A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

Objective.To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy.Approach.Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results.Main results.Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions.Significance.The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Respiratory Diaphragm Motion-Based Asynchronization and Limitation Evaluation on Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) typically causes airflow blockage and breathing difficulties, which may result in the abnormal morphology and motion of the lungs or diaphragm. Purpose: This study aims to quantitatively evaluate respiratory diaphragm motion using a thoracic sagittal magnetic resonance imaging (MRI) series, including motion asynchronization and limitations. Method: First, the diaphragm profile is extracted using a deep-learning-based field segmentation approach. Next, by measuring the motion waveforms of each position in the extracted diaphragm profile, obvious differences in the independent respiration cycles, such as the period and peak amplitude, are verified. Finally, focusing on multiple breathing cycles, the similarity and amplitude of the motion waveforms are evaluated using the normalized correlation coefficient (NCC) and absolute amplitude. Results and Contributions: Compared with normal subjects, patients with severe COPD tend to have lower NCC and absolute amplitude values, suggesting motion asynchronization and limitation of their diaphragms. Our proposed diaphragmatic motion evaluation method may assist in the diagnosis and therapeutic planning of COPD.

Pre-acquired CT-based attenuation correction with automated headrest removal for a brain-dedicated PET system.

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (µ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of µ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (µ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (µ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (µ-map-sameHr). Phantom images by VRAIN using each µ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using µ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the µ-map-noHr and the µ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN.

Prediction of oxygen supplementation by a deep-learning model integrating clinical parameters and chest CT images in COVID-19.

PURPOSE: As of March 2023, the number of patients with COVID-19 worldwide is declining, but the early diagnosis of patients requiring inpatient treatment and the appropriate allocation of limited healthcare resources remain unresolved issues. In this study we constructed a deep-learning (DL) model to predict the need for oxygen supplementation using clinical information and chest CT images of patients with COVID-19. MATERIALS AND METHODS: We retrospectively enrolled 738 patients with COVID-19 for whom clinical information (patient background, clinical symptoms, and blood test findings) was available and chest CT imaging was performed. The initial data set was divided into 591 training and 147 evaluation data. We developed a DL model that predicted oxygen supplementation by integrating clinical information and CT images. The model was validated at two other facilities (n = 191 and n = 230). In addition, the importance of clinical information for prediction was assessed. RESULTS: The proposed DL model showed an area under the curve (AUC) of 89.9% for predicting oxygen supplementation. Validation from the two other facilities showed an AUC > 80%. With respect to interpretation of the model, the contribution of dyspnea and the lactate dehydrogenase level was higher in the model. CONCLUSIONS: The DL model integrating clinical information and chest CT images had high predictive accuracy. DL-based prediction of disease severity might be helpful in the clinical management of patients with COVID-19.

Performance evaluation of VRAIN: a brain-dedicated PET with a hemispherical detector arrangement.

Objective.For PET imaging systems, a smaller detector ring enables less intrinsic spatial resolution loss due to the photon non-collinearity effect as well as better balance between production cost and sensitivity, and a hemispherical detector arrangement is more appropriate for brain imaging than a conventional cylindrical arrangement. Therefore, we have developed a brain-dedicated PET system with a hemispherical detector arrangement, which has been commercialized in Japan under the product name of VRAINTM. In this study, we evaluated imaging performance of VRAIN.Approach.The VRAIN used 54 detectors to form the main hemispherical unit and an additional half-ring behind the neck. Each detector was composed of a 12 × 12 array of lutetium fine silicate crystals (4.1 × 4.1 × 10 mm3) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm2active area) with the one-to-one coupling. We evaluated the physical performance of VRAIN according to the NEMA NU 2-2018 standards. Some measurements were modified so as to fit the hemispherical geometry. In addition, we performed18F-FDG imaging in a healthy volunteer.Main results.In the phantom study, the VRAIN showed high resolution for separating 2.2 mm rods, 229 ps TOF resolution and 19% scatter fraction. With the TOF gain for a 20 cm diameter object (an assumed head diameter), the peak noise-equivalent count rate was 144 kcps at 9.8 kBq ml-1and the sensitivity was 25 kcps MBq-1. Overall, the VRAIN provided excellent image quality in phantom and human studies. In the human FDG images, small brain nuclei and gray matter structures were clearly visualized with high contrast and low noise.Significance.We demonstrated the excellent imaging performance of VRAIN, which supported the advantages of the hemispherical detector arrangement.

Semiautomatic assessment of respiratory dynamics using cine MRI in chronic obstructive pulmonary disease.

Purpose: The quantitative assessment of impaired lung motions and their association with the clinical characteristics of COPD patients is challenging. The aim of this study was to measure respiratory kinetics, including asynchronous movements, and to analyze the relationship between lung area and other clinical parameters. Materials and methods: This study enrolled 10 normal control participants and 21 COPD patients who underwent dynamic MRI and pulmonary function testing (PFT). The imaging program was implemented using MATLAB®. Each lung area was detected semi-automatically on a coronal image (imaging level at the aortic valve) from the inspiratory phase to the expiratory phase. The Dice index of the manual measurements was calculated, with the relationship between lung area ratio and other clinical parameters, including PFTs then evaluated. The asynchronous movements of the diaphragm were also evaluated using a sagittal image. Results: The Dice index for the lung region using the manual and semi-automatic extraction methods was high (Dice index = 0.97 ± 0.03). A significant correlation was observed between the time corrected lung area ratio and percentage of forced expiratory volume in 1 s (FEV1%pred) and residual volume percentage (RV%pred) (r = -0.54, p = 0.01, r = 0.50, p = 0.03, respectively). The correlation coefficient between each point of the diaphragm in the group with visible see-saw like movements was significantly lower than that in the group without see-saw like movements (value = -0.36 vs 0.95, p = 0.001). Conclusion: Semi-automated extraction of lung area from Cine MRI might be useful for detecting impaired respiratory kinetics in patients with COPD.

Small nuclei identification with a hemispherical brain PET.

BACKGROUND: To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared 18F-fluorodeoxyglucose (FDG) brain images with whole-body PET images. METHODS: Ten healthy male volunteers (aged 22-45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants' age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images. RESULTS: Small nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman's correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET. CONCLUSIONS: This was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET. TRIAL REGISTRATION  : Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086 .

Feasibility of triple gamma ray imaging of10C for range verification in ion therapy.

Objective.In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive15O and11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient's body during ion therapy.Approach.In this work, we focus on investigating the performance of WGI for10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba.Main results.The average spatial resolution and sensitivity for the simulated10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the10C ion beam was measured, and the triple gamma image of10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas.Significance.The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of10C ion beams.

Brain PET motion correction using 3D face-shape model: the first clinical study.

OBJECTIVE: Head motions during brain PET scan cause degradation of brain images, but head fixation or external-maker attachment become burdensome on patients. Therefore, we have developed a motion correction method that uses a 3D face-shape model generated by a range-sensing camera (Kinect) and by CT images. We have successfully corrected the PET images of a moving mannequin-head phantom containing radioactivity. Here, we conducted a volunteer study to verify the effectiveness of our method for clinical data. METHODS: Eight healthy men volunteers aged 22-45 years underwent a 10-min head-fixed PET scan as a standard of truth in this study, which was started 45 min after 18F-fluorodeoxyglucose (285 ± 23 MBq) injection, and followed by a 15-min head-moving PET scan with the developed Kinect based motion-tracking system. First, selecting a motion-less period of the head-moving PET scan provided a reference PET image. Second, CT images separately obtained on the same day were registered to the reference PET image, and create a 3D face-shape model, then, to which Kinect-based 3D face-shape model matched. This matching parameter was used for spatial calibration between the Kinect and the PET system. This calibration parameter and the motion-tracking of the 3D face shape by Kinect comprised our motion correction method. The head-moving PET with motion correction was compared with the head-fixed PET images visually and by standard uptake value ratios (SUVRs) in the seven volume-of-interest regions. To confirm the spatial calibration accuracy, a test-retest experiment was performed by repeating the head-moving PET with motion correction twice where the volunteer's pose and the sensor's position were different. RESULTS: No difference was identified visually and statistically in SUVRs between the head-moving PET images with motion correction and the head-fixed PET images. One of the small nuclei, the inferior colliculus, was identified in the head-fixed PET images and in the head-moving PET images with motion correction, but not in those without motion correction. In the test-retest experiment, the SUVRs were well correlated (determinant coefficient, r2 = 0.995). CONCLUSION: Our motion correction method provided good accuracy for the volunteer data which suggested it is useable in clinical settings.

Marker-less and calibration-less motion correction method for brain PET.

Marker-less head motion correction methods have been well-studied; however, no reports discussing potential issues in positional calibration between a PET system and an external sensor remain limited. In this study, we develop a method for positional calibration between the PET system and an external range sensor to achieve practical head motion correction. The basic concept of the developed method involves using the subject's face model as a marker not only for head motion detection but also for the system positional calibration. The face model of the subject, which can be obtained easily using the range sensor, can also be calculated from a computed tomography (CT) image of the same subject. The CT image, which is acquired separately for attenuation correction in PET, has the same coordinates as the PET image because of the appropriate matching algorithm between CT and PET images. The proposed method was implemented in the helmet-type PET and the motion correction accuracy was assessed quantitatively using a mannequin head. The phantom experiments demonstrated the performance of the developed motion correction method; high-resolution images with no trace of the applied motion were obtained as if no motion was provided. Statistical analysis supported the visual assessment results in terms of the spatial resolution, contrast recovery; uniformity, and the results implied that motion with correction slightly improved image quality compared with the motionless case. The tolerance of the developed method against potential tracking errors had a minimum 10% difference in the amplitude of the rotation angle.

Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer.

BACKGROUND: In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery. METHODS: A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations. RESULTS: Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group. CONCLUSIONS: OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.

Design consideration of compact cardiac TOF-PET systems: a simulation study.

Myocardial perfusion imaging (MPI) with PET plays a vital role in the management of coronary artery disease. High sensitivity systems can contribute to maximizing the potential value of PET MPI; therefore, we have proposed two novel detector arrangements, an elliptical geometry and a D-shape geometry, that are more sensitive and more compact than a conventional large-bore cylindrical geometry. Here we investigate two items: the benefits of the proposed geometries for cardiac imaging; and the effects of scatter components on cardiac PET image quality. Using the Geant4 toolkit, we modeled four time-of-flight (TOF) PET systems: an 80 cm diameter cylinder, a 40 cm diameter cylinder, a compact ellipse, and a compact D-shape. Spatial resolution and sensitivity were measured using point sources. Noise equivalent count rate and image quality were examined using an anthropomorphic digital chest phantom. The proposed geometries showed higher sensitivity and better count rate characteristics with a fewer number of detectors than the conventional large-bore cylindrical geometry. In addition, we found that the increased intensity of the scatter components was a big factor affecting the contrast in defect regions for such a compact geometry. It is important to address the issue of the increased intensity of the scatter components to develop a high-performance compact cardiac TOF PET system.

245 ps-TOF brain-dedicated PET prototype with a hemispherical detector arrangement.

Brain PET, which has led research in molecular imaging and diagnosis of brain cancer, epilepsy and neurodegenerative disorders, is being spotlighted again to promote earlier diagnosis of dementia with the advent of amyloid and tau tracers. To meet this demand, in this paper, we developed a brain-dedicated PET imaging device with a hemispherical detector arrangement, which provides comparable sensitivity with fewer detectors than conventional cylindrical geometries. The introduction of the time-of-flight (TOF) measurement capability was a key point for the development to get a gain in the image signal-to-noise ratio. Currently, whole-body PET scanners with around 200-400 ps coincidence resolving time (CRT) are commercially available. In order to obtain the same TOF gain which can be obtained with 400 ps CRT for a 30 cm diameter object, 267 ps CRT will be required for a 20 cm diameter object such as the human head. In this work, therefore, we aimed at developing a TOF brain-dedicated PET prototype with the hemisphere detector arrangement and the CRT faster than 267 ps. The detector was composed of a 12 × 12 lutetium fine silicate (LFS) array coupled with a 12 × 12 multi-pixel photon counter (MPPC) array. Each LFS crystal with a size of 4.14 × 4.14 × 10 mm3 was individually coupled to a separate MPPC. Singles list-mode data from each detector were stored, and coincidences were identified using a coincidence-detection software algorithm. The CRT of 245 ps was finally achieved as the system average after a fine timing correction. For image reconstruction, we implemented the list-mode TOF-OSEM. For a small rod phantom, rods of 3 mm diameter were clearly separated. Also, images of the 3D Hoffman brain phantom, which demonstrated clear contrast between gray and white matter, supported the effect of TOF information.

Experimental investigation of the characteristics of radioactive beams for heavy ion therapy.

PURPOSE: This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in-beam whole-body positron emission tomography scanner for range verification quality assurance. METHODS: The energy deposited by monoenergetic beams of 11 C at 350 MeV/u, 15 O at 250 MeV/u, 12 C at 350 MeV/u, and 16 O at 430 MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose-mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon-on-insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron-emitting nuclei were measured for each beam in a gelatin phantom using the in-beam whole-body positron emission tomography scanner at HIMAC. The depth of maximum positron-annihilation density was compared with the depth of maximum dose deposition and the signal-to-background ratios were calculated and compared for images acquired over 5 and 20 min postirradiation of the phantom. RESULTS: In the entrance region, the h b o x RBE 10 was 1.2 ± 0.1 for both 11 C and 12 C beams, while for 15 O and 16 O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the RBE 10 was 2.7 ± 0.4 for 11 C and 2.9 ± 0.4 for 12 C, while for 15 O and 16 O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, RBE 10 could only be evaluated for carbon; the RBE 10 was 1.6 ± 0.2 and 1.5 ± 0.1 for 11 C and 12 C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal-to-background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5-fold and 11-fold increases in the ratios calculated for the 15 O and 11 C images compared with the values obtained for 16 O and 12 C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 ± 0.8 mm for 11 C, compared to -5.6 ± 0.8 mm for 12 C and 0.9 ± 0.8 mm for 15 O vs -6.6 ± 0.8 mm for 16 O. CONCLUSIONS: The RBE 10 values for 11 C and 15 O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, 11 C and 15 O beams produce much better quality images for range verification compared with 12 C and 16 O, in particular with regard to estimating the location of the Bragg peak.

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET.

In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.

Immuno-OpenPET: a novel approach for early diagnosis and image-guided surgery for small resectable pancreatic cancer.

Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (<1 cm) can significantly improve survival; however, imaging diagnosis and accurate resection of small PC remain challenging. Here, we report the feasibility of "immuno-OpenPET" as a novel approach enabling not only early diagnosis but also image-guided surgery, using a small (<1 cm) resectable PC orthotopic xenograft mouse model. For immuno-OpenPET, we utilized our original OpenPET system, which enables high-resolution positron emission tomography (PET) imaging with depth-of-interaction detectors, as well as real-time image-guided surgery, by arranging the detectors to create an open space for surgery and accelerating the image reconstruction process by graphics processing units. For immuno-OpenPET, 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ≥3 mm. In contrast, neither OpenPET with intravenous-administered 64Cu-cetuximab nor intraperitoneal/intravenous-administered 18F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.