Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder associated with traumatic memory, yet its etiology remains unclear. Reexperiencing symptoms are specific to PTSD compared to other anxiety-related disorders. Importantly, reexperiencing can be mimicked by retrieval-related events of fear memory in animal models of traumatic memory. Recent studies revealed candidate PTSD-associated genes that were related to the cyclic adenosine monophosphate (cAMP) signaling pathway. Here, we demonstrate the tight linkage between facilitated cAMP signaling and PTSD by analyzing loss- and gain-of-cAMP signaling effects on fear memory in mice and the transcriptomes of fear memory-activated mice and female PTSD patients with reexperiencing symptoms. Pharmacological and optogenetic upregulation or downregulation of cAMP signaling transduction enhanced or impaired, respectively, the retrieval and subsequent maintenance of fear memory in mice. In line with these observations, integrative mouse and human transcriptome analysis revealed the reduced mRNA expression of phosphodiesterase 4B (PDE4B), an enzyme that degrades cAMP, in the peripheral blood of PTSD patients showing more severe reexperiencing symptoms and the mouse hippocampus after fear memory retrieval. Importantly, more severe reexperiencing symptoms and lower PDE4B mRNA levels were correlated with decreased DNA methylation of a locus within PDE4B, suggesting the involvement of methylation in the mechanism of PTSD. These findings raise the possibility that the facilitation of cAMP signaling mediating the downregulation of PDE4B expression enhances traumatic memory, thereby playing a key role in the reexperiencing symptoms of PTSD patients as a functional index of these symptoms.

Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model.

The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.

Interactions between the amygdala and medial prefrontal cortex as upstream regulators of the hippocampus to reconsolidate and enhance retrieved inhibitory avoidance memory.

Memory reconsolidation is thought to maintain or enhance an original memory or add new information to the memory. Retrieved inhibitory avoidance (IA) memory is enhanced through memory reconsolidation by activating gene expression in the amygdala, medial prefrontal cortex (mPFC), and hippocampus. However, it remains unclear how these regions interact to reconsolidate/enhance IA memory. Here, we found the interactions between the amygdala and mPFC as upstream regulators of the hippocampus for IA memory reconsolidation. Pharmacological inactivation of the amygdala, mPFC, or hippocampus immediately after IA memory retrieval blocked IA memory enhancement. More importantly, inactivation of the amygdala or mPFC blocked the induction of c-Fos in the amygdala, mPFC, and hippocampus, whereas hippocampal blockade inhibited it only in the hippocampus. These observations suggest interactions between the amygdala and mPFC and they both function as upstream regulators of the hippocampus to reconsolidate IA memory. Our findings suggest circuitry mechanisms underlying IA memory enhancement through reconsolidation between the amygdala, mPFC, and hippocampus.

Tumor necrosis factor α negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

Neural inflammation is associated with cognitive decline, especially learning and memory. Tumor necrosis factor α (TNFα) is a major cytokine generated during neuroinflammation. Previous studies indicated that TNFα impairs hippocampus-dependent memory including contextual fear and spatial memories. However, it is unknown which memory processes are impaired by TNFα. Here, we show that TNFα blocked the retrieval and reconsolidation of contextual fear and spatial memories. Micro-infusion of TNFα into the dorsal hippocampus at 6-18 h before retrieval impaired the retrieval of contextual fear memory, although micro-infusion before contextual fear conditioning had no effect on memory formation. Interestingly, hippocampal TNFα micro-infusion before memory retrieval decreased freezing responses, even at 24 h after retrieval, suggesting that TNFα impairs the reconsolidation of contextual fear memory. Similarly, hippocampal TNFα micro-infusion impaired the retrieval and reconsolidation of spatial memory in the Morris water maze. Consistent with these observations, hippocampal TNFα micro-infusion before retrieval blocked the induction of c-fos expression in the hippocampus, which is a marker of neural activation, in response to the retrieval of contextual fear memory. Collectively, our findings indicate that TNFα negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

PURPOSE: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN). METHOD: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness. RESULT: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT. CONCLUSION: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.

Assessment of dysplasia in bone marrow smear with convolutional neural network.

In this study, we developed the world's first artificial intelligence (AI) system that assesses the dysplasia of blood cells on bone marrow smears and presents the result of AI prediction for one of the most representative dysplasia-decreased granules (DG). We photographed field images from the bone marrow smears from patients with myelodysplastic syndrome (MDS) or non-MDS diseases and cropped each cell using an originally developed cell detector. Two morphologists labelled each cell. The degree of dysplasia was evaluated on a four-point scale: 0-3 (e.g., neutrophil with severely decreased granules were labelled DG3). We then constructed the classifier from the dataset of labelled images. The detector and classifier were based on a deep neural network pre-trained with natural images. We obtained 1797 labelled images, and the morphologists determined 134 DGs (DG1: 46, DG2: 77, DG3: 11). Subsequently, we performed a five-fold cross-validation to evaluate the performance of the classifier. For DG1-3 labelled by morphologists, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91.0%, 97.7%, 76.3%, 99.3%, and 97.2%, respectively. When DG1 was excluded in the process, the sensitivity, specificity, PPV, NPV, and accuracy were 85.2%, 98.9%, 80.6%, and 99.2% and 98.2%, respectively.

Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation.

Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the late afternoon-early evening. However, functional roles of local brain circadian clocks in memory performance remains unclear. Here, we show that hippocampal clock controlled by the circadian-dependent transcription factor BMAL1 regulates time-of-day retrieval profile. Inducible transgenic dominant negative BMAL1 (dnBMAL1) expression in mouse forebrain or hippocampus disrupted retrieval of hippocampal memories at Zeitgeber Time 8-12, independently of retention delay, encoding time and Zeitgeber entrainment cue. This altered retrieval profile was associated with downregulation of hippocampal Dopamine-cAMP signaling in dnBMAL1 mice. These changes included decreases in Dopamine Receptors (D1-R and D5-R) and GluA1-S845 phosphorylation by PKA. Consistently, pharmacological activation of cAMP-signals or D1/5Rs rescued impaired retrieval in dnBMAL1 mice. Importantly, GluA1 S845A knock-in mice showed similar retrieval deficits with dnBMAL1 mice. Our findings suggest mechanisms underlying regulation of retrieval by hippocampal clock through D1/5R-cAMP-PKA-mediated GluA1 phosphorylation.

Cone Beam Computed Tomography Image Quality Improvement Using a Deep Convolutional Neural Network.

Introduction Cone beam computed tomography (CBCT) plays an important role in image-guided radiation therapy (IGRT), while having disadvantages of severe shading artifact caused by the reconstruction using scatter contaminated and truncated projections. The purpose of this study is to develop a deep convolutional neural network (DCNN) method for improving CBCT image quality. Methods CBCT and planning computed tomography (pCT) image pairs from 20 prostate cancer patients were selected. Subsequently, each pCT volume was pre-aligned to the corresponding CBCT volume by image registration, thereby leading to registered pCT data (pCTr). Next, a 39-layer DCNN model was trained to learn a direct mapping from the CBCT to the corresponding pCTr images. The trained model was applied to a new CBCT data set to obtain improved CBCT (i-CBCT) images. The resulting i-CBCT images were compared to pCTr using the spatial non-uniformity (SNU), the peak-signal-to-noise ratio (PSNR) and the structural similarity index measure (SSIM). Results The image quality of the i-CBCT has shown a substantial improvement on spatial uniformity compared to that of the original CBCT, and a significant improvement on the PSNR and the SSIM compared to that of the original CBCT and the enhanced CBCT by the existing pCT-based correction method. Conclusion We have developed a DCNN method for improving CBCT image quality. The proposed method may be directly applicable to CBCT images acquired by any commercial CBCT scanner.

Brain networks activated to form object recognition memory.

Object recognition memory allows discrimination of familiar and novel objects. Previous studies have shown the importance of several brain regions for object recognition memories; however, the mechanisms underlying the consolidation of object recognition (OR) memory at the anatomic level remain unknown. Here, we analyzed the brain network for the generation of OR memory in mice by measuring the expression of the immediate-early gene c-fos. We found that c-fos expression was induced in the hippocampus (CA1 and CA3 regions), insular cortex (IC), perirhinal cortex (PRh), and medial prefrontal cortex (mPFC) when OR memory was generated, suggesting that gene expression in these brain regions contributes to the formation of OR memory. Consistently, inhibition of protein synthesis in the mPFC blocked the formation of long-term OR memory. Importantly, network analyses suggested that the hippocampus, IC, PRh and mPFC show increased connectivity with other brain regions when OR memory is formed. Thus, we suggest that a brain network composed of the hippocampus, IC, PRh, and mPFC is required for the generation of OR memory by connecting with other brain regions.

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory.

Memory consolidation, reconsolidation, and extinction have been shown to share similar molecular signatures, including new gene expression. Calpain is a Ca2+-dependent protease that exerts its effects through the proteolytic cleavage of target proteins. Neuron-specific conditional deletions of calpain 1 and 2 impair long-term potentiation in the hippocampus and spatial learning. Moreover, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity. However, the role of hippocampal calpain in memory processes, especially memory consolidation, reconsolidation, and extinction, is still unclear. In the current study, we demonstrated the critical roles of hippocampal calpain in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of calpain in the hippocampus on these memory processes, using the N-Acetyl-Leu-Leu-norleucinal (ALLN; calpain 1 and 2 inhibitor). Microinfusion of ALLN into the dorsal hippocampus impaired long-term memory (24 h memory) without affecting short-term memory (2 h memory). Similarly, this pharmacological blockade of calpain in the dorsal hippocampus also disrupted reactivated memory but did not affect memory extinction. Importantly, the systemic administration of ALLN inhibited the induction of c-fos in the hippocampus, which is observed when memory is consolidated. Our observations showed that hippocampal calpain is required for the consolidation and reconsolidation of contextual fear memory. Further, the results suggested that calpain contributes to the regulation of new gene expression that is necessary for these memory processes as a regulator of Ca2+-signal transduction pathway.

Cone-beam CT reconstruction for non-periodic organ motion using time-ordered chain graph model.

PURPOSE: The purpose of this study is to introduce the new concept of a four-dimensional (4D) cone-beam computed tomography (CBCT) reconstruction approach for non-periodic organ motion in cooperation with the time-ordered chain graph model (TCGM) and to compare it with previously developed methods such as total variation-based compressed sensing (TVCS) and prior-image constrained compressed sensing (PICCS). MATERIALS AND METHODS: Our proposed reconstruction is based on a model including the constraint originating from the images of neighboring time phases. Namely, the reconstructed time-series images depend on each other in this TCGM scheme, and the time-ordered images are concurrently reconstructed in the iterative reconstruction approach. In this study, iterative reconstruction with the TCGM was carried out with 90° projection ranges. The images reconstructed by the TCGM were compared with the images reconstructed by TVCS (200° projection ranges) and PICCS (90° projection ranges). Two kinds of projection data sets-an elliptic-cylindrical digital phantom and two clinical patients' data-were used. For the digital phantom, an air sphere was contained and virtually moved along the longitudinal axis by 3 cm/30 s and 3 cm/60 s; the temporal resolution was evaluated by measuring the penumbral width of the air sphere. The clinical feasibility of the non-periodic time-ordered 4D CBCT image reconstruction was examined with the patient data in the pelvic region. RESULTS: In the evaluation of the digital-phantom reconstruction, the penumbral widths of the TCGM yielded the narrowest result; the results obtained by PICCS and TCGM using 90° projection ranges were 2.8% and 18.2% for 3 cm/30 s, and 5.0% and 23.1% for 3 cm/60 s narrower than that of TVCS using 200° projection ranges. This suggests that the TCGM has a better temporal resolution, whereas PICCS seems similar to TVCS. These reconstruction methods were also compared using patients' projection data sets. Although all three reconstruction results showed motion related to rectal gas or stool, the result obtained by the TCGM was visibly clearer with less blurring. CONCLUSION: The TCGM is a feasible approach to visualize non-periodic organ motion. The digital-phantom results demonstrated that the proposed method provides 4D image series with a better temporal resolution compared to TVCS and PICCS. The clinical patients' results also showed that the present method enables us to visualize motion related to rectal gas and flatus in the rectum.

Effective atomic number estimation using kV-MV dual-energy source in LINAC.

Dual-energy computed tomography (DECT) imaging can measure the effective atomic number (EAN) as well as the electron density, and thus its adoption may improve dose calculations in brachytherapy and external photon/particle therapy. An expanded energy gap in dual-energy sources is expected to yield more accurate EAN estimations than conventional DECT systems, which typically span less than 100kV. The aim of this paper is to assess a larger energy gap DECT by using a linear accelerator (LINAC) radiotherapy system with a kV X-ray imaging device, which are combined to provide X-rays in both the kV- and MV-energy ranges. Traditionally, the EAN is determined by parameterising the Hounsfield Unit; however, this is difficult in a kV-MV DECT due to different uncertainties in the reconstructed attenuation coefficient at each end of the energy spectrum. To overcome this problem, we included a new calibration step to produce the most likely linear attenuation coefficients, based upon the X-ray spectrum. To determine the X-ray spectrum, Monte Carlo calculations using GEANT4 were performed. Then the images were calibrated using information from eight inserts of known materials in a CIRS phantom (CIRS Inc., Norfolk, VA). Agreement between the estimated and empirical EANs in these inserts was within 11%. Validation was subsequently performed with the CatPhan500 phantom (The Phantom Laboratory, Salem). The estimated EAN for seven inserts agreed with the empirical values to within 3%. Accordingly, it can be concluded that, given properly reconstructed images based upon a well-determined X-ray spectrum, kV-MV DECT provides an excellent prediction for the EAN.

Microglial production of TNF-alpha is a key element of sustained fear memory.

The proinflammatory cytokine productions in the brain are altered in a process of fear memory formation, indicating a possibility that altered microglial function may contribute to fear memory formation. We aimed to investigate whether and how microglial function contributes to fear memory formation. Expression levels of M1- and M2-type microglial marker molecules in microglia isolated from each conditioned mice group were assessed by real-time PCR and immunohistochemistry. Levels of tumor necrosis factor (TNF)-α, but not of other proinflammatory cytokines produced by M1-type microglia, increased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Administration of inhibitors of TNF-α production facilitated extinction of fear memory. On the other hand, expression levels of M2-type microglia-specific cell adhesion molecules, CD206 and CD209, were decreased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Our findings indicate that microglial TNF-α is a key element of sustained fear memory and suggest that TNF-α inhibitors can be candidate molecules for mitigating posttraumatic reactions caused by persistent fear memory.

N-glycosylation in the hippocampus is required for the consolidation and reconsolidation of contextual fear memory.

Memory consolidation and reconsolidation have been shown to require new gene expression. N-glycosylation, one of the major post-translational modifications, is known to play essential or regulatory roles in protein function. A previous study suggested that N-glycosylation is required for the maintenance of long-term potentiation in hippocampal CA1 neurons. However, the role of de novo N-glycosylation in learning and memory, such as memory consolidation and reconsolidation, still remains unclear. Here, we show critical roles for N-glycosylation in the consolidation and reconsolidation of contextual fear memory in mice. We examined the effects of pharmacological inhibition of N-glycosylation in the hippocampus on these memory processes using three different inhibitors (tunicamycin, 1-deoxynojirimycin, and swainsonine) that block the enzymatic activity required for N-glycosylation at different steps. Microinfusions of the N-glycosylation inhibitors into the dorsal hippocampus impaired long-term memory (LTM) formation without affecting short-term memory (STM). Similarly, this pharmacological blockade of N-glycosylation in the dorsal hippocampus also disrupted post-reactivation LTM after retrieval without affecting post-reactivation STM. Additionally, a microinfusion of swainsonine blocked c-fos induction in the hippocampus, which is observed when memory is consolidated. Our observations showed that N-glycosylation is required for the consolidation and reconsolidation of contextual fear memory and suggested that N-glycosylation contributes to the new gene expression necessary for these memory processes.

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans.

PURPOSE: To investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans. METHODS AND MATERIALS: Three IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans. RESULTS: The relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively. CONCLUSIONS: This study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy.

PARP-1 activity is required for the reconsolidation and extinction of contextual fear memory.

BACKGROUND: Memory consolidation, reconsolidation, and extinction have been shown to require new gene expression. Poly ADP-ribosylation mediated by poly (ADP-ribose) polymerase-1 (PARP-1) is known to regulate transcription through histone modification. Recent studies have suggested that PARP-1 positively regulates the formation of long-term memory (LTM); however, the roles of PARP-1 in memory processes, especially processes after retrieval, remain unknown. RESULTS: Here, we show critical roles for PARP-1 in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of PARP-1 activity in the hippocampus or medial prefrontal cortex (mPFC) on these memory processes. Similarly with previous findings, a micro-infusion of the PARP-1 inhibitor 3-aminobenzamide or PJ34 into the dorsal hippocampus, but not mPFC, impaired LTM formation without affecting short-term memory (STM). Importantly, this pharmacological blockade of PARP-1 in the dorsal hippocampus, but not mPFC, also disrupted post-reactivation LTM without affecting post-reactivation STM. Conversely, micro-infusion of the PARP-1 inhibitors into the mPFC, but not dorsal hippocampus, blocked long-term extinction. Additionally, systemic administration of the PARP-1 inhibitor Tiq-A blocked c-fos induction in the hippocampus, which is observed when memory is consolidated or reconsolidated, and also blocked c-fos induction in the mPFC, which is observed when memory is extinguished. CONCLUSIONS: Our observations showed that PARP-1 activation is required for the consolidation, reconsolidation, and extinction of contextual fear memory and suggested that PARP-1 contributes to the new gene expression necessary for these memory processes.

[Dose reconstruction using respiratory signals and machine parameters during treatment in stereotactic body radiotherapy].

PURPOSE: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. The purpose of this study was to reconstruct the dose distribution from respiratory signals and machine parameters acquired during stereotactic body radiotherapy (SBRT). METHODS: The treatment plans created for VMAT-SBRT included the constraint of 1 mm/degree in multileaf collimator (MLC) for a moving phantom and three patients with lung tumors. The respiratory signals were derived from projection images acquired during VMAT delivery, while the machine parameters were derived from machine logs. The respiratory signals and machine parameters were then linked along with the gantry angle. With this data, the dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4D CT). The doses at the isocenter, the point of max dose and the centroid of the target were compared with those of the corresponding plans. RESULTS AND DISCUSSION: In the phantom study, the maximum dose difference between the plan and "in-treatment" results was -0.4% at the centroid of the target. In the patient study, the difference was -1.8 ± 0.4% at the centroid of the target. Dose differences of the evaluated points between 4 and 10 phases were not significant. CONCLUSION: The present method successfully reconstructed the dose distribution using the respiratory signals and machine parameters acquired during treatment. This is a feasible method for verifying the actual dose for a moving target.

Reconstruction of the treatment area by use of sinogram in helical tomotherapy.

BACKGROUND: TomoTherapy (Accuray, USA) has an image-guided radiotherapy system with a megavoltage (MV) X-ray source and an on-board imaging device. This system allows one to acquire the delivery sinogram during the actual treatment, which partly includes information from the irradiated object. In this study, we try to develop image reconstruction during treatment with helical tomotherapy. FINDINGS: Sinogram data were acquired during helical tomotherapy delivery using an arc-shaped detector array that consists of 576 xenon-gas filled detector cells. In preprocessing, these were normalized with full air-scan data. A software program was developed that reconstructs 3D images during treatment with corrections as; (1) the regions outside the field were masked not to be added in the backprojection (a masking correction), and (2) each voxel of the reconstructed image was divided by the number of the beamlets passing through its voxel (a ray-passing correction). The masking correction produced a reconstructed image, however, it contained streak artifacts. The ray-passing correction reduced this artifact. Although the SNR (the ratio of mean to standard deviation in a homogeneous region) and the contrast of the reconstructed image were slightly improved with the ray-passing correction, use of only the masking correction was sufficient for the visualization purpose. CONCLUSIONS: The visualization of the treatment area was feasible by using the sinogram in helical tomotherapy. This proposed method would be useful in the treatment verification.

Stereotactic body radiotherapy for small lung tumors in the University of Tokyo Hospital.

Our work on stereotactic body radiation therapy (SBRT) for primary and metastatic lung tumors will be described. The eligibility criteria for SBRT, our previous SBRT method, the definition of target volume, heterogeneity correction, the position adjustment using four-dimensional cone-beam computed tomography (4D CBCT) immediately before SBRT, volumetric modulated arc therapy (VMAT) method for SBRT, verifying of tumor position within internal target volume (ITV) using in-treatment 4D-CBCT during VMAT-SBRT, shortening of treatment time using flattening-filter-free (FFF) techniques, delivery of 4D dose calculation for lung-VMAT patients using in-treatment CBCT and LINAC log data with agility multileaf collimator, and SBRT method for centrally located lung tumors in our institution will be shown. In our institution, these efforts have been made with the goal of raising the local control rate and decreasing adverse effects after SBRT.