Background 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) has been an essential modality in oncology. We propose a semi-automated algorithm to objectively determine liver standardized uptake value (SUV), which is used as a threshold for tumor delineation.MethodsA large spherical volume of interest (VOI) was placed manually to roughly enclose the right lobe (RL) of the liver. For each voxel in this VOI, a coefficient of variation of voxel values (CVv) was calculated for neighboring voxels within a radius of d/2. The voxel with the minimum CVv was then selected, where a 30-mm spherical VOI was placed at that voxel in accordance with PERCIST criteria. Two nuclear medicine physicians independently defined 30-mm VOIs manually on 124 studies in 62 patients to generate the standard values, against which the results from the new method were compared.ResultsThe semi-automated method was successful in determining the liver SUV that was consistent between the two physicians in all the studies (d = 80 mm). The liver SUV threshold (mean +3 SD within 30-mm VOI) determined by the new semi-automated method (3.12±0.61) was not statistically different from those determined by the manual method (Physician-1: 3.14±0.58, Physician-2: 3.15±0.58). The semi-automated method produced tumor volumes that were not statistically different from those by experts' manual operation. Furthermore, the volume change in the two sequential studies had no statistical difference between semi-automated and manual methods.ConclusionsOur semi-automated method could define the liver SUV robustly as the threshold value used for tumor volume measurements according to PERCIST. The method could avoid possible subjective bias of manual liver VOI placement and is thus expected to improve clinical performance of volume-based parameters for prediction of cancer treatment response.

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BackgroundEfficient bioluminescence resonance energy transfer (BRET) from a bioluminescent protein to a fluorescent protein with high fluorescent quantum yield has been utilized to enhance luminescence intensity, allowing single-cell imaging in near real time without external light illumination.Methodology/Principal FindingsWe applied BRET to develop an autoluminescent Ca2+ indicator, BRAC, which is composed of Ca2+-binding protein, calmodulin, and its target peptide, M13, sandwiched between a yellow fluorescent protein variant, Venus, and an enhanced Renilla luciferase, RLuc8. Adjusting the relative dipole orientation of the luminescent protein's chromophores improved the dynamic range of BRET signal change in BRAC up to 60%, which is the largest dynamic range among BRET-based indicators reported so far. Using BRAC, we demonstrated successful visualization of Ca2+ dynamics at the single-cell level with temporal resolution at 1 Hz. Moreover, BRAC signals were acquired by ratiometric imaging capable of canceling out Ca2+-independent signal drifts due to change in cell shape, focus shift, etc.Conclusions/SignificanceThe brightness and large dynamic range of BRAC should facilitate high-sensitive Ca2+ imaging not only in single live cells but also in small living subjects.

MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. 4Results:All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p=0.007, p=0.04, and p=0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p=0.0028, p=0.037, and p=0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky Performance Scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. Conclusions:We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically-active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

On-chip integration of III-V laser diodes and photodetectors with silicon nanowire waveguides is demonstrated. Through flip-chip bonding of GaInNAs/GaAs laser diodes directly onto the silicon substrate, efficient heat dissipation was realized and characteristic temperatures as high as 132K were achieved. Spot-size converters for the laser-to-waveguide coupling were used, with efficiencies greater than 60%. The photodetectors were fabricated by bonding of InGaAs/InP wafers directly to silicon waveguides and formation of metal-semiconductor-metal structures, giving responsivities as high as 0.74 A/W. Both laser diode and the photodetector were integrated with a single silicon waveguide to demonstrate a complete on-chip optical transmission link.

Summary:Hepatic veno-occlusive disease (VOD) is one of the most serious complications in patients receiving stem cell transplantation (SCT). However, the cause of VOD remained to be elucidated. Vascular endothelial growth factor (VEGF) has been reported to have various physiological effects including neovascularization and acceleration of vasopermeability. Because we postulated that VEGF could be one of the causative factors in VOD after SCT, serum VEGF levels were measured by ELISA in 50 patients receiving SCT. Six of the patients showed typical manifestations of VOD and four of them died due to VOD. The mean maximum serum VEGF level in the six patients with VOD was markedly increased compared to that in the patients without VOD (P Ͻ 0.001) and in normal controls (P Ͻ 0.001). Moreover, the mean maximum serum VEGF level in patients with VOD before conditioning chemoradiotherapy for SCT was also high compared to patients without VOD (P = 0.0012) in the same period. Similarly, serum VEGF levels were significantly higher in patients whose plasma protein C activities decreased below 40% (P Ͻ 0.001). During the clinical course of VOD after SCT, the increase of serum VEGF synchronized fairly well with the development of VOD. Since VEGF causes the expression of tissue factor on circulating monocyte/ macrophages and results in hypercoagulability, our observation suggests that in the patients with VOD who showed high serum VEGF it might account for the development of VOD. Furthermore, this observation may indicate a novel therapeutic strategy for prevention of VOD. Bone Marrow Transplantation (2001) 27, 1173-1180.