Impact of Infrared Indocyanine Green Fluorescence imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis.

BACKGROUND: Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs. METHODS: Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5 mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins. RESULTS: Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074 mm. CONCLUSIONS: We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.

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.

Gastric intramural metastasis caused by needle tract seeding after preoperative fine needle aspiration for pancreatic body cancer subsequently resected by total pancreatectomy: a case report and literature review.

BACKGROUND: Recently, there has been an increase in the number of reports of needle tract seeding (NTS) of tumor cells after a biopsy as one of the adverse events related to endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). In most of the previously reported cases of NTS in pancreatic cancer, distal pancreatectomy was performed as the initial surgery, following which metachronous metastasis was discovered in the gastric wall, whose localization matched the puncture route of the EUS-FNA. We report a case of early metastasis from pancreatic cancer in the gastric wall, which was postulated to be caused by NTS. Our patient underwent a total pancreatectomy (TP), and the NTS was resected synchronously. CASE PRESENTATION: A 70-year-old woman with a diagnosis of pancreatic head-body-tail cancer presented to our department for surgery. Transgastric EUS-FNA and biopsy established the histological diagnosis in her case. We administered neoadjuvant chemotherapy (NAC) to the patient and performed a TP. Histopathological and immunohistochemical examination subsequently confirmed the diagnosis of pT3N1aM1 pancreatic adenocarcinoma and its gastric metastasis, which was caused by NTS. It is postulated that the tumor cells of NTS had progressed to develop the metastatic lesion in the gastric wall during the NAC period. This was also resected during the initial surgery. The patient developed an early postoperative recurrence in the peritoneum 8 months after the surgery. CONCLUSION: In pancreatic head cancer cases, the puncture route is often included in the resection area of radical surgery, and NTS is seldom considered as a potential clinical problem. However, NTS can progress rapidly and may be associated with early recurrence of malignancy. Therefore, when transgastrointestinal puncture is performed for the diagnosis of pancreatic cancer, the treatment strategy should be established considering the potential development of NTS.

Time limit to rescue intestine with viability at risk caused by blood flow disruption in patients presenting with acute abdomen.

PURPOSE: Early management is crucial for acute intestinal blood flow disorders; however, no published study has identified criteria for the time limit for blood flow resumption. This study specifically examines the time factors for avoiding intestinal resection. METHODS: The subjects of this retrospective cohort study were 125 consecutive patients who underwent emergency surgery for a confirmed diagnosis of intestinal strangulation (n = 86), incarceration (n = 27), or volvulus (n = 12), between January 2015 and March 2021. Intestinal resection was performed when intestinal irreversible changes had occurred even after ischemia was relieved surgically. We analyzed the relationship between the time from computed tomography (CT) imaging to the start of surgery (C-S time) and intestinal resection using the Kaplan-Meier method and calculated the estimated intestinal rescue rate. Patient background factors affecting intestinal resection were also examined. RESULTS: The time limit for achieving 80% intestinal rescue rate was 200 min in C-S time, and when this exceeded 300 min, the intestinal rescue rate dropped to less than 50%. Multivariate analysis identified the APACHE II score as a significant influencing factor. CONCLUSION: A rapid transition from early diagnosis to early surgery is critical for patients with acute abdomen originating from intestinal blood flow disorders. The times from presentation at the hospital to surgery should be reduced further, especially for severe cases.

Treatment strategy for pancreatic head cancer with celiac axis stenosis in pancreaticoduodenectomy: A case report and review of literature.

BACKGROUND: During pancreaticoduodenectomy in patients with celiac axis (CA) stenosis due to compression by the median arcuate ligament (MAL), the MAL has to be divided to maintain hepatic blood flow in many cases. However, MAL division often fails, and success can only be determined intraoperatively. To overcome this problem, we performed endovascular CA stenting preoperatively, and thereafter safely performed pancreaticoduodenectomy. We present this case as a new preoperative treatment strategy that was successful. CASE SUMMARY: A 77-year-old man with a diagnosis of pancreatic head cancer presented to our department for surgery. Preoperative assessment revealed CA stenosis caused by MAL. We performed endovascular stenting in the CA preoperatively because we knew that going into the operation without a strategy could lead to ischemic complications. Double-antiplatelet therapy (DAPT) - which is needed when a stent is inserted - was then administered in parallel with neoadjuvant chemotherapy (NAC). This allowed us to administer DAPT for a sufficient period before the main pancreaticoduodenectomy procedure while obtaining therapeutic effects from NAC. Subtotal stomach-preserving pancreaticoduodenectomy was then performed. The operation did not require any unusual techniques and was performed safely. Postoperatively, the patient progressed well, without any ischemic complications. Histopathologically, curative resection was confirmed, and the patient had no recurrence or complications due to ischemia up to six months postoperatively. CONCLUSION: Preoperative endovascular stenting, with NAC and DAPT, is effective and safe prior to pancreaticoduodenectomy in potentially resectable pancreatic cancer.

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.

Dose quantification in carbon ion therapy using in-beam positron emission tomography.

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

[A Case of Panperitonitis Caused by Spontaneous Bladder Rupture].

A female septuagenarian had poorly controlled diabetes mellitus for more than 20 years. She had persistent pyuria, but did not seek further examination. In 2019, she was transported to our hospital by ambulance for sudden abdominal pain. Physical examination showed a sign of panperitonitis with sepsis. Computed tomography showed ascites and intraperitoneal free air. In addition, there was also a defect in the bladder wall, suggesting bladder rupture. Blood tests showed a marked increase in serum creatinine in addition to increased inflammatory reactants. Because perforation of gastrointestinal tract could not be excluded, an emergency laparotomy was performed. An intraperitoneal perforation of the posterior wall of the bladder was revealed, though there was no intestinal damage. The bladder wall was repaired and cystostomy was performed followed by irrigation and drainage of the abdominal cavity. After the operation, her abdominal symptom resolved and her general status improved. We speculated that voiding disturbance due to neurogenic bladder associated with diabetes mellitus and chronic infection caused the spontaneous bladder rupture. Most cases of spontaneous bladder rupture are associated with a history of pelvic surgery or irradiation, which suggests that this case is extremely rare. In patients with repeated urinary tract infection and underlying disease affecting bladder function, evaluation and appropriate management of bladder dysfunction should be performed ; otherwise, spontaneous bladder rupture may occur.

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.

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.

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.

Comparative study of alternative Geant4 hadronic ion inelastic physics models for prediction of positron-emitting radionuclide production in carbon and oxygen ion therapy.

The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model.

Central pancreatectomy in portal annular pancreas for metastatic renal cell carcinoma: a case report.

BACKGROUND: Portal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC). CASE PRESENTATION: A 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein (anteportal type), and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation. CONCLUSIONS: Precise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF.

Monte Carlo investigation of the characteristics of radioactive beams for heavy ion therapy.

This work presents a simulation study evaluating relative biological effectiveness at 10% survival fraction (RBE10) of several different positron-emitting radionuclides in heavy ion treatment systems, and comparing these to the RBE10s of their non-radioactive counterparts. RBE10 is evaluated as a function of depth for three positron-emitting radioactive ion beams (10C, 11C and 15O) and two stable ion beams (12C and 16O) using the modified microdosimetric kinetic model (MKM) in a heterogeneous skull phantom subject to a rectangular 50 mm × 50 mm × 60 mm spread out Bragg peak. We demonstrate that the RBE10 of the positron-emitting radioactive beams is almost identical to the corresponding stable isotopes. The potential improvement in PET quality assurance image quality which is obtained when using radioactive beams is evaluated by comparing the signal to background ratios of positron annihilations at different intra- and post-irradiation time points. Finally, the incidental dose to the patient resulting from the use of radioactive beams is also quantified and shown to be negligible.

Performance evaluation of a whole-body prototype PET scanner with four-layer DOI detectors.

Parallax error caused by the detector crystal thickness degrades spatial resolution at the peripheral regions of the field-of-view (FOV) of a scanner. To resolve this issue, depth-of-interaction (DOI) measurement is a promising solution to improve the spatial resolution and its uniformity over the entire FOV. Even though DOI detectors have been used in dedicated systems with a small ring diameter such as for the human brain, breast and small animals, the use of DOI detectors for a large bore whole-body PET system has not been demonstrated yet. We have developed a four-layered DOI detector, and its potential for a brain dedicated system has been proven in our previous development. In the present work, we investigated the use of the four-layer DOI detector for a large bore PET system by developing the world's first whole-body prototype. We evaluated its performance characteristics in accordance with the NEMA NU 2 standard. Furthermore, the impact of incorporating DOI information was evaluated with the NEMA NU 4 image quality phantom. Point source images were reconstructed with a filtered back projection (FBP), and an average spatial resolution of 5.2 ± 0.7 mm was obtained. For the FBP image, the four-layer DOI information improved the radial spatial resolution by 48% at the 20 cm offset position. The peak noise-equivalent count rate (NECR) was 22.9 kcps at 7.4 kBq ml-1 and the scatter fraction was 44%. The system sensitivity was 5.9 kcps MBq-1. For the NEMA NU 2 image quality phantom, the 10 mm sphere was clearly visualized without any artifacts. For the NEMA NU 4 image quality phantom, we measured the phantom at 0, 10 and 20 cm offset positions. As a result, we found the image with four-layer DOI could visualize the 2 mm-diameter hot cylinder although it could not be recognized on the image without DOI. The average improvements in the recovery coefficients for the five hot rods (1-5 mm) were 0.3%, 4.4% and 26.3% at the 0, 10 and 20 cm offset positions, respectively (except for the 1 mm-diameter rod at the 20 cm offset position). Although several practical issues (such as adding end-shields) remain to be addressed before the scanner is ready for clinical use, we showed that the four-layer DOI technology provided higher and more uniform spatial resolution over the FOV and improved contrast for small uptake regions located at the peripheral FOV, which could improve detectability of small and distal lesions such as nodal metastases, especially in obese patients.

Modified NEMA NU-2 performance evaluation methods for a brain-dedicated PET system with a hemispherical detector arrangement.

Brain PET imaging has important roles in neurology, neuro-oncology and molecular imaging research. We have developed a helmet-type PET prototype and have shown that the proposed hemispherical geometry had high potential for realizing high-sensitivity and low-cost brain imaging. However, there is no standard performance evaluation method for helmet-type PET, which would be a bottleneck to its commercialization. Therefore, we investigated appropriate performance evaluation methods for a helmet-type PET based on the NEMA NU 2-2018 standards. For those measurement methods that are not applicable to the helmet-type PET, we changed them while keeping the basic concept of the original NEMA standards. We measured spatial resolution, sensitivity, scatter fraction, count rate characteristics, accuracy of corrections for count losses and randoms, and image quality. We partially changed the measurement methods by making brain-size phantoms and by optimizing the length or the position of radioactive sources. The spatial resolution was 2.8 mm at 1-cm offset position by the filtered back-projection method. Sensitivities measured by the NEMA original setup and the proposed setup were 13.4 and 57.1 kcps/MBq. The respective values measured with our developed brain-size scatter phantom and with the conventional whole-body-size scatter phantom were: scatter fractions of 35% and 35%; peak NECRs of 25.1 kcps at 3.2 kBq/ml and 19.8 kcps at 2.6 kBq/ml ; and maximum absolute biases of 5.5% and 16.0%. The image quality was evaluated with the developed brain-size phantom, and good image quality was obtained. The helmet-type PET prototype showed high-sensitivity even with the small number of 54 detectors. The spatial resolution was better than 4.0 mm over the field-of-view. In conclusion, we proposed the performance evaluation methods for a brain-dedicated PET system with a hemispherical geometry. The proposed method could facilitate evaluation of performance characteristics of brain-dedicated PET scanners and optimization of its scanning and reconstruction parameters.

[State-of-the-Art Technologies in Nuclear Medicine Imaging].

Nuclear medicine imaging is an important tool for cancer diagnosis, brain research, molecular imaging research and so on. Therefore, various imaging techniques and methods are being developed and investigated in nuclear medicine physics. In this report, we introduce state-of-the-art techniques, such as Compton camera imaging, time-of-flight positron emission tomography, semiconductor detectors for medical applications, image reconstruction and deep learning, which were reported in the 2017 IEEE Nuclear Science Symposium & Medical Imaging Conference.

Integrated treatment using intraperitoneal radioimmunotherapy and positron emission tomography-guided surgery with 64Cu-labeled cetuximab to treat early- and late-phase peritoneal dissemination in human gastrointestinal cancer xenografts.

Peritoneal dissemination is a common cause of death from gastrointestinal cancers and is difficult to treat using current therapeutic options, particularly late-phase disease. Here, we investigated the feasibility of integrated therapy using 64Cu-intraperitoneal radioimmunotherapy (ipRIT), alone or in combination with positron emission tomography (PET)-guided surgery using a theranostic agent (64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab) to treat early- and late-phase peritoneal dissemination in mouse models. In this study, we utilized the OpenPET system, which has open space for conducting surgery while monitoring objects at high resolution in real time, as a novel approach to make PET-guided surgery feasible. 64Cu-ipRIT with cetuximab inhibited tumor growth and prolonged survival with little toxicity in mice with early-phase peritoneal dissemination of small lesions. For late-phase peritoneal dissemination, a combination of 64Cu-ipRIT for down-staging and subsequent OpenPET-guided surgery for resecting large tumor masses effectively prolonged survival. OpenPET clearly detected tumors (≥3 mm in size) behind other organs in the peritoneal cavity and was useful for confirming the presence or absence of residual tumors during an operation. These findings suggest that integrated 64Cu therapy can serve as a novel treatment strategy for peritoneal dissemination.

Induced radioactivity of a GSO scintillator by secondary fragments in carbon ion therapy and its effects on in-beam OpenPET imaging.

The accumulation of induced radioactivity within in-beam PET scanner scintillators is of concern for its long-term clinical usage in particle therapy. To estimate the effects on OpenPET which we are developing for in-beam PET based on GSOZ (Zi doped Gd2SiO5), we measured the induced radioactivity of GSO activated by secondary fragments in a water phantom irradiation by a (12)C beam with an energy of 290 MeV u(-1). Radioisotopes of Na, Ce, Eu, Gd, Nd, Pm and Tb including positron emitters were observed in the gamma ray spectra of the activated GSO with a high purity Ge detector and their absolute radioactivities were calculated. We used the Monte Carlo simulation platform, Geant4 in which the observed radioactivity was assigned to the scintillators of a precisely reproduced OpenPET and the single and coincidence rates immediately after one treatment and after one-year usage were estimated for the most severe conditions. Comparing the highest coincidence rate originating from the activated scintillators (background) and the expected coincidence rate from an imaging object (signal), we determined the expected signal-to-noise ratio to be more than 7 within 3 min and more than 10 within 1 min from the scan start time. We concluded the effects of scintillator activation and their accumulation on the OpenPET imaging were small and clinical long-term usage of the OpenPET was feasible.

Adsorption Analysis of Lactoferrin to Titanium, Stainless Steel, Zirconia, and Polymethyl Methacrylate Using the Quartz Crystal Microbalance Method.

It is postulated that biofilm formation in the oral cavity causes some oral diseases. Lactoferrin is an antibacterial protein in saliva and an important defense factor against biofilm development. We analyzed the adsorbed amount of lactoferrin and the dissociation constant (K(d)) of lactoferrin to the surface of different dental materials using an equilibrium analysis technique in a 27 MHz quartz crystal microbalance (QCM) measurement. Four different materials, titanium (Ti), stainless steel (SUS), zirconia (ZrO2) and polymethyl methacrylate (PMMA), were evaluated. These materials were coated onto QCM sensors and the surfaces characterized by atomic force microscopic observation, measurements of surface roughness, contact angles of water, and zeta potential. QCM measurements revealed that Ti and SUS showed a greater amount of lactoferrin adsorption than ZrO2 and PMMA. Surface roughness and zeta potential influenced the lactoferrin adsorption. On the contrary, the K(d) value analysis indicated that the adsorbed lactoferrin bound less tightly to the Ti and SUS surfaces than to the ZrO2 and PMMA surfaces. The hydrophobic interaction between lactoferrin and ZrO2 and PMMA is presumed to participate in better binding of lactoferrin to ZrO2 and PMMA surfaces. It was revealed that lactoferrin adsorption behavior was influenced by the characteristics of the material surface.