 min and hepatic integrin αv or ß3 protein expression. CONCLUSIONS: We have demonstrated that the VT (IDIF) of 18F-FPP-RGD2, calculated using kinetic modelling, positively correlates with integrin αv and ß3 protein in the liver of NASH rats. These findings suggest that hepatic VT (IDIF) provides a quantitative assessment of integrin αvß3 protein in liver.

Performance demonstration of a hybrid Compton camera with an active pinhole for wide-band X-ray and gamma-ray imaging.

X-ray and gamma-ray imaging are technologies with several applications in nuclear medicine, homeland security, and high-energy astrophysics. However, it is generally difficult to realize simultaneous wide-band imaging ranging from a few tens of keV to MeV because different interactions between photons and the detector material occur, depending on the photon energies. For instance, photoabsorption occurs below 100 keV, whereas Compton scattering dominates above a few hundreds of keV. Moreover, radioactive sources generally emit both X-ray and gamma-ray photons. In this study, we develop a "hybrid" Compton camera that can simultaneously achieve X-ray and gamma-ray imaging by combining features of "Compton" and "pinhole" cameras in a single detector system. Similar to conventional Compton cameras, the detector consists of two layers of scintillator arrays with the forward layer acting as a scatterer for high-energy photons (> 200 keV) and an active pinhole for low-energy photons (< 200 keV). The experimental results on the performance of the hybrid camera were consistent with those from the Geant4 simulation. We simultaneously imaged [Formula: see text]Am (60 keV) and [Formula: see text]Cs (662 keV) in the same field of view, achieving an angular resolution of 10[Formula: see text] (FWHM) for both sources. In addition, imaging of [Formula: see text]At was conducted for the application in future nuclear medicine, particularly radionuclide therapy. The initial demonstrative images of the [Formula: see text]At phantom were reconstructed using the pinhole mode (using 79 keV) and Compton mode (using 570 keV), exhibiting significant similarities in source-position localization. We also verified that a mouse injected with 1 MBq of [Formula: see text]At can be imaged via pinhole-mode measurement in an hour.

Protein Deficiency-Induced Behavioral Abnormalities and Neurotransmitter Loss in Aged Mice Are Ameliorated by Essential Amino Acids.

Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions. We fed aged mice a low protein diet (LPD) for 2 months, which caused behavioral abnormalities, and examined the nutritional effect of essential amino acid administration under LPD conditions. The passive avoidance test revealed that LPD mice demonstrated learning and memory impairment. Similarly, the LPD mice showed agitation and hyperactive behavior in the elevated plus maze test. Moreover, LPD mice exhibited decreased concentrations of gamma-aminobutyric acid (GABA), glutamate, glycine, dopamine, norepinephrine, serotonin and aspartate in the brain. Interestingly, oral administration of seven essential amino acids (EAAs; valine, leucine, isoleucine, lysine, phenylalanine, histidine, and tryptophan) to LPD mice, which can be a source of neurotransmitters, reversed those behavioral changes. The oral administration of EAAs restored the brain concentration of glutamate, which is involved in learning and memory ability and may be associated with the observed behavioral changes. Although the details of the link between decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be examined in future studies, these findings suggest the importance of dietary protein and essential amino acids for maintaining brain function.