Katsuyuki Tanimoto

Carbon-Ion Pencil Beam Scanning Treatment With Gated Markerless Tumor Tracking: An Analysis of Positional Accuracy

PURPOSE Having implemented amplitude-based respiratory gating for scanned carbon-ion beam therapy, we sought to evaluate its effect on positional accuracy and throughput. METHODS AND MATERIALS A total of 10 patients with tumors of the lung and liver participated in the first clinical trials at our center. Treatment planning was conducted with 4-dimensional computed tomography (4DCT) under free-breathing conditions. The planning target volume (PTV) was calculated by adding a 2- to 3-mm setup margin outside the clinical target volume (CTV) within the gating window. The treatment beam was on when the CTV was within the PTV. Tumor position was detected in real time with a markerless tumor tracking system using paired x-ray fluoroscopic imaging units. RESULTS The patient setup error (mean ± SD) was 1.1 ± 1.2 mm/0.6 ± 0.4°. The mean internal gating accuracy (95% confidence interval [CI]) was 0.5 mm. If external gating had been applied to this treatment, the mean gating accuracy (95% CI) would have been 4.1 mm. The fluoroscopic radiation doses (mean ± SD) were 23.7 ± 21.8 mGy per beam and less than 487.5 mGy total throughout the treatment course. The setup, preparation, and irradiation times (mean ± SD) were 8.9 ± 8.2 min, 9.5 ± 4.6 min, and 4.0 ± 2.4 min, respectively. The treatment room occupation time was 36.7 ± 67.5 min. CONCLUSIONS Internal gating had a much higher accuracy than external gating. By the addition of a setup margin of 2 to 3 mm, internal gating positional error was less than 2.2 mm at 95% CI.

Role of glucose metabolism and cellularity for tumor malignancy evaluation using FDG-PET/CT and MRI.

ObjectiveStandardized uptake value (SUV) is affected by many factors. In that respect, the brain reference index (BRI: regions of interest of tumor/regions of interest of cerebellum) is one of the quantitative approaches to eliminate the variety of factors that affect SUV. MRI pulse sequence findings can also provide information about tissue cellularity. This information is useful for evaluating the malignancy of lesions. We evaluated the role of glucose metabolism and cellularity for the diagnosis of pancreatic tumor malignancy. MethodWe performed a radionuclide 2-18F-fluoro-2-deoxyglucose (18F-FDG) uptake analysis and a signal intensity analysis using MRI on 16 presurgery patients with either proven or suspected pancreatic cancer. The tumor glucose metabolism was evaluated with SUV and BRI in an FDG-PET study. Tumor cellularity was determined with the MRI factors, apparent diffusion coefficient (ADC), T2 value and tumor to nontumor ratio of proton density. We compared these results with the pathological findings. ResultsSUV (=0.855), BRI (=0.875), and ADC (=0.830) showed a larger the area under the curve than T2 value (=0.582) and tumor to nontumor ratio of proton density (=0.786) according to the receiver operating characteristics analysis, and we therefore considered that these three factors were better indexes for the diagnosis of tumor malignancy. SUV and BRI had a high specificity. In contrast, ADC had a high sensitivity. ConclusionThe glucose metabolism with PET/CT and cellularity with MRI are different indexes for the diagnosis of tumor malignancy. Both provide necessary information for making an accurate diagnosis. Using both types of information may therefore help in obtaining a highly accurate diagnosis.

Prognostic value of (18) F-fluoroazomycin arabinoside PET/CT in patients with advanced non-small-cell lung cancer.

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F‐fluoroazomycin arabinoside (FAZA) in patients with advanced non‐small‐cell lung cancer (NSCLC) compared with 18F‐fluorodeoxyglucose (FDG). Thirty‐eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor‐to‐muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression‐free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy‐treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.

PET/CT with 3'-deoxy-3'-[18F]fluorothymidine for lung cancer patients receiving carbon-ion radiotherapy.

ObjectiveThe aim of this study was to investigate the clinical value of 3′-deoxy-3′-[18F]fluorothymidine-positron emission tomography/computed tomography (FLT-PET/CT) for lung cancer patients receiving carbon-ion radiotherapy. MethodsTwenty consecutive patients with lung cancer underwent FLT-PET/CT before and after carbon-ion radiotherapy. Fifty minutes after intravenous injection of approximately 300 MBq of FLT, PET/CT data were acquired. Maximal standardized uptake value of the tumor was measured, from which the reduction rate of tumor FLT uptake was calculated. After treatment, the patients were followed (17–42 months for survivors) for the development of recurrence and survival. ResultsPrimary responses to carbon-ion radiotherapy were partial in 13 patients, stable disease in six patients, and nonevaluable in one patient. Although tumor FLT uptake significantly decreased after treatment (P<0.001), the presence of radiation pneumonitis hampered its precise evaluation. During the follow-up period, nine patients developed recurrence, and seven patients died including two deaths from other causes. Pretreatment FLT uptake of patients who developed recurrence and who died of lung cancer were significantly higher than that of patients who did not (P=0.008 and 0.007, respectively). Kaplan–Meier analysis using a cut-off value also supported the prognostic value of pre-carbon-ion radiotherapy FLT-PET/CT. ConclusionThis investigation suggests that FLT-PET/CT is feasible in evaluating lung cancer patients undergoing carbon-ion radiotherapy. The presence of radiation pneumonitis can influence tumor FLT uptake and needs special attention. Pre-carbon-ion radiotherapy FLT-PET/CT seems to have a prognostic value and may contribute to decision-making on the treatment strategy.

Effects of image reconstruction algorithm on neurotransmission PET studies in humans: comparison between filtered backprojection and ordered subsets expectation maximization

ObjectivesBoth reconstruction algorithms, filtered backprojection (FBP) and ordered subsets expectation maximization (OSEM), are widely used in clinical positron emission tomography (PET) studies. Image reconstruction for most neurotransmission PET scan data is performed by FBP, while image reconstruction for whole-body [18F]FDG scan data is usually performed by OSEM. Although several investigators have compared FBP and OSEM in terms of the quantification of regional radioactivity and physiological parameters calculated from PET data, only a few studies have compared the two reconstruction algorithms in PET studies that estimate neurotransmission, i.e., neuroreceptor and neurotransporter binding. In this study we compared mean regional radioactivity concentration in the late phase and binding potential (BP) between FBP and OSEM algorithms in neurotransmission PET studies for [11C]raclopride and [11C]DASB.MethodsDynamic PET scans with [11C] raclopride in 3-dimensional mode were performed on seven healthy subjects. Dynamic PET scans with [11C]DASB in 2-dimensional mode were performed on another seven subjects. OSEM images were post-filtered so that its transverse spatial resolution became similar to that of FBP with the same Hanning filter (Kernel FWHM 6 mm). In both PET studies we calculated the BP of [11C]raclopride and [11C]DASB by a reference tissue model for each ROI (region of interest).ResultsThere was no significant difference in mean regional radioactivity concentration between FBP and OSEM for [11C] raclopride and [11C]DASB. Only +2.4 - +3.2%, but still a significant difference in BP of [11C]raclopride between FBP and OSEM was observed in the striatum. There was no significant difference in BP between FBP and OSEM in other than the striatum for [11C]raclopride and in all regions for [11C]DASB. In addition, there was no significant difference in root mean square error between FBP and OSEM when BP was calculated.ConclusionsThe BP values were similar between FBP and OSEM algorithms with [11C] raclopride and [11C]DASB. This study indicates that OSEM can be used for human neurotransmission PET studies for calculating BP although OSEM was not necessarily superior to FBP in the present study.

Calculation method using Clarkson integration for the physical dose at the center of the spread-out Bragg peak in carbon-ion radiotherapy

PURPOSE In broad-beam carbon-ion radiotherapy performed using the heavy-ion medical accelerator in Chiba, the number of monitor units is determined by measuring the physical dose at the center of the spread-out Bragg peak (SOBP) for the treatment beam. The total measurement time increases as the number of treatment beams increases, which hinders the treatment of an increased number of patients. Hence, Kusano et al. [Jpn. J. Med. Phys. 23(Suppl. 2), 65-68 (2003)] proposed a method to calculate the physical dose at the center of the SOBP for a treatment beam. Based on a recent study, the authors here propose a more accurate calculation method. METHODS The authors measured the physical dose at the center of the SOBP while varying the circular field size and range-shifter thickness. The authors obtained the physical dose at the center of the SOBP for an irregularly shaped beam using Clarkson integration based on these measurements. RESULTS The difference between the calculated and measured physical doses at the center of the SOBP varied with a change in the central angle of the sector segment. The differences between the calculated and measured physical doses at the center of the SOBP were within ± 1% for all irregularly shaped beams that were used to validate the calculation method. CONCLUSIONS The accuracy of the proposed method depends on both the number of angular intervals used for Clarkson integration and the fineness of the basic data used for calculations: sampling numbers for the field size and thickness of the range shifter. If those parameters are properly chosen, the authors can obtain a calculated monitor unit number with high accuracy sufficient for clinical applications.

Hybrid segmentation-atlas method for PET-MRI attenuation correction

One of the major unsolved issues of PET-MRI is the PET attenuation correction using MR images. Conventionally, in PET or PET-CT, attenuation maps (μ-maps) have been obtained by a PET transmission scan, or a CT scan. For PET-MRI, in order to obtain Il-maps from MR images, many studies have been reported, and they can be classified into two methods; the atlas-based method (ABM) and the segmentation-based method (SBM). In the ABM, individual differences such as lesions are not supported. In the SBM, it is difficult to discriminate bone and air, which have large differences in their attenuation coefficients, because these tissues have similar MR signal values in the T1 weighted (T1w) MR images. In this work, therefore, we proposed a hybrid segmentation-atlas method (HSAM) to utilize the advantages and compensate for the disadvantages of both the ABM and the SBM. At first, the proposed method follows the SBM approach. In the bone and air regions where Tlw MRI signals are similar and low, the HSAM uses information from a standard Il-map obtained through the ABM. For evaluation, the head data from 6 healthy volunteers were obtained by PET (ECAT Exact HR+) and MRI (Philips Intera 1.5T). We estimated Il-maps by the ABM, the SBM and the HSAM, and PET images were reconstructed though attenuation correction with those μ-maps. In comparison of the μ-maps, the HSAM and ABM outperformed the SBM. In comparison of the final PET images, a similar tendency was seen. For patient data, which would contain different distribution from the database, the HSAM is expected to outperform the ABM.

First Human Brain Images of the jPET-D4 Using 3D OS-EM with a Pre-computed System Matrix

The JPET-D4 is a novel brain PET scanner which aims to achieve not only high spatial resolution but also high scanner sensitivity by measuring 4-layer depth-of-interaction (DOI) information. In this work, we present software strategies for 3D image reconstruction and imaging performance of the JPET-D4 prototype. The dimensions of a system matrix for the JPET-D4 become 4 billion (coincidence pairs) times 5 million (image elements) when a 25 cm diameter FOV is sampled by a 1.53 mm3 voxel. The size of the system matrix is estimated at 142 peta (P) byte with the accuracy of 8 byte per element. The on-the-fly calculation is usually used to deal with a huge system matrix. However we can not avoid the extension of calculation time when we improve the accuracy of system modeling. In this work, we proposed an alternative approach based on the pre-calculation of the system matrix. The 142 P byte system matrix was compressed into 13.4GB by (1) reducing zero elements, (2) applying the 3D-expanded DOI compression method, (3) factorizing with respect to ring differences and (4) restricting the maximum ring difference to 54 (with only 10% loss of the number of LORs). Histogram-based 3D OSEM based on geometrical system modeling was implemented. After evaluating basic imaging performance though phantom experiments, a normal volunteer was scanned and the first human brain images were obtained.

Scanned carbon-ion beam therapy throughput over the first 7 years at National Institute of Radiological Sciences

INTRODUCTION In the 7 years since our facility opened, we have treated >2000 patients with pencil-beam scanned carbon-ion beam therapy. METHODS To summarize treatment workflow, we evaluated the following five metrics: i) total number of treated patients; ii) treatment planning time, not including contouring procedure; iii) quality assurance (QA) time (daily and patient-specific); iv) treatment room occupancy time, including patient setup, preparation time, and beam irradiation time; and v) daily treatment hours. These were derived from the oncology information system and patient handling system log files. RESULTS The annual number of treated patients reached 594, 7 years from the facility startup, using two treatment rooms. Mean treatment planning time was 6.0 h (minimum: 3.4 h for prostate, maximum: 9.3 h for esophagus). Mean time devoted to daily QA and patient-specific QA were 22 min and 13.5 min per port, respectively, for the irradiation beam system. Room occupancy time was 14.5 min without gating for the first year, improving to 9.2 min (8.2 min without gating and 12.8 min with gating) in the second. At full capacity, the system ran for 7.5 h per day. CONCLUSIONS We are now capable of treating approximately 600 patients per year in two treatment rooms. Accounting for the staff working time, this performance appears reasonable compared to the other facilities.

A MRI-based PET attenuation correction with μ-values measured by a fixed-position radiation source

Several MRI-based attenuation correction methods have been reported for PET/MRI. The accuracy of the attenuation map (μ-map) from an MRI image depends on correctness of the segmentation of tissue and the attenuation coefficients to be assigned (μ-values). However, an MRI image does not reflect the attenuation of radiation and inaccurate assignment of μ-values affects the quantitative assessment of functional images of PET. Although installation of a transmission scan function on the PET/MRI can provide an accurate μ-map, it restricts the design of the scanner, increases the manufacturing cost and takes additional scanning time. In this study, we implemented an MRI-based μ-value estimation method with a non-rotational radiation source to construct the proper μ-map for PET/MRI and assessed it based on clinical data sets. The proposed method uses the accurately segmented tissue map, the partial path length of each tissue, and detected intensities of attenuated radiation from a fixed-position radiation source which usually rotates around the subject to obtain the μ-map with the tomographic procedure. According to the Lambert-Beer law, attenuated intensity is described as the function of partial path length and μ-values of every tissue. The partial path length could be estimated by the simulation of fixed-point radiation with the same scanner geometry using the known tissue map from MRI. The μ-values of every tissue could be estimated by inverting the function. The simulation results, based upon measurement data, showed the errors between μ-values of the conventional transmission scan and our proposed method were 2.3±0.9%, 18.6±8.0% and -11.1±5.5% for brain, bone and soft tissue other than brain, respectively. Although there were over- and under-estimations for bone and soft tissue, respectively, the present method is able to estimate the brain μ-value accurately in clinical situations and that strongly affects the quantitative value of PET images because of the large volumetric ratio of the brain.