Eku Shimosegawa

Evaluation of Response to Neoadjuvant Chemotherapy for Esophageal Cancer: PET Response Criteria in Solid Tumors Versus Response Evaluation Criteria in Solid Tumors

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). Methods: 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 18F-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). Results: There was a significant difference in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P < 0.0001). 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). Conclusion: 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.

Interference between PET and MRI sub-systems in a silicon-photomultiplier-based PET/MRI system

The silicon-photomultiplier (Si-PM) is a promising photodetector, especially for integrated PET/MRI systems, due to its small size, high gain, and low sensitivity to static magnetic fields. The major problem using a Si-PM-based PET system within the MRI system is the interference between the PET and MRI units. We measured the interference by combining a Si-PM-based PET system with a permanent-magnet MRI system. When the RF signal-induced pulse height exceeded the lower energy threshold level of the PET system, interference between the Si-PM-based PET system and MRI system was detected. The prompt as well as the delayed coincidence count rates of the Si-PM-based PET system increased significantly. These noise counts produced severe artifacts on the reconstructed images of the Si-PM-based PET system. In terms of the effect of the Si-PM-based PET system on the MRI system, although no susceptibility artifact was observed on the MR images, electronic noise from the PET detector ring was detected by the RF coil and reduced the signal-to-noise ratio (S/N) of the MR images. The S/N degradation of the MR images was reduced when the distance between the RF coil and the Si-PM-based PET system was increased. We conclude that reducing the interference between the PET and MRI systems is essential for achieving the optimum performance of integrated Si-PM PET/MRI systems.

Simultaneous imaging using Si-PM-based PET and MRI for development of an integrated PET/MRI system

The silicon photomultiplier (Si-PM) is a promising photo-detector for PET for use in magnetic resonance imaging (MRI) systems because it has high gain and is insensitive to static magnetic fields. Recently we developed a Si-PM-based depth-of-interaction PET system for small animals and performed simultaneous measurements by combining the Si-PM-based PET and the 0.15 T permanent MRI to test the interferences between the Si-PM-based PET and an MRI. When the Si-PM was inside the MRI and installed around the radio frequency (RF) coil of the MRI, significant noise from the RF sequence of the MRI was observed in the analog signals of the PET detectors. However, we did not observe any artifacts in the PET images; fluctuation increased in the count rate of the Si-PM-based PET system. On the MRI side, there was significant degradation of the signal-to-noise ratio (S/N) in the MRI images compared with those without PET. By applying noise reduction procedures, the degradation of the S/N was reduced. With this condition, simultaneous measurements of a rat brain using a Si-PM-based PET and an MRI were made with some degradation in the MRI images. We conclude that simultaneous measurements are possible using Si-PM-based PET and MRI.

A temperature-dependent gain control system for improving the stability of Si-PM-based PET systems

The silicon-photomultiplier (Si-PM) is a promising photodetector for the development of new PET systems due to its small size, high gain and relatively low sensitivity to the static magnetic field. One drawback of the Si-PM is that it has significant temperature-dependent gain that poses a problem for the stability of the Si-PM-based PET system. To reduce this problem, we developed and tested a temperature-dependent gain control system for the Si-PM-based PET system. The system consists of a thermometer, analog-to-digital converter, personal computer, digital-to-analog converter and variable gain amplifiers in the weight summing board of the PET system. Temperature characteristics of the Si-PM array are measured and the calculated correction factor is sent to the variable gain amplifier. Without this correction, the temperature-dependent peak channel shifts of the block detector were -55% from 20 °C to 35 °C. With the correction, the peak channel variations were corrected within ±8%. The coincidence count rate of the Si-PM-based PET system was measured using a Na-22 point source while monitoring the room temperature. Without the correction, the count rate inversely changed with the room temperature by 10% for 1.5° C temperature changes. With the correction, the count rate variation was reduced to within 3.7%. These results indicate that the developed temperature-dependent gain control system can contribute to improving the stability of Si-PM-based PET systems.

Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer

Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of 111In-labeled dendritic cells (DC) in combination with preoperative chemotherapy in 5 esophageal cancer patients. Mature DC were generated and traced by scintigraphy after their administration. No adverse events that were directly related to the intratumoral DC administration were observed. Delayed-type hypersensitivity skin tests against keyhole limpet hemocyanin, which was added to the culture medium, detected a positive response in 3 patients, and keyhole limpet hemocyanin antibody production was observed in 4 patients, suggesting that intratumorally administered DC migrate to the lymph nodes, where they function as antigen-presenting cells. However, scintigraphic images obtained after the DC administration demonstrated that the DC remained at the esophageal tumor injection sites in all cases, and no DC accumulation was observed elsewhere. The accumulation of CD83+ cells in the primary tumor was also observed in 2 out of 4 patients in an immunohistochemical analysis using surgically resected specimens. Although the induction of tumor-specific immune responses during chemoimmunotherapy was also analyzed in enzyme-linked immunosorbent assay against 28 tumor antigens, none of the antibodies against the antigens displayed enhanced titers. No changes of NY-ESO-1-specific cellular immune response was observed in a patient who displayed NY-ESO-1 antibody production before the DC administration. These results suggest that the intratumoral administration of 111In-labeled mature DC during chemotherapy does not lead to detectable DC migration from the primary tumor to the draining lymph nodes, and therefore, might not achieve an optimal clinical response.

Intratumoral heterogeneity of F-18 FDG uptake differentiates between gastrointestinal stromal tumors and abdominal malignant lymphomas on PET/CT

ObjectiveGastrointestinal 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.MethodsThe 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.ResultsGISTs exhibited heterogeneous uptake of F-18 FDG, whereas MLs showed rather homogeneous uptake on visual analysis (visual score: 2.67xa0±xa00.50 and 0.58xa0±xa00.79, respectively; pxa0<xa00.001). The AUC-CSH was significantly lower for the GISTs than for the MLs (0.41xa0±xa00.14 and 0.64xa0±xa00.08, respectively; pxa0<xa00.001). Significant correlations were observed between the visual score and the AUC-CSH (ρxa0=xa0−0.866, pxa0<xa00.001).ConclusionGISTs 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.

Development of a high-resolution Si-PM-based gamma camera system.

A silicon photomultiplier (Si-PM) is a promising photodetector for PET, especially for PET/MRI combined systems, due to its high gain, small size, and lower sensitivity to static magnetic fields. However, these properties are also promising for gamma camera systems for single-photon imaging. We developed an ultra-high-resolution Si-PM-based compact gamma camera system for small animals. Y(2)SiO(5):Ce (YSO) was selected as scintillators because of its high light output and no natural radioactivity. The gamma camera consists of 0.6 mm × 0.6 mm × 6 mm YSO pixels combined with a 0.1 mm thick reflector to form a 17 × 17 matrix that was optically coupled to a Si-PM array (Hamamatsu multi-pixel photon counter S11064-050P) with a 2 mm thick light guide. The YSO block size was 12 mm × 12 mm. The YSO gamma camera was encased in a 5 mm thick gamma shield, and a parallel hole collimator was mounted in front of the camera (0.5 mm hole, 0.7 mm separation, 5 mm thick). The two-dimensional distribution for the Co-57 gamma photons (122 keV) was almost resolved. The energy resolution was 24.4% full-width at half-maximum (FWHM) for the Co-57 gamma photons. The spatial resolution at 1.5 mm from the collimator surface was 1.25 mm FWHM measured using a 1 mm diameter Co-57 point source. Phantom and small animal images were successfully obtained. We conclude that a Si-PM-based gamma camera is promising for molecular imaging research.

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: 15O-Labeled Gas Inhalation PET with MRI Fusion

PET with 15O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), 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 15O gas steady-state inhalation method for normal anesthetized rats. Methods: Eight normal male Sprague–Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by 15O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm3; frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with 15O-CO2 and 15O-O2 gases delivered through the radioactive gas stabilizer. CBV was measured by 15O-CO gas inhalation and corrected for the intravascular hemoglobin-bound 15O-O2. 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. Results: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68–85) min. In both the 15O-CO2 and the 15O-O2 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; CMRO2, 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL. Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO2 using the original steady-state inhalation method of 15O-CO2 and 15O-O2 gases and measurement of CBV using the 15O-CO gas inhalation method in the brain of normal anesthetized rats.

Classification of delusions in Alzheimer's disease and their neural correlates

Background:u2002 Previous findings on neural correlates of delusion in Alzheimers disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data.

Diagnostic value of FDG‐PET for lymph node metastasis and outcome of surgery for biliary cancer

Histopathologically confirmed lymph node metastasis is a prognostic factor in the surgical treatment of biliary tract cancer, however, preoperative diagnosis is still difficult even with computed tomography. FDG‐PET has been used for the diagnosis of cancer and metastatic lesions. Herein, we retrospectively evaluated the utility of FDG‐PET for detection of lymph node metastasis in biliary tract cancer.