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Patients who undergo accelerator-based (AB) boron neutron capture therapy (BNCT) for head and neck cancer in the sitting position are generally uncomfortably immobilized, and patient motion during this treatment may be greater than that in other radiotherapy techniques. Furthermore, the treatment time of BNCT is relatively long (up to approximately 1 h), which increases the possibility of patient movement during treatment. As most BNCT irradiations are performed in a single fraction, the dosimetric error due to patient motion is of greater consequence and needs to be evaluated and accounted for. Several treatment parameters are required for BNCT dose calculation.To investigate the dosimetric impacts (DIs) against position errors using a simple cylindrical phantom for an AB-BNCT system under different treatment parameter settings.The treatment plans were created in RayStation and the dose calculation was performed using the NeuCure® dose engine. A cylindrical phantom (16 cm diameter × 20 cm height) made of soft tissue was modeled. Dummy tumors in the form of a 3-cm-diameter sphere were arranged at depths of 2.5 and 6.5 cm (denoted by TThe coefficients of the MRA of the DIs for LR, AP, and SI shifts were -0.08, 2.16, and -0.04 (p-values = 0.084, 0.01, and 0.334) for TThe DIs were largely affected by the shift in the AP direction and were influenced by the different treatment parameters.

This study was aimed at evaluating the metabolism of reactive astrocytes in the brains of patients with multiple sclerosis by quantitative 1-C-11 acetate positron emission tomography (PET). Magnetic resonance imaging and 1-C-11 quantitative PET were performed in eight patients with multiple sclerosis and 10 normal control subjects. The efflux rate (k2) of 1-C-11 acetate, which reportedly reflects the metabolic rate of 1-C-11 acetate, was calculated based on the one-tissue compartmental model. Fractional anisotropy was also determined to evaluate the integrity of the neuronal tracts. The values of k2 in the patients with multiple sclerosis were significantly higher than those in the normal control subjects, in both the white matter ( p = 0.003) and the gray matter ( p = 0.02). In addition, the white matter/gray matter ratio of k2 was significantly higher in the multiple sclerosis patients than in the normal control subjects ( p = 0.02). Voxel-based statistical analysis revealed most prominent increase in k2 in the neuronal fiber tracts, as well as decrease in fractional anisotropy in them in the multiple sclerosis patients. The present study clarified that the pathological changes associated with astrocytic reactivation in multiple sclerosis patients could be visualized by quantitative 1-C-11 acetate PET.

Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain.

Salvage surgery after radiation therapy is known to be associated with a high incidence of postoperative complications. We describe a case of a successful salvage surgery after BNCT. In our patient with head and neck carcinoma, cervical lymph node recurrence with adhesion to a large vessel occurred after conventional radiotherapy. This lesion responded well to BNCT. Salvage surgery was subsequently performed to remove the residual tumor. Histopathologically, the isolated tissue contained tumor cells in its center and the surrounding tissue showed severe fibrosis. However, the tissue outside of the irradiation area had almost no fibrosis. BNCT may facilitate salvage surgery after radiotherapy because it causes less injury to the surrounding tissue than conventional radiotherapy. Our experience suggests that BNCT may be a feasible preoperative treatment in patients with inoperable lesions or in those who strongly desire preservation of function.

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). 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. 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. 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.

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Generally, FDG-PET/CT image is acquired at the 60th minute after tracer administration. Depending on the clinical case, additional delayed scans may be useful. However, it is difficult to judge whether additional delayed scan is useful or not. The purposes of this study were creation and evaluation of educational programs to help radiological technologists to decide the usefulness of additional delayed scan of FDG-PET/CT. METHODS Educational programs consisted of the instructional materials and the judgment test of clinical cases. The instructional materials provided the valuable findings for differentiation between uptake in the wall of the colon and colon content, distinction between uptake in the lymph node and urinary tract, and evaluation of malignancy. The judgment test of clinical cases consisted of 10 cases selected by a nuclear medicine physician (for 5 of that cases additional delayed scan was decided to be useful). Five experienced technologists and five inexperienced technologists scored the volubility of additional delayed scan pre- and post-training using the instructional materials (the full marks of score is 5). RESULTS After the educational programs using the instructional materials, the score was improved with the significant difference in both experienced (pre: 3.6±1.4, post: 4.0±1.2) and inexperienced (pre: 2.8±1.5, post: 3.7±1.5) groups (p

Objective Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values. Methods Six healthy volunteers were injected with 18F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. Results The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise’s MA2 in all regions (mean AIC value − 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC − 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0 ± 1.9 ppm 1 h after, and 5.7 ± 1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4 ± 0.3 ppm 1 h, and 1.0 ± 0.3 ppm 2 h post-injection). Conclusion The 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2). Trail registry The UMIN clinical trial number: UMIN000022850. Electronic supplementary material The online version of this article (10.1007/s12149-019-01427-9) contains supplementary material, which is available to authorized users.

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Gottingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.

A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95 ± 0.84 vs 1.18 ± 0.24 in necrosis (P = 0.014); SUVmax in recurrence was 4.63 ± 1.23 vs 1.93 ± 0.44 in necrosis (P = 0.014); MTV in recurrence was 44.92 ± 28.93 mL vs 10.66 ± 8.46 mL in necrosis (P = 0.032); and mean TL FBPA uptake in recurrence was 121.01 ± 50.48 g vs 12.36 ± 9.70 g in necrosis (P = 0.0029).In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [

Objective Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO2 to the DMN. Methods Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15O-O2, 15O-CO gases and 15O-water PET. Quantitative CBF and CMRO2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson’s correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO2, respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO2. Results Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO2. Among them, 12 overlapping networks were observed between CBF and CMRO2. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO2, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. Conclusions We estimated the functional correlations in the DMN by means of quantitative PET using 15O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO2, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

Non-Hodgkin's lymphoma (NHL) cases with inconclusive biopsy findings are not infrequently referred for fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (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 andThe SUVmax of NHL tends to be higher in TOFBoth SUVmax10g/mL in non-TOF

Background Cerebral extraction of diffusively distributed substances like oxygen has been suggested to change according to the cerebral blood flow (CBF) and status of the microvasculature. The relationships between the cerebral extraction of diffusively distributed lipophilic tracers and the severity of cerebral ischemia has not yet been clarified. In the present study, we attempted to elucidate the association between the extraction fraction of the lipophilic tracer I-123 iomazenil (IMZ) (IMZ-EF) and the oxygen extraction fraction (OEF) derived from O-15 PET in patients with chronic steno-occlusive disease of internal carotid artery (ICA) or middle cerebral artery (MCA). Methods Seven patients with unilateral chronic severe stenosis or occlusion of the middle cerebral/internal cerebral artery were prospectively recruited for this study. All the patients underwent both O-15 PET and quantitative I-123 IMZ SPECT. Parametric images derived from the PET and SPECT scans were anatomically normalized and evaluated by automated image analysis based on the volume-of-interest template. Results The asymmetry index (AI) of IMZ-EF was shown to be significantly correlated with the AI of OEF (r = 0.562, P < 0.001) in the internal carotid artery perfusion area. Strong and significant correlation between the AI of the influx rate constant K1 of IMZ and the AI of the cerebral metabolic rate of oxygen (r = 0.552, P = 0.001) was clarified. Conclusions Our results suggested that the transportation efficiency of I-123 IMZ into the brain tissue was an indicator for evaluating severity of cerebral ischemia in patients with chronic steno-occlusive disease of ICA or MCA. Cerebral metabolic state can possibly be estimated by I-123 IMZ SPECT without cyclotron.

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation ofIn 6 healthy volunteers, whole-bodyThe maximum mean

The linear correlation between (11)C-methionine PET and tumor cell density is not well conserved at the tumor border in glioma. A novel imaging analysis method, voxelwise (18)F-FDG-(11)C-methionine PET decoupling analysis (decoupling score), was evaluated to determine whether it could be used to quantitatively assess glioma cell infiltration in MRI-nonenhancing T2 hyperintense lesions.Data collection was performed in a prospective fashion. Fifty-four MRI-nonenhancing T2 hyperintense specimens were stereotactically obtained from 23 glioma patients by intraoperative navigation guidance. The decoupling score and tumor-to-normal tissue (T/N) ratio of (11)C-methionine PET were calculated at each location. Correlations between the tumor cell density at these lesions, decoupling score, and T/N ratio of (11)C-methionine PET were then evaluated.Both the decoupling score and the T/N ratio showed a linear correlation with tumor cell density at these specimens (R(2) = 0.52 and 0.53, respectively). Use of the decoupling score (cutoff = 3.0) allowed the detection of specimens with a tumor cell density of more than 1,000/mm(2), with a sensitivity and specificity of 93.5% and 87.5%, respectively, whereas conventional (11)C-methionine PET (cutoff = 1.2 in T/N ratio) was able to detect with a sensitivity and specificity of 87.0% and 87.5%, respectively. Reconstructed images (decoupling map) using the decoupling score enabled the visualization of glioma lesions that were difficult to visualize by (11)C-methionine PET alone.The decoupling score showed better performance in detecting glioma cell infiltration than (11)C-methionine uptake alone, thus suggesting that (18)F-FDG-(11)C-methionine uptake decoupling analysis is a powerful imaging modality for assessing glioma invasion.

BACKGROUND AND PURPOSE: It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging–based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions. MATERIALS AND METHODS: Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging–based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions. RESULTS: The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development. CONCLUSIONS: The effectiveness of MR imaging–based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess chemotherapeutic response metabolically and quantitatively. The aim of this study was to evaluate therapeutic response to neoadjuvant chemotherapy for locally advanced esophageal cancer, comparing PERCIST with the currently widely used response evaluation criteria in solid tumors (RECIST).Fifty-one patients with locally advanced esophageal cancer who received neoadjuvant chemotherapy (5-fluorouracil, adriamycin, and cisplatin), followed by surgery were studied. Chemotherapeutic lesion responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methods. The PET/CT scans were obtained before chemotherapy and about 2 wk after completion of chemotherapy. Associations were statistically analyzed between survival (overall and disease-free survival) and clinicopathologic results (histology [well-, moderately, and poorly differentiated squamous cell carcinoma], lymphatic invasion, venous invasion, clinical stage, pathologic stage, resection level, reduction rate of tumor diameter, reduction rate of tumor uptake, chemotherapeutic responses in RECIST and PERCIST, and pathologic response).There was a significant difference in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P0.0001). Univariate analysis showed that lymphatic invasion, venous invasion, resection level, pathologic stage, and PERCIST were significant factors associated with disease-free or overall survival in this study. Although multivariate analysis demonstrated that venous invasion (disease-free survival: hazard ratio [HR] = 4.519, P = 0.002; overall survival: HR = 5.591, P = 0.003) and resection level (disease-free survival: HR = 11.078, P = 0.001) were the significant predictors, PERCIST was also significant in noninvasive therapy response assessment before surgery (disease-free survival: HR = 4.060, P = 0.025; overall survival: HR = 8.953, P = 0.034).RECIST based on the anatomic size reduction rate did not demonstrate the correlation between therapeutic responses and prognosis in patients with esophageal cancer receiving neoadjuvant chemotherapy. However, PERCIST was found to be the strongest independent predictor of outcomes. Given the significance of noninvasive radiologic imaging in formulating clinical treatment strategies, PERCIST might be considered more suitable for evaluation of chemotherapeutic response to esophageal cancer than RECIST.

BACKGROUND AND PURPOSE: CBR imaging is highly susceptible to a PVE produced by morphologic changes in the brain related to aging and brain laterality. We assessed the influence of PVE produced by regional age-related changes in gray matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in human CBR binding by using PVE-corrected SPECT images. MATERIALS AND METHODS: Nineteen right-handed healthy volunteers (range, 25–82 years; mean, 55 ± 21 years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The influence of age-related changes in rGMC on SPECT images before PVE correction was assessed. PVE correction of the SPECT images was performed by using an MR imaging–based method. Voxel-based linear regression analyses of the PVE-corrected SPECT images were performed by using SPM5. RESULTS: The age-related reductions in rGMC and BP without PVE correction revealed a significant direct proportional correlation. Voxel-based statistical analysis with PVE correction showed no significant age-related changes in BP. CONCLUSIONS: PVE correction was indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR binding in right-handed healthy humans.

Gastrointestinal stromal tumors (GISTs) and malignant lymphomas (MLs) in the abdomen are often observed as tumors of unknown origin on F-18 FDG PET/CT. The purpose of this study was to evaluate the intratumoral metabolic heterogeneity of F-18 FDG uptake on PET to determine if it might be helpful to discriminate between these tumors.The F-18 FDG PET/CT findings of 21 large abdominal tumors were retrospectively evaluated (9 GISTs and 12 MLs). Intratumoral heterogeneity was evaluated by visual scoring (visual score: 0, homogeneous; 1, slightly heterogeneous; 2, moderately heterogeneous; 3, highly heterogeneous) and by the cumulative standardized uptake value (SUV) histograms on transaxial PET images at the maximal cross-sectional tumor diameter. Percent tumor areas above a threshold from 0 to 100% of the maximum SUV were plotted and the area under curve of the cumulative SUV histograms (AUC-CSH) was used as a heterogeneity index, where lower values corresponded with increased heterogeneity. Correlation between the visual score and the AUC-CSH was investigated by the Spearman's rank test.GISTs exhibited heterogeneous uptake of F-18 FDG, whereas MLs showed rather homogeneous uptake on visual analysis (visual score: 2.67 ± 0.50 and 0.58 ± 0.79, respectively; p 0.001). The AUC-CSH was significantly lower for the GISTs than for the MLs (0.41 ± 0.14 and 0.64 ± 0.08, respectively; p 0.001). Significant correlations were observed between the visual score and the AUC-CSH (ρ = -0.866, p 0.001).GISTs exhibited significantly heterogeneous intratumoral tracer uptake as compared with the MLs. Evaluation of the intratumoral heterogeneity of F-18 FDG uptake may help in the discrimination between these tumors.

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF(b)), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by (15)O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF(b) (47.6 mL/100 mL/min, n = 7) was associated with normal CBF(b)/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBF(b) (31.8 mL/100 mL/min, n = 9) was associated with decreased CBF(b)/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF(b) regions with normal CPP, which has not been described in previous studies.

Local cerebral perfusion pressure (CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow (CBF) to cerebral blood volume (CBV) can be used as an index of the local CPP. In this study, we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of (15)O positron emission tomography. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by H2 (15)O bolus injection for CBF measurement and by C(15)O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization. Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum (19.3 ± 5.2/min), followed by the putamen (18.2 ± 3.9), pons (16.4 ± 4.6), thalamus (14.5 ± 3.3), cerebral cortices (13.2 ± 2.4), and centrum semiovale (11.5 ± 2.1). The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.

PET with (15)O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the (15)O gas steady-state inhalation method for normal anesthetized rats.Eight normal male Sprague-Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by (15)O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm(3); frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with (15)O-CO(2) and (15)O-O(2) gases delivered through the radioactive gas stabilizer. CBV was measured by (15)O-CO gas inhalation and corrected for the intravascular hemoglobin-bound (15)O-O(2). Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images.The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68-85) min. In both the (15)O-CO(2) and the (15)O-O(2) studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO(2), 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL.Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO(2) using the original steady-state inhalation method of (15)O-CO(2) and (15)O-O(2) gases and measurement of CBV using the (15)O-CO gas inhalation method in the brain of normal anesthetized rats.

Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of (11)C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OS(WT1)).Fourteen patients with recurrent malignant glioma were included in the study, and OS(WT1) was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of (11)C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy.The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in (11)C-methionine uptake pre- and posttreatment; 2) area with increased (11)C-methionine uptake posttreatment (PRM(+MET)); and 3) area with decreased (11)C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OS(WT1) (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM(+MET) area showed excellent correlation (p = 0.008) with OS(WT1).This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001.

Discriminating tumor infiltrative and vasogenic brain edema in malignant gliomas is important although challenging in clinical settings. This study challenged this issue by performing voxel-wise analysis of (18)F-fluorodeoxy glucose (FDG) and (11)C-methionine positron emission tomography (PET) in peritumoral brain edemas. The authors studied ten malignant glioma and nine meningioma patients with peritumoral brain edema. A voxel-wise analysis of FDG and (11)C-methionine PET was performed in order to quantify the correlation between uptake of these tracers in normal brain tissue and peritumoral brain edema. Decoupling score of the uptake of two tracers was calculated as the z-score from the estimated correlation between uptake of the two tracers in normal brain tissue. The decoupling score was also converted into images for visual inspection. Average decoupling score in the peritumoral brain edema was calculated and compared between those obtained from malignant gliomas and meningiomas. FDG and (11)C-methionine uptake showed a reproducible linear correlation in normal brain tissue. This correlation was preserved in peritumoral edema of meningioma, but not in that of malignant gliomas. In malignant gliomas, higher (11)C-methionine uptake compared to that estimated by the FDG uptake in normal brain tissue was observed, thus suggesting that decoupling was caused by tumor infiltration. Visual inspection of the decoupling score enabled discrimination of tumor infiltrative and vasogenic edema. The average decoupling scores of the peritumoral brain edema in malignant gliomas were significantly higher than those in meningiomas (2.9 vs. 0.7, P = 0.0003). As a conclusion, FDG/(11)C-methionine uptake decoupling score can be used for the discrimination of tumor infiltrative and vasogenic brain edema. The proposed method also suggests the possibility of accurately detecting tumor infiltration into brain tissues in gliomas, providing significant information for treatment planning and follow-up.

To demonstrate that positron emission tomography (PET)/magnetic resonance imaging (MRI) fusion was feasible in characterizing pancreatic tumors (PTs), comparing MRI and computed tomography (CT) as mapping images for fusion with PET as well as fused PET/MRI and PET/CT.We retrospectively reviewed 47 sets of (18)F-fluorodeoxyglucose ((18)F -FDG) PET/CT and MRI examinations to evaluate suspected or known pancreatic cancer. To assess the ability of mapping images for fusion with PET, CT (of PET/CT), T1- and T2-weighted (w) MR images (all non-contrast) were graded regarding the visibility of PT (5-point confidence scale). Fused PET/CT, PET/T1-w or T2-w MR images of the upper abdomen were evaluated to determine whether mapping images provided additional diagnostic information to PET alone (3-point scale). The overall quality of PET/CT or PET/MRI sets in diagnosis was also assessed (3-point scale). These PET/MRI-related scores were compared to PET/CT-related scores and the accuracy in characterizing PTs was compared.Forty-three PTs were visualized on CT or MRI, including 30 with abnormal FDG uptake and 13 without. The confidence score for the visibility of PT was significantly higher on T1-w MRI than CT. The scores for additional diagnostic information to PET and overall quality of each image set in diagnosis were significantly higher on the PET/T1-w MRI set than the PET/CT set. The diagnostic accuracy was higher on PET/T1-w or PET/T2-w MRI (93.0 and 90.7%, respectively) than PET/CT (88.4%), but statistical significance was not obtained.PET/MRI fusion, especially PET with T1-w MRI, was demonstrated to be superior to PET/CT in characterizing PTs, offering better mapping and fusion image quality.

We compared the diagnostic accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and PET/magnetic resonance imaging (MRI) fusion images for gynecological malignancies.A total of 31 patients with gynecological malignancies were enrolled. FDG-PET images were fused to CT, T1- and T2-weighted images (T1WI, T2WI). PET-MRI fusion was performed semiautomatically. We performed three types of evaluation to demonstrate the usefulness of PET/MRI fusion images in comparison with that of inline PET/CT as follows: depiction of the uterus and the ovarian lesions on CT or MRI mapping images (first evaluation); additional information for lesion localization with PET and mapping images (second evaluation); and the image quality of fusion on interpretation (third evaluation).For the first evaluation, the score for T2WI (4.68 +/- 0.65) was significantly higher than that for CT (3.54 +/- 1.02) or T1WI (3.71 +/- 0.97) (P0.01). For the second evaluation, the scores for the localization of FDG accumulation showing that T2WI (2.74 +/- 0.57) provided significantly more additional information for the identification of anatomical sites of FDG accumulation than did CT (2.06 +/- 0.68) or T1WI (2.23 +/- 0.61) (P0.01). For the third evaluation, the three-point rating scale for the patient group as a whole demonstrated that PET/T2WI (2.72 +/- 0.54) localized the lesion significantly more convincingly than PET/CT (2.23 +/- 0.50) or PET/T1WI (2.29 +/- 0.53) (P0.01).PET/T2WI fusion images are superior for the detection and localization of gynecological malignancies.

The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) for staging/restaging, evaluating the treatment response, and screening of recurrence in patients with malignant lymphoma (ML) during long-term follow-up, and to compare that with computer tomography (CT)/magnetic resonance imaging (MRI).The study was conducted in 59 ML patients who underwent whole-body 18F-FDG-PET examinations three times or more from October 1998 to August 2006. The location of the lesions in the patients with positive findings on 18F-FDG-PET and/or the corresponding CT/MRI was classified into supradiaphragmatic (n = 10), infradiaphragmatic (n = 7), and extranodal sites (n = 20), and the findings were compared on a site basis according to the gold standard, which consisted of all clinical information available, including follow-up results.A total of 156 18F-FDG-PET examinations for which the corresponding CT/MRI images were also available were evaluated, and a total of 305 sites showed positive findings on 18F-FDG-PET and/or CT/MRI. Concordant positive findings were obtained in 76% for staging/restaging, 34% for evaluation of the treatment response, and 50% for screening of recurrence. The accuracy of 18F-FDG-PET versus CT/MRI was 92% versus 84% (P = 0.06) for staging/restaging, 84% versus 50% (P0.05) for the evaluation of the treatment response, and 83% versus 72% (P = 0.21) for the screening of recurrence. At pathologic sites with discrepant findings between 18F-FDG-PET and CT/MRI (n = 122), the frequency of accurate diagnosis by 18F-FDG-PET (76%) was higher than that by CT/MRI (24%), especially for the evaluation of the treatment response.18F-FDG-PET is expected to play a significant role in the management of ML patients even after effective treatment is initiated.

The new RECIST criteria for evaluation of tumor response to chemotherapy and/or radiotherapy were proposed in 1999. We compared RECIST with the WHO criteria and also compared both methods with the histological findings, to evaluate RECIST.The subjects were 32 primary lung cancer patients operated on after chemotherapy and/or radiotherapy. Two radiologists measured the diameter of the tumors and compared the RECIST and WHO criteria using the McNemar test. We also compared both criteria with the histological results.Using RECIST, partial response (PR) was assessed in 12 cases, stable disease (SD) in 18, and progressive disease (PD) in 2. With the WHO criteria, PR was seen in 15, no change (NC) in 15, and PD in 2. The two evaluations corresponded in 29 of 32 cases, and the p-value was 0.2500. Ef.1b-2 (good histological effect) was much higher in PR, and to evaluate the size of the tumors was useful, although more than half of SD was Ef.1b-2.RECIST criteria corresponded almost perfectly with the WHO criteria, suggesting that RECIST is accurate and useful.

The purpose of this study was to assess the benefits of computed tomography(CT)-guided marking using dyes in patients undergoing lung resection for peripheral nodules.Between January 1997 and August 2002, the location of small pulmonary nodules was identified with the aid of CT-guided marking in 52 patients scheduled for surgery. Dye-injection was performed in 52 patients (indigo carmine, n = 15; indocyanine green, n = 37). The average nodule size was 9.2 mm (range, 3 to 18 mm).The procedure using dyes proved to be easy and safe: the dyes were easily injected near the nodules, and no serious complications ensued. Intraoperatively, indocyanine was superior to indigo carmine with respect to visualization of the dyed pleural surface.The preoperative CT-guided injection of indocyanine green proved to be the most useful and safest technique for identifying peripheral pulmonary nodules in patients scheduled for thoracoscopic surgery or minimal thoracotomy.