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Abnormalities of neuroinflammatory process and serotonergic system have been reported in major depressive disorder (MDD). However, most previous studies were performed in recurrent MDD and only a few studies explored the interaction of the two systems. This study examined both systems concurrently and their clinical relevance in first-episode drug-naive MDD. Thirty-four MDD patients and 34 age and gender matched healthy controls (HC) were recruited. Plasma concentrations of the cytokines of interleukin-1 (IL-1) family, including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2) were measured using enzyme-linked immune-sorbent assays. The serotonin transporter (SERT) availability in midbrain, thalamus, caudate, and putamen was examined by single-photon emission computed tomography with 123I-ADAM. There were significantly lower concentrations of pro-inflammatory IL-1β and its inhibitor, IL-1R2 in MDD than HC. The SERT availability was at the same level between groups. A negative association between IL-1Ra concentration and the SERT availability in midbrain was observed in MDD but not in HC. Both IL-1β concentration and the SERT availability in caudate negatively correlated with depression severity and the effect of IL-1β was not moderated or mediated by the SERT. In conclusion, this study demonstrated the involvement of IL-1 family in the early stage of MDD, especially for IL-1β. SERT was not the main central target of altered IL-1β and these two systems might contribute to MDD by different mechanisms. The pathophysiology might be varied between early and recurrent MDD and tuning treatment strategies at different clinical stages might be needed.

Mesenchymal stem cell–derived EVs (MSC-EVs) are demonstrated to have similar therapeutic effect as their cells of origin and represent an attractive cell-free stem cell therapy. With the potential to be the future medical regimen, the information of fate and behavior of MSC-EVs in the living subject should be urgently gathered. This study aimed to track MSC-EVs by 111In-labeling and μSPECT/CT imaging. Wharton’s jelly-MSC-EVs (WJ-MSC-EVs) were isolated using Exo-Prep kit followed by characterization of expressing markers and size. After labeled by 111In-oxine, 111In-EVs were injected into C57BL/6 mice followed by μSPECT/CT imaging. Organs were then taken out for ex vivo biodistribution analysis. The radiochemical purity of 111In-EVs was > 90 % and remained stable up to 24 h. The image results showed that with injection of 111In-EVs, the signal mainly accumulated in the liver, spleen, and kidney, compared to that in lung and kidney after 111In-oxine injection. The ex vivo biodistribution showed the similar pattern to that of imaging. Chelation of free 111In with EDTA was found necessary to reduce the nonspecific accumulation of signal. This study demonstrated the feasibility of radiolabeling WJ-MSC-EVs with 111In-oxine for in vivo imaging and quantitative analysis in a mouse model. This simple and quick labeling method preserves the characteristics of WJ-MSC-EVs. The results in this study provide a thorough and objective basis for future clinical study.

Alzheimer’s disease (AD) is the most common type of dementia, and its early diagnosis has become a crucial issue. Machine learning provides a systematic and objective approach in classification. Currently, there are many studies using several kinds of neuroimaging modalities to perform classification in dementia. Support vector machine (SVM) is one of machine learning based classification algorithm which is able to retain favorable classification accuracy even with small sample sizes. Our aim is to investigate the feasibility of using dual PET biomarkers in combination with SVM for AD diagnosis in small sample sizes. This study collected PET (18F-FDG and 11C-PiB) and T1 MRI image of 79 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including 20 AD, 27 mild cognitive impairment (MCI) subjects, and 32 normal controls (NCs), and performed classification using the SVM algorithm with the quantification of the two PET biomarkers, and finally compared the classification results of each brain region. In the classification between diseased (AD and MCI) and NC group, we found that the accuracy, sensitivity and specificity mean in temporal cortex are the highest. Overall, using dual PET biomarkers in combination with SVM shows a certain feasibility and clinical value in the diagnosis of AD, especially in the temporal cortex.

Single-photon emission computed tomography (SPECT) imaging, a relatively inexpensive nuclear imaging technique, has been used as a diagnostic tool for Parkinson’s disease (PD). The tracer 99mTc-TRODAT-1 is commonly used in Taiwan, where the imaging cost is covered under the national health insurance system. However, poor TRODAT-SPECT imaging resolution is a problem. Therefore, we developed a semi-quantitative program that can perform automatic region of interest (ROI) delineation for semi-quantifying striatal dopamine transporter activities. A total of 228 subjects were enrolled in this study, including PD patients (n = 62) and healthy controls (n = 166). The subjects received a 99mTc-TRODAT-1 brain SPECT scan. Some of the subjects (n = 40) also received a high-resolution magnetic resonance imaging (MRI) scan for the evaluation of the accuracy of the semi-quantitative assessment. In addition, the developed automatic ROI delineation method was used to calculate the striatal specific uptake ratio (SUR) in dopamine transporter imaging. The reproducibility of the SUR obtained using the method was compared to those in previous studies. Based on linear regression analysis (r2 = 0.92, correlation coefficient = 0.96), a correlation was found between the results obtained using the automatic ROI delineation method and those of the manual method in striatum with the corresponding MR images. The age-related decline of SUR availability measured in this study was 6.4% per decade. There was almost no difference between our results and those in related clinical studies. The proposed automatic ROI delineation program for SUR analysis was tested and used to estimate the ROIs in TRODAT-SPECT images to aid PD diagnosis. The program could be helpful for physicians who are inexperienced with TRODAT-SPECT images.

The tumor-to-normal tissue (T/N) boron ratio is determined in a patient prior to boron neutron capture therapy (BNCT) using 4-borono-2-18F-fluoro-l-phenylalanine (18F-FBPA) positron emission tomography (PET). The T/N ratio is used as a reference parameter to calculate BNCT dose and to evaluate treatment effects. The boronophenylalanine (BPA) dosage for BNCT treatment is higher than the 18F-FBPA dosage for PET diagnosis. Therefore, we aimed to determine whether the T/N ratios between diagnosis and treatment were correlated. In this study, SAS tongue cancer cells were used to develop an orthotopic nude mouse model. Micro-PET was performed after the mice were injected a dose of 3.7 ± 0.74 MBq of 18F-FBPA via the tail vein. The 18F radioactivity in the tumor, muscle, and heart blood pool was calculated using AMIND software. Organs and blood were collected for boron concentration analysis using inductively coupled plasma-atomic emission spectroscopy after the mice were injected with 400 mg/kg BPA at 15, 30, 45, and 60 min. Pharmacokinetics of the tumor and muscle from 45 to 60 min after 18F-FBPA and BPA injections were slightly increased, whereas that of blood was slightly decreased. Median T/N ratios at 60 min after 18F-FBPA and BPA injections were 3.5 and 3.43, respectively. Median value of the T/N ratio between them was 3.49 at 60 min. The T/N ratio at 60 min after 18F-FBPA injection was similar to that after BPA injection. However, median tumor-to-blood (T/B) boron ratios of 18F-FBPA and BPA at 60 min were 1.63 and 3.35, respectively. Median value between them was 1.83 at 60 min. In this study, the T/B ratios demonstrate the spread of a distribution between 18F-FBPA and BPA injections. At 60 min, the T/N ratio of the 18F-FBPA injection was similar to that of the BPA injection. Boron concentration in normal tissue was almost equal to that in blood. Therefore, the representative T/N ratio could be obtained at 60 min after 18F-FBPA injection, and it was used as a reference parameter for calculating accurate radiation dose.

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.

The accumulation of extracellular β-amyloid (Aβ) plaques within the brain is unique to Alzheimer’s disease (AD) and thought to induce synaptic deficits and neuronal loss. Optimal therapies should tackle the core AD pathophysiology and prevent the decline in memory and cognitive functions. This study aimed to evaluate the therapeutic performance of mesenchymal stem cell-derived exosomes (MSC-exosomes), which are secreted membranous elements encapsulating a variety of MSC factors, on AD. A human neural cell culture model with familial AD (FAD) mutations was established and co-cultured with purified MSC-exosomes. 2-[18F]Fluoro-2-deoxy-d-glucose ([18F]FDG) and novel object recognition (NOR) testing were performed before/after treatment to evaluate the therapeutic effect in vivo. The AD-related pathology and the expression of neuronal memory/synaptic plasticity-related genes were also evaluated. The results showed that MSC-exosomes reduced Aβ expression and restored the expression of neuronal memory/synaptic plasticity-related genes in the cell model. [18F]FDG-PET imaging and cognitive assessment revealed a significant improvement in brain glucose metabolism and cognitive function in AD transgenic mice. The phase of neurons and astrocytes in the brain of AD mice were also found to be regulated after treatment with MSC-exosomes. Our study demonstrates the therapeutic mechanism of MSC-exosomes and provides an alternative therapeutic strategy based on cell-free MSC-exosomes for the treatment of AD.

The zero echo time (ZTE) technique has improved the detection of lung nodules in PET/MRI but respiratory motion remains a challenge in lung scan. We investigated the feasibility and performance of fractionated deep-inspiration breath-hold (FDIBH) three-dimensional (3D) ZTE FDG PET/MRI for assessing lung nodules in patients with proved malignancy. Sixty patients who had undergone ZTE FDG PET/MRI and chest CT within a three-day interval were retrospectively included. Lung nodules less than 2 mm were excluded for analysis. Two physicians checked the adequacy of FDIBH ZTE and compared the lung nodule detection rates of FDIBH 3D ZTE and free-breathing (FB) four-dimensional (4D) ZTE, with chest CT as the reference standard. FDIBH resolved the effect of respiratory motion in 49 patients. The mean number and size of the pulmonary nodules identified in CT were 15 ± 31.3 per patient and 5.9 ± 4.6 mm in diameter. The overall nodule detection rate was 71% for FDIBH 3D ZTE and 70% for FB 4D ZTE (p = 0.73). FDIBH 3D ZTE significantly outperformed FB 4DZTE in detecting lung base nodules (72% and 68%; p = 0.03), especially for detecting those less than 6 mm (61% and 55%; p = 0.03). High inter-rater reliability for FDIBH 3D ZTE and FB 4D ZTE (k = 0.9 and 0.92) was noted. In conclusion, the capability of FDIBH 3D ZTE in respiratory motion resolution was limited with a technical failure rate of 18%. However, it could provide full expansion of the lung in a shorter scan time which enabled better detection of nodules (

Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naive MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naive MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD.

Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with 99mTc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.

Short imaging protocol to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) may enhance the clinical application of 13N-ammonia cardiac PET. We assessed the flow quantitation of 13N-ammonia PET implementing simple retention model and two-compartment model. Fourteen healthy volunteers (HVT) and twenty-three clinical patients received 13N-ammonia PET/CT. The simple retention model used the first 7-minute image to quantify MBF. Global and regional MBF and MFR of the two models were compared. Global and regional MBF and MFR of these two models were highly correlated with mildly inferior correlation in RCA territory (global R2: rest MBF = 0.79, stress MBF = 0.65, MFR = 0.77; regional R2: rest MBF ≥ 0.72, stress MBF ≥ 0.52, MFR ≥ 0.68). There were significant differences for MFR (4.04 ± 0.72, 3.66 ± 0.48, p = .02) and rest MBF (0.69 ± 0.12, 0.78 ± 0.12, p = .02) between the two models in the HVT group. 13N-ammonia global and regional MBF and MFR from the simple retention model demonstrate strong correlations with that from the two-compartment model. Significant differences of MFR and rest MBF are noted in the HVT group, with a proposed normal reference value for the 13N-ammonia short simple retention protocol.

Cerenkov luminescence imaging (CLI) has been an evolutional and alternative approach of nuclear imaging in basic research. This study aimed to measure the 131I thyroid uptake of mouse using CLI for assessment of thyroid function. Quantification of 131I thyroid uptake of mice in euthyroid, hypothyroid and hyperthyroid status was performed by CLI and γ-scintigraphy at 24 hours after injection of 131I. The 131I thyroid uptake was calculated using the equation: (thyroid counts − background counts)/(counts of injected dose of 131I) × 100%. Serum T4 concentration was determined to evaluate the thyroid function. The radioactivity of 131I was linearly correlated with the CL signals in both in vitro and in vivo measurements. CLI showed a significant decrease and increase of 131I thyroid uptake in the mice in hypo- and hyperfunctioning status, respectively, and highly correlated with that measured by γ-scintigraphy. However, the percent thyroid uptake measured by CLI were one-fifth of those measured by γ-scintigraphy due to insufficient tissue penetration of CL. These results indicate that CLI, in addition to nuclear imaging, is able to image and evaluate the 131I thyroid uptake function in mice in preclinical and research settings.

Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 106cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.

Introduction Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer’s disease (AD), an effective pre-screening tool for amyloid PET scans is needed. Methods Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ)1–40, Aβ1–42, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden’s index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs). Results Amyloid PET+ participants had lower plasma Aβ1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1–42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients. Conclusions Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.

Taking advantage of high energy and spatial resolution and high count sensitivity, the ultrafast cardiac γ-camera with cadmium-zinc-telluride (CZT)-based detectors has become popular in practice for myocardial perfusion imaging (MPI). The shorter imaging time with better imaging quality using CZT detectors compared to conventional ones makes it feasible to perform the left ventricular ejection fraction (LVEF) in the meantime of doing 201Tl MPI. The aim of this study was to compare LVEF from 201Tl MPI using a CZT with that from first-pass radionuclide angiography (FPRA) using a NaI camera.

The aim of this study was to evaluate the accuracy of myocardial blood flow (MBF) quantitation of 99mTc-Sestamibi (MIBI) single photon emission computed tomography (SPECT) compared with 13N-Ammonia (NH3) position emission tomography (PET) on the same cohorts. Recent advances of SPECT technologies have been applied to develop MBF quantitation as a promising tool to diagnose coronary artery disease (CAD) for areas where PET MBF quantitation is not available. However, whether the SPECT approach can achieve the same level of accuracy as the PET approach for clinical use still needs further investigations. Twelve healthy volunteers (HVT) and 16 clinical patients with CAD received both MIBI SPECT and NH3 PET flow scans. Dynamic SPECT images acquired with high temporary resolution were fully corrected for physical factors and processed to quantify K1 using the standard compartmental modeling. Human MIBI tracer extraction fraction (EF) was determined by comparing MIBI K1 and NH3 flow on the HVT group and then used to convert flow values from K1 for all subjects. MIBI and NH3 flow values were systematically compared to validate the SPECT approach. The human MIBI EF was determined as [1.0-0.816*exp(−0.267/MBF)]. Global and regional MBF and myocardial flow reserve (MFR) of MIBI SPECT and NH3 PET were highly correlated for all subjects (global R2: MBF = 0.92, MFR = 0.78; regional R2: MBF ≥ 0.88, MFR ≥ 0.71). No significant differences for rest flow, stress flow, and MFR between these two approaches were observed (All p ≥ 0.088). Bland-Altman plots overall revealed small bias between MIBI SPECT and NH3 PET (global: ΔMBF = −0.03Lml/min/g, ΔMFR = 0.07; regional: ΔMBF = −0.07 − 0.06 , ΔMFR = −0.02 − 0.22). Quantitation with SPECT technologies can be accurate to measure myocardial blood flow as PET quantitation while comprehensive imaging factors of SPECT to derive the variability between these two approaches were fully addressed and corrected.

Previously, we proposed interpolated averaged CT (IACT) for improved attenuation correction (AC) in thoracic PET/CT. This study aims to evaluate its feasibility and effectiveness on cardiac PET/CT.We simulated (18)F-FDG distribution using the XCAT phantom with normal and abnormal cardiac uptake. Average activity and attenuation maps represented static PET and respiration average CT (ACT), respectively, while the attenuation maps of end-inspiration/expiration represented 2 helical CTs (HCT). IACT was obtained by averaging the 2 extreme phases and the interpolated phases generated between them. Later, we recruited 4 patients who were scanned 1 hr post 315-428 MBq (18)F-FDG injection. Simulated and clinical PET sinograms were reconstructed with AC using (1) HCT, (2) IACT, and (3) ACT. Polar plots and the 17-segment plots were analyzed. Two regions-of-interest were drawn on lesion and background area to obtain the intensity ratio (IR).Polar plots of PETIACT-AC were more similar to PETACT-AC in both simulation and clinical data. Artifacts were observed in various segments in PETHCT-AC. IR differences of HCT as compared to the phantom were up to ~20%.IACT-AC reduced respiratory artifacts and improved PET/CT matching similarly to ACT-AC. It is a promising low-dose alternate of ACT for cardiac PET/CT.

Bipolar disorder (BD) is highly heritable and associated with dysregulation of brain glucose utilizations (GU). The mitochondrial DNA (mtDNA) 10398A polymorphism, as a reported BD risk factor, leads to deficient glycolytic energy production by affecting mitochondrial matrix pH and intracellular calcium levels. However, whether mtDNA-10398A has functional effects on the brain and how our body responds remain elusive. We compared peripheral and central glucose-utilizing patterns between mtDNA A10398G polymorphisms in BD and their unaffected siblings (BDsib). Since siblings carry identical mtDNA, we hypothesized that certain characteristics co-segregate in BD families. We recruited twenty-seven pairs of non-diabetic BD patients and their BDsib and 30 well-matched healthy control subjects (HC). The following were investigated: mtDNA, fasting plasma glucose/insulin, cognitive functions including Montreal Cognitive Assessment (MoCA), and brain GU at rest. Insulin resistance was rechecked in sixty-one subjects (19-BD, 18-BDsibib, and 24-HC) six months later. We found that BD-pairs (BD+BDsib) carried more mtDNA-10398A and had higher fasting glucose, even after controlling for many covariates. BD-pairs had abnormally lower dorso-prefrontal-GU and higher cerebellar-GU, but only BD demonstrated lower medio-prefrontal-GU and MoCA. Subjects carrying mtDNA-10398A had significantly lower prefrontal-GU (FWE-corrected p

Introduction The purpose of this study was to investigate the feasibility of using low-dose computed tomography (CT) in coronary artery calcium scoring and PET attenuation correction for patients in different weight categories undergoing cardiac PET/CT examinations. Materials and methods Calcium scoring computed tomography (CSCT) scans and PET scans of anthropomorphic cardiac phantoms simulating normal-weight, mildly obese, and severely obese patients were acquired with a hybrid PET/CT scanner. CSCT images were acquired at 120 kVp, with tube current ranging from 10 to 550 mA. PET scans were performed in three-dimensional mode, with acquisition time of 3 min/bed position. The image quality of cardiac PET/CT was evaluated by assessing the signal-to-noise ratio. CT-based coronary artery calcium quantification was performed using the Agatston scoring system. Results On the basis of our results, the CSCT protocols using tube currents of 50 and 150 mA should be able to achieve the lowest possible radiation dose while maintaining the desired image quality for normal-weight and mildly obese patients undergoing cardiac PET/CT examinations, respectively. When the proposed low-dose CSCT protocols were performed, radiation dose could be reduced by 83.34 and 50% compared with those from CSCT scans acquired with standard tube current settings for normal-weight and mildly obese patients, respectively. In the scanning of severely obese patients, an increase in tube voltage or current would help improve the reliability of image information provided by cardiac PET/CT. Conclusion Our study demonstrated the feasibility of low-dose CT protocols for coronary artery calcium scoring and PET attenuation correction in cardiac PET/CT to examine patients in different weight categories. The calculations performed in this work should be able to provide practical information to achieve necessary diagnostic information while keeping radiation dose as low as reasonably achievable.

Background Major depressive disorder (MDD) patients have shown elevated plasma levels of pro-inflammatory biomarkers compared to healthy controls. We hypothesized increased serum tumor necrosis factor-alpha receptor subtype 1 (TNF-α R1) is more associated with impaired brain function in patients with treatment-resistant depression (TRD) than those without TRD. Methods 34 MDD patients and 34 healthy subjects were recruited and we separated MDD patients to TRD group (n = 20) and non-TRD (n = 14) group. Pro-inflammatory cytokines were assessed by enzyme-linked immunosorbent assays. A standardized uptake values (SUV) of glucose metabolism measured by 18F-FDG positron-emission-tomography (PET) was applied to all subjects for subsequent region-of- interest analyses and whole-brain voxel-wise analyses. 18F-FDG-PET measures glucose uptake into astrocytes in response to glutamate release from neuronal cells, and was thus used as a proxy measure to quantify glutamatergic neurotransmission in the human brain. Results Post-hoc analysis revealed that TRD group had higher serum concentrations of TNF-α R1 compared to healthy control or non-TRD group. In the MDD group, higher serum concentrations of TNF-α R1 significantly correlated with decreased SUV in anterior cingulate cortex (ACC) and bilateral caudate nucleus. The ROI analysis further supported the negative correlations of plasma TNF-α R1 and SUV in the ACC and caudate nucleus. Such correlation is more consistent in TRD group than in non-TRD and HC groups. Limitation Glutamate neurotransmission and the effect of chronic stress on glutamate release in the brain were not measured directly. Conclusions Increased TNF-α R1 was associated with impaired glutamatergic neurotransmission of caudate nucleus and ACC in MDD patients, particularly in the TRD.

Purpose This study aimed to evaluate the efficacy of automatic exposure control (AEC) in order to optimize low-dose computed tomography (CT) protocols for patients of different ages undergoing cardiac PET/CT and single-photon emission computed tomography/computed tomography (SPECT/CT). Methods One PET/CT and one SPECT/CT were used to acquire CT images for four anthropomorphic phantoms representative of 1-year-old, 5-year-old and 10-year-old children and an adult. For the hybrid systems investigated in this study, the radiation dose and image quality of cardiac CT scans performed with AEC activated depend mainly on the selection of a predefined image quality index. Multiple linear regression methods were used to analyse image data from anthropomorphic phantom studies to investigate the effects of body size and predefined image quality index on CT radiation dose in cardiac PET/CT and SPECT/CT scans. Results The regression relationships have a coefficient of determination larger than 0.9, indicating a good fit to the data. According to the regression models, low-dose protocols using the AEC technique were optimized for patients of different ages. In comparison with the standard protocol with AEC activated for adult cardiac examinations used in our clinical routine practice, the optimized paediatric protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old children, respectively. The corresponding results for cardiac SPECT/CT are 8.4, 51.5 and 72.7%. Conclusion AEC is a practical way to reduce CT radiation dose in cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly for optimal effect. Our results show that AEC does not eliminate the need for paediatric protocols and CT examinations using the AEC technique should be optimized for paediatric patients to reduce the radiation dose as low as reasonably achievable.

We investigated the effects of scan protocols on CT-based material extraction to minimize radiation dose while maintaining sufficient image information in small animal studies. The phantom simulation experiments were performed with the high dose (HD), medium dose (MD) and low dose (LD) protocols at 50, 70 and 80 kV p with varying mA s. The reconstructed CT images were segmented based on Hounsfield unit (HU)-physical density ( ρ ) calibration curves and the dual-energy CT-based (DECT) method. Compared to the (HU; ρ ) method performed on CT images acquired with the 80 kV p HD protocol, a 2-fold improvement in segmentation accuracy and a 7.5-fold reduction in radiation dose were observed when the DECT method was performed on CT images acquired with the 50/80 kV p LD protocol, showing the possibility to reduce radiation dose while achieving high segmentation accuracy.

To study the impact of video game playing on the human brain, the effects of two video games playing on cerebral blood flow (CBF) in young adults were determined. Thirty healthy subjects comprising 18 males and 12 females who were familiar with video game playing were recruited. Each subject underwent three sessions of single photon emission computed tomography (SPECT) with a bolus injection of 20 mCi (99m)Tc ECD IV to measure their CBF. The first measurement was performed as baseline, the second and third measurements were performed after playing two different video games for 30 min, respectively. Statistic parametric mapping (SPM2) with Matlab 6.5 implemented on a personal computer was used for image analysis. CBF was significantly decreased in the prefrontal cortex and significantly increased in the temporal and occipital cortices after both video games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC) which was significantly correlated with the number of killed characters was found after the violent game playing. The major finding of hypo-perfusion in prefrontal regions after video game playing is consistent with a previous study showing reduced or abnormal prefrontal cortex functions after video game playing. The second finding of decreased CBF in the ACC after playing the violent video game provides support for a previous hypothesis that the ACC might play a role in regulating violent behavior.

Li C-T, Hsieh J-C, Wang S-J, Yang B-H, Bai Y-M, Lin W-C, Lan C-C, Su T-P. Differential relations between fronto-limbic metabolism and executive function in patients with remitted bipolar I and bipolar II disorder. Bipolar Disord 2012: 14: 831–842. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Objectives: The aim of this study was to investigate the relationship between resting brain glucose metabolism and cognitive profiles in patients with remitted bipolar I disorder (BD-I) and bipolar II disorder (BD-II). We hypothesized that BD-I patients (compared to BD-II patients) would perform worse on tests of cognitive function because of abnormal metabolism in the prefrontal cortex and other mood-related brain areas. Methods: Thirty-four patients with remitted bipolar disorder (BD) (BD-I = 17, BD-II = 17) under treatment and 17 well-matched healthy controls received both fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and neuropsychological tests of attention, memory, and executive function. Results: Clinical features in patients with BD-I and BD-II were comparable. Executive function, as indicated by performance on the Wisconsin Card Sorting Test, was significantly worse (i.e., higher percentage of errors, lower percentage of conceptual level responses, and fewer categories completed) in BD-I patients than in BD-II patients and healthy subjects. No difference in attention and memory tests was found among these three groups. Brain PET analysis showed that BD-I patients (compared to BD-II patients) had significantly lower glucose uptake in the bilateral anterior cingulum, insula, striatum, and part of the prefrontal cortex, and higher glucose uptake in the left parahippocampus. Further analyses revealed significant correlations between poor executive function and abnormal glucose uptake in other brain areas in BD-I patients. Conclusions: There are neurobiological differences between subtypes of BD. BD-I is associated with more impaired fronto-limbic circuitry, which might account for reduced executive function in BD-I patients during remission.

Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional 68Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 104 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and normal volunteers, to work towards ALARA (as low as reasonably achievable) concept for PET SPM studies.

The aim of this study was to examine the feasibility of (123)I-ADAM to image the serotonin transporter (SERT) in Asian (Taiwanese) subjects. Single photon emission computed tomography (SPECT) scans were performed on nine healthy volunteers who were s-allele carriers at the polymorphism within the serotonin transporter promoter region (SERTPR) after intravenous bolus injection of (123)I-ADAM. Quantification of (123)I-ADAM binding was performed using the ratio equilibrium method (REM) with specific uptake ratio (SUR) and a simplified reference tissue model (SRTM). Curve-fitting techniques were used to obtain the peak equilibrium point from 241 to 301 min (average 264+/-20 min) after injection of (123)I-ADAM for the midbrain and from 215 to 270 min (average 235+/-18 min) after injection of (123)I-ADAM for the striatum. Two sets of SUR were obtained by either curve fitting (estimated values) or integrated period from 240 to 270 min (observed values). The estimated values of SUR were 2.11+/-0.51 for the midbrain and 1.50+/-0.44 for the striatum, whereas the observed values were 2.11+/-0.83 for the midbrain and 1.24+/-0.31 for the striatum. The SRTM showed that the binding potential (BP) was 2.10+/-0.66 for the midbrain and 1.35+/-0.25 for the striatum. There was a good correlation between estimated SUR, observed SUR and SRTM in the midbrain but not in the striatum. The optimal scanning duration for both the midbrain and the striatum should be 220 to 280 min similar to that suggested by previous studies in Caucasians. However, due to the low signal-to-noise ratio in the striatum, (123)I-ADAM could be an ideal tracer for imaging SERT in the midbrain but not in the striatum.

Background Low-dose ketamine has been found to have robust and rapid antidepressant effects. A hypoactive prefrontal cortex (PFC) and a hyperactive amygdala have been suggested to be associated with treatment-resistant depression (TRD). However, it is unclear whether the rapid antidepressant mechanisms of ketamine on TRD involve changes in glutamatergic neurotransmission in the PFC and the amygdala. Methods A group of 48 TRD patients were recruited and equally randomized into three groups (A: 0.5 kg/mg-ketamine; B: 0.2 kg/mg-ketamine; and C: normal saline [NS]). Standardized uptake values (SUV) of glucose metabolism measured by 18F-FDG positron-emission-tomography before and immediately after a 40-min ketamine or NS infusion were used for subsequent region-of-interest (ROI) analyses (a priori regions: PFC and amygdala) and whole-brain voxel-wise analyses and were correlated with antidepressant responses, as defined by the Hamilton depression rating scale score. The 18F-FDG signals were used as a proxy measure of glutamate neurotransmission. Results The ROI analysis indicated that Group A and Group B, but not Group C, had increases in the SUV of the PFC (group-by-time interaction: F = 7.373, P = 0.002), whereas decreases in the SUV of the amygdala were observed in all three groups (main effect of time, P

The purpose of this study was to assess the use of 1-(11)C-acetate (ACE) as a metabolic tracer for the detection and characterisation of astrocytomas.Positron emission tomography (PET) studies with ACE and 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) were performed sequentially in 26 patients with primary astrocytomas. Images were analysed by visual interpretation and determination of the tumour to cortex ratio (T/C ratio) and standardised uptake value (SUV). The tumour uptake was visually scored into three grades as compared with the contralateral cortex: clearly lower (-), almost equal (+) and clearly higher (++).There were 85% of astrocytomas with ++ ACE uptake, 15% with + ACE uptake and none with - ACE uptake. Only 19% of astrocytomas had ++ FDG uptake. Thirty-seven percent of high-grade astrocytomas had + FDG uptake and 37% had - FDG uptake. The sensitivity and specificity of the FDG T/C ratio in discriminating high-grade from low-grade astrocytomas were 79% and 100%, respectively, at the cutoff value of 0.75. Using 2.33 as the cutoff value of the ACE T/C ratio, the sensitivity and specificity were 42% and 86%, respectively. FDG was better than ACE in discriminating high-grade from low-grade astrocytomas. T/C ratios and SUVs of FDG uptake of tumours correlated with the histological grades, but those of ACE uptake did not.ACE appears to be a promising tracer for use in the detection of primary astrocytomas, but is of limited value in the differentiation of high- and low-grade astrocytomas. ACE is complementary to FDG for the diagnosis and characterisation of astrocytoma.

The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images. Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123 I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t -test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans. The average of specific uptake ratio (SUR: target/cerebellum-1) of 123 I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us to understand reliability of I-123 ADAM SPECT imaging and further develop new strategy for the treatment of psychiatric disorders.

Misregistration resulting from the difference of temporal resolution in PET and CT scans occur frequently in PET/CT imaging, which causes distortion in tumor quantification in PET. Respiration cine average CT (CACT) for PET attenuation correction has been reported to improve the misalignment effectively by several papers. However, the radiation dose to the patient from a four-dimensional CT scan is relatively high. In this study, we propose a method to interpolate respiratory CT images over a respiratory cycle from inhalation and exhalation breath-hold CT images, and use the average CT from the generated CT set for PET attenuation correction. The radiation dose to the patient is reduced using this method. Six cancer patients of various lesion sites underwent routine free-breath helical CT (HCT), respiration CACT, interpolated average CT (IACT), and 18F-FDG PET. Deformable image registration was used to interpolate the middle phases of a respiratory cycle based on the end-inspiration and end-expiration breath-hold CT scans. The average CT image was calculated from the eight interpolated CT image sets of middle respiratory phases and the two original inspiration and expiration CT images. Then the PET images were reconstructed by these three methods for attenuation correction using HCT, CACT, and IACT. Misalignment of PET image using either CACT or IACT for attenuation correction in PET/CT was improved. The difference in standard uptake value (SUV) from tumor in PET images was most significant between the use of HCT and CACT, while the least significant between the use of CACT and IACT. Besides the similar improvement in tumor quantification compared to the use of CACT, using IACT for PET attenuation correction reduces the radiation dose to the patient.

The complexity of small oral cavity and intimate apposition of the oral cavity mucosal surfaces make CT identification of obvious masses difficult. Puffed-cheek CT improves the evaluation of oral cavity lesions. We used the puffed-cheek maneuver with 18F-FDG PET/CT scans to determine the feasibility and accuracy in clinical practice and to identify any benefits.Twenty-two patients with oral cancer were included. They were instructed to perform the puffed-cheek maneuver after a conventional 18F-FDG PET/CT scan. Two physicians reviewed the puffed-cheek and conventional 18F-FDG PET/CT images and achieved consensus about the cancer extent, location, and dental artifacts before classifying and grading the oral cancers. Dichotomous results of localized or extended cancer and artifact grading scores from the puffed-cheek and conventional 18F-FDG PET/CT methods were compared using McNemar test and the Wilcoxon signed-rank test. P0.05 was considered significant.The puffed-cheek maneuver with 18F-FDG PET/CT was practical and had incremental benefits. The conventional 18F-FDG PET/CT classified 12 patients correctly as having localized or extended cancer, and the puffed-cheek 18F-FDG PET/CT classified 21 patients correctly. Puffed-cheek 18F-FDG PET/CT found a synchronous skip cancer and provided detailed cancer delineation. This method might reduce the effects of dental artifacts without undesirable muscular FDG uptake.Puffed-cheek PET/CT is feasible in the current clinical setting and can improve the delineation of oral cancer extent and location, with a potential benefit of reducing dental artifacts.

Objective To investigate possible cerebral involvement in patients with spinal and bulbar muscular atrophy (SBMA) by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Design Ten patients with molecularly-confirmed SBMA and 5 age- and gender-matched healthy controls were recruited for brain FDG-PET studies. The data were analyzed and compared using the statistical parametric mapping (SPM) method. Results Glucose hypometabolism in frontal areas of the cerebrum was found in patients with SBMA. However, no significant correlation with clinical variables, such as CAG repeat length, age at onset, or serum testosterone levels, was noted. Conclusions The perturbation of cerebral glucose metabolism in patients with SBMA argues against SBMA being a pure lower motor and sensory neuron syndrome. Mutations in the androgen receptor gene might have a more widespread effect in the cerebrum than previously recognized.

This study aimed to define the potential of 1-(11)C-acetate PET, compared with (18)F-FDG, in detecting meningiomas and monitoring the effect of gamma-knife radiosurgery.Twenty-two patients with the neuroradiologic diagnosis of meningioma were examined by 1-(11)C-acetate and (18)F-FDG PET on the same day. There were 12 cases of histopathologically proven meningioma (8 grade I, 2 grade II, and 2 grade III), 1 of tuberculous granuloma, and 1 of degenerative tissue. 1-(11)C-acetate PET scans of fasting patients were obtained 10 min after intravenous administration of 740 MBq of 1-(11)C-acetate. (18)F-FDG PET was performed at 2 h after 1-(11)C-acetate scanning. The PET images were evaluated by a qualitative method and semiquantitative analysis using standardized uptake value and tumor-to-cortex ratio.The (18)F-FDG PET study revealed a hypometabolic focus in 17 meningiomas (8 grade I, 1 grade II, and 8 unknown grade) and hypermetabolism in 1 grade II and 2 grade III meningiomas. High uptake of 1-(11)C-acetate was observed in all 20 meningiomas, in contrast to the low uptake in surrounding normal brain tissue, allowing a clearer demarcation of the tumor boundary than that provided by (18)F-FDG. Dissociation of regional accumulation of 1-(11)C-acetate and (18)F-FDG within the tumor was also noted on the coregistered images. The standardized uptake value for 1-(11)C-acetate was not different from that for (18)F-FDG (mean +/- SD, 3.16 +/- 1.75 vs. 3.22 +/- 1.50, P = 0.601), but the tumor-to-cortex ratio for 1-(11)C-acetate was higher than that for (18)F-FDG (3.46 +/- 1.38 vs. 0.93 +/- 1.08, P0.005). (18)F-FDG was able to differentiate grade I from grade II-III meningiomas, whereas 1-(11)C-acetate was unable to do so. Tuberculous granuloma had a high 1-(11)C-acetate and (18)F-FDG uptake similar to that of grade II/III meningioma. Five patients received 1-(11)C-acetate and (18)F-FDG PET before and after gamma-knife surgery. 1-(11)C-acetate performed better than did (18)F-FDG in monitoring the response of tumor metabolism to radiosurgery.1-(11)C-acetate was found to be useful for detecting meningiomas and evaluating the extent of meningiomas and potentially useful for monitoring tumor response to radiosurgery. However, 1-(11)C-acetate was not useful for evaluating the tumor grade. (18)F-FDG was found to be less useful than 1-(11)C-acetate for evaluating the extent of meningiomas and the response to radiosurgical treatment but may be useful for differentiating benign from malignant meningiomas. (18)F-FDG and 1-(11)C-acetate are complementary for assessing diverse cell metabolism of meningioma.

18F-FDG PET/CT is a promising tool in detecting aortic graft infection. Present study investigated the value of dual-time-point 18F-FDG PET/CT imaging (DTPI) with delayed imaging in assessing aortic graft infection. Twenty-nine patients with suspected aortic graft infection were prospectively enrolled in this DTPI study. Two nuclear medicine physicians read all the images and achieved consensus about the measurement of maximal standardized uptake value (SUVmax) and grading of image quality. The percentages of SUVmax change between initial and delayed images were recorded as retention index (RI); sensitivity, specificity, and accuracy were calculated based on reference standard. All the 5 infected aortic grafts had positive RIs, which were generally higher than that of noninfected grafts. Those noninfected grafts had variable RIs. Seven patients had improved image quality in delayed imaging. DTPI with delayed image detected all the infected grafts with improved specificity (88%) and accuracy (90%), providing conspicuous delineation of the infected graft extent. In conclusion, noninfected aortic grafts had more variable RIs than infected ones. DTPI might be useful for detecting aortic graft infection, improving image quality, and enhancing delineation of the infected aortic grafts.

The purpose of this study was to investigate the regional patterns of cerebral metabolic deficits by voxel-based FDGPET analysis in patients with distinct spinocerebellar ataxia (SCA) genotypes, including SCA type 2 (SCA2), SCA3, and SCA6. Nine patients with SCA2, 12 with SCA3, seven with SCA6, and 23 healthy control subjects were recruited. The clinical severity of the patients' cerebellar ataxia was evaluated according to the International Cooperative Ataxia Rating Scale. The brain glucose metabolism was evaluated with 2- [fluorine 18]-fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography. Group data were analyzed and compared by voxelbased analysis. In SCA2, FDG utilization was significantly reduced in the cerebellum, pons, parahippocampal gyrus and frontal cortex. In SCA3, FDG metabolism in the cerebellum, parahippocampal gyrus of the limbic system, and lentiform nucleus was decreased. In SCA6, FDG metabolism was diminished in the cerebellum and the frontal and prefrontal cortices. On group comparisons, while all SCAs have impaired cerebellar functions, the cerebellar FDG metabolism was most severely compromised in SCA2. Instead, the FDG metabolism in the lentiform nucleus and medulla was characteristically worst in SCA3. There was no brainstem involvement in SCA6.

The International Cooperative Ataxia Rating Scale (ICARS) is a 100-point semiquantitative scale designed primarily to assess cerebellar dysfunction. However, little is known of the metric properties of this scale. We assessed the ICARS by rating the severity of cerebellar dysfunction in 27 patients with spinocerebellar ataxias (SCA), three patients with sporadic olivopontocerebellar ataxia and 24 healthy control subjects. [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) study was also performed on each subject. The statistical parametric mapping analyses revealed a significant correlation between the ICARS scores and functional impairment of the frontal regions within SCA patients. The glucose metabolism in the cerebellum, thalamus and caudate nucleus had significant differences between SCA patients and healthy control subjects. The results suggested that the clinical severity of SCA patients correlated with the functional impairment in the frontal regions, the targets of cerebellar efferent projections.

Various forms of cardiac pathology, such as myocardial ischemia and infarction, can be characterized with 13 NH 3 -PET images. In clinical situation, polar map (bullseye image), which derived by combining images from multiple planes (designated by the circle around the myocardium in the above images), so that information of the entire myocardium can be displayed in a single image for diagnosis. However, image artifact problem always arises from body movement or breathing motion in image acquisition period and results in indefinite myocardium disorder region shown in bullseye image. In this study, a 3-D motion and movement correction method is developed to solve the image artifact problem to improve the accuracy of diagnostic bullseye image. The proposed method is based on 3-D optical flow estimation method (OFEM) and cooperates with the particular dynamic imaging protocol, which snaps serial PET images (5 frames) in later half imaging period. The 3-D OFEM assigns to each image point in the visual 3-D flow velocity field, which associates with the non-rigid motion of the time-varying brightness of a sequence of images. It presents vectors of corresponding images position between frames for motion correction. To validate the performance of proposed method, 10 normal and 20 abnormal whole-body dynamic PET imaging studies were applied, and the results show that the bullseye images, which generated by corrected images, present clear and definite tissue region for clinical diagnosis.

Purpose: The temporal mismatch between PET and standard helical CT (HCT) causes substantial respiratory artifacts in PET reconstructed images when using HCT as the attenuation map. Previously we developed an interpolated average CT (IACT) method for attenuation correction (AC) and demonstrated its merits in simulations. In this study we aim to apply IACT in patients with thoracic lesions using an active breathing controller (ABC). Methods: Under local ethics approval, we recruited 15 patients with a total of 18 lesions in different thoracic regions: left upper lobe (2), right upper lobe (4), right hilum (3), right lower lobe (3), left hilum (2), and esophagus (4). All patients underwent whole body PET scans 1 h after 300–480 MBq18F-FDG injection, depending on the patients’ weight. The PET sinograms were reconstructed with AC using: (i) standard HCT [120 kV, smart mA (30–150 mA), 0.984:1 pitch] and (ii) IACT obtained from end-inspiration and end-expiration breath-hold HCTs (120 kV, 10 mA, 0.984:1 pitch) aided by ABC. IACT was obtained by averaging the intensity of two extreme phases and the interpolated phases between them, where the nonlinear interpolation was obtained by B-spline registration and with an empirical sinusoidal function. The SUVmax, SUVmean, and the differences of centroid-of-lesion (d) between PET and different CT schemes were measured for each lesion. Results: From visual inspection, the respiratory artifacts and blurring generally reduced in the thoracic region for PET IACT. Matching between CT and PET improved for PET IACT, with an average decrease of d for 1.34 ± 1.79 mm as compared to PET HCT. The SUVmax and SUVmean were consistently higher for PET IACT versus PET HCT for all lesions, with (30.95 ± 18.63)% and (22.39 ± 15.91)% average increase, respectively. Conclusions: IACT-ABC reduces respiratory artifacts, PET/CT misregistration and enhances lesion quantitation. This technique is a robust and low dose AC protocol for clinical oncology application especially in the thoracic region.

Hybrid positron emission tomography-computed tomography (PET-CT) system enhances better differentiation of tissue uptake of 18F-fluorodeoxyglucose (18F-FDG) and provides much more diagnostic value in the non-small-cell lung cancer and nasopharyngeal carcinoma (NPC). In PET-CT, high quality CT images not only offer diagnostic value on anatomic delineation of the tissues but also shorten the acquisition time for attenuation correction (AC) compared with PET-alone imaging. The linear accelerators equipped with the X-ray cone-beam computed tomography (CBCT) imaging system for image-guided radiotherapy (IGRT) provides excellent verification on position setup error. The purposes of our study were to optimize the CT acquisition protocols of PET-CT and to integrate the PET-CT and CBCT for IGRT. The CT imaging parameters were modified in PET-CT for increasing the image quality in order to enhance the diagnostic value on tumour delineation. Reproducibility and registration accuracy via bone co-registration algorithm between the PET-CT and CBCT were evaluated by using a head phantom to simulate a head and neck treatment condition. Dose measurement in computed tomography dose index (CTDI) was also estimated. Optimization of the CT acquisition protocols of PET-CT was feasible in this study. Co-registration accuracy between CBCT and PET-CT on axial and helical modes was in the range of 1.06 to 2.08 and 0.99 to 2.05 mm, respectively. In our result, it revealed that the accuracy of the co-registration with CBCT on helical mode was more accurate than that on axial mode. Radiation doses in CTDI were 4.76 to 18.5 mGy and 4.83 to 18.79 mGy on axial and helical modes, respectively. Registration between PET-CT and CBCT is a state-of-the-art registration technology which could provide much information on diagnosis and accurate tumour contouring on radiotherapy while implementing radiotherapy procedures. This novelty technology of PET-CT and cone-beam CT integration for IGRT may have a potential becoming more clinical use in the future.

Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, 18F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone. The results suggested that the number of inflammatory cells, astrocytes, and neovascularization significantly elevated in peri-infarct region from day 7 and a belt of macrophage/microglial and astrocytes was formed surrounding infarct lesion at day 14. Both vasogenic and cytotoxic edema, as well as blood brain-barrier leakage, occurred since day 1 after stroke induction and gradually attenuated with time. Numerous cells other than neuronal cells infiltrated into infarct lesion, which resulted in no visible TTC negative regional existence at day 14. Furthermore, recovery of cerebral blood flow and glucose utilization in peri-infarct zone were noted and more remarkably than that in infarct core following the stroke progression. In conclusion, these characterizations may be highly beneficial to the development of therapeutic strategies for ischemic stroke.